Asa 2013

Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved.
Note: This publication contains

material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual
refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
106
Page 1
Current Controversies in Adult Outpatient Anesthesia
Jeffrey L. Apfelbaum, M.D. Chicago,Illinois
Introduction
The fast paced world of ambulatory anesthesiology continues to present anesthesiologists with an ever-
changing array of challenges. This Refresher Course will provide an update on current controversial issues in adult
outpatient anesthesia, including fast tracking; preoperative assessment, evaluation, and preparation; recent changes
to ASA Basic Anesthesia Monitoring Standards; ramifications of recent changes to Interpretative Guidelines issued
by the Center for Medicare and Medicaid Services (CMS) on our practice; and Computer Assisted Personalized
Sedation (CAPS). Additionally we will consider a variety of breaking news areas of controversy which may
include topics such as patients with obesity/modified metabolic syndrome; advances in and recommendations to
enhance perioperative communication; treatment decisions for patients with coronary artery stents; opportunities to
incorporate ones personal outcomes data into your patient care plan and potential effect choice of anesthetic on
cancer recurrence rates.
Fast Tracking: Eliminating Intensive Post-Operative Care in Same Day Surgery Patients Using Short Acting
Fast Emergence Anesthetics
Many anesthetics have the pharmacokinetic and pharmacodynamic advantages of a shorter duration of
action and a more rapid rate of recovery which permit a faster emergence from anesthesia compared with their
predecessors. Less than 30 years ago, it was unthinkable that patients would be able to return home on the day of
surgery. Today, advances in surgery and anesthesiology make it possible to perform the vast majority of all surgical
procedures, safely and effectively on an ambulatory basis, with many patients ready to be reunited with their
families within minutes of emergence from anesthesia. In todays cost sensitive healthcare environment, the
processes of ambulatory surgical care must be continually re-evaluated to take advantage of advances in technology
and pharmacology and to optimize efficiency of the ambulatory surgical care without detriment to patient safety and
satisfaction.
Traditionally, ambulatory surgical patients go from the operating room to the postanesthesia care unit (PACU) or
recovery room (a highly specialized intensive care unit) for their immediate postoperative recovery from anesthesia
and then to a second stage recovery unit (SSRU) for preparation for home readiness. By its very nature as a
specialized ICU, the PACU is an expensive, labor-intensive environment. After a set of recovery criteria
1, 2, 3
are
met in the PACU, the patient is usually transferred to the SSRU. In the SSRU, the patient-to-nurse ratio is
considerably higher (i.e., nursing care in the SSRU is less labor intensive) than in the PACU. Only basic monitoring
and observation are performed as the patient and his or her escort are prepared for imminent discharge to home.
Because of the rapid recovery of patients undergoing anesthesia with the shorter acting, faster emergence
anesthetics, some have questioned if all ambulatory surgical patients need to receive intensive postoperative care in
the PACU setting or whether first stage recovery from anesthesia can be achieved safely while still in the
operating room (at least for some patients), thereby resulting in enormous potential savings.
The SAFE study evaluates the impact of selective patient bypass of the PACU on both the outcomes of
ambulatory surgical patients and the use of resources in the surgical arena.
4
This study was designed to evaluate the
rapid recovery of patients undergoing ambulatory surgery using short-acting, fast emergence anesthetic agents and
to determine if policies and procedures could be developed that would allow patients to safely bypass first stage

Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved. Note: This publication contains
106
Page 2
post-anesthesia care units (PACU) and whether such changes in the recovery paradigm would result in financial
savings for the surgical center. Five community based facilities (hospitals or surgery centers) participated in this
prospective observational study. While in the operating room at the end of the surgical procedure, anesthesiologists
were asked to assess all ambulatory surgical patients for recovery using standardizing discharge criteria typically
used at the end of a PACU stay (Table 1). If the patient met the discharge criteria, they were transferred from the
OR directly to the less labor intensive second stage recovery unit (SSRU). Financial data were provided from all
five sites detailing all costs associated with the recovery process. Clinical data on every elective ASA 1, 2 and 3
ambulatory surgical patient were collected over a three month period. During month one, data collected established
a baseline of case mix, time stamps, adverse events, bypass rates, and financial profile. During month two, an
educational intervention was provided on a multi-disciplinary basis to all units in the surgical center discussing the
implications of the bypass paradigm. After implementation of the paradigm (month three) weekly feedback reports
were provided to the site featuring the key outcomes of the study, and these reports were distributed to the health
care providers. Nearly 5,000 patients were entered into the study. The overall bypass rate increased from 15.9% in
the baseline month to 58.9% in the month following the educational intervention (p < 0.0001). The change in
process in this study went beyond reducing time spent in the PACU to eliminating the time spent in the PACU while
not increasing the time spent in the operating room or SSRU. In fact, the average (SD) time spent in the SSRU was
significantly shorter for patients who bypassed the PACU than for those who did not bypass the PACU. There were
no significant differences in other parameters of patient outcome. Annualized savings ranged from $50,000 to
$160,000 per site.
The Hows And Whys Of Preoperative Evaluation
The continued growth of outpatient surgery has created new roles for the anesthesiologist which seemingly
demands skills in addition to "giving a good anesthetic." The times from induction to emergence are no longer the
only important role for the perioperative physician. Particularly in the freestanding and office environments, it is
often the anesthesiologist who is most involved in the direct medical care of the patient; we are the physicians who
must insure that the patient is appropriately screened, evaluated, and informed prior to the day of surgery. Indeed,
the anesthesiologist/patient relationship which sometimes develops often takes on a primary care quality. Although
sometimes difficult to arrange, the preoperative interview and evaluation by a consultant anesthesiologist
(particularly in high risk patients) can be extraordinarily beneficial. In addition to lessening anxiety about the
surgery and anesthesia, in most cases, the anesthesiologist will be able to identify potential medical problems in
advance, determine their etiology, and if indicated, initiate appropriate corrective measures. Additionally, the
ambulatory anesthesiologist can play a critically important role in assuring that the patient understands and complies
with preoperative instructions. In most facilities, the goal is to resolve preoperative problems well in advance of the
day of surgery, thereby minimizing the numbers of both cancellations and complications.
At the present time, there are several commonly used approaches to screening patients for ambulatory
surgery. These include: (1) facility visit prior to the day of surgery, (2) office visit prior to the day of surgery, (3)
telephone interviews/no visit, (4) review of health survey/no visit, (5) preoperative screening and visit on the
morning of surgery, (6) virtual visit via the internet/no physical visit, and (7) the use of telemedicine technology.
Each system has its own advantages and disadvantages.
Should Patient Age or ASA Physical Status Influence Case Selection?
Although the vast majority of individuals scheduled for outpatient surgery are relatively healthy (ASA
Physical Status 1 and 2), practitioners are constantly being pressured by third party payors to consider "simple
outpatient surgery" for patients with significant baseline co-morbidities. A survey of members of the Society for
Ambulatory Anesthesia (SAMBA) revealed that half the respondents felt that their practice pushes the envelope of
patient safety by performing outpatient surgery on patients with serious pre-existing conditions, and that 40% of
respondents felt that their practice pushes the envelope of patient safety by performing complex or lengthy surgical
procedures on outpatients. In the past, many individuals had arbitrarily stated that freestanding ambulatory surgical
facilities were severely limited in the type of patients they could anesthetize, particularly with regard to age and
physical status. Clinical experience, however, suggests otherwise. In a retrospective study of over 1,500 cases of
patients anesthetized for ambulatory surgery, Meridy
6
was unable to demonstrate an age-related effect on the
duration of recovery or the incidence of postoperative complications. With regard to the issue of physical status, in
a prospective study involving over 13,000 patients at a freestanding ambulatory surgical center, Natof
7
concluded

106
Page 3
that ASA 3 patients whose systemic diseases were well controlled preoperatively were at no higher risk for
postoperative complications than ASA 1 or 2 patients. Chung examined predictors of adverse events in ambulatory
surgery in the elderly, as well as factors contributing to prolonged stay after ambulatory surgery in elderly patients.
This data demonstrated that outpatient surgery is safe in this patient population, with elderly patients sustaining
more minor cardiovascular events than their younger counterparts, and less postoperative nausea and vomiting, pain,
and drowsiness.
8, 9
. It is clear that geriatric and higher risk (physical status 3 and 4) patients may be considered
acceptable candidates for outpatient surgery if their systemic diseases are well controlled and the patients medical
condition is optimized preoperatively.
The Inappropriate Patient - Who's OK And Who's Not
There are few data to reliably categorize the inappropriate adult surgical outpatient. As anesthesiologists
have become more experienced with the anesthetic management of the problem surgical outpatient, the list of
"inappropriate" patients has dwindled. We must individualize our decision with regard to each patient; with few
exceptions, the appropriateness of a case for outpatient surgery is determined by a combination of factors including
patient considerations, surgical procedure, anesthetic technique, and anesthesiologist's comfort level.
At the University of Chicago Medical Center, we have distinguished several groups of patients who may
not be appropriate candidates for ambulatory surgery. As one might expect, this list is frequently modified to adapt
to the ever-changing conditions of our social and medicolegal environment.
Unstable ASA Physical Status 3 and 4: At the present time we are reluctant to proceed with elective ambulatory
surgery in a medically unstable patient. Instead, we use our anesthesia perioperative medicine clinic (APMC) to
screen these patients, and together with the primary care surgeon or interventionalist, establish a plan to proceed
with the surgery or intervention after medical stabilization. Contrary to the original "ground rules" of ambulatory
surgery, studies involving hundreds of thousands of patients seem to suggest that neither increasing age nor the
presence of stable pre-existing disease affect the incidence of postoperative complications in the surgical outpatient.
Malignant Hyperpyrexia: In our facility, overnight hospitalization and observation is usually indicated for patients
with a history of malignant hyperpyrexia or with identified susceptibility to malignant hyperpyrexia. However,
patients who are well educated, have a good understanding of their disease process, and have ready access to
medical care may be treated as outpatients by some centers.
Complex Morbid Obesity/Complex Sleep Apnea: Although patients who have a history of sleep apnea or who are
morbidly obese without systemic disease are acceptable candidates for ambulatory surgery, we prefer overnight
hospitalization and postoperative observation for morbidly obese surgical patients with significant pre-existing
cardiac, pulmonary, hepatic or renal compromise or those patients with a history of complex sleep apnea. Practice
guidelines for the perioperative management of patients with obstructive sleep apnea have recently been developed
by the American Society of Anesthesiologists and offer recommendations for preoperative evaluation, preoperative
preparation, intraoperative management, postoperative management, and site of surgery (inpatient vs.
outpatient).
10

Acute Substance Abuse: Because of the increased likelihood of acute untoward cardiovascular responses when
one administers an anesthetic to a patient who has recently abused illicit drugs, we preoperatively counsel these
patients and inform them that any sign of recent drug abuse on the day of surgery will result in immediate
cancellation of their anesthetic. We tell them that no elective surgical procedure "is worth dying for" and encourage
their preoperative participation in a rehabilitation program.
Anesthesiology directed perioperative medicine clinics are increasingly used to optimize the medical
condition of a patient in preparation for surgery. These clinics have been shown to enhance patient safety
11
,
improve patient satisfaction
12,13
, minimize preoperative consultation
14
, and reduce day of surgery case cancellations
and case postponements.
15

Changes to the ASA Standards for Basic Anesthesia Monitoring

106
Page 4
For the first time in nearly a decade, there has been a significant change to the ASA Standards for Basic
Anesthesia Monitoring.
16
The standard for monitoring of ventilation has undergone significant revision:
VENTILATION: 3.2.4: During regional anesthesia (with no sedation) or local anesthesia (with no sedation), the
adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs. During moderate or
deep sedation the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs
and monitoring for the presence of exhaled carbon dioxide unless precluded or invalidated by the nature of the
patient, procedure, or equipment. Many physicians have asked if these standards apply to cases where sedation is
administered in out of operating room locations. The Centers for Medicare and Medicaid (CMS) Revised Hospital
Anesthesia Services Interpretative Guidelines seemingly provide guidance on this issue. The first section in these
Interpretative Guidelines is entitled Types of Anesthesia Services and the first bullet in this section begins as
follows: Anesthesia services, which include both anesthesia and analgesia, are provided along a continuum,
ranging from the application of local anesthetics for minor procedures to general anesthesia for patients who
require loss of consciousness as well as control of vital body functions in order to tolerate invasive operative
procedures. This continuum also includes minimal sedation, moderate sedation/analgesia (conscious sedation),
monitored anesthesia care (MAC), and regional anesthesia.
CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines
CMS has recently issued significant revisions to the Anesthesia Services Interpretive Guidelines.
16
These
included significant revisions to the CMS compliance requirements for both pre and post anesthesia evaluations, as
well as a requirement that heretofore, ALL anesthesia and sedation services (including mild, moderate, and deep
sedation) , regardless of providers MUST be organized into a single anesthesia service under the direction of a
qualified doctor of medicine or doctor of osteopathy. Specific portions of these Interpretive Guidelines will be
addressed during the presentation.
Computer-Assisted Personalized Sedation (CAPS)
Ethicon Endo-Surgery, Inc. has developed a computer-assisted personalized sedation system (trade name
SEDASYS
) According to the manufacturer, the SEDASYS

System is the first computer-assisted personalized
sedation (CAPS) system designed for physician/nurse teams to provide minimal-to-moderate sedation levels with
propofol. By integrating drug delivery and patient monitoring, the SEDASYS
System enables physician/nurse

teams to deliver personalized sedation. It automatically detects and responds to signs of over-sedation (oxygen
desaturation and low respiratory rate/apnea) by stopping or reducing delivery of propofol, increasing oxygen
delivery and automatically instructing patients to take a deep breath.
On May 28, 2009, the Anesthesia and Respiratory Therapy Devices Advisory Committee of the US Food and
Drug Administration (FDA) concluded its deliberations and recommended to the FDA that the SEDASYS
device
be approvable for the administration of propofol by physician/nurse teams for the initiation and maintenance of
minimal to moderate sedation during screening and diagnostic procedures in patients undergoing colonoscopy and
esophagoduodenoscopy procedures with the following conditions:
1) The device may only be used in adult patients (ASA I, II, and III) 70 years old or younger;
2) The device may only be used in the presence of a 3 person clinical team where one person shall have the sole
responsibility of monitoring the patient, the device and managing the patient's airway. This dedicated person must
have advanced training and at least the skills of a nurse;
3) Physicians utilizing the device must complete training in advanced airway management, pharmacology of
propofol and opioids, patient selection, monitor training (such as SpO
2
monitoring), device set-up and maintenance
with the training provided by a clinician with credentials to provide deep sedation to general anesthesia. In addition,
there needs to be a program established for ongoing maintenance of training;
4) The manufacturer must complete all post-marketing studies as proposed at the time of the Advisory Panel
hearing.
5) The product launch is controlled.
On several occasions, representatives of the company have suggested that the device is compliant with
ASA guidelines on sedation/analgesia by non-anesthesiologists; as a result of this claim both medical professionals
and lay people have occasionally erroneously concluded that the device is consistent with ASA standards,
guidelines, statements and/or policies.
17
Indeed, some individuals have mistakenly concluded that ASA has

106
Page 5
endorsed the product. However, this conclusion is erroneous. In the AANA-ASA Joint Statement Regarding
Propofol Administration (April 14, 2004) the ASA position regarding the use of propofol is clearly stated as
follows:
18

Whenever propofol is used for sedation/anesthesia, it should be administered only by persons trained in the
administration of general anesthesia, who are not simultaneously involved in these surgical or diagnostic
procedures. This restriction is concordant with specific language in the propofol package insert, and failure to
follow these recommendations could put patients at increased risk of significant injury or death.
In April 2010, Johnson & Johnson, the parent company of Ethicon-Endo Surgery, Inc., announced that the
FDA sent the company a not approvable letter for the SEDASYS
Computer Assisted Personalized Sedation

System. The company had appealed this decision and on May 10, 2013 the company announced that the FDA had
granted PMA approval for the device. The SEDASYS
System is expected to be introduced on a limited basis

beginning in 2014. The company will collaborate with the gastroenterology, anesthesiology and nursing
communities to successfully integrate the SEDASYS
System, and conduct two post-approval studies to monitor the

use of the technology in actual clinical practice. During the session, we will review many of the specifics of this
device and present an update on its current approval status.
Summary
Today there is a continued trend to expand the indications for ambulatory surgery. Because outpatient
anesthesia is a break from our traditional training, we are constantly being confronted with the need for change in
our clinical practice patterns. We have recognized that the needs of the surgical outpatient may be very different
from the inpatient and are now trying to adapt our practice patterns to meet the psychologic and pharmacologic
requirements of the compacted perioperative management the outpatient receives. This Refresher Course has
focused on some of the controversial problems which we as practicing clinicians must deal with every day in our
practice of ambulatory anesthesia for adult patients.

106
Page 6
REFERENCES
1. Chung F: Are discharge criteria changing? J Clin Anesth 1993; 5:64S-68S.
2. Chung F: Recovery pattern and home-readiness after ambulatory surgery. Anesth Analg 1995; 80:896-902.
3. Aldrete JA: J Perianes Nurs 1998; 13(3):148-55.
4. Apfelbaum JL, et al: Anesthesiology 2002; 97:66-74.
5. Sandberg et al: Anesthesiology 2012; 117:4: 772-779.
6. Meridy HW. Anesth Analg 1982, 61:921-6.
7. Natof HE. Ambulatory surgery: Patients with pre-existing medical problems. Ill Med J 1984; 166(2):101.
8. Chung F, Mezeu G, Tong D. BJA 1999, 83(2): 262-70.
9. Chung F, Mezei G. Anesth Analg 1999, 89(6): 1352-9.
10. Gross JB, et al. Anesthesiology 2006; 104(5):1081-1093.
11. Parsa P, et al. Anesth Analg 2004; 100:S-147.
12. Parker BM, et al. J Clin Anesth 2000; 12:350-6.
13. Harnett, et al. Anesthesiology 2010; 112:66
14. Fischer SP. Anesthesiology 1996; 85:190-206.
15. Ferschl MB, et al. Anesthesiology 103(4):855-859.
16. http://www.asahq.org/For-Members/Clinical-Information/Standards-Guidelines-and-Statements.aspx
17. Pambianco, et al: GI Endoscopy 2008;68: 542-547
18. http://www.asahq.org/publicationsAndServices/standards/37.pdf

TABLE 1. DISCHARGE CRITERIA

Awake, alert, oriented, responsive (or return to baseline)
Minimal pain
No active bleeding
Vital signs stable (not likely to require pharmacologic intervention)
Minimal nausea
No vomiting
If nondepolarizing neuromuscular blocking agent used, patient can perform sustained five second head lift
Oxygen saturation of 94% on room air (three minutes or longer) OR return of oxygen saturation to baseline
or higher in order to be eligible to bypass Phase I recovery (PACU), the patient must meet ALL of the
above criteria, and in the judgment of the anesthesiologist, be capable of transfer to the step-down unit,
with appropriate care and facility for patient management at that location

Disclosure
This speaker has indicated that he or she has no significant financial relationship with the manufacturer of a
commercial product or provider of a commercial service that may be discussed in this presentation.

205
Page 1
Preoperative Evaluation of the Adult Outpatient
Barbara S. Gold, M.D. Minneapolis, Minnesota
Introduction
Preoperative evaluation is a fundamental component of anesthetic delivery because it guides anesthetic management
and postoperative care. This is especially true in the ambulatory surgical setting where preoperative evaluation also
informs patient selection. Patient selection, in turn, is the cornerstone for safe and efficient ambulatory anesthesia
care.
In the outpatient setting the preoperative anesthesia assessment which exists in a variety of forms - is a key tool for
both optimizing medical and administrative outcomes. Proactive identification and management of medical
problems avoids last minute surprises that at best interrupt ambulatory surgery center patient flow and at worst
contribute to adverse medical outcomes. This lecture will review: 1) the basic requirements for preoperative
evaluation as determined by payers and regulators 2) models of preoperative evaluation and their merits and 3)
preanesthetic evaluation of selected co-morbidities which are particularly relevant to the outpatient setting such as
obesity, sleep apnea, cardiac disease, and insulin requiring diabetes.
Ground Rules
The ground rules that govern US hospitals as set forth by the Joint Commission state that prior to any operative or
other high risk procedure the patient receives a medical history and physical examination no more than 30 days prior
to surgery. (Standard: RC.02.01.03, PC.01.02.03, EP 5) The American Society of Anesthesiologists has adopted
standards (last amended in 2010) for preanesthesia care which is more specific http://www.asahq.org/For-
Healthcare-Professionals/Standards-Guidelines-and-Statements.aspx; accessed 5/13)
Basic Standards for Preanesthesia Care
The anesthesiologist, before the delivery of anesthesia care, is responsible for:
1. Reviewing the available medical record.
2. Interviewing and performing a focused examination of the patient to:
a. Discuss the medical history, including previous anesthetic experiences and medical therapy.
b. Assess those aspects of the patients physical condition that might affect decisions regarding perioperative
risk and management.
3. Ordering and reviewing pertinent available tests and consultations as necessary for the delivery of anesthesia care.
4. Ordering appropriate preoperative medications.
5. Ensuring that consent has been obtained for the anesthesia care.
6. Documenting in the chart that the above has been performed.
Furthermore the ASA Statement on Documentation (last amended in 2008) lists specific elements of the
preanesthesia evaluation that should be recorded and further states that this is the responsibility of an
anesthesiologist. (www.asahq.org/publicationsAndServices/sgstoc.htm, accessed 5/13) The content of this
evaluation is to include medical history, anesthetic history, medications, appropriate physical exam including vital
signs and documentation of airway assessment, review of objective diagnostic data and medical records, medical
consultations when applicable, assignment of ASA physical status, formulation of anesthetic plan and
documentation of risks and benefits of the plan including discharge issues when indicated. The Center for
Medicare and Medicaid Services (CMS) issued Revised Hospital Anesthesia Services Interpretive Guidelines in
December 2009 (with a clarification in January 2011) which reflect the ASA Statement for documenting
preoperative assessment.
What then is the best approach for satisfying these minimum requirements and professional society expectations?
Clearly, the answer depends on the type of facility, patient population and procedures. Patient selection criteria, and
hence evaluation paradigms, for a free-standing or office based practice will undoubtedly differ from a hospital

205
Page 2

based practice in a tertiary care center. In spite of these differences, there are some unifying guiding principles that
apply to all settings.
For starters, the basic requirements as outlined above need to be satisfied in a manner that is consistent and efficient.
The goal is to determine who is fit for outpatient surgery and then to optimize those candidates. The extent and
focus of the preanesthesia assessment is determined by the patients co-morbidities and type of surgical procedure.
Secondly, a plethora of studies indicate that laboratory exams should be obtained for medical indication
only and that routine testing is of no value, especially in the ambulatory setting. (1-3) However, the information
gained from a thorough history and physical exam and clear communication with members of the perioperative team
is of considerable benefit. Investigators of the Australian Incident Monitoring Study database identified poor airway
assessment, communication problems, and inadequate preoperative evaluation as contributing factors in 197
preventable major adverse events (incidence 3.1%) including death and major morbidity. (4) While laboratory
exams may not be useful, basic patient evaluation and communication of salient features are still essential.
Over the past few decades, several models have been developed to facilitate preoperative communication,
triaging, and medical evaluation. All of these models have their strengths and weaknesses, depending on the facility
(free-standing center, office, hospital, etc.) and the patient population.

Models for Systematic Preoperative Evaluation
Patients can be evaluated on the day of surgery or seen in a preoperative evaluation clinic, or some hybrid version.
The preferred model depends on patient demographics and type of facility. Patients evaluated the day of surgery
have usually had a screening telephone interview with a preoperative nurse several days in advance of the procedure
with anesthesiologist consultation as necessary. This method can be quite effective and efficient if relevant patient
records (i.e., history and physical, laboratory values) are available at the time of the telephone screen, the nurses are
well trained at interviewing, and have algorithms for seeking physician consultation. At the other end of the
spectrum are preoperative evaluation clinics where patients are seen well in advance of surgery by an
anesthesiologist and/or advanced practice nurse. These clinics are usually found in larger tertiary medical centers
and face-to-face visits are reserved for patients with extensive co-morbidities. These clinics require institutional
support and delineated organizational infrastructure. (5)
Regardless of the method used, preoperative screening is cost effective and has the potential to yield
substantial dividends by minimizing delays, cancellations, and opportunity costs. (6-8) While data for ambulatory
surgery are limited, in a large urban medical center Ferschl and colleagues found same day surgery patients seen in
the preoperative evaluation clinic had a cancellation rate of 8.4% as compared with a cancellation rate of 16% for
same day patients who were not evaluated in clinic. Cancelations have significant negative financial impact, with
estimates of over $1500/hr of lost revenue for every hour the OR sits idle (contribution margin).
Data are beginning to emerge using preoperative assessment to predict future hospital costs. In the
National Surgical Quality Improvement Program (NSQIP), 51 preoperative risk factors such as Cr > 1.2 or previous
cardiac surgery, predicted post-operative cost variation due to complications and extended hospital stay. (9) The
authors speculate that preoperative optimization of these risk factors would mitigate the occurrence of postoperative
complications and hospital costs. This remains to be determined.
Whether telephone screens or preoperative clinic visits are used, the model chosen for ambulatory
anesthesia evaluation needs to emphasize patient selection using evidence-based algorithms developed by
anesthesiologists and broadly shared with surgeons and their offices. This will permit effective triaging of patients
and optimization of medical conditions preoperatively. For example, a patient with a drug-eluting cardiac stent
placed within the year who abruptly discontinued clopidigrel would not be an appropriate candidate for elective
surgery, irrespective of the venue. However, the same patient a year later may be perfectly appropriate for a
hospital-based surgery center but not an office setting, depending on the procedure and other co-morbidities.

Medical Evaluation
This discussion will encompass medical co-morbidities that have considerable relevance to the outpatient setting due
to the associated perioperative risks and dilemmas posed by discharging the patient within a few hours of surgery
and anesthesia. Areas of focus include cardiac disease with an emphasis on stents and implantable cardiac rhythm
devices, obesity and obstructive sleep apnea, and diabetes and perioperative glycemic control.

Cardiac
There is an abundance of data, guidelines and opinions to guide preoperative evaluation of cardiac risk. This section
will focus on key studies and guidelines that are applicable to outpatients since the type of surgery is usually limited

205
Page 3

in scope, with minimal fluid shifts. However, most studies, which form the backbone of current guidelines, were
extrapolated from (in) patients having extensive procedures.
In guideline parlance, outpatient procedures are generally considered low risk however, lumping these
procedures can be misleading (i.e., a cataract repair is not equivalent to a rigid bronchoscopy). Consequently, it
becomes incumbent on the anesthesiologist to sort out which patients are at risk and require more extensive
evaluation. Risk stratification methods are useful but they all have their limitations, namely they are often
observational studies at a single institution. Nevertheless, common themes emerge.
A landmark study of 4315 patients over 50 years having noncardiac elective surgery was used to identify
independent risk factors, comprising the Revised Cardiac Risk Index (RCRI). (10) Although major cardiac
complications were rare (2%) six independent risk factors were identified:
High risk surgery (intraperitoneal, intrathoracic, or suprainguinal vascular)
History if ischemic heart disease
History of congestive heart failure
History of cerebrovascular disease
Preoperative treatment with insulin
Preoperative serum creatinine > 2.0 mg/dL

The authors specifically note that (T)he Index is of uncertain generalizability in lower-risk populations, such as
patients who undergo minor procedures.. However, data specifically examining that population is lacking so this
risk index is widely used.
While risk indices can be quite useful, Reilly used a simple and practical - screening tool to predict
perioperative risk, namely self-reported exercise tolerance. Poor exercise tolerance, such as the inability to walk 3
blocks or climb 2 flights of stairs (< 4 METS), is an independent predictor of serious perioperative complications
(OR 1.94, CI 1.19-3.17). Moreover the likelihood of serious complications is inversely related to the number of
blocks walked or flights of stairs climbed. (11)
A decade later, in a single-center observational study, Kheterpal used NSQIP data to identify preoperative
and intraoperative predictors of adverse cardiac events. (12) Their findings are consistent with findings from a
decade earlier, with some modifications. Those independent predictors are:
Age > 68 yrs
Active CHF
BMI > 30 kg/m2
Emergency surgery
Previous cardiac intervention
Cerebrovascular disease
Hypertension
Operative duration > 3.8 hrs
Administration of one or more units of PRBCs
All of the aforementioned predictors except for two (emergency surgery and administration of > 1 unit of PRBC) are
commonly encountered in the ambulatory setting. On a related note, a supporting study by Correll and colleagues
found that age > 65 was an independent predictor of preoperative electrocardiogram abnormalities. (13)
The findings from the aforementioned studies and many, many others led to the most recent (2007)
American Heart Association/American College of Cardiology guidelines on perioperative evaluation for patients
having noncardiac surgery. (14) (These guidelines were updated in 2009 with respect to perioperative beta-
blockade.) There are some key points in these guidelines as they relate to ambulatory surgery. First, ambulatory
surgery is considered as one entity and all ambulatory procedures are considered low risk with reported cardiac
mortality < 1%. Secondly, in the absence of active cardiac conditions, interventions based on cardiovascular
testing in stable patients would rarely result in a change in management and it would be appropriate to proceed with
the planned surgery. In other words, in the absence of active cardiac conditions (unstable coronary syndromes,
decompensated heart failure, significant arrhythmias, and severe valvular disease), additional interventions would
rarely alter perioperative risk for low risk procedures. However, although additional testing may not be warranted
(because it would rarely lead to a meaningful intervention), a complete and thorough history and physical exam
which can probe the presence or absence of active cardiac conditions is essential. The AHA/ACC guidelines
recognize that there are clinical risk factors (which are based on Lees Revised Cardiac Risk Index cited earlier).
However, in the absence of active cardiac conditions, further action is rarely needed.

205
Page 4

Previous Coronary Interventions: Stents and Cardiac Rhythm Devices
Stents
Approximately two million patients per year in Western countries have cardiac stents placed and 90% of
those stents are drug eluting stents which will require long term antiplatelet therapy. About 5% of stented patients
will present for noncardiac surgery within the first year of stent placement. (15,16) The implications of cardiac
stents and antiplatelet therapy on preoperative assessment requires a clinical understanding of the associated risks
and well defined preoperative policies to guide patient selection and evaluation.
With any coronary stent, there are risks, especially during the period of re-endothelialization. Until the
period of re-endothelialization is complete, patients need to remain on dual antiplatelet therapy (i.e., aspirin and
clopidigrel). Bare metal stents (BMS) are layered with endothelial cells after about 4-6 weeks. However, there is a
risk that these stents are vulnerable to restenosis over time hence the development of drug eluting stents (DES).
DES are coated with agents which impair cellular proliferation. This can prevent restenosis but also results in a
longer period of time to stent re-endothelialization. During this period, patients must remain on dual antiplatelet
therapy.
Premature discontinuation of dual antiplatelet therapy, especially in the perioperative period, can be
catastrophic due to stent thrombosis. (17-22) If noncardiac surgery is performed immediately after stent placement
and without antiplatelet therapy, there is a 30% risk of perioperative MI and 20-40% of those are fatal. The risk of
MI and death is 5-10 times higher than waiting the appropriate amount of time.
Practice guidelines are unequivocal in stating that elective surgery be postponed until patients have
completed an appropriate course of antiplatelet therapy. (14,18,22) The duration of antiplatelet therapy is currently
estimated at minimum of 4 weeks for BMS and 12 months for DES, with aspirin continued indefinitely. However,
some patients may be more prone to thrombosis and may need to remain on antiplatelet therapy for longer periods.
Predictors of stent thrombosis are: bifurcated lesions, long stents, diabetes, renal failure and low ejection fractions.
However, until more data are available, the practice guidelines are unequivocal.
The ACC/AHA 2007 Perioperative Guidelines state: Elective procedures for which there is significant
risk of perioperative or postoperative bleeding should be deferred until patients have completed an appropriate
course of thienopyridine therapy (12 months after DES implantation if they are not at high risk of bleeding and a
minimum of 1 month for bare-metal stent implantation).(14) Similarly, an ASA Practice Alert affirms the position
of the ACC/AHA Perioperative Guidelines. (22)
Since ambulatory surgery procedures are usually elective, patients need to defer surgery until 4-6 weeks
after placement of a BMS and one year after DES. Aspirin should be continued in the perioperative period if at all
possible. To avoid confusion and compromised patient care, it is extremely useful for surgery centers to have
policies that reflect these guidelines.
Cardiac Rhythm Devices
The perioperative assessment management of the adult surgical outpatient with a cardiac implantable
electronic device (CIED) a pacemaker, an implantable defibrillator or both, is fairly common. This poses clinical
and administrative challenges. (23-25) Indeed, perioperative management of these devices is the topic of an updated
ASA Practice Advisory. (25)
The indications for the CIED should be fully appreciated, as this often reflects significant underlying
cardiac disease. (23) Permanent pacemakers are indicated for symptomatic third-degree heart block, type II second-
degree heart block, sinus node dysfunction, recurrent neurally mediated syncope as well as some forms of
cardiomyopathy. For example, biventricular pacemakers are considered in patients with significant heart failure
(ejection fraction <35%) despite medical therapy. Implantable Cardiac Defibrillators (ICDs) are indicated in
patients who have had a cardiac arrest that is not due to a temporary condition. This includes a wide array of
problems including ischemia, long QT syndrome, hypertrophic cardiomyopathy or familial cardiomyopathy. Thus
the first question to be asked is: WHY was THIS device placed? The second question is whether the patient (and
procedure) are appropriate for outpatient surgery given the status of the cardiac disease.
If the patient and procedure are appropriate for the facility, then basic information about the devices should
be obtained either during a preoperative visit or telephone call. This should be done well in advance of surgery, so
that there is time to 1) decide if device interrogation or reprogramming by appropriate personnel will be necessary
and 2) have enough time to coordinate personnel for preoperative and postoperative care.

Preoperatively, the following information should be obtained (ASA Practice Advisory):
1. Indication for CIED
2. Is patient device dependent?
3. Type of device and manufacturer (available from manufacturers identification card)

205
Page 5

4. Assess CIED function
Date of last interrogation and results
Current setting
Does the device capture when it paces?
Effect of magnet on pacemaker function (ie, defaults to DOO at # bpm)
Does CIED automatically reset to preoperative settings when a magnet is removed?

5. Likelihood of device interference
Will electromagnetic interference (EMI) be likely during the procedure? (EMI is unlikely if the
device is < 10 years old and bipolar cautery is > 15 cm from device lead or generator)
Based on the likelihood of EMI, is reprogramming the CIED to asynchronous mode or disabling
rate responsive function with a magnet or reprogramming indicated?
Should antitachyarrhythmia functions be suspended? (By whom?)

Appropriate arrangements need to be made preoperatively so that the device can be reprogrammed (if necessary) in
advance of the procedure and immediately after the procedure, without unduly inconveniencing patients or
providers. If the device required reprogramming by the cardiology service/manufacturers representative
preoperatively then original settings will need to be restored postoperatively and before discharge from PACU.
Until those settings are restored, patients need to have cardiac monitoring with the capability to defibrillate
immediately (i.e., defibrillator pads in place).

Obesity
Approximately 36% of the adult US population is obese and ~ 69% are overweight and obese
(http://www.cdc.gov/nchs/fastats/overwt.htm, accessed 5/13). Obesity poses considerable perioperative challenges,
and this is especially true in the outpatient setting where patients are expected to be discharged within a few hours
after surgery. Associated co-morbidities such as obstructive sleep apnea and pulmonary dysfunction impact
postoperative recovery/discharge and hence the patient selection process. A thorough understanding of the common
obesity associated co-morbidities is useful to help formulate not only ambulatory anesthetic management but also
patient selection criteria.
Cardiovascular
There is a direct and independent relationship between obesity and hypertension. (26-28) Furthermore,
obese patients without documented hypertension are prone to occult diastolic dysfunction, probably secondary to
increased circulating blood volume and chronic LV wall stress. (29) Systolic dysfunction associated with obesity is a
later development, and is most often seen among obese patients with body mass index (BMI) > 40kg/m2 for > 10
years. (30) Cardiac function can be difficult to assess preoperatively due to diminished functional capacity.
Consequently, non-invasive testing with appropriate modalities (such as stress echocardiography) may be required if
patients have multiple risk factors or have limited functional capacity. (31,32)
Reconciling the AHA/ACC cardiac evaluation and care algorithm for non-cardiac surgery in obese patients
having ambulatory surgery requires clinical judgment. Indeed, this issue was highlighted in the recent advisory
from the AHA regarding the cardiac evaluation of severely obese patients: (T)hese categorizatons (low,
intermediate and vascular surgery) are used in the decision algorithm for further testing but it is unknown if obesity
influences these categorizaitons. (33) Consequently, this AHA advisory recommends a preoperative ECG in
severely obese patients (BMI > 40 kg/m2) with one risk factor for heart disease. If there are signs of CV disease
(e.g., CAD, RVH consistent with pulmonary hypertension), additional workup based on functional capacity be
pursued if it will change management.
Obesity and obstructive sleep apnea are associated with pulmonary hypertension which poses considerable
perioperative risk. However, diagnostic criteria (such as signs of right heart failure) in the absence of an
echocardiogram are vague, especially in the morbidly obese. The associated postoperative mortality in patients with
pulmonary hypertension across several different inpatient procedures is estimated to be 7-10%. (35,36) Due to
several factors, including intense intra and postoperative monitoring, these patients may not be candidates for the
vast majority of ambulatory procedures and need to be carefully evaluated on a case by case basis.
Obstructive Sleep Apnea (OSA)
The prevalence of OSA in obese patients presenting for bariatric surgery is 71% -77%, depending on (BMI). (37)
OSA is usually not a solitary diagnosis in an obese patient; associated co-morbidities include:
hypertension and increased risk of cardiovascular disease (e.g., stroke and sudden death). (38-40) Sudden cardiac
death in (non-surgical) obese patients is associated with a nocturnal pattern, which is distinctly different than in

205
Page 6

other populations. A review of polysomnograms and death certificates from 112 persons who experienced sudden
cardiac death demonstrated that those with OSA had peak in sudden death from cardiac causes during sleeping hours
(midnight to 6am). In contrast, those without OSA had peak incidence of sudden death after 6am. (41)
In the perioperative setting, patients with OSA have an increased incidence of postoperative complications:
Hwang measured home nocturnal desaturations preoperatively in 172 subjects. Patients with > 5 desaturations/hr
had significantly higher rate of postop complications (15%) vs. those with < 5 events/hour (3%). Complications
were primarily respiratory. (42) Chung evaluated 177 patients deemed at risk for OSA by various screening tools
and then performed polysomnography. (43) Those with apnea-hypopnea index (AHI) >5 as confirmed by
polysomnography had postoperative complication rate that was more than double those with AHI < 5 (27% vs.
12%).
Discerning who actually has OSA is challenging, as the diagnostic gold standard is polysomnography, which
many patients do not obtain. Diagnosis based on screening questionnaires is unreliable. A meta-analysis of clinical
screening tests for OSA illustrates that it is possible to predict severe OSA with a high degree of accuracy.
However, aside from severe OSA, false negative rates range from 14-38% which will miss a significant proportion
of patients. (44)
Nevertheless, simple screening methods have been developed for preoperative use including the STOP-
BANG questionnaire which has a sensitivity from 84% (AHI>5) to 100% (AHI >30). Patients who answer yes to
three or more items are considered to be at high risk of OSA. (43) Other similar validated tools incorporate upper
airway anatomy to enhance predictive modeling. (45)

STOP-BANG (Chung 2008)
1. Snoring
Do you snore loudly (louder than talking or loud enough to be heard
through closed doors)?
5. BMI
BMI more than 35 kg/m2?
2. Tired Do you often feel tired, fatigued, or sleepy during daytime?

6. Age over 50 yr old?
3. Observed
Has anyone observed you stop breathing during your sleep?
7. Neck circumference greater than 40 cm?
4. Blood pressure
Do you have or are you being treated for high blood pressure?
8. Male gender?

A main concern for patients with OSA is their suitability for ambulatory surgery. Is it safe to send these patients
home to an unmonitored setting after anesthesia and surgery? Data are scant since important determinants such as
severity of OSA, type of anesthetic and type of procedure have not been individually examined. Instead, we have
expert opinions extrapolated from inpatient setting and used as guide. The ASA Practice Guidelines for the
Perioperative Management of Patients with OSA (2006) state that literature is insufficient to make recommendations
and those guidelines are based on consultant opinion. (46) Moreover, the clinical screening tool suggested in ASA
Guideline has not been clinically validated. The ASA Guidelines recommend that anesthesiologists determine
whether a given surgical procedure and individual patient with (or at risk for) OSA is appropriate for outpatient
setting. Factors to consider include:
(1) severity of sleep apnea status
(2) anatomical and physiologic abnormalities
(3) status of coexisting diseases
(4) nature of surgery
(5) type of anesthesia
(6) need for postoperative opioids
(7) patient age
(8) adequacy of postdischarge observation
(9) capabilities of the outpatient facility

Specifically in reference to outpatients, the ASA Guidelines recommends: These patients should not be
discharged from the recovery area to an unmonitored setting (i.e., home or unmoniotored hospital bed) until they are
no longer at risk for postoperative respiratory depression. The Guidelines also recommend observing patients
while breathing room air in an unstimulated environment and note that this may require a longer ambulatory stay
(i.e., 3 hours longer than non-OSA counterparts and median of 7h after last episode of airway obstruction or

205
Page 7

hypoxemia while breathing room air in an unstimulating environment). Practical application has been challenging
because patients frequently do not have formal preoperative diagnosis of OSA and severity is difficult to estimate.
Most likely, recommendations in this arena will continue to evolve as more relevant data become available.
Obesity Hypoventilation Syndrome
Obesity Hypoventilation Syndrome (OHS) exists in about 10-20% of patients with both obesity and OSA,
and is characterized by the triad of obesity, daytime hypoventilation and sleep disordered breathing. Findings in
patients with OHS include upper airway obstruction, restrictive chest physiology, blunted central respiratory drive,
pulmonary hypertension and increased mortality. The mainstay of treatment is continuous positive airway pressure
and weight loss. However, these patients are at higher risk for morbidity and mortality as compared to based who
are eucapneic and obese. There are limited data on the perianesthetic management of these high risk patients, in any
setting. (47)

Diabetes
Approximately 14% of US adults aged >20 years and ~27% of individuals >65years have diabetes or impaired
fasting glucose. (http://www.cdc.gov, accessed 5/13) In order to evaluate potential end-organ damage and maintain
metabolic homeostasis these patients require a focused assessment to a) gauge appropriateness for procedure on an
outpatient basis, with a focus on potentially difficult airway in patients with long-standing Type I diabetes and b)
guide preoperative fasting and insulin instructions.
Cardiovascular disease is the major cause of morbidity and mortality amongst patients with diabetes, with
the most common conditions being hypertension and dyslipidemias. The most recent American Diabetes
Association guidelines (2012) recommend that patients with diabetes be treated to a blood pressure < 130 mm Hg
systolic and < 80 mmHg diastolic. (48) Furthermore, it is recommended that all patients with diabetes have serum
creatinine measured and cardiovascular risk factors such as dyslipidemia, hypertension, smoking, positive history of
coronary disease and presence of mico- or macroalbuminemia assessed annually. This is part of routine health
maintenance and is independent of surgical need. Further cardiac testing irrespective of the need for surgery -
should be considered in diabetics with typical or atypical anginal symptoms or an abnormal resting ECG. (48)
Patients with diabetes may be on complicated regimens to achieve glycemic goals in order to reduce the
risk of micro and macrovascular complications. In addition to insulin and conventional oral hypoglycemic agents,
treatment may include relatively new classes of gastrointestinal hormones namely incretins and amylin which
impact glucose homeostasis. (49) In adults glycemic goals are: A1C < 7 % and preprandial glucose 70-130mg/dl
and peak postprandial glucose < 180 mg/dl. (48) Due to concerns about perioperative hypoglycemia as delineated in
the NICE-SUGAR study, perioperative glycemic goals as suggested by the ADA are in the range of 120 180
mg/dl. (48,52)
To achieve those targets and simplify preoperative instructions, ambulatory surgery centers usually have
protocols which address the type and quantity of insulin (and other hypoglycemic agents) to be administered
preoperatively, recommendations for monitoring blood sugar preoperatively and treating hypoglycemia while
adhering to NPO guidelines. A common feature in these protocols is to include a basal form of insulin on the day of
surgery (usually as a fraction of the typical intermediate acting insulin or long acting insulin) and withhold oral
hypoglycemic agents and incretins. (48-50) A basic understanding of the time course of commonly used insulins,
as outlined below, is integral to developing effective preoperative instructions.
Insulin Comparison
Action Generic name Onset Peak Duration
Rapid Insulin Aspart 15 min 45-90 min 3-5 hrs
Short Regular Human Insulin 30 min 2.5-5 hrs 8 hrs
Intermediate NPH Insulin 1.5 hrs 4-12 hrs ~24 hrs
Long Insulin Glargine ~1 hr - up to 24 hrs
Long Insulin Detemir ~3 hrs ~6-8 hrs up to 24 hrs
Mixtures Insulin Aspart Protamine, Insulin Aspart 60 min 1-4 hrs up to 24 hrs
Mixtures Insulin NPH/ Regular, 70/30 ~30 min 2-12 hrs ~24 hrs

205
Page 8

Summary
Outpatient evaluation is the basis for patient selection, which is fundamental for safe and efficient ambulatory
anesthetic management. Models of evaluation include: assessment on the day of surgery, telephone triage, or
preoperative clinic visit. Each model has its advantages, and adoption depends on the facility and patient
demographics. Irrespective of the method, patients are evaluated with discharge planning in mind. Patients should
be suitable for elective surgery with the expectation that they can be safely discharged home within a few hours of
their procedure. Several co-morbidities affect this process and serve to refine patient assessments and selection
criteria.

References
1) Chung F, Yuan H, et al. Elimination of preoperative testing in ambulatory surgery. Anesth Analg 2009; 108:467-75
2) Finegan B, et al Selective ordering of preoperative investigations by anesthesiologist reduces the number and cost of tests. Can J Anesth 2005;
52:575-80
3) Schein OD, et al. The value of routine preoperative medical testing before cataract surgery. N Engl J Med 2000; 342:168-75
4) Kluger M, Tham E, et al. Inadequate pre-operative evaluation and preparation. Anaesthesia 2000; 55:1173-1178
5) Bader AM, Correll DJ. Organizational infrastructure of the preoperative evaluation center. In, Preoperative Assessment and Management. 2
nd

edition. Editor: BobbieJean Sweitzer, M.D. Lippincott Williams & Wilkins/Wolters Kluwer. 2008
6) Correll D, Bader A, et al. Value of preoperative clinic visits in identifying issues with potential impact on operating room efficiency.
Anesthesiology 2006; 105:1254-9
7) Ferschl M, Tung A, et al. Preoperative clinic visits reduce operating room cancellations and delays. Anesthesiology 2005; 103:855-9
8) Gibby G. How preoperative assessment programs can be justified financially to hospital administrators. Int Anesthesiol Clin. 2002; 40:17-30
9) Davenport D, Henderson W. et al. Preoperative risk factors and surgical complexity are more predictive of costs that postoperative
complications. Annals of Surgery 2005; 242:463-471
10) Lee T, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation
1999; 100:1043-1049
11) Reilly D, et al. Self-reported exercise tolerance and the risk of serious perioperative complications Arch Intern Med 1999; 159:2185-2192
12) Kheterpal S, OReilly M, et al. Preoperative and Intraoperative predictors of cardiac adverse events after general, vascular, and urological
surgery. Anesthesiology 2009; 110:58-66
13) Correll D, Hepner D. et al. Preoperative Electrocardiograms. Anesthesiology 2009; 110:1217-22
14) Fleisher L, Beckman, et al. ACC/AHA Guidelines on perioperative cardiovascular evaluation for noncardiac surgery. Circulation 2007; 116
15) Vicenzi M, Meislitzer T. et al. Coronary artery stenting and non-cardiac surgery. Br. J Anaesth 2006; 96:686-93
16) Spaulding C, et al. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007; 356:989-97
17) Chassot P-G, Delabays A, et al. Perioperative antiplatelet therapy. Br J Anaesth 2007; 99:316-28
18) Grimes C, Bonow R, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents.
Circulation 2007; 115:813-818
19) Mehta S, Yusuf S. et al. PCI-Cure Study. Lancet 2001; 358:527-33
20) Rabbits J, Nuttall G. et al Cardiac risk of noncardiac surgery after percutaneous coronary intervention with durg-eluting stents.
21) Nuttall G, Brown M. et al. Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention. Anesthesiology 2008;
109:588-95
22) Practice alert for the perioperative management of patients with coronary artery stents. Anesthesiology 2009; 110:223
23) Myerberg R. Implantable cardioverter-debrillators after myocardial infarction. N Engl J Med 2008; 359:2245-53
24) Stone M, Apinis A. Current perioperative management of the patient with a cardiac rhythm management device. Semin Cardiothorac Vasc
Anesth 2009; 13:31-43
25) Practice Advisory:Perioperative Management of Cardiac Implantable Electronic Devices: Pacemakers and Implantable Cardioverter-
Defibrillators. Anesthesiology 2011; 114:24761
26)Kannel WB, Brand N, Skinner J, Dawber T, McNamara P. The relation of adiposity to blood pressure and development of hypertension
Annals Int Med 1967; 67:48-59
27) Havlik R, Hubert H, et al. Weight and hypertension. Annals of Internal Medicine 1983; 98:855-859
28) Jones D, Kim J, Andrew M. Kim S. Hong Y. Body mass index and blood pressure in Korean men and women. J Hypertension 1994; 12:1433
29) Pascual M, Pascual D, Soria F, et al. Effects of isolated obesity on systolic and diastolic left ventricular function. Heart 2003; 89:1152-1156
30) Alpert M. Obesity cardiomyopathy: Pathophysiology and evolution of the clinical syndrome. Am J Medical Sciences 2001; 321:225-236
31) Gugliotti D, Grant P, et al. Challenges in cardiac risk assessment in bariatric surgery patients. Obes Surg 2008; 18:129-133
32) Kuruba R, et al. Preoperative assessment and perioperative care of patients undergoing bariatric surgery. Med Clin N Am 2007; 339-351
33) CV evaluation and management of severely obese patients undergoing surgery: A science advisory from the American Heart Association.
Circulation 2009; 120;86-95
34) Subramaniam K, Yared J, Management of pulmonary hypertension in the operating room. Semin Cardiothorac Vasc Anesth 2007; 11:119
35) Lai H-C, et al. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth 2007; 99:184-90
36) Ramadrishna G, Sprung J, et al. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors for preoperative
morbidity and mortality. J Am Coll Cardiol 2005; 45:1691-9
37) Lopez P, et al. Prevalence of sleep apnea in morbidly obese patients for weight loss surgery evaluation. Am Surg 2008; 74:834-38
38) Isono S. Obstructive sleep apnea of obese adults. Anesthesiology 2009; 110:908-21

205
Page 9

39) Lawate N, et al. Epidemiology, risk factors, and consequences of OSA and short sleep duration. Prog CV Dis 2009; 51:285-293
40) Yaggi H, Concata J, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034-41
41) Gami A, Howard D, Olson E, Somers V. Day-night pattern of sudden death in obstructive sleep apnea. N Engl Med 2005; 352:1206-14
42) Hwang D, Shakir N, et al. Association of sleep-disordered breathing with postoperative complications. Chest 2008; 133:1128-1134
43) Chung F, Yegneswaran B, et al. Validation of the Berlin questionnaire and ASA checklist as screening tools for obstructive sleep apnea in
surgical patients. Anesthesiology 2008; 108:822-30
44) Ramachandran S, Josephs L. A meta-analysis of clinical screening tests for obstructive sleep apnea. Anesthesiology 2009; 110:92839
45) Ramachandran S, et al . Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg 2010; 110:1007-15)
46) Practice guidelines for the perioperative management of patients with obstructive sleep apnea. Anesthesiology 2006; 104:108193
47) Chau EHL, et al Obesity Hypoventilation Syndrome: Review of Epidemiology, Pathophysiology, and Perioperative Considerations
Anesthesiology 2012; 117:188205
48) Standards of Medical Care in Diabetes2012. Diabetes Care 2012; 35:S11-S63
49) Chen D, Lee S, et al. New therapeutic agents for diabetes mellitus: implications for anesthetic management. Anesth Analg 2009; 108:1803-10
50) Mooradian A, Bernbaum M. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med 2006; 145:125-134
51) Clements S, Briathwaite S, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care 2004; 27:553
52) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283-97

Disclosure

Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved. Note: This publication
contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using
individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
212
Page 1
Anesthesia for Outpatient Diagnostic or Therapeutic Radiology
Thomas W. Cutter, M.D. Chicago Illinois
Diagnostic radiology procedures are anatomic or functional, minimally to non-invasive, cause little
pain or discomfort, and are most frequently performed without anesthesia services. When anesthesia care is
requested, it is typically because of the patients unique physiological or psychological needs or desires.
Therapeutic techniques are often more invasive and more likely to require an anesthesiologist because of the
complexity of the procedure and the comorbidities and discomfort of the patient. All therapeutic procedures are
to some degree interventional, but many diagnostic procedures are not, although an interventional radiologist
may perform them. Conducting anesthetics in the radiology department can be challenging because of the
patients comorbidities, the procedure, the anesthetic, the radiology equipment, and the environment.
Anesthetics can be one of three types: monitored anesthesia care (MAC), regional anesthesia, or
general anesthesia. Selection depends on the procedure and the relative risks and benefits to the patient.
Monitored anesthesia care, the least invasive anesthetic, is indicated when a procedure may nominally require
deep sedation or increased monitoring.
1
The anesthesiologist administers intravenous sedation and analgesia; the
proceduralist may give an additional local anesthetic at the site. Monitored anesthesia care is a physician service
that is distinct from moderate sedation because the anesthesia provider must be able to apply resources to
support life and ensure patient comfort and safety during diagnosis or therapy.
2

Diagnostic Radiology
Iodinated contrast media is used in both diagnostic and interventional radiology and may cause adverse
(anaphylactoid) reactions or renal dysfunction. Adverse reactions involve direct cellular effects, including
enzyme induction and activation of the complement, fibrinolytic, kinin, and other systems.
3
Manifestations
range from relatively benign itching to life-threatening cardiovascular or ventilatory collapse. Prophylaxis and
treatment for the former include antihistamines and steroids, while advanced cardiac life support measures may
be needed for the latter. Anaphylaxis is quite rare and is probably not a result of the iodine in the contrast
material.
4

Patient-specific risk factors for renal complications include chronic renal disease, diabetes mellitus, heart
failure, older age, anemia, and left ventricular systolic dysfunction. Contrast-specific risk factors are high
osmolarity, viscosity, volume, and ionic media. For patients with renal disease, diabetes, proteinuria,
hypertension, gout, or congestive heart failure, serum creatinine levels should guide the radiologists
administration of the contrast material. Adequate intravascular volume, bicarbonate, and low volumes of iso- or
low-osmolar contrast are indicated. Diabetic patients with preexisting renal dysfunction who also take
metformin have developed severe lactic acidosis after an iodinated contrast study. Thus, metformin should be
discontinued at the time of or before the procedure, withheld for 48 hours subsequent to the procedure, and
reinstituted only after renal function has been re-evaluated and found to be normal.
5
Intravenous gadolinium for
magnetic resonance imaging (MRI) contrast studies is not problematic during the anesthetic. Ultrasound contrast
is achieved through the intravenous administration of echogenic microbubbles, which carry an FDA warning
that patients with pulmonary hypertension or unstable cardiopulmonary conditions be closely monitored during
and for at least 30 minutes after administration.
6
Although barium is not an intravenous contrast, it should be
mentioned because it may pose an aspiration risk after ingestion during deep sedation or general anesthesia.
Anatomic Imaging
The ASA has issued a specific practice advisory
7
emphasizing a location or position for optimal patient
observation and vigilance during delivery of anesthesia in the MRI. The American College of Radiologists and
the Joint Commission on the Accreditation of Healthcare Organizations have also established standards,
guidelines, and recommendations for the MRI suite.
8-10
Anesthesia equipment must conform to the criteria of
the American Society for Testing and Materials and the Food and Drug Administration.
Patient monitoring and the administration of an anesthetic in the MRI suite are difficult because the
anesthesia provider is physically separated from the patient during the study. The patient must be observed
continually, either through a window into the scanner room or with a camera trained on the patient and a video
monitor in the control booth. Vital signs must be monitored through a window or via a camera trained on a
monitor in the scanner room or a slave monitor in the control room.
Monitor placement and the length and routing of leads, wires, and tubing should be considered to prevent
entanglement or traction as the MRI tables moves. Coiling monitor wires (e.g., pulse oximeter,

212
Page 2

electrocardiogram) should be avoided because this can cause patient burns.
11
Patient temperature should be
monitored because it may increase from the heat of radiofrequency radiation within the magnetic field,
12
or it
may decrease by radiation, conduction, convection, and evaporation. Monitoring temperature intermittently
instead of continuously may avoid the possibility of burns from the thermistor during long sessions or in
critically ill patients.
13

Medical emergencies must be anticipated and a plan in place to treat them. Although advanced cardiac life
support may be instituted on a patient still in the scanner, prompt relocation outside the scanner room gives
better access to the patient and is safer for the staff. If an emergency requires the magnet to be shut down
quickly, (quenching)
14
the liquid cryogen boils off rapidly and releases enormous amounts of helium vapor, so
an evacuation plan must be in place. The scanner is noisy and there have been reports of patient hearing loss
following MRI scan, so some form of ear protection is advisable, even for unconscious patients.
15

Airway management must be scrupulous and conservative because of the distance and barriers between the
anesthesiologist and the patient. It may be best to secure the airway outside of the scanner room and then
transport the patient into the room.
Electromagnetic waves (X-rays) have been incorporated into a number of different imaging modalities,
including static two-dimensional X-rays, dynamic two-dimensional X-rays (fluoroscopy) and three-
dimensional computed tomography (CT). Major issues include the anesthesia providers radiation exposure and
distance from the patient. The former is addressed by distance, lead, and personal dosimetry; the latter, by
following protocols for monitoring similar to those in the MRI suite. The U.S. Occupational Safety and Health
Administration has established limits for the exposure of individuals to radiation in restricted areas,
16
and
institutional guidelines should adhere to these standards. Radiology equipment (e.g., C-arm or CT aperture) can
make airway management and access to the patient difficult, and the anesthesia equipment often adds to the
difficulty of maneuvering in the suite, as can the encumbrance of a lead apron. The configuration of the table
and other equipment means that patient positioning, especially lateral or prone, can be problematic.
For diagnostic fluoroscopy procedures, the contrast material may be ingested (e.g., barium swallow),
administered per rectum (e.g., barium enema), or injected intravenously (e.g., intravenous pyelogram) or
intrarterially (e.g., aortogram). Many procedures can be performed without anesthesia support, unless a patients
comfort, comorbidities, or cooperation requires it. For example, diagnostic angiography is often performed with
no or only light to moderate sedation and analgesia by cardiologists; percutaneous transhepatic cholangiography
may be performed by a radiologist using the same regimen.
Computed tomography is an easily tolerated procedure for most patients and is relatively safe for personnel
since the X-ray beam is tightly focused. Although studies are performed in a few seconds or minutes, they
require a still patient, so cooperation must be assured either through patient reassurance or medications.
Like diagnostic X-rays, diagnostic ultrasound imaging is noninvasive and easily tolerated. In the absence of
invasive techniques, anesthesia support is not warranted; if it is indicated, no encompassing techniques or
precautions are necessary.
Functional (Brain) Imaging
Functional brain imaging reveals blood flow, metabolism, or electrical activity. Electrical activity is
represented by the electroencephalogram (EEG), which directly measures the electrical potential between two
scalp electrodes. The EEG is spatially limited by the number of electrodes, a limitation that has been improved
by high-density arrays of over 120 electrodes.
17
Magnetoencephalography is a more sensitive technology that
records local magnetic fields produced by neuronal electrical activity in the brain via extremely sensitive
instruments such as superconducting quantum interference devices.
Other functional brain imaging techniques rely on the remarkably consistent relationship between regional
changes in the cellular activity of the brain and changes in the blood flow and metabolism of the region.
18
Blood
flow is revealed by functional MRI (fMRI), positron emission tomography (PET), and single-photon emission
computed tomography (SPECT). A functional MRI distinguishes between the distinct magnetic resonance
signals of oxygenated hemoglobin (diamagnetic) and deoxygenated hemoglobin (paramagnetic). A less common
technique uses arterial spin labeling to magnetically alter the protons in the water molecules of the arterial blood
in the neck and then identify them as they perfuse the brain. Functional MRI has been useful in determining the
functional relationship between tumors and surrounding tissues.
19

A PET scan involves injecting a radionuclide molecule that emits positrons which annihilate electrons and
produce gamma rays that are then detected by the scanner. The amount of imaged tracer reflects blood flow and
concomitant brain activity. Regional metabolic activity can be seen if the radionuclide molecule contains [F]-2-
fluoro-deoxy-d-glucose (FDG),
20
which concentrates in the more active areas. Positron emission tomography is
often combined with CT or MRI to correlate anatomy with function. Like PET, SPECT detects gamma rays but
the tracer material itself emits gamma radiation as it decays. More material indicates greater blood flow.
Metabolic activity also can be revealed through magnetic resonance spectroscopy, which detects signals
specifically from hydrogen or phosphorous to determine the concentration of brain metabolites in tissue; greater
levels indicate greater metabolic activity.

212
Page 3
These procedures are often performed on awake individuals, although occasionally a patients psychological
or physical condition may require the use of sedation or general anesthesia. Administering anesthetic
psychotropes may result in artifacts that disrupt the remarkably consistent relationship between regional
changes in the cellular activity of the brain and changes in its circulation and metabolism. Isoflurane is
associated with a relatively global reduction in brain glucose metabolism during PET with FDG.
21
Propofol
causes a larger absolute metabolic reduction, a greater suppression of cortical metabolism, and significantly less
suppression of basal ganglia and midbrain metabolism.
22
Propofol preferentially decreased cerebral blood flow
in brain regions previously implicated in the regulation of arousal, performance of associative functions, and
autonomic control and had more regional impact.
23
Using fMRI, morphine demonstrates a regional effect,
decreasing the signal in cortical areas as do propofol and midazolam, but activating endogenous analgesic
regions such as the periaqueductal gray, the anterior cingulate gyrus (decreased signal), and hypothalamus
(increased signal).
24
Midazolam impacts fMRI by significantly altering the signal in the brains auditory and
visual cortices.
25
Mechanical maneuvers can also influence imaging outcomes, such as an increased mean
airway pressure (e.g., continuous positive airway pressure) reducing the fMRI signal in the primary visual
cortex.
26

There are no strong recommendations for anesthetic technique for these diagnostic procedures. Indeed,
functional brain imaging techniques such as PET and fMRI have been used to study the effects of general
anesthesia on the brain, and a systematic baseline response to anesthetics has not yet been developed.
27-29
If an
anesthetic is required, the anesthesiologist should consider the anesthetics impact on cerebral blood flow,
metabolism, and electrical activity and choose agents with minimal effect, combine agents to minimize their
effects, and maintain steady-state anesthetic conditions during the study.
Therapeutic Radiology
Therapeutic radiology has grown from relatively simple percutaneous procedures for aspiration/drainage to
complex embolizations of arteriovenous malformations and the placement of arterial stents. It epitomizes the
adage, There is no body structure that cannot be reached with a number 14 needle and a good strong arm,
especially now that structures can be visualized in real time. Minor procedures such as biliary tube placement or
exchange, tunneled catheter placement, vascular interventions, and other catheter insertions have been
performed using moderate sedation, during which nurses, trained in critical care, monitor the patient and
administer low-dose midazolam and fentanyl.
30
Adverse events are few and minor without clinical impact.
30
Less rather than more sedation is the rule in Europe, although general anesthesia is more common in Europe
when anesthesia is utilized. In one East Coast academic center, MAC or general anesthesia was used for only
10% of cases for interventional radiology.
31

As it increases in volume and complexity, interventional radiology is more often being performed in emergency
settings and also includes more high-risk patients who cannot tolerate a more invasive (e.g., surgical)
intervention, making an anesthesiologist necessary.
32
The conditions for performing an anesthetic for
therapeutic radiology procedures include those for diagnostic radiology: monitoring from afar, avoiding
radiation exposure, working with radiology equipment and prohibiting ferrous materials in the MRI suites. The
choice of anesthetic technique for interventional radiology is procedure specific with wide variations, depending
on the patient and the skill sets of the interventionalist and associated personnel. The anesthetic presents more
challenges because the procedure is invasive and the patient may have several comorbidities. The goal of a
completely still patient, both for the success of the procedure and the safety of the patient, can sometimes be
attained by sedation and analgesia administered either by the proceduralist or an anesthesia provider. If a
predictable ventilatory pattern in the patient is desired, it can be achieved by the judicious administration of
medications to a cooperative patient or by general anesthesia with controlled ventilation. Some particularly
painful procedures (e.g., radiofrequency ablation of osteoid osteomas) require a subarachnoid block or general
endotracheal intubation by an anesthesiologist .
31
Other procedures associated with extreme fluid shifts (e.g.,
drainage of ascites fluid or blood loss during a uterine artery embolization) benefit from the presence of
someone who is well versed in intravenous access. Some procedures may require anticoagulation and the means
to measure its effects (e.g., activated coagulation time).
Fluoroscopy is the imaging modality typically used for endovascular stent placement. There is a significant
procedural potential for complications and the patient may have been considered too sick for open surgery.
33

Among the anesthetic techniques used for endovascular aortic repair are general, epidural, combined
epidural/spinal,
34
spinal, and continuous spinal.
35
Even when performed under MAC, one must be prepared for
significant blood loss and invasive monitoring.
36
Mild hypotension, and an immobile patient are important when
deploying the stent. Spinal cord injury may be decreased by limiting hypotension, monitoring evoked potentials
and cerebrospinal fluid (CSF) pressure, and measuring CSF proteins (S100 !) during thoracic aneurysm
stenting.
37
An intrathecal drain may be beneficial for thoracic aneurysm procedures,
38
but it may also lead to
catheter-related complications.
39

Carotid artery stenting may be superior to traditional carotid endarterectomy in patients who are at overall
increased surgical risk.
40
Aspirin and clopidrogel are often administered before the procedure and heparin is

212
Page 4
given intraoperatively while activated clotting time is monitored. Stenting may be performed in a patient under
MAC, with close attention paid to central nervous system changes and bradycardia,
33
or under general
anesthesia. General anesthesia depresses barorecepter reflex sensitivity and induces hemodynamic stability,
potentially decreasing complications.
41

Stenting to improve blood flow through iliac, popliteal, subclavian, or renal arteries does not mandate the
presence of an anesthesiologist
42
unless the patients comorbidities require it. Stenting of venous outflow has
been used for chronic nonmalignant or malignant obstruction of the femoroiliocaval vein,
43
and patients with
neoplastic superior vena cava syndrome have received palliative stents without sedation.
44

A transjugular intrahepatic portosystemic shunt relieves portal hypertension by using an expandable metallic
stent to create an artificial channel between the branches of the portal and hepatic veins. It is typically
performed under MAC or general anesthesia,
45
with the patients mental status, ability to tolerate the procedure
without moving, overall hemodynamic status, and ease of airway management dictating the type of anesthesia.
Significant comorbidities can include pathological shunting in vascular beds, leading to increased cardiac output
and heart failure. Ascites, pleural effusions, intrapulmonary shunting, pulmonary hypertension, hepatorenal
syndrome, encephalopathy, and coagulopathies are common in these patients. Because of hepatic insufficiency,
the anesthetic agents selected should not depend on the liver for clearance.
46
A cirrhotic cardiomyopathy is
prone to a prolonged Q-Tc interval, which may deteriorate into a torsades de pointes arrhythmia.
Thrombolysis results from the local infusion of tissue plasminogen activators that create plasmin with
ensuing fibrinolysis. Common agents include streptokinase, urokinase, and recombinant formulations.
Thrombolysis is used in patients with myocardial infarction, ischemic stroke, pulmonary embolism, thrombosed
dialysis access, portal vein thrombosis, and acute limb ischemia. Anesthesia is seldom required, but if it is, the
anesthetic depends on the patients comorbidities and avoiding trauma during airway maneuvers. Neuraxial
regional anesthesia is contraindicated.
47

Inferior vena cava filters are placed in patients who have a history of or who are at risk for deep vein
thromboses in the lower extremities. Access is obtained through the right internal jugular vein or a femoral vein.
The procedure may be performed without sedation, although anxiolysis or moderate sedation may be
administered by the interventional radiologist. General anesthesia or MAC is occasionally necessary.
In balloon angioplasty, a narrowed or obstructed blood vessel is widened with a balloon-tipped catheter.
Carotid angioplasty has been performed with deep cervical plexus blockade,
48
MAC, or general anesthesia. The
same concerns apply as for carotid stenting, which is often preceded by balloon angioplasty. Relatively minor
procedures, such as percutaneous transluminal angioplasty of the infrarenal aorta, can be safely performed with
only local anesthesia by the interventionalist.
49

Chemoembolization is currently limited to either primary or metastatic hepatic tumors,. A catheter is inserted
into the femoral artery and guided under fluoroscopy into the hepatic artery. Contrast material is then injected to
identify the arterial supply to the tumor. A chemotherapeutic agent such as doxorubicin is then injected,
followed by an embolic agent such as iodized poppy seed oil, which both limits the tumors blood supply and
traps the agent in close proximity to the tumor. Combination therapy with cisplatin, doxorubicin, and mitomycin
C often enhances the tumor-specific toxicity.
50
The procedure is typically performed without an
anesthesiologist. If anesthesia is requested, the primary anesthetic concerns are patient comorbidities,
coagulopathies, and hepatic insufficiency.
Vascular access is the placement of catheters in large veins for the infusion of medications (e.g.,
chemotherapy, parenteral feedings, antibiotics), dialysis, or blood sampling. Adults seldom require an anesthetic
for catheter placement, but if anesthesia is needed, special attention is given to the patients coexisting diseases
and to the risk of air emboli through an open, large-bore catheter during spontaneous ventilation.
Uterine fibroids, varicoceles, esophageal varices, and arteriovenous malformations can be embolized under
fluoroscopy. A catheter is inserted through a large artery or vein with the tip positioned near the structure to be
embolized. Particles (e.g., gelfoam or particulate agents such as gelatin-impregnated acrylic polymer spheres),
sclerosing agents (e.g., alcohols), metal coils, or liquid glue are used. The procedure is typically performed
without an anesthesiologist.
For uterine artery balloon occlusion in parturients at risk for hemorrhage, both general
51
and epidural
52
anesthesia have been utilized. An epidural catheter is placed before the balloon catheter is inserted to avoid
displacement of the balloon when the patient is positioned and to provide analgesia should the patient undergo a
cesarean section. Preparations should be in place for adequate intravenous access and invasive monitoring.
In percutaneous nephrolithotomy, medium-sized or larger kidney stones are removed from the urinary tract
with a nephroscope. The patient is placed prone and a track is created through a small incision above the kidney,
through which dilators and finally the nephroscope are inserted. If the stones are small, they may be removed
directly. For larger stones, percutaneous nephrolithotripsy can break up the calculi into manageable pieces; this
procedure typically requires a neuraxial block or general anesthesia.
53
Risks include excessive fluid absorption,
dilutional anemia, hypothermia, the potential for significant blood loss,
54
and renal insufficiency. Potential
complications are many and include pneumothorax or hydrothorax, pneumonia/atelectasis, paralytic ileus,

212
Page 5
nephrostomy tube dislodgment, urine drainage from the flank lasting more than 1 week, infection, urinoma
formation, renal pelvic laceration, ureteral avulsion, ureteropelvic or ureteral stricture, bowel injury, or escape of
stone fragments into the retroperitoneum.
55

Percutaneous biliary drainage may be performed with local anesthesia at the site of the drain tube and with
supplemental intravenous sedation and analgeisa. When pain is anticipated from large drainage catheters or
dilatation of the transhepatic tracts, epidural or general anesthesia is recommended.
56
Hepatic insufficiency and
the potential for blood loss should be considered.
Ablative therapies demand cross-sectional images for accurate needle, probe, or catheter placement, which is
accomplished with CT, MRI or ultrasound imaging. The same general imaging-specific caveats apply as for
other therapeutic and diagnostic procedures. Thus, radiation exposure in the CT suite is monitored, and
precautions against ferrous materials are taken in the MRI suite. The preanesthesia evaluation focuses on patient
comorbidities.
Hyperthermic ablation includes radiofrequency (RFA), microwave, or laser ablation. In RFA, the most
common procedure, electrical currents in the radiofrequency range heat an electrode that has been
percutaneously or directly placed within a tumor, with kidney, lung, breast, bone, and liver being common
targets. Because healthy tissue is better able to withstand heat, radiofrequency energy preferentially destroys the
tumor and only a small edge of normal tissue around its edge. The heat also cauterizes small blood vessels,
potentially reducing hemorrhage. Moderate sedation is often adequate for the percutaneous approach.
57
General
and epidural anesthesia are often used for RFA of renal cell tumors.
58
Since the ablation process produces heat,
precautions must be taken when the electrode is adjacent to critical structures. For example, during RFA for a
mediastinal lymph node, a temperature probe was applied to the endotracheal tube cuff to monitor the tracheal
temperature. When temperature rose, chilled saline was substituted for air in the cuff to prevent tracheal
trauma.
59

Cryoablation is used for tumors in the lung, liver, breast, kidney, or prostate. Liquid nitrogen or
gaseous argon destroys tissue by direct freezing, denaturation of cellular proteins, cell rupture, cell dehydration,
and ischemia. Patient comfort and safety have been provided with local or general anesthesia.
60
In lung
cryoablation, inflammation may result from the thawing phase of the ablated tissue. Cracking of a cryoablated
liver may cause significant hemorrhage.
50

Interventional Neuroradiology
Interventional neuroradiologists use imaging techniques combined with catheters and other devices to treat
vascular lesions in the central nervous system (CNS) and surrounding tissues. They either occlude blood flow
through abnormal vessels or increase blood flow in occluded vessels.
61
Cross-sectional imaging techniques
assist in diagnosis, and the procedures are performed under fluoroscopy.
Anesthesiologists are often needed because of the complexity of the procedure, the medical status of the
patient, or the need for immobility. The preanesthesia assessment focuses on the patients neurologic status and
comorbidities. An anesthetic plan must consider the potential for disease progression or iatrogenic
complications. Consultation with a neuroradiologist determines whether the patient must be responsive for
continuous CNS evaluation or whether rapid emergence from general anesthesia is preferred. Anesthetic
medications for a responsive (MAC) patient include propofol, dexmedetomidine, and fentanyl; for general
anesthesia, propofol, sevoflurane, and desflurane.
62
Nitrous oxide should be avoided because of the potential for
enlarging emboli. Laryngeal mask airways may be considered for airway management.
Intraprocedural concerns include elevated intracranial pressure, hemorrhage, blood pressure, and
cerebrovascular occlusion. Control of carbon dioxide may be necessary for certain procedures. Hypercapnia has
been used to vasodilate cerebral vessels for catheter entry, to enhance catheter propagation during superselective
cerebral catheterization, and to increase cerebral venous outflow, thereby favoring movement of an embolizing
agent away from intracranial drainage pathways.
63
Hypocapnia may be used to decrease cerebral blood flow and
lower intracranial pressure. Patient considerations include temperature, either warm for comfort or cool for
cerebral protection.
64
Bladder distention may be a concern because these are often lengthy procedures and
intravascular volume/renal perfusion must be maintained in the presence of a dye load.
In addition to routine monitors, an arterial line may be helpful if the procedure requires hypertension or
hypotension. An arterial line also enables the anesthesiologist to maintain the delicate balance between
intracranial pressure and cerebral perfusion pressure and to better diagnose and treat hemorrhage. If arterial
monitoring will be needed after the procedure, a peripheral site (e.g., radial artery) may be preferred to the side
port of the introducer sheath. Intravenous access should always be adequate and blood products should be
available as indicated.
Vertebroplasty and kyphoplasty are typically used to treat vertebral compression fractures. Patients are
typically elderly with significant comorbidities, including diminished pulmonary function associated with the
vertebral fracture. The procedures may be performed with general anesthesia or local anesthesia with sedation
and analgesia. After the patient is placed prone, trocars are inserted on each side of the involved vertebral body
under fluoroscopic or CT guidance. Polymethylmethacrylate (PMMA) is injected via a trocar into the medulla

212
Page 6
of the vertebral body under direct visualization. In kyphoplasty, a balloon is inserted through the trocar to
restore the intervertebral distance before PMMA is injected.
65
If PMMA leaks into perivertebral veins, it can
cause radiculopathy, embolization, or interference with pulse oximetry readings. The most severe complication
of PMMA leakage is spinal cord compression that requires immediate surgical decompression. Other
complications associated with PMMA leaks are hypotension, hypoxemia, cardiac arrhythmias, and pulmonary
embolism.
66

Anesthesia for the endovascular coiling of cerebral aneurysms ranges from none to general anesthesia. Many
radiologists prefer general anesthesia for patient comfort and safety and to obtain optimal conditions for
imaging, even though general anesthesia may mask the clinical signs that guide the progress of the procedure.
67

Patients with a subarachnoid hemorrhage because of a leaking or ruptured aneurysm are at risk for increased
intracranial pressure, cerebral ischemia, and hydrocephalus. Patients with a ventricular drain are at risk for
transmural pressure changes and re-bleeding with elevated arterial pressure.
62

Patients with an arteriovenous malformation (AVM), a steal phenomenon that may lead to the loss of
autoregulation in the surrounding brain tissue as chronic vasodilation compensates for the steal, may suffer
spontaneous hemorrhage and have seizures or other neurological symptoms because of ischemia or venous
hypertension.
68

General anesthesia is often preferred for embolization of an AVM because it facilitates visualization of
structures and prevents patient movement. Hypertension is controlled by reducing the anesthetic or
administering vasoactive agents that may help float a flow-directed catheter into the desired vessels. The most
common AVM embolic agent is the fast-polymerizing liquid adhesive n-butyl cyanoacrylate (n-BCA); a new
liquid agent, Onyx, has recently been introduced.
69
During injection, Valsalva maneuvers and controlled
hypotension may reduce the gradient across the AVM and diminish the amount of distal adhesive
embolization.
69
When the AVM is embolized and steal ceases, the surrounding brain may suffer hyperperfusion
injury unless the cerebral blood flow is aggressively controlled with nitroprusside or other agents.
Pial and dural arteriovenous fistulas (AVFs) are direct shunts between an artery and a vein and may be
associated with extremely high blood flow. Clinical characteristics include bruit, neurologic symptoms or
intracranial hemorrhage. Children may have concomitant high-output cardiac failure.
70
Transarterial
embolization for high-flow, single-hole fistulas is performed with balloons, coils, stents, or n-BCA.9
62

Cerebral thrombolytic procedures are most often performed on awake individuals, but their tenuous medical
status may mandate an anesthesiologists presence. Anesthesia concerns include altered mental status, airway
protection, control of patient movement, and management of intracranial pressure.
Embolization of cerebral tumors also may be associated with the consequences of a steal phenomenon
because of the hypervascular nature of these tumors. Hypotension should be avoided before embolization and
hypertension should be avoided after it. Other concerns include greater intracranial pressure from brain edema,
which may be treated with steroids.
Neurophysiologic monitoring helps gauge the progress of an intervention. In a patient under general
anesthesia, it signals impairment so that the insult may be reversed promptly. The EEG, somatosensory evoked
potentials (SSEPs), and brainstem auditory evoked potentials can be critical for the successful endovascular
treatment of cerebral aneurysms under general anesthesia.
71
Muscle motor evoked potentials can indicate spinal
cord perfusion in the anterior spinal artery during endovascular procedures and complement SSEPs.
72

Transcranial Doppler ultrasonography directly measures regional cerebral blood flow (rCBF) in arteriovenous
malformations, aneurysms, and arterial stenoses.
63
Other direct measures of rCBF include radionuclide CBF
(e.g., technetium) studies and xenon CT.
71
Since anesthetics often have an effect on measurements, the
anesthesiologist must be in close communication with monitoring personnel to distinguish between an
anesthetic artifact and a new neurologic deficit.
Two devastating complications of interventional neuroradiology procedures are intracranial hemorrhage and
thromboembolic stroke.
73
The incidence of these two complications during coiling of cerebral aneurysms is
2.4% and 3.5%, respectively; during embolization of arteriovenous malformation it is 1%8%.
74
Arterial
pressure can increase suddenly with acute intracranial hemorrhage and should be controlled immediately.
Heparin reversal may be necessary along with a decrease in arterial pressure. Hyperventilation and mannitol
should be considered to reduce intracranial pressure. Hemorrhage due to perforation can often be treated with
coiling, although emergency craniotomy and clipping may be required if coiling fails.
Occlusive events can be thrombotic, embolic, or vasospastic. For all, the arterial pressure should be raised to
increase collateral blood flow while normocarbia is maintained. Thrombi may be treated by mechanical lysis
with a guidewire, normal saline, or thrombolytics. Misplaced coils may be retrieved endovascularly or via
craniotomy. Vasospasm may be treated with papaverine or nicardipine,
75
cerebral angioplasty
76
or by
increasing arterial pressure and volume while decreasing blood viscosity through hemodilution.
62
Maintaining
hypotension with antihypertensive agents such as labetolol or esmolor may be beneficial after AVM
embolization to prevent cerebral edema and hemorrhage. Using phenylephrine or norepinephrine, a mean

212
Page 7
arterial pressure 20%30% above normal can maintain cerebral perfusion in patients with occlusion or
vasospasm.
62

Recovery
Recovery of any anesthetized patient is governed by the ASA standards for postoperative care.
1
Ideally, nursing care should conform to the Standards of the American Society of Perianesthesia Nurses, and
the facilities and equipment for recovery should be commensurate with the complexity of the patient. Medically
stable patients who have undergone innocuous procedures under MAC (MRI, inferior vena cava filter) can often
recover en suite, provided that the nurses are trained and an anesthesiologist is available. Patients who have
received regional or general anesthesia or who are at risk for pain (e.g., radiofrequency ablation for
hepatocellular carcinoma) or procedural complications (e.g., aortic stent graft) recover in a dedicated
postanesthesia care unit or an intensive care unit. Resuscitation equipment, oxygen, and monitors should be
available for transport from the radiology suite.
Summary
As radiologic interventions become more common, the need for anesthesia care will increase. While a
patients comorbidities are addressed and other concerns are similar to those in a surgical setting, the additional
requirements and constraints of the imaging environment and the procedure call for specific approaches and
techniques. Just as in the operating room, there is frequently no single best anesthetic technique for a given
procedure. The technique is designed and implemented according to the demands of the procedure and the skill
sets of the providers. Patient safety always takes precedence, and a location should never be permitted to
compromise care. In any case, the patient deserves care that is consistent with the parameters, guidelines, and
standards established by the various accrediting agencies and professional societies.
REFERENCES
1. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists.
Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002; 96:1004-1017
2. American Society of Anesthesiologists. Distinguishing monitored anesthesia care (mac) from moderate
sedation/analgesia (conscious sedation). Available at: http://www2.asahq.org/publications/pc-106-3-asa-
standards-guidelines-and-statements.aspx. Accessed on July 30, 2008
3. Bush WH, Swanson DP. Acute reactions to intravascular contrast media: types, risk factors, recognition, and
specific treatment. Am J Roentgenol. 1991;157:1153-1161
4. Almen T. The etiology of contrast medium reactions. Invest Radiol. 1994;29(suppl 1):s37-45
5. Bush WH, Bettmann MA. Update on metformin (glucophage ) therapy and the risk of lactic acidosis:
change in fda-approved package insert. ACR Bulletin. 1998;54(3):15
6.
Http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125574.
htm Accessed on May 29, 2013
7. American Society of Anesthesiologists. Practice advisory on anesthetic care for magnetic resonance imaging:
a report by the American Society of Anesthesiologists Task Force on Anesthetic Care for Magnetic Resonance
Imaging. Anesthesiology. 2009;110:459-479
8. American College of Radiology. ACR practice guideline for adult sedation/analgesia, revised 2005. Available
at: http://www.acr.org/secondarymainmenucategories/quality_safety/guidelines/iv/adult_sedation.aspx.
Accessed on July 18, 2010
9. Joint Commission on Accreditation of Healthcare Organizations. Standard and intents for sedation and
anesthesia care: comprehensive accreditation manual for hospitals. Report TX. 2-2.4.1 Chicago: JCAHO; 2001
10. Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document for safe MR Practices: (2007). Am J
Roentgenol. 2007;188:1-27
11. Dempsey MF, Condon B. Thermal injuries associated with MRI. Clin Radiol. 2001;56(6):457-465
12. Bryan YF, Templeton TW, Nick TG, et al. Brain magnetic resonance imaging increases core body
temperature in sedated children. Anesth Analg. 2006;102:1674-1679
13. Hall SC, Stevenson GW, Suresh S. Burns associated with temperature monitoring during magnetic
resonance imaging (letter). Anesthesiology. 1992;76:152
14. Bucsko JK. MRI facility safety: understanding the risks of powerful attraction. Radiol Today. 2005;6:22
15. Peden CJ, Menon DK, Hall AS, et al. Magnetic resonance for the anaesthetist. Part II Anaesthesia and
monitoring in the MR units. Anaesthesia. 1992;47:508-517
16. Http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10098
Accessed on May 29, 2013
17. Lantz G, Grave de Peralta R, Spinelli L, Seeck M, Michel CM. Epileptic source localization with high
density EEG: how many electrodes are needed? Clin Neurophysiol. 2003;114(1):63-69
18. Raichle ME. Functional brain imaging and human brain function. J Neurosci. 2003;23(10):3959-3362
19. Jack CR Jr, Thompson RM, Butts RK, et al. Sensory motor cortex: correlation of presurgical mapping with
functional MR imaging and invasive cortical mapping. Radiology. 1994;190:85-92

212
Page 8
20. Kapoor V, McCook BM, Torok FS. An Introduction to PET-CT Imaging, RadioGraphics, 2004:24:523-
543.
21. Alkire MT, Haier RJ, Shah NK, Anderson CT. Positron emission tomography study of regional cerebral
metabolism in humans during isoflurane anesthesia. Anesthesiology. 1997;86:549-557
22. Alkire MT, Pomfrett C. Functional brain imaging during anesthesia in humans: effects of halothane on
global and regional cerebral glucose metabolism. Anesthesiology. 1999;90:701-709
23. Fiset P, Paus T, Daloze T, et al. Brain mechanisms of propofol-induced loss of consciousness in humans: a
positron emission tomographic study. J Neurosci. 1999;19(13):5506-5513
24. Becerra L, Harter K, Gonzalez RG, Borsook D. Functional magnetic resonance imaging measures of the
effects of morphine on central nervous system circuitry in opioid-naive healthy volunteers. Anesth Analg.
2006;103:208-216.
25. Kiviniemi VJ, Haanp H, Kantola JH, et al. Midazolam sedation increases fluctuation and synchrony of the
resting brain BOLD signal. Magn Reson Imaging. 2005;23(4):531-537
26. Lorenz IH, Kolbitsch C, Hrmann C, et al. Increasing mean airway pressure reduces functional MRI (fmri)
signal in the primary visual cortex. Magn Reson Imaging. 2001;19(1):7-11
27. Purdon PL, Pierce ET, Bonmassar G, et al. Simultaneous electroencephalography and functional magnetic
resonance imaging of general anesthesia. Ann NY Acad Sci. 2009;1157(1):61-70
28. Ramani R, Wardhan R. Understanding anesthesia through functional imaging. Curr Opin Anaesthesiol.
2008;21(5):530-536
29. Rogers R, Wise R, Painter D, et al. Noninvasive brain imaging: an investigation to dissociate the analgesic
and anesthetic properties of ketamine using functional magnetic resonance imaging. J Pain. 2004;5(suppl 1):S2
30. Arepally A, Oechsle D, Kirkwood S, et al. Safety of conscious sedation in interventional radiolo32. Gy.
Cardiovasc Intervent Radiol. 2001;24(3):185-190
31. Callstrom MR, Charboneau W, Goetz MP, et al. Painful metastases involving bone: feasibility of
percutaneous CT-and US- guided radio-frequency ablation I. Radiology. 2002;224:87-97
32. Watkinson AF, Francis IS, Torrie P, et al. Commentary: the role of anaesthesia in interventional radiology.
Br J Radiol. 2002;75:105-106
33. Ellis JE, Pai SS. Pro. Vascular stents in the radiology suitean anesthesiologist is needed. J Cardiothorac
Vasc Anesth. 2005;19:801-804
34. Aadahl P, Lundbom J, Hatlinghus S, et al. Regional anesthesia for endovascular treatment of abdominal
aortic aneurysms. J Endovasc Surg. 1997;4:56-61
35. Mathes DD, Kern JA. Continuous spinal anesthetic technique for endovascular aortic stent graft surgery. J
Clin Anesth. 2000;12:487-490
36. Henretta JP, Hodgson KJ, Mattos MA, et al. Feasibility of endovascular repair of abdominal aortic
aneurysms with local anesthesia with intravenous sedation. J Vasc Surg. 1999;29:793-799
37. Winnerkvist A, Anderson RE, Hansson Lo, et al. Multilevel somatosensory evoked potentials and
cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery. Eur J
Cardiothorac Surg. 2007;31:637-642
38. Tiesenhausen K, Amann W, Koch G, et al. Cerebrospinal fluid drainage to reverse paraplegia after
endovascular thoracic aortic aneurysm repair. J Endovasc Ther. 2000;7:132-135
39. Cheung AT, Pochettino A, McGarvey ML, et al. Strategies to manage paraplegia risk after endovascular
stent repair of descending thoracic aortic aneurysms. Ann Thorac Surg. 2005;80:1280-1288
40. Touz E, Calvet D, Chatellier G, et al. Carotid stenting. Curr Opin Neurol. 2008; 21:56-63
41. Nagata S, Kazekawa K, Aikawa H, et al. Hemodynamic stability under general anesthesia in carotid artery
stenting. Radiat Med. 2005;23(6):427-431
42. Steib A, Collange O. Anesthesia for other endovascular stenting. Curr Opin Anesthesiol. 2008;21:519-522
43. Neglen P, Holis KC, Olivier J, et al. Stenting of the venous outflow in chronic venous disease: long-term
stent-related outcome, clinical, and hemodynamic result. J Vasc Surg. 2007;46:979-990
44. Bierdrager E, Lampmann LE, Lohle PN, et al. Endovascular stenting in neoplastic superior vena cava
syndrome prior to chemotherapy or radiotherapy. Neth J Med. 2005;63:20-23
45. Pivalizza EG, Gottschalk LI, Cohen A, et al. Anesthesia for transjugular intrahepatic portosystemic shunt
placement. Anesthesiology. 1996;85:946-947
46. Scher C. Anesthesia for transjugular intraheptaic portosystemic shunt. Int Anesthesiol Clin. 2009;47(2):21-
28
47. Slaughter TF. Ambulatory regional anesthesia and anticoagulation. In: Steel SM, Nielsen KC, Klein SM,
eds. The Ambulatory Anesthesia and Perioperative Analgesia Manual. New York: McGraw-Hill; 2004: 445-451
48. Alessandri C, Bergeron P. Local anesthesia in carotid angioplasty. J Endovasc Surg. 1996;3(1):31-34
49. De Vries JP, van Den Heuvel DA, Vos JA, et al. Freedom from secondary interventions to treat stenotic
disease after percutaneous transluminal angioplasty of infrarenal aorta: long-term results. J Vasc Surg.
2004;39:427-431

212
Page 9
50. Leyendecker JR, Dodd GD III. Minimally invasive techniques for the treatment of liver tumors. Semin Liver
Dis. 2001;21(2):283-291
51. Sundaram R, Brown AG, Koteeswaran SK, et al. Anaesthetic implications of uterine artery embolisation in
management of massive obstetric haemorrhage. Anaesthesia. 2006;61:248-252
52. Harnett MJ, Carabuena JM, Tsen LC, Kodali BS. Anesthesia for interventional radiology in parturients at
risk of major hemorrhage at cesarean secion delivery. Anesth Analg. 2006;103:1329-1330
53. Kuzgunbay B, Turunc T, Akin S, Ergenoglu P, Aribogan A, Ozkardes H. Percutaneous nephrolithotomy
under general versus combined spinal-epidural anesthesia. J Endourol. 2009;23:1835-1838
54. Rozentsveig V, Neulander AZ, Roussabrov E, et al. Anesthetic considerations during percutaneous
nephrolithotomy. J Clin Anesth. 2007;19:351-355
55. Lee WJ, Smith AD, Cubelli V, et al. Complications of percutaneous nephrolithotomy. Am J Roentgenol.
1987;148:177-180
56. Barth KH. Percutaneous biliary drainage for high obstruction. Radiol Clin North Am. 1990;28(6):1223-1135
57. McGhana JP, Dodd GD III. Radiofrequency ablation of the liver: current status. Am J Roentgenol.
2001;176:3-16
58. Ukimura O, Kawauchi A, Fujito A, et al. Radio-frequency ablation of renal cell carcinoma in patients who
were at significant risk. Int J Urol. 2004;11:1051-1057
59. Hanazaki M, Taga N, Nakatsuka H, et al. Anesthetic management of radiofrequency ablation of mediastinal
metastatic lymph nodes adjacent to the trachea. Anesth Analg. 2006;103:1041-1042
60. Shingleton WB, Sewell PE Jr. Percutaneous renal tumor cryoblation with magnetic resonance imaging
guidance. J Urol. 2001;165:773-776
61. Taylor W, Rodesch G. Recent advances: interventional neuroradiology. BMJ. 1995;311:789-792
62. Varma MK, Price K, Jayakrishnan V, et al. Anaesthetic considerations for interventional neuroradiology. Br
J Anaesth. 2007; 99(1):75-85
63. Lai YC, Bulusu R, Manninen PH. Anesthesia for interventional neuroradiology: general considerations.
Semin Anesthesia Perioperative Med Pain. 2000;19(4):248-253
64. Busto R, Dietrich WD, Globus MY, et al. Small differences in intraischemic brain temperature critically
determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab. 1987;7:729-738
65. Wiles MD, Nowicki RW, Hancock SM, et al. Anaesthesia for vertebroplasty and kyphoplasty. Current
Anaesth Crit Care. 2009;20:38-41
66. Frost EA, Johnson DM. Anesthetic considerations during vertebroplasty, kyphoplasty, and intradiscal
electrothermal therapy. Int Anesthesiol Clin. 2009;4(2):45-55
67. Jones M, Leslie K, Mitchell P. Anaesthesia for endovascular treatment of cerebral aneurysms. Clin
Neurosci. 2004;11:468-470
68. Crawford PM, West CR, Chadwick DW, Shaw MD. Areteriovenous malformations of the brain: natural
history in unoperated patients. J Neurol Neurosurg Psychiatry. 1986;49:1-10
69. Van Rooij WJ, Sluzewski M, Beute GN. Brain AVM embolization with Onyx. Am J Neuroradiol.
2007;28:172-177
70. Sderman M, Pavic L, Edner G, et al. Natural history of dural arteriovenous shunts. Stroke. 2008;39:1735-
1739
71. Liu AY, Lopez JR, Do HM, et al. Neurophysiological monitoring in the endovascular therapy of aneurysms.
Am J Neuroradiol. 2003;24:1520-1527
72. Sala F, Niimi Y, Berenstein A, Deletis V. Neuroprotective role of neurophysiological monitoring during
endovascular procedures in the spinal cord. Ann NY Acad Sci. 2001;939:126-136
73. Young WL. Anesthesia for endovascular neurosurgery and interventional neuroradiology. Anesthesiol Clin.
2007;25(3):391-412
74. Martin NA, Khanna R, Doberstein C, Bentson J. Therapeutic embolization of arteriovenous malformations:
the case for and against. Clin Neurosurg. 2000;46:295-318
75. Badjatia N, Topcuoglua MA, Pryor JC, et al. Preliminary experience with intra-arterial nicardipine as a
treatment for cerebral vasospasm. Am J Neuroradiol. 2004;25:819-826
76. Brothers MF, Holgate RC. Intracranial angioplasty for treatment of vasospasm after subarachnoid
hemorrhage: technique and modifications to improve branch access. Am J Neuroradiol. 1990;11(2):239-247
Disclosure
218
Page 1
The Geriatric Outpatient: Cognitive Dysfunction and Other Concerns
Kathryn E. McGoldrick, M.D. Valhalla, New York
Introduction
The elderly (!65 yr) are a rapidly growing demographic segment in the United States as well as in many other parts
of the developed world. This reality has profound implications for anesthesiologists and surgeons. Aging, for
example, increases the probability that an individual will require a surgical procedure. Whereas approximately 12%
of those aged 45 to 60 yr undergo surgery annually, this number increases to >21% in the elderly (1). Although
operative mortality has decreased in the geriatric population in recent decades, perioperative morbidity continues to
be more common in the elderly and perioperative mortality rates, especially in the presence of co-existing disease,
remain higher than those encountered with younger patients. Using the Cox proportional hazards model, the risk of
postoperative long-term mortality increases 1.42 times per decade of age (2). Clearly, as an ever-increasing
proportion of the surgical outpatient population falls into the geriatric category, anesthesiologists are becoming
geriatric subspecialists to a certain extent. Thus, it seems appropriate to summarize our current knowledge about the
physiology of aging and to discuss the implications of these issues for the perioperative management of the elderly
outpatient.
Physiology and Pathophysiology of Aging
Age alters both the pharmacokinetic and pharmacodynamic aspects of anesthetic management. As an individual
ages, he or she experiences a loss of reserve and a diminished ability to tolerate stress. The functional capacity of
organs declines and co-existing disease further contributes to this decline. Advanced age, in conjunction with
comorbidity, is a risk factor for increased perioperative mortality, and age itself may further amplify the negative
prognostic value of impaired physical status (3).
The effects of aging at the subcellular level are ubiquitous, and these effects are apparent when one considers organ
function in the elderly. In terms of cardiac function, it is well known that geriatric patients have reduced beta-
adrenergic responsiveness, and they experience an increased incidence of bradyarrhythmias and hypertension.
Fibrotic infiltration of cardiac conduction pathways and replacement of myocardial elastic fibers render the elderly
individual vulnerable to conduction delay and to atrial and ventricular ectopy. It is well known that postoperative
atrial arrhythmias, and atrial fibrillation (AF) and flutter specifically, are seen in 6.1% of elderly patients undergoing
noncardiothoracic surgery and in 10% to 40% of patients after cardiothoracic operations (4-7). Because reliance on
atrial kick is critically important for older adults, should we prophylactically treat high-risk patients to prevent
postoperative AF? If so, should we use rate control or rhythm control drugs? Elderly patients also have an increased
reliance on the Frank Starling mechanism for cardiac output. It is important, therefore, to consider fluid as a drug
that the elderly individual may or may not need. In the noncompliant older heart, small changes in venous return will
produce large changes in ventricular preload and cardiac output. Owing to reduced diastolic myocardial function,
baroreceptor-mediated heart rate control, adrenergic receptor responsiveness, and vascular compliance, the elderly
person compensates poorly for hypovolemia. Similarly, overtransfusion is also poorly tolerated.
COPD, pneumonia, and sleep apnea are common in the elderly. Closing volume increases with age, and FEV1
declines 8% to 10% per decade owing to reduced pulmonary compliance and muscle power (8). Arterial oxygen
tension decreases progressively with age-induced V/Q mismatch, diffusion block, and anatomical shunt (9). [Owing
to these abnormalities in gas exchange, it is recommended that elderly patients be transported to the PACU with 2-4
L/min of oxygen via nasal cannula, even after relatively minor ambulatory surgery (10)]. Given these deleterious
changes, it is not surprising that postoperative respiratory complications are common in geriatric patients. However,
the most important clinical predictor of adverse pulmonary outcome is the site of surgery, with thoracic and upper
abdominal surgery having the highest pulmonary complication rates (11, 12).

218
Page 2
Because the central nervous system is the target for so many of our drugs, age-related alterations in nervous system
function have extremely compelling implications for anesthetic management. Indeed, aging universally produces a
reduction in total nervous system tissue mass, neuronal density, and concentration of neurotransmitters, as well as
various receptors. Drug interactions are a very real concern in the elderly because senior citizens typically undergo
physiologic changes related to disease as well as to normal aging. Moreover, although elders represent
approximately 13% of the population in the United States, they consume one-third of all medications and are seven
times more likely to experience an adverse drug reaction than their younger counterparts. In fact, the elderly account
for 50% of all medication-related deaths. Important to an understanding of geriatric pharmacokinetics is an
appreciation of the role that reduced drug excretion plays in adverse interactions. With advancing age, the number of
functioning glomeruli declines, as do glomerular filtration rate and renal blood flow.

Intraoperative Management
Because of the pulmonary changes discussed previously, it is imperative to appreciate that desaturation occurs faster
in older adults. Additionally, elderly patients are more vulnerable to desaturation-related cardiac events. Therefore,
proper preoxygenation is critical. Benumof points out that maximal preoxygenation is achieved with 8 large breaths
of 100% oxygen within 60 sec with an oxygen flow of 10 L/min (13).
Advanced age is associated with a reduction in median effective dose requirements for all agents that act within the
central nervous system regardless of whether these drugs are administered via the oral, parenteral, or inhalational
route. Indeed, the ED50 equivalent for anesthetics falls linearly with age, such that the typical healthy 80-yr-old
will require only about two-thirds of the anesthetic dose needed to produce comparable effects in a young adult. An
octagenarian with notable comorbidities will require even lower doses. This reduction in anesthetic requirement is
agent-independent and probably reflects fundamental neurophysiologic changes in the brain, such as reduced
neuronal density or altered concentrations of neurotransmitters. Elderly patients require less propofol (and other
agents) for induction, and it is also important to appreciate that the concurrent use of midazolam, ketamine, and/or
opioids with propofol synergistically increases the depth of anesthesia. Even with an appropriate dose reduction of
propofol, hypotension is common. Less hypotension has been reported with appropriately titrated administration of
mask sevoflurane for induction compared with a propofol infusion (14). Interestingly, gender differences have been
described in the pharmacokinetics of propofol given by continuous infusion in elderly patients (15).
Several neuromuscular blocking agents, including vecuronium and rocuronium, have an increased onset time in
elderly patients, possibly as a result of a less dynamic circulation and, thus, an increased transfer time to the effector
site (16). The time required for clinical recovery from neuromuscular blockade is markedly increased in older adults
for nondepolarizing agents that undergo organ-based clearance from plasma, but is minimally different for
atracurium, cisatracurium, or mivacurium because they undergo hydrolysis in plasma. Those neuromuscular
blockers with prolonged duration of action in the elderly are associated with delayed elimination, which may be a
result of the reduced total body water and decreased liver mass that often accompany aging. The likelihood of
postoperative respiratory complications after long-acting muscle relaxants increases with advanced age. It is not
unusual for patients who meet rigorous extubation criteria in the OR to deteriorate in the PACU. Hence, it seems
advisable to administer a short- or intermediate-acting muscle relaxant to any elderly patient for whom extubation is
planned at the end of the surgical procedure. Importantly, sugammadex has been shown to facilitate rapid reversal
from moderate rocuronium-induced neuromuscular blockade in adults of all ages, but recovery to a train-of-four
ratio of 0.9 is 0.7 min faster in young and middle-aged adults compared with patients !65 yr (17).
In planning an expeditious emergence, anesthesiologists should be aware that end-tidal gas monitoring
underestimates the brain concentration of the more soluble agents. Failure to appreciate this hysteresis effect leads to
prolonged emergence. Moreover, MAC awake is more favorable if the vaporizer is turned down gradually rather
than turned off abruptly (18). Not surprisingly, it has been reported that use of shorter-acting drugs (propofol,
desflurane, sevoflurane), in conjunction with BIS monitoring, can provide more rapid emergence in geriatric patients
and facilitate PACU bypass (19). Whether this approach will have a favorable effect on longer-term outcomes
remains to be determined.
When one considers selection of anesthetic technique, it is important to appreciate that there are no controlled,
randomized studies in elderly patients to show that regional anesthesia is clearly superior to general anesthesia for
ambulatory surgery. In fact, neuraxial, plexus, or peripheral nerve blocks (PNBs) in the elderly may be associated
with an increased risk of persistent numbness, nerve palsies, and other neurological complications. It has recently
been demonstrated that age is a major determinant of duration of complete motor and sensory blockade with PNB,
perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the
elderly (20). That said, PNBs offer some appealing features, especially in terms of postoperative pain control.
Clonidine is a valuable adjunct that enhances both local anesthetic and narcotic efficacy, and its addition to the local

218
Page 3
anesthetic mixture may afford some hemodynamic advantages compared with epinephrine. However, one should
select a dose of clonidine that will not produce postoperative sedation or hypotension. When administering epidural
blockade to elderly patients, it is important to remember that a given dose will produce a higher level of block in
seniors, and is typically accompanied by a greater incidence and degree of hypotension and bradycardia as well as a
longer duration of anesthesia (21). Sedation requirements are dramatically reduced under conditions of central
neuraxial block. Sensory input to the brain is attenuated and the BIS50 is shifted to a higher index. Although recent
data have supported a relaxation of the requirement for voiding before discharge after outpatient neuraxial blockade
with short-acting drugs for low-risk surgical procedures in low-risk patients, it is important to appreciate that elderly
patients do not meet these criteria (22). Current thinking is that elderly (!70 yr) patients who received neuraxial
block, regardless of the duration of the block, should be required to void before discharge.

Postoperative Management
Perioperative hypothermia is prevalent in both young and elderly surgical patients, but it is more frequent,
pronounced, and prolonged in the elderly, who have compromised ability to regain thermoregulatory control
quickly. Adverse consequences of postoperative hypothermia include cardiac ischemia, arrhythmias, increased
blood loss, wound infection, decreased drug metabolism, and prolonged hospitalization. Indeed, it has been shown
that maintaining normothermia decreases cardiac morbidity by 55 percent (23).
Postoperative pain increases the risk of adverse outcome in geriatric patients by contributing to tachycardia,
hypertension, cardiac ischemia, and hypoxemia. Effective analgesia can decrease the incidence of myocardial
ischemia and pulmonary complications, accelerate recovery, promote early mobilization, shorten hospital stay, and
reduce medical costs. However, postoperative pain control often is inadequate in the elderly because of concerns
about drug overdose, adverse response, drug interactions, and other issues. Pain control is further complicated by the
fact that the patients perception and expression of pain may be affected by changes in mental status. Current
postoperative analgesic techniques include the use of opioids by various routes, nonsteroidal anti-inflammatory
drugs, local anesthetic techniques (neuraxial, intra-articular, PNB, etc), and nonpharmacologic (transcutaneous or
percutaneous electrical nerve stimulation, acupuncture, acupressure, etc) methods. Pre-emptive, multimodal
approaches have been favored to minimize the risk of such opioid-related side effects as hypoxemia, constipation,
and pruritus. However, the recent discovery of data fabrication by a major researcher in the area of pre-emptive
analgesia has far-reaching and serious consequences. There is, for example, no longer unequivocal evidence
supporting the pre-emptive effect of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors.
Additionally, the ability of a multimodal pre-emptive analgesic regimen to prevent the development of chronic pain
after major orthopedic surgery remains unproven (24).

Postoperative Cognitive Impairment
Reports of postoperative cognitive deterioration in elderly patients surfaced several decades ago, and anesthesia
had often been implicated as a possible cause or contributing factor. Although improvements in surgical techniques
and anesthetic agents and methods have led to improved outcomes in the elderly, a troubling proportion of these
patients experience postoperative cognitive impairment (25-28), at least on a short-term (~3 months) basis.
The syndrome of postoperative cognitive impairment can be classified into two main categories: postoperative
delirium and postoperative cognitive dysfunction (POCD)(29). Delirium is defined as an acute change in cognitive
function that develops over a brief period of time, often lasting for a few days to a few weeks and typically having a
fluctuating course. It is characterized by inattention, as well as either disorganized thinking and/or altered
level of consciousness. Prospective studies have cited an incidence of delirium that ranges from 3% to >50% and is
dependent upon the type of surgery, the patient's preoperative physical and cognitive status, and the age of the
patient (29). Recently, Rudolph and Marcantonio reported an incidence of postoperative delirium ranging from 35%
to 65% for hip fracture repair, down to 4% for cataract surgery (30). In general, older patients undergoing
emergency or long, complex surgical procedures tend to have a higher frequency of delirium, which appears to be
less problematic in outpatients who recover in their familiar home environment. Delirium is a costly complication
that has been associated with increased postoperative morbidity and mortality. Although the risk factors for
postoperative delirium vary among studies, greater preoperative age, alcohol use, major comorbidities, and cognitive
impairment are generally thought to confer a higher risk of postoperative delirium. Recently, Smith et al (31)
reported that preoperative executive dysfunction and depression are independent risk factors for postoperative
delirium.The etiology of delirium is probably multifactorial and may include drug intoxication or withdrawal, drug
interactions, anticholinergic agents, metabolic disturbances, hypoxia, abnormal carbon dioxide levels, sepsis,
inadequate analgesia, and organic brain disease (32). Neurotransmitter imbalances involving acetylcholine,
dopamine, and gamma-aminobutyric acid appear to be heavily involved in the multifactorial pathophysiology of

218
Page 4
delirium. Recent evidence suggests that deregulation in the homeostasis of tryptophan, the precursor to serotonin,
may have a critical role in the pathogenesis of postoperative delirium (33). Because abnormalities in the regulation
of serotonin have consistently been linked with depression (34), this may have important implications for explaining
the association of depression with delirium. It has also been suggested that occult white matter damage to the
frontal-striatal areas of the brain predisposes some patients to develop delirium (31). It is perhaps possible that this
mild loss of white matter could manifest preoperatively as impaired executive performance and/or greater levels of
depression (31). Interestingly, the use of melatonin to treat delirium has produced some benefit, presumably by
resetting the circadian sleep-awake cycle of older surgical patients (35). Although common in the elderly, the
incidence of postoperative delirium may be reduced by protocol-driven perioperative treatment. Marcantonio and
colleagues reported a reduction in postoperative delirium in hospitalized patients by more than one-third, and of
severe delirium by more than one-half, by adherence to multifaceted recommendations that included elimination or
minimization of benzodiazepines, anticholinergics, antihistaminics, and meperidine, as well as encouraging early
mobilization and providing appropriate environmental stimuli (36).

POCD is defined as a deterioration of intellectual function in one or more neuropsychological domains that
often presents as impaired memory or concentration. Other neuropsychological domains, including executive
function, perceptual organization, language, attention, and psychomotor function, may be affected. Moller and
colleagues (25) evaluated cognitive function in patients aged 60 yr or older after major abdominal and orthopedic
surgery. These investigators found that approximately 25% of the patients had measurable cognitive dysfunction a
week after their surgery and 10% had cognitive changes 3 months postoperatively. This finding contrasted with a
3% incidence of cognitive deterioration in healthy control subjects in the same age range who did not undergo
anesthesia and surgery. Interestingly, neither perioperative hypoxemia nor hypotension correlated with the
occurrence of prolonged cognitive dysfunction. The identified risk factors for early (1 week) postoperative cognitive
dysfunction were increasing age and duration of anesthesia, low education level, a need for a second operation,
postoperative infection, and respiratory complications. The major risk factor for late (3 months) postoperative
cognitive dysfunction was age. Although the incidence of late postoperative cognitive dysfunction was 14% for
patients >70 yr, this rate decreased to only 7% for patients between the ages of 60 to 70 yr.
An additional large, prospective study conducted by Monk and colleagues evaluated the relationship of age to
POCD (28). Using the same methodology as the first multinational study (25), Monk and colleagues reported that
cognitive decline occurred in 16% of patients aged 60 yr or older at 3 months after major noncardiac surgery, but
was present in only 3% to 5% of younger patients (28). This study also determined that rates of cognitive decline
were higher in those >70 yr compared with younger elderly patients. More recently (2008), Monk explored the
predictors of cognitive dysfunction after major noncardiac surgery (37). Independent risk factors for POCD at 3
months after surgery were increasing age, lower educational level, a history of previous CVA without residual
impairment, and POCD at hospital discharge. Patients who had POCD at both hospital discharge and 3 months
after surgery were more likely to die in the first year after surgery, but whether this suggests a causal link or is
related to patients comorbidities is unknown (37).
There are few prospective studies on long-term cognitive outcomes after outpatient surgery, but an analysis of
cognitive recovery after major and minimally invasive surgery exists. Monk classified the type of surgical procedure
as minimally invasive (laparoscopic or superficial surgery), major intra-abdominal surgery, or orthopedic surgery
(28). The incidence of POCD was significantly greater for patients undergoing major abdominal or orthopedic
procedures compared with minimally invasive surgery. Because outpatient surgery is usually minimally invasive,
these results suggest that outpatients may have a better cognitive outcome than patients who require hospitalization.
The International Study of Postoperative Cognitive Dysfunction (ISPOCD) group, however, recently conducted a
longitudinal study comparing the incidence of POCD after inpatient versus outpatient surgery in patients older than
60 yr (38). At 7 days after surgery, the incidence of POCD was substantially lower in the outpatient group, but this
difference was not detected 3 months later. These results suggest that elderly outpatients have better cognitive
outcomes at discharge than elderly inpatients, but we currently have no explanation for the difference. Possible
explanations for the improved early outcome in outpatients include the healthier status of patients who qualify for
outpatient surgery, the briefer surgical and anesthesia times, the minimally invasive nature of most outpatient
procedures, or avoidance of hospitalization. Interestingly, a recent (2011) study by Evered et al found that POCD
was independent of the type of surgery and anesthetic (39). Specifically, at 3 months post procedure, 21% of
geriatric patients having coronary angiography under sedation had POCD. The incidence of POCD in geriatric
patients who underwent either total hip replacement or CABG surgery was 16% in each group.
It is important to understand that full return of cognitive function to preoperative levels may require several days,
even after ambulatory surgery in young, healthy patients (32, 40). Indeed, Lichtor (41) has suggested that even

218
Page 5
young adults may be sleepy for 8 hr after receiving IV sedation with midazolam and fentanyl, and the elderly
outpatient suffering from balance disturbances or age-related gait impairment may be at high risk of falling owing to
residual drowsiness. Nonetheless, it remains unclear which patient populations are most vulnerable and what the
causative factors might be for the serious problem of POCD. Although we have much to learn about postoperative
delirium and cognitive decline, it is clear that pre-existing subclinical decrements in functional status may become
evident during the perioperative period. Indeed, if a cognitive deficit is noted preoperatively, it may be a harbinger
of further postoperative decline. The data on the predictive value of preoperative cognitive status for the
development of delirium (42) and the ability of that assessment to result in successful intervention (as may be the
case with delirium) (36) offer compelling reasons to conduct a simple, brief mental status examination as part of the
preoperative interview. Indeed, Evered and colleagues recently identified that 20% of patients !60 hr having total
hip replacement had preexisting cognitive impairment, and 22% had amnestic mild cognitive impairment (MCI); 7%
had both (43). These findings underscore the need for a robust, reproducible, practical tool to assess preoperative
cognitive function in our elderly patients (44). Additionally, Vaurio and colleagues recently demonstrated that
elevated levels of preoperative pain and a postoperative increase in pain levels are independent predictors of
postoperative delirium in elderly surgical patients (45). These findings suggest that elderly surgical patients with
substantial preoperative pain should be targeted for more intensive pain control postoperatively.
Our current understanding of POCD suggests the etiology is multifactorial and may include the preoperative
status of the patient, as well as intraoperative events related to surgery (e.g., microemboli), and anesthetic factors.
The potential roles of inflammation and anesthetic depth remain to be more fully determined. However, recent
prospective studies that have combined neuroimaging, pain, and functional assessments have shown that when
surgery successfully treats chronic pain and inflammation, cognition improves and gray matter volume increases in
areas such as the dorsolateral prefrontal cortex, the anterior cingulate gyrus, and the amygdala (46). Although we
currently have no reliable neuroprotective intervention to offer our patients, a marker for POCD might influence the
decision to have such elective procedures as cosmetic surgery. Hopefully, future studies will lead to a clearer
definition of the incidence, mechanisms, and prevention of POCD (47).
Finally, it should be mentioned that interest has grown recently in exploring a potential relationship between
anesthesia and the onset and progression of such neurodegenerative conditions as Alzheimers disease (48). Our
knowledge in this area is limited, and anesthesia has been both implicated and exonerated. There is, however, some
laboratory evidence that anesthesia may affect the processing of amyloid beta peptide. It has also been speculated
that risk factors for POCD may overlap with those for Alzheimers disease, although any shared mechanism remains
conjectural. Available human studies on anesthesia and Alzheimers disease are inconclusive because they are
under-powered or confounded by coexisting disorders, independent risk factors for dementia, and, of course, surgery
(49-51). Increasingly, we are realizing that many of our elderly patients have MCI at baseline. The cognitive loss of
some of these patients may not be readily apparent preoperatively, and is unmasked by the perioperative experience.
Perhaps the concerning cognitive changes that are identified postoperatively indicate more about our patients than
about our anesthetic agents.
Interestingly, in April 2011, the first new diagnostic guidelines released in 27 years in the United States for
Alzheimers disease recognized MCI as a precursor to Alzheimers disease. The National Institute on Aging and the
Alzheimers Association now describe the disorder as a disease that occurs gradually over many years, starting with
changes in the brain, then mild memory problems, and finally progressing to florid dementia. This preclinical stage,
happening about a decade before dementia develops, may be the best place to intervene in the disease, with many
researchers believing that most Alzheimers drugs have been disappointing because they were tried in people whose
disease was too advanced to be halted or reversed. Although not yet ready for prime time, the development of new
imaging agents for PET scans, spinal fluid tests, and other biomarkers that predict or detect Alzheimers in its
earliest stages will be increasingly important to researchers, drug companies, and clinicians.

Summary

Elderly patients are uniquely vulnerable and particularly sensitive to the stresses of trauma, hospitalization, and
surgery/anesthesia in ways that are only partially understood. The ambulatory environment offers many potential
benefits for geriatric patients having elective procedures. Accordingly, minimizing perioperative risk in the
elderly population requires thoughtful preoperative assessment of organ function and reserve, meticulous
intraoperative management of coexisting disorders, maintenance of normothermia, and vigilant postoperative
monitoring and pain control.

References

218
Page 6
1. Ergina P, Gold S, Meakins J. Perioperative care of the elderly patient. World J Surg 1993;17:192-8.
2. Manku K, Bacchetti P, Leung JM. Prognostic significance of postoperative in-hospital complications in elderly
patients. I. Long-term survival. Anesth Analg 2003;96:583-9.
3. Forrest JB, Rehder K, Cahalan MK, Goldsmith CH. Multicenter study of general anesthesia III : Predictors of
severe adverse outcomes. Anesthesiology 1992;76:3-15.
4. Polanczyk CA, Goldman L, Marcantonio ER, et al. Supraventricular arrhythmias in patients having noncardiac
surgery: Clinical correlates and effect on length of stay. Ann Intern Med 1998;129:279-85.
5. Amar D, Roistacher N, Burt M, et al. Clinical and echocardiographic correlates of symptomatic
tachydysrhythmias after noncardiac thoracic surgery. Chest 1995;108:349-54.
6. Aranki SF, Shaw DP, Adams DH, et al. Predictors of atrial fibrillation following coronary artery
bypass graft surgery: Current trends and impact on hospital resources. Circulation 1996;94:390-7.
7. Mathew JP, Parks R, Savino JS, et al. Atrial fibrillation following coronary artery bypass graft surgery:
Predictors, outcomes, and resource utilization. JAMA 1996;276:300-6.
8. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory
flow-volume curve with growth and aging. Am Rev Respir Dis 1983;127:725-34.
9. Sorbini CA, Grassi V, Solinas E, Muiesan G. Arterial oxygen tension in relation to age in healthy
subjects. Respiration 1968;25:3-13.
10. Mathes DD, Conaway MR, Ross WT. Ambulatory surgery: Room air versus nasal cannula oxygen
during transport after general anesthesia. Anesth Analg 2001;93:917-21.
11. Klotz HP, Candinas D, Platz A, et al. Preoperative risk assessment in elective general surgery. Br J
Surg 1996;83:1788-91.
12. Vodinh J, Touboul C, Lefloch JP, et al. Risk factors of postoperative pulmonary complications after vascular
surgery. Surgery 1988;105:360-5.
13. Benumof J. Preoxygenation: Best method for both efficacy and efficiency (editorial). Anesthesiology 1999;
91:603-5.
14. Kirkbride DA, Parker JL, Williams GD, Buggy DJ. Induction of anesthesia in the elderly ambulatory
patient: A double-blind comparison of propofol and sevoflurane. Anesth Analg 2001;93:1185-7.
15. Vuyk J, Oostwouder CJ, Vletter AA, Burm AGL, Bovill JG. Gender differences in the
pharmacokinetics of propofol in elderly patients during and after continuous infusion. Br J Anaesth
2001;86:183-8.
16. Matteo RS, Ornstein E, Schwartz AE, et al. Pharmacokinetics and pharmacodynamics of rocuronium (Org
9426) in elderly surgical patients. Anesth Analg 1993;77:1193-7.
17. McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy, safety, and pharmacokinetics of sugammadex for the
reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology 2011;114:318-29.
18. Katoh T, Suguro Y, Kimura T, Ikeda K. Cerebral awakening concentration of sevoflurane and
isoflurane predicted during slow and fast alveolar washout. Anesth Analg 1993;77:1012-7.
19. Fredman B, Sheffer O, Zohar E, et al. Fast-track eligibility of geriatric patients undergoing short
urologic procedures. Anesth Analg 2002;94:560-4.
20. Pagueron X, Boccara G, Bendahou M, Coriat P, Riou B. Brachial plexus nerve block exhibits
prolonged duration in the elderly. Anesthesiology 2002;97:1245-9.
21. Simon MJG, Veering BT, Stienstra R, van Kleek JW, Burm AGL. The effects of age on neural
blockade and hemodynamic changes after epidural anesthesia with ropivacaine. Anesth Analg
2002;94:1325-30.
22. Mulroy MF, Salinas FV, Larkin KL, Polissar NL. Ambulatory surgery patients may be discharged
before voiding after short-acting spinal and epidural anesthesia. Anesthesiology 2002;97:315-9.
23. Frank SM, Higgins MS, Breslow MJ, et al. The catecholamine, cortisol, and hemodynamic responses
to mild perioperative hypothermia: A randomized clinical trial. Anesthesiology 1995;82:83-93.
24. White PF, Kehlet H, Liu S. Perioperative analgesia: What do we still know? (editorial). Anesth Analg 2009;
108:1364-7.
25. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the
elderly: ISPOCD1 study. The Lancet 1998;351:857-61.
26. Williams-Russo P, Sharrock NE, Mattis S, Szatowski TP, Charlson ME. Cognitive effects after
epidural vs. general anesthesia in older adults. JAMA 1995;274:44-50.
27. Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth
1998;81:449-62.
28. Monk TG, Garvin CW, Dede DE, van der Aa MT, Gravenstein JS. Predictors of postoperative

218
Page 7
cognitive dysfunction following major surgery (abstract). Anesthesiology 2001;95:A50.
29. Moller JT. Cerebral dysfunction after anaesthesia. Acta Anaesthesiol Scan (supp) 1997;110:13-6.
30. Rudolph JL, Marcantonio ER. Postoperative delirium: acute change with long-term implications. Anesth Analg
2011; 112:1202-11.
31.Smith PJ, Attix DK, Weldon BC, Greene NH, Monk TG. Executive function and depression as independent risk
factors for postoperative delirium. Anesthesiology 2009;110:781-7.
32. OKeefe ST, Chonchubhair AN. Postoperative delirium in the elderly. Br J Anaesth 1994;73:673-87.
33. Lewis MC, Barnett SR. Postoperative delirium: the tryptophan dysregulation model. Med Hypotheses
2004;63:402-6.
34. Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron 2002;34:13-25.
35. Hanania M, Kitain E. Melatonin for the treatment and prevention of postoperative delirium. Anesth
Analg 2002;94:338-9.
36. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: A
randomized trial. J Am Geriatr Soc 2001;49:516-22.
37. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery.
Anesthesiology 2008;108:18-30.
38. Canet J, Rasmussen LS, Raeder J, et al. Cognitive dysfunction after minor surgery in the elderly. Acta
Anaesthesiol Scand 2003;47:1204-10.
39. Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery
and anesthetic. Anesth Analg 2011;112:1179-85.
40. Tzabar Y, Asbury AJ, Millar K. Cognitive failure after general anaesthesia for day-case surgery. Br J
Anaesth 1996;76:194-7.
41. Lichtor JL, Alessi R, Lane BS. Sleep tendency as a measure of recovery after drugs used for
ambulatory surgery. Anesthesiology 2002;96:878-83.
42. Inouye SK. Predisposing and precipitating factors for delirium in hospitalized older patients. Dement
Geriatr Cogn Disorders 1999;10:393-400.
43. Evered LA, Silbert BS, Scott DA, et al. Preoperative cognitive impairment and mild cognitive impairment in
subjects presenting for total hip joint replacement. Anesthesiology 2011;114:1297-304.
44. Crosby G, Culley DJ, Hyman B. Preoperative cognitive assessment of the elderly surgical patient: A call for
action (editorial). Anesthesiology 2011;114:1265-8.
45. Vaurio L, Sands L, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain
management. Anesth Analg 2006;102:1267-73.
46. Seminowicz DA, Wideman TH, Naso L, et al. Effective treatment of chronic low back pain in humans reverses
abnormal brain anatomy and function. J Neurosci 2011;31:7540-50.
47. Newman S, Stygall J, Hirani S, et al. Postoperative cognitive dysfunction after noncardiac surgery: A systematic
review. Anesthesiology 2007;106:572-90.
48. Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement: International workshop on anesthetics and
Alzheimers disease. Anesth Analg 2009; 108:1627-30.
49. Bohnen N, Warner MA, Kokmen E, et al. Alzheimers disease and cumulative exposure to anesthesia: A case-
control study. J Am Geriatr Soc 1994;42:198-201.
50. Bohnen N, Warner MA, Kokmen E, Kurland LT. Early and midlife exposure to anesthesia and age of onset of
Alzheimers disease. Intern J Neurosci 1994;77:181-5.
51. Knopman DS, Petersen RC, Cha RH, et al. Coronary artery bypass grafting is not a risk factor for dementia or
Alzheimer disease. Neurology 2005;65:986-90.

Disclosure

318
Page 1
The Adult Patient With Morbid Obesity and/or Obstructive Sleep Apnea
For Ambulatory Surgery:An Update
Girish P. Joshi, MB BS, M.D., FFARCSI Dallas, Texas
Introduction
The prevalence of obesity is rapidly increasing worldwide. Pathophysiological changes associated with obesity
influence multiple organs and increase the risk of comorbidities [1]. One of the major co-morbidities associated
with obesity includes obstructive sleep apnea (OSA), reported in 60-70% of morbidly obese (body mass index
[BMI]>40 kg/m
2
) [2]. Therefore, this patient population is at a higher risk of perioperative morbidity and mortality.
This update discusses the current literature related to perioperative care of the obese, with emphasis on adult patients
with OSA, scheduled for ambulatory surgery.
Selection of Adult Obese Patients For Ambulatory Surgery
The suitability of ambulatory surgery in the obese and/or OSA patients remains controversial. Although it is
generally recommended that body weight or BMI alone should not be used as the sole indicator of suitability for
surgery or its location [3], most anesthesiologists use a body weight or BMI cut off in their ambulatory anesthesia
practice. In recent years, several large observational trials have evaluated the incidence of perioperative
complications in the obese population [4-8]. The factors contributing to increased adverse outcome include patient
characteristics (e.g., coexisting medical conditions such as presence of OSA, history of deep vein thrombosis (DVT)
or pulmonary embolism (PE), history of bleeding disorder, and impaired functional status) as well as surgical
characteristics (i.e., degree of invasiveness) and surgeons experience.
A recent systematic review of the literature addressing perioperative complications in adult obese patients
scheduled for ambulatory surgery included 23 studies (13 prospective and 10 retrospective studies), and one
systematic review [8]. A total of 106,119 patients (n=62,476 in the prospective trials and n=43,643 in retrospective
trials) were included in the analysis. Of these, 39,548 patients underwent laparoscopic gastric banding (not
including the systematic review of laparoscopic bariatric surgery, which included 2549 patients). This systematic
review revealed that BMI alone is not influence perioperative complications or unplanned admission after
ambulatory surgery. However, the patients undergoing non-bariatric surgical procedures had an average BMI of 30
kg/m
2
, which typically has a low burden of comorbidities. The patients undergoing bariatric surgery had BMI of
>40 kg/m
2
. However, the bariatric surgical population underwent screening for comorbidities, which were
optimized, preoperatively. This systematic review also revealed that super obesity (i.e., BMI >50 kg/m
2
) might be
associated with a higher risk of postoperative complications, particularly if these patients have significant
comorbidities such as OSA, obesity-related hypoventilation syndrome, pulmonary hypertension, resistant systemic
hypertension, significant coronary artery disease, resistant cardiac failure, bleeding disorder, and chronic renal
failure on dialysis [9].
Selection of Adult Patients With OSA For Ambulatory Surgery
The ASA-OSA practice guidelines propose a scoring system that may be used to estimate the perioperative risk
of complications and determine the suitability for ambulatory surgery [10]. However, this scoring system is not yet
validated. In addition, these guidelines also recommend that patients undergoing intra-abdominal and upper airway
procedures are not suitable for ambulatory surgery. However, numerous large observational case series have
reported that laparoscopic adjustable gastric banding (LABG) can be safely performed on an outpatient basis [11-
13]. Thus, invalidating the recommendation that intra-abdominal procedures are not suitable for ambulatory surgery.
A recent systematic review of published studies assessed the perioperative complications in patients with OSA
undergoing ambulatory surgery [11]. There were no differences between the OSA and non-OSA patients with
respect to anesthesia-related complciations and unanticipated hospital admission. However, it must be emphasized
that most studies used a protocol-based perioperative care, which may have contributed to a safe perioperative

318
Page 2
course. There was emphasis on limiting opioid dose and exercising caution in patients who develop prolonged and
frequent respiratory events (e.g., sedation analgesic mismatch with opioids, desaturation, and apneic episodes).
The predictors for surgical morbidity and mortality include age, male gender, coexisting medical conditions,
invasiveness of surgical procedure, surgeons experience, and postoperative opioid dose. Thus, preoperative
optimization of medical conditions and limiting opioid use is critical for patient safety. Overall, patients with
inadequately treated co-morbid conditions are not suitable for ambulatory surgery. Patients with a known diagnosis
of OSA (who are typically prescribed CPAP preoperatively) may be considered for ambulatory surgery if their
comorbid medical conditions are optimized and they are able to use a CPAP device in the postoperative period. It
appears that postoperative CPAP use may be protective against opioid-induced respiratory depression. Patients who
are unable or unwilling to use CPAP after discharge may not be appropriate for ambulatory surgery. Patients with a
presumed diagnosis of OSA, based on screening tools such as the STOP-Bang questionnaire, can be considered for
ambulatory surgery if their comorbid conditions are optimized and if postoperative pain relief can be provided
predominantly with non-opioid analgesic techniques. Of note, no guidance could be provided for OSA patients
undergoing upper airway surgery due to limited evidence. In addition, the ability of the facility to manage these
patients should also be taken into consideration.
Similar recommendations have been proposed recently by the American Society for Metabolic and Bariatric
Surgery, which also emphasized that the high risk population include males, age>50 years, BMI >60, and severe
OSA [13].

Preoperative Considerations
The comorbidities associated with obesity and OSA should be evaluated and optimized preoperatively. A
focused preoperative evaluation includes assessment of the airway, cardiovascular, respiratory, and endocrine
systems. In addition to assessment of functional status, patients should be questioned to determine symptoms of
angina, paroxysmal nocturnal dyspnea, orthopnea, and arrhythmia (i.e., palpitations). Because OSA is undiagnosed
in an estimated 60-70% of patients, screening for OSA should be part of routine preoperative evaluation. The STOP-
BANG screening tool is a user-friendly questionnaire that could be included in routine preoperative evaluation to
identify unrecognized OSA [14]. However, in contrast to original recommendations, use of 5 to 6 positive responses
out possible 8 questions on the STOP-BANG determine a possibility of moderate-to-severe OSA [15, 16]. If OSA is
suspected during preoperative evaluation, one could proceed with a presumptive diagnosis of severe OSA or obtain
a sleep study.

Preoperative Testing
It is well recognized that preanesthesia tests should be based on clinical indications and the invasiveness of the
surgical procedure. The American College of Cardiology (ACC) and American Heart Association (AHA) proposed
recommendations for perioperative care of morbidly obese patients undergoing surgery [17]. It is recommended that
ECG be obtained in patients with at least one risk factor for CHD and/or poor exercise tolerance. ECG signs of right
ventricular hypertrophy including right-axis deviation and right bundle-branch block would suggest pulmonary
hypertension, while a left bundle-branch block may suggest occult CHD. In addition, chest X-ray should be
obtained on all morbidly obese patients as it may suggest undiagnosed heart failure, cardiac chamber enlargement,
or abnormal pulmonary vascularity suggestive of pulmonary hypertension, which warrants further cardiovascular
investigation. Further testing, such as exercise and/or pharmacological stress echocardiography, may be performed
in presence of !3 risk factors of CAD (i.e., history of CHD, history of congestive heart failure, history of cerebro-
vascular disease, preoperative treatment with insulin, and preoperative serum creatinine levels >2 mg/dL).

Preoperative Medications
Obese patients may be on multiple medications including prescription and non-prescription (i.e., over-the-
counter or herbal diet drugs) that might have detrimental cardiopulmonary effects as well as adversely interact with
anesthetic drugs. Patients should be asked to continue their preoperative medications until the day of surgery,
except for antidiabetic therapy that might need some modification [18]. Because morbid obesity is one of the major
risk factors for the development of PE, prophylaxis for DVT, low dose heparin in combination with intermittent
pneumatic compression, are recommended [19]. Preoperative prophylaxis against acid aspiration (e.g., H
2
-receptor
antagonists and proton pump inhibitors) is commonly used. However, their routine use is questioned, as the risk of
regurgitation of gastric contents for the morbidly obese and the non-obese appears to be similar [20].

318
Page 3
Intraoperative Considerations
Although the surgical procedure and the need for postoperative opioids, rather than the choice of anesthetic
technique appear to be more important determinants of perioperative complications in the morbidly obese
particularly those with OSA, local or regional anesthesia should be preferred. Local/regional anesthesia obviates the
need for airway manipulation as well as avoids hypnotic-sedatives, opioids, and muscle relaxants. In addition, these
techniques provide postoperative analgesia and reduce postoperative opioid requirements.

Sedation and Analgesia in the Obese and OSA Patients
Because OSA surgery is not always successful, it is suggested that drug-induced sleep endoscopy (DISE) could
be used to assess the level and mechanism of obstruction and develop specific therapy [21-23]. Thus,
anesthesiologists will be involved in providing deep sedation/general anesthesia without a secured airway required
for DISE. Patients with OSA are more sensitive to sedative-hypnotics and opioids, which cause dose-dependent
upper airway collapse, respiration depression, and reduced respiratory responses to hypoxia and hypercapnia. Of
note, during sedation OSA may develop in previously unrecognized patients. Therefore, monitoring should include
continuous capnography as it allows detection of upper airway obstruction much prior to oxygen desaturation.
Because CPAP counteracts sedation-induced airway closure, it should be considered during moderate sedation,
particularly in patients using CPAP preoperatively.
Midazolam and propofol have a similar propensity for upper airway obstruction at similar levels of sedation
[24]. However, respiratory problems disappear more quickly (within 15 min) with propofol. Dexmedetomidine, a
highly selective alpha-2 adrenergic agonist with sedative, amnestic, analgesic, and sympatholytic properties with no
respiratory depression, can be used to provide sedation/analgesia. In addition, it reduces salivary secretions through
sympatholytic and vagomimetic effects. Of note, it is generally assumed that dexmedetomidine is a short-acting
drug; however, it may have prolonged sedative effects. Addition of low-dose ketamine (up to 1 mg/kg) to
dexmedetomidine may potentiate the analgesics effects and reduce the hemodynamic adverse effects with
influencing respiration [25].

General Anesthesia
The optimal general anesthetic technique would allow rapid and clear-headed recovery including early return of
the patients protective airway reflexes, which would allow maintenance of a patent airway. In addition, early
recovery should reduce postoperative cardiac complications due to residual anesthetic effects.

Pre-induction Considerations
Alterations in pulmonary function (e.g., reduced FRC and oxygen reserves) in the obese may result in severe
hypoxemia even after short periods of apnea. Positioning of the patient in the head elevated laryngoscopy position
(HELP), which can be achieved by stacking with blankets or a specially designed foam pillow, structurally
improves maintenance of the passive pharyngeal airway and may be beneficial for mask ventilation as well as
improve the success of tracheal intubation. Other techniques used to avoid post-induction hypoxemia include the
use of 10 cm H
2
O CPAP with the patient in head-up position [26]. The end point for preoxygenation should be to
achieve end-tidal oxygen concentration of at least 90%. Preinduction techniques followed by 10 cm H
2
O PEEP
during mask ventilation and after intubation have been shown to reduce post-intubation atelectasis and improve
arterial oxygenation [27]. Also, PEEP increases the pressure in the esophagus, which may act as a barrier against
regurgitation [28].

Airway Management
Because BMI alone is not a predictor of difficult intubation [29], awake tracheal intubation may not always be
necessary. Nevertheless, OSA has been reported to be a predictor of difficult airway [2]. Predictors of difficult
tracheal intubation include high Mallampati score (III or IV), neck circumference !40 cm, limited mandibular
protrusion, and severe OSA (AHI !40). If awake intubation is necessary, sedatives and opioids must be utilized
judiciously as they may cause airway obstruction before the airway is secured.

Induction of General Anesthesia
Because of concerns of regurgitation and difficult tracheal intubation, rapid sequence induction (RSI) of general
anesthesia is commonly performed in the morbidly obese. However, the need for RSI is increasing questioned [30].
Recent studies, in morbidly obese patients, have shown than the barrier pressure (lower esophageal pressure - gastric
pressure) remains positive throughout induction of anesthesia [20]. This suggests that the risk of gastric
regurgitation in the morbidly obese may be similar to that in the non-obese patients. Controlled induction of

318
Page 4
anesthesia should allow adequate ventilation prior to intubation attempt and avoid hypoxia between induction and
tracheal intubation. Most anesthesia drugs including intravenous anesthetic drugs and opioids should be dosed
according to lean body weight (not actual body weight), except for neuromuscular blocking drugs, which should be
dosed according ideal body weight [31].

Maintenance of General Anesthesia
There is lack of evidence for superiority of a specific maintenance technique (e.g., inhalation vs. total
intravenous anesthesia). Nevertheless, inhalation anesthesia remains the mainstay of current anesthesia practice
because of the ease of titration. In addition, inhaled anesthetics exert some neuromuscular blocking effect, which
may reduce the need for muscle relaxants. Several studies have reported that in the morbidly obese, desflurane
allows earlier emergence compared with sevoflurane [32]. A study analyzing data from published randomized trials
as well as data from an electronic database found that desflurane reduced the average extubation time and the
variability of extubation time compared with sevoflurane. [33].
Because of its amnestic and analgesic properties, nitrous oxide (N
2
O) reduces anesthetic and analgesic
requirements and facilitates recovery. Nevertheless, the use of N
2
O is questioned due to concerns of increased
incidence of postoperative nausea and vomiting (PONV) and pressure effects through expansion of closed spaces.
However, a systematic review concluded that use of propofol for induction of anesthesia and antiemetic prophylaxis
(current standard of care for ambulatory surgery) [34]. Another benefit of N
2
O is that it facilitates the removal of
other inhaled anesthetics (i.e., second gas effect), and allows rapid emergence from anesthesia [35]. Furthermore,
the analgesic effects of N
2
O should reduce the need for intraoperative opioids and reduce opioid-related adverse
effects [36]. Thus, there is no convincing reason to avoid N
2
O.
Determining the optimal anesthetic concentrations that would parallel the varying surgical stimuli, while
preventing intraoperative awareness, remains challenging. Recent evidence suggests that titration of inhaled
anesthetic using end-tidal concentrations (0.7-1.3 minimum alveolar concentration [MAC] values) and propofol
TIVA using bispectral index (BIS) monitoring should prevent intraoperative awareness with recall [37].
Opioids continue to play an important role in anesthesia practice; however, opioid-related sedation, airway
obstruction, and respiratory depression are of concern in this patient population. Therefore, opioids should be used
sparingly. Remifentanil (titrated to hemodynamics) may be preferable in the obese because of its unique
pharmacokinetics and ultra-short duration. Opioid requirements in patients with OSA has been reported lower than
those without OSA probably because recurrent hypoxia observed in this patient population may affect endogenous
opioid mechanisms that may alter responsiveness to exogenous opioid administration [38]. Because lower opioid
doses may be sufficient to achieve adequate analgesia, opioid therapy in OSA patients should be individualized and
carefully titrated. Importantly, opioids should be administered according to lean body weight NOT actual body
weight [31].
Because even minor degree of residual neuromuscular blockade (usually not appreciated clinically), particularly
the obese and OSA patients, can increase postoperative morbidity such as inadequate ventilation, hypoxia, and the
need for reintubation, muscle relaxants should be used sparingly [39, 40]. Current evidence suggests that the dose of
neostigmine should be titrated to the intensity of neuromuscular blockade at the time of reversal [41, 42]. Of note,
patients having TOF monitoring of the eye muscles had a greater than 5-fold higher risk of postoperative residual
paralysis than those who had monitoring of the adductor pollicis [43].

Mechanical Ventilation
Obesity is associated with changes in pulmonary function (e.g., reduction in lung volumes, increase in peak
inspiratory pressures, and decrease in pulmonary compliance). Lung protective ventilation strategies in the obese
would include the use of pressure-controlled ventilation with low tidal volumes (6-8 ml/kg IBW) and PEEP of 5-10
cmH
2
O [44]. There appears to be no difference between pressure-controlled ventilation and volume-controlled
ventilation. Recruitment maneuvers are beneficial in obese patients and should be applied, particularly at the start
and end of surgery. It is important to avoid hyperventilation (and hypocapnia), as this may result in metabolic
alkalosis and lead to postoperative hypoventilation. Mild hypercapnia (i.e., ETCO
2
of 40 mmHg) can improve
tissue oxygenation through improved tissue perfusion resulting from increased cardiac output and vasodilatation as
well as increased oxygen off-loading from the shift of the oxyhemoglobin dissociation curve to the right [45].

Pain, Nausea and Vomiting Prophylaxis
Preventive analgesia with non-opioids (e.g., local/regional anesthetic techniques, acetaminophen,
NSAIDs/COX-2 specific inhibitors, and dexamethasone) should reduce perioperative opioid requirements and lower
opioid-related side effects as well as improve postoperative pain relief [46-48]. Incorporation of procedure-specific

318
Page 5
pain therapies in clinical pathways should improve compliance with protocols and thus improve perioperative
outcome as well as allow early return to activities of daily living [48].
Patients undergoing ambulatory surgery are at a higher risk of PONV and should receive prophylactic
multimodal antiemetic therapy (e.g., combinations of 5-HT
3
-receptor antagonists and dexamethasone). Although it
is recommended that the number of antiemetics be based on the patients level of risk as determined by risk factor
assessment, routine antiemetic prophylaxis is optimal for this patient population [49, 50].

Emergence From Anesthesia
Towards the end of surgery, it is common practice to reduce the respiratory rate in an effort to build up end-tidal
CO
2
levels and facilitate respiration. However, the reduced minute ventilation resulting from this practice may
delay removal of inhaled anesthetic, and thus delay emergence from anesthesia. Therefore, the primary aim at the
end of the surgery should be to maintain the minute ventilation in an effort to washout the inhaled anesthetic and
facilitate emergence [45]. One of the major concerns in obese patients, particularly those with OSA, is the risk of
airway obstruction after tracheal extubation [51, 52]. Thus, prior to tracheal extubation the patient must be fully
awake, alert, and follow verbal commands (i.e., deep extubation is not advisable). Importantly, coughing and reflex
movements of the hand towards the tracheal tube should not be confused as purposeful movements. Extubation
should be performed in a semi-upright (25-30 head-up) position, when possible. Also, use of a nasal airway, placed
before tracheal extubation, may avoid postextubation airway obstruction.

Postoperative Considerations
Potential postoperative complications include airway obstruction, respiratory failure, need for reintubation, life
threatening hypoxia as well as systemic hypertension, ischemia, and cardiac arrhythmia. Once in the PACU,
patients should be maintained in a semi-upright (25-30 head-up) position, if possible.

Postoperative CPAP/BiPAP
Although supplemental oxygen is beneficial for most patients, it should be administered with caution as it may
reduce hypoxic respiratory drive and increase the incidence and duration of apneic episodes. Because obese patients
might have unrecognized OSA, recurrent hypoxemia may be better treated with CPAP or bi-level positive airway
pressure (BiPAP) along with oxygen rather than oxygen alone. Because determination of optimal CPAP settings
may be difficult in patients who have not previously used the device, use of automatic self-adjusting or auto-
adjusting positive airway pressure (APAP) devices may be preferred in the postoperative period. The APAP devices
change the pressure level based on feedback from various patient measures such as airflow, pressure fluctuations, or
measures of airway resistance. The pressure titration with APAP devices allows for the changes in upper airway
pressures that might occur in the immediate postoperative period due to varying degrees of residual anesthetic and
muscle relaxant effects.

Post-PACU Discharge Care
Prior to discharge from the PACU the oxygen saturation on room air should return to baseline and the patient
should not become hypoxic or develop airway obstruction when left undisturbed in the recovery area. It has been
suggested that most significant postoperative complications in OSA patients usually occur within 2 hours after
surgery. Therefore, it may be worthwhile to observe these patients in the recovery room for at least 2 h. Of note,
complaints of postoperative shoulder, hip, or buttock pain along with unexplained elevations in serum creatinine and
creatine phosphokinase (>5000 IU/L) levels should raise suspicion of rhabdomyolysis [53].
Discharge home might be considered if the patient can maintain baseline oxygen saturation on room air, and the
propensity to develop airway compromise and respiratory depression no longer exists. The ASA-OSA Practice
Guidelines suggest that OSA patients be monitored for a median of 3 hours longer than their non-OSA counterparts
before discharge from the facility [10]. In addition, the monitoring should continue for a median of 7 hours after the
last episode of airway obstruction or hypoxemia while breathing room air in an unstimulated environment.
Unfortunately, the recommendations for longer postoperative stays are not based upon any scientific evidence. In
fact, recent studies in bariatric surgical population found that the time to discharge between the OSA and non-OSA
population was similar [54].

Patient Information
Education of the patients and their caregivers regarding the need for increased vigilance after discharge home is
critical [18]. Because opioids are the biggest culprits in post-discharge complications, patients should be advised
asked to limit opioid use. Patients on preoperative CPAP should be advised to use their CPAP device whenever

318
Page 6
sleeping even during the daytime, and for several days postoperatively. Also, patients should be advised against
sleeping in the supine position. Patients who are assumed to have OSA based on the screening questionnaire should
be advised to follow-up with their primary physician for possible sleep study. Because there is a possibility that
OSA patients may not always meet criteria for safe home discharge, the option of admission should be discussed
with the patient prior to surgery.

Post-Discharge Considerations
One of the major concerns after ambulatory surgery is nocturnal apnea with catastrophic consequences. Of
note, postoperative sleep disturbances appear to be related to the location and invasiveness of the surgical procedure
and opioid usage. Postoperative surgical stress response, anxiety, pain, and opioid use can cause sleep deprivation
and fragmentation, which may reduce REM sleep. Upon resolution of the stress response rebound REM sleep may
ensue [55], which may exacerbate sleep disorders and increase the potential airway obstruction and life-threatening
apnea. Because the risk of respiratory complications may last for several days after surgery, it is important that the
post-discharge instructions emphasize the potential for aggravation of OSA and the need to use opioids judiciously
for several days after recovery from the surgical procedure.

Summary
Obese patients, particularly those with OSA, are at a high risk of perioperative complications that might last for
several days after surgery. Because undiagnosed OSA is common and failure to recognize OSA preoperatively is
one of the major causes of perioperative complications, a focused history and physical examination can help identify
patients with OSA. Clearly, selecting a patient for an ambulatory procedure is a dynamic process, which depends on
the complex interplay between patient characteristics (i.e., coexisting medical conditions), invasiveness of the
procedure, and anesthetic technique as well as postoperative opioid requirements. Therefore, attempts to address
individual factors without consideration of others is fraught with flaws.
Prudent perioperative management should be guided by the awareness of the potential complications based on
the severity of comorbidities, invasiveness of diagnostic or therapeutic procedure, and requirement of postoperative
opioids. Use of fast-track anesthesia techniques with pain and PONV prophylaxis should allow rapid emergence,
reduce postoperative cardiopulmonary complications, and hasten recovery. Patients should be educated regarding
the deleterious effects of opioids and asked to limit their use. Patients on preoperative CPAP should be instructed to
use CPAP at night for several days postoperatively. Patients who are placed on OSA protocol based on clinical
indicators should be asked to follow-up with their primary physician for possible sleep study. Finally, developing
and implementing protocols (clinical pathways) is the best way to avoid adverse events and improve postoperative
outcome [62].

References
1. Cullen A, Ferguson A. Perioperative management of the severely obese patient: a selective pathophysiological
review. Can J Anaesth 2012; 59: 974-96.
2. Adesanya AO, et al. Perioperative management of obstructive sleep apnea. Chest 2010; 138: 1489-98.
3. Verma R, et al. Day case and short stay surgery: 2, Anaesthesia 2011; 66: 417-34.
4. Elliott JA, et al. Fast-track laparoscopic bariatric surgery: a systematic review. Updates Surg. 2013.
5. Dorman RB, et al. Risk for hospital readmission following bariatric surgery. PLoS ONE 2012; 7(3):e32506.
6. Memtsoudis SG, et al. Factors influencing unexpected disposition after orthopedic ambulatory surgery. J Clin
Anesth 2012; 24: 89-95.
7. Nandipati K, et al. Factors predicting the increased risk for return to the operating room in bariatric patients: a
NSQIP database study. Surg Endosc. 2013;27:1172-7.
8. Thomas H, Agrawal S. Systematic review of same-day laparoscopic adjustable gastric band surgery. Obes Surg
2011; 21: 805-10.
9. Kakarla VR, et al. Are laparoscopic bariatric procedures safe in superobese (BMI !50 kg/m
2
) patients? An
NSQIP data analysis. Surg Obes Relat Dis 2011; 7: 4528.
10. Gross JB, et al. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: a
report by the American Society of Anesthesiologists Task Force on perioperative management of patients with
obstructive sleep apnea. Anesthesiology 2006; 104: 1081-93.
11. Joshi GP, et al. Society for Ambulatory Anesthesia (SAMBA) consensus statement on preoperative selection of
patients with obstructive sleep apnea scheduled for ambulatory surgery. Anesth Analg 2012; 115: 1060-8.
12. Lockhart EM, et al. Obstructive sleep apnea screening and postoperative mortality in a large surgical cohort.
Sleep Medicine; 2013; 14: 407-15.

318
Page 7
13. American Society for Metabolic and Bariatric Surgery (ASMBS). Peri-operative management of obstructive
sleep apnea ASMBS Clinical Issues Committee. Surgery for Obesity and Related Diseases 2012; 8:e27e32.
14. Chung F, et al: STOP Questionnaire: A tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;
108:812- 21.
15. Farney RJ, et al. The STOP-Bang equivalent model and prediction of severity of obstructive sleep apnea:
relation to polysomnographic measurements of the apnea/hypopnea index. J Clin Sleep Med 2011; 7: 45965B.
16. Chung F, et al. High STOP-Bang score indicates a high probability of obstructive sleep apnoea. Br J Anaesth
2012; 108: 768-75.
17. Poirier P, Alpert MA, Fleisher LA, et al: Cardiovascular evaluation and management of severely obese patients
undergoing surgery a science advisory from the American Heart Association. Circulation 2009; 120: 86-95.
18. Joshi GP, et al. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose
management in diabetic patients undergoing ambulatory surgery. Anesth Analg 2010; 111: 13788.
19. Magee CJ, et al: Extended thromboprophylaxis reduces incidence of postoperative venous thromboembolism in
laparoscopic bariatric surgery. Surg Obes Relat Dis. 2010; 6: 322-5.
20. de Leon A, et al: High-resolution solid-state manometry of the upper and lower esophageal sphincters during
anesthesia induction: a comparison between obese and non-obese patients. Anesth Analg 2010; 111: 149-53.
21. Eichler C, et al. Does drug-induced sleep endoscopy change the treatment concept of patients with snoring and
obstructive sleep apnea? Sleep Breath 2013; 17: 63-68.
22. Borek RC, et al. Quantitative airway analysis during drug-induced sleep endoscopy for evaluation of sleep
apnea. Laryngoscope 2012.
23. Victores AJ, Takashima M. Effects of nasal surgery on the upper airway: a drug-induced sleep endoscopy
study. Laryngoscope, 2012.
24. Norton JR et al: Differences between midazolam and propofol sedation on upper airway collapsibility using
dynamic negative airway pressure. Anesthesiology 2006; 104: 1155-64.
25. Eikermann M, et al. Ketamine activates breathing and abolishes the coupling between loss of consciousness
and upper airway dilator muscle dysfunction. Anesthesiology 2012; 116: 35-46
26. Tagaito Y et al: Sitting posture decreases collapsibility of the passive pharynx in anesthetized paralyzed patients
with obstructive sleep apnea. Anesthesiology 2010; 113: 812-8.
27. Futier E, et al. Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during
and after intubation of morbidly obese patients: a randomized controlled study. Anesthesiology 2011; 114:
1354-63.
28. de Leon A, et al. Effects of different respiratory maneuvers on esophageal sphincters in obese patients before
and during anesthesia. Acta Anaesthesiol Scand 2010; 54: 1204-9.
29. Lundstrom LH, et al. High body mass index is a weak predictor for difficult and failed tracheal intubation: a
cohort study of 91,332 consecutive patients scheduled for direct laryngoscopy registered in the Danish
anesthesia database. Anesthesiology 2009; 110: 266-74.
30. Freid EB. The rapid sequence induction revisited: obesity and sleep apnea syndrome. Anesthesiol Clin North
Am 2005; 23: 551-64.
31. Ingrande J, Lemmens HJM. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth 2010; 105
(S1): i16i23.
32. Jakobsson J. Desflurane: a clinical update of a third-generation inhaled anaesthetic. Acta Anaesthesiol Scand
2012;56:420-32.
33. Dexter F et al: Statistical modeling of average and variability of time to extubation for meta-analysis comparing
desflurane to sevoflurane. Anesth Analg 2010; 110: 570-80.
34. Fernandez-Guisasola J et al: Association between nitrous oxide and the incidence of postoperative nausea and
vomiting in adults: a systematic review and meta-analysis. Anaesthesia 2010; 65: 379-87.
35. Peyton PJ, et al. Nitrous oxide diffusion and the second gas effect on emergence from anesthesia.
Anesthesiology. 2011;114:596-602.
36. Echevarra G, et al. Nitrous oxide (N2O) reduces postoperative opioid-induced hyperalgesia after remifentanil
propofol anaesthesia in humans. Br J Anaesth 2011;107: 959-65.
37. Avidan MS, Mashour GA. Prevention of intraoperative awareness with explicit recall: making sense of the
evidence. Anesthesiology 2013; 118: 449-56.
38. Brown KA. Intermittent hypoxia and the practice of anesthesia. Anesthesiology 2009; 110: 922-27.
39. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. part I: definitions, incidence, and
adverse physiologic effects of residual neuromuscular block. Anesth Analg 2010; 111: 120-8.

318
Page 8
40. Brull SJ, Murphy GS: Residual neuromuscular block: lessons unlearned. part II: methods to reduce the risk of
residual weakness. Anesth Analg 2010;111:129-40.
41. Herbstreit F, et al. Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases
upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal
pressure. Anesthesiology 2010; 113: 1280-8.
42. Fuchs-Buder T, et al. Antagonism of low degrees of atracurium-induced neuromuscular blockade. Doseeffect
relationship for neostigmine. Anesthesiology 2010; 112: 34-40.
43. Thilen SR, et al. Intraoperative neuromuscular monitoring site and residual paralysis. Anesthesiology 2012;
117: 964-72.
44. Aldenkortt M, et al. Ventilation strategies in obese patients undergoing surgery: a quantitative systematic
review and meta-analysis. Br J Anaesth 2012; 109: 493-502.
45. Joshi GP. The role of carbon dioxide in facilitating emergence from inhalation anesthesia: then & now. Anesth
Analg 2012; 114: 933-4.
46. Ong CK, et al. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative
systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010; 110: 1170-9.
47. Maund E, et al. Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the
reduction in morphine-related side-effects after major surgery: a systematic review. Br J Anaesth 2011; 106:
292-7.
48. Joshi GP, Kehlet H. Procedure-specific pain management: the road to improve postsurgical pain management?
Anesthesiology 2013; 118: 780-2.
49. Gan TJ, et al. Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and
vomiting. Anesth Analg 2007; 105: 1615-28.
50. Apfel CC, et al. Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology
2012; 117: 475-86.
51. Popat M, et al. Difficult Airway Society guidelines for the management of tracheal extubation. Anaesthesia
2012; 67: 318-40.
52. Cavallone LF, Vannucci A. Extubation of the difficult airway and extubation failure. Anesth Analg 2013; 116:
368-83.
53. Ankichetty S, et al. Case report: rhabdomyolysis in morbidly obese patients: anesthetic considerations. Can J
Anesth 2012.
54. Kurrek MM, et al. Morbidity in patients with or at high risk for obstructive sleep apnea after ambulatory
laparoscopic gastric banding. Obes Surg 2011;DOI:10.1007/s11695-011-0381-6.
55. Dette F, et al. Occurrence of rapid eye movement sleep deprivation after surgery under regional anesthesia.
Anesth Analg 2013; 116: 939-43.
56. Bryson GL et al: Unplanned admission after day surgery: A historical cohort study in patients with obstructive
sleep apnea. Can J Anaesth 2012; 59: 842-51.

Disclosure
Pfizer, Self, Honoraria; Baxter, Self, Honoraria; Pacira, Self, Honoraria ; Cadence, Self, Honoraria, Edwards Life
Sciences, Honoraria
324
Page 1
Effective Management of Pain, Postoperative Nausea and Vomiting and Opioid Related
Side Effects in Ambulatory Surgical Patients
Tong J. Gan, M.D., M.H.S. Durham, North Carolina
Postoperative nausea and vomiting (PONV) and pain are two of the most common and unpleasant side effects
following anesthesia and surgery. Although both are predictable part of the postoperative experience, inadequate
management of these symptoms is common and can have profound implications. Unrelieved postoperative pain
may result in clinical and psychological changes that increase morbidity, mortality, costs as well as decrease
quality of life and potentially increase the incidence of chronic pain
1
. Negative clinical outcomes resulting from
ineffective postoperative pain management include deep vein thrombosis and pulmonary embolism, coronary
ischemia and myocardial infarction, pneumonia, poor wound healing, insomnia and demoralization
2,3
. Associated
with these complications are economic and humanistic implications such as extended lengths of stay, readmissions,
and patient dissatisfaction with medical care.
4,5
A recent study suggests that pain in ambulatory surgical patients is
still undermanaged and the incidence of moderate to severe pain remains high.
6
The overall incidence of PONV has decreased from 60 % when ether and cyclopropane were used, to approximately
30% more recently.
7
However, in certain high-risk patients the incidence is still as high as 70%. It is estimated that
an episode of vomiting prolongs PACU stay by about 30 min.
8
Furthermore, it is estimated that approximately 0.2%
of all patients may experience intractable PONV, leading to unanticipated hospital admission following ambulatory
surgery, thereby increasing medical costs. The estimated cost of PONV to a busy ambulatory surgical unit was
estimated to range from $0.25 million to $1.5 million per year in lost surgical revenue.
9
The results of several studies suggest that patients not only rank the absence of PONV and pain as being important
10
but also rank it more important than an earlier discharge from an ambulatory surgical unit.
11
Because patients
convalesce at home after surgery, pain and nausea and vomiting must be effectively assessed, monitored, and
treated within the surgical setting and anticipated during the recovery at home. This article will discuss the
management of PONV and pain following ambulatory surgery, the use of an effective, multimodal and novel
therapy as well as recommendations for the prophylaxis and treatment of PONV and pain.
Management of Postoperative Pain
Pharmacological Options
Opioids
Opioids are effective analgesics for moderate to severe pain. They act on opioid receptors in the peripheral
12,13
and
central nervous system. However their efficacy is limited by side effects. Opioids and/or NSAIDs combined with
local anesthetic infiltration or regional block has proven to be a useful technique for controlling pain in patients
after ambulatory surgery and should be considered whenever possible. In most studies local anesthetic infiltration
with systemic opioids or NSAIDs showed improvement in analgesia, better recovery
14
and shortening of discharge
time from day surgery unit.
15,16
Acetaminophen
Acetaminophen (Paracetamol) is an effective analgesic for mild to moderate pain with favorable side effect profile.
17
It is an effective adjuvant to opioid analgesia and a reduction in opioid requirement by 20-30% can be achieved
when combined with a regular regimen of IV, oral or rectal acetaminophen. It has been shown that 1 g of
propacetamol results in significant reduction in postoperative morphine consumption over 6 h period.
18
A meta-
analysis of analgesic efficacy suggested that acetaminophen and tramadol is an effective analgesic combination in
324
Page 2

dental and post surgical pain. However, more patients experienced side effects like dizziness, nausea and vomiting
with this combination.
19
IV acetaminophen, commonly used in Europe, has the flexibility of being able to be used in
the perioperative period and may be a viable alternative to NSAIDs in minor surgery and a useful adjunct in
conjunction with other analgesics.
18,20

Non-Steroidal Anti-inflammatory Drugs and Cyclo-oxygenase (COX-2) Inhibitors
Non-steroidal anti-inflammatory drugs (NSAIDs) have become the cornerstone in the treatment of acute pain in
the early postoperative period because of its opioid sparing effect.
21
Administration of ibuprofen and oxycodone in
combination provides superior and effective analgesia in the postoperative period.
22
The combination of ibuprofen
and acetaminophen has also been reported to reduce the need for early analgesia up to 34% in children undergoing
tonsillectomy.
23
The use of COX-2 inhibitors have been shown to be an effective opioid adjunct in the
perioperative period without the increased risk of bleeding. Recently data suggest that oral regimen of ibuprofen
(1200 mg/d) or celecoxib (400 mg/d) improves analgesia and quality of recovery in ambulatory patients.
24
The
recent availability of IV ibuprofen may provide further option of administration in the perioperative setting.

Tramadol and Tapentadol
Tramadol is a synthetic, centrally acting analgesic with a weak opioid action. It also inhibits serotonin and
noradrenaline reuptake.
25
The tramadol metabolite, O-desmethyl tramadol is a more potent analgesic than
tramadol.
26
Unlike other opioids, it lacks the respiratory depressant effects and exhibits lower risk of bowel
dysfunction
27
at conventional doses. A meta-analysis
28
of acetaminophen and tramadol combination confirmed
superior analgesia without additional toxicity. The most common adverse effects noted were dizziness, headache,
nausea and vomiting. Combination of tramadol with acetaminophen increases tolerability.
29
More recently,
tapentadol has been approved in the US for the treatment of acute pain, It acts on opioid receptors as well as by
inhibiting norepineprine pathway. More studies are needed to define its clinical utility in an ambulatory setting.

Ketamine
Ketamine acts as an antagonist on the NMDA receptor. Used more widely as an anesthetic before the availability of
newer induction and maintenance agents, it has received renewed interest for its role in enhancing postoperative
analgesia. Several studies have focused on demonstrating use of subanesthetic doses of ketamine for various
surgical procedures to enhance pain relief and reduce total analgesic consumption.
30-35
Central excitatory
neurotransmitters acting on N-methyl-D aspartate receptor (NMDA) have been identified in the development and
perpetuation of pathologic pain states causing hyperalgesia and allodynia.
36

There is ample evidence to suggest that ketamine has opioid sparing effect and may confer advantage in patients
where large amount of postoperative opioid consumption is anticipated. At low doses ketamine can provide
analgesia in opioid resistant pain.
37
Continuous infusion of ketamine has been used perioperatively. Adam et
al., evaluated IV ketamine with an initial bolus (0.5 mg/kg) followed by continuous infusion of 3 mcg/kg/min
intraoperatively in combination with continuous femoral nerve block in patients undergoing total knee arthroplasty.
In this multimodal approach, ketamine group required significantly less morphine and tolerated early mobilization
of knee.
38
These drugs have to be used with caution in the ambulatory setting due to its potential side effects
including sedation and hallucinatory effects in some individuals, though administering only a bolus dose and
avoiding the infusion regimen can reduce the incidence of adverse events.

Wound infiltration with local anesthetics
Infiltration of surgical wound with local anesthetics is probably the simplest method of achieving wound analgesia.
This method has been shown to be effective in providing analgesia in patients undergoing inguinal hernia repair and
other ambulatory procedures. There is lack of evidence for any clinically useful effect for other more extensive
abdominal procedures.
39
For example, wound infiltration does not provide beneficial effect on pulmonary function
after surgery in one study.
40
Inadequate dosing and relatively short duration of action of the local anesthetics may
explain the poor results in some trials. Prolonged release technology of local anesthetics (e.g. depobupivacaine) has
recently approved for clinical use. In two pivotal studies, depobupivacine (Exparel
) would infiltration has been

shown to improve postoperative analgesia and reduced opioid consumption in bunionectomy and
hemorrhoidectomy surgery.
41,42
Further trials on its efficacy for peripheral nerve blocks are on-going. The role of
other adjuvants to local anesthetics is unclear. For example, wound infiltration of bupivacaine and ketamine has
not shown a decrease in pain score or the need for rescue analgesia but the duration of analgesia has been reported
to be prolonged by the addition of ketamine.
43

324
Page 3

Intra-articular analgesics
There are conflicting reports about the efficacy of intra-articular analgesics in the literature.
44-46
. In a systematic
review Moiniche S et al.
47
observed that the effect of intra-articular local anesthetics seemed to provide
moderate pain relief of short duration. Although the pain relief in the early postoperative period was statistically
significant, evidence was not overwhelming in favor of intra-articular local anesthetics because majority of the
studies did not demonstrate improved pain relief beyond the immediate postoperative period. Peripheral Nerve
Blocks (PNB)
Appropriate nerve blocks depending on the site of surgery are useful in providing short to intermediate-term pain
relief after surgery. Direct visualization of neural tissue with ultrasound technology and the utility of stimulating
catheters has made placement of indwelling catheters safer and more accurate. Continuous infusion of local
anesthetics through a peripheral nerve catheter is becoming increasingly popular in both hospital and ambulatory
setting to achieve prolonged analgesia.
48,49
For example, continuous femoral nerve block has been shown to reduce
duration of hospital stay and the frequency of serious complications.
50
Similarly, several other studies have
demonstrated the benefits of PNB including reduced length of stay and costs,
49
decreased incidence of PONV
51
and lower rates of unexpected hospital admissions after ambulatory surgery.
49,50,52
Systemic agents co-
administered during PNB such as opioids and clonidine have been found to enhance intraoperative and
postoperative analgesia. Two systematic reviews of 15 studies that used opioids as adjuvant, six reported a
statistically significant benefit in analgesia. Of the six studies that evaluated clonidine,
53
five found improvement
in analgesia.

Other Pharmacological and Non-Pharmacological Options
Numerous other adjunctive analgesia including gabapentin, pregabalin, corticosteroids, neostigmine, magnesium
have some usefulness in an ambulatory settings but more evidence need to be gathered to determine their specific
roles. A recent study suggests that patients anesthetized with propofol was associated with less pain compared to
sevoflurane anesthesia although the exact mechanism is not known.
54
Non-pharmacological therapy should be
considered as complimentary to pharmacological options for postoperative pain management. They may provide
additional benefits in reducing the total dose of analgesics required and therefore minimizing the adverse effects of
the analgesics. Techniques include acupuncture, hypnosis, relaxation, music therapy, etc.
55,56

Rationale for multimodal analgesia
The ideal analgesic regimen would provide effective pain relief, reduce opioid related side effects and surgical
stress response and improve clinical outcome e.g. morbidity, mortality and hospital stay. The concept of
multimodal analgesia was introduced to achieve these goals by combining various analgesic techniques and
different classes of drugs to improve postoperative outcome.
57
However, available data are conflicting and do not
necessarily resulted in improved outcome and concomitant reduction in adverse effects of opioids.
58-60
The
failure to improve clinical outcome may be due to inappropriate combination and dosing of analgesics. Apart from
adequate analgesia,
postoperative morbidity and hospital stay depend on other factors such as initiation of early nutrition, mobilization
and comprehensive rehabilitation program.
61
Although, there is insufficient evidence to recommend pre-emptive
analgesia routinely it is prudent to attenuate postoperative pain as effectively as possible during the intraoperative
period and initiating effective analgesic therapy in the early phase of perioperative period.

The effectiveness of individual analgesics is enhanced by the additive or synergistic effect of two or more drugs
acting by different mechanisms. For example, the synergism between alpha-adrenergic and opioid systems has been
demonstrated.
62
Similarly, combination of acetaminophen and non-steroidal anti-inflammatory drugs provides
additive analgesic effect in mild to moderate acute pain.
63
The addition of COX-2 inhibitors or NSAIDs reduces
opioid requirements by 20-30% with the reduction of opioid related side effects and better analgesia. Similarly,
ketamine has been shown to reduce the pain scores and lower analgesic requirement when added to a multimodal
epidural analgesia.
64
Adding ketamine in patient controlled epidural analgesia along with morphine, bupivacaine
and epinephrine has been demonstrated to result in enhanced analgesic effect. Chia et al.,
65
showed that the mean
visual analogue score in the ketamine group during movement and cough were lower than the control group. The
cumulative total analgesic consumption in the ketamine group was lower by 30% than the control group 24 h
following surgery. In another study, it was demonstrated that the combination of intraoperative ketamine and
epidural analgesia may confer a long-term benefit in reducing incidence of chronic pain.
66

324
Page 4

Management of PONV

Risk factors for PONV
Identification of patients at high risk for PONV enables targeting prophylaxis to those who will benefit most from it.
Universal PONV prophylaxis is not cost effective, is unlikely to benefit patients at low risk for PONV and would
put them at risk from the potential side effects of antiemetic agents. Patient, anesthesia, and surgery related risk
factors have been identified. Anesthesia related risk factors include the use of volatile agents
67
, nitrous oxide
68
,
opioids
67,69
and high doses of neostigmine (>2.5 mg) for the reversal of neuromuscular blockade.
70
Patient related
factors include female gender
69,71
, history of PONV or motion sickness
69,71,72
, and non-smoking status.
69,71
Highlevels of anxiety and postoperative pain, especially of pelvic or visceral origin, may also be associated with a
higher
incidence of PONV.
73-75

A recent systematic review of the results of all available studies suggest that the phase of the menstrual cycle has no
impact on the occurrence of PONV.
76
An increased Body Mass Index (BMI) is not a risk factor for PONV.
77
However, long surgical duration
71
and certain types of surgery also carry a greater risk of PONV.
71,78,79
In adults,
high incidences of PONV are found in intra-abdominal surgery, major gynecological surgery, laparoscopic surgery,
breast surgery, neurosurgery, eye and ENT surgery. Pediatric operations at high risk for PONV include strabismus,
adenotonsillectomy, hernia repair, orchidopexy, penile surgery and middle ear procedures.
80-82
However, in a
prospective validation study, an association between type of surgery and the risk of PONV was not apparent.
69
It
was suggested that the high incidence of PONV after certain operations might be caused by the involvement of
high risk patients. The incidence of PONV increases after the age of 3 years with a peak incidence of about 40 %
in the 11 14 year age group.
69,83,84
Prior to puberty, gender differences for postoperative vomiting have not been
identified.
85
A recent study suggests black South African as an independent factor in reducing PONV risk.
86

A number of PONV risk scoring systems have been developed. Apfel et al developed a simplified risk score
consisting of four predictors: female gender, history of motion sickness or PONV, non-smoking status and the use of
opioids for postoperative analgesia.
69
A recent study identifies five independent predictors for postdischarge nausea
and vomiting: female sex, age<50 years, history of PONV, opioid use in the PACU, and nausea in the PACU.
87

Reduction of Baseline Risks
There are several effective strategies which can be easily employed to reduce the baseline risk for PONV.
Adequate hydration is simple and inexpensive and has been shown to reduce the incidence of PONV.
88
Liberal
fluid regimen is associated with a lower incidence of vomiting and improved pulmonary function in patients
undergoing knee arthroplasty compared with restricted fluid regimen.
89
While earlier studies suggest a protective
effect of higher concentration of oxygen, a recent meta-analysis concluded that 80% FiO2 should no longer be
considered an effective or reliable method to reduce overall PONV.
90
Reducing the use of opioid by adding other
adjunctive analgesia, e.g. NSAID, COX-2 inhibitor, acetaminophen, local anesthetic infiltration, gabapentin etc
can lower incidence of PONV.
91
Avoidance of deep inhalational anesthesia guided by bispectral index has also
been shown to
reduce the risk of PONV. Dexmedetomidine infusion (0.20.8 !g " kg
1
" h
1
) has recently been shown to reduce
rescue antiemetic use in bariatric surgical patients.
92
Most importantly, the use of propofol as the maintenance
anesthetic have the greatest impact in further reducing the incidence.
93

Combination Antiemetic Therapy
There are at least four major receptor systems involved in the etiology of PONV. The concept of combination
antiemetic therapy was first introduced in 1988 in chemotherapy induced nausea and vomiting (CINV).
94
Its success
prompted similar research in the field of PONV. Over 100 randomized controlled trials have been published
comparing the relative efficacy of combination versus single agent antiemetic prophylaxis. Most of these studies
suggested better efficacies against PONV can be achieved by the use of two or more antiemetics acting at different
receptors compared with monotherapy.
95-97
The choice of combination is not critical. In a meta-analysis, Habib et al.
found no statistically significant difference in the incidence PONV when a 5-HT3 receptor antagonist was combined
with either droperidol or dexamethasone. Both combination regimens provided significantly better PONV
prophylaxis compared with 5-HT3 receptor antagonists alone.
98
.

324
Page 5

In a large prospective study using a multifactorial design, Apfel et al. evaluated 3 antiemetic interventions
(ondansetron 4 mg, droperidol 1.25 mg, dexamethasone 4 mg) and 3 anesthetic interventions (TIVA with propofol,
omitting nitrous oxide, and substituting remifentanil for fentanyl) for the prophylaxis of PONV. The data suggest
that antiemetics with different mechanisms of action have additive rather than synergistic effects on the incidence of
PONV. Each antiemetic reduced the risk of PONV by about 25 %. When combinations of interventions were used,
the benefit of each subsequent intervention was always less than that of the first intervention.
95
. Interestingly, a
recent study showed superior efficacy in reducing vomiting when aprepitant was combined with dexamethasone
instead of ondansetron-dexamethasone combination in neurosurgical patients.
99

Multimodal Approach
In addition to using a combination of anti-emetics acting at different receptor sites, the multifactorial etiology of
PONV might be better addressed by the adoption of a multimodal approach other than pharmacotherapy. This
is especially important in patients at high risk for PONV. Scuderi et al reported a multimodal approach to the
management of PONV in females undergoing outpatient laparoscopy. Their multimodal algorithm consisted of
total intravenous anesthesia with propofol and remifentanil, avoiding nitrous oxide and neuromuscular
blockade, aggressive intravenous hydration (25 ml/kg), triple prophylactic antiemetics (ondansetron 1 mg,
droperidol 0.625 mg and dexamethasone 10 mg), and ketorolac 30 mg. Multimodal management resulted in a
98% complete response rate (no PONV and no antiemetic rescue) in PACU.
100
More recently, a multimodal
approach incorporating TIVA with propofol, a combination of ondansetron and droperidol, and omitting nitrous
oxide, was associated with a higher complete response rate and greater patient satisfaction in the PACU,
compared to similar antiemetic prophylaxis with isoflurane/nitrous oxide based anesthetic.
98
A combination of
ondansetron and transdermal scopolamine (TDS) proves to be effective in reducing PONV up to 48 hours after
ambulatory surgery.
101
A recent meta-analysis suggests a similar effective reduction in PONV with both early
(the night before surgery) and late patch (same day of surgery) application. Apart from a higher prevalence of
visual disturbances after surgery with TDS, there was no difference in the other anticholinergic side effects
when compared to placebo.
102

Droperidol
Following the FDA black box warning on droperidol due to concerns of prolonged QTc interval, its use has
declined dramatically. A recently published pro and con debate weighed the justification of the FDAs action
103,104
.
Increasingly, clinicians begin to use haloperidol, another drug in the butyrophenone class, due to its lack of black
box warning. Haloperidol in doses of 1 mg has been shown to be effective without significant side effects.
105,106
Its efficacy is enhanced when combined with dexamethasone.
107

Novel Antiemetics

Neurokinin-1 Antagonists
Substance P, a member of the tachykinin family of neuropeptides, is an important neurotransmitter in afferent
pathways of emesis.
108
Substance P may be released from enterochromaffin cells in the stomach and intestine (e.g.
postoperative trauma) or from sensory neurons (e.g. radiation, chemotherapeutic agents).
108
Tachykinin peptide
activity is tied to at least three G-proteincoupled receptor subtypes found in the peripheral or central nervous tissue:
neurokinin receptor subtype 1 (NK1), type 2 (NK2), and subtype 3 (NK3). The NK1 receptors are located in the area
postrema and are thought to play a particularly important role in emesis. However, NK1 receptor antagonists (NK1
RAs) are thought to exert their mechanism of action on neurons in the afferent relay station situated between the
medial NTS and the central pattern generator for vomiting.
108
The potential NK1 receptor blocking activity located
deeper in the brain stem is thought to prevent both acute and delayed emesis, whereas 5-HT3 RAs are largely
effective against acute emesis,
108
leading to considerable interest in the use of NK1 RAs for prophylaxis of PONV.
NK1 receptor antagonists are effective for the prophylaxis and treatment of PONV.
109,110
In one study in females
undergoing gynecologic surgery, an NK1 receptor antagonist, CP-122,721 provided better prophylaxis against
vomiting compared with ondansetron. The combination of both agents also significantly prolonged the time to the
need for rescue compared with either drug alone, and was associated with a low incidence of emesis (2 %).
110

Aprepitant is the only NK-1 receptor antagonist currently approved by the FDA for the prophylactic management
for PONV. It is available in oral capsule in 40 mg to be administered between 1-3 hours before surgery. It has a long
half-live of about 48 hours. It appears to have better efficacy in the prevention of PONV when compared with
ondansetron. In two identically designed, randomized, double-blind, active-controlled studies, patients scheduled for
324
Page 6

mostly major gynecological surgery under general anesthesia were randomized to either aprepitant 40 mg, aprepitant
125 mg or ondansetron 4 mg. In the combined analysis, aprepitant 40 mg was superior to ondansetron for no nausea
(39.6% v 33.1%), no vomiting (86.7% v 72.4%), and no nausea, no vomiting, and no use of rescue (37.9% v 31.2%)
(p<0.05 for the odds ratio for each comparison).
111,112
Rolapitant, with a half-life of 180 h, also has superior efficacy
in the reduction of postoperative emesis when compared with ondansetron.
113
There are a number of other NK-1
antagonists currently under development.
114

Long Acting Serotonin Antagonist
Palonosetron has the longest elimination half-life of all the currently available serotonin antagonists at about 40
hours.
115
Its long duration of action can also be explained by its high binding affinity for 5-HT3 receptors.
116
Polanosetron was first introduced into the US market in for the management of (CINV) and it is also recently
approved for PONV. Recent studies suggest palonosetron 0.075 mg i.v. is effective for the reduction of the
incidence of nausea and vomiting in patients up to 72 h postoperatively. Palonosetron also reduces nausea severity
and interference in postoperative patient functioning due to PONV
117
. It would be interesting to see if the longer
half-life of this drug translates into prolonged clinical efficacy when compared with other serotonin antagonists.

Recommended strategy for PONV prophylaxis
The risk of PONV should be estimated for each patient. No prophylaxis is recommended for patients at low risk for
PONV except if they are at risk for medical consequences from vomiting e.g. patients with wired jaws, aesthetic
procedures or at patients request. For patients at moderate to high risk for PONV, regional anesthesia should be
considered. If this is not possible or contraindicated and a general anesthetic is used, strategies to minimize the
baseline risk of PONV should be adopted, e.g. minimize the use of opioids, avoid high dose neuromuscular reversal
drugs and the use of propofol maintained anesthesia. The use of combination antiemetic therapy and more
appropriately a multimodal approach in high-risk patients is recommended. However, the best available combination
and the optimum doses of antiemetic agents when used in combination are yet to be established. Ondansetron should
be considered in any prophylactic regimen as it is now generic and hence has a low acquisition cost.

Recommendations for the treatment of established PONV
There is a paucity of data on the use of antiemetics for the treatment of PONV in patients who failed prophylaxis or
did not receive prophylaxis. This is due to the difficulty in performing such studies since a large number of patients
would need to be recruited in order to obtain the required number of patients who eventually experience PONV.
The 5-HT3 receptor antagonists were the most commonly tested drugs in rescue clinical trials. Similar to their use in
PONV prophylaxis, the anti-vomiting efficacy of the 5-HT3 receptor antagonists is more pronounced than their anti-
nausea efficacy. There is no evidence of dose-responsiveness for these agents when used for rescue. As
ondasnetron is now generic, a 4 mg dose is recommended.

In patients who fail ondansetron prophylaxis, there is evidence to suggest that the use of ondansetron for rescue is no
more effective than placebo. A drug acting at a different receptor might be more effective in this case.
118
Droperidol
was not different from ondansetron when used for the treatment of established PONV.
119
On the other hand,
ondansetron 4 mg was more effective than metoclopramide 10 mg in this setting.
120,121

When evaluating PONV following surgery, the role of medication and mechanical factors should be considered
first. Such contributing factors might include opioids, blood draining down the throat, or bowel obstruction. Then
rescue therapy should be initiated as soon as possible. If PONV occurs within 6 hours postoperatively, patients
should not receive a repeat dose of the prophylactic antiemetic; a drug from a different class should be used for
rescue. Beyond 6 hours, PONV can be treated with any of the antiemetics used for prophylaxis except
dexamethasone and scopolamine, which are longer acting.

In summary, PONV and pain are very common following ambulatory surgery and should be managed
aggressively. The thorough understanding of the mechanism of these common symptoms and a careful assessment
of risk factors provide a rationale for appropriate management of PONV and pain. The adoption of a
comprehensive and multimodal approach for both symptoms will likely ensure success in the management.

324
Page 7

References

1. Jain S, et al. Chest Surg Clin N Am 1997;7:773-99.
2. Breivik H, et al. Eur J Anaesthesiol 1998;15:748-51.
3. Carr DB, et al. Lancet 1999;353:2051-8.
4. American Society of Anesthesiologists. Anesthesiology 1995;82:1071-81.
5. Twersky R, et al. Anesth Analg 1997;84:319-24.
6. Apfelbaum JL, et al. Anesth Analg 2003;97:534-40.
7. Gan TJ. JAMA 2002;287:1233-6.
8. Habib AS, et al. Current Medical Research & Opinion 2006;22:1093-9.
9. Hill RP, et al. Anesthesiology 2000;92:958-67.
10. Gold B, et al. JAMA 1989;262:3008-10.
11. Philip BK. Journal of Clinical Anesthesia 1992;4:355-8.
12. Likar R, et al. J Pain Symptom Manage 2001;21:330-7.
13. Likar R, et al. Pain 1998;76:145-50.
14. Michaloliakou C, et al. Anesth Analg 1996;82:44-51.
15. Bisgaard T, et al. Anesth Analg 1999;89:1017-24.
16. Eriksson H, et al. Acta Anaesthesiol Scand 1996;40:151-5.
17. Kehlet H, et al. Drugs 2003;63 Spec No 2:15-22.
18. Sinatra RS, et al. Anesthesiology 2005;102:822-31.
19. Edwards JE, et al. J Pain Symptom Manage 2002;23:121-30.
20. Zhou TJ, et al. Anesth Analg 2001;92:1569-75.
21. Alexander R, et al. Journal of Clinical Anesthesia 2002;14:187-92.
22. Van Dyke T, et al. Clin Ther 2004;26:2003-14.
23. Pickering AE, et al. Br J Anaesth 2002;88:72-7.
24. White PF, et al. Anesth Analg 2011;112:323-9.
25. Raffa RB, et al. J Pharmacol Exp Ther 1992;260:275-85.
26. Horishita T, et al. Pharmacology 2006;77:93-9.
27. Wilder-Smith CH, et al. Br J Clin Pharmacol 1997;43:71-5.
28. Moore RA, et al. Pain 1997;69:287-94.
29. Smith AB, et al. Am J Surg 2004;187:521-7.
30. Aida S, et al. Anesthesiology 2000;92:1624-30.
31. Kararmaz A, et al. Anesth Analg 2003;97:1092-6, .
32. Kwok RF, et al. Anesth Analg 2004;98:1044-9, .
33. Menigaux C, et al. Anesth Analg 2001;93:606-12.
34. Reeves M, et al. Anesth Analg 2001;93:116-20.
35. Snijdelaar DG, et al. Anaesthesia 2004;59:222-8.
36. Wilcox GL. Pain Research and Clinical Management 1991:97-118.
37. Weinbroum AA. Anesth Analg 2003;96:789-95, .
38. Adam F, et al. Anesth Analg 2005;100:475-80.
39. Moiniche S, et al. Br J Anaesth 1998;81:377-83.
40. Ballantyne JC, et al. Anesth Analg 1998;86:598-612.
41. S.R. G, et al. Dis Colon Rectum 2011;54:1552-9.
42. Golf M, et al. Adv Ther 2011;28:776-88.
43. Tverskoy M, et al. Neurosci Lett 1996;215:5-8.
44. Calmet J, et al. Knee Surg Sports Traumatol Arthrosc 2004;12:552-5.
45. Dal D, et al. Arthroscopy 2004;20:300-5.
46. Dauri M, et al. Acta Anaesthesiol Scand 2003;47:20-5.
47. Moiniche S, et al. Reg Anesth Pain Med 1999;24:430-7.
48. Buckenmaier CC, 3rd, et al. Anesth Analg 2003;97:715-7.
49. White PF, et al. Anesth Analg 2003;97:1303-9.
50. Chelly JE, et al. J Arthroplasty 2001;16:436-45.
51. Singelyn FJ, et al. Anesth Analg 1997;84:383-6.
52. Chelly JE, et al. Minerva Anestesiol 2001;67:613-9.
53. Murphy DB, et al. Anesth Analg 2000;90:1122-8.
54. Tan T, et al. Anesth Analg 2010;111:83-5.
324
Page 8

55. Pyati S, et al. CNS Drugs;21:185-211.
56. Sun Y, et al. Br J Anaesth;101:151-60.
57. Kehlet H, et al. Anesth Analg 1993;77:1048-56.
58. Kehlet H, et al. Br J Anaesth 2001;87:62-72.
59. Kehlet H, et al. Langenbecks Arch Surg 2004;389:244-9.
60. Kehlet H, et al. Drugs 1999;58:793-7.
61. Werner MU, et al. Anesth Analg 2002;95:1361-72.
62. Spaulding TC, et al. Eur J Pharmacol 1979;58:19-25.
63. Altman RD, et al. Clin Exp Rheumatol 2004;22:110-7.
64. Suzuki M, et al. Anesth Analg 2005;101:777-84.
65. Chia YY, et al. Anesth Analg 1998;86:1245-9.
66. Lavand'homme P, et al. Anesthesiology 2005;103:813-20.
67. Apfel CC, et al. BJA 2002;88:659-68.
68. Tramer M, et al. Br J Anaesth 1996;76:186-93.
69. Apfel CC, et al. Anesthesiology 1999;91:693-700.
70. Tramer MR, et al. Br J Anaesth 1999;82:379-86.
71. Sinclair DR, et al. Anesthesiology 1999;91:109-18.
72. Koivuranta M, et al. Anaesthesia 1997;52:443-9.
73. Andersen R, et al. Can Anaesth Soc J 1976;23:366-9.
74. Jenkins LC, et al. Can Anaesth Soc J 1971;18:434-41.
75. Rees MR, et al. Br J Clin Pharmacol 1980;10:551-4.
76. Eberhart LH, et al. Anaesthesist 2000;49:532-5.
77. Kranke P, et al. Acta Anaesthesiol Scand 2001;45:160-6.
78. Fabling JM, et al. Anesth Analg 2000;91:358-61.
79. Gan TJ, et al. Anesthesiology 1996;85:1036-42.
80. Haigh CG, et al. Br J Anaesth 1993;71:517-22.
81. Honkavaara P. Br J Anaesth 1996;76:49-53.
82. Larsson S, et al. Acta Anaesthesiol Scand 1990;34:227-30.
83. Lerman J. Br J Anaesth 1992;69:24S-32S.
84. Rowley MP, et al. Anaesth Intensive Care 1982;10:309-13.
85. Gan TJ, et al. Anesth Analg 2007;105:1615-28.
86. Rodseth RN, et al. Anesth Analg 2010;110:1591-4.
87. Apfel CC. Anesthesiology 2012 (in press).
88. Yogendran S, et al. Anesth Analg 1995;80:682-6.
89. Holte K, et al. Anesth Analg 2007;105:465-74.
90. Orhan-Sungur M, et al. Anesth Analg 2008;106:1733-8.
91. Gan TJ, et al. Anesth Analg;98:1665-73.
92. Tufanogullari B, et al. Anesth Analg 2008;106:1741-8.
93. Visser K, et al. Anesthesiology 2001;95:616-26.
94. Parikh PM, et al. Cancer 1988;66:2263-4.
95. Apfel CC, et al. New England Journal of Medicine 2004;350:2441-51.
96. Henzi I, et al. Anesth Analg 2000;90:186-94.
97. Tramer MR. Acta Anaesthesiol Scand 2001;45:14-9.
98. Habib AS, et al. Canadian Journal of Anaesthesia 2004;51:311-9.
99. Habib AS, et al. Anesth Analg 2011;112:813-8.
100. Scuderi PE, et al. Anesth Analg 2000;91:1408-14.
102. Apfel CC, et al. Clin Ther 2010;32:1987-2002.
103. Ludwin DB, et al. Anesth Analg 2008;106:1418-20.
105. Rosow CE, et al. Anesth Analg 2008;106:1407-9.
107. Chu CC, et al. Anesth Analg 2008;106:1402-6.
108. Saito R, et al. J Pharmacol Sci 2003;91:87-94.
109. Diemunsch P, et al. Br J Anaesth 1999;82:274-6.
110. Gesztesi Z, et al. Anesthesiology 2000;93:931-7.
324
Page 9

114. Altorjay A, et al. Archives of Surgery 2011;146:201-6.
115. ALOXI (palonosetron hydrochloride) injection [prescribing information]. Lugano, Switzerland. 2006.
116. Aapro M. Oncology 2005;69:97-109.
117. Candiotti KA, et al. Anesth Analg 2008;107.
118. Gan TJ, et al. Anesthesia & Analgesia 2003;97:62-71.
119. Tramer MR, et al. BMJ 1997;314:1088-92.
121. Polati E, et al. Anesth Analg 1997;85:395-9.

Disclosure
Merck, Funded Research ; Fresenius, Funded Research, Honoraria ; Pacira, Funded Research, Honoraria ;
Accel Rx
404
Page 1
Ultrasound-guided Regional Anesthesia for Ambulatory Patients
Meg A. Rosenblatt, M.D. New York, New York
Introduction
Outpatient surgeries now account for more than two-thirds of all surgeries performed in the United States and after
GI endoscopies, and ophthalmologic procedures, orthopedic operations (surgery of the muscle, tendon, fascia and
bursa) are the next most frequently performed .
1
The advantages that regional anesthesia (RA) confers over general
anesthesia (GA), especially in the outpatient setting, are numerous. Specifically, orthopedic patients are the group
of ambulatory patients with the highest incidence (16.1%) of pain in the PACU.
2
Peripheral nerve blocks (PNBs)
offer predictable intraoperative anesthesia, as well as provide analgesia into the postoperative period, the
opportunity to bypass Phase I recovery, and the avoidance of airway manipulations. Ultrasound (US) imaging
permits direct visualization of peripheral nerves, needle location and distribution of local anesthetic. The use of US-
guidance to perform nerve blocks is associated with decreased time to onset and quality of block which is equal to or
better than PNBs performed with nerve stimulator (NS) techniques,
3,

4
and the use of US facilitates the placement
of blocks in patients who are obese, may be on anticoagulants and those with challenging external anatomy.
Since the mastery of US-guided PNBs frequently does not occur during residency, their successful incorporation
into practice requires that an anesthesiologist continues to acquire skills while often having to work in a rapid
turnover environment and meet high surgeon and patient expectations. Performing US-guided nerve blocks requires
an entirely new skill set for practitioners. Firstly, one must learn to operate ultrasound equipment and then use this
to identify anatomy as it appears on a two-dimensional screen. Secondly, one must be able to simultaneously use
both hands (one holding the ultrasound transducer and the other holding the block needle), watch the display screen,
and manipulate the needle into the nerve sheath. Lastly, it is necessary to learn to identify patterns of local
anesthetic spread that are associated with optimal plexus blockade. Smith designed a learner-centered curriculum
which describes the three elements that need to be acquired. They are the use of the US equipment (management of
the machine, choice of probe, medical record documentation), scanning techniques and sonoanatomy (performing
the exam, distinguishing anatomical elements, recognizing artifacts) and sonographic needle guidance
(understanding needle/probe orientation, optimizing needle visualization).
5

Enlisting the surgeon to introduce the concept of PNBs when they offer patients their preoperative instructions will
improve patient acceptance. Local anesthetics should be chosen to minimize onset times and limit the use of GA in
order to prevent operating room delays. Meticulous follow-up until resolution of all blocks along with
communication with the surgeons can add to overall satisfaction.
Local Anesthetics and Adjuvants
Local anesthetic (LA) agents should be chosen according to the desired duration of action and the required degree of
motor blockade. An insensate extremity in a patient whose procedure may not produce much post-operative
discomfort may be at risk for injury secondary to the loss of protective reflex to pain, or place the patient at risk
secondary to a loss of proprioceptionblocks of the longest possible duration are not always the wisest choice.
Whereas some practitioners combine LAs to decrease onset time while providing long duration, combining
chloroprocaine 2% and bupivacaine 0.5% causes pH changes that create a block that resembles one produced by
bupivacaine alone. Galindo concluded that mixing LAs leads to unpredictable blockade characteristics.
6
Gratenstein
looked at US-guided interscalene blocks with 30 mL in 3 different solutionsmepivacaine 1.5%, bupivacaine0.5%
and a 50:50 mixture of the two, and found that mixing the short and long-acting agents does not result in a
significant difference in onset time compared with either solution alone.
7
LAs diffuse into nerves and the rate of
diffusion is determined by the concentration, therefore higher concentrations of LAs result in more rapid onset of

404
Page 2
blockade. Ropivacaine 0.75% has been shown to have similar or shorter onset times for femoral, sciatic and
interscalene blocks, while providing significantly longer postoperative analgesia than mepivacaine and
bupivacaine.
8,9
The effect of alkalinization of agents on the speed of onset of the block is unclear. It has been shown
to offer no advantage in perivascular blocks with 0.5% bupivacaine,
10
but improvement in onset and quality of
analgesia in axillary blocks with 1.25% mepivacaine,
11
and in femoral and sciatic blocks with 2% mepivacaine has
been demonstrated.
12
Adding sodium bicarbonate to lidocaine has been shown to have no effect on the onset of
axillary block,
13
and in rats it has been shown to decrease the intensity and duration of the block.
14
In one study
fentanyl improved the sensory blockade achieved with an axillary block using 1.5% lidocaine, but the pH changes it
conferred delayed the onset of analgesia.
15
Other studies have not shown efficacy of either fentanyl or morphine in
the improvement of onset or quality of axillary blocks.
16,17
Clonidine, an !
2
-agonist, is known to prolong the
duration of sensory and motor blockade, particularly when added to local anesthetics of intermediate duration. One
study of 56 patients undergoing carpal tunnel release under axillary block with 1% lidocaine and varying amounts of
clonidine, showed a reduction in block onset time. However, even with doses as small as 30g, patients experienced
sedation. More than 50% of patients were reported to fall asleep intermittently at 140 minutes after performance of
the block.
18

Recently the utility of adding dexamethasone to upper extremity blocks. The addition of dexamethasone 8 mg to 30
mL mepivaciane has been shown to significantly prolong the duration of a supraclavicular block.
19
Eight mg of
dexamethasone was shown to prolong the duration of action of ropivacaine (11.8 vs 22.2 hrs) and bupivacaine (14.8
vs 22.4 hrs) when added to 30 mL of local anesthetic for interscalene anesthesia.
20
Tando and colleagues found no
difference in the duration of analgesia between adding 4 mg and 8 mg doses of dexamethasone to interscalene
blocks using 40mL bupivacaine.
21
There exact mechanism of this prolongation of action is yet to be elucidated.

The 5 US-Guided PNBs Every Ambulatory Practitioner Needs and When to Use Them
The following is a discussion of useful blocks and their specific applications for outpatients. Mastery of the
interscalene (ISB), supraclavicular, femoral, popliteal and transverses abdominis plane (TAP) blocks will be
adequate for almost all of the needs of the anesthesiologist who has an ambulatory-based practice. Learning the
infraclavicular block may be advantageous if the practitioner will be providing continuous postoperative analgesia
after surgery of the elbow, forearm or hand. All can be performed with a linear array probe which is 13 to 16 mHz
and 25 mm wide and a 22g, 50 mm needle.
Upper Extremity US-Guided Peripheral Nerve Blocks
This author is of the belief that one needs to master only two single-shot PNBs to be able to adequately anesthetize
the entire upper extremity for ambulatory surgeryISB and supraclavicular block. Both of these blocks can be
accomplished by learning a simple scanning technique. The patient is placed in the supine position with his or her
head flat on the bed (without pillows) and turned towards the contralateral shoulder. The region to be blocked is
sterilely prepped:
22

!" Identify the carotid artery and internal jugular vein, with the probe in the horizontal position, just above
the clavicle.
2) Moving the probe laterally along the clavicle and aiming the beam caudad, towards the first rib, the
subclavian artery is identified as the next pulsatile structure that is visualized. The brachial plexus at the level of the
divisions appears as a bag of grapes located lateral to the artery. To perform a supraclavicular block at that level, a
22 gauge block needle is inserted in-plane (parallel to the probe), until it reaches the location that is bordered by the
subclavian artery medially, the first rib inferiorly, and the divisions of the brachial plexus superior laterally--the
eight ball in the corner pocket position.
23
This block is ideal for all procedures of the elbow and distally. 30- 40 ml
of local anesthetic will be more than adequate to provide a block.
3) It is then possible to choose the largest of the nerves, appearing as a radiolucent circle and trace it
cephalad, as the probe is kept in the horizontal position. When the C-6 level is reached, this nerve and the others of
the brachial plexus are seen in a vertical orientation, between the anterior and middle scalene muscles. The 22-
gauge block needle is inserted either in-plane or out-of-plane and directed towards the previously identified nerve,
within the sheath. The out-of-plane approach may be preferable to an in-plane one for practitioners who have
experience with using a vessel finder for central venous line placement. Again, 30-40 ml of local anesthetic will
provide adequate anesthesia. In a study looking at 170 patients undergoing shoulder surgery, Spence sought to
describe the ideal location to inject LAeither peri-plexus (between the middle scalene muscle and brachial
plexus), or intra-plexus (injection within the brachial plexus sheath). After injecting 30 mL bupivacaine 0.5%, they

404
Page 3
looked for loss of shoulder abduction. Onset times and block quality were equal, but the intra-plexus blocks resulted
in statistically significantly longer block duration (2.6 hrs, p=0.03).
24

Data show that when 5mL vs. 20 ml of ropivacaine are used for in ISB combined with GA for the surgical
procedure, patients have fewer respiratory and other complications with no change in postoperative analgesia.
25

More recently this group showed that with the use of US, the minimum effective analgesic volume of ropivacaine
0.5% in an ISB required to provide analgesia in the immediate post op period is 0.9mL.
26
Although studies show
that much less LA can be used, the effect on the adequacy of these smaller volumes as the sole anesthetic for surgery
has not been described. Interestingly, 61 patients were undergoing US-guided ISB performed with insulated needles
for ambulatory shoulder surgery. After the needle tip was determined to be in the interscalene groove the nerve
stimulator was turned on and the lowest current eliciting a response was noted. The sensory analgesia achieved
between the groups with responses at <0.5 mA and >0.5 mA was similar, thus confirming that US-guided blocks
produce successful analgesia regardless of the motor stimulation evoked.
27

The use of US has been shown to speed the execution and improve the quality of supraclavicular blocks.
28
Perlas et
al described their experience with 510 consecutive US-guided supraclavicular blocks, and reported a 94.6% success
at achieving surgical anesthesia with a single attempt. Complications included symptomatic hemidiaphragmatic
paresis (1%), Horner syndrome (1%), vascular puncture (0.4%) and transient sensory deficit (0.4%). They
concluded that this US-guided block is a safe and effective technique.
29
A prospective registry of 1,169 US-guided
ISB and supraclavicular blocks for shoulder surgeries shows a 0% incidence of vascular puncture, 0.4%incidence of
short-term postoperative neurologic symptoms and a 0% incidence of permanent nerve injury.
30

Since Sauter used MRI to define the anatomic location of the cords of the infraclavicular brachial plexus, we know
that needle placement at the VIII oclock position adjacent to the axillary artery in the cranioposterior quadrant
and observing satisfactory spread of local anesthetic between the III oclock and IX oclock positions will predict
a successful infraclavicular block.
31
The use of US-guidance (with the probe in a sagital position medial to the
corticoid process and employing an in-plane technique) for single shot infraclavicular blocks yields high success
rates and trends toward improved block quality.
32

Practitioners who perform US-guided axillary blocks find that there is a greater success rate for achieving surgical
anesthesia and shorter performance times than when nerve stimulation or transarterial techniques are used.
33
Thirty
to 40 ml of local anesthesia is injected to ensure circumferential spread around the axillary artery. Mccairre
described using US-guided median and ulnar nerve blocks at the wrist to provide anesthesia for endoscopic carpal
tunnel release. Through a single injection site located 5 to 10 cm proximal to the wrist crease in the anterior
forearm, both nerves are blocked under direct vision, each with 4 ml of 1.5% mepivacaine. This is supplemented
with 1-2 ml of local anesthetic at the level of incision in the wrist crease in order to block the palmaris ramus of the
median nerve.
34

Lower Extremity US-guided Peripheral Nerve Blocks
US-guided blocks of the lower extremity that are useful in ambulatory practice include femoral, saphenous and
popliteal blocks. The femoral nerve is located by placing the linear probe in the inguinal crease. It is the dense
white structure, lateral to the hypoecoic pulsatile femoral artery and deep to both the fascia lata and fascia iliaca.
This can be blocked with a 22g needle in an in- or out- of plane approach and a successful block is anticipated when
local anesthesia spread is seen surrounding the nerve. This block is particularly useful for patients undergoing
repairs of the anterior cruciate ligament or surgical procedures involving the patella. Performing a fascia iliaca
block is an alternative to the femoral nerve block, and may be more successful for blocking the lateral femoral
cutaneous nerve and occasionally the obturator nerve. A line drawn between the anterior superior iliac spine and
pubic tubercle is divided in thirds. At the junction between the middle and lateral thirds an ultrasound probe is
placed in a transverse position and the fascia lata and iliaca are identified. The needle is placed under the fascia
iliaca, and 30 ml of local anesthetic is injected. Spread of local anesthetic in medial and lateral directions under the
fascia iliaca is evidence of correct needle placement.

For surgical procedures below the knee, the sciatic nerve in the popliteal fossa can be blocked either from a posterior
or lateral approach. The posterior approach requires placing the patient in a prone position and the hyperechoic
nerve is located at the midpoint between the tendons of the biceps femoris and the semitendinosus/semimembranosis
muscles. The popliteal artery is located medial and deep to the nerve, and is an excellent landmark from which to

404
Page 4
begin scanning superior and laterally. It is essential to identify the point of division of the sciatic nerve into the
common peroneal and anterior tibial nerves, and place the needle proximal to this point to ensure that both divisions
are blocked. US-guidance has been shown to increase success of block and decrease onset time compared to a NS
technique.
35
For the lateral approach, the patient remains in the supine position and it is helpful to have the patients
leg placed on a bolster, with the US probe placed underneath. A 100 mm needle is inserted parallel to the probe and
directed towards the hyperechoic nerve, again insuring that it has not yet divided. For either approach, 30 ml of local
anesthetic will ensure an adequate block.

To provide complete analgesia of the lower extremity with the popliteal block, anesthesia of the saphenous
distribution (medial side of the lower extremity) is necessary. And, in order to preserve quadriceps muscle function
(which would not be possible with a femoral nerve block), the saphenous nerve can be blocked at the level of the
tibial tuberosity. This can be accomplished by locating the saphenous vein in the short axis view, and then
delivering 5 ml of local anesthesia both medial and lateral to the vessel.
36
Because it may be difficult to identify the
saphenous nerve at this level, it may be easier to identify the nerve as it travels deep to the sartorius muscle, adjacent
to a descending branch of the femoral artery. With the patients lower extremity externally rotated at the hip, the
probe is placed perpendicular to the extremity 7 cm proximal to the popliteal crease. Using an in-plane approach, 10
ml of local anesthesia is deposited deep to the sartorious muscle anterior and superior to the artery, where the nerve
is visualized.
37

US is now being used to improve the success rate of PNBs nerve blocks at the ankle. The sural nerve has been
shown to lie adjacent to the lesser saphenous vein. Redborg placed his patients in a prone position with a tourniquet
around the proximal tibia, to allow easy identification of the vein, and using a 27 gauge needle in an out-of-plane
technique, injected 5 ml of local anesthetic. The endpoint was to observe the spread of local anesthesia completely
around the lesser saphenous vein. Although the US blocks took longer to perform than anatomically based ones
(172 sec vs. 70 sec), they were considered to be denser in quality.
38
She also described using US to block the tibial
nerve at the ankle. Again, patients were placed in the prone position, and the probe was placed in a horizontal plane
posterior to the medial malleolus. The nerve can be identified posterior to the posterior tibial artery. The flexor
hallucis longus tendon travels with the neurovascular structures at that level and may look like the nerve; therefore
the author suggests demonstrating motion of the tendon with movement of the great toe in order to differentiate it
from the nerve. Using 5 ml of local anesthetic and demonstrating circumferential spread around the nerve is
associated with block success.
39

Truncal Blocks
The TAP block is gaining popularity as a method for postoperative analgesia for procedures of the abdomen,
including laparoscopic appendectomy
40
and cholecystectomy.
41
The block is accomplished by placing a linear array
probe horizontally at the T10 level and moving laterally until it is possible to identify the following abdominal
layers: skin/subcutaneous tissue, external oblique muscle, internal oblique muscle, and transversus abdominis
muscle (below which is peritoneal cavity). Using a 22 gauge block needle and an in-plane approach, 20 ml of
0.25% bupivacaine is deposited on one or both sides, depending upon the location of the surgical incisions. This
block has been shown to reduce both the intraoperative and postoperative use of narcotic analgesics. US-guidance
has also been described to place ilioinguinal and iliohypogastric blocks to provide analgesia following outpatient
inguinal herniorrhaphy. After identifying the anterior superior iliac spine, the anterior abdominal muscle layers, and
the peritoneum, a needle is inserted into the fascial plane between the internal oblique muscle and transversus
abdominis muscle. Occasionally it is possible to identify the iliohypogastric nerve. Lastly, the rectus sheath block
has been described to block the lower thoracic nerves and provide analgesia for midline incisions and procedures
around the umbilicus. Needles are inserted 5 cm above and below the umbilicus and 5 cm bilaterally, and injecting
10 ml of local anesthetic in each quadrant between the anterior and posterior rectus sheaths.
42

Indwelling Catheter Techniques
For ambulatory practitioners who place indwelling catheters, US-guidance has proven to provide analgesia equal to
that achieved when a NS technique is employed, with statistically significant shorter time from needle placement
under to catheter insertion and lower catheter insertion pain scores.
43
For interscalene catheters, some advocate a
posterior approach to the interscalene groove, which provides postoperative analgesia and offers the advantages of
avoidance of the external jugular vein and placement of the catheter further away from the surgical field.
44
However
the use of GA is necessary since the nerves of the superficial cervical plexus and the skin around the shoulder are
not anesthetized. When placing catheters for forearm and hand procedures, an infraclavicular approach offers the

404
Page 5
advantage of a more secure position under both the pectoralis major and minor muscles. In this position there is less
leakage around the catheter than from more superficially placed ones (i.e., supraclavicular and interscalene
catheters). And US-guided infraclavicular catheters result in higher primary block success and decreased secondary
catheter failure when compared to traditional insertion techniques.
45

There are conflicting data regarding the ideal solutions for ambulatory catheters. For example, Lee found that low
concentrations of anesthetic at higher basal rate provided superior analgesia to patients with interscalene catheters.
46

Conversely, Ilfeld showed that for continuous popliteal-sciatic nerve blocks, concentrated solutions of small volume
provided excellent analgesia, with a lower incidence of insensate limbs.
47

Interestingly, Clendenen just reported a series of 5 cases of difficult removal of stimulating catheters placed in the
interscalene groove of ambulatory patients. In each case the polyurethane sheath sheared from stainless steel coil
and the coil was retained, requiring 4 of the patients to return to the hospital. Therefore, it may be prudent to avoid
the use of stimulating catheters in the ambulatory population.
48

Patient Instructions and Follow-Up
Whenever a regional anesthetic is performed, detailed instructions must be given to the patient,
49
offering an
expectation of the duration and extent of their block, the requirement to protect the insensate limb, and the need to
begin analgesic medications prior to his/her experiencing severe pain. Timely follow-up must be conducted to
ensure complete block resolution. Borgeat specifies in his study following 521 patients after interscalene block, that
sulcus ulnaris syndrome, carpal tunnel syndrome or complex regional pain syndrome must be excluded in the
presence of persistent paresthesia, dysesthesia or pain not related to the surgery, because specific interventions may
be necessary to treat those conditions.
45
Should any persistent neurologic deficit be discovered during a
postoperative interview, the patient should be reassured that it will resolve, and that the anesthesiologists
participation in the follow-up is certain. Discussion with the surgeon should include a plan for neurologic
evaluation.

Conclusions
The use of PNBs is associated with shortened post-procedure operating room, PACU and discharge times, provision
of postoperative analgesia, and a high level of patient satisfaction. Numerous techniques have been described in
order to provide anesthesia and analgesia for ambulatory surgical procedures. The introduction of US into the
practice of regional anesthesia offers new and exciting challenges for todays regionalists. Regional techniques
should be both encouraged and employed for procedures in outpatients.

References
1
Cullen KA, Hall MJ, Golosinsky A. Ambulatory Surgery in the United States, 2006. National Health Statistics
Reports, U.S. Department of Health and Human Services, CDC 2009;11:1-28.
2
Chung F, Ritchie W, Su J. Anesth Analg 1997;85:808-16.
3
Williams SR, Chouinard P, Arcand G, et al. Anesth Analg 2003;97:1518-23.
4
Marhofer P, Schrogendorfer K, Koinig H. Anesth Analg 1997;85:854-7.
5
Smith HM, Kopp SL Jacob AK et al. RAPM 2009;34:88-94.
6
Galindo A, Witcher T. Anesth Analg 1980;59:683-5.
7
Gratenstein K, Mirza F, Malaikai T, et al. ASA 2009; abstract A416.
8
Casati A, Fanelli G, Aldegheri G, Berti M, et al. Br J Anaesth 1999;83:872-5.
9
Fanelli G, Casati A, Beccaria P, et al. Anesth Analg 1998;87:597-600.
10
Bedder MD, Kozody R, Craig DB. Anesth Analg 1988;67:48-52.
11
Quinlan JJ, Oleksey K, Murphy FL. Anesth Analg 1992;74:371-4.
12
Capogna G, Celleno D, Laudano D, Giunta F. Reg Anesth 1995;20:369-77.
13
Chow MYH, Sia ATH, Koay CK, Chan YW. Anesth Analg. 1998;86:566-8.
14
Sinnott CJ, Garfield JM, Thalhammer JG, Strichartz GR. Anesthesiology 2000;93:1045-52.
15
Nishikawa K, Kanaya N, Nakayama M et al. Anesth Analg 2000;91:384-7.
16
Fletcher D,Kuhlman G, Samii K. Reg Anesth 1994;19:183-8.
17
Raca H , Gunning K, Della Santa D, Forster A. Anesth Analg 1991;72:769-72.
18
Bernard JM, Macaire P. Anesthesiology 1997;87:277-84.

404
Page 6

19
Parrington SM, ODonnell D, Chan VWS et al. RAPM 2010;35:422-26.
20
Cummings KC, Napierkowski DE, Parra-Sanchez I. BJA 2011;107:446-53.
21
Tandoc MD, Fan L, Kolesnikov S, et al. J Anesth 2011;25:704-9.
22
Soffer RJ, Rosenblatt MA. JCA 2007;19:241-2.
23
Soares LG, Brull R, Lai J, Chan VW. Reg Anesth Pain Med 2007;32:94-5.
24
Spence BC, Beach ML, Gallagher JD, Sites BD. Anaesthesia 2011;66:509-14.
25
Riazi S, Carmichael N, Awad I, et al. Br J Anaesth 2008;101:549-56.
26
McNaught A, Sastri U, Carmichael N. Br J Anaesth 2011;106:124-30.
27
Sihna SK, Abrams JH, Weller RS. Anesth Analg 2007;105:848-52.
28
Williams SR, ChouinardP, Arcand G, et al. Anesth Analg 2003;97:1518-23.
29
Perlas A, Lobo G, Lobo N, et al. RAPM 2009;34:171-6.
30
Liu SS, Gordon MA, Shaw PM, et al. Anesth Analg 2010;1111:617-22.
31
Sauter AR, Smith HJ, Stubhaug A, et al. Anesth Analg 2006;103:1574-6.
32
Gurkan Y, Acar S. Solak M, Toker K. Acta Anaesthesiol Scand 2008;52:851-55..
33
Lo N, Brull R, Perlas A, et al. Can J Anesth 2008;55:408-13.
34
Maccaire P, Singelyn F, Narchi P, Paqueron X. Anesth Analg 208;33:363-8.
35
Pwerlas A, Brull R, Chan VWS, et al. Reg Anesth Pain Med 2008;33:259-65.
36
Gray AT, Collins AB. Reg Anesth Pain Med 2003;28:148.
37
Krombach J, Gray AT. Reg Aneth Pain Med 2007;32:370-1.
38
Redborg KE, Sites BD, Chinn CD., et al. Reg Anesth Pain Med 2009;34:24-28.
39
Redborg KE, Antonakakis JG, Beach ML, et al. Reg Anesth Pain Med 2009;34:256-60.
40
Mukhtar K, Singh S. Br J Anaesth 2009;102:143-4.
41
El-Dawlatly AA, Turkistani A, Kettner SC et al. Br J Anaesth 2009;102:763-7.
42
Dolan J, Lcie P, Gear T, et al. Reg Anesth Pain Med 2009;34:247-50.
43
Fredrickson MJ, Ball CM Dalgleish AJ et al. Anesth Analg 2009;108:1695.
44
Mariano ER, Afra R, Loland VJ, et al. Anesth Analg 2009;108:1688-94.
45
Dhir S, Ganapathy S. Acta Anaesthesiol Scand 2008;52:1158-66.
46
Lee LT, Loland VJ, Mariano ER et al. Reg Anesth Pain Med 2008;33:518-525.
47
Ilfeld BM, Loland VJ, Gerancher JC. Anesth Analg 2008;107:701-06.
48
Clendenen SR, Robards CB, Greengrass RA, Brull SJ. Can J Anesth 2011;58:62-67.
49
da Conceicao DB, Helayel PE. Rev Bras Anestesiol;2008;58::51-4.

Disclosure

410
Page 1
Outcomes and the ASC: the Role of the Medical Director and Measurement in Improving
Clinical and Business Outcomes
Douglas G. Merrill M.D. MBA Lebanon, New Hampshire
Its not what we dont know that hurts us.
Its what we know for sure that just aint so.
Mark Twain
Introduction
Measurements and analysis of financial and functional performance to support the achievement of individual and
organizational goals are required tools of management for any business enterprise. The use of outcomes to direct
strategic management decisions to attain goals is integral to the theory of knowledge management, a core aspect of
modern business management.
1
The learning organization theory grew from the need to respond to customer
demand with rapid process improvement. Defined by one writer
2
as the process whereby organizations understand
and manage their experiences, it includes the use of customer-focused data collection and assessment, employee-
centric management, benchmarking and best practice implementation and process re-engineering in response to
data.
3
This methodology is what Argyris and Schon defined as the employees response when they
4

experience a surprising mismatch between expected and actual results of action and
respond to that mismatch through a process of thought and further action that leads them
to modify their images of organization or their understandings of organizational
phenomena and to restructure their activities so as to bring outcomes and expectations
into line
A surprising mismatch is an apt description for the response of many physicians, nurses and other healthcare
providers when they first are given objective evidence of their patients perioperative experience. Most providers do
not know their specific, individual performance on the metrics that matter to their patients and to the success of the
business enterprise.
Before we go further, ask yourself if you know your personal nausea and vomiting rates (both) for the recovery
room (PACU) and also after discharge home. Do you know exactly how many of your patients would return to your
facility if the need arose, or to have you again as their provider, given a choice? These metrics are as important to
the health and survival of your practice as are market penetration or contribution margin, yet the majority of us do
not know them. PONV and PDNV top the list of patient concerns
5
and, with the increasingly competitive business
environment for healthcare, such data may be reflected in your profile on Angies List, Yelp, or on any of the
myriad physician grade websites.
Further, attempts to improve your facilitys clinical and financial performance are dependent upon your ability to
convince your physicians and nurses of the need to change. Given the highly intelligent and high degree of
resistance to change that characterizes most our professions, without data showing that a problem (the euphemistic
opportunity) exists, you will not be successful in gaining their support for change, and thus it will not occur. In
addition to the general human resistance to change, practitioners are susceptible to bias and more expert providers
may actually be more susceptible to all forms of bias.
6

7
The foundation of successful intentional process change
is credible measurement that reveals the gap between the current and the desired state to those who must
create and sustain the change.
In the past 50 years, this management by measurement has become an integral tactic to the administration of the
health care enterprise and has stimulated the large body of literature on healthcare quality as represented by
Donabedians work on quality improvement.
8

9
These techniques are now widely applied in healthcare.
10

11
Indeed,

410
Page 2
outcome measurement is critical to quality improvement.
12
However, collection of data and sharing with providers
so that they can experience a surprising mismatch is not widespread in perioperative practice. Here, we will
examine the value of such measurement and discuss the role of the Medical Director and her or his team in the
management of that data and its use in altering care, process, business and accreditation outcomes for the better.
Finally, we will discuss the potential positive impact of measurement as a means of changing the culture of an
institution, change that is extremely difficult but necessary to most facilities success (and survival).

The Role of the Medical Director
Inherent in this lecture is the assumption that the Medical Director serves as a leader in the ASCs management. In
most cases, the Medical Director in an ambulatory surgery center (ASC) has long since become an integral part both
of the medical team and the business team that manages the ASC. Gone are the days (we hope!) of the medical
director merely filling a daily role of waiting for the discharge of the last patient. Instead, he or she should expect to
fully participate in the creating of policies and procedures that will improve the safety of the patients and the high
quality of their surgical, anesthesia and nursing care. As well, the Medical Director is most often accountable for
decisions regarding marketing to and credentialing of surgeons and other providers, a significant part of the strategic
management of the ASC. It is the intent here to show the value of including the Medical Director in such decision
making and the reason that physicians should demand outcomes data access, if offered the opportunity to serve in
such a capacity.

Evidence Based Medicine and Clinical Outcome Measurement
Two complaints sometimes raised about Evidence-Based Medicine (EBM) are that it stymies care innovation by
encouraging standardized practice (care pathways) and is of little value in guiding much of routine clinical practice,
because the randomized controlled trials it requires have not or cannot be performed in many clinical situations.
However, the early proponents of EBM actually stated that, the practice of evidence based medicine means
integrating individual clinical expertise with the best available external clinical evidence from systematic
research.
13
In reality, EBM is actually a construct of expertise garnered locally, combined with the best that the
literature can offer. The cornerstone of EBM is actually its de-emphasis of expert opinion in favor of the lessons of
local experience. The appropriate means to garner accurate local experience in a useful format is the copious
collection of outcomes in a database. Then, the application of EBM is accomplished by the careful scrutiny of those
data, assessment for trends and linkages between practice and outcome, and a resulting focus on quality
improvement efforts unencumbered by anecdote or defensiveness.
14
Done well, with objective, equanimous and
open sharing of data, exchange of ideas and decisions on action followed by careful re-assessment and open
discussion of outcomes, this measurement can form the cornerstone of effective quality improvement efforts in any
perioperative environment.

Requirements of Measurement and Sharing of Data
To support the goals discussed here, the metrics chosen must meet certain criteria: accuracy, risk adjustment, regular
presentation to all stakeholders, and controllable by those providers who are being held accountable. As well, there
must be an ongoing tailoring of the metrics to meet changes in strategic goals of the organization.
The concept of publishing data and identifying responsible caregivers has been done with post-cardiac surgery
mortality data, but no effect upon improving outcomes was shown.
15
Mortality is a complex outcome, however,
created by a multiplicity of treatment and co-morbidity factors such that simply reporting it would be unlikely to
decrease its incidence. Of course, complex measures like mortality, stroke, MI and transfers are recorded to comply
with accreditation and licensing requirements in the outpatient surgery venue, but they otherwise rarely are caused
by variation in practice nor are they thankfully frequent. Therefore, they have little value as metrics to guide
quality improvement in an ASC.
However, open sharing and attaching names to providers data have been successful in this authors practice as a
means of generating process improvement through the magic of friendly competition that is aimed at the universal
success of all team members in the ASC. The metrics shared should include process outcomes (e.g., time in recovery
room, time of turnover, first case start on time history, etc.). Frequently that is the only type of information collected
and shared because it is easy to obtain. However, clinical outcomes must be included. Posting PONV and PDNV
outcome data with names attached has been particularly useful as a means of reducing this negative outcome that is
so pernicious to outpatients.
Posting of identified data should be done in a protected site (the clean core, med room, etc.) in a locked trophy
case where patients and families cannot see it and others cannot obtain it. It should not be emailed. There will be

410
Page 3
initial resistance to the concept of such data sharing and so it is ideal to discuss it in advance with staff and
physicians, giving an opportunity to discuss the reasons for its use. Some will feel that embarrassment is the goal
of such sharing, but repeated public emphasis on emulation of the best outcomes rather than focus on the stragglers
will improve outcomes and thereby convince most disbelievers.
This approach is different from that required for de-identified or Center outcome data, such as the Centers waiting
times, PONV rates, patient satisfaction, etc. These may be placed in a site where patients and families can see the
information (although still in a trophy case, so it cant be taken or copied). Employees and physicians rightfully take
pride in accomplishment of excellent outcomes and such transparency is of course welcomed by patients and
families.

Matching chosen metrics to goals
Our goals are threefold:
A. to exceed patient and family expectations,
B. to achieve superb clinical and financial outcomes, and
C. to create high provider (surgeon and staff) satisfaction.
To accomplish these, we craft our systems and improvement processes to focus on them. Thus, the metrics we
choose to measure and share must reflect them, as well.
Surveying patient and family satisfaction is a primary means of assessing customer satisfaction in healthcare and
is related to - but may not precisely reflect - the quality of outcomes delivered.
16
Given their baseline expectation of
safety in the ASC venue, patients and families value excellent service, the absence of PONV and PDNV, and respect
for their time.
1718
Measures that examine their satisfaction with each stage of their care and the people who provided
it, time measures (on-time starts, accuracy in scheduling case durations, and the absence of delays in turnover) and
PONV and PDNV are appropriate to choose, to be sure that the staff are keeping patient expectations in the forefront
of their daily work.
Clinical outcomes we measure include PDNV, PONV and pain scores, and adequacy of home pain medication.
Post-operative infection, unplanned transfers, unplanned urinary catheter placement, use of opioid or benzodiazepine
reversal agents, spinal headache, failed regional or neuraxial block, and prolonged stays in the PACU are relatively
easy to measure and are significant (if rare) indicators of quality of care. Individual practitioners vary in their
techniques of care and that will result in variation in outcomes
19
, so the process of identifying and emulating best
practice can be applied in this arena.
Financial measures include cost per case, such as supplies, implants and cost of FTE. Including the latter is
reasonable to help all practitioners to concentrate on decreasing that cost over time. However, when comparing
surgeon to surgeon on same-case data, eliminating the cost of FTE is reasonable as it should be considered
equivalent, unless overtime is routinely needed by a given practitioner. An exception would be if the facility sends
staff home without pay when the work is done. In that case, minutes in the O.R. should be tracked by surgeon.
Contribution margin (CM) is an excellent measure to track and useful for strategic planning as well as focusing all
on cost reduction. More so than utilization, CM is a reasonable metric upon which to base allocation of O.R. time
20
,
but the measurement of income and expense must be absolutely dependable and should be shared solely with the
surgeon and/or department involved. The measurements of capacity and utilization, combined with cost will
generate a pathway for reducing cost while increasing capacity.
21

Staff and provider satisfaction can be measured overtly by surveys, but also by staff retention rates and (for
surgeons) by the case volumes they bring to you (vs. those at competitor facilities, if you have those). Peer reviews
can be of great value in helping practitioners understand if they are outliers in comportment or collegiality. This data
is of great value in one-to-one counseling sessions.

Risk Stratification
In the simplest construct, risk stratification for clinical measures can be accomplished by categorizing outcomes by
surgical specialty. For instance, the PONV rate for an anesthesiologist or surgeon who performs pediatric cases
under general anesthesia cannot fairly be compared to the PONV generated by cataract cases done under local with
I.V. sedation. As the electronic health record (EHR) reaches more ASCs, the opportunities increase to use more and
more discrete metrics to stratify risk: e.g., ASA status, co-morbidities, age, CPT, duration of the case, etc. These
metrics can be automatically downloaded into local and national databases from an increasing number of EHRs (see
Table 1).

410
Page 4
Process Improvement and Benchmarking: AQI and SCOR!
As noted, measurement of the right outcomes can lead to improvement in the quality of practice.
2223
Measurement
of outcomes can reveal repetitive error in care choices, even leading to changing indications for surgery with
resulting decreases in morbidity and mortality.
24
A great tool in gaining consensus for improvement of care is
benchmarking with external but similar facilities. A single ASCs practice will most often not be large enough to
meet statistical significance when assessing trends, particularly for individual physicians.
25
Using external
benchmarks can provide risk stratified targets for the individual ASCs quality improvement when insufficient
numbers of a particular procedure or patient populations prevent identification of best practice within the Centers
own data. This can best be managed by joining a national database overseen by a professional society, such as

SAMBAs SCOR! (www.scordata.org ) or ASAs AQI (http://www.aqihq.org ), or both. The AQI has been
accepting data of all kinds for two years, with an early emphasis on administrative data but now taking clinical data
as well. SCOR! is exclusively collecting data describing outpatient surgical and anesthesia care. In SCOR!, outcomes
for individual caregivers can be monitored by the ASC, as well as aggregate reports. AQI and SCOR! are working
with several electronic health record vendors to provide direct download capability between a Centers system and
the AQI database. SCOR! and AQI are now linked with one another, so that entry of data into SCOR! will allow
measurement against the many outpatient cases in AQI, but with stratification by similar facility size and type (and
vice versa).

Business Decision Making
Data such as contribution margin should guide decisions regarding allocation of scarce resources, including
operating rooms and equipment purchases. An ASC can also make it clear to staff and physicians alike that
citizenship metrics are as important those that indicate income to the Center (such as APCs (Ambulatory Payment
Classifications) or RVUs (Relative Value Units)) in determining the ASCs willingness to provide investment
support. Providing resources to the practice of a surgeon who values teamwork and respects the staff is a far safer
investment than supporting a surgeon who is disrespectful of staff or patients time, showing up late or without
paperwork done in advance, for instance. The latter will not make a good long-term partner for the ASC. Counseling
of such a surgeon is made far easier with his or her personal data in hand.

Accreditation
The various accreditation organizations and CMS all value evidence of a cohesive quality assessment and
improvement program.
26
Showing that staff are provided with individual outcomes is particularly positive in the
eyes of an inspector who is seeking evidence of a patient-centric, employee-empowered just culture. As well,
proving that an ASCs administration is intent upon meeting its stated goals and supports this by matching metrics to
those goals is a significant positive to portray at the time of assessment. Professional accreditation (e.g., MOCA)
should also be supported by the practitioners access to such data.

Management by Outcomes: Culture change
Upon completion of residency, physicians have a body of knowledge that includes facts like medication doses and
expected ranges of patient physiologic responses to interventions. However, their education typically provides little
emphasis on the need for outcome measurement to be sure that patients respond to care in the ways we were taught
they would. In fact, for many physicians and other caregivers, it is a large leap to the conclusion that the facts we
were taught are not actually correct and that the best means to discover these new facts is to continuously review
the literature and to monitor our local outcomes. By not emphasizing the need to experience surprising
mismatches, our educational process has supported anecdotal care delivery.
Our professions reluctance to measure and share data has obstructed progress in care pathway creation, discovery of
best practice, self-discovery and accountability. Nonaka stated, knowledge is justified true belief. Individuals
justify the truthfulness of their beliefs based on their interactions with the world.
27
Twains much earlier
observation echoed our willingness to believe in self-swerving fictions. If our interactions with the world include no
information about the outcomes of our actions, then we lack justification for our beliefs. In business, it would be
unacceptable to make an investment in a particular service line or product without an understanding of its
profitability and ongoing assessment of its performance in the market place.
Yet healthcare has not embraced such measurement, so some of the safety assessment techniques long accepted in
business are only nascent in healthcare, including assessment of data and outcomes regarding practice techniques,
even though these are of clear value in improved patient safety.
28
Studies have shown that physicians do vary in
their ability to follow guidelines, based on gender, age, and type of facility and specialty but also on individual

410
Page 5
characteristics, even when they recognize that the guidelines are valid.
29
The need to tailor re-education to
individuals is obvious and such quality improvement would be aided by providing individual outcome data.
The literature on the topic of organizational culture is extensive, in business and as in healthcare where the topics of
patient-centered, change-oriented, and just culture behaviors and techniques are well reviewed.
30

31
Inherent to
all of these methodologies is the timely assessment and informing of providers of the outcomes of their actions,
acceptance of personal responsibility in a blame-free environment, empowerment to make change in your domain of
influence, and patient-centric behavior. The basis of successful change creation is repetitive and congenial decisions
to alter cherished beliefs about medical practice facts based on data.

Management by Outcomes: Financial Improvement
Providing data to staff and physicians about cost (of individual supplies, whole cases, patient types) will arm them to
focus on the opportunities for savings that can inform changes in purchasing or platform use that will decrease your
annual costs by 5% or more (a reasonable target). Offering alternative platforms for arthroscopy, for implants, etc. to
surgeons and staff with information about best pricing and the potential impact on annual costs can generate support
among those teams for change. At the very least, our surgeons, armed with such information, have been effective
advocates for best pricing in meetings with industry sales representatives. So, even if we didnt change platforms,
costs were reduced. This is particularly effective if staff and physicians have a stake in the financial outcome of the
facility (either via incentive bonuses, shareholder status, or the availability of capital for other desired purposes once
savings are known).

Management by Outcomes: the key to your success in the future
The best value of this transparent use of outcomes is the improvements in patient care quality and safety with lower
costs. The secondary value is the ability to stay in business, in the midst of the coming changes in healthcare
payment policies. Whatever facility you administer, it must grapple with the upcoming tenets of value-based
payment systems, embraced by the government and private payers alike. The requirements of these new models are
that facilities and physicians must prove that they are creating ever-improving outcomes AND at doing so at ever
lower cost. Establishing the outcomes measurement programs we have described will ready you, your group and
your facility to provide the data surrounding quality that you (not Yelp, not Angies List, not Healthgrades)
consider appropriate. The time to set these systems up is already passing by as you ready yourselves to succeed in
the next and potentially capricious and unpredictable iterations of healthcare payment policy.

Conclusions
The use of local outcomes combined with national benchmarking and review of the literature allows and ASC to use
the best evidence to identify best practice and to use that as a template to create care pathways. In the management
of individual patients, the evidence and pathways must be further leavened by patient choice and by the individual
practitioners skill and judgment. Outcome measures should be chosen to reflect the goals of the Center including
clinical, financial and citizenship metrics. In addition to guiding best practice, the collection of outcomes can allow
the Medical Director to focus investment and process improvement projects on those care systems that yield the
most value to patients and the Center. It is the ideal tool to manage a busy and complex care delivery system.

Bill James - writer, mathematician and baseball statistician - once observed that Education is the process of
opening minds to possibilities, souls to justice, and bodies to implementation.
32
Observing our own work is the
epitome of life-long learning, an attribute often cited in the definition of a physician. The difference between
children and adults, the difference between an educated and an uneducated populous is openness to or even the
ability to conceive of change. By observing the outcomes of our work, discussing them openly, and by crafting
means of improvement as a result of that data, we can educate ourselves. That education will improve the care
delivered to patients and the experience of its delivery for caregivers, and will create an environment that is the
safest and most efficient that it can be.

410
Page 6
Table 1: Useful Outcome Metrics to Consider for an Ambulatory Surgery Center

PATIENT SATISFACTION ASSESSMENTS
Would you refer a friend or family member to use our facility if they needed surgery and could have it here?
Would you return for surgery here if you were given the choice of another facility?
How would you rate your care today? (poor, fair, average, good, excellent) we only count excellent towards our
satisfaction rate.
Did anyone in particular provide notably excellent service to you or your family while you were here?
Did anyone in particular provide less than satisfactory service to you or your family while you were here?
Did you feel that we valued your time?
What could we do differently that would have made your experience here more positive?

FINANCIAL MEASURES
Days in accounts receivable and (if a stand-alone ASC) Days Cash on Hand.
Projected vs Actual Net profit (gross income less expenditure) by week, by month, by quarter
Cost (total operating expense) per case or per 100 O.R. minutes (used and available)
Full time equivalent (FTE) per case, or per 100 O.R. minutes (used and available)
Cost per FTE (total operating expense per month/total no. of FTEs per month) it may be useful to track both paid
hours and worked hours to elicit the burden of vacation and leaves.
Cost of supplies, implants, instruments, etc.
Total operating expenses (rolled up from Personnel vs. Non-personnel expense)
Cases per month (actual vs budgeted)
Gross charges (day, week, month, quarter, year to date)
Collection rate (budgeted vs actual)

OPERATIONAL MEASURES
Cases per day (average) actual vs. budget (take the overall case budget and divide by 252 working days/year)
this is a number that works well to help staff get a general sense of a good day vs. a slow day.
Turnover time, average, same surgeon following self (wheels out to wheels in)
Turnover time, average, all cases
Incidence of delay: location and causes ask Pre-op and O.R. RNs to keep a log (Excel) with delays and pre-chosen
categories (e.g., patient would refer to patient late arrival or lack of ride; paperwork, surgeon delay,
anesthesia delay, equipment or supply delay)
Minutes patient in room (MPIR) per room per day
Minutes of operation (MOO) (skin to skin) per room per day
MOO/MPIR
Minutes from room entry to skin incision
Minutes from skin closure to room exit
Utilization (MPIR/Blocked time allocated) by service or surgeon
Case time estimation accuracy: estimates that are either too long or too short (> <15% of actual case time)

CLINICAL MEASURES while the list below is large (and not exhaustive), only a few should be collected in the
absence of an electronic record. The Center should choose the measures in a collective and multidisciplinary
manner. Be willing to change those decisions if little is gained by the ones chosen (e.g., occurrence is too rare).
ASA Score
BMI
Smoker current or recent past (quit < 3mos ago)
CHF
CAD or Previous MI
AICD
Pacemaker
COPD
CRF
Previous difficult airway
OSA
Neurologic disease, pre-existing
HTN
CVA or TIA
Mental alteration pre-op
New Mental alteration PACU
On site nausea or vomiting
Post discharge nausea or vomiting
Highest pain score in PACU
Highest pain core in the first 48 hours
Did pain medication provided for home provide you
sufficient relief?
Use of opioid or benzodiazepine reversal agent OR
Opioid/benzodiazepine reversal agent PACU

410
Page 7
Use of opioid pre- or intra-op
Use of IV/IM/SQ atropine or epinephrine
Arrival in PACU with LMA or ET in place
RR below 10 in PACU
Failed intubation
Return to the OR
Re-intubation or airway device replacement
Nebulizer treatment in PACU, unplanned
Unexpected need to call or visit a physician in the
first 48 hours after surgery
Unexpected admission to the E.D. or hospital in the
30 days following discharge
Infection of the wound site in the 30 days following
discharge
Unexpected need for urinary catheter in the PACU
or at home
Did you experience any mental fogginess, memory
loss or dizziness that lasted longer than the day of
surgery?
CVA, TIA, PE or MI in the 30 days following
discharge
Unexpectedly prolonged numbness or dysfunction

410
Page 8

1
Nonaka, I. A Dynamic Theory of Organizational Knowledge Creation. Organ. Sci. 1994; 5(1) 1437.
2
Wang CL, Ahmed PK. Organisational Learning; a critical review. The Learning Org 2003; 10:8-17.
3
Nonaka I, von Krogh G. Tacit Knowledge and Knowledge Conversion: Controversy and Advancement in
Organizational Knowledge Creation Theory. Organ Sci 2009; 20 (3): 635652.
4
Argyris C, Schon D. Organisational Learning: A theory of action perspective. 1978 Addison-Wesley, NY, NY.
5
Macario A. et al. Which Clinical Anesthesia Outcomes Are Important to Avoid? The Perspective of Patients.
Anesth Analg 1999;89:6528.
6
Mamede S. Effect of availability bias and reflective reasoning on diagnostic accuracy among internal medicine
residents. JAMA 2010;304 (11):1198-1203.
7
Croskerry P. Achieving Quality in Clinical Decision Making: Cognitive Strategies and Detection of Bias. Acad
Emer Med 2002; 9:11841204.
8
Donabedian A. Evaluating the quality of medical care. Milbank Memorial Fund Quarterly 1966; 44:166-206.
9
Schiff GD, Rucker TD. Beyond Structure-Process-Outcome: Donabedians seven pillars and eleven buttresses of
quality. Jt Comm J. Qual Imp. 2001; 27(3):169-174.
10
de Lusigna S, Pritchard K, Chan T. A knowledge management model for clinical practice. J Postgrad Med.
2002; 48:297303.
11
Bontis, N. and Serenko, A. Longitudinal knowledge strategising in a long-term healthcare organization. Int. J.
Technology Management, 2009; 47:276297.
12
Kuo AMH et al. A healthcare lean six sigma system for post-anesthesia care unit workflow improvement. Q
Manage Health Care 2011; 20: 414.
13 Sackett DL et al. Evidence based medicine: what it is and what it isn't. BMJ 1996; 1996; 312:71.
14
Ting HH et al. Quality improvement: science and action. Circulation. 2009; 119:1962-1974.
15 Bridgewater B. Mortality data in adult cardiac surgery for named surgeons: retrospective examination of
prospectively collected data on coronary artery surgery and aortic valve replacement. BMJ 2005 March 5;
330(7490): 506510.
16
Sequist TD, et al. Quality monitoring of physicians: linking patients experiences of care to clinical quality and
outcomes. J Gen Intern Med. 2008; 23(11):1784-1790.
17
Macario A. et al. Which Clinical Anesthesia Outcomes Are Important to Avoid? The Perspective of Patients.
Anesth Analg 1999; 89:6528.
18
Saila T. et al. Measuring patient assessments of the quality of outpatient care: a systematic review. J. Evaluation in
Clinical Practice ISSN 1356-1294.
19
Mukamel D. et al. Variations in risk-adjusted outcomes in a managed acute/long-term care program for frail
elderly individuals. Inter J Qual Health Care 2004; 16:293301.
20
Wachtel R and Dexter F. Tactical Increases in Operating Room Block Time for Capacity Planning Should Not Be
Based on Utilization. Anesth Analg 2008; 106:21526.
21
Kaplan RS, Porter ME How to solve the cost crisis in health care. Harv Bus Rev 2011; 89:46-52.
22
Tremper KK. Anesthesiology: from patient safety to population outcomes. Anesthesiology 2011; 114:755-70.
23
Shortell SM, et al. Improving patient care by linking evidence-based medicine and evidence-based management.
JAMA 2007; 298(6):673-6.
24
Moonesinghe SR et al. High-Risk Surgery: Epidemiology and Outcomes. Anesth Analg 2011; 112:891901.
25
Berwick DM. Measuring Physicians Quality and Performance: adrift on Lake Wobegon. JAMA 2009;302:2485-6.
26
Garcia JL, Wells KK. Knowledge-Based Information to Improve the Quality of Patient Care. J. Healthcare
Quality 2009; 31(1):30-35.
27
Nonaka I, von Krogh G. Tacit Knowledge and Knowledge Conversion: Controversy and Advancement in
Organizational Knowledge Creation Theory. Organ Sci 2009; 20 (3): 635652.
28
McDonald TB et al. Responding to patient safety incidents: the seven pillars. Quality & Safety in Health Care.
2010; 19(6):e11.
29
Mohan D et al. Sources of non-compliance with clinical practice guidelines in trauma triage: a decision science
study. Implementation Sci 2012;7:103-114.
30
Batt R. Managing customer services: human resource services, human resource practices, quit rates and sales
growth. Acad Manage J. 2002; 45 (3):587-97.
31
Gorenflo G. Achieving a culture of quality improvement. J Public Hlth Manage & Pract. 2010; 16(1):83-4.
32
http://www.jpods.com/bill/LetterOnEducation.pdf

410
Page 9

Disclosure

416
Page 1
Office Based Anesthesia: Challenges and Success
Rebecca S. Twersky, M.D., MPH Brooklyn, New York
Introduction
Although there are no good national registries to accurately determine the amount of office based surgery (OBS),
performed in the United States, the projections have ranged from 17-24% of all elective ambulatory surgery [1, 2],
to an estimate in 2005 of 10 million elective procedures [1]. This phenomenon has paralleled and was certainly
driven by the huge increase in demand for cosmetic surgery over the past ten years. Newer surgical and anesthetic
techniques have allowed more invasive procedures to be performed in non-hospital settings. Economic advantages
and physician and patient convenience have driven the rapid growth of OBS and office-based anesthesia (OBA).
Other advantages of OBS include ease of scheduling, greater privacy, lower cost, no risk for nosocomial infection,
increased efficiency, and consistency in nursing personnel [3]. Despite these advantages, OBS is not for every
surgeon nor is it appropriate for every patient or every surgical procedure. In addition, OBA requires a different
approach than that is used in hospitals and ambulatory surgery centers (ASCs). This venue may not be suited for all
anesthesia providers. The rapid growth of OBA has not been uniformly accompanied by adherence to safety
standards used in hospitals or ASCs. This lecture will address the current status of OBA and challenges faced by the
office-based anesthesiologists regarding patient safety, patient and procedure selection, and anesthesia management
for adult patients.
Facility Considerations
Is OBS/OBA as safe as that is done at hospitals or ASCs? Media coverage of high profile liposuction deaths and
other tragic mishaps exposed OBA as the Wild, Wild West of Health Care [4]. Such press is more powerful than
the medical literature in the minds of patients. Lack of regulatory oversight of OBA is the fundamental difference
between OBS and surgery done at hospitals or ASCs. With minimal safety standards, OBS may be performed in an
environment with limited or outdated equipment, inadequate emergency resources, too few qualified healthcare
providers, or insufficient policies and procedures. In addition, quality of care plans for performance improvement,
peer review and emergency preparedness are often lacking in OBS. Office personnel may be untrained and
providers of anesthesia care may have varying levels of skill ranging from physician anesthesiologists, nurse
anesthetists, surgeons, dental anesthetists, to personnel without anesthesia training. Only 2% of Anesthesiology
residency programs provide formal training in OBA leaving a void in properly educating anesthesiologists on how
to prepare themselves for offices [5].
In response to this gap, ASA has established a framework from which clinicians can establish their own practice.
The ASA Guidelines for OBA underscore that the level of care in an office should be equal to that in a hospital [6].
Together with the ASA guidelines, the ASA-SAMBA OBA Manual on Office Based Anesthesia: Considerations
for Anesthesiologists in Setting Up and Maintaining a Safe Office Anesthesia Environment has addressed major
administrative and clinical aspects on OBA such as facility and safety, quality improvement and professional
liability, controlled medications, practice management, patient and procedure selection, perioperative care,
monitoring and equipment, pediatric and dental anesthesia, emergencies and transfers [7]. All ASA documents are
relevant to OBA practice (www.asahq.org/publicationsAndServices/sgstoc.htm accessed May 31, 2013).
Anesthesiologists must examine each practice with vigilance, and discuss with surgeons about steps needed to
provide safe perioperative care. Before agreeing to provide anesthesia, anesthesiologists should allow time to inspect
the office and evaluate the anesthesia work area and space requirements with focus on adequacy of facility design,
medication, equipment and supplies, perioperative patient flow, hospital transfer arrangement, emergency equipment
and protocols, competency and designated responsibilities of staff including credentialing and licensure of providers,

416
Page 2
malpractice coverage, and ongoing peer review and quality assurance. The practice should comply with all
applicable federal, state and local laws, building codes and regulation. Environmental safety features that are often
taken for granted should be verified in the office. These include fire safety, air handling, electrical systems and
alternate back-up power, inspection and preventive maintenance of all operative equipment, setup and maintenance
of medical gases, handling of controlled drugs, equipment disinfection and biohazardous waste and sharps [8].

The OBS infrastructure should support the safe delivery of anesthesia and surgery. In particular, anesthesiologists
and surgeons need to come to terms of agreement regarding the clinical and fiscal responsibilities of common
aspects of the practice. No anesthesiologist should provide services for a facility that demonstrates disregard for
standard of care for surgery, anesthesia and nursing care. Anesthesiologists would set a high bar for safety if they
practice only in accredited or licensed facilities. When not accredited, their anesthetic practice should at least reflect
accreditation and professional society standards. Anesthesiologists can distinguish themselves by assisting the
practice in becoming accredited.

Rules/Regulations/Accreditation
Improved state regulations may help to address patient safety problems in OBA, however, there are still many states
lacking any type of oversight of OBS/OBA and the regulations vary significantly from state to state. At present,
nearly 30 states have statutes, regulations or guidelines regarding OBA, and several states also require the reporting
of adverse events (www.asahq.org/Washington/rulesregs.htm,
www.fsmb.org/pdf/GRPOL_Regulation_Office_Based_Surgery.pdf accessed May 31, 2013). Accreditation is
another option to address OBA patient safety and is voluntary in most US states. Many third-party payers will only
reimburse the facility fee for procedures performed in accredited offices. Medicare reimburses professional fees but
not facility fees. Accreditation of office-based practices is conducted by three major accrediting organizations: The
Joint Commission (TJC, http://www.jointcommission.org/ accreditation/ accreditation_main.aspx), The
Accreditation Association for Ambulatory Healthcare (AAAHC, http://www.aaahc.org/en/accreditation/office-
based-surgery-centers/), and the American Association for Accreditation of Ambulatory Surgery Facilities
(AAAASF, http://www.aaaasf.org/pub/site/index-4.html) similarly address key components of OBS, however, they
differ in their requirements for adverse event (AE) reporting, peer review process, credentialing and privileging of
practitioners without hospital privileges and enforcement [9]. In addition, the American Medical Association (AMA,
www.ama-assn.org/ama/) identifies 10 core principles for establishing safety standards in offices, which has been
embraced by medical specialties and state medical boards.

Practice Management
By proactively making the experience pleasant for patients, staff, surgeons and other parties involved, the
anesthesiologist can help facilitate growing the practice Successful OBA practices hinge on certain business sense,
even more so than in other venues. Anesthesiologists that assume a management role will be in a better position to
align the financial incentives of surgeons with anesthesiologists. Providing extra services includes helping with
facility operations, providing drugs and supplies, staffing, and/or helping with accreditation issues, or including
everything as a turn-key approach. Competition will dictate which services to provide and how much to charge for
them. Anesthesiologists should be sensitive to potential kickback issues in connection with providing extra services
and ensure that they receive fair market value compensation not a bonus for the extra services they provide.
Examples of problematic practices include providing services at below-market rates or paying above-market rates to
rent an office in the surgeons building. Whether or not providing anesthesia drugs/supplies would be deemed to be
an illegal kickback depends upon the intent of the parties, and whether or not the person providing anesthesia
drugs/supplies received fair market value payment for such items [7]. Understanding federal and state regulations
affecting anesthesia practice and billing prior to starting an OBA practice is essential. Legal counsel should be
sought where appropriate. Probably one of the best known federal laws is Stark II which prohibits physicians from
making referrals to an entity that they, or a family member, has financial interest in. Other legal issues to consider
are exclusive contracts with hospitals, which may contain noncompete clauses [7].

Payment for services rendered is a key component of a successful OBA practice. There is no one single model for
reimbursement of anesthesia services, allowing each practice to determine the optimum arrangement. Billing for
anesthesia services should be clear to all participating parties during initial negotiations to provide service. The
anesthesia provider will need to decide which method to bill for its services and how much to charge. Recently, the
Office of Inspector General of the U.S. Department of Health and Human Services issued an advisory opinion on
certain types of anesthesia practices. The advisory warned that some anesthesia reimbursement arrangements had

416
Page 3
potential for prohibited remuneration under the Federal Anti-Kickback Statute, Federal False Claims Act, as well as
state laws prohibiting fee-splitting, self-referrals, and kickbacks. Appropriate counsel is recommended before
entering into any monetary arrangements, as violations can result in imprisonment, exclusion from federal health
care programs, and significant fines that can often be assessed per claim.( http://www.asahq.org/For-
Members/Advocacy/Washington-Alerts/Frequently-Asked-Questions-About-the-Company-Model.aspx (accessed
June 4, 2013)

Patient Safety in Office-Based Anesthesia
Notwithstanding the often-repeated advantages, death rates associated with OBA still precipitated significant
professional and public concern about the level of safety in this setting. Quality and safety in anesthesia is usually
monitored by analysis of perioperative morbidity-mortality (M & M) and incidents. To date, the largest QI database
(over 1 million outpatient procedures) from accredited facilities reports a mortality rate of 0.002% or 2.02 deaths per
100,000 procedures, with PE the most common cause of death (56.5%) [10]. In reviewing ASA closed claims
analysis of 63 office-based claims 1990-2009, Domino reported that the severity of injury for office-based claims
was greater than for other ambulatory anesthesia claims: 40% of office-based claims were for death, compared to
25% of ambulatory anesthesia claims. Respiratory events including airway obstruction, bronchospasm, inadequate
oxygenation-ventilation and esophageal intubation accounted for 29% of office based claims in 2009, with the
trends in complications changing. There has been a reduction in the claims for medication related claims (18%) yet
nearly three-fold increase for equipment reasons (17%) [K. Domino and K. Posner, ASA Closed Claims Database
project, Personal communication]. These events were judged to be preventable by monitoring, especially in the
postoperative period [11]. Several areas for improvement relevant to office based anesthesia safety were identified:
oversedation during MAC with failure to recognize and treat respiratory depression in a timely fashion, hazards of
anesthesia in nonoperating room locations, prevention of cautery-induced burns, and management of the difficult
airway particularly at extubation. Analysis of these rare events can improve practice and patient safety [12, 13].

A 2003 Florida Board of Medicine report cited causes of death due to poorly-trained personnel, inadequate
resuscitation equipment, deep venous thrombosis (DVT)/pulmonary embolus with inadequate prophylaxis, local
anesthetic overdose, airway mishap, and or failure to vigilantly maintain the same anesthetic monitoring techniques
used in the ASC or hospital [14]. More recent published reviews of the 10 years of prospective, independently
collected verifiable data on office surgery mortality in Florida concluded that office and other outpatient surgery are
safe if performed in an accredited facility by American Board of Medical Specialties, certified surgeons who are
credentialed for the same procedures in a hospital [15]. An NIH-funded conference concluded that evidence speaks
to the safety of OBS with even lower rates of adverse events and mortality (adverse event rate of 0.24/100,000 and
death rate of 0.41/100,000 procedures) [16]. This is supported further by Fleisher et al., in a comparative study of
outcomes in Medicare patients (> 65 yrs) by location of ambulatory surgery. They reported a death rate on day of
surgery /100,000 procedures of zero in offices, compared to 2.3 deaths in ASCs and 2.5 in hospital-based units.
Comparative admission rate/1000 procedures were 91 in office-based settings 8.4 for ASCs, and 21 in the hospital-
based ambulatory setting [17]. An extensive review of patient safety in OBS identified risk factors for adverse
events [18], urging more prospective research.

Anesthesiologists Role in Patient Safety
Much of the work on patient safety is reported from dentistry and oral and maxillofacial surgery, and focuses on
surgical outcomes, with almost no mention of anesthetic complications such as nausea and vomiting, pain, delayed
discharge, patient satisfaction or post-discharge symptoms. Recent data compiled from the SAMBA Committee on
OBA reported outcomes and complications in a database of 50,520 OBA cases from 6 practices for 2008-10. Deep
sedation without an airway device accounted for 83% of cases. Only 6% of cases required intubation, most from a
single, primarily dental OBA practice. Overall complication rates were very low with cancelations being the most
frequent event (3.3%). This higher rate than ASCs reflects more conservative approach for safe practice. The rates
for minor complications were all below 1%. Unplanned admission rates were 0.07%. Of note, there were 11
incidents of medication error, 4 aspirations, 2 wrong site surgeries, and 2 patients discharged without escort. No
deaths were reported. These sites showed that OBA compared favorably with safety and outcome data from
ambulatory, hospital-based practices [19, personal communication Michael T. Walsh, MD]. An OBA specific
checklist has been tested in several office sites and was reported to improve safety, documentation, and assessment
of patient satisfaction [20]. It is anticipated that with more participation in anesthesia registries, i.e. SAMBA

416
Page 4
Clinical Outcome Registry (SCOR) (http://www.scordata.org) and ASA Anesthesia Quality Institute (AQI) Data
Registry (http://www.aqihq.org) comparative benchmarks of anesthesia outcomes will become available.

The challenges for anesthesiologists are to collaborate with their surgical colleagues to improve the culture of safety
including educating patients to seek out the safest venue to have their surgery. The ASA-SAMBA OBA Manual
serves as a good companion for a quality driven and patient-safety oriented practice [7]. Familiarity with
professional guidelines of OBS specialties is helpful to ensure consistency with our clinical approach.
Anesthesiologists should actively participate in the OBS quality improvement (QI) plan. A review of anesthesia and
surgical morbidity and "adverse" or "sentinel" or outcome events should be integral to the plan. Examples include
patient deaths within 30 days, postoperative infection, transfer to a hospital/ ED for more than 24 hours,
unscheduled hospital admission within 72 hours of procedure, wrong site surgery or other serious or life threatening
events [7]. AE reporting should be standardized and registered on a national level to allow risk assessment by large
scaled studies. The low rate of anesthesia AE can be attained by ensuring trained anesthesia providers; careful
patient selection; utilizing full preoperative evaluation, intraoperative care and monitoring consistent with ASA
standards; and sufficient postoperative care to enable safe discharge.

Facility Readiness
As different anesthesiologists and surgeons might be providing care in the same offices on either a rotating or
permanent basis, all personnel, should be properly oriented to policies, procedures, physical layout, and the location
of emergency equipment. Facilities must establish written protocols for emergency management of rare but
catastrophic events and conduct regular drills that include the anesthesiologists and surgeons. Critical management
of emergencies most likely will require stabilization of the patient and quick transfer of the patient to an acute care
facility [7, 21]. Anesthesiologists should be comfortable with the qualifications of surgeon providers, especially
when performing the newer high-tech procedures. The office must be equipped to deliver positive pressure
ventilation with self-inflating resuscitation bag and there must be an identifiable source of oxygen. Suction may be
delivered via a portable or installed system. All anesthesia equipment should have a reliable back-up power source
in the event of equipment failure. Functioning resuscitation equipment and defibrillator, emergency airway
equipment, ACLS drugs and ACLS trained personnel must be available in the event of any emergency. A protocol
should be on hand to deal with the rare occurrence of malignant hyperthermia. A guide has been released to assist
the office practitioner in the event of this potentially catastrophic event and dantrolene must be readily available to
treat MH if triggering anesthetics are used [22]. Equipment should be maintained and inspected according to
manufacturers specifications. There should be sufficient space to accommodate all the necessary equipment,
adequate lighting and expeditious access to the patient. In locations administering only local anesthesia, intralipid
20%, other appropriate drugs, monitors and equipment should be on hand in the event of untoward reaction [7]. Fire
safety is also an emerging topic of interest in office based practice. Four of the 11 reported OBA ASA closed claims
for equipment involved cautery fires (personal communication, K. Domino and K. Posner, ASA Closed Claims
Database project, September 2012). Patients receiving oxygen under MAC for facial procedures are at risk for
surgical fires and anesthesiologists should take precautions to reduce airway fires. It is recommended that the
practice be compliant with National Fire Protection Agency and building code standards and have protocols and
policies in place to be followed in the event of a patient fire [23]. Regularly scheduled fire drills would also be
prudent. Clinicians should be mindful of using supplemental oxygen proximate to the surgical cautery [23, 24]

Patient Selection
As with all ambulatory anesthesia venues, not all patients or procedures are suitable for the office setting. When
evaluating patients to determine suitability for office procedures, surgeons should be alerted to those high risk
medical conditions that would exclude patients from OBA. Criteria of excluding patients from OBA include
unstable ASA 3 or greater, MI within 6 months; severe cardiomyopathy; uncontrolled HTN; brittle or poorly-
controlled diabetes mellitus; active multiple sclerosis; acute substance intoxication (drugs and alcohol); history of
malignant hyperthermia (MH); morbid obesity with poorly controlled comorbidities, severe COPD or obstructive
sleep apnea, pacemaker or AICD, end-stage renal disease, sickle cell disease, patient on transplant list, dementia (not
oriented), psychologically unstable (rage/anger problems), stroke within 3 months, myasthenia gravis or lack of
adult escort [21,25,26]. A list of exclusions from OBA should be shared with surgeons, and screening questionnaires
should be completed by patients. Office staff should confirm suitability of the patient for this venue and forward all
evaluations to be reviewed by anesthesiologists, preferably before the day of surgery. A review of prescription, non
prescription drugs and use of herbal and dietary supplements are important as drug interactions may occur.
Preoperative tests and consultations should be requested when indicated. Anesthesiologists, assuming the role of

416
Page 5
medical consultant, remain the best qualified professional to evaluate patients overall risk for OBA. However, since
most patients are seen for the first time by anesthesiologists on the morning of the procedure, surgeons must ensure
that patients have been adequately evaluated and undergone appropriate preoperative testing beforehand.
Oftentimes, this falls to the office staff, which needs clear direction from the surgeon providers.

Good communication between surgeons and anesthesiologists is crucial in determining accurate risk for patients
with older age or comorbidities. Surgeons should screen patients for potential difficult airway and the need for
further medical optimization. OBS staff should also ensure that patients receive proper preoperative instructions
regarding NPO and continuation of any chronic medications. The office surgeons should pay specific attention to
instructions for discontinuation of antiplatelet medications or other anticoagulation treatment; or whether
perioperative antibiotics are need, as the anesthesiologists will only evaluate the patient face-to-face on the morning
of surgery.

Types of Procedures
OBS procedures should be of duration and degree of complexity that will permit patients to recover and be
discharged from the facility as soon as possible. Anesthesiologists should ensure that OBS procedures are within the
scope of the physicians practice as well as the capabilities of the facility. As several OBA procedures are not
commonly done in the hospitals or ASCs, anesthesiologists must familiarize themselves with the physiological and
anesthetic implications of the newer and technologically updated surgical procedures [27]. Among the procedures
considered appropriate for OBA are cosmetic surgeries (liposuction, rhytidectomies, breast augmentation/reduction,
and rhinoplasty), ophthalmology, dental, gynecology, orthopedic, urologic and GI endoscopies. Procedures with
potential risk of significant blood loss such as major intra-abdominal, intrathoracic and intracranial surgeries are
inappropriate for OBA [8, 25, 28]. There are few prospective studies about using duration of surgery as a predictor
of adverse outcomes and results are still controversial. Some recommended that procedures not to exceed 6 hours to
decrease the risk of hypothermia and DVT, especially during high volume liposuction (> 5000 ml) combined with
other procedures [28, 29]. However, duration of surgery and anesthesia was not demonstrated to be an indicator of
patient morbidity and mortality in facial plastic surgery performed on 1200 patients lasting more than 4 hours in an
accredited OBS facility with board certified anesthesiologists [30]. A recent retrospective review of 2595
consecutive patients who had office-based cosmetic surgery in a single practice reported on the outcomes of patients
who received TIVA general anesthesia using propofol/remifentanil infusion with either LMA or endotracheal
intubation [31]. They found an increase in the occurrence of minor surgical complications such as PONV (2.8% vs.
5.7%, P = 0.0175) and urinary retention (0.7% vs. 7.6%, p < 0.0001) in the greater than 4-hour anesthesia duration
group. There were no statistically significant differences in major morbidity or mortality, including hospitalization
and reoperation rates in patients who received GA < or > than 4 hours.

Perioperative Care
The definition of appropriate level of anesthesia remains debatable in the non-anesthesia literature, though several
publications identify it as any safe technique provided by appropriate anesthesia professional in accredited facilities
[10, 32]. However, there is no one preferred technique. Choice of agents and techniques should be appropriate to
patients health and surgical procedures, the equipment, which might depend on whether the platform in the office is
fixed or mobile; and whether it allows a rapid recovery to normal function with minimal postoperative pain, nausea
and other side-effects. The same anesthetic techniques that are used in hospitals and ASCs can be used in OBA
(including local, monitored anesthesia care or MAC, regional or general anesthesia).

MAC with or without local anesthesia is more commonly used [33-36], though with increasing complexity there is
growing demand for general anesthesia (GA). GA may be preferable in complex or extended procedures because of
safety provided by airway protection, consistent level of anesthesia and the ability of allowing surgeons to
concentrate on procedures. Commonly utilized sedatives and anesthetics include midazolam, ketamine, fentanyl and
propofol, either alone or combined. Intravenous acetaminophen, ketorolac, ibuprofen, and other nonsteroidal anti-
inflammatory agents (NSAIDs) can be used as adjuvant non-opioid analgesics. Sevoflurane and desflurane are used
for inhalation anesthesia [37, 38]. Adjuvant treatment with clonidine or dexmedetomidine has been reported to be
beneficial in plastic surgery procedures [39]. In general, opioid use is minimized and substituted with generous use
of local anesthetic and NSAIDs to augment analgesia through the recovery period and avoid opioid-induced
postoperative nausea and vomiting (PONV).

416
Page 6
For GA, some practitioners prefer total intravenous anesthesia (TIVA) over inhalation agents for several reasons:
lack of capacity to deliver inhalation agents or nitrous oxide and need for adequate waste scavenging system;
avoidance of MH-triggering agents that would otherwise require the immediate availability of Dantrolene; improved
infusion pumps and computerized TIVA delivery systems. TIVA for OBA generally consists of propofol, preferably
with none or minimal opioids, with spontaneous or assisted patient ventilation, either with or without laryngeal mask
airway or other supraglottic device. Avoiding muscle relaxation permits muscle tone in the extremities which can
reduce DVT and subsequent PE. A recent retrospective chart review of over 2600 patients undergoing TIVA with
propofol and/or ketamine by board certified anesthesiologists or moderate sedation with midazolam and fentanyl by
plastic surgeons in AAAASF accredited facilities reported no deaths, cardiac events, or transfers to the hospital in
any patients, regardless of the type of sedation utilized [40]. Generally, muscle relaxants and endotracheal intubation
are used sparingly, although airway equipment for intubation must always be available during all cases of GA. It is
important that the equipment and machines used are maintained, tested and inspected on a regular basis and not
become a repository for obsolete equipment (http://www.asahq.org/For-Members/Standards-Guidelines-and-
Statements.aspx, http://www.apsf.org/newsletters/html/2004/winter/05guidelines.htm accessed May 31, 2013). The
bispectral index (BIS) system has been used in OBA to guide timing of intubation without neuromuscular blockers
[41].

Office-based practice, perhaps even more than others, has zero tolerance for PONV. Therefore, interventions against
PONV should be aggressively implemented [42]. New data have reported that postdischarge (PDNV) occurs in
patients who might not have experienced PONV. Apfel et al reported a 30-50% incidence of PDNV. Risk factors for
PDNV are similar to the ones for PONV with some differences [43]. History of nonsmoking and type of surgery
were not predictive for PNDV as they were for PONV. Patients who experienced nausea in the PACU had a 3-fold
increased risk of PDNV development [43]. Options for PDNV include long acting prophylactic antiemetics such as
dexamethasone, aprepitant, palonsetron, transdermal scopolamine, and even acupoint stimulation. More research in
this area is likely to emerge.

My recipe for OBA is premedication with antiemetic, intraoperative use of long acting local anesthetics, use of
anesthesia agents that minimize PONV, PDNV and pain and target toward a rapid emergence and ambulation.
Preventing or mitigating postoperative pain is a goal of OBA. Multimodal approaches that use multiple drugs and
combinations of techniques to improve pain relief and minimize side effects are growing in popularity. Clinical
studies have shown preoperative oral or intravenous co-administration of acetaminophen or nonsteroidal anti-
inflammatory drugs (NSAIDs) can decrease the use of opioids and opioid-related adverse effects and can be safely
used for the treatment of postoperative pain after ambulatory surgery [44-46].

Regardless of the type of OBA, patients must transition through the standard postoperative care. Traditional
stretchers are not used in the office setting; therefore patients must transfer directly from the operating table to a
lounge chair, wheelchair or walk with assistance to the designated recovery area. While the objective is to have the
patient fully awake to at the conclusion of the surgery, sometimes this is not feasible, given patients diverse age and
baseline condition [47]. Nonetheless, fast-tracking patients are met by selecting an intraoperative anesthetic
technique that maximizes rapid emergence with minimal side-effects. Postoperative recovery of patients in the office
should be provided by a qualified PACU nurse, freeing up the anesthesiologists to return to the procedure room;
although the anesthesiologists should remain responsible for overall postoperative recovery and discharge.
Discharge criteria for the office setting should use the same standards as for all ambulatory surgery settings.

Conclusion
OBA has undergone tremendous growth in the last ten years and is slowly becoming regulated and standardized.
As technology progresses, surgical techniques become less invasive and more cost conscious. Office-based facilities
will continue to perform more outpatient procedures. While safety has been questioned in the past, most OBA is
probably safe when performed by properly trained physicians working within their scope of practice and following
the standards and guidelines developed by professional societies. We should continue to advocate for outcomes
registries, uniform reporting of adverse events (AEs), allowing proper analysis and ongoing assessments of patient
outcomes. In the hands of skilled professionals, and with proper patient selection and perioperative care,
anesthesiologists can serve as pivotal leaders in ensuring that OBA can be as a safe as those done at hospitals or
ASCs.

416
Page 7
References:
1. AHA, TrendWatch issue from July 2006. The Migration of Care to Non-hospital Settings: Have Regulatory
Structures Kept Pace with Care Delivery?
http://www.aha.org/research/reports/tw/twjuly2006migration.ppt#256,1 (Accessed May 31, 2013)
2. AHA. TrendWatch Chartbook 2011.Trends affecting hospitals and health systems Chapter 3: Utilization and
Volume, p.36. Available at: http://www.aha.org/research/reports/tw/chartbook/2012/chart3-14.ppt. (Accessed
May 31, 2013).
3. Byrd HS, Barton FE, Orenstein HH, et al. Safety and efficacy in an accredited outpatient plastic surgery
facility: A review of 5316 consecutive cases. Plast Reconstr Surg 2003; 112 (2) 636-641.
4. Quattrone MS. Is physician office the wild, Wild West of health care? J Ambul Care Manage 2000; 23:64.
5. Hausman LM, Levine AI, Rosenblatt MA: A survey evaluating the training of anesthesiology residents in
office-based anesthesia. J Clin Anesth 2006; 18 (7): 499-503.
6. ASA Guidelines for office-based anesthesia. Affirmed on October 19, 2009. Available at:
http://www.asahq.org/Home/For-Members/Clinical-Information/Standards-Guidelines-and-Statements
(Accessed May 31, 2013)
7. Twersky RS et al. ASA Committee on Ambulatory Surgical Care and the SAMBA Committee on Office-Based
Anesthesia. Office-based Anesthesia: Considerations for Anesthesiologists in setting up and maintaining a safe
office anesthesia environment. https://ecommerce.asahq.org/p-319-office-based-anesthesia-considerations-in-
setting-up-and-maintaining-a-safe-office-anesthesia-environment.aspx (Accessed May 31, 2013).
8. Kurrek MM, Twersky RS. Office-based anesthesia: how to start an office-based practice. Anesth Clin 2010;
28(2):353-67.
9. Kurrek MM, Twersky RS. Office-based anesthesia. Can J Anesth 2010; 57:256-272.
10. Keyes G, Singer R, Iverson R, et al. Mortality in Outpatient Surgery. Plast Reconstr Surg 2008; 122: 245-250.
11. Domino KB. Office based anesthesia: Lessons learned from the closed claims database. ASA Newsletter
2001; 65(6): 9-11. Available at: Closed Claims: Office-Based Anesthesia: Lessons Learned Accessed May 25,
2012.
12. Metzner J, Posner KL, Lam MS, et al. Closed claims analysis. Best Pract Res Clin Anesthesiol 2011;
25(2):263-76.
13. Urman RD, Punwani N, Shapiro FE. Patient safety and office based anesthesia. Curr Opin Anaesthesiol. 2012
Dec; 25(6):648-53
14. Vila H, Soto R, Cantor AB, Mackay D. Comparative outcome analysis of procedures performed in physician
offices and ambulatory surgery center. Arch Surg 2003; 138: 991-5.
15. Starling J 3
rd
, Thosani MK, Coldiron BM: Determining the safety of office-based surgery: What 10 years of
Florida data and 6 years of Alabama data reveal. Dermatol Surg 2012; 38: 171-7.
16. Balkrishnan R, Hill A, Feldman SR, Graham GF: Efficacy, safety and cost of office-based surgery: A
multidsciplinary perspective. Dermatol Surg 2003; 29(1): 1-6.
17. Fleisher LA, Pasternak LR, Herbert R, et al. Inpatient hospital admission and death after outpatient surgery in
elderly patients. Arch Surg 2004; 139 (1):67-72.
18. Lorincz CY, Drazen E, Sokol PE, et al: Research in Ambulatory Patient Safety 20002010: A 10-Year Review.
Chapter IV:Ambulatory safety in office-based surgery and anesthesia research. p 51-56. American Medical
Association, Chicago IL 2011. Available at: www.ama-assn.org/go/patientsafety. Accessed May 31, 2013
19. Walsh MT, Kurrek MM, Desai M. Anesthesia outcomes in office-based anesthesia. Proceedings of the 2010
Annual meeting of the American Society Anesthesiologists. A798.
20. Rosenberg NM, Urman RD, Gallagher S, Stenglein J, Liu X, Shapiro FE. Effect of an office-based surgical
safety system on patient outcomes. Eplasty. 2012; 12:e59. Epub 2012 Dec 25.
21. Ahmad S. Office based-is my anesthetic care any different? Assessment and management. Anesth Clinics 2010;
28(2):369-84.
22. Larach MG, Dirksen SJ, Belani KG et al: Creation of a Guide for the Transfer of Care of the Malignant
Hyperthermia Patient from Ambulatory Surgery Centers to Receiving Hospital Facilities. Anesth Analg 2012;
114: 94-100.
23. Apfelbaum JL, Caplan RA, Barker SJ, et al.: Practice advisory for the prevention and management of operating
room fires: An updated report by the American Society of Anesthesiologists Task Force on Operating Room
Fires. Anesthesiology 2013; 118:27190
24. Engel SJ, Patel NK, Morrison CM, et al. Operating room fires: Part II. Optimizing safety. Plast Reconstr Surg
2012; 130(3): 681-689.

416
Page 8
25. Vila, H, Desai M, Miguel R, Office-Based Anesthesia In: Twersky RS, Philip BK, eds. The Ambulatory
Anesthesia Handbook, 2nd edition. New York: Springer, Inc, 2008, p 283-324.
26. Iverson RE, Lynch DJ, Twersky RS and the ASPS Task Force on Patient Safety in Office-Based Surgery
Facilities. Patient safety in office-based surgery facilities: II. Patient Selection. Plast Reconstr Surg 2002; 110:
1785-90.
27. Pace MM, Chatterjee A, Merrill DG, Stotland MA, Ridgway EB; Local anesthetics in liposuction:
considerations for new practice advisory guidelines to improve patient safety Plast Reconstr Surg. 2013
May;131(5):820e-6e
28. Iverson RE, Twersky RS, and the ASPS Task Force on Patient Safety in Office-based Surgery Facilities. Patient
safety in office-based surgery facilities: I. Procedures in the office-based surgery setting. Plast Reconstr Surg
2002; 110:1337-42.
29. Iverson RE, Lynch DJ, and the ASPS Committee on Patient Safety. Practice advisory on liposuction. Plast
Reconstr Surg 2004; 113(5):1478-90.
30. Gordon NA, Koch ME: Duration of anesthesia as an indicator of morbidity and mortality in office-based facial
plastic surgery: A review of 1200 consecutive cases. Arch Facial Plast Surg 2006; 8: 47-53.
31. Phillips BT, Wang ED, Rodman AJ, et al: Anesthesia duration as a marker for surgical complications in office-
based plastic surgery. Ann Plast Surg. 2012 Oct; 69(4):408-11
32. Hoefflin SM, Bornstein JB, Gordon M. General anesthesia in an office-based plastic surgery facility: a report on
more than 23,000 consecutive office-based procedures under general anesthesia with no significant anesthetic
complications. Plast Reconstr Surg 2001; 107: 243-51.
33. Badrinath S, Avramov M, Shadrick M. The use of a ketamine-propofol combination during monitored
anesthesia care. Anesth Analg 2000; 90: 858-862.
34. Jourdy DN, Kacker A: Regional anesthesia for office-based procedures in otorhinoloaryngology. Anesthesiol
Clin 2012; 28: 457-68.
35. Olabi NF, Jones JE, Saxen MA et al. The use of office-based sedation and general anesthesia by board certified
pediatric dentists practicing in the United States. Anesth Prog 2012; 49: 12-7.
36. Hausman LM, Eisenkraft JB, Rosenblatt MA. The Safety and Efficacy of regional Anesthesia in an office-based
setting. J Clin Anesth 2008; 20 (4): 271-5.
37. Shapiro FE. Manual of office-based anesthesia procedures, ed. Lippincott Williams & Wilkins: Philadelphia,
PA, 2007, p.40-51.
38. Tang J, White PF, Wender RH, et al: Fast-track Office Based Anesthesia: A comparison of propofol vs.
desflurane with antiemetic prophylaxis in spontaneously breathing patients. Anesth Analg 2001; 92: 95-99.
39. Taghinia, AH, Shapiro FE, Slavin SA. Dexmedetomidine in Aesthetic Facial Surgery: Improving Anesthetic
Safety and Efficacy,Plast Reconstr Surg 2008; 121: 269-276.
40. Failey C, Aburto J, de la Portilla HG, et al. Office-based outpatient plastic surgery utilizing total intravenous
anesthesia. Aesthet Surg J. 2013 Feb 1; 33(2):270-4
41. Messieha ZS, Guirguis A, Hanna S. Bispectral index monitoring (BIS) as a guide for intubation without
neuromuscular blockade in office-based pediatric general anesthesia: a retrospective evaluation. Anesth Prog
2011; 58(1):3-7
42. Gan TJ, Meyer TA, Apfel CC, et al. Society for Ambulatory Anesthesia Guidelines for the Management of
Postoperative Nausea and Vomiting. Anesthesia and Analgesia, Dec 2007; 105(6): 1615-1628.
43. Apfel CC, Phillip BK, Cakmakkayya OS, et al. Who is at risk for postdischarge nausea and vomiting after
ambulatory surgery? Anesthesiology, Sep 2012; 117(3): 475-486.
44. Wininger SJ, Miller H, Minkowitz HS, et al: A randomized, double-blind, placebo-controlled, multicenter,
repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal
laproscopic surgery. Clin Ther. 2010;32(14):2348-69
45. White PF, Tang J, Wender RH, et al. The effects of oral ibuprofen and celecoxib in preventing pain, improving
recovery outcomes and patient satisfaction after ambulatory surgery. Anesth Analg. 2011,112(2):323-329
46. Bookstaver PB, Miller AD, Rudisill CN, et al. Intravenous ibuprofen: the first injectable product for the
treatment of pain and fever. J Pain Res. 2010,25;3:67-79
47. Twersky RS, Sapozhnikova S, Toure B. Risk factors associated with fast-track ineligibility after monitored
anesthesia care in ambulatory surgery patients. Anesth Analg 2008; 106(5):1421-6.

Disclosure
432
Page 1
Malignant Hyperthermia in the Outpatient Setting
Ronald S. Litman, D.O. Philadelphia, Pennsylvania
In this refresher course lecture, we will review basic principles of MH pathophysiology, susceptibility,
diagnosis, and treatment. We will also discuss unique aspects of treating acute MH in the ambulatory setting,
preparing your free-standing ambulatory center for potential MH, and anesthetizing the known MH susceptible
patient in a free-standing ambulatory center. Even in this current era of sophisticated means of detecting, diagnosing
and treating MH, mortality from MH in unsuspected individuals is not zero. In the past several years, at least ten
cases of MH-related death in ambulatory surgery patients are known to the Malignant Hyperthermia Association of
the United States (MHAUS). The incidence of acute MH in the general population is approximately 1:30,000
general anesthetics, but this doesnt account for unreported cases, or unrecognized, mild, or atypical reactions.
Furthermore, MH-susceptible patients may not develop the acute syndrome during any given anesthetic exposure.
Although acute MH may develop during the patients first exposure to a triggering agent, many MH-susceptible
patients will trigger upon subsequent anesthetic exposures.
Between 1996 and 2006, the rate of surgical procedures in a free-standing ambulatory surgery center
increased 300 percent. In 2006, approximately 53 million procedures were performed during 35 million ambulatory
surgery visits. Almost half of these visits occurred in a free-standing center.
1
Since malignant hyperthermia (MH)
susceptibility almost always occurs in phenotypically normal individuals, it is impossible to predict the risk of MH
in any given seemingly healthy ambulatory surgery patient.
MH Pathophysiology
MH susceptibility results from a familial or spontaneous mutation in a gene that encodes for one of the
components of a muscle cell that plays a role in regulation of intracellular calcium. The most commonly affected
structure is the ryanodine receptor, which regulates the movement of calcium from the sarcoplasmic reticulum into
the intracellular space of the myocyte.
2
The inheritance is autosomal dominant with variable penetrance. Affected
individuals are often healthy appearing, and, except for extremely rare cases of heat- or stress-related MH,
3
will only
develop signs of acute MH when exposed to one of the anesthetic triggering agents (i.e., volatile anesthetics or
succinylcholine). The specific mechanism by which anesthetics interact with these abnormal receptors to trigger an
MH crisis is unknown.
During an acute MH crisis, abnormal levels of calcium accumulate inside the muscle cell. This results in a
massive overload of actin-myosin cross-bridging, which leads to sustained muscle contracture, cellular hypoxia,
ATP depletion, and cell death (rhabdomyolysis). Hyperthermia results from the sustained muscle contraction, which
generates more heat than the body is able to dissipate.
Diseases Associated with MH
The gene for the ryanodine receptor, RYR1, is located on chromosome 19. The diseases that are known to
be linked with MH susceptibility are invariably also caused by mutations on chromosome 19 in the same region as
that which encodes for ryanodine. These are relatively rare and include central core myopathy,
4,5
multiminicore
myopathy,
6
King-Denborough syndrome,
7
Native American myopathy,
8
and possibly hypokalemic periodic
paralysis.
9

An interesting group of patients with possible MH susceptibility are those individuals with a history of
exercise- or heat-induced rhabdomyolysis.
10,11
Although many of these patients will not test positive, those with a
convincing history of severe heat- or exercise-induced rhabdomyolysis should probably be considered to be MH
susceptible unless proven negative by contracture testing.
A number of other diseases have been erroneously linked with MH susceptibility because patients have
developed rhabdomyolysis upon exposure to triggering agents. These include Duchenes and Beckers myopathy,
12

McArdles disease (glycogen storage disease, type V),
13
myoadenylate deaminase deficiency,
14
and carnitine
palmitoyltransferase type 2 (CPT-2) deficiency.
15
The mechanism of the relationship between these diseases and
anesthetic-induced rhabdomyolysis is unknown.
16

432
Page 2
Additional diseases that are not associated with MH susceptibility include the mitochondrial myopathies,
Noonans syndrome, arthrogryposis, osteogenesis imperfecta, and neuroleptic malignant syndrome.

Clinical Features of Acute MH
MH manifests clinically as signs and symptoms of hypermetabolism and the sequelae of muscle
breakdown. An early important sign of hypermetabolism is hypercapnia that is out of proportion to increases in
minute ventilation. Tachycardia and hypertension may also occur. Spontaneously breathing patients will develop
marked tachypnea in an attempt to compensate for respiratory acidosis. Signs of ongoing rhabdomyolysis include
metabolic acidosis, localized or generalized rigidity (with or without neuromuscular blockade), hyperkalemia-
induced arrhythmias, myoglobinuria (tea-colored urine), and rapid temperature elevation. In some patients, masseter
muscle spasm in response to administration of succinylcholine is a harbinger of acute MH.
17
Death from MH almost
always results from acute hyperkalemia or hyperthermia-induced disseminated intravascular coagulation (DIC).
Muscular individuals appear to have the greatest risk of severe complications from MH, presumably because of the
relatively larger amount of muscle damage that contributes to hyperkalemia and hyperthermia.
18
They are also more
susceptible to recrudescence of MH following initial treatment with dantrolene.
19

Intraoperative or postoperative hyperthermia without additional signs of hypermetabolism is not an
observed presentation of acute MH.
20
In fact, the notion of acute MH first presenting several hours after completion
of the general anesthetic is unproven. Postoperative hyperthermia, even if striking, should prompt a search for other
causes unless accompanied by muscle rigidity or rhabdomyolysis. The most common mimic of acute MH is
hypercapnia caused by hypoventilation, from any one of a number of causes related to impaired ventilation.

Treatment of Acute MH
When clinical signs indicate a strong possibility of acute MH, the diagnosis should be confirmed by blood
gas analysis (when available), which shows the characteristic mixed respiratory and metabolic acidosis. In some
cases of severe acute MH, such as that seen with marked hypercapnia along with generalized rigidity, metabolic
acidosis may not yet be evident. Nevertheless, triggering agents should be immediately discontinued and the surgical
procedure should be aborted or completed as quickly as possible while administering intravenous (nontriggering)
anesthetics. An endotracheal tube should be placed if not already present, the minute ventilation should be increased
to offset respiratory acidosis, and the inspired oxygen should be increased to 100 percent. Simultaneously, all
available personnel are summoned, and the MH emergency cart (Table 1) is brought into the room. If the surgery is
being performed in a free-standing facility, plans for transport to the nearest full-service medical center should be
arranged. The concentration of the volatile gas remaining in the patient can be decreased most rapidly by increasing
fresh gas flows and by inserting into the anesthesia circuit a charcoal filter.
21

Immediate administration of dantrolene is the most important aspect of treatment of acute MH all
personnel should be focused on its administration as quickly as possible. Dantrolene is supplied as a lyophilized
powder (20 mg) and also contains 3 g of mannitol. It is reconstituted with sterile water, which when warmed will
enhance solubility.
22
A newer formulation manufactured by JHP Pharmaceuticals will solubilize within 20 seconds.
The initial dose of dantrolene is 2.5 mg/kg; subsequent bolus doses of 1 mg/kg should be administered until the
signs of acute MH begin to reverse. Some patients (e.g., muscular males) may require initial doses approaching 10
mg/kg; however, the need for higher than usual doses should prompt an exploration for alternative diagnoses. As
soon as feasible, the MH hotline should be called to speak with a knowledgeable expert who can assist with
diagnosis, treatment, and follow-up care (1-800-MH-HYPER).
The most important aspects of treatment of acute MH are listed in Table 2.

Preparing Your Ambulatory Surgery Center for Unexpected Acute MH
Since patients with significant neuromuscular disease are usually excluded from receiving general anesthesia in
an ambulatory facility, it is most likely that any patient that develops MH will be otherwise healthy. Therefore, each
facility should be optimally prepared to treat patients that unexpectedly develop acute MH. Each facility should have
a completely stocked MH cart (Table 1) and a readily available source of ice and cold intravenous fluids. A full
component of dantrolene (36 vials) should be available at every ambulatory facility that uses any anesthetic
triggering agent, and the facility should proactively identify a mechanism to rapidly attain additional dantrolene in
the event that the patient requires more than is immediately available. MH treatment drills should be performed at
least yearly. An in-service video and manual for management of MH in ambulatory centers is available from
MHAUS.

432
Page 3
Anesthesia for MH Susceptible Patients in the Ambulatory Setting
MH susceptible patients are eligible for outpatient surgery in a free-standing facility. A non-triggering
technique should be used for general anesthesia after properly preparing the anesthetic machine according to the
manufacturers recommendations. Insertion of a charcoal filter into the anesthesia machine circuit allows rapid
clearance of residual anesthetic gases without prolonged flushing with fresh gas.
21
The patient should be carefully
monitored, especially with a focus on end-tidal carbon dioxide and core temperature. Prophylactic dantrolene is not
indicated. MH susceptible patients that receive a non-triggering anesthetic technique do not require extended
postoperative monitoring as long as their anesthetic course was uneventful. Following discharge, the patient is
instructed to call their physician or go to the emergency room if they develop elevated temperature or brownish
discoloration of their urine, which indicates myoglobinuria.

Case Example
During the RCL, I will discuss this recently encountered real case: A healthy 5 yr old girl presented for
tonsillectomy. Her paternal aunt (fathers sister) had a suspicious episode of MH in 1981 and has been treated as if
she is MH susceptible ever since. The aunt never had a biopsy or genetic testing. No one else in the family has ever
been tested but they have always considered themselves MH susceptible.

Questions:
Does the pt need a non-triggering technique?
Should she receive prophylactic dantrolene?
Postoperatively, do standard discharge criteria apply?
Can she have her surgery at a freestanding ASU?
Who should now be tested, and how?
What are the advantages/disadvantages of always considering the aunt (and family) MH susceptible?

432
Page 4
Table 1. Suggested Emergency MH Cart Supplies

Drugs
Dantrolene 20 mg vials 36 vials
Sterile water 2 1-liter bags
Sodium bicarbonate 8.4 percent, 50 mL 5 prefilled syringes or vials
Dextrose 50 percent, 50 mL 2 vials
Furosemide 10 mg/mL, 10 mL 2 vials
Calcium chloride 10 percent, 10 mL 2 vials
Lidocaine 2 percent, 5 mL 4 prefilled syringes or vials
Amiodarone 50 mg/mL, 3 mL 2 vials

Refrigerated drugs and solutions
Insulin regular 100 units/mL, 10 mL 1 vial
0.9% normal saline, 1000 mL for IV cooling 4 bags and sterile pour bottles
Cold packs 8 (freezer)

General equipment
Syringes, 60 mL to dilute dantrolene 5
Mini-spike or similar IV additive pins and transfer set to reconstitute
dantrolene.
2
IV catheters: 16G, 18G, 20G 2 inch, 22 g 1 inch, 24G ! inch (for IV
access and arterial line)
4 each
NG tubes Various sizes
60 cc irrigation syringes 2
Drip IV set, chamber, extension 4
Syringes (insulin, ABG, 60 mL, 10 mL, 3 mL) 4 to 6 each
18G needles 6
Charcoal filter (Vapor-Clean, Dynasthetics LLC, Salt Lake City, UT) 2

Monitoring equipment
Esophageal or tympanic temperature probes 2
Rectal or bladder and skin temperature probes 2

Nursing supplies
Large sterile Steri-Drape 1
Urine meter 1
Irrigation tray with piston (60 cc irrigation) syringe 1
Small and large clear plastic bags for ice 4 each
Bucket for ice 1
Test strips: urine analysis for hemoglobin and finger stick glucose 1 vial

432
Page 5
Table 2. Treatment of Acute MH

Initial Steps:
Call for help, dantrolene, and MH emergency supply cart.
Notify surgeon to abort or complete procedure rapidly.
Discontinue triggering agents and switch to non-triggering intravenous anesthetics if surgery ongoing.
Hyperventilate with 100% oxygen, place charcoal filter into breathing circuit; endotracheal intubation.
Administer dantrolene: dissolve 20 mg dantrolene in 60 mL sterile water; 2.5 mg/kg IV rapid push, and then 1
mg/kg every 10-15 minutes until reversal of acute signs of MH.
Place bladder catheter to monitor urine output and color.
If feasible, call MH Hotline during any part of treatment process: 1-800-644-9737 (1-315-464-7079 outside U.S.).

Ongoing Monitoring and Treatment:
Potassium, ABG, glucose levels at least every 20 minutes, CK levels every 6 hours for first 48 hours.
Treat hyperkalemia with hyperventilation, calcium chloride (10 - 20 mg/kg) or calcium gluconate (50 - 100 mg/kg).
Additional treatment of hyperkalemia: 10 units insulin IV push with 50 mL 50% dextrose glucose (for adults); 0.1
units insulin/kg IV push with 2 mL/kg 25% dextrose glucose (for pediatric patients).
Treat metabolic acidosis with sodium bicarbonate, 1-2 mEq/kg, IV push over 5 to 10 minutes.
Treat hyperthermia with cooling methods such as IV cold saline, ice to body surface, or cold lavage to open body
cavities; stop cooling when core body temperature decreases to 38
o
C.
Life-threatening dysrhythmias usually caused by hyperkalemia. Do not administer calcium channel blockers
(contraindicated with dantrolene treatment).
Maintenance dantrolene: 1 mg/kg every 4 to 6 hours, or 0.25 mg/kg/hr continuous infusion. Maintain for 24-48 hrs
after last sign of acute MH.
Treat myoglobinuria with induced diuresis (furosemide 1 mg/kg/dose) and sodium bicarbonate to alkalinize urine if
CK >10,000 IU/L.
Monitor coagulation studies for disseminated intravascular coagulation if rhabdomyolysis or hyperthermia severe.

432
Page 6
References

1. Cullen KA, Hall MJ, Golosinskiy A: Ambulatory surgery in the United States, 2006. Natl Health Stat Report
2009; 1-25
2. Sei Y, Sambuughin NN, Davis EJ, Sachs D, Cuenca PB, Brandom BW, Tautz T, Rosenberg H, Nelson TE,
Muldoon SM: Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I
ryanodine receptor gene. Anesthesiology 2004; 101: 824-30
3. Groom L, Muldoon SM, Tang ZZ, Brandom BW, Bayarsaikhan M, Bina S, Lee HS, Qiu X, Sambuughin N,
Dirksen RT: Identical de novo mutation in the type 1 ryanodine receptor gene associated with fatal, stress-
induced malignant hyperthermia in two unrelated families. Anesthesiology 2011; 115: 938-45
4. Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P: Mutations in RYR1 in malignant hyperthermia
and central core disease. Hum Mutat 2006; 27: 977-89
5. Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H, Nonaka I, Noguchi S, Hayashi YK,
Nishino I: Central core disease is due to RYR1 mutations in more than 90% of patients. Brain 2006; 129:
1470-80
6. Mathews KD, Moore SA: Multiminicore myopathy, central core disease, malignant hyperthermia
susceptibility, and RYR1 mutations: one disease with many faces? Arch Neurol 2004; 61: 27-9
7. D'Arcy CE, Bjorksten A, Yiu EM, Bankier A, Gillies R, McLean CA, Shield LK, Ryan MM: King-
denborough syndrome caused by a novel mutation in the ryanodine receptor gene. Neurology 2008; 71: 776-7
8. Stamm DS, Aylsworth AS, Stajich JM, Kahler SG, Thorne LB, Speer MC, Powell CM: Native American
myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant
hyperthermia. Am J Med Genet A 2008; 146A: 1832-41
9. Marchant CL, Ellis FR, Halsall PJ, Hopkins PM, Robinson RL: Mutation analysis of two patients with
hypokalemic periodic paralysis and suspected malignant hyperthermia. Muscle Nerve 2004; 30: 114-7
10. Capacchione JF, Muldoon SM: The relationship between exertional heat illness, exertional rhabdomyolysis,
and malignant hyperthermia. Anesth Analg 2009; 109: 1065-9
11. Tobin JR, Jason DR, Challa VR, Nelson TE, Sambuughin N: Malignant hyperthermia and apparent heat
stroke. JAMA 2001; 286: 168-9
12. Gurnaney H, Brown A, Litman RS: Malignant hyperthermia and muscular dystrophies. Anesth Analg 2009;
109: 1043-8
13. Bollig G, Mohr S, Raeder J: McArdle's disease and anaesthesia: case reports. Review of potential problems
and association with malignant hyperthermia. Acta Anaesthesiol Scand 2005; 49: 1077-83
14. Fricker RM, Raffelsberger T, Rauch-Shorny S, Finsterer J, Muller-Reible C, Gilly H, Bittner RE: Positive
malignant hyperthermia susceptibility in vitro test in a patient with mitochondrial myopathy and
myoadenylate deaminase deficiency. Anesthesiology 2002; 97: 1635-7
15. Wieser T, Kraft B, Kress HG: No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant
hyperthermia susceptible individuals. Neuromuscul Disord 2008; 18: 471-4
16. Litman RS, Rosenberg H: Malignant hyperthermia-associated diseases: state of the art uncertainty. Anesth
Analg 2009; 109: 1004-5

432
Page 7
17. O'Flynn RP, Shutack JG, Rosenberg H, Fletcher JE: Masseter muscle rigidity and malignant hyperthermia
susceptibility in pediatric patients. An update on management and diagnosis. Anesthesiology 1994; 80: 1228-
33
18. Larach MG, Brandom BW, Allen GC, Gronert GA, Lehman EB: Cardiac arrests and deaths associated with
malignant hyperthermia in north america from 1987 to 2006: a report from the North American Malignant
Hyperthermia Registry of the Malignant Hyperthermia Association of the United States. Anesthesiology
2008; 108: 603-11
19. Burkman JM, Posner KL, Domino KB: Analysis of the clinical variables associated with recrudescence after
malignant hyperthermia reactions. Anesthesiology 2007; 106: 901-6
20. Litman RS, Flood CD, Kaplan RF, Kim YL, Tobin JR: Postoperative malignant hyperthermia: an analysis of
cases from the North American Malignant Hyperthermia Registry. Anesthesiology 2008; 109: 825-9
21. Birgenheier N, Stoker R, Westenskow D, Orr J: Activated charcoal effectively removes inhaled anesthetics
from modern anesthesia machines. Anesthesia & Analgesia 2011; 112: 1363-70
22. Mitchell LW, Leighton BL: Warmed diluent speeds dantrolene reconstitution. Can J Anaesth 2003; 50: 127-
30

Disclosure

102
Page 1
Update on Cardiac Anesthesia
Glenn P. Gravlee, M.D. Aurora, Colorado
As for any physician in any specialty, new challenges and therapeutic options continue to emerge for cardiac
anesthesiologists. In particular, we are spending more and more time caring for patients undergoing nonsurgical or
combined surgical/nonsurgical interventions. Examples include thoracic endovascular aortic repairs and the
LARIAT procedure. In addition, a fibrinogen concentrate has been approved by the Food and Drug Administration
and introduced in the United States after considerable experience in Europe. This product might displace
cryoprecipitate and reduce activated Factor VII use. Finally, longstanding controversy about when to place stents vs
perform coronary artery bypass grafting (CABG) has heated up as a result of recent studies that may tip the scales
back toward CABG.
Thoracic Endovascular Aortic Repair (TEVAR)
Background. In recent years TEVAR has grown rapidly as an alternative to open descending thoracic aortic graft
placement. This experience has been the natural outgrowth of favorable results with abdominal aortic endovascular
repairs. Although the literature lacks randomized prospective clinical trials, retrospective or prospective case-
control studies strongly suggest TEVAR superiority over open descending aortic grafts for many important short-
and medium-term outcomes such as 30-day mortality, paraplegia, cardiac complications, blood transfusion, renal
impairment, pulmonary complications, and length of hospital stay (Cheng). Any survival benefit at one year and
beyond remains unproven, but this may change as long-term follow-up continues. The differences were risk-
adjusted for many important co-morbidities. TEVAR can be utilized for a variety of descending thoracic aortic
pathology including acute and chronic dissections, atherosclerotic aneurysms, and traumatic aortic disruptions.
Experience to date precludes any recommendation for aortic arch or ascending aortic aneurysms, and it appears that
most centers still approach these aneurysms with open surgery.
Preparation for surgery. These cases range in urgency from elective atherosclerotic aneurysms to acute traumatic
contained ruptures threatening to blow any minute. Common to all is the potential need to convert to open
thoracotomy because of free natural rupture or because the TEVAR intervention causes bleeding, creates new
downstream ischemia, or fails to correct the pathology. Consequently, it makes sense to prepare for substantial
blood loss and emergency open thoracotomy just in case. Many centers use a hybrid operating room for these
procedures, i.e., one that simultaneously permits state-of-the-art radiographic imaging while also allowing
thoracotomy and extracorporeal circulation if needed. Standard American Society of Anesthesiologists (ASA)
monitors plus one or more arterial catheters and large-bore IV catheters are baseline expectations (Ellard). Central
venous access of some type may be helpful as well. Transesophageal echocardiography may be helpful if there is
diagnostic uncertainty about ascending aortic dissection (or if needed for intra-anesthetic cardiac diagnosis and
management), but most often intravascular ultrasound fulfills the intraoperative needs of the surgeon. Rapid or
immediate availability of adjuncts such as autotransfusion, a rapid infuser, and fluid warmers are advisable. A
double-lumen endobronchial tube or bronchial blocker should be rapidly available in the event of conversion to
thoracotomy.
For patients with acute dissections and ruptures, preoperative hemodynamic stabilization with a beta-adrenergic
blocker such as esmolol and a vasodilator such as nitroprusside, clevidipine, or nicardipine will help prevent
extension of the dissection or rupture by reducing wall tension on the torn segment. For intraoperative use, the
same vasoactive drugs one would prepare for an open descending aortic or thoraco-abdominal aortic repair should
be immediately available. In addition, large doses of adenosine may be used during deployment of the stent.

102
Page 2
Another consideration is the potential need for a separate or simultaneous carotid-to-left subclavian bypass
procedure if the aortic stent landing zone will likely occlude the left subclavian artery ostium.

Anesthesia management: Arterial catheter placement varies in both number and site. Sometimes our surgeons
want bilateral radial artery catheters for a combination of monitoring and wire access. A right radial catheter may
facilitate endovascular graft placement in the descending thoracic aorta by mating from above with a retrograde
wire advanced from below. Sometimes anticipated left subclavian artery coverage (i.e., partial or complete
obstruction) precludes a left radial artery catheter while making the left hand a desired site for the pulse oximeter (as
a monitor for loss of signal) (Jazaeri). Depending upon the anticipated length of the stent graft and what may
already be known about a patients spinal cord blood supply, a spinal cord drain may be desired (Ullery). The closer
the anticipated distal end of the stent will be to the diaphragm and the longer the anticipated length of the
endovascular graft, the more likely the surgical team is to request a spinal drain. The benefit of spinal drains is
much less well substantiated for endovascular aortic stents than for open thoracic aortic or thoraco-abdominal aortic
grafts. If a spinal drain is used, the prevailing norm is to maintain cerebrospinal fluid (CSF) pressure at 8-12 mmHg
while limiting CSF drainage to 15-20 mL/hr.

Substantial retrospective data show better outcomes (mortality, pulmonary complications, length of stay, cardiac
complications) when regional anesthesia or local/MAC is chosen over general anesthesia for abdominal aortic
endovascular repair (Bakker, Cheng). One retrospective study suggests similar benefit for thoracic aortic
endovascular repairs, even to the extent of using the spinal drain to provide intermittent boluses of local anesthetic
drug and keeping the patient awake (Lee). General anesthesia currently is used exclusively for TEVARs at
University of Colorado Hospital. The potential need for deliberate short-term reduction in cardiac output during
proximal stent deployment complicates intraprocedural management. Techniques used to achieve this cardiac
output reduction include high-dose adenosine, rapid right ventricular pacing, and balloon inflation in the right
atrium. If used, these techniques offer less appeal in an awake patient than in an asleep, intubated one. Spinal
anesthesia would also render evoked potential monitoring ineffective, and could delay post-procedural neurologic
assessment.

Fibrinogen: Underappreciated Factor?

Fibrinogen concentrates are increasingly available in Europe, and are now available in the USA after FDA approval
for congenital deficiencies. Consequently, their use in intraoperative coagulopathies would be off-label;
nevertheless several studies report its use. Some show fibrinogen to be the first factor to diminish to the point of
deficiency during consumptive processes (as cardiopulmonary bypass can be) (Levy). Fibrinogen concentrate is
available as a lyophilized, reconstituted human product. As compared to fresh-frozen plasma, fibrinogen is much
more concentrated and expensive. As compared to cryoprecipitate, it is approximately the same concentration but
probably carries a lower risk of viral transmission and immunomodulation, and it is likely to be more rapidly
available (if it is locally available at all). As compared to recombinant factor VIIa, fibrinogen is less expensive and
is thought to require thrombin rather than generate it. In theory, the latter distinction suggests a lower risk of
hypercoagulable and hyperinflammatory states. Blome et al. correlated even low normal fibrinogen concentration
with post-cardiopulmonary bypass (CPB) bleeding (Blome). Karlsson et al. found that prophylactic fibrinogen
after CPB decreased 12-hr blood loss (Karlsson). Two nonrandomized studies found that fibrinogen administered
as the first intervention in post-CPB coagulopathy decreased transfusion of other components, one of which also
showed lower blood loss (Solomon, Rahe-Meyer). A recent editorial stated that fibrinogen concentrates have
replaced cryoprecipitate as a source of fibrinogen in several European countries. This same editorial noted that
dose-finding studies are needed, and that five prospective cardiac surgical clinical trials are ongoing (Ranucci).

Conclusive recommendations as to optimal use of fibrinogen concentrates in cardiac surgery cannot yet be made, but
in the meantime it appears reasonable to discuss these concentrates within your institution as a possible substitute for
cryoprecipitate when fibrinogen supplementation is indicated. It also seems reasonable to aggressively pursue a
diagnosis of hypofibrinogenemia in higher risk situations such as CPB times > 2 hours, redo cardiotomies, and
circulatory arrest procedures. In such cases, toward the end of CPB or immediately after protamine administration
one should strongly consider either traditional measurement of plasma fibrinogen concentration or a
thromboelastographic (TEG) equivalent such as ROTEM FIBTEM or the alpha-angle of a traditional TEG.
Whereas in the past a plasma fibrinogen concentration <100 mg/dL was considered to be the intervention threshold
for cryoprecipitate, currently the presence of coagulopathy in combination with a fibrinogen concentration < 200

102
Page 3
mg/dL supports administration of either cryoprecipitate (10 bags) or fibrinogen concentrate (approximately 4 grams)
as a primary intervention. There is insufficient evidence to support prophylactic administration of fibrinogen
concentrates after CPB.

LARIAT Procedure (and variants)

The LARIAT Procedure (device manufacturer SenterHEART, Inc) percutaneously lassoes the left atrial
appendage (LAA). This is typically performed by cardiologists with general anesthesia in an electrophysiology
procedure room, typically with a cardiac surgical team immediately available on standby. The principal indication
is chronic atrial fibrillation in a patient at high risk for thromboembolic phenomena who is also unable to receive
appropriate anticoagulants. The procedure involves placing a magnetized balloon catheter into the LAA via the
femoral vein and right atrium, then through the foramen ovale into the left atrium. A second catheter then is placed
percutaneously into the pericardium through a subxiphoid needle. A magnetic wire loop (LARIAT) is passed
through this introducer catheter to find the LAA via magnetic attraction to the balloon catheter. Once the LARIAT
has surrounded the LAA, it is guided to the LAA neck, the balloon catheter inside the LAA is inflated, the loop is
partially cinched down over the catheter, appropriate positioning is confirmed using ultrasound (often 3D
transesophageal echocardiography), the balloon is deflated and its catheter withdrawn, the lariat is tightened to
occlusion, and the pericardial catheter is withdrawn. Early studies suggest 95% efficacy in occluding the LAA,
which surprisingly is better than most reported surgical closure rates.

Obviously the biggest acute concerns are cardiac puncture during placement of the pericardial needle and rupture
of the left atrium while tightening the LARIAT. Because of the precision required for the procedure and its
attendant desire for short periods of apnea, most centers seem to be doing these procedures with general anesthesia,
although I could not find any series reported.

At least three experimental devices are being used to occlude the LAA from within. All are distensible devices
analogous to stents that, once deployed, have geometric shapes that variously resemble a parachute (WATCHMAN
device, Boston Scientific), a toadstool (Amplatzer device, St. Jude Medical), and a football (PLAATO device, ev3
Inc), respectively. Unlike LARIAT, these three devicets do not yet have Food and Drug Administration (FDA)
approval. Like LARIAT, hese devices have the potential for atrial rupture, but they also can migrate or embolize.
Here again, it appears that initially general anesthesia is being used predominantly, but it seems more likely that
these procedures could eventually move toward management with sedation than the LARIAT Procedure, because
they can be performed using femoral vein trans-septal access alone. Unlike LARIAT, the indwelling LAA occluder
devices require long-term anticoagulation, but possibly aspirin alone may prove adequate.

For all of these procedures, the anesthetic considerations are fairly obvious. The patients cardiac and other
comorbidities will play important roles in technique selection. Use of an arterial catheter seems very reasonable,
especially for the LARIAT procedure, and perhaps for the others as well at least initially.

CABG Comeback?

As recently as 10 years ago, coronary artery bypass grafting (CABG) was the dominant cardiac surgical operation
and one of the five most common surgical procedures in the US. How times have changed! Recent clinical studies
fuel a possible move back toward CABG for significant numbers of patients that have instead been undergoing
coronary stent placements in recent years. In a very large (190,000 patients) retrospective database study of
Medicare patients, Weintraub et al. compared outcomes in patients with 2- or 3-vessel coronary artery disease for
percutaneous coronary interventions vs surgical coronary artery bypass grafting (Weintraub). Inverse probability
weighting was used for risk adjustment. CABG patients had lower long-term mortality with a median follow-up of
2.67 years. Farkouh et al. found a lower long-term event rate after CABG in a prospective, randomized study of
1,900 diabetics with multivessel disease (Farkouh). The stent patients in this study predominantly received drug-
eluting stents, which allays concerns about the technology always staying ahead of the published studies.
There have been a number of interesting exchanges between invasive and noninvasive cardiologists about this latter
topic. In an accompanying editorial, Mark Hlatky, a noninvasive cardiologist, states, the comparative effectiveness
of CABG and PCIremains similar whether PCI is performed without stents, with bare-metal stents, or with drug-
eluting stentsMortality has been consistently reduced by CABG.The controversy should finally be settled.
Hlatky also opines that, Many percutaneous coronary interventions today are performed at the time of diagnostic

102
Page 4
coronary with the same physician making the diagnosis, recommending the treatment, and performing the
procedure. This conflict of interest has seemed obvious for years, yet it appears that little has been done about it.
With ever-increasing regulation of health care in the US, including pre-procedural insurance approvals, it seems
possible that pre-approval for diagnostic cardiac catheterizations might cease to be accompanied by routine pre-
approval for coronary intervention, especially in elective scenarios and in diabetic patients. This could initiate a
CABG comeback time will tell.

References

TEVAR
Cheng D, Martin J et al, JACC 2010:55:986-1001.
Ellard L, Djaiani G, Anaesthesia 2013 68 (Suppl 1): 72-83.
Bakker EJ, van de Luijtgaarden KM et al, Eur J Vasc Endovasc Surg 2012;44:121-5.
Edwards MS, Andrews JS et al, J Vasc Surg 2011;54:1283-82.
Jazaeri O, Gupta R et al, Semin Cardiothorac Vasc Anes 2011;15:141-62.
Ullery B, Wang G et al, Semin Cardiothorac Vasc Anes 2011;15:123-40.
Lee WA, Daniels MJ et al, Circulation 2011;123:2938-45.

Fibrinogen

Levy JH, Anesth Analg 2012;114:261.
Blome M, Thromb Haemost 2005;93:1101.
Karlsson M, Thromb Haemost 2009;102:137.
Rahe-Meyer N, Brit J Anaesth 2009;102:785.
Solomon C, Scand J Clin Lab Invest 2012;72:121.
Ranucci M. J Thorac Cardiovasc Anes 2013;27:12.

Lariat Procedure

www.mymethodist.net/services/cardiovascular/lariat-procedure, accessed March 8, 2013.
Cheng A, Nonpharmacologic therapy to prevent embolization in patients with atrial fibrillation, UpToDate, April
29, 2013, accessed May 30, 2013.
Bartus K et al, Heart Rhythm 2011;8:188.
Shetty R, J Invasive Cardiol 2012:24:E289.

CABG Comeback?

Weintraub WS, NEJM 2012;366:1467
Farkouh ME, NEJM 2012;367:2375.
Hlatky MA, NEJM 2012;367:2437.

Disclosure

108
Page 1
Anesthesia for Patients With Valvular Heart Disease for Non-cardiac Surgery
Steven Konstadt, M.D., MBA, FACC Brooklyn, New York
INTRODUCTION
This talk will describe an approach to the patient with heart disease who is undergoing non-cardiac surgery.
Emphasis will be placed on the pathophysiology of the lesion, the pre-operative evaluation, anesthetic goals and
pertinent therapeutic options. Because of the time limitations of the presentation, not all cardiac conditions will be
addressed. Instead, this talk will focus on five important lesions that have been chosen because of their severity and
prevalence: aortic stenosis, hypertrophic obstructive cardiomyopathy, rheumatic mitral stenosis, and mitral valve
prolapse. In managing patients with valvular heart disease there are two important philosophies to remember. First,
"the enemy of good is better." Most valvular lesions cannot be completely treated by medical management. In other
words, don't over-treat these patients; aim for stability, not "normal" hemodynamics. Second for the reasons that will
become clearer in the discussion of aortic stenosis, in patients with multiple valvular lesions which may suggest
contradictory anesthetic goals, always give the highest priority to the aortic stenosis.
AORTIC STENOSIS
Aortic stenosis derives its position as the most important valvular lesion because of its potential for sudden
death(15-20%), and because of the inability to obtain adequate systemic perfusion by external cardiac massage
during a cardiac arrest. The three main etiologies of aortic stenosis are congenital, senile calcification and rheumatic
disease. The normal aortic valve is 2-3 cm
2
. As the valve orifice narrows, resistance to flow develops and a pressure
gradient across the valve also occurs. This pressure gradient leads to a pressure overload of the left ventricle.
There is compensatory concentric hypertrophy to normalize the wall stress, but other abnormalities persist:
increased oxygen demand, reduced oxygen delivery, and reduced diastolic relaxation and compliance. Symptoms ,

108
Page 2
i.e., angina, CHF, syncope, and sudden death, usually begin to occur when the valve area falls below 1 cm
2
.
Preoperative evaluation of a systolic ejection murmur will generally begin with an echocardiogram, and if the
symptoms or echo indicate, cardiac catheterization will be performed. The important measurements obtained during
catheterization are the aortic valve gradient, the aortic valve area, LVEDP, and LVEF. The main anesthetic goals are
to maintain normal sinus rhythm, adequate intravascular volume, and systemic vascular resistance. Perioperative
mortality in patients with critical aortic stenosis (AVA<.6cm
2
) has been reported as high as 11%. In addition to the
usual pharmacologic agents, there are two additional interventions to consider. One is the preoperative placement of
an IABP to improve coronary perfusion, and the other option in patients who are not candidates for aortic valve
replacement, is to perform percutaneous valve replacement to reduce the stenosis prior to non-cardiac surgery.

Hypertrophic Obstructive Cardiomyopathy(HOCM)
One rationale for including this lesion is that like aortic stenosis, HOCM can precipitate sudden death. It is
also included because of its unique dynamic physiology and unusual treatments. HOCM results in obstruction to LV
ejection in the LV outflow tract. Like aortic stenosis it also causes a pressure overload of the LV. In addition to the
pressure overload, systolic anterior motion (SAM) of the mitral valve induced by a Venturi effect, often precipitates
mitral regurgitation. Another possible physiologic mechanism of the LVOT obstruction relates to the position of the
papillary muscles. It is believed that the muscles can become anteriorly displaced and this moves the mitral valve
apparatus into the LVOT.

Factors such as hypovolemia, tachycardia, systemic vasodilation, and increased contractility all exacerbate
the obstruction. The clinical presentation includes angina, CHF, syncope and sudden death. Preoperative evaluation
includes baseline and provocative (Valsalva, or nitrates) echocardiography. The important measurements are the
LVOT diameter, the gradient across the LVOT, and the severity of the mitral regurgitation. The main anesthetic
goals are to maintain normal sinus rhythm, intravascular volume, systemic vascular resistance, and to avoid
hypercontractile states. In the acute perioperative period therapy is limited to pharmacologic agents, but in the
chronic care of HOCM, the synchronous contractile pattern induced by pacing may be therapeutic.

108
Page 3
Pulmonary Hypertension
Pulmonary hypertension (PHTN) can occur from a variety of causes including pulmonary disease, valvular
heart disease, and intrinsic vascular disease. Patients undergoing non cardiac surgery with pulmonary hypertension
usually do well intraoperatively but frequently have severe postop morbidity and mortality. In a retrospective review
of 145 patients with PHTN, there was a 7% periop mortality. Also the investigators identified several factors that
dramatically increased risk: history of pulmonary embolism, >class II NYHA, intermediate and high risk surgery,
and operations lasting more than 3 hours.
Rheumatic Mitral Stenosis
Mitral stenosis is a narrowing of the mitral valve orifice that results in left atrial hypertension, limited
filling of the LV, pulmonary congestion, and in moderate to severe cases, pulmonary arterial hypertension and right
ventricular pressure overload. Dyspnea is the most common presenting symptom, and many of the patients are in
atrial fibrillation. Echocardiography can demonstrate left atrial enlargement, mitral valve fibrosis and calcification,
and a gradient across the mitral valve. Cardiac catheterization will also determine the gradient across the valve, the
mitral valve area, LV function, and the right sided pressures. The anesthetic goals for patients with mitral stenosis
are to control the heart rate and if possible restore and preserve sinus rhythm, insure adequate intravascular volume,
and to prevent systemic arterial vasodilation. Additionally in patients with pulmonary hypertension, hypercarbia and
hypothermia, which may exacerbate the increased PVR should be avoided. Several special therapeutic options for
these patients exist. Balloon valvuloplasty may be performed, and cardioversion for atrial fibrillation may be useful.
There are also some new pharmacologic agents for treatment of refractory severe pulmonary hypertension: inhaled
prostacyclin and nitric oxide.
Mitral Valve Prolapse Syndrome (MVP)
MVP is the most common valvular abnormality occurring in 3 to 8 % of the population. Anatomically it is
characterized by billowing of one of the mitral valve leaflets into the left atrium. There may be minimal or
significant mitral regurgitation associated with this condition. In addition to the valvular abnormalities, there may be
an increased risk of autonomic dysfunction. Patients experience palpitations, chest pain, dyspnea, fatigue, and
orthostatic hypotension. Though there is some debate over the exact criteria to diagnose MVP, echocardiography is
still the diagnostic method of choice. Because of the leaflet abnormalities some of these patients receive anti-platelet
or other anticoagulant therapy. Other than infective endocarditis prophylaxis for those patients with abnormal
leaflets, there are few defined anesthestic goals for these patients.

References
1.Report of the American College of Cardiology/American Heart Association Task Forece on Practice guidelines
(Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Guidlines for perioperative
cardiovascular evaluation for noncardiac surgery JACC 27;910-48;1996
2.Cardiac Anesthesia, ed J.A. Kaplan, W.B. Saunders, Phila, PA 1993
3.Hayes et al, Palliative percutaneous aortic balloon valvuloplasty before noncardiac operations and invasive
diagnostic procedures. Mayo Clin Proc, 64:753-7,1989
4.Clinical Transesophageal Echocardiography, eds Oka and Konstadt, Lippincott-Raven, Phila PA, 1996.
5.O'Keefe et al, Risk of noncardiac surgical procedures in patients with aortic stenosis. Mayo Clin Proc, 64:400-
5,1989
6. Torsher et al: Risk of Patients with severe aortic stenosis in non-cardiac surgery. Am J Cardiol; 1998;81:448-52
7. Haering et al: Cardiac risk of non-cardiac surgery in patients with asymmetric septal hypertrophy. Anesthesiol;
1996;85:254-9
8. Jollis JG et al: Effects of Fen-phen, Circ 2000 101:2071-7
9. Kaluza et al: Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000
35:1288-94
10. Eagle et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery
executive summary: A report of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines JACC 39:542-53, 2002
11. Malouf et al: Aortic Stenosis and Pulmonary Hypertension. JACC 2002:40:789-9
12. Maron B et al: Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic
cardiomyopathy, NEJM: 2003; 348(4):295-303
13. Maron B : Hypertrophic cardiomyopathy, JAMA 2002;287:1308-1320
14. Kertai et al: Aortic stenosis: an underestimated risk factor for perioperative complications in patients undergoing
noncardiac surgery. AJMed January 2004, 8-13.
15. Poliac, et al: Hypertrophic Cardiomyopathy, Anesthesiology 104: 183-92, 2006.

108
Page 4
16. Cecchi, et al: Coronary Microvascular Dysfunction and Prognosis in Hypertrophic Cardiomyopathy. 349: 1027-
35, 2003
17. Amato, et al : Treatment Decision in asymptomatic aortic valve stenosis: role of exercise testing. Heart, 86:381-
6, 2001
18. ACC/AHA Guidelines for the management of patients with valvular heart disease. JACC 48: 1-148, 2006.
19.
Davenport DL, Ferraris VA, Hosokawa P, Henderson WG, Khuri SF, Mentzer RM.: Multivariable predictors of postoperative cardiac events
after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg 2007;204:1199-1210

20. Mittnacht, Fanshawe and Konstadt: Anesthetic considerations in the Patient with Valvular Heart Disease for Non
Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, Vol. 12, No. 1, 33-59 (2008)
21. Gautam Ramakrishna, MD, Juraj Sprung, MD, PHD, Barugur S. Ravi, MD, et al
Impact of Pulmonary Hypertension on the Outcomes of Noncardiac Surgery Predictors of Perioperative Morbidity
and Mortality, J Am Coll Cardiol
2005;45:16919

Disclosure

117
Page 1
Preconditioning the Heart:How it works and does it matter?
Judy R. Kersten, M.D. Milwaukee, Wisconsin
Objectives:
1) Identify the basic mechanisms of pre- and post-conditioning the heart against ischemic injury
2) Describe the evidence that supports or refutes the clinical use of anesthetics to protect the heart
3) Identify factors that interfere with clinical cardioprotection and strategies to mitigate the impact of disease
Preconditioning the heart against myocardial infarction was first described in 1986 by Murry, Jennings and
Reimer
1
. These investigators demonstrated that a brief period of myocardial ischemia that was insufficient to
damage myocardium protected against a more prolonged period of coronary artery occlusion and reperfusion in dogs
and infarct size was reduced by 50%. Subsequently, ischemic preconditioning (IPC) has been demonstrated in every
model and species in which it has been tested, including humans. Volatile anesthetics have also been shown to
precondition against myocardial ischemia and reperfusion injury
2
. These agents exhibited a memory period
during which myocardial protection persisted despite discontinuation of the anesthetic for up to 2 hr (anesthetic
preconditioning: APC) before index ischemia The protection of both IPC and APC waned and reappeared 24-48 hr
later during a second window or late preconditioning phase. A significant disadvantage of IPC and APC is that the
preconditioning stimulus must be applied before the period of index myocardial ischemia, thus limiting the clinical
utility of this approach. Interestingly, repetitive brief ischemia (stuttered reperfusion) or brief administration of
volatile anesthetics during the first seconds of reperfusion produced protection against ischemia and reperfusion
injury, a phenomenon referred to as post-conditioning (PoC). PoC has been shown to be equally efficacious as
compared to preconditioning strategies, and may be of greater clinical relevance as the period of prolonged ischemia
need not be anticpated. Recently, remote preconditioning (RIPC) has also become an attractive alternative to IPC
and PoC because coronary artery manipulation is avoided. During remote preconditioning, a regional ischemic
stimulus (e.g. limb ischemia and reperfusion) protected remote virgin myocardium against infarction
3
.
The mechanisms responsible for ischemic and anesthetic pre- and post-conditioning have been extensively
investigated in animal models. The mitochondrion appears to represent a final common pathway during
cardioprotection
4
. Mitochondria play essential roles not only in cellular energy metabolism, but also in signal
transduction, and regulation of apoptosis/cell death pathways. These organelles are an important source of reactive
oxygen species (ROS), that when released in small quantities, serve as triggers of IPC and APC. Conversely,
mitochondria are targets of injury during ischemia and reperfusion. For example, mitochondria play a critical role to
maintain intracellular calcium homeostasis. During ischemia and reperfusion, increases in cytosolic calcium lead to
mitochondrial calcium overload and excessive ROS production. These events provoke opening of the mitochondrial
permeability transition pore (mPTP), a large multi-protein channel connecting the inner and outer mitochondrial
membranes, resulting in collapse of the mitochondrial membrane potential and cell death. APC initiates a series of
intracellular signaling events including activation of membrane bound receptors, inhibitory G-proteins, intracellular
kinases, endothelial nitric oxide synthase (eNOS), and adenosine triphosphate-regulated potassium (KATP) channels
that ultimately attenuates opening of the mPTP and confer protection against ischemia and reperfusion injury. PoC
appears to protect the heart through similar reperfusion injury salvage kinase pathways, however, anesthetics also
have direct effects on mitochondria that are protective and do not require time-dependent signaling events. For
example, anesthetic PoC preserved an acidic mitochondrial matrix pH after reperfusion, an action that prevented
opening of the mPTP. Although the mechanisms involved in APC and APoC have been investigated in detail, much
less is known about the mechanism of RIPC. Blood borne mediators such as adenosine, nitric oxide, opioids, and
bradykinin have been suggested to play a role
5
.

117
Page 2
The potent cardioprotective effects of APC that were seen in animal studies were rapidly translated to use
in cardiac surgery where a well defined period of myocardial ischemia and reperfusion could be anticipated and
treated. Several small early studies indicated that troponin concentrations were reduced and left ventricular function
preserved in patients receiving volatile anesthetics compared to intravenous anesthetics
6
. However, not all studies
demonstrated a cardioprotective effect of volatile agents. It has been suggested that variations in mode of
administration, anesthetic concentration, presence of an anesthetic washout period (memory), and use of aprotinin
and other drugs all could have influenced the results. Thus, volatile anesthetics administered either throughout the
entire surgical procedure (evoking pre- and post-conditioning and anti-ischemic effects) or as a repetitive APC
stimulus may be most effective at decreasing myocardial injury
7
.
RIPC against myocardial infarction was first demonstrated in patients admitted with MI and randomized to
receive percutaneous coronary artery intervention either without or with RIPC (intermittent arm ischemia induced
with 4 cycles of 5 min blood pressure cuff inflations/deflations). Myocardial salvage was significantly improved by
RIPC
8
. RIPC has also been used to reduce troponin concentrations in patients undergoing cardiac surgery; however,
the results are conflicting. One study showed that RIPC was effective in isoflurane- but not propofol-anesthetized
patients
9
, while other studies have shown that RIPC does not modify myocardial injury in patients that are already
protected with volatile anesthetics. Lack of additional protection by RIPC during anesthesia with volatile
anesthetics
10
could be explained by activation of similar signaling pathways by RIPC or by decreased intensity of the
regional ischemic stimulus secondary to anesthetic effects on blood flow and oxygen consumption.
The beneficial effects of volatile anesthetics to protect against myocardial injury in patients at risk for
ischemia have been evaluated during non-cardiac surgery as well. For example, in a recent RCT of 385 patients,
sevoflurane did not decrease the incidence of myocardial ischemia compared to patients anesthetized with
propofol
11
. The evidence for a clear benefit of volatile anesthetics to protect myocardium against ischemic injury in
patients undergoing cardiac or non-cardiac surgery is equivocal despite overwhelming pre-clinical evidence that
volatile anesthetics possess potent cardioprotective effects. There are several important factors that may explain the
apparent lack of clinical cardioprotection in some studies
12
. The timing and mode of administration (stuttered versus
continuous), and dose of volatile anesthetic influences the efficacy of these drugs to reduce ischemic injury and was
not standardized in many investigations. Opioids have also been demonstrated to protect against myocardial
ischemia and reperfusion injury through activation of opioid receptor subtypes, including delta-, kappa-, and mu-
receptors. In addition, clinical studies frequently do not include an assessment of myocardium at risk for ischemic
injury. A recent consensus statement suggested that advanced myocardial imaging (e.g. SPECT) should be used to
precisely determine both risk area and the extent of myocardial injury during clinical trials that aim to determine the
efficacy of cardioprotective strategies. Asymptomatic myocardial ischemia is observed in nearly 50% of ambulatory
patients with stable coronary artery disease, and the degree of silent ischemia (frequency and severity) may be more
important in predicting cardiac events than the mere presence of ischemia. It has been suggested that the specific
anti-ischemic regimen that is utilized (that may include a variety of drugs such as beta blockers, statins, aspirin,
ACE inhibitors/ARBs) may be of less importance than insuring that heart rate is adequately suppressed.
Disease states or their treatment may influence the ability of anesthetics to modulate ischemia and
reperfusion injury
13
. APC and APoC were abolished by hyperglycemia, diabetes and in aged myocardium.
Sulfonylurea drugs used to treat diabetes stimulate insulin release by closing KATP channels in the beta cells of the
pancreas. They also blocked myocardial KATP channels and the beneficial effects of IPC and APC. Thus,
discontinuing sulfonylurea drugs 24-48 hrs before elective surgery is recommended.
Finally, statins are an important class of drugs that decrease cardiovascular morbidity and mortality, and
produce favorable actions to restore APC during hyperglycemia. The results of a meta-analysis highlight the
potential for statin therapy to positively impact cardiovascular risk reduction in patients undergoing cardiac and non-
cardiac surgery
14
. Additionally, evidence suggests that administration of statins to statin nave patients may be
beneficial in cardiac and non-cardiac surgery. Although there remains a small risk of rhabdomyolysis in patients in
whom statins are continued in the perioperative period, mortality rate may be substantially increased in patients in
whom statins are withdrawn
15
. Thus, patients who are chronically treated with statins should continue to receive
these drugs perioperatively.

In conclusion, volatile anesthetics produce potent effects to reduce myocardial ischemia and reperfusion
injury in experimental models but the benefits of these agents to decrease injury in patients during cardiac or non-
cardiac surgery are less clear. The results of clinical studies are difficult to interpret due to confounding factors such
as inability to accurately assess ischemic burden and area at risk for infarction. Concomitant treatment with other
drugs that significantly impacts cardiovascular outcome (e.g. statins, beta-blockers, ACE inhibitors, ARBs, alpha2-
agonists) also complicates the interpretation of clinical trial data. Although no single drug may be the magic bullet

117
Page 3
to improve cardiovascular outcome, the use of volatile anesthetics may be an important part of a multimodal
approach to protect the heart in patients with cardiovascular disease.

References

1.Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic
myocardium. Circulation 1986;74:1124-1136

2.Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC: Isoflurane mimics ischemic preconditioning via
activation of KATP channels: Reduction of myocardial infarct size with an acute memory phase. Anesthesiology
1997; 87:361-370.

3. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic preconditioning protects remote
virgin myocardium from subsequent sustained coronary occlusion. Circulation 1993;87:893899

4. Di Lisa F, Canton M, Carpi A, Kaludercic N, Menabo R, Menazza S, Semenzato M. Mitochondrial injury and
protection in ischemic pre- and postconditioning. Antioxidants & Redox Signaling 2011;14:881-890

5. Weiwei Shi and Jakob Vinten-Johansen. Endogenous cardioprotection by ischaemic postconditioning and remote
conditioning. Cardiovascular Research (2012) 94, 206216

6. De Hert, SG, Van der Linden, PJ; Cromheecke, S, Meeus, R, Nelis, A, Van Reeth, V, ten Broecke, PW, De Blier,
IG, Stockman, BA, Rodrigus, IE. Cardioprotective properties of sevoflurane in patients undergoing coronary
surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology
2004;101:299310

7. Frdorf, Borowski, Ebel, Feindt, Hermes, Meemann, Weber, Mllenheim, Weber, Preckel, Schlack. Impact of
preconditioning protocol on anesthetic-induced cardioprotection in patients having coronary artery bypass surgery.
J Thorac Cardiovasc Surg 2009;137:14361442

8. Btker H, Kharbanda R, Schmidt M, Bttcher M, Kaltoft A, Terkelsen C, Munk K, Andersen N, Hansen T,
Trautner S, Flensted Lassen J, Christiansen E, Krusell L, Kristensen S, Thuesen L, Nielsen S, Rehling M, Srensen
H, Redington A, Nielsen T. Remote ischaemic conditioning before hospital admission, as a complement to
angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.
Lancet 2010; 375:727-734

9. Heusch G, Musiolik J, Kottenberg E, Peters J, Jakob H, Thielmann M. STAT5 activation and cardioprotection by
remote ischemic preconditioning in humans. Circulation Research 2012;110:111-115

10. Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan A, Finegan B, Zaugg M. Remote ischemic
preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing
on-pump coronary artery bypass graft surgery. Anesthesiology 2012; 116:296-310

11. Buse G, Schumacher P, Seeberger E, Studer W, Schuman R, Fassl J, Kasper J, Filipovic M, Bolliger D,
Seeberger M. Randomized comparison of sevoflurane versus propofol to reduce perioperative myocardial ischemia
in patients undergoing noncardiac surgery. Circulation 2012;126:2696-2704

12. Kersten J. A recipe for perioperative cardioprotection: What matters most? The ingredients or the chef?
Circulation 2012; 126:2671-2673

13. Gu W, Pagel PS, Warltier DC, Kersten JR: Modifying cardiovascular risk in diabetes mellitus. Anesthesiology
2003; 98:774-9

14. Hindler K, Shaw AD, Samuels J, Fulton S, Collard CD, Riedel B: Improved postoperative outcomes associated
with preoperative statin therapy. Anesthesiology 2006; 105:1289-90

117
Page 4

15. Schouten O, Hoeks SE, Welten GM, Davignon J, Kastelein JJ, Vidakovic R, Feringa HH, Dunkelgrun M, van
Domburg RT, Bax JJ, Poldermans D: Effect of statin withdrawal on frequency of cardiac events after vascular
surgery. Am J Cardiol 2007; 100:316-20

Disclosure

123
Page 1
Regional Versus General Anesthesia for Vascular Surgery Patients
Peter Rock, M.D., MBA Baltimore, Maryland
Introduction
Vascular surgery patients are at increased risk for complications. These patients may have congestive heart
failure (CHF), a history of cigarette smoking, chronic obstructive pulmonary disease, hypertension, renal failure, and
diabetes (DM). There is an increased incidence of coronary artery disease (CAD) in this population and an increased
risk of myocardial infarction (MI) after vascular surgery. The AHA/ACC guidelines for patients undergoing non-
cardiac surgery categorize vascular surgery as high-risk [1]. Patients who are in jeopardy of developing
perioperative complications would benefit from anesthetic techniques that improve outcomes. Cardiac and
pulmonary complications, graft and deep venous thrombosis, gastrointestinal (GI) and central nervous system
(CNS) function, and mortality are important outcomes to evaluate. This review will address these issues, focusing on
major aortic and lower extremity arterial bypass surgery using general (GA) or regional anesthesia (RA) with either
spinal (SA) or epidural (EA) anesthesia. Since not all aspects of improvement in outcomes have been studied in
vascular surgery patients, it will be necessary to extrapolate to such patients the results of studies performed in other
surgical disciplines. There is conflicting data regarding whether regional analgesia results in superior outcomes
compared to other forms of analgesia. The line between intraoperative anesthesia and postoperative analgesia is
often blurred but the results of analgesic interventions are relevant to perioperative outcomes.
Potential Advantages and Disadvantages of RA and GA
RA does not require airway manipulation or neuromuscular blockade. Volatile agents are not used; there is
less effect on ventilatory control. A hypercoagulable state is seen after surgery. RA, by attenuating the stress
response to surgery, may modify the tendency to clot and decrease the incidence of postoperative venous, arterial,
and graft thrombosis [2, 3]. RA using local anesthetics (LA) and opioids can be administered continuously
postoperatively. RA may permit early ambulation, faster rehabilitation, and a decreased hospital length of stay
(LOS). EA provides better postoperative analgesia compared to intravenous patient-controlled analgesia (PCA) [4].
RA may be more time consuming than GA and is expensive if performed in the OR. Recent studies have
illustrated the risks associated with RA. A prospective study of 103,740 regional anesthetics (40,640 SA; 30,413
EA; 32,687 other) examined the incidence of adverse outcomes. [5]. There were 29 cardiac arrests, most of which
occurred during SA. Neurologic injury was reported in 34 patients. The risk of seizures after injection of LA was
2.2/10,000 and the risk of death was 0.7/10,000. A follow-up study confirmed the previous findings (56 major
complications in approximately 158,083 regional anesthetics) [6]. A recent study of over 1.7 million regional
anesthetics found 127 neurologic complications including permanent neurologic damage in 85 patients [7]. A review
of 8,210 epidural catheters inserted for postoperative pain control revealed a significant incidence of neuraxial injury
[8]. These studies should not discourage the use of RA but illustrate that all anesthetics are associated with
complications. Spinal or epidural hematoma may occur even in patients with normal coagulation function and can
result in devastating neurological consequences. Patients with vascular disease may receive anticoagulants or
antiplatelet agents, which increase the risk of neuraxial bleeding. The recent outbreak of fungal meningitis
associated with epidural steroid injection is an illustration of how seemingly low-risk procedures can be associated
with catastrophic adverse outcomes. Other potential drawbacks of RA include: airway control is assumed; airway
secretions cannot be suctioned; and there is no control over ventilation and oxygenation. But, GA requires airway
manipulation and can induce bronchospasm. Inhalational anesthetics attenuate the response to hypercarbia and
hypoxemia, and neuromuscular blockade is often employed.
RA might improve outcomes by attenuating the perioperative stress response; GA does not attenuate the
stress response as well as RA. Elevations in heart rate and blood pressure increase myocardial oxygen demand and
result in myocardial ischemia or infarct in individuals with CAD. Coronary vasoconstriction, as a result of an

123
Page 2
increase in circulating catecholamines, decreases coronary blood flow and myocardial oxygen delivery. EA ablates
the catecholamine response to lower extremity vascular surgery and attenuates the catecholamine response to
surgery above the umbilicus [9]. Postoperative norepinephrine correlates with postoperative hypertension [10].
Impaired fibrinolysis and increases in platelet aggregation after surgery might result in coronary artery thrombosis.

Meta-Analysis and Randomized Clinical Trials (RCTs)
Meta-analyses have suggested the superiority of epidural analgesia over other types of postoperative pain
relief, producing superior pain control and a reduction in the rate of postoperative MI [11]. However, it is possible
that adequate pain relief, regardless of how it is achieved, may reduce the rate of perioperative MI. Older studies
included in meta-analyses have flawed study design. They did not control hemodynamics, temperature, post-
operative care, and analgesic care, between RA and GA groups. Inclusion of such studies in a meta-analysis will
lead to false conclusions. Improvements in clinical practice over time may render the results of a meta-analysis
irrelevant to modern practice. Meta-analyses frequently do not agree with RCTs published on the same topic. One
study concluded if there had been no subsequent RCT the meta-analysis would have led to the adoption of an
ineffective treatment 32% of the time and to the rejection of a useful treatment 33% of the time [12]. New evidence
that changes conclusions of systematic reviews arises frequently within a short time [13]. But, RCTs alter usual
clinical care limiting the ability to generalize the results beyond the conditions of the trial. The MI rate is often lower
in RCTs, where clinical care is controlled, than in studies where perioperative management is not tightly controlled.

Deep Venous Thrombosis (DVT) and Graft Thrombosis
Surgery produces a hypercoagulable state. Increased levels of plasminogen activator inhibitor may result in
impaired fibrinolysis and predispose to arterial or venous thrombosis following surgery [2]. RA may attenuate this
response. Infusing stress hormones to normal subjects does not cause increases in procoagulant proteins and platelet
reactivity or decreases in fibrinolytic proteins [14]. Systemic inflammation and the acute phase response that
accompanies major surgery may lead to synthesis of coagulation proteins and inflammation-related changes in
platelet function. Anesthetic choice might not influence hypercoagulability after surgery.
Few studies in vascular surgery patients address the issue of whether there is an outcome advantage to RA
with respect to DVT. Patients undergoing endovascular abdominal aortic aneurysm surgery have a 6% incidence of
DVT without advantage for RA over GA [15]. An older meta-analysis suggested that RA is associated with a 31%
reduction in the incidence of DVT compared to GA in individuals undergoing hip surgery [16]. Although the
incidence of DVT was decreased, overall mortality was unchanged, and prophylaxis for DVT was not given
routinely or described. There was no standardization of perioperative care, anesthetic regimens or ambulation
protocols, which could have influenced the findings. It is probable that such a large difference in DVT incidence, if
there were a difference at all, would not be found in modern studies employing routine DVT prophylaxis. There are
still conflicting results in the literature regarding the effectiveness of RA over GA in terms of reducing DVT in
orthopedic patients [17, 18]. The overall incidence of DVT and pulmonary embolism is low in orthopedic patients
[19]. A recent Cochrane review suggested RA was superior to GA in reducing the incidence of DVT but noted this
conclusion is insecure due to possible selection bias in the subgroups in which this outcome was measured [20].
It has been proposed that a benefit of RA over GA is reduction in the incidence of graft occlusion, perhaps
through its ability to attenuate the hypercoagulable state that accompanies major surgery. Early studies suggested a
decrease in graft occlusion in vascular surgery patients receiving RA [3, 21]. Recent studies have failed to reveal a
benefit to RA with respect to graft occlusion [22, 23]. In one such study, patients (n=315) were randomized to
receive EA, SA, or GA, monitored with a pulmonary artery catheter (PAC), and admitted to an ICU for 48 72
hours after surgery [23]. There were no differences between the groups with respect to graft patency. In the real
world, it is unlikely that many vascular surgery patients receive a PAC and a three-day ICU stay.

Cardiac Outcomes
In 1987 Yeager published the results of a RCT of EA and light GA vs. GA in high risk surgical patients
(n=53) [24]. There was a decreased rate of cardiovascular complications in the EA group. Perioperative care (e.g.
invasive hemodynamic monitoring) and analgesia were not standardized (analgesia levels differed between groups).
In 1991, Baron reported a RCT in patients (n=173) receiving combined EA and GA vs. GA for abdominal aortic
surgery. There was no difference in cardiovascular morbidity between groups [25]. Tuman reported on the results of
a RCT involving major vascular surgery of the abdominal aorta and lower extremities [3]. Patients (n=80) received
either combined EA and GA or GA alone. Cardiovascular complications were reduced in the EA group. The EA
group had excellent pain control while pain scores were not measured in the control group. Christopherson reported
on a RCT in patients (n=100) receiving either EA or GA for lower extremity bypass grafting surgery [21]. Cardiac

123
Page 3
outcomes were similar between the two groups. There was standardization and optimization of patient care and
equal pain control was achieved in both groups. Bode reported a RCT in 423 patients receiving EA, SA, or GA for
peripheral vascular surgery [22]. Cardiovascular morbidity and mortality were not different between groups. The
low mortality rate, 3.1%, means it would have been necessary to study more than 24,000 patients to have sufficient
power to detect a 50% reduction in mortality between groups. Rigg reported the results of a RCT (n=915) in high-
risk patients (DM, renal failure, respiratory insufficiency, CHF, CAD) undergoing high-risk procedures (aortic or
major GI, genitourinary, or gynecologic surgery) and who received combined EA, GA and epidural analgesia or GA
and PCA [26]. There were no differences between groups with respect to cardiovascular events.

Anesthetic Techniques vs. Standardization and Optimization of Perioperative Care
Norris tested the hypothesis that reduction in variation in care and control and optimization of perioperative
pain management and hemodynamics can reduce morbidity and mortality to levels that eliminate the impact of
anesthetic technique. The primary endpoint was hospital LOS. Patients (n = 168) undergoing major aortic surgery
were randomized to one of four groups who received combinations of intraoperative anesthetic type and
postoperative analgesia (thoracic EA/light GA/epidural PCA; thoracic EA/light GA/iv PCA; sham thoracic
EA/GA/epidural PCA; sham thoracic EA/GA/iv PCA)[27]. Protocols standardized perioperative care. There were no
differences with respect to LOS, death, MI, pneumonia, or pain control. LOS is an integrated outcome measure;
an individual that suffered significant morbidity would presumably spend a longer time in the hospital. Perioperative
care rather than a specific anesthetic regimen may be the most important factor in outcome after surgery.

Regional Anesthesia and Analgesia and Postoperative Pulmonary Complications (PPCs)
Because RA does not require the use of neuromuscular blockade, airway instrumentation, or volatile
anesthetics, it might reduce PPCs. It has been difficult to demonstrate the benefits of RA over GA with respect to
reducing PPCs. Use of meta-analysis is problematic as there is no standard definition of a PPC and studies are not
comparable. Meta-analyses suggest that RA, especially epidural local anesthetics, decrease pulmonary infections
(pneumonia) and complications (poorly defined) [28-30]. Older RCTs did not demonstrate a significant
improvement in PPCs as a result of RA although they were not designed with PPCs as a primary outcome [3, 21,
25]. Jayr performed a RCT investigating the impact of analgesia and anesthesia (GA with postoperative parenteral
morphine or GA with postoperative epidural analgesia) on PPCs in patients (n=153) undergoing major surgery [31].
Despite better pain control in the RA group, no benefit could be attributed to RA with respect to LOS or PPCs in
either the group as a whole or in the subgroup of patients with underlying lung disease. In the PIRAT II study
(Norris) there were no differences between anesthetic groups with respect to PPCs [27]. PPCs in a RCT conducted
by Fleron were not reduced by regional analgesia in patients undergoing abdominal aortic surgery [32].
Rigg found that respiratory failure (prolonged ventilation, PaO
2
< 50 mmHg, or PaCO
2
> 50 mmHg) was
more common in the control group [26]. This definition of respiratory failure is problematic as few define a PPC as
a mild increase in PaCO
2
,

especially when associated with narcotic analgesia. Postoperative hypoxemia, common
after major abdominal surgery, has not been linked to more significant morbidity (e.g. increased ICU or hospital
LOS) or increased mortality. A recent re-analysis of Riggs data found there was a small reduction in duration of
postoperative ventilation (0.3 vs. 0.2 hours) but no difference in the number of patients requiring mechanical
ventilation > 24 hours in any subgroup [33]. The authors concluded there was no evidence that perioperative
epidural analgesia influences morbidity or mortality after abdominal surgery. A recent systematic review compared
PCA opioid therapy with epidural analgesia for pain control after intra-abdominal surgery in terms of side effects,
patient satisfaction and surgical outcome and found no differences in hospital length of stay or other adverse effects
[34]. Warner has written although regional techniques may provide excellent analgesia, it is not yet clear that they
consistently improve clinical respiratory outcome [35]. A recent systematic review concluded that the evidence
regarding the efficacy of regional analgesia and anesthesia in reducing PPCs is conflicting or insufficient [36].

Mortality
Yeagers study reported a decrease in mortality in patients receiving RA but the studies of Tuman, Baron,
Christopherson and Norris did not. The meta-analysis of Rogers found mortality at 30 days post-surgery was
reduced in the RA group [29]. However, that analysis included four trials with a much higher mortality rate than all
the others and which may have influenced the results. Park reported the results of a RCT in patients undergoing
aortic or major GI surgery suggesting that EA resulted in a lower mortality rate than patients receiving GA and
parenteral opioid therapy [37]. There were no protocols implemented and there was superior pain control in the RA
group. Hemodynamic monitoring and management was neither specified nor controlled. Urwin reported the results

123
Page 4
of a meta-analysis that demonstrated a difference in 1 month but not 3-, 6-, or 1-year mortality rates and concluded
there were marginal advantages for RA compared to GA in patients with hip fracture [18]. Peytons re-analysis of
Riggs data failed to demonstrate a mortality benefit of anesthetic technique in high risk patients [33]. Wu recently
reported on a nationally random sample of the Medicare database examining the effect of analgesia on outcome in
patients undergoing total hip arthroplasty. Epidural analgesia was not associated with a lower incidence of mortality
[38]. Using similar methodology not confined to patients undergoing hip surgery, Wu found a reduction in death at
seven days after surgery with EA [39]. Liu published a recent meta-analysis that did not demonstrate a reduction in
mortality in patients undergoing CABG as a result of thoracic EA [40].
Wijeysundera used administrative databases to perform a retrospective study of more than 259,000 patients
who underwent elective intermediate or high-risk non-cardiac surgical procedures. EA and epidural analgesia were
associated with a very small decrease in 30-day mortality (0.3% absolute reduction) resulting in a number needed to
treat of 477. They concluded our studydoes not provide compelling evidence that epidural anesthesia improves
postoperative survival [41]. Recently, Svircevic randomized 654 patients to either thoracic EA (TEA) or usual care
in patients undergoing cardiac surgery. The investigators were unable to demonstrate a benefit of TEA on the
frequency of major complications. Monk reported that duration of deep hypnotic time was an independent predictor
of one-year mortality after surgery but others have not confirmed this finding [42, 43]. Recently, Sessler investigated
the association between blood pressure, deep hypnotic time and anesthetic dose in 24,120 patients undergoing
noncardiac surgery. LOS and mortality was increased in patients having a "triple low" of low blood pressure, low
bispectral index, and low minimum alveolar concentration of volatile anesthesia [44]. In conclusion, there is
conflicting evidence regarding anesthetic technique-related differences in mortality.

Central Nervous System Function, Anesthesia And Surgery
GA, by definition, changes cerebral function while a patient is anesthetized. RA avoids that issue. It has
been proposed that GA may produce long-term alterations in brain function (post-operative cognitive dysfunction,
POCD) although some investigators question whether POCD even occurs [45]. No difference in POCD was
observed in a RCT (n=64; mean age 69) involving knee arthroscopy under RA or GA [46]. A report of 53 men
(mean age 71) undergoing prostate resection receiving GA or EA concluded that the type of anesthesia does not
result in POCD [47]. A RCT involving knee replacement (n=262; median age 69) found that the type of anesthesia
did not affect POCD [48]. The results of an investigation involving 1,218 patients undergoing major surgery found
POCD was present in 26% of patients one week after surgery and in 10% three months after surgery, compared with
3% of controls at the same time points [49]. Risk factors for POCD included age and duration of anesthesia but not
the type of anesthesia. An investigation of POCD (n=508; median age 51) found that risk factors for POCD
included: duration of anesthesia, administration of N
2
0, upper abdominal surgery, heart disease, and interestingly,
the use of epidural analgesia [50]. Two recent meta-analyses concluded the use of RA does not reduce the incidence
of POCD [51, 52]. Evered studied 678 patients and concluded that POCD is independent of surgical type and
anesthetic [53]. Heyer found the same rate of POCD in patients undergoing carotid endarterectomy under regional
block as those done under GA [54]. There is no evidence of POCD related to the type of anesthetic. However,
emerging evidence suggests that GA may result in long-term CNS changes or damage to the developing brain or in
older patients at risk for Alzheimers disease. Ikonomidou, Jevtovic-Todorovic, Xie, and Eckenhoff have variously
reported that GA results in apoptotic neurodegeneration and enhancement of amyloid beta oligomerization, a peptide
associated with Alzheimers disease [55-59].

Other Outcomes: GI Function; Cancer Recurrence; Surgical Site infections (SSIs); and Rehabilitation
Patients that receive EA using local anesthetics (LA) experience faster return of bowel function and meet
discharge criteria sooner than patients receiving parenteral opioids [60, 61]. Systemic absorption of LA could be
responsible for the improvement in bowel function observed after epidural administration of LA [62]. Anesthetic-
related differences in improvement in bowel function may also reflect the effect of opioids on gut motility. Selective
inhibition of gastrointestinal opioid receptors can counteract the effects of systemically administered opioids on the
GI tract while not interfering with pain relief. Their administration speeds recovery of bowel function and shortens
the duration of hospitalization [63]. These antagonists may thus minimize a potential advantage of RA over GA.
Patients undergoing colon surgery who receive EA get out of bed faster, have faster return of bowel function, greater
intake of food, and better exercise tolerance and health related-quality of life than a group receiving PCA at both 3
and 6 weeks after surgery whereas hip surgery patients receiving EA may not have enhanced rehabilitation [64, 65].
There are also intriguing reports suggesting regional anesthesia or analgesia may lessen the risk of cancer
recurrence [66, 67]. Other studies have been unable to confirm these findings [68, 69]. Cummings recently reported
that EA may improve survival in patients with nonmetastatic colorectal cancer undergoing resection but was unable

123
Page 5
to find an association between EA and decreased cancer recurrence [70]. Using an administrative database, Chang
investigated whether anesthetic type influences the development of SSIs [71]. In 3,081 patients undergoing total
joint replacement, those receiving GA had a higher risk of SSI compared with RA. A RCT might help further
elucidate the role of anesthetic type on SSIs and also suggests that anesthetic choice may have long-term
consequences deserving of further study.
It is not clear whether or how postoperative analgesia affects outcomes that are important to patients such
as quality of life, quality of recovery, and even patient satisfaction. One study suggested there is no evidence that
postoperative analgesia leads to improvements in patient-centered outcomes such as quality of life and quality of
recovery. The authors concluded modest reductions in pain scores do not necessarily equate to clinically
meaningful improved pain relief for the patient [72].

Vascular Surgery, Neuraxial Block, and Modification of the Coagulation System
Many vascular surgery patients undergo modification of the coagulation system to prevent thrombus
formation in diseased vessels, or to prevent graft occlusion or embolic events. When patients are on anticoagulants
or receiving anti-platelet agents, RA may be inadvisable because of the risk of neuraxial bleeding. Spinal or epidural
hematoma can occur spontaneously in relation to anticoagulation therapy and can also occur when there has been
vascular trauma related to attempts at neuraxial block [73]. The Society of Regional Anesthesia and Pain
Management has developed recommendations regarding the use of neuraxial techniques in patients receiving
anticoagulation [74]. The increasing use of agents that modify the coagulation system may make future comparisons
of RA vs. GA more difficult; it will be more difficult to achieve true randomization and changes in the coagulation
system may further reduce vascular events resulting in myocardial ischemia.

The Future
Perioperative beta-blockade (PBB) is thought to improve cardiac outcomes in patients at risk undergoing
major surgery [75, 76]. Questions remain regarding timing of therapy before surgery, target heart rate, duration of
treatment and optimal beta-blocker. A large retrospective study confirmed the benefit of PBB but the recent POISE
study demonstrated an increased rate of stroke and death in patients receiving PBB [77, 78]. These conflicting
results are likely to continue the controversy about indications for and the optimal dose and timing of PBB and result
in more cautious use of beta-blockade in the perioperative time period. Future studies of the ability of RA to
improve outcomes should be performed in the setting of PBB or pharmacologic interventions designed to prevent
DVT. Other outcomes should be examined to demonstrate value and cost-effectiveness of regional analgesia and
RA. Organizational characteristics of ICUs can improve outcomes, lower costs, and reduce length of stay [79-81]. It
will be important to reconcile conflicting results of meta-analyses regarding the role of epidural anesthesia and
analgesia in improving outcomes [82-85]. Efforts to improve outcomes should focus on global perioperative care
rather than on specific anesthetic techniques. It will be important to define the role of RA in improving outcomes in
real world settings where optimization of all aspects of perioperative care may not have been achieved.

Conclusions
Evidence in the literature suggests that RA and GA produce equivalent outcomes. Methodological flaws
bias older studies in favor of RA. Carefully conducted RCTs have not demonstrated improvements in cardiac
outcomes, mortality, or LOS with RA for vascular surgery. RA has not been demonstrated to result in superior
pulmonary outcomes, or decrease the incidence of POCD, even in high-risk groups, in carefully performed RCTs.
Demonstration of equivalent outcomes between RA and GA have been performed under the conditions of a tightly
controlled RCT, with protocol-driven management. Optimization and standardization of perioperative care may
result in improvements in outcome independent of the type of anesthetic. RA should be employed carefully in the
setting of perioperative modification of the coagulation system. It is possible that RA may offer advantages in
settings where optimization of care has not been achieved. In the real world, the choice of anesthetic may be
crucial. Clinical practice might change, perhaps in favor of RA, if a firm connection is established between GA and
neurotoxicity in humans, if it is conclusively demonstrated that the depth of anesthesia increases mortality after
surgery, or if evidence builds that regional techniques favorably influence cancer treatment. In the meantime, Royse,
in an editorial in Anesthesiology, suggested: Perhaps it is time to move away from trying to prove that anesthetic
interventions will reduce morbidity or mortality and to focus on tangible benefits to patients or their families.
Epidurals are used primarily to provide excellent analgesia, and any other benefits are a bonus [86].

123
Page 6
References
1. Fleisher, L.A., et al., ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for
Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative
Cardiovascular Evaluation for Noncardiac Surgery). Circulation, 2007. 116: 1971-96
2. Rosenfeld, B.A., et al., The effects of different anesthetic regimens on fibrinolysis and the development of
postoperative arterial thrombosis. Anesthesiology, 1993. 79: 435-43.
3. Tuman, K.J., et al., Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular
surgery. Anesth Analg, 1991. 73: 696-704.
4. Wu, C.L., et al., Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus
intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology, 2005. 103: 1079-88.
5. Auroy, Y., et al., Serious complications related to regional anesthesia: results of a prospective survey in France.
Anesthesiology, 1997. 87: 479-86.
6. Auroy, Y., et al., Major complications of regional anesthesia in France. Anesthesiology, 2002. 97: 1274-80.
7. Moen, V., N. Dahlgren, and L. Irestedt, Severe neurological complications after central neuraxial blockades in
Sweden 1990-1999. Anesthesiology, 2004. 101: 950-9.
8. Cameron, C.M., et al., A review of neuraxial epidural morbidity: experience of more than 8,000 cases at a single
teaching hospital. Anesthesiology, 2007. 106: 997-1002.
9. Breslow, M.J., et al., Determinants of catecholamine and cortisol responses to lower extremity revascularization.
10. Parker, S.D., et al., Catecholamine and cortisol responses to lower extremity revascularization: correlation with
outcome variables. Crit Care Med, 1995. 23: 1954-61.
11. Beattie, W.S., N.H. Badner, and P. Choi, Epidural analgesia reduces postoperative myocardial infarction: a
meta-analysis. Anesth Analg, 2001. 93: 853-8.
12. LeLorier, J., et al., Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N
Engl J Med, 1997. 337: 536-42.
13. Shojania, K.G., et al., How quickly do systematic reviews go out of date? A survival analysis. Annals Intern
Med, 2007. 147: 224-33.
14. Rosenfeld, B.A., et al., Neuroendocrine stress hormones do not recreate the postoperative hypercoagulable state.
Anesth Analg, 1998. 86: 640-5.
15. Eagleton, M.J., et al., Endovascular treatment of abdominal aortic aneurysm is associated with a low incidence
of deep venous thrombosis. J Vasc Surg, 2002. 36: 912-6.
16. Sorenson, R.M. and N.L. Pace, Anesthetic techniques during surgical repair of femoral neck fractures. A meta-
analysis. Anesthesiology, 1992. 77: 1095-1104.
17. Brinker, M.R., et al., Comparison of general and epidural anesthesia in patients undergoing primary unilateral
THR. Orthopedics, 1997. 20: 109-15.
18. Urwin, S.C., M.J. Parker, and R. Griffiths, General versus regional anaesthesia for hip fracture surgery: a meta-
analysis of randomized trials. Br J Anaesth, 2000. 84: 450-5.
19. Mantilla, C.B., et al., Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and
death following primary hip or knee arthroplasty. Anesthesiology, 2002. 96: 1140-6.
20. Parker, M.J., H.H. Handoll, and R. Griffiths, Anaesthesia for hip fracture surgery in adults. Cochrane Database
Syst Rev, 2004: CD000521.
21. Christopherson, R., et al., Perioperative morbidity in patients randomized to epidural or general anesthesia for
lower extremity vascular surgery. Anesthesiology, 1993. 79: 422-34.
22. Bode, R.H., Jr., et al., Cardiac outcome after peripheral vascular surgery. Comparison of general and regional
anesthesia. Anesthesiology, 1996. 84: 3-13.
23. Pierce, E.T., et al., Anesthesia type does not influence early graft patency or limb salvage rates of lower
extremity arterial bypass. J Vasc Surg, 1997. 25: 226-32.
24. Yeager, M.P., et al., Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology, 1987. 66:
729-36.
25. Baron, J.F., et al., Combined epidural and general anesthesia versus general anesthesia for abdominal aortic
surgery. Anesthesiology, 1991. 75: 611-8.
26. Rigg, J.R., et al., Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet,
2002. 359: 1276-82.
27. Norris, E.J., et al., Double-masked randomized trial comparing alternate combinations of intraoperative
anesthesia and postoperative analgesia in abdominal aortic surgery. Anesthesiology, 2001. 95: 1054-67.

123
Page 7
28. Ballantyne, J.C., et al., The comparative effects of postoperative analgesic therapies on pulmonary outcome:
cumulative meta-analyses of randomized, controlled trials. Anesth Analg, 1998. 86: 598-612.
29. Rodgers, A., et al., Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia:
results from overview of randomised trials. BMJ, 2000. 321: 1493.
30. Popping, D.M., et al., Protective effects of epidural analgesia on pulmonary complications after abdominal and
thoracic surgery: a meta-analysis. Archives of Surgery, 2008. 143: 990-9.
31. Jayr, C., et al., Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus
parenteral opioids. Anesthesiology, 1993. 78: 666-76.
32. Fleron, M.H., et al., A comparison of intrathecal opioid and intravenous analgesia for the incidence of
cardiovascular, respiratory, and renal complications after abdominal aortic surgery. Anesth Analg, 2003. 97: 2-12.
33. Peyton, P.J., et al., Perioperative epidural analgesia and outcome after major abdominal surgery in high-risk
patients. Anesth Analg, 2003. 96: 548-554.
34. Werawatganon, T. and S. Charuluxanun, Patient controlled intravenous opioid analgesia versus continuous
epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev, 2005: CD004088.
35. Warner, D.O., Preventing postoperative pulmonary complications: the role of the anesthesiologist.
36. Lawrence, V.A., J.E. Cornell, and G.W. Smetana, Strategies to reduce postoperative pulmonary complications
after noncardiothoracic surgery: systematic review for the ACP. Ann Intern Med, 2006. 144: 596-608.
37. Park, W.Y., J.S. Thompson, and K.K. Lee, Effect of epidural anesthesia and analgesia on perioperative outcome:
a randomized, controlled Veterans Affairs cooperative study. Ann Surg, 2001. 234: 560-9.
38. Wu, C.L., et al., Effect of postoperative epidural analgesia on morbidity and mortality after total hip replacement
surgery in medicare patients. Reg Anesth Pain Med, 2003. 28: 271-8.
39. Wu, C.L., et al., Effect of postoperative epidural analgesia on morbidity and mortality following surgery in
medicare patients. Reg Anesth Pain Med, 2004. 29: 525-33.
40. Liu, S.S., B.M. Block, and C.L. Wu, Effects of perioperative central neuraxial analgesia on outcome after
coronary artery bypass surgery: a meta-analysis. Anesthesiology, 2004. 101: 153-61.
41. Wijeysundera, D.N., et al., Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery:
a population-based cohort study. Lancet, 2008. 372: 562-9.
42. Monk, T.G., et al., Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg, 2005.
100: 4-10.
43. Kertai, M.D., et al., Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and
intermediate-term mortality after noncardiac surgery in the B-Unaware Trial. Anesthesiology, 2011. 114: 545-56.
44. Sessler, D.I., et al., Hospital Stay and Mortality Are Increased in Patients Having a "Triple Low" of Low Blood
Pressure, Low Bispectral Index, and Low Minimum Alveolar Concentration of Volatile Anesthesia. Anesthesiology,
2012. 116: 1195-1203.
45. Avidan, M.S., et al., Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or
major illness. Anesthesiology, 2009. 111: 964-70.
46. Nielson, W.R., et al., Long-term cognitive and social sequelae of general versus regional anesthesia during
arthroplasty in the elderly. Anesthesiology, 1990. 73: 1103-9.
47. Haan, J., et al., Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly
men. J Am Geriatr Soc, 1991. 39: 596-600.
48. Williams-Russo, P., et al., Cognitive effects after epidural vs general anesthesia in older adults. A randomized
trial. JAMA, 1995. 274: 44-50.
49. Moller, J.T., et al., Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD
investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet, 1998. 351: 857-61.
50. Johnson, T., et al, Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology 2002. 96: 1351-7.
51. Wu, C.L., et al., Postoperative cognitive function as an outcome of regional anesthesia and analgesia. Reg Anesth
Pain Med, 2004. 29: 257-68.
52. Bryson, G.L. and A. Wyand, Evidence-based clinical update: general anesthesia and the risk of delirium and
postoperative cognitive dysfunction. Can J Anaesth, 2006. 53: 669-77.
53. Evered, L., et al., Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth
Analg, 2011. 112: 1179-85.
54. Heyer, E.J., et al., A study of cognitive dysfunction in patients having carotid endarterectomy performed with
regional anesthesia. Anesth Analg, 2008. 107: 636-42.
55. Eckenhoff, R.G., et al., Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity.

123
Page 8
56. Ikonomidou, C., et al., Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.
Science, 1999. 283: 70-4.
57. Jevtovic-Todorovic, V., et al., Early exposure to common anesthetic agents causes widespread
neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci, 2003. 23: 876-82.
58. Jevtovic-Todorovic, V., et al., Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult
rat brain. Neuroscience, 2003. 122: 609-16.
59. Xie, Z., et al., The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein
accumulation. J Neurosci, 2007. 27: 1247-54.
60. Jorgensen, H., et al., Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative
gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev, 2000: CD001893.
61. Liu, S.S., et al., Effects of perioperative analgesic technique on rate of recovery after colon surgery.
62. Groudine, S.B., et al., Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain,
and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg, 1998. 86: 235-9.
63. Taguchi, A., et al., Selective postoperative inhibition of gastrointestinal opioid receptors. N Engl J Med, 2001.
345: 935-40.
64. Carli, F., et al., Epidural analgesia enhances functional exercise capacity and health-related quality of life after
colonic surgery: results of a randomized trial. Anesthesiology, 2002. 97: 540-9.
65. Foss, N.B., et al., Effect of postoperative epidural analgesia on rehabilitation and pain after hip fracture surgery:
a randomized, double-blind, placebo-controlled trial. Anesthesiology, 2005. 102: 1197-204.
66. Biki, B., et al., Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective
analysis. Anesthesiology, 2008. 109: 180-7.
67. Exadaktylos, A.K., et al., Can anesthetic technique for primary breast cancer surgery affect recurrence or
metastasis? Anesthesiology, 2006. 105: 660-4.
68. Gottschalk, A., et al., Association between epidural analgesia and cancer recurrence after colorectal cancer
surgery. Anesthesiology, 2010. 113: 27-34.
69. Wuethrich, P.Y., et al., Potential influence of the anesthetic technique used during open radical prostatectomy on
prostate cancer-related outcome: a retrospective study. Anesthesiology, 2010. 113: 570-6.
70. Cummings, K.C., et al., A comparison of epidural analgesia and traditional pain management effects on survival
and cancer recurrence after colectomy: a population-based study. Anesthesiology, 2012. 116: 797-806.
71. Chang, C.C., et al., Anesthetic management and surgical site infections in total hip or knee replacement: a
population-based study. Anesthesiology, 2010. 113: 279-84.
72. Liu, S.S. and C.L. Wu, The effect of analgesic technique on postoperative patient-reported outcomes including
analgesia: a systematic review. Anesth Analg, 2007. 105: 789-808.
73. Dahlgren, N. and K. Tornebrandt, Neurological complications after anaesthesia. A follow-up of 18,000 spinal
and epidural anaesthetics performed over three years. Acta Anaesthesiol Scand, 1995. 39: 872-80.
74. Horlocker, T.T., et al., Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy:
American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines. Reg Anesth Pain Med,
2010. 35: 64-101.
75. Mangano, D.T., et al., Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.
Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med, 1996. 335: 1713-20.
76. Poldermans, D., et al., The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk
patients undergoing vascular surgery. DECREASE Study Group. N Engl J Med, 1999. 341: 1789-94.
77. Wallace, A.W., S. Au, and B.A. Cason, Association of the pattern of use of perioperative beta-blockade and
postoperative mortality. Anesthesiology, 2010. 113: 794-805.
78. Devereaux, P.J., et al., Effects of extended-release metoprolol succinate in patients undergoing non-cardiac
surgery (POISE trial): a randomised controlled trial. Lancet, 2008. 371: 1839-47.
79. Amaravadi, R.K., et al., ICU nurse-to-patient ratio is associated with complications and resource use after
esophagectomy. Intensive Care Med, 2000. 26: 1857-62.
80. Dimick, J.B., et al., Intensive care unit physician staffing is associated with decreased length of stay, hospital
cost, and complications after esophageal resection. Crit Care Med, 2001. 29: 753-8.
81. Pronovost, P.J., et al., Organizational characteristics of intensive care units related to outcomes of abdominal
aortic surgery. JAMA, 1999. 281: 1310-7.
82. Ballantyne, J.C., et al., Does the evidence support the use of spinal and epidural anesthesia for surgery? J Clin
Anesth, 2005. 17: 382-91.

123
Page 9
83. Liu, S.S. and C.L. Wu, Effect of postoperative analgesia on major postoperative complications: a systematic
update of the evidence. Anesth Analg, 2007. 104: 689-702.
84. Nishimori, M., J.C. Ballantyne, and J.H. Low, Epidural pain relief versus systemic opioid-based pain relief for
abdominal aortic surgery. Cochrane Database Syst Rev, 2006. 3: CD005059.
85. Choi, P.T., et al., Epidural analgesia for pain relief following hip or knee replacement. Cochrane Database Syst
Rev, 2003: CD003071.
86. Royse, C., Epidurals for cardiac surgery: can we substantially reduce surgical morbidity or should we focus on
quality of recovery? Anesthesiology, 2011. 114: 232-3.

Disclosure

202
Page 1
Perioperative Myocardial Ischemia and Infarction in Non-cardiac Surgery
Peter Nagele, M.D., MSc St. Louis, Missouri
Myocardial infarction (MI) is a common and serious complication after non-cardiac surgery. This refresher course
will discuss the epidemiology, pathophysiology, preoperative risk stratification, prevention, management and
outcomes of perioperative myocardial infarction after non-cardiac surgery and highlight the role of cardiac
biomarkers.
Definition
Perioperative myocardial infarction is defined as suffering a new myocardial infarction in the immediate
pre-, intra- and postoperative period. Typically 30 days after non-cardiac surgery are considered the postoperative
period. The diagnosis of myocardial infarction is based on the Universal Definition of Myocardial Infarction which
was recently updated.
1
Accordingly, an MI is diagnosed when there is evidence of myocardial necrosis in a clinical
setting consistent with acute myocardial ischemia. In the perioperative setting, typically two criteria are most
commonly used: the rise (and/or) fall of a cardiac biomarker [preferably cardiac troponin] with at least one value
above the 99
th
percentile of the upper reference limit plus ECG changes consistent with acute myocardial ischemia
such as new ST-segment changes.
Epidemiology
Perioperative MI is often referred to as a hidden epidemic. It is estimated that among the 230 million
surgical procedures worldwide each year, more than 1 million patients suffer from perioperative MI or cardiac
death. A recent study among 85,000 inpatient surgeries showed an overall incidence rate of 0.5% for perioperative
MI, which was associated with a 30-40% mortality rate.
2
The risk for perioperative MI is at least on an order of
magnitude higher among patients with preexisting coronary artery disease undergoing major non-cardiac surgery
(reported risk: 5-6%).
3-5
When using sophisticated continuous monitoring methods such as 12-lead Holter ECG or
high-sensitivity cardiac troponin, it turns out that nearly all patients with pre-existing coronary artery disease
develop periods of myocardial ischemia in the perioperative period.
6,7

Pathophysiology
The majority of perioperative MI events are silent, i.e., not accompanied by specific symptoms such as
chest pain. The main reason for silent MIs is the presence of potent analgesic drugs that most patients receive after
surgery.
8
Two major causes of perioperative MI can be distinguished: (1) supply and demand mismatch resulting in
demand ischemia and (2) coronary thrombosis. More than 95% of all perioperative MIs are caused by demand
ischemia. It is caused by an imbalance between myocardial oxygen demand and supply. In the setting of stable
coronary artery disease with fixed atherosclerotic lesions, higher oxygen demands in the myocardium cannot be met
by the limited blood flow and subsequently lead to myocardial ischemia and infarction. Common reasons for high
myocardial oxygen demand and/or reduced oxygen supply in the perioperative period include tachycardia, acute
hemorrhage, hypotension, hypoxemia, hypertension (increased myocardial wall stress), fever, and sepsis syndrome.
In addition, endothelial dysfunction also plays a crucial role. Clinically, this type of perioperative MI often
resembles a non-ST segment elevation MI (NSTEMI) and is typically associated with a smaller increase in cardiac
biomarkers than an acute coronary occlusion due to a thrombus.
Acute coronary thrombosis is the cause for perioperative MI in approximately 5% of cases, but associated
with a markedly increased risk of cardiac death. Acute thrombosis occurs when an unstable vulnerable
atherosclerotic plaque ruptures followed by instantaneous acute coronary artery thrombosis, and subsequent
myocardial ischemia and infarction. Causes for plaque destabilization in the perioperative period are manifold, but
the most apparent are surgical stress resulting in hypertension, tachycardia and increased catecholamine levels, and

202
Page 2
hypercoagulability caused by surgical trauma. Patients who suffer from acute coronary thrombosis are often
symptomatic, become hemodynamically unstable and not infrequently undergo emergent coronary angiography.

Risk Stratification and Prevention
Several preoperative risk stratification models have been developed. The most commonly known and used
is the Lees Revised Cardiac Risk Index that integrates both pre-existing co-morbidities such as renal disease and the
magnitude of the surgical procedure.
9
Understandably, patients are at highest risk to develop perioperative MI when
they have several pre-existing cardiac risk factors and undergo major non-cardiac surgery. A classic example is a
patient with pre-existing ischemic cardiomyopathy undergoing open AAA repair. In this scenario, the risk may
exceed 25%. In order to improve pre-operative risk stratification, recent research has evaluated several biomarkers
such as brain natriuretic peptide [BNP]/N-terminal fragment of BNP [NT-proBNP], C-reactive protein (CRP), or
high sensitivity cardiac troponin. The relevance of these biomarkers in preoperative cardiac risk stratification is
currently unclear, but appears promising.
Prevention of perioperative MI has historically largely focused on the use of beta-blockers. Until the
publication of the POISE trial, beta blockers were considered the gold standard in the prevention of perioperative MI
and had a class I recommendation from the American Heart Association. Given the prominent influence of
myocardial stress in the pathophysiology of perioperative MI and the similarly prominent potency of beta-
blockers to reduce myocardial stress, it was only logical that perioperative beta-blockade became such a
cornerstone of perioperative MI prevention. The POISE trial, where more than 8,000 beta-blocker nave patients
were randomized to either extended-release metoprolol or placebo, showed that metoprolol was highly efficacious in
reducing the rate of perioperative MI but also significantly increased the risk of stroke and death.
10
Combined with
recent evidence, it appears that perioperative beta-blockade is a double-edged sword.
11
As long as the patient does
not experience hypotension and even more importantly significant hemorrhage, beta-blockade is predominantly
beneficial and leads to a marked reduction in perioperative cardiac risk. However, in the presence of hypotension
and hemorrhage, the tables are turned and now patients are at substantially increased risk of stroke and death,
probably because the presence of beta-blockers prevents the necessary increase in heart rate to maintain adequate
cardiac output.
12
At present, the role of perioperative beta-blockade is therefore unclear. Other drugs have been
sparsely investigated in the prevention of perioperative MI and no strong recommendations exist.

Management
During the last decades, the majority of research was focused on the prevention of perioperative MI and not
the treatment. It was assumed that postoperative patients who suffered from an acute MI should be managed in an
identical fashion to patients with an acute coronary syndrome in the emergency department or CCU. Thus, no
specific guidelines for the management of perioperative MI exist and until recently very limited research was
conducted to answer even the most basic questions. Two recent studies showed that even minor postoperative
cardiac troponin elevations, often referred to as troponin leaks, have significant prognostic importance and
identify patients at risk for long-term cardiac morbidity and mortality.
13,14
These troponin elevations that are much
more common when measured with a high-sensitivity assay are clearly not a major cardiac event in itself but
rather represent a red flag indicating a significantly elevated cardiac risk. At present, patients who develop
perioperative troponin elevation or MI are treated according to the most recent but generic AHA guidelines for the
treatment of acute coronary syndromes that include MONA (morphine, oxygen, nitrates, aspirin), possibly beta-
blockers, and in the case of a massive MI often emergent coronary catheterization.
15,16

202
Page 3

References:
1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, The Writing Group on behalf of
the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction: Third
universal definition of myocardial infarction. Circulation 2012; 126: 2020-35
2. Ghaferi AA, Birkmeyer JD, Dimick JB: Variation in hospital mortality associated with inpatient surgery. N
Engl J Med 2009; 361: 1368-75
3. Badner NH, Knill RL, Brown JE, Novick TV, Gelb AW: Myocardial infarction after noncardiac surgery.
Anesthesiology 1998; 88: 572-8
4. Landesberg G, Mosseri M, Zahger D, Wolf Y, Perouansky M, Anner H, Drenger B, Hasin Y, Berlatzky Y,
Weissman C: Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST
depression-type ischemia. J Am Coll Cardiol 2001; 37: 1839-45
5. Le Manach Y, Perel A, Coriat P, Godet G, Bertrand M, Riou B: Early and delayed myocardial infarction
after abdominal aortic surgery. Anesthesiology 2005; 102: 885-91
6. Landesberg G, Luria MH, Cotev S, Eidelman LA, Anner H, Mosseri M, Schechter D, Assaf J, Erel J,
Berlatzky Y: Importance of long-duration postoperative ST-segment depression in cardiac morbidity after
vascular surgery. Lancet 1993; 341: 715-9
7. Nagele P, Brown F, Gage BF, Gibson DW, Miller PJ, Jaffe AS, Apple FS, Scott MG: High-Sensitivity
Cardiac Troponin T in Prediction and Diagnosis of Myocardial Infarction and Long-Term Mortality after
Non-Cardiac Surgery. American Heart Journal 2013; in press
8. Landesberg G, Beattie WS, Mosseri M, Jaffe AS, Alpert JS: Perioperative myocardial infarction.
Circulation 2009; 119: 2936-44
9. Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson
MC, Poss R, Ho KK, Ludwig LE, Pedan A, Goldman L: Derivation and prospective validation of a simple
index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999; 100: 1043-9
10. POISE Study Group, Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D,
Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Mlaga G, Avezum A, Chan M, Montori VM,
Jacka M, P. C: Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery
(POISE trial): a randomised controlled trial. The Lancet 2008; 371: 1839-1847
11. London Mj HKSGGHWG: ASsociation of perioperative !-blockade with mortality and cardiovascular
morbidity following major noncardiac surgery. JAMA 2013; 309: 1704-1713
12. Le Manach Y, Collins GS, Ibanez C, Goarin JP, Coriat P, Gaudric J, Riou B, Landais P: Impact of
perioperative bleeding on the protective effect of beta-blockers during infrarenal aortic reconstruction.
13. Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study I, Devereaux PJ, Chan MT,
Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A,
Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F,
Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN,
Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga
G, Nagele P, Le Manach Y, Leuwer M, Yusuf S: Association between postoperative troponin levels and
30-day mortality among patients undergoing noncardiac surgery. JAMA 2012; 307: 2295-304
14. van Waes JA, Nathoe HM, de Graaff JC, Kemperman H, de Borst GJ, Peelen LM, van Klei WA:
Myocardial Injury after Noncardiac Surgery and its Association with Short-Term Mortality. Circulation
2013
15. Members WC, Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE, Ettinger SM,
Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP:
2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable
Angina/NonST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011
Focused Update): A Report of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines. Circulation 2012; 126: 875-910
16. O'Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O'Neil BJ, Travers
AH, Yannopoulos D: Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122: S787-817

Disclosure
Roche Diagnostics, Self, Funded Research
208
Page 1
Utility of Perioperative Transesophageal Echocardiography in Non-Cardiac Surgery
Stanton Shernan, M.D. Boston, Massachusetts
Since the introduction of intraoperative echocardiography into clinical practice in the 1980s, its popularity
has steadily increased. Although not as well established as for cardiac surgery, the benefit of perioperative
echocardiography for non-cardiac surgery is becoming increasingly more appreciated
1-3
. Selective or emergent
intraoperative transesophageal echocardiography (TEE) has been reported as beneficial in 40% to 80% of patients
respectively
4,5
. In over one-third of patients, intraoperative TEE may be associated with a change in medical
therapy, including treatment of myocardial ischemia, valvular pathology, and/or right ventricular (RV) and left
ventricular (LV) failure
4,5
. Furthermore, in approximately 25% of patients, intraoperative TEE has been associated
with a change in surgical procedure
4
. Based upon these findings, intraoperative echocardiography is rapidly
becoming recognized for its impact on perioperative decision-making during non-cardiac surgery.
Indications for Intraoperative Echocardiography
Indications for emergent TEE during non-cardiac surgery have included hemodynamic instability,
evaluation for chest trauma, hypoxemia, and pre-incision cardiac evaluation prior to emergent surgery
6
. In 1996
practice guidelines were published from the American Society of Anesthesiologists (ASA) and the Society of
Cardiovascular Anesthesiologists (SCA) Task Force on TEE
7
. Recommendations are divided into three categories
based on the strength of supporting evidence and/or expert opinion that TEE improves clinical outcomes. Category I
indications are supported by the strongest evidence or expert opinion that TEE is frequently useful in improving
clinical outcomes in these settings, and is often indicated. Category II indications are supported by weaker evidence
and expert consensus that TEE may be useful in improving clinical outcomes in these settings but absolute
indications are less certain. Category III indications have little scientific or expert support, and appropriate
indications are uncertain. An updated revision of this document authored by members of the ASA and SCA is
currently underway.
Although the ASA/SCA practice guidelines are perhaps most applicable for cardiac surgery, they also have
relevance for non-cardiac surgery. One of the most common Category I indications for the use of intraoperative TEE
during non-cardiac surgery, is the role of rescue TEE for the evaluation of acute persistent and life-threatening
hemodynamic disturbances in which ventricular function and its determinants are uncertain or have not responded to
treatment.
8
In a study investigating the usefulness of TEE during intraoperative cardiac arrest in non-cardiac surgery,
a primary suspected diagnosis of the underlying pathological process was established in 19 of 22 patients with TEE,
including 9 with thromboembolic events, 6 with acute myocardial ischemia, 2 with hypovolemia, and 2 patients with
pericardial tamponade
9
. A definitive diagnosis could not be made in 3 patients with TEE. In 18 patients, TEE
guided specific management beyond implementation of Advanced Cardiac Life Support protocols, including the
addition of surgical procedures in 12 patients. A related Category II indication includes the perioperative use of
TEE in patients with increased risk of hemodynamic disturbances. In several single center and multicenter studies,
intraoperative TEE for non-cardiac surgery has been to shown to influence surgical and anesthetic management in
30-40% of patients, including those who already had invasive hemodynamic monitors (i.e., radial arterial lines and
pulmonary artery catheters)
4,5,10,11
. Changes in management have been based upon confirming or invalidating a
prior diagnosis, detection of new diagnoses, and acquisition of pertinent information acquired during periods of
hemodynamic instability leading to changes in drug or goal-directed fluid therapy, unplanned surgical re-
interventions and further evaluation in the postoperative period. While many of the cases in the literature would be
considered Category I indications for the utility of intraoperative TEE, others have reported a consistent impact of
intraoperative TEE on perioperative clinical decision-making even for Category II indications among non-cardiac
surgical patients. Thus, in addition to earlier reports suggesting a primary benefit for intraoperative TEE as a

208
Page 2
diagnostic tool for evaluating myocardial ischemia during non-cardiac surgery
12
, more recent reports also confirm
its utility as a monitor of hemodynamic status and overall cardiovascular performance.

Perioperative Ischemia Monitoring

Ischemic changes detected by two-dimensional echocardiography include new systolic wall motion
abnormalities (SWMA) and decreased systolic wall thickening. Echocardiography is also useful for evaluating
complications of myocardial ischemia including myocardial infarction (MI), congestive heart failure (CHF),
valvular regurgitation, septal defects, thrombi, pericardial effusions, and ventricular free wall rupture. Controlled
studies have demonstrated a clear association between SWMA, coronary ischemia and cardiac events
13
. Data from
perioperative TEE studies have reported specificities and negative predictive values >90%. However, sensitivity
and positive predictive values for MI are less than 40%, possibly because not all ischemia results in MI
12
. In
addition, SWMA often overestimate the area of injury, and may result from etiologies other than ischemia including
myocardial stunning, hibernation and tethering as well as changes in loading conditions. While monitoring,
diagnosing and treating myocardial ischemia is important, it is not clear that routine TEE is either cost-effective or
more beneficial than ECG monitoring with ST segment analysis
14
. However, TEE may be a worthwhile monitor
and a diagnostic tool of choice for the initial assessment of myocardial ischemia or MI-related complications for
high-risk patients undergoing non-cardiac surgery.

Vascular Surgery

SWMA occur frequently during vascular surgery, but are less frequently associated with perioperative MI,
CHF, and cardiac death. In one study, 55% of patients undergoing aortic reconstruction experienced new SWMA at
the time of aortic clamping, with a greater incidence seen following supra-celiac clamping (92%) compared to
suprarenal (33%), and infra-renal (0%)
15
. In this particular series, only 1 patient (in the supra-celiac group) suffered
a perioperative MI.
As previously stated, SWMA may result from a variety of etiologies other than ischemia. Furthermore,
even if all SWMA were indicative of ischemia or ventricular dysfunction, ischemia does not always result in a
significant cardiac event. Anesthetic agents, metabolic changes, blood loss, and placement of the aortic cross clamp
are known causes of SWMA. Since these are transient processes, the occurrence of an adverse cardiac event is
reduced. The low positive predictive value of SWMA may also be associated with rapid detection and subsequent
prompt treatment. Nonetheless, the utilization of TEE during major vascular procedures may influence
perioperative management and outcome.
Liver and Lung Transplantation

Despite the presence of a coagulopathy and gastroesophageal varices, TEE has been used safely in patients
undergoing liver transplantation, with a reported bleeding complication rate of 1-2%
16
. During liver
transplantation, TEE monitoring has demonstrated new findings in > 50% of patients, improved hemodynamic
management, and has been shown to impact overall perioperative care in 11% of patients
16
. During lung
transplantation, TEE has been used to assess severity and etiology of pulmonary hypertension, intraoperative
ventricular function, and surgical anastomotic integrity. Diagnoses such as pulmonary artery (PA) thrombi, patent
foramen ovale, atrial septal and ventricular septal defects in 25% of patients, resulted in the requirement for
additional surgery in one study
17
. Furthermore, echocardiographic visualization of pulmonary vascular anastomoses
suggests that up to 30% may be abnormal, thus prompting additional surgical procedures
17
.

Orthopedics

Patients undergoing total hip replacement (THR) are vulnerable to perioperative cardiac complications due
to comorbidity and hemodynamic instability occurring during certain aspects of the surgical procedure. Emboli
released during preparation of the femur are readily diagnosed with TEE and have been associated with decreases in
blood pressure, increases in PA pressure, RV and LV SWMA, and occasionally cardiovascular collapse
18
. Emboli
have also been diagnosed in patients undergoing total knee replacement following thigh tourniquet release
19
.
However, in comparison to THR, the hemodynamic consequences of these embolic events may not be as severe
19
.
Although TEE may not be indicated for all patients undergoing orthopedic procedures, elderly patients and those

208
Page 3
with significant cardiovascular and pulmonary comorbidity may benefit from its utility as a monitor and diagnostic
tool for evaluating perioperative hemodynamics.
Neurosurgery

Hemodynamic instability during major neurological surgery is affected by a number of variables including
patient demographics, anesthetic agents and surgical techniques. Venous air embolism (VAE), which may cause
hemodynamic and pulmonary instability, occurs in 25-50% of neurosurgical procedures, and has been reported in as
many as 76% of craniotomies performed in the sitting position
20
. Although precordial Doppler echocardiography or
TEE is believed to be the most sensitive monitor for VAE, actual utilization varies from 25-87%
20
. Patients
scheduled to undergo craniotomy in the sitting position should have a pre-surgical echocardiographic evaluation
either preoperatively or immediately after induction of anesthesia to determine the presence of any intracardiac
shunts.
Obstetrics

It is becoming increasingly more common for high-risk obstetrical patients with cardiac disease including
congenital heart diseases, CAD, cardiomyopathies, and heart transplantation to present for peripartum care. In
addition, a number of pregnancy-related conditions, including pregnancy-induced-hypertension, pulmonary emboli,
hemorrhage, and peripartum cardiomyopathy have a significant influence on tolerance for the normal hemodynamic
changes associated with pregnancy. Although echocardiographic analysis during normal deliveries is not cost-
effective, use in assessing high-risk obstetric patients may be warranted
21
.

Trauma and Critical Care

Prompt and accurate diagnoses of traumatic cardiac injuries are crucial to improving survival. In one study
of penetrating chest injury, echocardiographic evaluation and diagnosis was achieved within 15 minutes, compared
to 42 minutes in the non-echo group. The survival was 100% in the former and 57% in the latter. Compared to
transthoracic echocardiography (TTE), TEE also significantly contributes to the diagnostic and hemodynamic
evaluation of cardiac and vascular injury, and can be performed in as quickly as 9-15 minutes
22,23
.
There is strong support for the use of echocardiography in critically ill patients
2,3
. Common indications for
postoperative echocardiography include evaluation of hypotension, LV and RV function, MR, prosthetic valves,
aortic injury, pericardial pathology, myocardial ischemia, complications following MI, cardiac masses and sources
of emboli or infection
24-28
. Echocardiographic evaluation of hemodynamic instability, trauma, and hypoxemia are
particularly common
23/24-27/28
.
When compared to clinical impression, echocardiography has been shown to provide new information in
80% of critically ill patients, changed medical management in 60%, and led to a surgical procedure in as many as
30% of patients
6,24
. Comparative analyses have shown that TEE improved cardiac evaluation compared to TTE in
as many as 50-70% of patients
20-28
.

National Board of Echocardiography Certification in Basic Perioperative TEE

In October of 2006, the ASA House of Delegates approved the development of a basic echocardiography
education training program, and resolved that ASA uniquely or collaboratively explore a pathway for
anesthesiologists to obtain experience and privileges in echocardiography as a basic perioperative monitor. Through
a collaborative effort between the ASA and the SCA, a strategic plan was developed to make available to ASA
members, a CME course on basic perioperative echocardiography. These courses are designed to introduce

practitioners to the fundamental principles and applications of a focused perioperative echocardiographic
examination, and are geared to those who are intent upon gaining sufficient knowledge and experience to integrate
this modality into their clinical practice outside of the cardiac surgical environment. The ASA finalized an
agreement with the National Board of Echocardiography (NBE) in 2010 to (1) develop a Basic Perioperative TEE
examination and (2) to develop criteria for a certification pathway to achieve diplomate status in Basic Perioperative
Echocardiography under the scope of practice which includes non-diagnostic monitoring within the customary
practice of anesthesiology; a focus on intraoperative monitoring rather than specific diagnosis; and with the
understanding that except in emergent situations, diagnoses requiring intraoperative cardiac surgical intervention
or post-operative medical/surgical management must be confirmed by an individual with advanced skills in TEE or
by an independent diagnostic technique. A Basic PTEE Exam and Certification process has been available from the

208
Page 4
NBE since 2010. The next Basic PTEE Examination will also be given in July 2014. Current criteria for Basic
Perioperative TEE Certification proposed by the NBE include:

Requirement 1. Applicants must have passed the Basic PTE Exam or the PTEeXAM
Requirement 2. Applicants must hold a current and unrestricted license to practice medicine at the time of
application
Requirement 3. Applicants must be board certified in anesthesiology
Requirement 4. Specific Training in PTEE: performance/review of 150 basic PTEE examinations with
variations in +/- supervision, +/- CME, time frame for completion (2 - 4 yrs), depending upon the pathway:

1) Supervised Training Pathway
2) Practice Experience Pathway (availability through 6/2016)
3) Extended CME Pathway

Conclusions

Perioperative echocardiography for non-cardiac surgical patients is useful for diagnosing cardiovascular
pathology and assessing hemodynamics. A recent consensus statement of the ASE and SCA entitled Basic
Perioperative Transesophageal Echocardiography Examination highlights the multidisciplinary recognition of this
important utility of perioperative TEE.
29
Echocardiographic evaluation of cardiac performance compares favorably
to other gold standards, and expands on the ability to obtain a comprehensive cardiovascular exam. In recognition
of the utility of intraoperative TEE for non-cardiac surgery, the ASA, SCA and National Board of Echocardiography
have collaborated to develop a pathway for certification in basic perioperative TEE (www.echoboards.org). In
addition, the ECHO-in-ICU group and the American College of Emergency Physicians (ACEP) and a joint effort
by boith the ASE and ACEP have all proposed limited scope training guidelines for the focused use of
echocardiography in the initial management of critically ill patients
30
in the ICU and emergency room respectively
31-34
. As the popularity of echocardiography increases and the indications for its perioperative utility evolves,
appreciation for its value in the non-cardiac surgical population will continue to develop.

References

1. Eagle KA, Brundage BH, Chaitman BR, et al for the committee on perioperative cardiovascular evaluation for
non-cardiac surgery. Guidelines for perioperative cardiovascular evaluation for non-cardiac surgery: Report of the
American College of Cardiology/American Heart Association task force on practice guidelines.
Circulation 1996;93:1278-1317.
2. Cheitlin MD, Alpert JS, Armstrong WF, et al for American College of Cardiology and the American Heart
Association Task Force on Practice Guidelines. ACC/AHA guidelines for the clinical application of
echocardiography. Circulation 1997;95:1686-1744.
3. Thys DM, Abel M, Bollen BA, et al. Practice guidelines for perioperative transesophageal echocardiography: A
report by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task
Force on Transesophageal Echocardiography. Anesthesiology 1996;84:986-1006.
4. Suriani RJ, Neustein S, Shore-Lesserson L, Konstadt S. Intraoperative transesophageal echocardiography during
non-cardiac surgery. J CardioThorac Vasc Anesth 1998;12:274-280.

5. Denault AY, Couture P, McKenty S, et al. Perioperative use of transesophageal echocardiography by
anesthesiologists: impact in non-cardiac surgery and in the intensive care unit. Can J Anesth 2002;40:287-293.

6. Brandt RR, Oh JK, Abel MD, et al. Role of emergency intraoperative transesophageal echocardiography.
J Am Soc Echocardiogr 1998;11:972-977.
7. American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task Force on
Transesophageal echocardiography. Practice guidelines of perioperative transesophageal echocardiography.
Anesthesiology 1996;84:9861006.

208
Page 5
8. Shillcutt S, Markin N, Montzingo C, Brakke T. Use of rapid rescue perioperative echocardiography to improve
outcomes after hemodynamic instability in noncardiac surgical patients. JCTVA 2012; 26: 362-370

9. Memtsoudis S, Rosenberger P, Noveva M, et al. Usefulness of transesophageal echocardiography during
intraoperative cardiac arrest Anesth Analg 2006;102:1653-1657.

10. Schmidlin D, Bettex D, Bernard E, et al. Transesophageal echocardiography in cardiac and vascular surgery:
implications and observer variability. Br J Anaesth 2001;86:497505.

11. Lambert AS, Mazer CD, Duke PC. Survey of the members of the cardiovascular section of the Canadian
Anesthesiologists Society on the use of perioperative transesophageal echocardiography a brief report. Can J
Anesth 2002;43L:94296.

12. Eisenberg MJ, London MJ, Leung JM, et al. for the study of Perioperative Ischemia Research Group. Monitoring
of myocardial ischemia during non-cardiac surgery: a technology assessment of transesophageal echocardiography
and 12-lead electrocardiography. JAMA 1992;268:21016.

13. Comunale ME, Body SC, Ley C, et al. for the Multicenter Study of Perioperative Ischemia (McSPI) Research
Group. The concordance of intraoperative left ventricular wall-motion abnormalities and electrocardiographic S-T
segment changes. Association with outcome after coronary revascularization. Anesthesiology 1998;88:945-54.

14. Benson MJ, Cahalan MK. Cost-benefit analysis of transesophageal echocardiography in cardiac surgery.
Echocardiography 1995;12:171-183.

15. Roizen MF, Beaupre PN, Alpert RA, et al. Monitoring with two-dimensional transesophageal echocardiography:
Comparison of myocardial function in patients undergoing supraceliac, suprarenal-infraceliac, or infrarenal aortic
occlusion. J Vasc Surg 1984;1:300-05.

16. Prah GN, Lisman SR, Maslow AD, et al. Transesophageal echocardiography reveals an unusual cause of
hemodynamic collapse during orthotopic liver transplantation: Two case reports. Transplantation 1995;59:921-925.
17. Michel-Cherqui M, Brusset A, Liu N, et al. Intraoperative transesophageal echocardiographic assessment of
vascular anastamoses in lung transplantation: A report on 11 cases. Chest 1997;111:1229-1235.
18. Koessler MJ, Fabiani R, Hamer H, Pitto RP. The clinical relevance of embolic events detected by
transesophageal echocardiography during cemented total hip arthroplasty: A randomized clinical trial. Anesth Analg
2001;92:49-55.

19. Permet JL, Horrow JC, Singer R, et al. Echogenic emboli upon tourniquet release during total knee arthroplasty:
Pulmonary hemodynamic changes and emboli composition. Anesth Analg 1994;79:940-945.

20. Porter JM, Pidgeon C, Cunningham AJ. The sitting position in neurosurgery: a critical appraisal.
Br J Anaesth 1999;82:117-128.

21. Belfort MA, Rokey R, Saade GR, Moise KJ Jr. Rapid echocardiographic assessment of left and right heart
hemodynamics in critically ill obstetric patients. Am J Obstet Gynecol 1994;171:884-892.
22. Brooks SW, Young JC, Cmolik B, et al. The use of transesophageal echocardiography in the evaluation of chest
trauma. J Trauma-Injury Infect & Crit Care 1992;32:761-768.

23. Karalis DG, Victor MF, Davis GA, et al. The role of echocardiography in blunt chest trauma: a transthoracic and
transesophageal echocardiographic study. J Trauma-Injury Infect & Crit Care 1994;36:53-58.

24. Khoury AF, Afridi I, Quinones MA, Zoghbi WA. Transesophageal echocardiography in critically ill patients:
feasibility, safety, and impact on management. Am Heart J 1994;127:1363-1371.

208
Page 6
25. Heidenreich PA, Stainback RF, Redberg RF, et al. Transesophageal echocardiography predicts mortality in
critically ill patients with unexplained hypotension. J Am Coll Cardiol 1995;26:152-158.
26. Kaul S, Stratiendko AA, Pollock SG,et al. Value of two-dimensional echocardiography for determining the basis
of hemodynamic compromise in critically ill patients: A prospective study.J Am Soc Echocardiogr 1994;7:598-606.
27. Fontes ML, Bellow W, Ngo L, Mangano DT. Assessment of ventricular function in critically ill patients:
limitations of pulmonary artery catheterization. Institution of the McSPI research group.
J Cardiothorac Vasc Anesth 1999;13:521-527.
28. Tousignant CP, Walsh F, Mazer CD. The use of transesophageal echocardiography for preload assessment in
critically ill patients. Anesth Analg 2000;90:351-355.
29. !""#"$ &' ()*+", -' &./01$ 2' "3 1+4 Basic Perioperative transesophageal echocardiography examination: A
consensus statement of the American Society of Echocardiography and the Society of Cardiovascular
Anesthesiologists. .J Am Soc Echocardiogr 2013;26:443-56

30.Vieillard-Baron A, Slama M, Cholley B, et al.. Echocardiography in the intensive care unit: from evolution to
revolution? Intensive Care Med 2008; 34:243-9.
31. American College of Emergency Physicians. ACEP emergency ultrasound guidelines-2001.
Ann Emerg Med 2001;38:470-81.
32. Beaulieu Y. Bedside echocardiography in the assessment of the critically ill.Crit Care Med. 2007;35:S235-S249.
33. Beaulieu Y, Marik PE. Bedside ultrasonography in the ICU: part 1. Chest. 2005;128:881-895.
34. Labovitz A, Noble V, Bierig M, et al. Focused cardiac ultrasound in the emergent setting: A consensus statement
of the American Society of Echocardiography and American College of Emergency Physicians. J Am Soc
Echocardiogr 2010;23:1225-30.

Disclosure
Philips Healthcare, Inc, Self, Other Material Support

214
Page 1
Anesthesia for Cardiac Patients Outside of the Operating Room
Douglas C. Shook, M.D. Boston, Massachusetts
Over the past ten years the scope and complexity of procedures performed in the cardiac catheterization lab (CCL)
and electrophysiology lab (EPL) has changed dramatically. Interventional procedures have moved from diagnostic
to therapeutic treatment of patients with a wider range of pathology and acuity of disease. Simple sedation for this
new and changing patient population needs to be re-evaluated with greater involvement of the anesthesiologist as a
periprocedural physician to guide safe and optimal outcomes. This requires collaboration with the cardiologist,
interventionalist, and cardiac surgeon to develop safe and effective patient management strategies for existing
procedures and new ones being developed in the future. As in the operating room, the anesthesiologist is best suited
to help guide the development of these strategies across multiple specialties.
A thorough understanding of the procedure to be performed is required in order for anesthesiologists to define and
delineate the extent of their involvement and is a clear prerequisite for the formulation of a safe and effective
anesthetic plan. Common CCL and EPL procedures are listed below.
Patient care in these off-site locations requires an understanding of the types of patients that will undergo the
procedure and their need for anesthesia consultation, knowledge about the lab environment to deliver a safe
anesthetic, and details of the procedure including potential complications.
Consultation
Many emergencies can be avoided with appropriate pre-procedure planning. The trigger for anesthesia consultation
usually revolves around presenting patient factors and/or the complexity of the procedure.
Non-anesthesia personnel in the CCL and EPL should be taught how to perform basic airway histories and exams in
order to establish the need for consultation. Patient airway characteristics that should trigger an anesthesia
consultation include:
Morbid obesity
Obstructive sleep apnea
Inability to lie flat
Known or suspected difficult airways (Mallampati Class III or IV)
It can be very challenging to manage an airway in an oversedated or unstable patient in the CCL/EPL. The head of
the patient is often surrounded by fluoroscopy equipment. The fluoroscopy table doesnt have the same
functionality as an operating room table. In addition, control of the table is at the foot of the bed away from the
anesthesiologist. Personnel in the CCL and EPL typically do not have training in advanced airway management and
Cath Lab:
Diagnostic cardiac catheterizations
Percutaneous coronary interventions
Peripheral vascular procedures
Percutaneous ventricular assist devices
Placement of septal occlusion devices
Percutaneous valve repair and replacement
EP Lab:
Diagnostic EP studies
Atrial and ventricular ablation procedures
Electrical cardioversion
Implantation and removal of rhythm
management devices

214
Page 2
are often not helpful or even unintentionally obstructive in an emergency. Therefore, airway assessment is critical in
this environment.

Other patient factors that may trigger an anesthesia consultation include:
Chronic obstructive pulmonary disease
Low oxygen saturation
Current congestive heart failure
Hemodynamic instability
Psychiatric disorders
Medications that could complicate the administration of sedative agents

Procedure factors that may prompt a provider to seek an anesthesia consultation include the potential for an outcome
that requires immediate surgical back up such as unprotected left-main coronary artery stenting or investigational
percutaneous valve procedures. If the case is likely to precipitate instability i.e., valvuloplasties in very elderly and
frail patients or implantation of ventricular assist devices, a consultation is also warranted. These types of
procedures can be long and complicated requiring the full attention of the interventionalist. There is benefit in
having an anesthesiologist in the room whose attention is focused solely on airway and hemodynamic control. In the
EPL, complex arrhythmia ablation procedures (atrial fibrillation and ventricular tachycardia or fibrillation) and
complicated lead extractions (laser lead extraction) should also have anesthesia consults. Obviously, any procedure
that requires general anesthesia needs pre-procedure anesthesia evaluation and planning.

Establishing criteria for anesthesia consultation will eventually lead to more efficient and safe patient care. An
interdisciplinary approach to determine the best route for catheterization (radial versus femoral), optimal patient
positioning to reduce sedation induced airway obstruction, and type and amount of sedative medications can reduce
intra-procedural complications. Non-anesthesia personnel delivering sedation will be more comfortable caring for
the patient, cardiologists can focus on the task at hand, and anesthesiologists are alerted to the possible
complications they maybe called to manage.

The Patient
Many patients arrive in the pre-procedure area after failed interventions, recent myocardial infarctions, acute
exacerbations of heart failure, or with uncontrolled arrhythmias. This is not the typical patient population seen in
the operating room. In addition to the typical pre-anesthetic work-up a comprehensive review of all previous cardiac
interventions must be obtained:
Diagnostic catheterizations
Coronary stent placement (type, location and age)
Known left and right sided cardiac pressures
Previous surgical interventions
Arrhythmia interventions and ablations
Echocardiograms (ventricular function and dimensions, valve disease)
Chest x-rays
A comprehensive medication list along with any recent changes to the medication regimen

Frequently the patient has just arrived from an outside hospital. The interventionalist may be focused on the
technical aspects of the procedure at hand. Therefore the anesthesiologist may be the only provider aware of recent
changes to the health status of the patient due to the urgency of the procedure. What may seem essential to an
anesthesiologist may seem of secondary importance to a cardiologist, and vice versa. Patient optimization prior to
the procedure is essential to a successful outcome. Collaboration and communication with the patient care team is
necessary to determine a sedation plan or need for general anesthesia. Radial artery catheterization instead of a
femoral approach may be a better option in some patients, since this allows the patient to sit up more during the
procedure. Some patients need the procedure emergently which limits options and necessitates direct involvement
of an anesthesiologist for sedation or general anesthesia.

As stated previously, airway assessment is critical in this patient population. Not only should ease of endotracheal
intubation be assessed, but also the ability to mask ventilate should be evaluated as this can bridge a moment of
oversedation during a procedure. A history of difficult intubation or possible difficult intubation does not preclude

214
Page 3
sedation, but should be a warning that oversedation can be dangerous. Early communication of and prompt response
to sedation problems during the procedure is imperative.

The Lab
All labs include a separate control station and procedure room. The control station is shielded from radiation and
usually has a technician recording the progress of the procedure. The technician communicates with the cardiologist
frequently and controls many aspects of the case including patient monitoring, video recording and editing, and
digital record keeping.

The procedure room is where the cardiologist, anesthesiologist, nurses, and other technicians care for the patient
during the procedure. The anesthesiologist should become familiar with the contents of each procedure room, which
vary from institution to institution. Gas outlets and suction, monitors for vital signs, cardioverter/defibrillator,
emergency medications and airway equipment are critical and may not be optimally or even obviously placed.
Locations for a ventilator, anesthesia cart, and possible difficult airway cart should also be planned if needed. Other
equipment regularly used during cases includes ventricular assist devices, intra-aortic balloon pumps, and
echocardiography.

CCLs and EPLs are designed for the cardiologist and not for the needs of the anesthesiologist. Space is always an
issue in complex cases. The fluoroscopy table and fluoroscopy equipment are controlled by the cardiologist and can
move unexpectedly during the procedure. Long intravenous lines, extra oxygen tubing, and long breathing circuits
must be utilized to allow for both movement of the table and fluoroscopy equipment.

Basic anesthesia monitoring equipment may not be present in the CCL and EPL. It is essential that all sedation in
the CCL and EPL be performed with capnography. It is much harder to assist when called to the cath lab if
capnography isnt being utilized. Since an anesthesia workroom is not typically located near the CCL or EPL,
stocking labs with airway equipment and an emergency airway cart is essential. Having an anesthesia cart stocked
with extra IVs, medications, and other items located in the CCL and EPL helps during emergent consultations. All
personnel in the lab should know the location and names of emergency equipment since the anesthesiologist will be
occupied with the patient if called emergently to a procedure area.

Sedation
Non-anesthesia personnel administering mild to moderate sedation should be trained in the pharmacology of
commonly used agents and in the use of monitoring equipment. Early recognition and management of abnormal
respiratory patterns and hemodynamic problems, which evolve during mild, moderate, and deep sedation, is also
important. Caregivers must understand the potentially synergistic drug interactions of benzodiazepines, opioids, and
other commonly administered sedatives such as diphenhydramine (given to patients who have IV contrast reactions),
especially in patients with complicated airways or diminished respiratory capacity. Anesthesiologists should take an
active role in developing and maintaining sedation standards for non-anesthesia personnel throughout the hospital.

Management of sedation needs must be based on a firm understanding of the procedure and a thorough grasp of the
patients co-morbidities. It is critical to know when the patient is likely to be stimulated so that deeper sedation can
be administered. Tachypnea and tachycardia resulting from inadequate sedation can be just as dangerous as airway
obstruction and/or snoring from over sedation. Both situations can make interventions more difficult for the
cardiologist and less safe for patients. In circumstances where brief unconsciousness is necessary during a
procedure, the assistance of an anesthesiologist should be sought (i.e., ICD testing after implantation or
cardioversion during ablation). In some patients given the complexity of the procedure and/or respiratory and airway
compromise of the patient, sedation isnt appropriate and general anesthesia is administered. In most instances, it is
safer to start a procedure with general anesthesia then convert during the procedure.

Monitoring the Patient
Patient Monitoring in the CCL and EPL is often designed with the cardiologist in mind. The fluoroscopy screen and
patient vital signs are easy for the cardiologist to see, but maybe difficult to see if the anesthesiologist is at the head
of the bed. Monitoring the fluoroscopy screen helps determine the flow of the procedure and anticipate changes in
patient comfort and hemodynamics.

214
Page 4
Certain simple functions such as blood pressure cuff cycling and pulse oximetry volume are typically controlled
outside of the actual procedure room so the anesthesiologist may want to add their own equipment in this case.
During prolonged cases or with compromised patients (or both), invasive arterial monitoring with a display visible
to the anesthesiologist may be preferable. It is worth remembering that blood pressure cuffs may not function during
fast or erratic heart rhythms.

Many cases employ transesophageal echocardiography (TEE) to guide and monitor the patient during the procedure.
Familiarity with standard views and assessment of cardiac function assists the anesthesiologist in determining the
progress of the case including success and complications of the procedure. If hemodynamic instability occurs, TEE
provides instant assessment of contractility, volume status, and valve function.

Medications
In addition to the standard medications used for sedation and general anesthesia, the anesthesiologist must be
familiar with the medications commonly used in the CCL and EPL:
Heparin
Glycoprotein IIb/IIIa platelet receptor inhibitors
Clopidogrel
Direct thrombin inhibitors such as bivalirudin
Vasoactive and intropic medications
Sodium channel blockers (class 1: quinidine, lidocaine, flecainide)
Beta-blockers (class 2: metoprolol, sotalol)
Potassium channels blockers (class 3: amiodarone, sotalol, ibutilide, dofetilide)
Calcium channel blockers (class 4: verapamil, diltiazem)

Prior to the procedure, it must be clear how medications will be delivered to the patient, and who will do it. In
addition, the cardiologist may directly bolus medications such as nitroglycerine or calcium channel blockers directly
into cardiac catheters, which can have a profound effect on the patients hemodynamics. Communication must be
clear so that cardiologists and anesthesiologists are both aware of when drugs are administered so that subsequent
hemodynamic effects can be anticipated and double dosing can be avoided.

Percutaneous Ventricular Assist Devices
Percutaneous ventricular assist devices are placed in patients who are having high-risk PCI, high-risk ablation
procedures, or who are hemodynamically compromised. The TandemHeart (Cardiac Assist, Inc., Pittsburg, Pa,
USA) and the Impella Recover LP 2.5 and 5.0 (Abiomed Inc., Danvers, MA, USA) are two commercially available
percutaneous ventricular assist devices. The TandemHeart and Impella LP 5.0 can produce cardiac outputs that can
completely replace left ventricular function. During this time pulse oximetry and non-invasive blood pressure cuffs
may not work properly because blood flow may not be pulsatile. The Impella LP 2.5 uses a smaller cannula that
achieves a maximum cardiac output of 2.5 liter/min. Therefore the patient must have some intrinsic cardiac function
to maintain hemodynamic stability.

Large bore IV access is desirable since a large amount of blood loss is possible during the procedure. Blood loss is
more likely with the TandemHeart or Impella LP 5.0 since the cannulas used are larger. Surgical back up may be
necessary during these procedures. The anesthesiologist may be consulted for these procedures because the patient is
usually already unstable or the procedure can have both airway and hemodynamic complications. Depending on the
procedure and state of the patient, either sedation or general anesthesia can be used to safely care for the patient.
Communication with the cardiologist helps determine the type of anesthetic most appropriate for the case and the
patient.

Percutaneous Closure of Septal Defects
These procedures are used to close patent foramen ovale (PFO), atrial septal defects (ASD) and ventricular septal
defects (VSD). There are a number of percutaneous closure devices available to close septal defects. The
complications of device placement are similar across the platforms available. Complications of percutaneous
closure devices include but are not limited to: intra-procedure air embolism; device embolization; device
malpositioning; device thrombosis and embolization (cerebral embolization may occur from either air, a piece of the

214
Page 5
device itself or thrombus) during or following the procedure; device related arrhythmias (usually atrial but include
sudden death); and cardiac perforation with or without cardiac tamponade.

The placement of intra-cardiac septal occluder devices requires an anesthesiologist if TEE is used to guide
placement of the device, the alternative is for the cardiologist to use intra-cardiac or intra-vascular echo. Patient
history is important to determine the reason to close the defect. Closure of PFOs tends to be simpler than closure of
ASDs. In patients with ASDs, it is important to determine if right ventricular function and pulmonary arterial
pressures are normal since the right side of the heart has been volume overloaded due to the typical left to right
shunt through the ASD. In patients with VSDs, the anesthesiologist needs to determine if the VSD is congenital or
acquired (post myocardial infraction) and the direction of flow through the defect. Typically VSDs have left to right
flow. Patients with post myocardial infarction VSDs can be hemodynamically unstable and more likely to have
complications (hypotension, arrhythmias) during closure of the defect.

Echocardiography is used during the procedure to help guide placement and confirm a successful result. If TEE is
used, then general anesthesia will be necessary for the procedure. Intra-cardiac echocardiography (ICE) can also be
used to guide the procedure. If ICE is used, the procedure can be performed under sedation. An arterial line usually
isnt need for either an ASD or PFO closure but recommended for most VSD closures. Two IVs should be available
so that one can be used for boluses and the other for infusions. The cardiologist can place a femoral venous line for
infusions if necessary. The determination of sedation versus general anesthesia should be based on the complexity
of the closure and patient medical history.

Percutaneous Valve Repair and Replacement
Percutaneous valve repair and replacement represent the changing paradigm of interventional cardiology procedures.
The procedures are more complex with increased patient acuity. At the present time cardiac surgical mitral valve
repair is the procedure of choice for the treatment of symptomatic mitral regurgitation or mitral regurgitation with
impaired left ventricular function (EF < 60%). Current techniques under investigation for percutaneous mitral
valve repair include coronary sinus annuloplasty, direct annuplasty, leaflet repair and chamber + annular
remodeling.

The MitraClip (Abbott Vascular) is the most extensively studied in US patients. The current COAPT Trial is
randomizing patients with functional mitral regurgitation who are not surgical candidates. The femoral vein is
accessed and the clip is delivered via an atrial trans-septal puncture and passed into the left ventricular cavity. The
clip is then opened and pulled back to contact both the anterior and posterior mitral leaflets. Positioning is performed
with both fluoroscopy and TEE. The clip is then closed to create a double-orifice mitral valve with improvement of
mitral regurgitation. The results of the current study are still 12-24 months away.

Percutaneous mitral valve repairs are performed under general anesthesia with fluoroscopic and TEE guidance. The
type of device and approach should be communicated prior to the procedure. During these cases, the procedure
room is very crowed and establishing space to care for the patient can be difficult. Two peripheral IVs should be
placed for infusions and boluses. Endotracheal intubation is preferred and arterial invasive monitoring should be
considered depending on the patients ventricular function. Communication during the procedure is vital to
successful placement of the device as the case can be long and multiple attempts maybe needed to ensure proper
device placement with an acceptable result.

Percutaneous aortic valve replacement or transcatheter aortic valve replacement (TAVR) is a relatively new
treatment for aortic stenosis. Currently there are two devices in patient clinical trials in the United States. The
CoreValve (Medtronic) is a porcine self-expanding prosthesis sutured into a Nitinol stent. The Sapien valve
(Edwards Lifesciences) is a bovine pericardial prosthesis sutured into a balloon-expandable metal stent. In the
United States, the Sapien valve received FDA approval in November 2011 for placement in patients with severe
aortic stenosis who are deemed inoperable. Current trials are comparing TAVR to surgical AVR. The most recent
study published in the New England Journal of Medicine (June 9. 2011) showed that TAVR survival was non-
inferior to surgical AVR at one and two years. Unfortunately TAVR patients have a higher stroke rate and more
paravalve leaks. On the other hand they had fewer bleeding complications and shorter hospital lengths of stay.
Despite this study commercial use of TAVR is limited to non-operative patients only.

214
Page 6
Access to the aortic valve is via either a transfemoral, trans-apical (via the left ventrical), or trans-aortic (ascending
aorta) approach. Transfemoral arterial access is the preferred route to place the valve if the femoral and iliac arteries
are big enough to allow the larger cannulas and sheaths to pass.

Patients receive general endotracheal anesthesia and invasive monitoring (arterial line and pulmonary artery
catheters). Like percutaneous mitral valve repairs, fluoroscopy and TEE are used to guide device placement.
Patients frequently become hemodynamically unstable during the case and can develop myocardial ischemia and
significant arrhythmias both before and after device placement. Rapid ventricular pacing is needed to place the
device and can result in prolonged hypotension and ischemia. The cannulas used to place these devices are large
and can result in large blood loss and damage to the femoral and iliac vessels if done via the trans-femoral access.
Other complications include: AV nodal block, abnormal valve deployment (paravalve leaks, aortic insufficiency,
embolization), coronary occlusion, cardiovascular collapse (needing cardiopulmonary bypass), and stroke.

Catheter Ablation
Radiofrequency is used to treat arrhythmias that are refractory to pharmacologic therapy as well as a first-line
treatment for other arrhythmias. Catheter ablation is used to treat supraventricular tachyarrhythmias such as atrio-
ventricular nodal re-entry tachycardia; Wolf-Parkinson-White syndrome related tachycardias, atrial tachycardia,
atrial flutter, atrial fibrillation, and ventricular tachyarrhythmias (both structural and idiopathic).

Both venous and arterial access to the heart may be needed to place the mapping and ablation catheters. Complex
mapping techniques are utilized to identify the source of the arrhythmia so as to specify the exact intra-cardiac
location to which the radiofrequency energy must be applied. Different types of mapping techniques include pace
mapping, activation mapping, entrainment mapping, and anatomic mapping. The patients must remain still during
the mapping and ablation portions of the procedure. The decision to use sedation versus general anesthesia is
determined both by the patients co-morbidities and the type of arrhythmia. A patient with severe sleep apnea who
cannot lay flat will likely do better with general anesthesia for a 4-6 hour procedure. On the other hand, right-sided
idiopathic VT is commonly suppressed by general anesthesia so sedation is preferred. Pulmonary vein isolation
ablation performed for paroxysmal atrial fibrillation is primarily anatomically mapped so general anesthesia has less
effect on the outcome. It is important to discuss the patients co-morbidities and arrhythmia prior to designing the
anesthetic technique to optimize patient outcomes and minimize procedural risk.

Radiofrequency ablation procedures are becoming more tedious and more time consuming. Patients with atrial
fibrillation often require a procedure time of at least 4-6 hours, followed by a prolonged observation time post
ablation with repeat electrophysiology testing to ensure success of the procedure. Patients can be young and
essentially healthy or have extensive co-morbidities. Coughing, snoring, and partial airway obstruction can be
problematic during intra-cardiac mapping since they precipitate a swinging motion of the intra-atrial septum and
make trans-septal catheter placement difficult as well as mapping the arrhythmia. Drugs that affect the sympathetic
nervous system should be avoided during mapping of ectopic foci and tracts. In patients with ventricular
dysfunction, intropic and vasoactive agents maybe necessary in order to both anesthetize and maintain
hemodynamic stability during arrhythmia induction and ablation. Communication with the cardiologist is necessary
in these situations to maintain patient safety and still allow the mapping process to proceed.

Complications from ablations procedures include:
Hemorrhage, hematoma, AV fistula most common
Hypotension
Heart failure/fluid overload
Pulmonary vein stenosis (4-10% for afib ablations)
Left atrial-esophageal fistula (rare but high fatality rate in afib ablations)
Steam pops ! the radiofrequency current used for ablations causes steam formation that can explode
through the tissue (tamponade can occur).
The risk of tamponade is greater with ablations involving the right ventricle (thin walled).
Risk of thrombus formation with ablation catheters.
Damage to the aortic or mitral valve gaining access to the LV.
Vascular access complications.
Cerebral or systemic embolism (up to 2.7%)

214
Page 7
Atrioventricular nodal block (especially with VT that originates from the septum)
With epicardial ablation risk of coronary artery injury is a major concern
Damage to the left phrenic nerve as it courses down the lateral aspect of the LA and LV

Device Placement and Testing
Many of these patients have multiple co-morbidities including a history of ventricular tachycardia/fibrillation,
ejection fraction < 30%, and coronary artery disease as these are indications for implantable cardioverter-
defibrillator (ICD) placement. Other indications include arrhythmogenic right ventricular dysplasia, long QT
syndrome, and hypertrophic cardiomyopathy.

Most of these devices are placed with mild to moderate sedation and standard monitors. Testing the device requires
deep sedation. ICD placement and testing can be accomplished without an arterial line. External
cardioverter/defibrillator pads are placed on the patient at the beginning of the procedure. When testing ICDs, they
are used induce ventricular fibrillation and to serve as back-up if the implanted device fails.

Implanted ICD may be tested at the end of the procedure. Repeated testing is usually well tolerated without
deterioration of ventricular function even in patients with ejection fractions < 35%. In patients with evidence of
untreated coronary disease, recent stent placement or evidence of atrial or ventricular thrombus, testing is sometimes
omitted. Significant coronary artery disease is a concern when testing with prolonged hypotension as a possible
complication. It is important to remember that ICD testing is always an elective procedure should the patient
demonstrate deterioration during implantation.

Some patients needing ICDs are also having biventricular pacemakers placed for cardiac resynchronization therapy.
These patients have low ejection fractions and associated co-morbidities including valvular heart disease, pulmonary
hypertension, and right ventricular dysfunction. Patients may not be able to lie flat comfortably and can easily
become hemodynamically unstable with sedation. Oversedation can lead to hypercapnia that may not be tolerated in
patients with pulmonary hypertension and/or right ventricular dysfunction. The anesthesiologist must be ready to
convert to general anesthesia at anytime during the case. Complications from these procedures include possible
cardiac injury (perforation/tamponade), myocardial infarction, stroke, and pneumothorax from the subclavian
venous access.

Conclusion
Anesthesiologists, in collaboration with cardiologists, must establish guidelines for their involvement in patient care
and procedure planning in the CCL and EPL. The goal is to improve patient safety and procedural efficiency while
advancing the frontiers of medical care in an expanding and exciting new venue.

Reviews and Articles to Read:
1. Shook DC, Gross W: Offsite anesthesiology in the cardiac catheterization lab. Curr Opin Anaesthesiol 20:352,
2007
2. Shook DC, Savage RM. Anesthesia in the cardiac catheterization laboratory and electrophysiology laboratory.
Anesthesiol Clin 2009; 27(1):47-56
3. Patel K, Crowley R, Mahajan A. Cardiac electrophysiology procedures in clinical practice. Int Anesthesiol Clin
2012;50(2):90-110
4. Hayman M, Forrest P, Kam P. Anesthesia for Interventional Cardiology. J Cardiothorac Vasc Anes;26(1):134-
147.
5. Elkassabany NM, Mandel JE. Con: A general anesthesiologist with a certain skill set is qualified to provide
services in the interventional cardiology and electrophysiology laboratory. J Cardiothorac Vasc Anes
2011;25(3):557-58
6. Mahajan A, Chua J. Pro: A cardiovascular anesthesiologist should provide services in the catheterization and
electrophysiology laboratory. J Cardiothorac Vasc Anes 2011;25(3):553-556
7. Gaitan BD, Trentman TL, Fassett SL. Sedation and analgesia in the cardiac electrophysiology laboratory: a
national survey of electrophysiologists investigating the who, how, and why? J Cardiothorac Vasc Anes
2011;25(4):647-659
8. Wazni O, Wilkoff B, Saliba W. Catheter ablation for atrial fibrillation. N Engl J Med 2011;365:2296-304
9. Stevenson WG, Soejima K. Catheter Ablation for Ventricular Tachycardia. Circulation 2007;115:2750-2760

214
Page 8
10. Cesario DA, Mahajan A, Shivkumar K. Lesion-forming technologies for catheter ablation of atrial fibrillation.
Heart Rhythm 2007;4(3):s44-s50
11. Holmes D, Mack M, Kaul S, et al. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter
aortic valve replacement. J Thorac Cardiovasc Surg 2012;144(3):e29-e84
12. Fassl J, Augoustides J. Transcatheter aortic valve implantation-part 2: anesthesia management. J Cardiothorac
Vasc Anes 2010;24(4):691-699

References:
1. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 96:1004, 2002
2. Kushner, FG, Hand, M, Smth, SC, et.al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of
Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and
ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007
Focused Update).Journal of the American College of Cardiology Vol. 54, No. 23, 2009, December 1,
2009:2205-41.
3. Smith Jr. SC, Feldman TE, Hirshfeld Jr. JW, et al: ACC/AHA/SCAI 2005 Guideline update for percutaneous
coronary intervention: A report of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous
Coronary Intervention). J Am Coll Cardiol 2006; 47(1): e1-121.
4. Kar B, Adkins LE, Civitello AB, et al. Clinical Experience with the TandemHeart Percutaneous Ventricular
Assist Device. Texas Heart Institute Journal 2006; 33(2): 111-115.
5. Siegenthaler MP, Brehm K, Strecher T, et al. The Impella Recover microaxial left ventricular assist device
reduces mortality for postcardiotomy failure: a three-center experience. Journal Thoracic Cardiovascular
Surgery 2004; 127:812-822
6. Windecker S and Meier B. Impella assisted high-risk percutaneous coronary intervention. Karddiovaskulare
Medizin 2005; 8:187-189
7. Henriques JP, Remmelink M, Baan J, Jr., et al: Safety and feasibility of elective high-risk percutaneous
coronary intervention procedures with left ventricular support of the Impella Recover LP 2.5. Am J Cardiol
97:990, 2006
8. Pretorius M, Hughes AK, Stahlman MB, et al: Placement of the TandemHeart percutaneous left ventricular
assist device. Anesth Analg 103:1412, 2006
9. Delaney JW, Li JS, and Rhodes JF. Major complications associated with trans-catheter atrial septal occluder
implantation: a review of the medical literature and the manufacturer and user facility device experience
(MAUDE) database. Congenit Heart Dis 2007 Jul,2 (4):256-64.
10. Chessa M, Carminati M, Walsh K, et. al. Early and Late Complications associated with transcatheter occlusion
of secundum atrial septal defect. J Am Coll Cardiol 2002, 39:1061.
11. LaRosee K, Krause D, Becker M, et.al. Transcatheter Closure of atrial septal defects in adults. Practicality and
safety of four different closure systems used in 102 patients. Dtsch Med Wochenschr. 2001 Sep
21;126(38):1030-6.
12. Carroll JD, Dodge S, and Groves BM Percutaneous patent forman ovale closure. Cardiol Clin 23 (2005) 13-33.
13. Martinez MW, Mookadam F, Sun Y, et al: Transcatheter closure of ischemic and post-traumatic ventricular
septal ruptures. Catheter Cardiovasc Interv 69:403, 2007
14. Garay F, Cao QL, Hjazi ZM: Percutaneous closure of post-myocardial infarction ventricular septal defect. J
Interv Cardiol 19:S67, 2006
15. Creager MA and Libby P. Libby: Braunwalds Heart Disease: A Textbook of Cardiovascular Medicine, 8th
Edition. Copyright2007 Saunders, an Imprint of Elsevier. Chapter 57 Peripheral Arterial Diseases.
16. Norgen L, Hiatt WR, Dormandy JA, et al. Inter-Society consensus for the management of peripheral arterial
disease (TASC II). J Vasc Surg 2007; 45: Suppl S: S5.
17. Feldman T. Percutaneous mitral valve repair. J of Int cardio vol 20, no. 6, pp. 488-494, 2007.
18. Block PC: Percutaneous transcatheter repair for mitral regurgitation. J Interv Cardiol 19:547, 2006
19. Rajagopal V, Kapadia SR and Tuzcu EM. Advances in the percutaneous treatment of aortic and mitral valve
disease. Minerva Cardioangiol 2007; 55:83-94.
20. Webb JG. New treatment options in aortic stenosis. ACCEL April 2008, vol. 40, No. 4, disc 1.
21. ACC/AHA/HRS Writing Committee Circulation: Dec 5, 2006: ACC/AHA/HRS 2006 Key Data Elements and
Definitions for Electrophysiological Studies and Procedures: A Report of the American College of
Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing

214
Page 9
Committee to Develop Data Standards on Electrophysiology Circulation 2006; 114; 2534-2570; originally
published online Nov 27, 2006
22. Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial
infarction and reduced ejection fraction. N Engl J Med 346:877, 2002
23. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of
Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline
Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with
the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1,
2008

Disclosure
Philips Medical, Sorin, Edwards, Honoraria

221
Page 1
Cerebral Protection During Cardiac Surgery
Charles W. Hogue, M.D. Baltimore, Maryland
Clinical stroke occurs in 13% of patients after cardiac surgery, predisposing affected patients to high mortality,
excessive medical cost, and impaired quality of life.
1-3
Cerebral injury may have manifestations other than focal
neurologic deficits. Postoperative cognitive dysfunction (POCD) is reported in 3040% of patients early after
cardiac surgery and in 2030% of patients 4 to 6 weeks postoperatively.
4-8
Psychometric testing is associated with
many methodological limitations (e.g., timing of testing, definitions of decline, interpretation alongside preexisting
cognitive dysfunction, test-retest improvement, etc.) that confound its ability to serve as an accurate marker of brain
injury after cardiac surgery.
9
Whether POCD is relevant to long-term cognition is still controversial. Although early
investigations suggested a link between POCD and long-term cognitive decline, those studies did not include a
control group. Selnes et al
10
, however, reported the results of a longitudinal study that compared cognition of
patients undergoing CABG surgery to a control group with known coronary artery disease undergoing medical
management. In patients who underwent cardiac surgery, cognitive performance recovered by 6 months after
surgery and the rate of further decline over 6 years of follow-up was no different than that observed in controls.
Further, Van Dijk et al
11
reported no differences between cognition in patients 5 years after CABG surgery
(performed with or without cardiopulmonary bypass, CPB) and that in a group of subjects without cardiac disease.
More recently, Evered et al
12
reported that the incidence of POCD was similar for patients 3 months after coronary
angiography (21%), total hip joint replacement surgery (16%), and CABG surgery (16%; p=0.13). Data from a
meta-analysis of 28 studies involving 2043 patients who underwent CABG surgery suggested improvement in
cognitive function during the first year after surgery.
13
Taken together, the current data suggest that any impact of
CABG surgery on cognition is short-lived, and further decrements are explained by natural progression of cerebral
vascular disease. Delirium is an acute form of cerebral dysfunction that affects as many as 3040% of patients after
cardiac surgery. This condition is characterized by an acute fluctuation in level of consciousness associated with
changes in cognition, attention, and perception.
14
Delirium is associated with prolonged hospitalization, reduced
functional status, mortality, and future cognitive decline.
15
The mechanism of delirium after cardiac surgery is
likely multifactorial and is dependent on the interaction of preexisting patient factors and perioperative
perturbations.
Investigations involving sensitive diffusion-weighted brain MRI (DWI) scanning of patients after cardiac surgery
have provided important insight into the frequency of clinically silent brain injury after cardiac surgery.
4;

16;

17;

18;

19

DWI is an MR sequence that detects acute brain ischemic injury within minutes to 2 weeks after its occurrence. In a
systematic review of studies involving 446 patients undergoing cardiac surgery, 29% of patients exhibited new
ischemic lesions on DWI after surgery.
20
The lesions are usually multiple and small (1 to 10 mm) and located in all
vascular territories, but usually in frontal and watershed regions. Because these lesions are usually not accompanied
by evidence of stroke, some controversy exists as to the clinical significance of their presence in an otherwise
asymptomatic patient. Longitudinal studies in the general population, though, have shown that brain infarctions that
are initially clinically silent subsequently progress in volume, causing patients to have a greater eventual risk for
cognitive decline and dementia than patients without MRI evidence of brain infarction.
20
;
21
Thus, cerebral injury
after cardiac surgery may have multiple manifestations that are both clinically obvious (stroke, delirium) and
clinically silent (POCD, DWI lesions). The aim of neuroprotection should be to prevent all forms of cerebral injury,
even those that may not necessarily be accompanied by clinical signs and symptoms.
Proposed Mechanisms
Two mechanisms have been proposed for cerebral injury from cardiac surgery: cerebral macro/microembolism and
cerebral hypoperfusion.
3,4
It is hypothesized that the clinical manifestations depend on the size and location of the
injury (e.g., motor areas vs. areas involved with cognition). Importantly, embolism and hypoperfusion do not
necessarily occur in isolation; they can co-exist in the same or different areas in a given patient.
22
Although, primary
221
Page 2
cerebral hemorrhage is believed to be a rare cause of cerebral injury, MRI imaging for micro-bleeding suggests that
punctuate hemorrhages can occur after surgery in some patients, such as those with endocarditis.
23
Inflammatory
processes resulting from CPB, organ ischemia/reperfusion, and genetic susceptibility may further contribute to
injury.
3,24-26

Atherosclerosis of the ascending aorta is a potential source of cerebral macro- and micro- (<200 m)
emboli, based on prospective ultrasound investigations, intraoperative transcranial Doppler (TCD) monitoring, and
autopsy studies.
4,27
Fat arising from the cardiotomy suction aspirate has been suggested as another source of
microemboli.
28
Although early studies implicated cerebral microemboli as a cause of POCD by correlating the
number of TCD-detected cerebral embolic signals with cognitive decline after CABG surgery, these findings were
not confirmed.
29,30,31,32
It is likely that the composition and not the number of microemboli is more important for the
manifestations of cerebral injury. Cerebral injury from hypoperfusion may be more common in contemporary
practice because of a growing number of patients with preexisting, and typically clinically asymptomatic,
cerebrovascular disease.
4
This concern is reinforced by data showing that as many as 2743% of patients experience
regional or global cerebral O
2
desaturations during CPB, indicating cerebral O
2
demand/delivery mismatch.
33

Further, one study found that 68% of strokes that occurred after cardiac surgery were hypoperfusion-type watershed
strokes based on diffusion-weighted MRI.
34
Cerebral hypoperfusion might be of particular concern during off-
pump surgery, when displacement of the heart results in systemic hypotension and cerebral venous hypertension.
One study showed that 15% of patients undergoing off-pump CABG surgery exhibited EEG evidence of cerebral
hypoxemia and near-infrared spectroscopy (NIRS) desaturations.
35

Approaches to Cerebral Protection
Cerebral ischemic injury is broadly classified as global or regional. Brain energy stores are rapidly depleted during
ischemia, leading to depolarization and release of excitatory neurotransmitters. Cerebral ischemia triggers activation
of multiple pathways (ischemic cascade) over a period of hours to days that determine the ultimate extent of injury
and functional outcome.
36
Other injury pathways that are activated lead to altered calcium homeostasis, free radical
production, activation of proteases, and initiation of apoptosis. Vulnerability to injury varies between cell subtypes,
with neurons located in the hippocampus, cortex, cerebellum, corpus striatum, and thalamus having particular
susceptibility.
37
The central area of ischemic injury is surrounded by viable tissue that is vulnerable to infarction
(the ischemic penumbra) from the secondary events that follow the initial injury. Prevention of cerebral injury
from cardiac surgery is distinguished from rescue therapies for patients who present with a stroke in progress,
such as those in non-surgical settings. Cerebral protective measures can be categorized into several basic strategies:
1) prevention of injury from cerebral emboli; 2) ensuring cerebral O
2
delivery/demand balance; and 3) prevention of
secondary brain injury to the ischemic penumbra.

Reducing Cerebral Emboli
Performing CABG surgery off pump has been proposed as a means for reducing the injurious consequences of CPB,
including the introduction of microemboli into the systemic circulation.
38
Nonetheless, several prospectively
randomized trials comparing off- and on-pump CABG surgery have failed to demonstrate that avoiding CPB
provides a clear reduction in stroke rate or risk for POCD.
39,40
;
41-43
.
40
The decision to carry out CABG surgery off
pump must be individualized, but the current data do not indicate that this surgical approach substantially improves
neurologic outcomes.
Atherosclerosis of the ascending aorta is a known source of cerebral emboli that may cause stroke and possibly
POCD.
4
In patients presenting with stroke, aortic atherosclerosis is associated with blood hypercoagulability, which
increases the risk for recurrent stroke and death.
44
Detection and surgical management of atherosclerosis of the aorta
are distinct clinical issues. Epiaortic ultrasound is more sensitive than direct palpation or transesophageal
echocardiography for detecting atherosclerosis of the ascending aorta.
45,46
This method allows the surgeon to
identify and avoid atheroma during aortic cannulation and cross-clamping. Approaches to surgical management of
patients who have been found to have an atherosclerotic aorta include: 1) converting to off-pump surgery; 2) using
alternative sites for CPB cannulation; 3) using the single cross-clamp technique to avoid partial aortic occlusion
clamping for proximal bypass graft anastamosis; 4) using fibrillatory arrest rather than cardioplegic arrest to avoid
cross-clamping; 5) avoiding proximal anastomosis by using arterial grafts; and 6) replacing the ascending aorta
under circulatory arrest.
4
Improved neurologic outcomes have been reported with epiaortic ultrasound-guided
surgery and with practices that minimize the risk for embolization.
47-49
A meta-analysis of 7 studies found that the
rate of stroke was 0.31% for patients undergoing off-pump CABG with minimal aortic manipulations but 1.35% for
patients undergoing off-pump CABG with a side-clamp or proximal graft anastomosis device (p=0.003).
50

Insufflation of CO
2
into the mediastinum may increase the rate of absorption of intravascular emboli by
221
Page 3
substituting the more soluble CO
2
for air in the surgical wound.
4
The effectiveness of this strategy for reducing
neurologic complications is not clear, but its use has few associated risks. Cardiotomy suction aspirate is high in
lipid content and is a source of cerebral lipid microemboli in experimental canine CPB.
4,51
Based on animal data and
inferential data from humans, many centers have adopted a practice of either discarding cardiotomy suction aspirate
or processing it with a cell-salvage device before returning it to the CPB circuit. As platelets and coagulation factors
are lost with either approach, these practices might increase the frequency of blood transfusions when the suction
volume is high. This possibility is an important consideration, as transfusion of allogeneic packed red blood cells
(PRBC) and platelets is associated with increased risk for stroke after cardiac surgery.
52
Rubens et al
53
reported no
difference in the frequency of POCD 1 week or 3 months after CABG and/or aortic valve surgery between patients
whose cardiotomy blood was processed with a cell saver and those who had direct return to the CPB circuit.
However, Djaiani et al
54
found that processing cardiotomy blood with a continuous-flow cell saver led to a
significantly lower rate of POCD 6 weeks after CABG surgery. Neither study showed a difference in the number of
TCD embolic signals between cell-saver and control groups. In both studies, patients in the cell-saver group had
higher rates of transfusion than did controls. Thus, the data are conflicting on whether routine processing of
cardiotomy suction aspirate with a cell saver improves neurologic outcomes. Any benefits might depend on the
volume of aspirated blood and/or the type of device used.

Improving Cerebral Oxygen Balance
Blood Pressure Management: Cerebral blood flow (CBF) autoregulation remains functional when alpha-stat pH
management is used during CPB. Thus, low mean arterial pressure (MAP) is believed to be tolerated because CBF is
ensured to blood pressures of 50 mmHg or even lower.
7
Whether this practice is appropriate for the rising proportion
of patients with cerebrovascular disease is not clear. Gottesman et al,
34
for example, found a relationship between a
decrease in MAP by !10 mmHg from baseline during CPB and a risk for watershed stroke detected by MRI. Other
data suggest that maintaining MAP between 80 and 90 mmHg during CPB is associated with less delirium and less
early cognitive dysfunction.
55
Our group has reported in animal and clinical studies that real-time continuous
monitoring of CBF autoregulation with TCD or NIRS may provide a novel approach for individualizing MAP
targets during CPB.
56,57
This method allows for MAP to be optimized within an individuals autoregulatory range,
thus reducing the potential for cerebral hypoperfusion. We have found that the average MAP at the lower limit of
CBF autoregulation in adults during CPB is 66 mmHg (95% CI, 6558 mmHg). The range of pressures, though, at
the autoregulation threshold was 40 to 90 mmHg. Importantly, patients with stroke had a higher MAP at the
autoregulatory threshold than did patients without stroke (CVA, 7415 mmHg; no CVA, 6612 mmHg, p=0.054).
We have also found a link between the product of the magnitude and duration that the MAP is below the lower limit
of CBF autoregulation and acute postoperative kidney injury.
58
Our growing experience suggests that monitoring
CBF autoregulation in real-time might be necessary to identify the optimal MAP for CPB. Further, individualizing
MAP with this approach may lead to better organ perfusion and possibly better patient outcomes.

Red Cell Transfusion: In retrospective analyses, anemia has been linked to adverse outcomes, including stroke,
particularly when Hct is <21% during CPB.
59,60
The TRACS study examined whether treatment of anemia with
transfusion of PRBC improves patient outcome in a clinical trial of 502 patients undergoing cardiac surgery with
CPB.
61
Patients were randomly assigned to a liberal or restrictive transfusion group (Hct !30% or ! 24%,
respectively). The hemoglobin level in the liberal transfusion group (10.5 g/dL) was higher than that in the
restrictive group (9.1 g/dL, p<0.001). The frequency of the primary composite endpoint of 30-day all-cause
mortality or severe morbidity (cardiogenic shock, ARDS, or acute renal injury requiring dialysis or hemofiltration)
was similar between groups (10% liberal vs. 11% restrictive, p=0.85]. Non-leukocyte-depleted blood was used in
this study, but the PRBC units were stored for a median of 3 days before transfusion. These variables have been
associated with reduced risk from PRBC transfusion.
62,63
Further, cell salvage was not used in the study patients.
The number of transfused PRBC units was an independent risk factor for clinical complications or death at 30 days
(hazard ratio per unit transfused, 1.2; 95% CI, 1.11.4; p=0.002). The Society of Thoracic Surgeons and Society of
Cardiovascular Anesthesiologists clinical practice guidelines opine that For patients on CPB with risk for critical
end-organ ischemia/injury, it is not unreasonable to keep hemoglobin level at 7 g/dL or more.
64

Temperature Management: Extensive laboratory data have demonstrated that hypothermia provides neuronal
protection from ischemic injury via multiple mechanisms.
4
Clinically, hypothermia has been shown to improve
neurologic recovery in comatose survivors of cardiac arrest.
37
Hypothermia may extend the time that circulatory
arrest is tolerated during complex aortic surgery, but there is little clinical evidence that it provides robust
neuroprotection during routine cardiac surgery.
65
The ineffectiveness of hypothermia might be explained by the
221
Page 4
absence of hypothermia during all periods of cerebral risk or inadvertent hyperthermia with rewarming.
4
The latter
might result from the proximity of the aortic cannula (returning warm blood) to cerebral vessels and/or inaccurate
patient temperature monitoring that underestimates brain temperature. Rewarming to 34
o
C rather than to 37
o
C
resulted in improved neurocognitive outcome after CABG surgery.
66
However, at 3 months after CABG surgery, the
rates of POCD did not differ among patients who were maintained at 37
o
C (with a circulating warming blanket)
during CPB and those who were maintained at 34
o
C without rewarming.
67
Our group has shown that CPB re-
warming is associated with impaired CBF autoregulation in a high proportion of patients.
68
These results indicate
that CBF is pressure-passive in some patients during rewarming at a time when systemic vascular resistance is
typically low and cerebral metabolic rate is elevated. These conditions might lead to a CBF that is inadequate for
metabolic demand. In that study, there was an association between impaired CBF autoregulation and stroke.

Neuromonitoring: NIRS is used to monitor regional cerebral O
2
saturation (rScO
2
) during cardiac surgery. We have
recently performed a systematic review to evaluate evidence regarding the relationship between rScO
2
desaturations
and POCD and stroke.
69
Several case reports and many observational studies offered anecdotal evidence that rScO
2

monitoring has value for identifying CPB cannula malposition. Nine observational studies evaluated the potential
association between acute rScO
2
desaturation and POCD based on the Mini-Mental Status Examination (n=3
studies) or more detailed cognitive testing (n=6 studies). Six of the studies found an association, but three did not.
Two retrospective studies reported a relationship between rScO
2
desaturation and stroke or type I and II neurologic
deficits after surgery compared with historical controls. The observational studies have many limitations, including
small sample size, assessments only during the immediate postoperative period, and failure to perform risk-
adjustments. Moreover, these studies have failed to determine whether the relationship between rScO
2
desaturation
represents a modifiable risk factor for poor neurologic outcome or whether it is an epiphenomenon that identifies
patients generally of higher risk for poor outcome.
70
Two randomized studies attempted to answer the question of
whether interventions for rScO
2
desaturation improve patient outcomes. The results of one are difficult to interpret
owing to poor adherence with the protocol for treating rScO
2
desaturations. In the other study of 200 CABG surgical
patients, NIRS-guided interventions were associated with less major organ injury (death, MI, stroke) and shorter
ICU length of stay compared to standard care.
71
Algorithms have been proposed for treating cerebral O
2

desaturation.
72
Interventions include ensuring adequate CPB flow, increasing MAP, avoiding hypocarbia
(decreasing gas-inflow), deepening anesthesia, increasing the FiO
2
, instituting pulsatile CPB flow, considering
transfusion if indicated, administering anticonvulsant drugs when indicated, and considering hypothermia.

Protecting the Ischemic Penumbra
Areas of brain infarction are surrounded by viable but vulnerable tissue termed the ischemic penumbra. The viability
of the ischemic penumbra is threatened by the multiple injury pathways that comprise the ischemic cascade
referenced earlier. Microcirculatory changes resulting from brain injury, particularly inflammatory and hemostatic
activation, can contribute to cerebral hypoperfusion due to the no reflow phenomenon. Thus, measures aimed at
neuroprotective hemodynamic management may be critical to protection from secondary brain injury. Other
measures for protecting the ischemic penumbra are mostly pharmacologic, including avoidance of hyperglycemia.

Blood Glucose Control: Hyperglycemia worsens experimental cerebral injury and is associated with poor neurologic
outcome after stroke in humans via multiple mechanisms.
73
The relationship between serum glucose and stroke
severity appears to be J shaped. Experimentally, the nadir glucose level associated with best neurologic outcome
appears to be around 120 mg/dL.
74
Initial results showing that intensive insulin treatment improves outcomes of
critically ill patients were rapidly extrapolated to patients undergoing cardiac surgery.
75
Data from the NICE-
SUGAR study, though, demonstrated in a multicenter, randomized trial that a glucose target of 81 to 108 mg/dL was
associated with higher mortality than a target of "180 mg/dL in adult critically ill patients. Importantly, these trials
were conducted in the ICU.
76
Data in cardiac surgery patients have not supported intensive insulin therapy for
improving neurologic outcomes. In a randomized trial of 400 patients undergoing cardiac surgery, the frequency of
the composite outcome of death, cardiac morbidity, stroke, or renal failure was higher for patients given an insulin
infusion to maintain intraoperative glucose between 80 and 100 mg/dL than for patients who received conventional
treatment [insulin given when glucose was >200 mg/dL (p=0.02)].
77
A prospectively randomized trial found no
difference in the frequency of neurologic complications 6 weeks or 6 months after CABG surgery between patients
who received intraoperative insulin when glucose was >100 mg/dL and those who received insulin when glucose
was >200 mg/dL.
78
A recent meta-analysis identified 7 randomized studies of intravenous insulin administration for
acute stroke.
79
Administration of insulin when glucose is >140 mg/dL is recommended for nonsurgical patients with
stroke.
80

221
Page 5

Drugs for Cerebral Protection: Little progress has been made in the clinical translation of pharmacologic agents that
target key pathways of the ischemic cascade as a clinically relevant approach for cerebral protection. Multiple
agents that showed promising effects in vitro via multiple mechanisms have failed to provide clinical protection
against ischemic cerebral injury, including barbiturates, propofol, Ca
2+
channel blockers, NMDA receptor
antagonists, anti-inflammatory agents, antioxidants, GABA receptor blockers, 17!-estradiol, piracetam, and
others.
4,81-84
Volatile anesthetics and xenon have laboratory-proven cerebroprotective effects. However, based on a
systematic literature review, Schifilliti et al
85
concluded that evidence was insufficient to choose one anesthetic over
another for the purposes of cerebral protection. Magnesium was investigated as a cerebral protectant in a
randomized, blinded, placebo-controlled trial of 350 patients undergoing cardiac surgery.
86
At a dose that increased
serum levels to 1# to 2 times normal, Mg
2+
use was associated with improved cognitive performance compared with
placebo use 24 to 96 hours after surgery, but these benefits were not present 3 months after cardiac surgery.
Experimentally, ketamine protects against ischemic neuronal injury by blocking NMDA receptors and by
attenuating inflammation.
87
In a small randomized pilot study (n=52), the frequency of POCD 1 week after cardiac
surgery was lower in patients who received ketamine than in those who received placebo (33% vs. 81%, p<0.001).
83

Likewise, the frequency of delirium was lower for patients given ketamine during surgery than for those given
placebo.
88
A recent retrospective study involving 1134 patients reported better outcomes among patients who
received dexmedetomidine than among those who received other types of sedation after CABG plus/minus valve
surgery.
89
In hospital (1.23% vs. 4.59%; odds ratio, 0.34; 95% CI, 0.1920.614; p<0.0001), 30-day (1.76% vs.
5.12%; adjusted OR, 0.39; 95% CI, 0.2260.655; p<0.0001), and 1-year (3.17% vs. 7.95%; adjusted OR, 0.47; 95%
CI, 0.3120.701; p=0.0002) mortalities were lower for patients who received dexemedetomidine than for patients
who did not receive it. Dexmedetomidine therapy reduced the risk of overall complications (OR, 0.80; 95% CI,
0.680.96; p=0.0136) and delirium (5.46% vs. 7.42%; adjusted OR, 0.53; 95% CI, 0.370.75; p=0.003). These
findings are consistent with a meta-analysis of strategies to reduce postoperative delirium in which
dexmedetomidine sedation was found to be associated with less delirium than were other drugs (2 randomized trials
with 415 patients, pooled risk ratio, 0.39; 95% CI, 0.160.95).
90

Conclusions
A comprehensive approach to cerebral protection that includes interventions to reduce cerebral embolism and ensure
cerebral O
2
supply/demand balance may result in improved neurologic outcomes.
4
Strategies for improving
neurologic outcomes from cardiac surgery are summarized in the Table.

Table. Evidence-based recommendations for cerebral protection during cardiac surgery.

Strategies Supported by Clinical Investigations
Epiaortic ultrasound for detection of atherosclerosis of the ascending aorta
Avoidance of hyperthermia during CPB rewarming
Strategies With Reasonable Level of Clinical Evidence
The use of a membrane oxygenator and an arterial line filter ("40 $m) during CPB
"-stat pH management during CPB
Single cross-clamp technique for proximal CABG anastamosis patients at risk for atheroembolism
Arterial blood pressure kept >70 mmHg during CPB in high-risk patients
Strategies That Are Acceptable and Considered Reasonable Treatment by Most Experts
NIRS monitoring, especially in high-risk patients
Insulin infusion should be considered for serum glucose > 140 mg/dL
Consider processing cardiotomy suction aspirate with a cell-saver device
Transfusion of packed red blood cells should be considered in high-risk patients when hemoglobin is "7 g/dL or
higher depending on other patient-specific considerations.
221
Page 6
Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved. Note: This publication contains material
copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual refresher course
lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
References
1. N Engl J Med 335:1857-63, 1996.
2. Stroke 41:499-503, 2010.
3. Anesth Analg 107:21-8, 2008.
4. Anesth Analg 103 21-37, 2006.
5. Ann Thorac Surg 59:1326-30, 1995.
6. N Engl J Med 344:395-402, 2001.
7. Anesth Analg 66 825-32, 1987.
8. Lancet 368:694-703, 2006.
9. N Engl J Med 344:451-2, 2001.
10. Ann Neurol 63:581-90, 2008.
11. Ann Thorac Surg 85:60-4, 2008.
12. Anesth Analg 112:1179-85, 2011.
13. Neurosci Biobehav Rev 36:2118-29, 2012.
14. N Engl J Med 354:1157-65, 2006.
15. N Engl J Med 367:30-9, 2012.
16. Nucl Med Commun 24:893-900, 2003.
17. Arch Neurol 58:571-6, 2001.
18. Eur J Cardiothorac Surg 25:791-800, 2004.
19. Ann Thorac Surg 83:1389-95, 2007.
20. J Am Coll Cardiol 60:791-7, 2012.
21. Stroke 33:2376-82, 2002.
22. Arch Neurol 55:1475-82, 1998.
23. Circulation 120:585-91, 2009.
24. J Am Coll Cardiol 49 1934-42, 2007.
25. Stroke 36 1854-8, 2005.
26. J Thorac Cardiovasc Surg 134:996-1005, 2007.
27. Br J Anaesth 91:656-61, 2003.
28. Ann Thorac Surg 59 1304-7, 1995.
29. Stroke 25:1393-9, 1994.
30. J Cardiothorac Vasc Anesth 10 113-8, 1996.
31. J Neurol Neurosurg Psychiatry 65 5736, 1998.
33. Ann Thorac Surg 58 1702-8, 1994.
34. Stroke 37:2306-11, 2006.
35. Heart Surg Forum 3:198-202, 2000.
36. Ann Emerg Med 36:483-506, 2000.
37. Circulation 118:2452-83, 2008.
39. Eur Heart J 29:2601-16, 2008.
40. N Engl J Med 361:1827-37, 2009.
41. N Engl J Med 368:1179-88, 2013.
42. N Engl J Med 368:1189-98, 2013.
44. J Am Coll Cardiol 52:855-61, 2008.
45. J Thorac Cardiovasc Surg 103 453-62, 1992.
46. Circulation 100:642-7, 1999.
47. Ann Thorac Surg 75:1387-91 2003.
48. Ann Thorac Surg 78:1579-85, 2004.
49. J Thorac Cardiovasc Surg 131:114-21 2006.
50. Heart Lung Circ 20:318-24, 2011.
51. Ann Thorac Surg 65 1651-5, 1998.
52. Transfusion 44:1143-8, 2004.
53. Circulation 116:I89-I97, 2007.
54. Circulation 116 1888-95, 2007.
55. Eur J Cardiothorac Surg 40:200-7, 2011.
56. Stroke 38:2818-25, 2007.
57. Stroke 41:1951-6, 2010.
58. Crit Care Med 41:464-71, 2013.
59. Ann Thorac Surg 80 1381-7, 2005.
60. Circulation 116:471-9, 2007.
61. J Am Med Assoc 304:1559-67, 2010.
62. Circulation 109:2755-60, 2004.
63. N Engl J Med 358:1229-39, 2008.
64. www.sts.org.
65. Cochrane Database Syst Rev:CD002138, 2001.
66. Circulation 104 I85-I91, 2001.
68. Anesth Analg 110:321-8, 2010.
69. Anesth Analg 116:663-76, 2013.
70. Anesthesiology 114:58-69, 2011.
71. Anesth Analg 104:51-8, 2007.
72. Semin Cardiothorac Vasc Anesth 4:274-81, 2007.
73. Neurology 59:669-74, 2002.
74. Arch Neurol 67:1123-30, 2010.
75. N Engl J Med 354:449-61, 2006.
76. N Engl J Med 360:1283-97, 2009.
77. Ann Intern Med 146 233-43, 2007.
78. J Thorac Cardiovasc Surg 130 1319, 2005.
79. Cochrane Database Syst Rev:CD005346, 2011.
80. Stroke 38:1655-711, 2007.
81. Stroke 38 2048-54, 2007.
82. Stroke 40:880-7, 2009.
83. Med Sci Monit 14:PI53-7, 2008.
84. Ann Thorac Surg 87:820-5, 2009.
85. CNS Drugs 24:893-907, 2010.
87. J Cardiothorac Vasc Anesth 24:131-42, 2010.
88. Acta Anaesthesiol Scand 53:864-72, 2009.
89. Circulation, 2013.
90. Crit Care 17:R47, 2013.

Disclosure
Covidien Self Funded Research Honoraria; Ornim Self Other Material

223
Page 1
Introducing Blood Conservation Into Clinical Practice:
Can the New Guidelines Lead Us?
Colleen G. Koch, M.D., MS, MBA Cleveland, Ohio
Objectives
Understand the role practice guidelines in the clinical practice setting.
Become aware of the issues and controversies involved with adoption and implementation of practice
guidelines.
Recognize that guidelines represent one component to comprehensive blood conservation and blood
management programs.
Become aware of components to effective blood conservation and blood management through examples of
an institutional blood management program whose outcomes involve more effective use of blood and
product management.
Practice guidelines serve to aide physicians in making patient care decisions and in particular, in the setting of
considerable practice variation, serve as useful tools to more effectively manage and guide patient care. Guidelines
are meant to provide the best evidence for decision-making from currently available research with the ultimate
goal of providing a more methodological approach to evidence-based patient care along with the most efficient use
of healthcare resources. Whether practice guidelines in general, and more specifically the current: Perioperative
blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons (STS) and the
Society of Cardiovascular Anesthesiologists (SCA) clinical practice guidelines have been widely accepted and
implemented into clinical practice by caregivers is under debate. While development of practice guidelines follows
formal well-described procedures, the actual adoption and implementation is reportedly variable in a number of
practice settings. A recent investigation reported on the effect of the perioperative blood transfusion and blood
conservation in cardiac surgery clinical practice guidelines by the STS and SCA on clinical practice. Among the
groups surveyed were members of the SCA, the American Academy of Cardiovascular Perfusion, Canadian Society
of Clinical Perfusion and the American Society of Extracorporeal Technology. The authors used a standardized
survey instrument to evaluate the change to clinical practice based on the available STS/SCA guidelines. Responses
were received from 891 institutions; 78% of anesthesiologists and 67% of perfusionists who responded reported
reading the all/ part of the guideline document however overall little change to clinical practices was attributed to
the guidelines. Of note, among reasons put forth for poor adoption of the clinical practice guidelines were that the
number of recommendations were based on limited/very limited scientific evidence. It is the lack of evidence on
when and who to transfuse RBC that limits adoption of guidelines that are based on expert opinion rather than
results of randomized controlled trials.
Blood and component therapy are limited and costly resources and have been associated with an increased morbidity
risk following surgical and interventional procedures and in the intensive care unit settings. A recent investigation
reported considerable variation on a national level with red blood cell (RBC) use from a large national surgical
database. Despite similar surgical procedures and patient population comorbidity, there was wide variability in RBC
and component product use-- despite the availability of the STS/SCA updated guidelines. This investigation and
other investigations on RBC transfusion and patient outcomes highlight a number of issues: 1). We continue to be

223
Page 2
challenged in our ability to identify specific patients who will and will not benefit from RBC transfusion, 2). There
is continued lack of sufficient high-level evidence to form the foundation for evidence-based guidelines on

transfusion thresholds and 3). Insufficient availability of bedside technology to determine tissue oxygenation to
access need for RBC transfusion.

Blood management programs serve as multidisciplinary programs with the aim of appropriately allocating blood
products, ensuring safety and providing value to the patient and institution. Guidelines may be a component to blood
management however only in so much as they provide sound evidence for evidence-based practice decisions. Local
educational initiatives, physician and nursing engagement and accountability, culture change and process
improvements are all important components to a successful blood management program. Blood management
performance outcome measures may soon be part of formal measurement tools to gauge success of blood
management programs.

References

1. Ferraris V et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of
Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guidelines. Ann Thorac
Surg 2007;83:S27-86.
2. Woolf S et al. Clinical guidelines: potential benefits, limitations and harms of clinical guidelines. BMJ
1999;318:527-30.
3. Grol R et al. Attributes of clinical guidelines that influence use of guidelines in general practice: observational
study. BMJ 1998:317:858-61.
4. Grilli R et al. Evaluating the message: the relationship between compliance rate and the subject of a practice
guideline. Med Care 1994;32:202-213.
4. Timmermans S. From autonomy to accountability: the role of clinical practice guidelines in professional power.
Perspect Biol Med 2005;48:490-501.
5. Likosky D et al. Effect of perioperative blood transfusion and blood conservation in cardiac surgery clinical
practice guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon
clinical practice. Anesth Analg 2010;111:316-23.
6. Koch CG, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in
isolated coronary artery bypass grafting. Critical Care Medicine 2006;34:1608-1616.
7. Koch CG, et al. Persistent effect of red cell transfusion on health-related quality of life after cardiac surgery.
Annals of Thoracic Surgery 2006;82:13-20.
8. Murphy G, et al. Increased mortality, postoperative morbidity and cost after red blood cell transfusion in patients
having cardiac surgery. Circulation 2007;116:2544-2552.
9. Koch CG, et al. Duration of red-cell storage and complications after cardiac surgery. New England Journal of
Medicine. 2008;358:15-25.
10. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Role of Transfusion in Lung Injury and
Pulmonary Morbidity after Cardiac Surgery, Annals of Thoracic Surgery 2009;88:1410-8.
11. Koch CG, Li L, Duncan A, Mihalijvec T, Starr N, Blackstone E. Perioperative red blood cell transfusion is
associated with reduced long-term survival in isolated coronary artery bypass grafting, Annals of Thoracic Surgery
2006;81:1650-7.
12. Vivacqua A, Koch CG, Nowicki E, Houghtaling P, Blackstone EH, Sabik J. Morbidity of Bleeding after Cardiac
Surgery: Is It Blood Transfusion, Reoperation for Bleeding or Both? Annals of Thoracic Surgery 2011;91:1780-
1790.
13. Kumar A, Figueroa P, Gowans LK, Parker B, Proctor A, Benitez Santana SM, Koch CG. An Evolution in Blood
Management: Past, Present and Future. Quality Management in Healthcare 2011;20(4):311-321.
14. Bennett-Guerrero E, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA
2010;304:1568-1575.

Disclosure

301
Page 1
Perioperative Pacemaker and Defibrillator Management: What You Need to Know
Marc A Rozner, Ph.D, M.D. Houston, Texas
Introduction Battery operated pacemakers (PM) were developed in 1958, and implantable cardioverter-
defibrillators (ICDs) followed in 1980. The complexity of these cardiac implantable electrical devices (CIED) limits
generalizations that can be made about the perioperative care of these patients. Population aging, continued
enhancements, and new indications for implantation of CIED will lead to increased implantations. Initially, ICDs
treated only sudden cardiac arrest (SCA), whether from ventricular tachycardia (VT) or ventricular fibrillation (VF).
Now, any patient with an ejection fraction < 35%, regardless of the etiology and without induction testing for VT or
VF, is considered a likely ICD recipient.
Many technical issues conspire to create confusion in this field. All ICDs have the ability to provide brady
pacing, but ICDs never provide asynchronous pacing without reprogramming, even with magnet placement.
Second, ICDs respond to, and process, electromagnetic interference (EMI) differently than a PM. Third, case
Preoperative Key Points (HRS-ASA; ASA)
Identify the manufacturer and model of the cardiac
implantable electrical device (CIED).
Establish preoperative contact with the patients
CIED physician / clinic to obtain appropriate
records and perioperative prescription (HRS).
Have the CIED interrogated (ASA) by a
competent authority shortly before the anesthetic.
Obtain a copy of this interrogation. Obtain
perioperative prescription from the CIED
physician (HRS). Ensure that any ICD treatment
settings are appropriate and that the CIED will
pace the heart.
Consider replacing any CIED near its elective
replacement period in a patient scheduled to
undergo either a major surgery or surgery within
25 cm of the generator.
Determine the patients underlying rhythm / rate to
determine the need for backup pacing support.
Ensure that all magnet behavior (pacing, suspend
shock therapy) is appropriate if magnet use is
planned.
Program minute ventilation rate responsiveness off,
if present.
Program all rate enhancements off.
Consider increasing the pacing rate to optimize
oxygen delivery to tissues for major cases.
Disable antitachycardia therapy if a defibrillator.
Although a magnet might work, magnet use has
been associated with inappropriate ICD discharge.
Intraoperative Key Points
Monitor cardiac rhythm / peripheral pulse with pulse
oximeter (plethysmography) or arterial waveform.
Consider disabling the artifact filter on the ECG
monitor.
Avoid use of monopolar electrosurgery (ESU).
Use bipolar ESU only; if not possible, then pure cut
(monopolar ESU) is better than blend or coag.
Place the ESU dispersive electrode to prevent
electricity from crossing the generator-heart
circuit, even if it must be placed on the distal
forearm and the wire covered with sterile drape.
If the ESU causes ventricular oversensing and pacer
quiescence, limit the period(s) of asystole.
Consider avoiding sevoflurane, isoflurane or
desflurane in the patient with long QT syndrome.
Postoperative Key Points
Consider postoperative interrogation if monopolar
ESU has been used, blood transfused, or
preoperative reprogramming took place.
Optimum heart rate and pacing parameters should
be determined and programmed if needed.
ICD patients must be monitored until the
antitachycardia therapy is restored.

301
Page 2
reports, often with misidentified issues, and very small case series are used to justify policy. Fourth, asymptomatic
patients can have nonfunctioning devices.
1,2

These issues led the American Society of Anesthesiologists (ASA) to publish a Practice Advisory for these
patients,
3
and the Heart Rhythm Society has now published an Expert Consensus Statement.
4
Other guidelines
have been published as well,
5-7
although not all authors recommend ICD disablement in the perioperative period.
8,9

ALL ICDs perform cardiac pacing, so ICD issues related primarily to brady pacing should be reviewed in the Pacing
section.
Notices regarding potential failures for PMs,
10-13
ICD leads,
14
and ICDs
15-17
get published often.
18
Retrospective
analysis suggests that outright failure occurs in 4.6 (PM) and 20.7 (ICD) per 1,000 implants,
19
and outright lead
failure is not rare.
20
Also, for about 46,000 ICDs, Guidant has found that the device improperly enters the magnet
mode, which prevents any detection (and, therefore, treatment) of tachyarrhythmias. As a work-around, Guidant
has recommended the permanent disabling of the magnet mode through programming.
16
Finally, devices
resembling cardiac pulse generators are being implanted at increasing rates for pain control, thalamic stimulation to
control Parkinsons disease, phrenic nerve stimulation to stimulate the diaphragm in paralyzed patients, and vagus
nerve stimulation to control epilepsy and possibly obesity.
21

The subcutaneous ICD introduced to the US by Boston Scientific late last year (present in EU since 2009 by
Cameron Health) behaves differently from the transvenous ICDs, since it has no antitachycardia pacing and no
permanent brady pacing support.
Disagreement between the ASA Perioperative Advisory
3
and the HRS-ASA Consensus document
22
center
primarily over: 1) the recommendation for a de-novo preoperative interrogation (ASA) versus contact with the
patients CIED physician (HRS); 2) the use of programming (ASA) rather than magnet application (HRS) to
mitigate the effects of EMI; and 3) the timing of a postoperative evaluation, should one be needed. Regardless,
important information must be conveyed to the CIED physician by the perioperative team (Table 1) and a
perioperative prescription must be communicated by the CIED physician to the perioperative team (Table 2).
Nevertheless, application of a magnet in the place of a preoperative evaluation has led to harm in several patients.
23

Pacemaker Overview More than 2,500 PM models have been produced by 26 companies, and more than 300,000
adults and children in the US undergo new PM placement yearly. Nearly 3 million US patients have PMs. Outdated
literature, limited or inadequate training, and conventional wisdom lead to confusion in this field.
Pacing systems consist of an impulse generator and lead(s). Leads can have one (unipolar), two (bipolar), or
multiple (multipolar) electrodes with connections in multiple chambers. In unipolar pacing, the generator case serves
as an electrode, and tissue contact can be disrupted by pocket gas.
24
PMs with unipolar leads produce larger
spikes on an analogue-recorded ECG, and they are more sensitive to EMI. Most PM systems use bipolar pacing /
sensing configuration, since bipolar pacing usually requires less energy and bipolar sensing is more resistant to
interference from muscle artifacts or stray electromagnetic fields. Often, bipolar electrodes can be identified on the
chest film since they will have a ring electrode 1 to 3 cm proximal to the lead tip. But generators with bipolar leads
can be independently programmed to the unipolar mode for pacing, sensing, or both.
The Pacemaking Code of the North American Society of Pacing and Electrophysiology (NASPE) and the
British Pacing and Electrophysiology Group (BPEG) describes basic pacing behavior (Table 3).
25
Most PMs in the
US are programmed either to the DDD (dual chamber) or VVI mode (single chamber). DDI is used for atrial
dysrhythmias, and VDD pacing (single wire device providing AV synchrony) can be found in patients with AV
nodal disease but normal sinus node function. Atrial-only pacing (AAI) is uncommon in the US. Biatrial pacing is
Table 1: Information Provided to CIED Service by
Perioperative Team
Type of procedure
Anatomic location of procedure
Patient position for procedure
Need and site for monopolar electrosurgery or other EMI
Planned cardioversion or defibrillation
Surgical venue (OR, office, surgicenter)
Postprocedural plan (hospital admission, outpatient)
Unusual circumstances (surgery encroaching leads or
generator
Table2: Information Provided by CIED Service to
Perioperative Team
Device type, manufacturer, model
Date of last interrogation; remaining battery longevity
Indication for placement, lead revisions if within 3
months
Current settings
Pacing dependence
Magnet behavior
Individualized prescription and follow-up plans
Unusual circumstances such as alert status

301
Page 3
being investigated as a means to prevent atrial fibrillation,
26
and biventricular (BiV) pacing (also called Cardiac
Resynchronization Therapy [CRT]) is used to treat dilated cardiomyopathy (D-CMP).
27-29

Indications Permanent pacing indications (Table 4) are reviewed in detail elsewhere.
30
In order to be effective,
BiV, HOCM, and D-CMP pacing must provide the stimulus for ventricular activation, and A-V synchrony must be
preserved.
31
PM inhibition, loss of pacing (from native conduction, junctional rhythm, EMI), or AV dys-synchrony
can lead to deteriorating hemodynamics. BiV pacing can lengthen the Q-T interval in some patients, producing
torsade-de-pointes.
32
Thus access to rapid defibrillation is required for the patient with BiV pacing.

Pacemaker Magnets Despite oft-repeated folklore,
magnets were never intended to treat PM
emergencies or prevent EMI effects. Rather, magnet-
activated switches were incorporated to produce
pacing behavior that demonstrates remaining battery
life and, sometimes, pacing threshold safety factors.
Placement of a magnet over a generator might
produce no change in pacing since NOT ALL PACEMAKERS SWITCH TO A CONTINUOUS
ASYNCHRONOUS MODE WHEN A MAGNET IS PLACED. Also, not all models from a given company behave
the same way. Common effect(s) of magnet placement on conventional PMs are shown in Table 5. Magnet
behavior can be altered or disabled via programming in many devices. For generators with programmable magnet
behavior [Biotronik, BOS, CPI, Guidant Medical, Pacesetter, St Jude Medical], only a magnet test or interrogation
with a programmer can reveal current settings. HRS recommends magnet placement to create asynchronous pacing
when needed where the magnet behavior is known, appropriate for the patient, the patient is supine, the magnet can
be observed, and access to the magnet is possible.
22

Table 3: NASPE / BPEG Generic Pacemaker Code (NBG) [Revised 2002]
Position I Position II Position III Position IV Position V
Chambers
Paced
Chambers
Sensed
Response to
Sensing
Programmability Multisite Pacing
O = None O = None O = None O = None O = None
A = Atrium A = Atrium I = Inhibited R = Rate Modulation A = Atrium
V = Ventricle V = Ventricle T = Triggered V = Ventricle
D = Dual (A+V) D = Dual (A+V) D = Dual (T+I) D = Dual (A+V)
Table 4: Permanent Pacemaker Indications
Sinus Node Disease
Atrioventricular (AV) Node Disease
Long Q-T Syndrome
Hypertrophic Obstructive Cardiomyopathy (HOCM)
33,34

Dilated Cardiomyopathy (D-CMP)
34

301
Page 4

Preanesthetic Evaluation and Pacemaker
Reprogramming Preoperative management of
the patient with a PM includes evaluation and
optimization of coexisting disease(s). No
special laboratory tests or x-rays are needed for
the patient with a conventional PM. A patient
with a BiV PM or ICD might need a chest film
to document the position of the coronary sinus
(CS) lead, especially if central line placement is
planned, since spontaneous CS lead
dislodgement can occur.
35,36

Important features of the preanesthetic
device evaluation are shown in Preoperative
Key Points. Current HRS and Medicare
guidelines include frequent telephonic (q3-12
months, depending upon device type and age)
and a comprehensive device interrogation with
a programmer at least once per year.
37,38

Direct interrogation with a programmer
remains the only reliable method for evaluating
battery status, lead performance, and adequacy
of current settings. Some devices retain pacing
histograms and information about
tachydysrhythmia(s). Appropriate
reprogramming (Table 6) is the safest way to
avoid intraoperative problems, especially if
monopolar "Bovie" electrosurgery will be used.
Some PM manufacturers stand ready to assist with this task (see Appendix for company telephone numbers);
however, any industry-employed allied professional (i.e., the rep) should be supervised by an appropriately trained
physician.
39

Reprogramming the pacing mode to
asynchronous, at a rate greater than the
patients underlying rate, usually ensures that
no over- or undersensing from EMI will take
place. However, setting a device to
asynchronous mode has the potential to create a
malignant rhythm in the patient with
structurally compromised myocardium.
42

Reprogramming a device will not protect it
from internal damage or reset caused by EMI.
In general, rate responsiveness and
"enhancements" (dynamic atrial overdrive,
hysteresis, sleep rate, A-V search, etc.) should
be disabled by programming.
43-45
Note that for
many older Guidant and/or CPI devices,
Guidant Medical recommended increasing the
pacing voltage to "5 volts or higher" when
monopolar electrosurgery will be used. Few
cardiologists know or follow this recommendation, but there are reports of threshold changed during both
intrathoracic
46
and non-chest surgery.
47,48
Some disease states might increase pacing threshold.
49
Special attention
must be given to any device with a minute ventilation (bioimpedance) sensor (Table 7), since inappropriate
tachycardia has been observed secondary to mechanical ventilation,
50,51
monopolar (Bovie) electrosurgery,
50,52,53

Table 5: Pacemaker Magnet Behavior
Most common responses - Asynchronous high rate pacing (85-
100 bpm), not always in the best interest of the patient.
Biotronik (ONLY when programmed to asynchronous mode,
[not the default state]) 90 bpm, 80 if battery depleted (BUT
can be programmed OFF)
BOS/Guidant Medical / CPI (current models since 1990)
generally 100 bpm (but can be 90), 85 if battery depleted
(BUT can be programmed OFF)
Medtronic (most models) 85 bpm, 65 if battery depleted
Sorin (was ELA Medical (current models since 1989) > 80
bpm (max 96 bpm), 80 if battery depleted. ELA devices
take 8 additional asynchronous cycles (six at magnet rate,
then two at programmed rate) upon magnet removal.
Magnet placement increases the pacing voltage to 5v
St Jude Medical (current models since 1990) > 87 bpm (max
100 bpm), 86.3 if battery depleted (BUT can be
programmed OFF)
Brief (10-100 beats) asynchronous pacing, then return to program
values (all Intermedics; most Biotronik models when
programmed to their default state)
Continuous or transient loss of pacing
Pacing threshold problems
Discharged battery (some pre-1990 devices)
Diagnostic "Threshold Test Mode" (Siemens)
Table 6: Pacemaker Reprogramming Likely Needed
Any rate responsive device see text (problems are well known,
and have been misinterpreted with potential for patient injury,
and the FDA has issued an alert regarding devices with minute
ventilation sensors (Table 5)
Special pacing indication (HOCM, D-CMP, pediatrics)
Pacing-dependent patient
Major procedure in the chest or abdomen
Rate enhancements are present that should be disabled
Special Procedures
Lithotripsy
Transurethral or Hysteroscopic Resection
Electroconvulsive Therapy
Succinylcholine use (although no convincing evidence)
MRI (usually contraindicated by device manufacturers),
possible in some patients
40,41

301
Page 5
and connection to an ECG monitor with respiratory
rate monitoring.
54-59
Sometimes, inappropriate
<anesthetic> therapy has been delivered in these
settings with bad results.
51,60

Intraoperative (or Procedure) Management of
Pacemakers No special technique or monitoring is
needed for the PM patient, but attention must be given
to a number of concerns (Table 8). Monopolar
"Bovie" electrosurgery (ESU) use remains the
principal intraoperative issue for the patient with a
PM. Between 1984 and 1997, the US FDA was
notified of 456 adverse events with pulse generators,
255 from electrosurgery, and a significant number
of device failures.
61
Monopolar ESU is more likely
to cause problems than bipolar ESU.
62
Magnet
placement during electrosurgery might prevent
aberrant PM behavior. Spurious reprogramming with
magnet placement is unlikely. If monopolar
electrosurgery is to be used, then the ESU current-
return pad must be placed to ensure that ESU current
path does not cross the pacemaking system. Some
authors recommend placement of this pad on the
shoulder for head and neck procedures or the distal
arm (with sterile draping of the wire) for breast and axillary procedures.
62,63

Choice of anesthetic agents should be dictated by the patients underlying physiology as well as the procedure.
However, the use of drugs that suppress the AV or SA node (such as potent opiates or dexmedetomidine) can
abolish any underlying rhythm that might be present and render the patient truly PM dependent. Also, some potent
inhalational agents (isoflurane, sevoflurane, and desflurane) might exacerbate the long Q-T syndrome.
64-67

Pacemaker Failure PM failure has three etiologies: 1) failure to capture; 2) lead failure; or 3) generator failure.
Failure to capture can result from myocardial ischemia / infarction, acid-base disturbance, electrolyte abnormalities,
or abnormal antiarrhythmic drug level(s). External pacing might further inhibit PM output at pacing energies that
will not produce myocardial capture.
68,69
Sympathomimetic drugs generally lower pacing threshold. Outright
generator and/or lead failure is rare.

Post Anesthesia Pacemaker Evaluation Any PM that was reprogrammed for the operating room should be reset
appropriately. For non-reprogrammed devices, most manufacturers recommend interrogation to ensure proper
functioning and remaining battery life if any electrosurgery was used.

Implantable Cardioverter-Defibrillator (ICD) Overview For the patient with VT or VF, ICDs clearly reduce
deaths,
70,71
and they remain superior to antiarrhythmic drug therapy.
72
Initially approved by the US FDA in 1985,
more than 100,000 devices will be placed this year, and more than 250,000 patients have these devices today.
Further, data showing ICD placement in patients without evidence of tachyarrhythmias (Multicenter Automatic
Defibrillator Implantation Trial II [MADIT-II] - ischemic cardiomyopathy, ejection fraction less than 0.30
73
and
Sudden Cardiac Death Heart Failure Trial [SCD-HeFT] any cardiomyopathy, ejection fraction less than 0.35
74
)
has significantly increased the number of patients for whom ICD therapy is indicated. ICD placement reduces
mortality from arrhythmia even in patients on optimal heart failure therapy.
75
Like PMs, ICDs have a four-place
code (Table 9).
76
The Pacemaker Code can be used instead of Position IV.
ICDs measure each cardiac R-R interval and categorize the rate as normal, too fast (short R-R interval), or too
slow (long R-R interval). When enough short R-R intervals are detected, an antitachycardia event is begun. The
internal computer chooses antitachycardia pacing (ATP - less energy use, better tolerated by patient) or shock,
depending upon the presentation and device programming. Newer Medtronic ICDs begin a run of ATP while
charging for shock. Most ICDs are programmed to reconfirm VT or VF after charging to prevent inappropriate
therapy. Typically, ICDs deliver 6 18 shocks per event. Once a shock is delivered, no further ATP can take place.
Table 7: Devices with Minute Ventilation Sensors
BOS, Guidant Medical and/or CPI Advantio, Altrua
(S401-404, S601-606), Ingenio, Insignia Plus (1194,
1297, 1298), Pulsar (1172, 1272), Pulsar Max (1170,
1171, 1270), Pulsar Max II (1180, 1181, 1280)
Medtronic Kappa 400 series (401, 403)
Sorin (was ELA) Medical Brio (212, 220, 222), Chorus
RM (7034, 7134), Opus RM (4534), Reply DR,
Rhapsody, Symphony, Talent (113, 133, 213, 223, 233)
Telectronics / St Jude Meta (1202, 1204, 1206, 1230,
1250, 1254, 1256), Tempo (1102, 1902, 2102, 2902)
Table 8: Essentials of Device Monitoring
ECG monitoring of the patient must include the ability to
detect PM discharges (artifact filter disabled)
Perfused (peripheral) pulse must be monitored with a
waveform display
The pacing rate might need to be increased due to an
increased oxygen demand
BiV and HOCM patients probably need beat-to-beat cardiac
output monitoring
Appropriate equipment must be on hand to provide backup
pacing and/or defibrillation

301
Page 6
Despite improvements in detection of ventricular dysrhythmias (Table 10),
77
more than 10% of shocks are for
rhythm other than VT or VF.
78
Recent data suggests that any high energy therapy (either ATP or shock) injure the
myocardium,
79
these myocardial injuries shorten life,
80
and that in-hospital EMI leading to shock is an unrecognized
source of harm for patients.
81

ICDs measure each cardiac R-R interval and categorize
the rate as normal, too fast (short R-R interval), or too
slow (long R-R interval). When enough short R-R
intervals are detected, an antitachycardia event is begun.
The internal computer chooses antitachycardia pacing
(ATP - less energy use, better tolerated by patient) or
shock, depending upon the presentation and device
programming. Newer Medtronic ICDs begin a run of
ATP while charging for shock. Most ICDs are
programmed to reconfirm VT or VF after charging to
prevent inappropriate therapy. Typically, ICDs deliver
6 18 shocks per event. Once a shock is delivered, no
further ATP can take place. Despite improvements in
detection of ventricular dysrhythmias (Table 8),
77
more
than 10% of shocks are for rhythm other than VT or VF.
78

Supraventricular tachycardia remains the most common etiology of inappropriate shock therapy,
82,83
and causes
of inappropriate shock have been reviewed elsewhere.
84
Lead degradation also has led to unexpected and
inappropriate shock.
14,85
Most ICDs will begin <brady> pacing when the R-R interval is too long. ICDs with
sophisticated, dual and three chamber pacing modes (including rate responsiveness) are approved for patients who
need permanent pacing (about 20% of ICD patients). Note that the use of dual chamber (DDD) pacing in an ICD
patient might decrease survival when compared to single chamber (VVI) pacing.
86

ICD Indications Initially, ICDs were placed for VT or
VF. Currently, any patient with significant
cardiomyopathy (EF ! 35%) will likely be a candidate for
ICD placement. Table 11 shows current ICD indications.
Note that CMS requires 40 days from an ischemic event
or mechanical intervention to ICD implant.

ICD Magnets Like PMs, magnet behavior in many ICDs
can be altered by programming. Most ICDs will suspend
tachydysrhythmia detection (and therefore therapy) when
a magnet is appropriately placed. ICDs from BOS and St
Jude Medical can be programmed to ignore magnet
placement. Guidant now recommends permanently
disabling the magnet mode on 45,000 ICDs under alert for magnet switch failure.
16
In general, magnets will not
affect the brady pacing mode or rate. Sorin (was ELA) devices change pacing rate (VVI mode) to reflect battery
voltage. Interrogating the device and calling the manufacturer remain the most reliable method for determining
magnet response.

Table 9: NASPE / BPG Generic Defibrillator Code (NBD)
Position I Position II Position III
Position IV
(or use Pacemaker Code)
Shock Chambers
Antitachycardia Pacing
Chambers
Tachycardia Detection
Antibradycardia Pacing
Chambers
O = None O = None E = Electrogram O = None
A = Atrium A = Atrium H = Hemodynamic A = Atrium
V = Ventricle V = Ventricle V = Ventricle
D = Dual (A+V) D = Dual (A+V) D = Dual (A+V)
Table 10: ICD Features to Reduce Undesired Shock
Onset criteria - usually, VT onset is abrupt, whereas
SVT onset has sequentially shortening R-R intervals
Stability criteria - R-R intervals of VT is relatively
constant, whereas R-R intervals of a-fib with rapid
ventricular response is quite variable
QRS width criteria - usually, QRS width in SVT is
narrow (<110 msec), whereas QRS width in VT is
wide (>120 msec)
"Intelligence" in dual chamber devices attempting to
associate atrial activity to ventricular activity
Morphology waveform analysis with comparison to
stored historical templates
Table 11: ICD Indications
Ventricular tachycardia
Ventricular fibrillation
Post-MI patients with EF ! 30% (MADIT II)
Cardiomyopathy from any cause with EF ! 35%
(SCD-HeFT)
Hypertrophic cardiomyopathy
Awaiting heart transplant
Long Q-T syndrome
Arrhythmogenic right ventricular dysplasia

Brugada syndrome (right bundle branch block, S-T
segment elevation in leads V1-V3)

301
Page 7
Preanesthetic Evaluation and ICD Reprogramming The patient with an ICD likely has a significant
cardiomyopathy (CMP). Guidelines from the ACC / AHA recommend beta blockade and afterload reduction for al
most every CMP patient.
87,88
Since benefits of this can therapy accrue quickly,
89
consideration might be given to
delaying a case for 1-2 weeks after initiation of therapy.
Prior to any surgery, every ICD patient should undergo preoperative ICD interrogation (ASA). ALL ICDs
should have antitachycardia therapy disabled if monopolar Bovie use is planned
43,90
or there are lead problems
predisposing to inappropriate shock.
14,85
HRS suggests that magnet placement is appropriate provided that magnet
function is enabled, the patient is supine, the magnet can be observed, and access to the magnet is unimpeded by the
surgical field.
22
The comments in the Pacing Section apply here for antibradycardia pacing.

Intraoperative (or Procedure) ICD Management No special monitoring or anesthetic technique (due to the ICD)
is required for the ICD patient. ECG monitoring and the ability to deliver external cardioversion or defibrillation
must be present during the time of ICD disablement. Note that an inappropriate shock can be delivered without
prior ECG changes if a lead is damaged or defective.
85
If emergency cardioversion or defibrillation is needed, the
defibrillator pads should be placed to avoid the pulse generator to the extent possible. Nevertheless, one should
remember that the patient, not the ICD, is being treated. The recommendations in the section Intraoperative (or
Procedure) Management of Pacemakers apply here as well. ICDs should be disabled prior to insertion of a central
line to prevent inappropriate shock, possible ICD failure, or patient injury.
91

Post Anesthesia ICD Evaluation The ICD must be reinterrogated and re-enabled, and pacing parameters should
be checked and reset as necessary. Postop interrogation might be unnecessary if no monopolar ESU was used, no
blood transfused, limited fluid administered, and no untoward issues were identified. For a disabled ICD, the
patients ECG should be continuously monitored with immediate access to defibrillation equipment until
reactivation takes place.
92,93
All ICD events should be reviewed and counters should be cleared.

Summary Electronic miniaturization has permitted the design and use of sophisticated electronics in patients who
have need for artificial pacing and/or automated cardioversion / defibrillation of their heart. These devices are no
longer confined to keeping the heart beating between a minimum rate (pacing function) and a maximum rate (ICD
functions), as they are being used as therapy to improve the failing heart. The aging of the population and our
ability to care for a patient with increasingly complex disease suggest that we will be caring for many more patients
with these devices, and we must be prepared for this situation. Safe and efficient clinical management of these
patients depends upon our understanding of implantable systems, indications for their use, and the perioperative
needs that they create.

Reference List

1. Rozner MA. J Cardiothorac Vasc Anesth 2008;
22:341
2. Boriani G et al. J Cardiothorac Vasc Anesth 2008;
22:423
3. Practice advisory for the perioperative
management of patients with cardiac implantable
electronic devices: pacemakers and implantable
cardioverter-defibrillators: an updated report by the
American Society of Anesthesiologists task force on
perioperative management of patients with cardiac
implantable electronic devices. Anesthesiology 2011;
114:247
4. Crossley G.H. et al. Heart Rhythm. 2011.
URL=www.hrsonline.org/content/download/1432/20
Appendix: Company Phone Numbers
Angeion (discontinued products) 651-484-4874 Medtronic 800-505-4636
Biotronik 800-547-0394 Pacesetter (SJM) 800-722-3774
Biotronik 800-227-3422 St Jude Medical (SJM) 800-722-3774
Cardiac Pacemakers, Inc - CPI
(BOS)
800-227-3422 Telectronics (SJM) 800-722-3774
ELA Medical 800-352-6466 Ventritex (SJM) 800-722-3774
Guidant Medical 800-227-3422 Vitatron (Medtronic) 800-505-4636
Intermedics (BOS) 800-227-3422

301
Page 8
125/file/2011-
HRS_ASA%20Perioperative%20Management.pdf
5. Goldschlager N et al. Arch Intern Med 2001;
161:649
6. Healey JS et al. Can J Anaesth 2012; 59:394
7. Medicines and Health Care products Regulatory
Agency. 2006.
URL=http://www.mhra.gov.uk/home/groups/dts-
bi/documents/websiteresources/con2023451.pdf
8. Stevenson WG et al. Circulation 2004; 110:3866
9. Cheng A et al. Pacing Clin Electrophysiol 2008;
31:344
10. Medtronic. 2009. URL=
http://www.medtronic.com/kappasigma/downloads/P
hysicianLetterKappaSigma.pdf
http://www.medtronic.com/crmLetter.html
12. Guidant Insignia Pacemakers. Product
Advisories. 2005 Sep 2005
13. Guidant PDM Pacemakers. Product Advisories.
2005 Jul 2005
http://www.medtronic.com/fidelis/physician-
letter.html
http://wwwp.medtronic.com/ProductLookup/lookup.
html?faId=62&alId=62
16. Boston Scientific. 2005. URL=
http://www.bostonscientific.com/templatedata/import
s/HTML/PPR/ppr/support/current_advisories.pdf
17. Guidant Prizm 2 [1861] ICD. Product Advisories.
2005 Jun 2005
18. Carlson MD et al. Heart Rhythm 2006; 3:1250
19. Maisel WH et al. JAMA 2006; 295:1901
20. Borleffs CJ et al. Circulation: Arrhythmia and
Electrophysiology 2009; 2:411
21. Kazatsker M et al. J Cardiovasc Electrophysiol
2002; 13:522
22. Crossley GH et al. Heart Rhythm 2011; 8:1114
23. Schulman PM, Rozner M.A. Anesthesia &
Analgesia 2013; in press
24. Lamas GA et al. Am J Cardiol 1985; 56:995
25. Bernstein AD et al. PACE 2002; 25:260
26. Delfaut P, Saksena S. J Interv Card
Electrophysiol 2000; 4 Suppl 1:81
27. Peters RW, Gold MR. Cardiol Clin 2000; 18:55
28. Abraham WT et al. N Engl J Med 2002; 346:1845
29. Hare JM. N Engl J Med 2002; 346:1902
30. Epstein, Andrew E. et al. Journal of the American
College of Cardiology. 2008. 21.
URL=http://content.onlinejacc.org/cgi/citmgr?gca=ja
cc;51/21/e1
31. Gras D et al. PACE 1998; 21:2249
32. Medina-Ravell VA et al. Circulation 2003;
107:740
33. Hayes DL. Am J Cardiol 1999; 83:161D
34. Auricchio A et al. Am J Cardiol 1999; 83:130D
35. Valls-Bertault V et al. Europace 2001; 3:60
36. Alonso C et al. Heart 2001; 86:405
38. Wilkoff BL et al. Heart Rhythm 2008; 5:907
39. Hayes JJ et al. PACE 2001; 24:398
40. Martin ET et al. J Am Coll Cardiol 2004; 43:1315
41. Rozner MA et al. Journal of the American
College of Cardiology 2005; 45:161
42. Preisman S, Cheng DC. Anesthesiology 1999;
91:880
43. Eagle, K. A. et al. 2002. URL=
http://www.acc.org/qualityandscience/clinical/guideli
nes/perio/clean/pdf/perio_pdf.pdf
44. Andersen C, Madsen GM. Anaesthesia 1990;
45:472
45. Levine PA. Anesthesiology 1997; 87:1261
46. Levine PA et al. Ann Thorac Surg 1986; 41:313
47. Pili-Floury S et al. Eur J Anaesthesiol 2008;
25:514
48. Rozner,MA, Nguyen,AD. Anesthesiology 2002;
96:A1070
49. Levine PA. In: Tse H-F, Lee KL et al., eds.
Proceedings of the XII world congress on cardiac
pacing and electrophysiology. Bologna, Italy:
Medimond International Proceedings; 2003: 601
50. Madsen GM, Andersen C. Br J Anaesth 1989;
63:360
51. von Knobelsdorff G et al. Anaesthesist 1996;
45:856
52. Van Hemel NM et al. PACE 1989; 12:1720
53. Wong DT, Middleton W. Anesthesiology 2001;
94:710
54. Chew EW et al. PACE 1997; 20:276
55. Rozner MA, Nishman RJ. Anesthesia and
Analgesia 1999; 88:965
56. Wallden J et al. Anesthesia and Analgesia 1998;
86:1339
57. Center for Devices and Radiologic Health. 1998.
URL=http://www.fda.gov/MedicalDevices/Safety/Al
ertsandNotices/PublicHealthNotifications/UCM0645
36
58. Southorn PA et al. Br J Anaesth 2000; 84:508
59. Rozner MA, Nishman RJ. Anesthesiology 2002;
96:773
60. Lau W et al. Pacing Clin Electrophysiol 2006;
29:438
61. Pressly, N. FDA User Facility Reporting #20.
1997. URL=http://www.fda.gov/cdrh/fuse20.pdf
62. Rozner MA. PACE 2003; 26:923
63. Trankina MF et al. Anesthesiology 2000;
93:A1193
64. Michaloudis D et al. Eur J Anaesthesiol 1998;
15:623

301
Page 9
65. Gallagher JD et al. Anesthesiology 1998; 89:1569
66. Paventi S et al. Minerva Anestesiol 2001; 67:637
67. Yildirim H et al. Eur J Anaesthesiol 2004; 21:566
68. Mychaskiw G, Eichhorn JH. J Clin Anesth 1999;
11:669
69. Moskowitz DM et al. Anesthesiology 1998;
89:531
70. Moss AJ et al. N Engl J Med 1996; 335:1933
71. A.V.I.D.Investigators. N Engl J Med 1997;
337:1576
72. Buxton AE et al. N Engl J Med 1999; 341:1882
73. Moss A et al. The New England Journal of
Medicine 2002; 346:877
74. Bardy GH et al. N Engl J Med 2005; 352:225
75. Kadish A et al. N Engl J Med 2004; 350:2151
77. Swerdlow CD. J Cardiovasc Electrophysiol
2001; 12:606
78. Hurst TM et al. PACE 1997; 20:1328
79. Stempniewicz P et al. Journal of Cardiovascular
Electrophysiology 2011; 22:554
80. Moss AJ et al. N Engl J Med 2012;
81. Powell BD et al. PACE 2012; 35:863
82. Prasad K et al. Indian Heart J 1997; 49:403
83. Schumacher B et al. PACE 1997; 20:125
84. Rozner MA. Progress in Anesthesiology 1999;
13:43
85. Ellenbogen KA et al. J Am Coll Cardiol 2003;
41:73
86. Wilkoff BL et al. JAMA 2002; 288:3115
87. Hunt SA. J Am Coll Cardiol 2005; 46:1116
88. Hunt SA et al. J Am Coll Cardiol 2009; 53:e1-
e90
89. Krum H et al. JAMA 2003; 289:712
90. Practice advisory for the perioperative
management of patients with cardiac rhythm
management devices: pacemakers and implantable
cardioverter-defibrillators: a report by the American
Society of Anesthesiologists Task Force on
Perioperative Management of Patients with Cardiac
Rhythm Management Devices. Anesthesiology 2005;
103:186
91. Varma N et al. PACE 2001; 24:394
92. Sullivan R, Ferriter A. Nursing 2008; 38:17
93. Rozner MA et al. Nursing 2008; 38:8

Disclosure
308
Page 1
The Pulmonary Artery Catheter in 2013: Past, Present, and Is There a Future?
Jonathan B. Mark, M.D. Durham, North Carolina
Pulmonary Artery Catheterization and Patient Outcome
The PAC has been surrounded by controversy since its introduction into clinical medicine by Swan and
Ganz more than 40 years ago (Swan 1970). A number of early clinical trials identified excess mortality in patients
receiving PAC monitoring, but these studies were criticized for their retrospective design and other shortcomings.
The SUPPORT Trial was perhaps the most widely publicized of these studies, as it was a large trial conducted in
critically ill medical and surgical patients from five major medical centers. The patients with PAC monitoring were
carefully matched to other ICU patients through use of a propensity score, but still had increased hospital length of
stay, increased hospital costs, and higher mortality than patients who were not monitored with PACs (Connors
1996). Widespread use of these catheters continued, in part owing to concerns that randomized prospective clinical
trials were still not available. However, several studies over the past decade have provided more recent and more
convincing data.
Sandham et. al. randomized the use of PACs in nearly 2,000 ASA III and IV patients undergoing urgent or
elective major surgery and found identical survival in patients with and without PAC monitoring (Sandham 2003).
Although the authors did not identify excess mortality associated with PAC usage, there were more pulmonary
complications in the PAC group, including pulmonary embolism, hemorrhage, and infarction. Another seminal
randomized prospective investigation was conducted in 1,041 patients from 65 intensive care units in the United
Kingdom. This PAC-Man Trial showed no difference in hospital mortality in patients monitored with PACs
compared with control patients (Harvey 2005).
A third randomized prospective study, the ESCAPE Trial, evaluated PAC use in hospitalized patients with
severe congestive heart failure and found no effect on mortality or days alive out of hospital (ESCAPE 2005). And
perhaps of greatest clinical impact, a meta-analysis of 13 randomized clinical trials conducted between 1985 and
2005 in 5,051 patients, half of whom were surgical, showed that PAC monitoring had NO EFFECT on mortality or
days hospitalized (Shah 2005).
Use of PACs for management of patients with Acute Respiratory Distress Syndrome (ARDS) was
addressed by the NIH sponsored ARDS Clinical Trial Network in 2006. The Fluid and Catheter Treatment Trial
(FACTT) randomized patients with ARDS to two different fluid resuscitation strategies (restricted vs. liberal) and
two different monitoring strategies (PAC vs. central venous pressure [CVP]) (Wheeler 2006). Once again, with a
rigorous randomized controlled methodology, these trials confirmed that patients managed with PAC monitoring
had no improvement in mortality or ventilator-free days, compared with those who received CVP guided therapy.
Taken together, these most recent publications suggest that we have little clinical evidence that PAC
monitoring benefits high-risk surgical patients, or those with severe congestive heart failure or ARDS.
Consequently, it is not surprising that use of PACs is decreasing. Between 1993 and 2004, data derived from the
National Inpatient Sample (part of the Agency for Healthcare Research and Quality [AHRQ] Healthcare Cost and
Utilization Project) demonstrated a 65% reduction in use of PACs in hospitalized medical patients and a similar
reduction in surgical patients (Wiener 2007). A similar trend has been identified in a recent review of PAC use in
27,000 critically ill patients, which showed a 68% reduction in PAC monitoring in intensive care (Berthiaume
2009).


308
Page 2
Notwithstanding these practice trends, many critical care experts and anesthesiologists still use PACs in
high-risk patients and believe they are needed to manage complex hemodynamic conditions (Chatterjee 2009).
Furthermore, despite recent randomized controlled trials that have failed to demonstrate benefit from PAC
monitoring, it is quite possible that trials have not been conducted in patient cohorts likely to reap these benefits,
such as complex cardiac surgical patients or those with the most severe cardiopulmonary disorders. A recent report
from the ESCAPE Trial investigators showed that patients who were excluded from randomization but included in a
parallel trial registry of PAC monitoring had a higher mortality than randomized trial patients who received PACs

(Allen 2008). In the words of these authors, ESCAPE investigators enrolled quite different patients into the
randomized trial compared with those relegated to the registry The perceived need for hemodynamic
measurement itself identified a high-risk population. Perhaps more relevant for the typical clinical practice of
anesthesiologists, the most recent American College of Cardiology/American Heart Association practice guideline
for coronary artery bypass graft surgery recommends PAC monitoring for patients presenting in cardiogenic shock
(Class I, Level C Evidence) and patients with acute hemodynamic instability (Class IIa, Level B Evidence), and
possibly for coronary bypass surgery in otherwise stable patients (Class IIb, Level C Evidence) (Hillis 2012).
Strong evidence derived from robust clinical trials for the use of PACs in this population remains unavailable.

Improving the Safety of Pulmonary Artery Catheter Monitoring

Given the currently available evidence, it seems clear that the continued use of PAC monitoring requires a
renewed commitment to safe practice and more selective use of this diagnostic tool. Less widespread use of PACs
has important implications for training and maintenance of competency (Rubenfeld 2007). For years, many have
argued that clinicians, both doctors and nurses, who use PACs are inadequately trained in their use and have
inadequate knowledge to use these devices safely (Iberti 1990). This problem may be even greater today. If we are
to continue using this invasive monitoring tool, we must understand its limitations, the physiologic principles
underlying interpretation of the data provided, and recognize the potential associated complications before they
harm patients.

Eliminating Complications of Central Venous and Pulmonary Artery Catheterization

Central venous catheterization (CVC) remains a common procedure for the care of intensive care and high-
risk surgical patients. The complications are well recognized, and the more common include:

1. Bleeding (adjacent arterial injury, hematoma formation, airway compromise, or cardiac tamponade)
2. Pneumothorax, hemothorax, and chylothorax
3. Nerve injury
4. Infection (bacteremia, sepsis, endocarditis)
5. Venous thromboembolism
6. Venous (and paradoxical) air embolism

Numerous other complications have been reported, and the ASA Closed Claims Analysis (Domino 2004) suggested
that nearly 2% of claims in the database pertain to CVC-associated injuries. Compared to other claims in this
database, CVC claims were associated with a higher average severity of injury and increased fatality. The most
common claim related to catheter or wire embolism, undoubtedly the result of a medical error, and other common
complications described were as noted above. Perhaps of greatest importance, the authors determined that nearly
half of these injuries were preventable by use of pressure waveform monitoring (Ezaru 2009), chest radiography, or
ultrasound-guided cannulation. Growing use of ultrasound for CVC (Ortega 2010) is based on clinical evidence of
reduced failure rates and complications compared to standard techniques that are based on surface anatomy and
palpation (Randolph 1996). Consequently, the recently published ASA practice guideline for central venous
catheterization (Rupp 2012) recommends ultrasound guidance for all elective internal jugular vein catheterization,
based on unequivocal level A1 evidence. Inexpensive ultrasound devices are widely available, easy to use, and
should be considered routinely for all internal jugular cannulation procedures. For example, a thrombosed jugular
vein can be identified prior to prepping and draping, the easily compressible internal jugular vein can be rapidly
identified and distinguished from the adjacent carotid artery, and successful placement of the guidewire can be
confirmed.


308
Page 3

Pulmonary artery catheterization carries additional risks beyond those associated with central venous
catheterization, including risks associated with catheter flotation through the right heart chambers and prolonged
catheter residence in the pulmonary artery (Roizen, ASA Task Force on PAC 2003). During passage of a
pulmonary artery catheter (PAC) through the right heart chambers, non-sustained atrial and ventricular dysrhythmias
are common and of no clinical significance. Less frequent but more life threatening complications include right
bundle branch block leading to complete heart block in patients with pre-existing left bundle branch block or
sustained ventricular dysrhythmias, including ventricular fibrillation, particularly in patients with myocardial
ischemia involving the right ventricle (Lopez-Sendon 1990). Catheter residence within the pulmonary artery for
hours or days can be complicated by infection (endocarditis and sepsis), pulmonary infarction, and pulmonary artery
rupture, conditions that are often fatal.

The infectious risks of both PAC and CVC placement can be reduced by adherence to practice guidelines for
catheter placement promulgated by JCAHO and the Institute for Healthcare Improvement (IHI) (Berwick 2006).
The IHI 100,000 Lives Campaign identified six areas for improving patient care, including prevention of CVC-
related infection by proper hand hygiene, maximal barrier precaution (including a large patient drape), chlorhexidine
skin preparation, optimal catheter site selection, and prompt removal of unnecessary catheters. As anesthesiologists,
we need to be concerned with complications that may result from our care but not clinically manifest for days after
surgery. The above-mentioned ASA practice guideline (Rupp 2012) supports these recommendations.

Physiologic Basis for CVP and PAC Waveforms and Interpretation of Cardiac Filling Pressures

The normal CVP waveform consists of three
peaks (a, c, v) and two descents (x, y). The most
prominent wave is the a wave, which results from atrial
contraction following the ECG P wave at end-diastole.
This atrial contraction provides the end-diastolic atrial
kick, which loads the right ventricle through the open
tricuspid valve. Atrial pressure decreases following the
a wave, as the atrium relaxes. This decline in atrial
pressure is interrupted by the c wave at the beginning of
systole. The c wave results from isovolumic right
ventricular contraction, which closes the tricuspid
valve, causing it to bow back toward the right atrium in
early systole and produce an increase in atrial pressure.
The c wave must follow onset of the ECG QRS, since it

Transverse ultrasound image of right internal
jugular (IJ) vein lying slightly lateral and superficial
to the right carotid artery (CA).
Long axis ultrasound image of right internal jugular
vein showing the guidewire in the lumen (arrow).
IJ
CA


308
Page 4
30-
is an early systolic event. Atrial pressure continues its decline in mid-systole, owing to ongoing atrial relaxation and
changing atrial geometry produced by ventricular contraction and ejection. This is the x

descent or systolic collapse in atrial pressure. The x descent can be divided into x and x' descents, denoting the
portions before and after the c wave. However, the x descent generally should be considered to be the systolic
decline in atrial pressure. The last atrial pressure peak is the v wave, caused by venous filling of the right atrium,
through the vena cava, during late systole while the tricuspid valve remains closed. The v wave peaks just after the
ECG T wave. Atrial pressure then decreases as the tricuspid valve opens and blood flows from atrium to ventricle.
This is the y descent or diastolic collapse in atrial pressure.

During flotation of a PAC through the right heart chambers, typical pressure waveforms are recorded from
the right atrium, right ventricle, and pulmonary artery. Note that right atrial (RA) pressure is equal to CVP and of
similar waveform morphology. As the PAC crosses the tricuspid valve, the increase in systolic pressure identifies
arrival of the catheter in the right ventricle (RV), and flotation across the pulmonic valve is identified by an increase
in diastolic pressure in the pulmonary artery (PA). Occasionally, distinguishing RV from PA pressure is difficult,
but careful examination of the diastolic portion of these two pressure waveforms clarifies these different catheter tip
locations. During diastole, RV filling results in a pressure increase in the RV, while diastolic flow from the PA
toward the lung results in a pressure decrease (Red Arrows).

Advancing the balloon tipped PAC
further into the PA will allow the catheter to
wedge and record the PA wedge pressure or
PA occlusion pressure. When the PAC is
wedged, the pressure recorded from the catheter
tip is isolated from the proximal PA pressure by
the occluding balloon, and the tip records
downstream pulmonary venous and left atrial
pressure. Normal PA wedge pressure
waveforms display the same characteristic peaks
and descents previously described for CVP or
RA pressure waveforms. However, PA wedge
pressure is an indirect measure of left atrial
pressure. Left atrial pressure waves (a, c, and v)
must be transmitted in a retrograde fashion, from
the left atrium, through the pulmonary veins,
capillaries, and arteries to arrive at the wedged
PAC. As a result, PA wedge pressure is a
delayed, damped reflection of left atrial
pressure. Left atrial pressure a and v waves are
recorded in a pulmonary artery wedge pressure
trace approximately 150-200 msec after they are
inscribed in the left atrial pressure trace, largely owing to the transmission time through the interposed pulmonary
vascular bed. In general, the wedge pressure a wave follows the ECG R wave owing to this delay (compare CVP
and PA wedge pressures in red box). If these a and v waves are prominent, they can be detected in the unwedged
PA pressure trace, the a wave distorting the systolic upstroke, and the v wave obscuring the dicrotic notch.

ECG
0-
-
0-
-
30-
RA
RV
PA
PA Wedge


308
Page 5

A wide variety of hemodynamic abnormalities can be identified through careful analysis of CVP and PAC
waveforms. Dysrhythmias have characteristic signatures. In atrial fibrillation the CVP a wave disappears, and the
c wave becomes more prominent, since atrial volume is greater at end-diastole and onset of systole, owing to the
absence of atrial contraction. Isorhythmic atrioventricular dissociation or junctional rhythm alters the normal
sequence of atrial and ventricular contraction. When there is retrograde conduction of the pacemaker impulse from
AV node to the atrium, atrial contraction occurs during ventricular systole, when the tricuspid valve is closed,
thereby inscribing a tall cannon a wave in the CVP waveform. Absence of normal atrioventricular synchrony during
ventricular pacing can be identified in similar fashion by searching for venous cannon waves. In these instances, the
CVP helps diagnosis the cause of arterial hypotension since loss of the normal end-diastolic ECG P wave may not
be as clearly evident as the cannon a waves in the CVP trace. Valvular heart disease may also be identified,
particularly AV valve regurgitation. Tricuspid regurgitation produces abnormal systolic filling of the right atrium
through the incompetent valve. A broad, tall systolic c-v wave is inscribed, which begins in early systole and
obliterates the systolic x descent in atrial pressure. The CVP trace is said to be ventricularized, resembling RV
pressure. This regurgitant wave differs in onset, duration and magnitude from a normal CVP v wave caused by end-
systolic atrial filling from the vena cavae. Right ventricular end-diastolic pressure is overestimated by the numeric
readout on the bedside monitor, which reports a single mean value for CVP. Instead, right ventricular end-diastolic
pressure is estimated best by measuring the CVP value at the time of the ECG R wave, prior to the regurgitant
systolic wave. In a similar manner, a tall systolic c-v wave noted in the PA wedge pressure trace is the typical
hallmark of severe mitral regurgitation. As noted above, a tall v can be noted to distort the PA waveform in the
unwedged PA pressure trace.

ECG
ART
CVP
200-
0-
-
-
-
0-
20-
-
-
-
c
v
R
y

45-
-
0-
-
PA
R R
90-
-
-
v
v v
PA Wedge

0-
-
120-
-
-0
-
-30
-
ECG
PA
PA Wedge
CVP
ART
R R
Mitral Regurgitation
Tricuspid Regurgitation


308
Page 6
Perhaps the most clinically important pressure waveform abnormalities are those introduced during the
respiratory cycle and caused by cyclic variations in intrathoracic pressure. During spontaneous breathing,
inspiration causes a decrease in pleural and pericardial pressures that is transmitted to the RA and produces a decline
in transduced CVP (as well as other measured central vascular pressures). Note that the decrease in the transduced
CVP measured during inspiration may actually reflect an increase in transmural CVP, which is calculated as the
difference between the pressure measured inside the RA and pericardial pressure outside the atrium. In clinical
practice, transmural pressures are rarely determined owing to the difficulties in assessing pleural or pericardial
pressures. Instead, end-expiratory pressure should always be recorded to provide the best estimate for transmural
filling pressures. Since pleural and pericardial pressures approach atmospheric pressure at end-expiration whether
the patient is breathing spontaneously or receiving positive pressure mechanical ventilation, pressures recorded at
this point in the respiratory cycle will provide the best estimate for transmural pressure and cardiac preload. End-
expiratory pressure values can be determined by visual inspection of the CVP, PA, and wedge waveforms on a
calibrated monitor screen or paper recording.

An understanding of transmural pressure is the key
to proper interpretation of intravascular pressure recordings
and their relationship to cardiac filling volume or preload
(Gelman 2008). Increased filling pressure can result from
increased chamber volume, increased chamber wall stiffness,
or increased pressure surrounding the heart (pericardial or
intrathoracic pressure). This is the physiologic basis for
recording intravascular pressures at end-expiration and
explains why high CVP or PA wedge pressures may not
always indicate hypervolemia or increased chamber volume.
For example, when there is diastolic left ventricular
dysfunction from myocardial ischemia (impaired relaxation)
or hypertrophy (increased wall stiffness), the shape of the
ventricular pressure-volume relationship is shifted up and to the left. Under normal conditions, a fluid challenge
would increase ventricular preload with little change in filling pressure (Point A ! Point B). Owing to the
curvilinear relationship between chamber pressure and volume, marked increases in chamber filling will be
accompanied by an increased filling pressure (Point C). On the other hand, when there is diastolic dysfunction, the
same elevated filling pressure may not reflect increased preload, but rather abnormal chamber stiffness or increased
surrounding pressure (Point D). It is likely that these physiologic considerations confound simple interpretation of
PAC-derived data and contribute to the limited value of PAC monitoring found in many clinical trials.

The 40-year saga of the PAC is not likely at an end. It is up to us to assure safe and effective PAC use, with
appropriate clinical education, following established practice guidelines, and selecting this monitoring technique for
appropriate patients.

Measurement of CVP
at End-Expiration


308
Page 7
All figures modified courtesy of Jonathan B. Mark, Atlas of Cardiovascular Monitoring, 1998 (Churchill Livingstone)

References and Additional Reading

1. Allen LA, Rogers JG, Warnica JW, et al. High mortality without ESCAPE: The registry of heart failure
patients receiving pulmonary artery catheters without randomization. J Cardiac Failure 2008;14:661-9.
2. Berthiaume LR, Peets AD, Schmidt U, et al. Time series analysis of use patterns for common invasive
technologies in critically ill patients. J Crit Care 2009;471:e9-14.
3. Berwick DM, Calkins DR, McCannon CJ, Hackbarth AD. The 100 000 Lives Campaign: Setting a Goal and a
Deadline for Improving Health Care Quality. JAMA 2006;295:324-7.
4. Braner DAV, Lai S, Eman S, Tegtmeyer K. Central venous catheterization - subclavian vein. N Engl J Med
2007;357:e26.
5. Chatterjee K. The Swan-Ganz Catheters: Past, present, and future. A viewpoint. Circulation 2009;119:147-52.
6. Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of
critically ill patients. JAMA 1996;276:889-97.
7. Courtois M, Fattal PG, Kovacs SJ, Tiefenbrunn AJ, Ludbrook PA. Anatomically and physiologically based
reference level for measurement of intracardiac pressures. Circulation 1995;92:1994-2000.
8. Domino KB, Bowdle TA, Posner KL, Spitellie PH, Lee LA, Cheney FW. Injuries and liability related to central
vascular catheters: a closed claims analysis. Anesthesiology 2004;100:1411-8.
9. ESCAPE I. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness.
The ESCAPE Trial. JAMA 2005;294:1625-33.
10. Ezaru CS, Mangione MP, Oravitz TM, Ibinson JW, Bjerke RJ. Eliminating arterial injury during central venous
catheterization using manometry. Anesth Analg 2009;109:130-4.
11. Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology 2008;108:735-48.
12. Gnaegi A, Feihl F, Perret C. Intensive care physicians' insufficient knowledge of right-heart catheterization at
the bedside: Time to act? Crit Care Med 1997;25:213-20.
13. Gordon AC, Saliken JC, Johns D, Owen R, Gray RR. Ultrasound-guided puncture of the internal jugular vein:
Complications and anatomic considerations. Journal of Vascular and Interventional Radiology 1998;9:333-8.
14. Graham AS, Ozment C, Tegtmeyer K, Lai S, Braner DAV. Central venous catheterization. N Engl J Med
2007;356:e21.
15. Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery catheters
in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet 2005;366:472-7.
16. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery:
Executive Summary. Anesth Analg 2012;114:11-45.
17. Iberti TJ, Daily EK, Leibowitz AB, et al. Assessment of critical care nurses' knowledge of the pulmonary artery
catheter. Crit Care Med 1994;22:1674-8.
18. Iberti TJ, Fischer EP, Leibowitz AB, et al. A multicenter study of physicians' knowledge of the pulmonary
artery catheter. JAMA 1990;264:2928-32.
19. Jacka MJ, Cohen MM, To T, Devitt JH, Byrick R. Pulmonary artery occlusion pressure estimation: How
confident are anesthesiologists? Crit Care Med 2002;30:1197-203.
20. Lopez-Sendon J, Lopez de Sa E, Maqueda IG, et al. Right ventricular infarction as a risk factor for ventricular
fibrillation during pulmonary artery catheterization using Swan-Ganz catheters. Am Heart J 1990;119:207-9.
21. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review
of the literature and the tale of seven mares. Chest 2008;134:172-8.
22. Mark JB. Central venous pressure monitoring: clinical insights beyond the numbers. J Cardiothorac Vasc
Anesth 1991;5:163-73.
23. Mark JB. Atlas of cardiovascular monitoring. New York: Churchill Livingstone; 1998.
24. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med
2003;348:1123-33.
25. Ortega R, Song M, Hansen CJ, Barash P. Ultrasound-guided internal jugular vein cannulation. N Engl J Med
2010;362:e57.
26. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement of central venous
catheters: A meta-analysis of the literature. Crit Care Med 1996;24:2053-8.


308
Page 8
27. Roizen MF, Berger DL, Gabel RA, et al. Practice guidelines for pulmonary artery catheterization. An updated
report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization.
28. Rubenfeld GD, McNamara-Aslin E, Rubinson L. The pulmonary artery catheter, 1967-2007: rest in peace?
Jama 2007;298:458-61.
29. Rupp SM, Apfelbaum JL, Blitt C, et al. Practice Guidelines for Central Venous Access. A report by the
American Society of Anesthesiologists Task Force on Central Venous Access. Anesthesiology 2012;116:539-
73.
30. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters
in high-risk surgical patients. N Engl J Med 2003;348:5-14.
31. Schroeder RA, Barbeito A, Bar-Yosef S, Mark JB. Cardiovascular monitoring. In: Miller RD, ed. Miller's
Anesthesia. Seventh Edition. Philadelphia: Churchill Livingstone Elsevier; 2010:1267-328.
32. Shah MR, Hasselblad V, Stevenson LW, et al. Impact of the pulmonary artery catheter in critically ill patients:
meta-analysis of randomized clinical trials. JAMA 2005;294:1664-70.
33. Sharkey SW. Beyond the wedge: Clinical physiology and the Swan-Ganz catheter. Am J Med 1987;83:111-22.
34. Sharkey SW. A guide to interpretation of hemodynamic data in the coronary care unit. Philadelphia, PA:
Lippincott-Raven; 1997.
35. Squara P, Bennett D, Perret C. Pulmonary artery catheter. Does the problem lie in the users? Chest
2002;121:2009-15.
36. Swan HJC, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with
use of a flow-directed balloon-tipped catheter. N Engl J Med 1970;283:447-51.
37. Teplick RS. Measuring central vascular pressures: a surprisingly complex problem. Anesthesiology
1987;67:289-91.
38. Trottier SJ, Taylor RW. Physicians' attitudes toward and knowledge of the pulmonary artery catheter: Society
of Critical Care Medicine Membership Survey. New Horizons 1997;5:201-6.
39. Tsui JY, Collins AB, White DW, Lai J, Tabas JA. Placement of a femoral venous catheter. N Engl J Med
2008;358:e30.
40. Wheeler AP, Bernard GR, Thompson BT, et al. Pulmonary-artery versus central venous catheter to guide
treatment of acute lung injury. N Engl J Med 2006;354:2213-24.
41. Wiener RS, Welch HG. Trends in the use of the pulmonary artery catheter in the United States, 1993-2004.
JAMA 2007;298:423-9.
42. Wu S, Ling Q, Cao L, Wang J, Xu M, Zeng W. Real-time two-dimensional ultrasound guidance for
central venous cannulation. A meta-analysis. Anesthesiology 2013;118:361-75.

Disclosure

Note: This publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission.
Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright
holders.
313
Page 1
Cardiac Pharmacology: Ideas for Advancing Your Clinical Practice
Roberta Hines M.D. New Haven, Connecticut
Presentation begins on page 2
Disclosure
Cardiac Pharmacology:
Ideas For Advancing
Your Clinical Practice
Roberta L. Hines, M.D.
Nicholas M. Greene Professor
Chair, Department of Anesthesiology
Yale University School of Medicine
New Haven, CT
Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved. Note: This publication contains material copyrighted by others. Individual refresher course lectures are
reprinted by ASA with permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
313
Page1
WHY
ADMINISTER
CARDIOTONIC
AGENTS ?
313
Page2
KEY QUESTION
? Patient Outcome ?
Cardiotonic
Agents
313
Page3
CAN WE IDENTIFY
PATIENTS WHO
MAY BENEFIT FROM
CARDIOTONIC
AGENTS?
313
Page4
In Patients Chronically Treated
with Metoprol, the Demand of
Inotropic Catecholamine Support
After CABG is Determined by the
Arg 389 Alg-
1
Adrenoceptor
polymorphism
Ach Pharmacol 375:303-309, 2007
313
Page5
313
Page6
LECTURE OBJECTIVES
Natriuretic Peptides
Biology/Actions
Prognostic/Diagnostic Valve
Clinical Applications
Pulmonary Vasodilators
Physiological Advantage (Inhaled)
PDE-V Inhibitors
Vasopressin
Hemodynamic Effects
313
Page7
LECTURE OBJECTIVES
Vasoplegic Syndrome
Thyroid Hormone
Emerging Drugs:
Levosimendan
Pharmacology
Clinical Indications
313
Page8
NATRIURETIC
PEPTIDE
313
Page9
Site of Synthesis
Heart
ANP atria in response to stretch
BNP (Brain/B-type) ventricle
Clinical effects
modulated via specific receptors
cGMP is second messenger
313
Page10
Pre-proBNP
1-134
proBNP
1-108
Inactive
components
Active
components
proBNP
1-108
BNP
1-32
BNP
3-32
BNP
7-32
NT-proBNP
313
Page11
BNP
CLINICAL APPLICATIONS
Diagnostic Modality
(Bio marker)
Treatment Modality
CHF (dyspnea)
Noncardiac Surgery
Cardiac Surgery
CHF
Cardiac Surgery
313
Page12
BNP and
Pro-B-Type Natriuretic
Peptide
Diagnostic
Applications
313
Page13
BNP, Age and Heart failure
90%, young healthy,
BNP 25pg/ml
NT-proBNP 75pg/ml
Daniels LB, Maisel AS: J Am Coll Cardiol: 2007;50:2357
313
Page14
Clinical Caveat
The Introduction of
Beta Blockade Increase
Plasma BNP and
NT-pro BNP Levels
J Cardiovasc Pharmacol Therap 12(2):85-89, 2007
313
Page15
BNP
Congestive Heart Failure
Diagnostic
Estimate filling pressures
Prognosticate adverse outcomes
(dyspnea)
Confirm diagnosis
(BNP > 100 pg/ml)
Circulation 105: 2392-2397, 2002
N Engl J Med 345: 1014-1021, 2001
313
Page16
Does BNP Have a
Role in Perioperative
Risk Assessment?
313
Page17
Heart 2006;92;1645
313
Page18
Prognostic Value of Brain
Natriuretic Peptide in
Noncardiac Surgery
(A Meta-Analysis)
Anesthesiology 111:311-9, 2009
313
Page19
Meta-Analysis
Results
(n = 15 publications)
Preoperative BNP MACE
All Cause Mortality
Cardiac Death
Results revealed risk for both
short term (< 43 days) and long
term (> 6 mos) complications
313
Page20
BNP and Postoperative Outcomes
Possible Etiologies
BNP identifies patient with impaired CV
function
BNP identifies patients with ischemic
burden
Preoperative BNP level strongly
associated with short-term (major
adverse cardiac events) MACE
Anesthesiology 111:311-9, 2009
313
Page21
Nt-Pro BNP in Cardiac
Surgery Patients
Is It Helpful?
Levels Associated
Need for inotropic Agents
IABP Insertion
Renal Failure
ICU Stay
Anaesth Scand 52:182-187, 2008
313
Page22
BNP
Treatment
Applications
313
Page23
Brain Natriuretic
Peptides
HEMODYNAMIC EFFECTS
Vasodilation
(preferentially acts on the venous system)
CVP
PCWP
SVR
PVR
No direct inotropic effect
313
Page24
Nesiritide Administration
in Patients with Left
Ventricular Dysfunction
Undergoing CABG
J Am Coll Cardiol 2007; 45:727-728
313
Page25
NAPA : Objectives
To explore the effects of
perioperative administration of
nesiritide on clinical outcomes
and safety in heart failure
patients undergoing cardiac
surgery
313
Page26
NAPA
Trial Design
Multi-center (54 centers)
Randomized
Double-blind
Placebo-controlled
313
Page27
NAPA
Trial Design
LV dysfunction (EF < 40%)
NYHA Class II IV
Undergoing CABG + MVS
Using cardiopulmonary
bypass
313
Page28
NAPA
Findings
Improved survival at 180 days
Improved Postop Renal Function
Greater improvement in patients
with renal dysfunction at
baseline
Decreased LOS
313
Page29
313
Page30
PULMONARY
VASODILATORS
313
Page31
Selective Pulmonary
Vasodilators
Inhaled Agents
Nitric Oxide
Nitroglycerin
Prostacyclin/Prostaglandins
PDE-III / PDE-V Inhibitors
Oral Agents (PDE-V Inhibitors)
Sildenafil
Tadalafil
313
Page32
PULMONARY VASODILATORS
CLINICAL INDICATIONS
(Inhaled)
Management of pulmonary
hypertension (acute and chronic)
Rx of right ventricle dysfunction
Challenges
Selectivity
Matching ventilation / perfusion
313
Page33
ORAL AGENTS
PDE-V
INHIBITORS
313
Page34
PDE V
Inhibitors
Primary pulmonary hypertension
Secondary pulmonary hypertension
Valvular disease
PIH
CHF
Congenital heart disease
313
Page35
PDE V
Inhibitors
Half Life
Sidenafil (4-5 hours)
Tadalafil (17.5 hours)
313
Page36
COMBINATION
THERAPY
cAMP + cGMP
313
Page37
Pulmonary
Endothelial
Cell
Guanylate Cyclase
cGMP
GTP
Relaxation
Vascular
Smooth
Muscle
Cell
NO
SNP
TNG
ACh
A232877
G
q
Ca
2+
Phospholipase C
G
i
Adenylate Cyclase
Pertussis Toxin
L-Arginine
L-Citrulline
EDRF/NO
NO Synthase
UK 14304
+
+
+
Bradykinin
313
Page38
Treatment of Pulmonary
Hypertension
New Strategies
Inhalational Agents
New Oral Agents
(PDE-V)
Combination Therapy
(cAMP + cGMP)
313
Page39
313
Page40
VASOPRESSIN
313
Page41
Dx
Vasodilatory Shock
313
Page42
Vasodilatory Shock
Components
MAP < 65 mmHg
SVR < 650 dynes/sec/cm
-5
CI > 2.5 l/min/m
2
Catecholamine resistance
313
Page43
Vasodilatory Shock
Etiology
Levels of Endogenous
AVP
313
Page44
AVP : Hemodynamic
Effects
BP
SVR
Catecholamine requirements
+ Urinary output
Caveat
Should not be used for Rx of
BP/CO unless : SVR
CI
313
Page45
VASOPLEGIC
SYNDROME
313
Page46
Preoperative Risk Factors and
Clinical Outcomes Associated
with Vasoplegia in Recipients of
Orthotopic Heart Transplantation
in the Contemporary Era
Patarroyo M, Simbaqueba C, Shrestha K,
Starling RC, et al
J Heart Lung Transplant (2011)
313
Page47
Vasoplegic Syndrome
SVR (<800 dynes)
Despite : > 2 pressors
Epinephrine > 4mcg/min
Norepi > 4 mcg/min
Dopamine > 5mcg/kg/min
Vasopressin > 1 U/hr
Preserved CI > 2.5 L/min
Time of onset 6-48 hrs after surgery
Rx : Methylene Blue (Patarroyo et al: J Heart Lung Transplant, 2011)
313
Page48
Results
(n = 348 OHTs)
11% developed vasoplegia
Risk Factors (demonstrated in previous studies)
Unos Status 1A
BSA, BMI
Preop ASA
Previous cardiac surgery
Mechanical Support
(Patarroyo et al: J Heart Lung Transplant, 2011)
313
Page49
Newly Identified Risk Factors
Hypothyroidism ( TSH, T
4
or Free T
4
)
Additional New Findings:
Inotropic support with Milrinone (preop)
Conferred protection against vasoplegia
(Patarroyo et al: J Heart Lung Transplant, 2011)
313
Page50
Thyroid
Hormone
(CPB)
313
Page51
Thyroid Hormone and
Cardiac Surgery
Impact of CPB on Thyroid Function
Low T3 Syndrome
Serum T
3
Normal T
4
and TSH
rT
3
Total serum and free T
3
levels
from 50-70% in post CPB period
Decrease persists for 1-4 days
313
Page52
Low T
3
Syndrome and
CPB
Proposed Mechanisms:
Hypothermia
Hemodilution
Activation of inflammatory
mediators
Peripheral conversion
of T
4
/ T
3
313
Page53
Clinical Studies
In High Risk Patients
Demonstrate : CO SVR
Incidence of atrial fibrillation
need for inotropic agents
in post ischemic hearts
J Thorac Cardiovasc Surg 98:972-975, 1998
Engl J Med 333:1522-1527, 1995
313
Page54
T
3
Adult Cardiac Surgery
CABG : (conflicting evidence)
May reduce need for inotropes in patients
EF<40
May have a role as part of multi modal
therapy for pts with EF
Anesth Analg 85:30-36, 1997; JAMA 275:687-692, 1996
J Thorac Cardio Vasc Surg 98:972-977, 1989
313
Page55
Role of Thyroid Hormone
Administration in Potential
Organ Donors
Following BSD: Low T
3
states
Administration of T
3
reverses hemo-
dynamic derangements
May donor pool (by vasopressor
requirements)
313
Page56
EMERGING
DRUGS
313
Page57
Emerging Drugs
Levosimendan
313
Page58
Levosimendan
Mechanisms of Action
Inotrope/vasodilator (inodilator)
Calcium sensitizing properties
Increases sensitivity of contractile proteins
to Ca
Binds calcium-dependently to cardiac
troponin-C
No change in cytosolic Ca
Opens K
ATP
Channels
313
Page59
Levosimendan
Hemodynamic Effects
CO (+ myocardial 0
2
consumption)
Peripheral vasodilation
Coronary artery dilation
+ Lusotrophic effect
LV filling pressures
No effect on PVR
Half Life 1 hour
313
Page60
Levosimendan
Early Clinical Applications
Decompensated CHF
Combination Therapy
Worsening or refractory CHF
Cardiac Surgery (EF<30%)
Eur Heart J 22:1527-1560, 2001
Anesth Analg 90:5-11, 2000
Lancet 360:196-202, 2002
313
Page61
Levosimendan in Cardiac
Surgery: A Unique Drug for the
Treatment of Perioperative Left
Ventricular Dysfunction or Just
Another Inodilator Searching for
a Clinical Application
Question:
Anesth Analg 164:766-773, 2007
Will it Result in Improved Outcomes?
313
Page62
SUMMARY
Natriuretic Peptide
Pulmonary Vasodilators
Vasopressin
Thyroid Hormone
313
Page63
SUMMARY
Emerging Drugs:
Levosimendan
? Clinical Application ?
313
Page64
313
Page65
313
Page66
402
Page 1
Delirium after Cardiac Surgery: Risk Factors and Management Strategies
Hilary P. Grocott, M.D., FRCPC, FASE Manitoba, Canada
A wide array of adverse neurologic outcomes manifest in the early postoperative period in patients having
undergone cardiac surgery. While acute stroke often presents as a dramatic catastrophe, it is thankfully an
uncommon event, with the reported incidence generally being well under 5%, highly dependent upon both patient
and procedural risk factors, and usually around 2% in the largest of studies. (1) At the other end of the
neurologic spectrum, considerable attention has been directed toward more subtle adverse outcomes, such as
postoperative cognitive dysfunction (POCD). (2) Decades of research have focused on POCD, and although this
occurs far more commonly than stroke, its precise causative relationship to cardiac surgery is, at best,
uncertain. (3) Between the dramatic and the subtle, lay other encephalopathic states, with delirium being
most notable.
Delirium is generally considered one of the most common acute neurologic consequences of cardiac
surgery yet has a reported incidence that varies widely. This large variability in incidence (from 5-80%), is
in part due to differences in the diagnostic criteria used to define it, but is also due to differences in patient
risk factors. (4-8) When it does occur, it portends significant major morbidity as well as mortality. (9,10)
Coupled with this, delirium results in a substantive increase in the utilization of healthcare resources. (11) As
a result, post-cardiac surgery delirium is a common problem of major significance impacting quality of
recovery, morbidity and mortality, as well as healthcare costs. (9,11,12) Despite its enormous significance,
unfortunately few, if any, preventative or therapeutic strategies are available to meaningfully address it.
Delirium is best characterized as a neurobehavioral syndrome resulting from an ill- defined but
fluctuating disruption of normal neural activity. It is further defined by its acute onset, altered level of
consciousness, and inattention. (13) Accurately defining delirium is of central importance, firstly to aid in the
understanding of its etiology, but also to establish clear diagnostic criteria so that there is no confusion as
to what the clinical entity encompasses. Without certainty as to what defines it, efforts cannot be
appropriately directed towards its prevention and treatment. The importance of accurately linking its
definition and diagnosis is further highlighted by the fact that although many cases of delirium present
dramatically with agitation and obvious confusion, a large number of cases are of a distinctly hypoactive
subtype.
(14) Using the criteria of new onset of disorganized thought, inattention and confusion, the contemporary
diagnosis of delirium after cardiac surgery largely rests on either objective measures such as confusion
assessment method intensive care unit (CAM-ICU) (11,15), or generically as non-specific postoperative
encephalopathy (with or without the need for treatment), which likely underestimates the incidence
considerably. (16) Formal use of the Diagnostic and Statistical Manual of Mental Disorders fourth edition
(DSM-IV) criteria have been used in various reports (17), but the utility of readily available bedside tools, such as
CAM-ICU, have substantially enhanced our ability to focus efforts on this distressing (to the patient, family
and staff) clinical entity.
The previously described wide variability in incidence (in a similar fashion to variable stroke rates),
is driven by the large variability in patient risk factors (i.e. predictors) present. Indeed, there are numerous
risk factors for delirium, but the larger cohort studies have consistently identified age, preexisting cognitive
impairment, sleep deprivation (18,19), excessive alcohol use, visual or hearing impairment, excess sedation (20),
metabolic disturbances, complexity of cardiac operation, and coexistent medical conditions as some of the most


402
Page 2
important risk factors. (19,21-23) One of the other risk factors for delirium that is receiving increasing attention is
patient frailty. A number of indices for frailty have been examined in the cardiac surgical setting and intuitively,
those patients with a high degree of frailty, who are very marginally functional with their activities of daily living
and have little physiological reserve, are at high risk for perioperative delirium. The association of delirium with
other neurologic disorders warrants specific mention. Those with pre-existing cognitive difficulties are at higher
risk for postoperative delirium, as are those with depression. Whether delirium portends longer term cognitive
dysfunction, either in an associative or causative manner, remains to be seen. Lastly, delirium is much more
common in those patients having a history of stroke, both preoperative (24) and postoperative (10).

The precise etiology and pathophysiology is incompletely defined but is likely complex and
multifactorial. (25) A number of potential contributing pathophysiologic mechanisms may precipitate and cause
delirium. Cerebral ischemia (26), physiologic stress (27), altered neurotransmitter (notably acetylcholine) levels
(28-30), inflammatory cytokines (31), and other interneural signal transduction abnormalities (32) all may
contribute. It is likely that a multiplicity of factors is responsible. (33) The complexity (and uncertainty) of its
pathophysiology has made identification of therapeutic options difficult. That said, numerous studies have
attempted to reduce the incidence and severity using both pharmacologic and nonpharmacologic approaches.
(34)

An important aspect to the preoperative considerations for delirium resides in the discussions of
postoperative expectations and should be part of every preoperative anesthetic evaluation. Although the above-
mentioned predictors highlight the various risk factors for delirium, they are often too generic to be meaningful
in preoperative discussions with patients and families. The preoperative identification of patients at risk for
delirium is important, not only for allowing careful and considerate preoperative discussion with patients and
their families regarding outcome expectations after surgery, but also to allow for the potential triage of higher
risk patients whom may be considered for potential preventive therapies. Furthermore, in identifying high risk
patients, it allows for more targeted pharmacotherapy, which themselves may have some costs and risks if used
for a non-selective population undergoing cardiac surgery. That is, if one chooses to treat delirium
prophylactically, one should do so in those who are at higher risk in order to avoid unnecessary treatment (with
all its costs and potential risks) in those who are less likely to develop

Drug therapy has largely centered on treatment rather than prevention. Indeed, haloperidol has been
the most widely used therapy for delirium. However, although it can reduce the severity and is still considered a
first line therapy, its prophylactic use has largely failed to meaningfully decrease the overall incidence. (35)
Several other pharmacologic therapies have been used with variable success. Recently, considerable focus has
been directed to the alpha-2 adrenergic agonist dexmedetomidine, as well as antipsychotics such as
risperidone. (36) Dexmedetomidine has received considerable attention for its unique ability to help
maintain restful sleep in the ICU. (22,37) Whether its main effect on reducing delirium is a unique
pharmacologic effect, or secondary to a reduction in sleep deprivation is not known. Overall, a unilateral
pharmacologic approach applied to deliriums multifactorial etiology likely contributes to the relative lack of
success with drug therapy. That is, it is unlikely that one magic bullet can address all the issues associated with
its development. Furthermore, differences between incidence and severity are important to consider. Success of
therapy may not always be seen with a reduction in incidence, instead impacting the severity of symptoms.

Prevention, or at the very least, anticipation of whom it may affect should always be considered.
Proactive geriatric consultation may be beneficial, as would consideration for the various risk factors. For
example, minimizing the sensory deprivation by providing hearing aids and glasses early in the postoperative
course will help. Recently, the impact of the physical structure of the ICU was identified as a potential
means to reduce delirium when ICUs are designed. An age specific effect was identified in a recent large
(n=1200) observational study.
(45) In this study, an ICU that maximized natural light and minimized noise pollution appeared to reduce the
incidence of delirium.

Intuitively, it would make sense that direct monitoring of the brain might have a role in detecting or
mitigating this brain disease. Indeed, processed electroencephalography (EEG; BIS) and near infrared
spectroscopy (NIRS) cerebral oximetry have been examined with interesting results. The use of NIRS cerebral
oximetry has repeatedly demonstrated a relationship between cerebral desaturation and severe neurologic


402
Page 3
outcomes. Murkin et al first demonstrated an effect at potentially reducing stroke. (38) Slater also showed an
increase in POCD in patients with prolonged cerebral desaturation. (39) Colak et al reported a similar
relationship between adverse neurologic outcomes and desaturation. (40) Schoen et al identified those patients
with lower baseline cerebral saturations were at much higher risk of developing delirium after cardiac
surgery. (41,42) Whether this indicates that cerebral desaturation (indicative of cerebral ischemia) is at the root
cause of delirium remains unknown. There have been no interventional studies using NIRS-guided strategies to
reduce delirium. Although BIS likely has less granularity in being able to discriminate between those with or
without risk of delirium, it has also seen some interesting investigations. Chan et al reported a relationship
between low BIS and delirium in a randomized trial of 921 elderly patients undergoing major non-cardiac
surgery who had either standard of care or a BIS guided anesthetic (with a target of 40-60). The BIS guided
group had significant reduction in delirium (15.6% vs. 24.1%, P=0.01). (44) Cerebral monitoring continues to
be a ripe area for future research.

In summary, delirium after cardiac surgery is a common multifactorial problem with numerous risk
factors identified. It is a highly significant postoperative problem that reduces quality of recovery, increases
morbidity and mortality, and incurs significant additional healthcare costs. Although no therapies have
definitively demonstrated a reduction in this complication, significant advancements have been made as the
problem is being redefined and appropriately targeted with both pharmacologic and nonpharmacologic
therapies. Continued research will be driven by a better understanding of its pathophysiology with continued
efforts also focusing on dynamic brain monitoring.

References
1. Newman MF, Mathew JP, Grocott HP, Mackensen GB, Monk T, Welsh-Bohmer KA, Blumenthal
JA, Laskowitz DT, Mark DB. Central nervous system injury associated with cardiac surgery. Lancet
2006;368:694-703.
2. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG,
Blumenthal JA. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.
N Engl J Med 2001;344:395-402.
3. Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and
neurologic outcomes after coronary-artery bypass surgery. N Engl J Med 2012;366:250-7.
4. Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and
the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009;50:206-17.
5. Sockalingam S, Parekh N, Bogoch, II, Sun J, Mahtani R, Beach C, Bollegalla N, Turzanski S, Seto E,
Kim J, Dulay P, Scarrow S, Bhalerao S. Delirium in the postoperative cardiac patient: a review. J Card
Surg 2005;20:560-7.
6. Tan MC, Felde A, Kuskowski M, Ward H, Kelly RF, Adabag AS, Dysken M. Incidence and predictors
of post-cardiotomy delirium. Am J Geriatr Psychiatry 2008;16:575-83.
7. Santos FS, Velasco IT, Fraguas R, Jr. Risk factors for delirium in the elderly after coronary
artery bypass graft surgery. Int Psychogeriatr 2004;16:175-93.
8. van der Mast RC, Roest FH. Delirium after cardiac surgery: a critical review. J Psychosom Res
1996;41:13-30.
9. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr., Inouye SK, Bernard GR,
Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care
unit. JAMA 2004;291:1753-62.
10. Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Selnes OA, McKhann
GM. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol 2010;67:338-
44.
11. Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR,
Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med
2004;32:955-62.
12. Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R,
Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive
Care Med 2001;27:1892-900.
13. Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care


402
Page 4
Clin 2008;24:657-722, vii.
Meagher DJ, O'Hanlon D, O'Mahony E, Casey PR, Trzepacz PT. Relationship between symptoms and
motoric subtype of delirium. J Neuropsychiatry Clin Neurosci 2000;12:51- 6.
14. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S,
Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of
the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-10.
15. Martin BJ, Buth KJ, Arora RC, Baskett RJ. Delirium: a cause for concern beyond the immediate
postoperative period. Ann Thorac Surg 2012;93:1114-20.
16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM IV,
Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000.
17. Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of
sleep in nine patients receiving postoperative care. Br Med J (Clin Res Ed) 1985;290:1029-32.
18. Weinhouse GL, Schwab RJ. Sleep in the critically ill patient. Sleep 2006;29:707-16.
19. Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A. Association between psychoactive
medications and delirium in hospitalized patients: a critical review. Psychosomatics 2005;46:302-16.
20. Maldonado JR. Pathoetiological model of delirium: a comprehensive understanding of the
neurobiology of delirium and an evidence-based approach to prevention and treatment. Crit Care Clin
2008;24:789-856, ix.
21. Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium
with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized
controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology
2009;111:1075-84.
22. Koster S, Oosterveld FG, Hensens AG, Wijma A, van der Palen J. Delirium after cardiac surgery and
predictive validity of a risk checklist. Ann Thorac Surg 2008;86:1883-7.
23. Lin Y, Chen J, Wang Z. Meta-analysis of factors which influence delirium following cardiac
surgery. J Card Surg 2012;27:481-92.
24. Chaput AJ, Bryson GL. Postoperative delirium: risk factors and management: continuing professional
development. Can J Anaesth 2012;59:304-20.
25. Seaman JS, Schillerstrom J, Carroll D, Brown TM. Impaired oxidative metabolism precipitates delirium:
a study of 101 ICU patients. Psychosomatics 2006;47:56-61.
26. Kalman J, Juhasz A, Bogats G, Babik B, Rimanoczy A, Janka Z, Penke B, Palotas A. Elevated
levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are
predictors of cognitive decline. Neurochem Int 2006;48:177-80.
27. Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium
in surgical patients. Am J Psychiatry 1987;144:1218-20.
28. Flacker JM, Cummings V, Mach JR, Jr., Bettin K, Kiely DK, Wei J. The association of serum
anticholinergic activity with delirium in elderly medical patients. Am J Geriatr Psychiatry 1998;6:31-
41.
29. Mach JR, Jr., Dysken MW, Kuskowski M, Richelson E, Holden L, Jilk KM. Serum
anticholinergic activity in hospitalized older persons with delirium: a preliminary study. J Am Geriatr Soc
1995;43:491-5.
de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J
Psychosom Res 2007;62:521-5.
30. van der Mast RC. Pathophysiology of delirium. J Geriatr Psychiatry Neurol 1998;11:138-
45; discussion 57-8.
31. Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-65.
32. Cavaliere F, D'Ambrosio F, Volpe C, Masieri S. Postoperative delirium. Curr Drug Targets
2005;6:807-14.
33. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van
Gool WA. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized
placebo-controlled study. J Am Geriatr Soc 2005;53:1658-66.
34. Raiten JM, Gutsche JT. Use of risperidone in cardiac surgery patients with subsyndromal delirium.


402
Page 5
Anesthesiology 2012;117:1141; author reply -3.
35. Ji F, Li Z, Nguyen H, Young N, Shi P, Fleming N, Liu H. Perioperative dexmedetomidine improves
outcomes of cardiac surgery. Circulation 2013;127:1576-84.
36. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B,
Irwin B, Fox S. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized,
prospective study. Anesth Analg 2007;104:51-8.
37. Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM, 3rd, Rodriguez AL, Magovern CJ,
Zaubler T, Freundlich K, Parr GV. Cerebral oxygen desaturation predicts cognitive decline and longer
hospital stay after cardiac surgery. Ann Thorac Surg 2009;87:36-44.
38. Colak Z, Borojevic M, Ivancan V, Gabelica R, Biocina B, Majeric-Kogler V. The relationship between
prolonged cerebral oxygen desaturation and postoperative outcome in patients undergoing coronary
artery bypass grafting. Coll Antropol;36:381-8.
39. Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU. Preoperative regional
cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients:
a prospective observational trial. Crit Care 2011;15:R218.
40. Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue CW. Cerebral near-infrared spectroscopy
monitoring and neurologic outcomes in adult cardiac surgery patients: a systematic review. Anesth
Analg 2013;116:663-76.
41. Hughes CG, Morandi A, Girard TD, Riedel B, Thompson JL, Shintani AK, Pun BT, Ely EW,
Pandharipande PP. Association between endothelial dysfunction and acute brain dysfunction during
critical illness. Anesthesiology 2013;118:631-9.
42. Chan MT, Cheng BC, Lee TM, Gin T. BIS-guided anesthesia decreases postoperative delirium and
cognitive decline. J Neurosurg Anesthesiol 2013;25:33-42.
43. Arenson BG, MacDonald LA, Grocott HP, Hiebert BM, Arora RC. Effect of intensive care unit
environment on in-hospital delirium after cardiac surgery. J Thorac Cardiovasc Surg 2013;(in press).

Disclosure
414
Page 1
Figure 1: Starling Equation describing the movement of fluid across a capillary
Synthetic Colloids in Cardiac Surgery: What are the Indications?
Roman M. Sniecinski, M.D. Atlanta, Georgia
Introduction
In the early days of cardiac surgery, large priming volumes were required for cardiopulmonary bypass (CPB)
circuits and, as a result, blood was almost universally used. As the circuits became more refined and the perfusion
benefits of hemodilution became embraced, (1) crystalloid solutions began to replace blood for priming purposes.(2)
Myocardial edema, however, became recognized as a problem with crystalloid CPB primes.(3) Around the same
time, following the Vietnam War, there was an interest in decreasing the amount of crystalloid administered to
trauma patients in order to decrease tissue edema resulting from large volume resuscitations.(4) It was demonstrated
that colloids were able to produce a greater plasma volume expansion with less volume administered, thus more
rapidly restoring plasma volume and potentially leading to less fluid accumulation in the lung and interstitial
space.(5) These observations have guided the resulting search for the ideal fluid for CPB priming, as well as for
resuscitation commonly required in cardiac surgical patients.
Basic Principles
The Starling Equation summarizes the exchange of fluid across the capillary wall (Figure 1).(6) Hydrostatic forces
fall across the capillary from
about 30 mmHg at the
arterial end to about 15
mmHg at the venous end. It
becomes obvious from the
Starling Equation, that the
higher the capillary (i.e.
intravascular) osmotic
pressure, the less fluid will
migrate into the interstitium.
The colloid osmotic pressure
(COP) is a function of the
number of molecules
exerting an effect, so
colloids are additive. The
COP of blood is essentially
that of plasma, since large
molecules such as platelets
and red blood cells are
relatively few in number
compared to other protein
molecules such as albumin.
The initial volume effect of colloids will be greater than an equal volume of administered crystalloid since more of
the fluid will be retained in the intravascular space. It is important to keep in mind, however, that different capillary
beds will allow the movement of colloid molecules into the interstitium to varying degrees. The typical reflection
coefficient (!) for systemic capillaries is about 0.95, while it is about 0.7 in the pulmonary beds.(7) Inflammation
and trauma will further decrease these reflection values.

414
Page 2
Types of Synthetic Colloids
There are three types of synthetic colloids in clinical use: gelatins, dextrans, and hydroxyethyl starches. While all
will raise COP, they vary in their molecular weight and pharmacological profiles. Unlike human albumin, which is
considered a monodisperse colloid, the synthetic colloids are polydisperse. This means that the molecules within
any given solution will range significantly in size. Lower molecular weight molecules will exert a greater oncotic
effect with lower viscosity since there will be a greater number of them. However, the larger molecular weight
molecules will persist longer before being filtered at the glomerulus or lost to the interstitium. A comparison of
volume effects for common fluids is provided in Table 1.

Gelatins are prepared from bovine collagen by first submersing it in alkali and boiling water, then cross-linking the
subunits with either hexamethyl di-isocyanate (urea-linked gelatin) or succinyl anhydride (succinylated gelatin).(8)
Of the synthetic colloids, gelatins have the smallest molecular weight, about 30 35 kiloDaltons (kD) and are
readily filtered at the glomerulus, providing only 2-3 hours of volume expansion.(9)

Dextran is a branched polysaccharide derived from the action of Leuconostic mesenteroides bacteria on sucrose.
The major derivations in clinical use are Dextran-40 and Dextran-70, having molecular weights of 40 kD and 70 kD
respectively. Both dextrans have the propensity to coat blood cells and the endothelium, reducing their interactions
and promoting peripheral blood flow. The duration of volume expansion for Dextran-40 is about 3-4 hours, and
about 5 hours for the larger Dextran-70.(10) Deserved or not, dextrans had the reputation for causing more
anaphylactic reactions compared to the other synthetic colloids. This has largely been overcome by the current
practice of pre-treatment with Dextran-1, which acts as a hapten inhibitor to existing antibodies.(11)

Hydroxyethyl starches (HES) are derived from amylopectin that has hydroxyethyl residues attached to the
anhydrous glucose molecules within the polymer. The degree of substitution determines how easily amylase can
break down the starch.(12) Hetastarch refers to a degree of substitution of about 0.7, and is less easily
metabolized than pentastarch (degree of substitution of 0.5) or tetrastarch (degree of substitution of 0.4). The
duration of plasma expansion varies significantly among HES solutions and is more dependent on the degree of
substitution and where the hydroxyethyl groups are located than on the molecular weight.(13) Difficulty in clearing
highly substituted HES can lead to persistence in the tissues resulting in prolonged pruritis.(14)

Table1: Summary of Various Agents Volume Expansion Effects (adapted from (9),(12))
Agent Initial Volume Effect
(plasma expansion for infused volume)
Duration of Volume Effect
(in healthy volunteers)
5% glucose in water 6.7%
0.9% saline crystalloid 20%
Gelatin
3.5% urea or 4% succinylated
70 90% 2-3 hours
3.5% Dextran-40 100% 3-4 hours
6% Dextran-70 120% 5 hours
HES 6% 450/0.7 100% 6-12 hours*
HES 6% 200/0.5 100% 3.5 9 hours*
HES 6% 130/0.4 100% 4-6 hours*
* HES pharmacokinetics are complex and will vary depending upon where hydroxyethyl groups are located

Adverse Effects of Synthetic Colloids
All colloids can lead to fluid overload and can also result in significant hemodilution. Of particular interest in
cardiac surgery, however, are the potential adverse effects synthetic colloids can have on both renal function and the
coagulation system.

While low kidney perfusion is clearly a risk factor for renal failure, it has been known for many years that high
plasma oncotic pressure can be detrimental as well.(15) Colloid-induced kidney injury has been reported for all
synthetic colloids, although the mechanism is not well understood.(16) Possibilities include macromolecules being
absorbed by the renal tubular cells leading to osmotic nephrotic lesions, or hyperviscous urine causing sludging
within the tubules.(17,18) Of the synthetic colloids, HES has undergone the most scrutiny. A recent meta-analysis
including more than 8700 patients, and excluding all potentially tainted studies (i.e. those from J. Boldt, found guilty

414
Page 3
of scientific misconduct), reported an increased risk of acute kidney failure for all types of HES administration.(19)
With the lowest molecular weight among the synthetic colloids, gelatin may be the least nephrotoxic, although there
are few published studies to validate its safety in this regard.(20)

Von Willebrand Factor (vWF) is involved in platelet adhesion to damaged vessel walls. All synthetic colloids share
the property of decreasing vWF levels, and can thus impair coagulation.(21) This observation lead to the 2003 FDA
warning on Hespan (6% hetastarch in normal saline): Not recommended for use as a CPB pump prime while the
patient is on CPB or in the immediate post-CPB period because of the risk of increasing coagulation abnormalities
and bleeding in patients whose coagulation status is already impaired. Coagulation impairment by HES seems to
be dose dependent, and may be less of an issue with lower molecular weight agents with less degree of substitution.
Gelatins, once thought to have very little effect on coagulation, have been shown to impair clot formation via
ROTEM parameters to the same degree as HES.(22) Dextrans, often used in vascular or plastic surgery for their
anti-thrombotic effects, additionally enhance fibrinolysis.(23)

Current Use of Synthetic Colloids in Cardiac Surgery
Early studies in cardiac surgical patients demonstrated a decrease in COP of about 50% upon initiation of CPB with
a crystalloid prime.(24) As a result, some experts advocated the use of colloids in the pump prime to lessen this
dilution.(25) There have been numerous studies published over the past 2 decades comparing the synthetic colloids
to both crystalloid and albumin for purposes of priming the CPB circuit without a clear-cut winner. It is not
surprising that surveys have shown a wide variety of practice patterns in this regard.(26) In truth, the CPB prime
fluid is likely much less important in modern systems since the volume required is now more on the order of 1 1.5
liters versus 2 2.5 L. Additionally, with the technique of retrograde autologous priming, the patient may
experience an initial volume load of <500 ml upon CPB institution.

The agent of choice for fluid resuscitation also varies widely among centers and countries.(27) The crystalloid
versus colloid debate in critical care medicine has raged on for decades. The 2004 SAFE study, which compared the
natural colloid albumin to normal saline for fluid resuscitation, found no difference in any key clinical outcomes
between the two fluids.(28) However, the study specifically excluded cardiac surgical patients, a common problem
with most of the recent fluid trials (see Table 2). The most recent meta-analysis from the Cochrane Collaboration
showed no benefit of any colloid, be it gelatin, dextran, or HES, compared to crystalloid solutions in fluid
resuscitation.(29) It is currently not known whether results of these general ICU trials should be applied to cardiac
surgical patients.

Table 2: ICU Fluid Trials Published in 2012
Clinical Trial Study Population Major Finding
CRYSTMAS study(30)
6% HES 130/0.4 vs NS
196 ICU patients
(27% surgical)
" volume needed in HES group with no
difference in ARF or 90 day mortality
6S trial(31)
6% HES 130/0.42 vs LR
798 ICU patients
(29% surgical)
# risk of death at 90 days and # need for
RRT in HES group
CHEST trial(32)
6% HES 130/0.4 vs NS
6742 ICU patients
(42% surgical)
No difference in 90 day mortality, but #
use of RRT in HES group
HES=hydroxyethyl starch; NS=normal saline; LR=lactated Ringers; RRT=renal replacement therapy

Perhaps the most relevant recent study was a small pilot published in 2010 by Magder et al, which compared 10%
HES 250/0.5 to normal saline in post cardiac surgical patients.(33) Using a PA catheter-based algorithm, the
authors demonstrated quicker weaning of catecholamine support, less need for pacing, and fewer infection in the
HES group with no increase in kidney injury. The HES group did, however, require a statistically significant greater
amount of plasma.

In conclusion, the indications for synthetic colloids in cardiac surgery remain unclear. Until large scale clinical
trials specifically aimed at this patient population are undertaken, use of synthetic colloids will likely remain a
matter of preference. What is probably more important, however, is avoiding the over-use of fluid therapy. It has
recently been shown that a 10% fluid overload in cardiac surgical patients is independently associated with
mortality.(34) So rather than debate the proposed benefits or colloids or crystalloids, the bigger challenge is likely
finding out how to judiciously use both of them.

414
Page 4
References

1. Greer AE, Carey JM, Zuhdi N. Hemodilution principle of hypothermic perfusion. A concept obviating
blood priming. The Journal of thoracic and cardiovascular surgery 1962;43:640-8.
2. Verska JJ, Ludington LG, Brewer LA, 3rd. A comparative study of cardiopulmonary bypass with nonblood
and blood prime. The Annals of thoracic surgery 1974;18:72-80.
3. Foglia RP, Lazar HL, Steed DL, Follette DM, Manganaro AJ, Deland E, Buckberg GD. Iatrogenic
myocardial edema with crystalloid primes: effects on left ventricular compliance, performance, and
perfusion. Surgical forum 1978;29:312-5.
4. Santry HP, Alam HB. Fluid resuscitation: past, present, and the future. Shock 2010;33:229-41.
5. Haupt MT, Rackow EC. Colloid osmotic pressure and fluid resuscitation with hetastarch, albumin, and
saline solutions. Critical care medicine 1982;10:159-62.
6. Salmon JB, Mythen MG. Pharmacology and physiology of colloids. Blood reviews 1993;7:114-20.
7. Taylor AE. Capillary fluid filtration. Starling forces and lymph flow. Circulation research 1981;49:557-75.
8. Saddler JM, Horsey PJ. The new generation gelatins. A review of their history, manufacture and properties.
Anaesthesia 1987;42:998-1004.
9. Lange M, Ertmer C, Van Aken H, Westphal M. Intravascular volume therapy with colloids in cardiac
surgery. Journal of cardiothoracic and vascular anesthesia 2011;25:847-55.
10. Niemi TT, Miyashita R, Yamakage M. Colloid solutions: a clinical update. Journal of anesthesia
2010;24:913-25.
11. Ljungstrom KG. Dextran 40 therapy made safer by pretreatment with dextran 1. Plastic and reconstructive
surgery 2007;120:337-40.
12. Jungheinrich C, Neff TA. Pharmacokinetics of hydroxyethyl starch. Clinical pharmacokinetics
2005;44:681-99.
13. Westphal M, James MF, Kozek-Langenecker S, Stocker R, Guidet B, Van Aken H. Hydroxyethyl starches:
different products--different effects. Anesthesiology 2009;111:187-202.
14. Bork K. Pruritus precipitated by hydroxyethyl starch: a review. The British journal of dermatology
2005;152:3-12.
15. Moran M, Kapsner C. Acute renal failure associated with elevated plasma oncotic pressure. The New
England journal of medicine 1987;317:150-3.
16. Davidson IJ. Renal impact of fluid management with colloids: a comparative review. European journal of
anaesthesiology 2006;23:721-38.
17. Hartog CS, Bauer M, Reinhart K. The efficacy and safety of colloid resuscitation in the critically ill.
Anesthesia and analgesia 2011;112:156-64.
18. Schortgen F, Brochard L. Colloid-induced kidney injury: experimental evidence may help to understand
mechanisms. Crit Care 2009;13:130.
19. Zarychanski R, Abou-Setta AM, Turgeon AF, Houston BL, McIntyre L, Marshall JC, Fergusson DA.
Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill
patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA : the journal of the
American Medical Association 2013;309:678-88.
20. Thomas-Rueddel DO, Vlasakov V, Reinhart K, Jaeschke R, Rueddel H, Hutagalung R, Stacke A, Hartog
CS. Safety of gelatin for volume resuscitation--a systematic review and meta-analysis. Intensive care
medicine 2012;38:1134-42.
21. de Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation: a comparative review.
Critical care medicine 2001;29:1261-7.
22. Schramko A, Suojaranta-Ylinen R, Kuitunen A, Raivio P, Kukkonen S, Niemi T. Hydroxyethylstarch and
gelatin solutions impair blood coagulation after cardiac surgery: a prospective randomized trial. British
journal of anaesthesia 2010;104:691-7.
23. Eriksson M, Saldeen T. Effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen
activator inhibitor-1 (PAI-1) during surgery. Acta anaesthesiologica Scandinavica 1995;39:163-6.
24. Yeoman PM, Vence-Pastor DE, Rithalia SV. Changes in colloid osmotic pressure in patients undergoing
cardiothoracic surgery. Resuscitation 1981;9:307-13.
25. London MJ. Pro: colloids should be added to the pump prime. Journal of cardiothoracic anesthesia
1990;4:401-5.
26. Lilley A. The selection of priming fluids for cardiopulmonary bypass in the UK and Ireland. Perfusion
2002;17:315-9.

414
Page 5
27. Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J. Resuscitation
fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care
2010;14:R185.
28. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for
fluid resuscitation in the intensive care unit. The New England journal of medicine 2004;350:2247-56.
29. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients.
Cochrane Database Syst Rev 2013;2:CD000567.
30. Guidet B, Martinet O, Boulain T, Philippart F, Poussel JF, Maizel J, Forceville X, Feissel M, Hasselmann
M, Heininger A, Van Aken H. Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch
130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study. Crit Care
2012;16:R94.
31. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH,
Elkjaer JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Soe-Jensen P, Bestle M,
Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K,
Kjaeldgaard AL, Fabritius ML, Mondrup F, Pott FC, Moller TP, Winkel P, Wetterslev J. Hydroxyethyl
starch 130/0.42 versus Ringer's acetate in severe sepsis. The New England journal of medicine
2012;367:124-34.
32. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C,
McGuinness S, Rajbhandari D, Taylor CB, Webb SA. Hydroxyethyl starch or saline for fluid resuscitation
in intensive care. The New England journal of medicine 2012;367:1901-11.
33. Magder S, Potter BJ, Varennes BD, Doucette S, Fergusson D. Fluids after cardiac surgery: a pilot study of
the use of colloids versus crystalloids. Critical care medicine 2010;38:2117-24.
34. Stein A, de Souza LV, Belettini CR, Menegazzo WR, Viegas JR, Costa Pereira EM, Eick R, Araujo L,
Consolim-Colombo F, Irigoyen MC. Fluid overload and changes in serum creatinine after cardiac surgery:
predictors of mortality and longer intensive care stay. A prospective cohort study. Crit Care 2012;16:R99.

Disclosure
Acute Care Medical Education, Self, Honoraria

420
Page 1
Strategies for Blood Conservation in Cardiovascular Surgery Patients
Linda Shore-Lesserson MD, FASE New Hyde Park, NY, USA
Introduction
The hematologic management of the cardiac surgical patient entails a complex balance between extreme degrees of
anticoagulation and the restoration of normal hemostasis after the procedure. These two opposing processes must
be managed carefully and modified with respect to preoperative disease state, duration of cardiac surgery, use of
extracorporeal circulation, and the desired hemostatic outcome. During cardiopulmonary bypass (CPB), optimal
anticoagulation dictates that microvascular coagulation and platelet activation and minimal so that coagulation,
fibrinolytic, and inflammatory cascades are not activated. However, the large increase in interventional cardiology
procedures to treat coronary artery disease (stents, lasers, etc.) have made anticoagulation and anti-thrombotic a
mainstay of the medical treatment of cardiovascular patients. The increase in heparin exposure has heightened our
awareness of heparin resistance and heparin-induced thrombocytopenia.
Uncontrolled hemorrhage has been anecdotally treated with success using activated Factor VII, yet the
safety of this agent has not been confirmed in large scale trials. This has caused an increase in the use of other
prothrombin complex concentrates throughout the world. The increased complexity of the cardiac surgery
population has made the treatment of hemorrhage an area of research for new pro-coagulant therapies. This
complex hemostatic picture is coupled with the concurrent use of anti-thrombotic medication in the cardiovascular
patient in both the preoperative and the postoperative periods. The frequent and prevalent use of multiple anti-
platelet medications is of great concern to the cardiovascular anesthesiologist due to increased bleeding and
increased bleeding-related complications after surgery. Monitoring the anti-platelet effects of these agents may help
to prevent, or at least predict patients who are at risk for hemorrhagic complications after CPB.
Heparin Resistance and Antithrombin
Heparin resistance is marked by the inability to raise the activated clotting time (ACT) to therapeutic levels after the
administration of heparin. Acquired resistance to heparin occurs in patients who have been treated with heparin.
I

These patients were initially responsive to heparin as evidenced by an elevated ACT, but with continued treatment
with heparin, resistance, or altered responsiveness to its anticoagulant effects occurs. Patients on preoperative
heparin therapy traditionally require larger heparin doses to achieve a given level of anticoagulation. Possible
etiologies for this resistance include antithrombin III (AT) depletion, enhanced factor VIII activity, platelet
activation, or any combination of these factors.
Heparin is known to activate platelets which will shorten ACT values. Data now suggest that LMWH also
contributes to platelet activation and heparin resistance.
II
Non-responsiveness to heparin can be due to a congenital
deficiency or abnormality of the activity of AT. In congenital states, the only way to elicit a response to heparin
therapy is to administer exogenous AT, either in the form of plasma or a factor concentrate. In vitro addition of AT
enhances the ACT response to heparin. Further, low levels of AT are associated with negative outcomes in cardiac
surgery.
III
This has led to the STS/SCA Blood Conservation Guidelines Class IA recommendation to use
ATsupplementation in patients demonstrating heparin resistance.
IV
But it is unclear if a low AT level portends
adverse outcomes because of the diminished anticoagulant response to heparin, or because it serves as a marker
for a patient with a more advanced risk profile (on preoperative heparin). The true heparin requirement during CPB
in patients with altered heparin responsiveness is not yet known since it is not known if a certain ACT or AT level is
necessary to ensure safe outcomes.
V,VI,VII
The administration of fresh frozen plasma as a source of AT for heparin
resistance is not recommended due to the risks of allogeneic transfusion of blood products. AT concentrate is
available as a heat-treated concentrate or as a recombinant formulation. Neither formulation is approved for use in
acquired heparin resistance in CPB and thus it is being used off-label for this purpose. Prospective studies have
shown that exogenous AT improves anticoagulation, minimizes the activation of the coagulation system, and
reduces heparin resistance, all of which could potentially lead to improved cardiovascular outcomes.
VIII
Though this

420
Page 2
has not been demonstrated in randomized prosopective trials. Exogenous AT in cardiac surgery has also been
shown to result in an increase in postoperative bleeding in patients receiving large doses or doses set to achieve AT
levels higher than 100%.
IX
Thus its benefit/risk profile has not been fully elucidated.
X

Heparin Induced Thrombocytopenia Syndrome (HIT, HITS)
The syndrome known as HITS develops in anywhere from 5% to 28% of patients receiving heparin. There is a
general reduction in platelet count due to platelet membrane increased adhesiveness that occurs when platelets are
exposed to heparin. This is a benign situation and is characterized by an early and mild decrease in platelet count.
HITS or HIT is a pathologic condition that most often occurs after more than 5 days of heparin administration
(average onset time, 9 days), and is mediated by antibody binding to the complex formed between heparin and
platelet factor 4 (PF4).
XI
Among patients developing HIT, the incidence of thrombotic complications approximates
20%, which in turn may carry a mortality rate as high as 40%. A highly specific enzyme-linked immunosorbent
assay for the heparin/PF4 complex has been used to delineate the course of IgG and IgM antibody responses in
patients exposed to unfractionated heparin during cardiac surgery. Bedside antibody tests that utilize ELISA
techniques or particle gel immunoassays have been introduced but these do not have the sensitivity of the standard
ELISA. Although bedside tests may speed the diagnosis of HIT and allow functional testing to be performed more
rapidly. During testing for HIT, heparin therapy should be discontinued and an alternative anticoagulant begun.
The agents most commonly chosen as heparin alternatives are the direct thrombin inhibitors, discussed later.

Demonstration of heparin-induced proaggregation of platelets confirms the diagnosis of HIT. This can be
accomplished with a heparin-induced serotonin release assay, or a specific heparin-induced platelet activation assay.
The risks and appropriate courses of action in patients with HIT are unclear because the antibodies associated with
heparin-induced thrombocytopenia often become undetectable several weeks after discontinuing heparin. Also the
clinical syndrome does not always recur upon reexposure to the drug and sometimes resolves despite continued drug
therapy. Many patients never develop thrombosis and disseminated intravascular coagulation despite positive
laboratory testing. Heparin-induced thrombocytopenia should possibly be considered in the differential diagnosis of
intraoperative heparin resistance in patients receiving preoperative heparin therapy. The options for treating these
patients are few. If one has the luxury of being able to discontinue the heparin for a few weeks, often the antibody
will disappear and allow a brief period of heparinization for CPB without complication.
XII
Supplementing heparin
administration with pharmacologic platelet inhibition using prostacyclin, iloprost, or tirofiban have been reported,
all with favorable outcomes.
XIII
Plasmapheresis may be used to reduce antibody levels. The use of heparin could be
avoided altogether by using a direct thrombin inhibitor as the anticoagulant.

Direct Thrombin Inhibitors (DTIs)
Hirudin is a coagulation inhibitor isolated from the salivary glands of the medicinal leech (Hirudo medicinalis), and is a
potent inhibitor of thrombin. Currently available via recombinant genetics (Lepirudin), this substance is a polypeptide
(molecular weight of approximately 7,000 Daltons). The aPTT prolongation correlates well with plasma hirudin
concentrations but does not correlate well with chromogenic antifactor II levels. For this reason, a surrogate APTT using
the snake venom ecarin for activation has been described.
XIV
Platelet aggregation is also better preserved with hirudin
than with heparin. Hirudin does not activate platelets nearly as much as unfractionated heparin does. This property of
direct thrombin inhibitors makes it more bio-friendly than unfractionated heparin and is partly responsible for the
enhanced anti-ischemic effects seen relative to heparin in coronary intervention patients. In addition, the smaller
molecular size enables greater inhibition of thrombin bound to fibrin. Using direct thrombin inhibitors preserves platelet
activity and reduces release of platelet activation markers as compared to unfractionated heparin. And finally another
major advantage with DTIs is that AT is not required.

Comparison of DTIs to unfractionated heparin can be found in
the Table.
The use of direct thrombin inhibitors in medical treatment or prevention of thrombosis has increased recently
with the introduction of dabigatran for use in atrial fibrillation. Reversal of these agents is difficult as there is no specific
antidote drug such as protamine is for heparin. It has not yet been established that patients presenting for cardiac surgery
having ingested DTIs pose a greater bleeding risk for post-CPB bypass. This may be a result of there not being a large
enough sample size or experience with these drugs in outpatient settings. However, the known platelet protective effects
of the DTIs may be a benefit and may enhance anticoagulation and suppress activation of fibrinoysis during CPB and
thus make bleeding less likely. A description of some of the common DTIs follows.

420
Page 3
!"#$% '%(")*+ ,*)%-. !/)01#*+ 2+/*#*.0)3
405% 06 "-.*0+ 2+5*)%-. ,*)%-.
7"."$83. +%%5%5 9%3: "+.*:./)01#*+ ; <0
2+/*#*.3 -$0.:#0=+5 ./)01#*+ <0 9%3
>-.*?".%3 ($".%$%.3 9%3 @A4B' 105%)".%$8 8%3C <0
>+.*D%+*-*.8 9%3 <0 @#*?"$*)=5*+C 9%3 @/*)=5*+C
>+.*50.% 5)=D 9%3: ()0."1*+% <0

Bivalirudin is a synthetic peptide formerly known as Hirulog and currently marketed as Angiomax (The
Medicines Company, Parsippany, NJ, USA). A bivalent thrombin inhibitor, bivalirudin consists of one moiety that binds
thrombin on its activesite cleft, and a second hirudin-like C-terminal region that binds thrombin at its positively charged
surface groove known as the anion-binding exosite. Bivalirudin is a synthetic derivative of hirudin and thus acts as a
direct thrombin inhibitor. Thrombin itself cleaves the part of the bivalirudin molecule that binds to it, so bivalirudin
activity elimination is independent of specific organ metabolism. Bivalirudin has been used successfully as an
anticoagulant in interventional cardiology procedures as a replacement for heparin. In fact, in interventional cardiology,
bivalirudin has been associated with less bleeding and equivalent ischemic outcomes when compared to heparin plus a
platelet inhibitor. Bivalirudin anticoagulation induces less P-selectin expression than do either unfractionated or low
molecular weight heparin (LMWH), indicating less platelet reactivity and possibly platelet protection. In off-pump
coronary artery bypass surgery, Merry et al. found equivalent bleeding outcomes with bivalirudin and heparin, and the
bivalirudin patients exhibited higher graft flows.
XV
A prospective randomized trial in 150 patients undergoing CPB
surgery demonstrated similar procedural outcomes and adverse event rates with bivalirudin and heparin.
XVI
This CPB
trial dosed bivalirudin at 1 mg/kg as in intravenous bolus followed by 2.5 mg/kg/hr as in infusion. When bivalirudin is
used, care must be exercised to ensure the absence of stasis in the CPB circuit lest thrombin be formed and metabolize
bivalirudin.
Desirudin, a new injectable direct thrombin inhibitor is now available for subcutaneous injection in patients
who cannot receive heparin. New oral direct thrombin inhibitors such as dagibatran etexilate are also in the commercial
market as replacements for warfarin in the treatment of patients with atrial fibrillation.
Monitoring the direct thrombin inhibitors is one of the current challenges in the use of these agents. The ecarin
clotting time better correlates with anti-IIa activity and plasma drug concentrations than does the ACT, and it is available
using the Cascade POC Testing Device (Helena Inc, Beaumont TX). Modified ACT (1 to 1 dilution of patient blood
with FFP) and the standard ACT have also been used safely to monitor the anticoagulant effects of bivalirudin. In
multicenter clinical trials using bivalirudin during CPB, an ACT of two and one half times the baseline value was
accepted as therapeutic.
Argatroban (MW 527 Daltons) is a synthetic derivative of arginine that inhibits thrombin by binding only
to its catalytic site. It is approved for use as an alternative anticoagulant to heparin for patients with HIT and it is
frequently the drug of choice for the treatment of medical (non-surgical) patients who cannot receive heparin. Like
hirudin and bivalirudin (and unlike heparin), argatroban inhibits both circulating and fibrin-bound thrombin. The
plasma elimination half-life is approximately 40 minutes, and the agent is metabolized by the liver with biliary
elimination. Thus, argatroban offers appeal in patients with severe renal insufficiency or renal failure. Argatroban
anticoagulation for CPB is initiated (with or without a loading dose) with a bolus of 0.1-0.2 mg/kg followed by an
intravenous infusion at 5-10 !g/kg/min (less if there is hepatic insufficiency), and the dose is then adjusted to
maintain the aPTT 1.5 3 times normal. The ACT may also be used to guide therapy, in which case the optimal
ACT level appears to be 300-400 seconds.
Argatroban has been used safely as a heparin substitute for CPB, however many bleeding complications
have been reported. Argatroban has also been used successfully for anticoagulation during pediatric cardiac surgery
with CPB and for extra-corporeal membrane oxygenation. Problems with both bleeding and clotting (even in the

420
Page 4
same patient) have been reported, so the drug may be unsatisfactory for CPB, or alternatively the optimal dosing and
monitoring may have not yet been determine.

Bivalrudin Lepirudin Argatroban Desirudin
Monitoring aPTT, ACT aPTT aPTT,ACT aPTT
Elimination 80% Enzymatic
20% Renal
Renal Hepatic Renal
Half-life (min) 25 80 45 SC -120
IV - 60
Antidote none none none none
Point of Care Testing: Anti-Platelet Therapeutics and Transfusion Algorithms
Anti-thrombotic therapy for the treatment of acute coronary syndromes and interventional cardiology procedures is
increasing and the development of new drugs continues. Treatment of patients after implant of a drug-eluting stent
includes 12 months of anti-thrombotic therapy which poses a risk for patients who require surgery in that time
period.
XVII
Cardiovascular patients who are maintained on drugs such as clopidogrel and prasugrel, have increased
bleeding complications and morbidity after cardiac surgery.
XVIII
There is evidence that an increased risk of infection
exists in cardiac surgical patients who have taken clopidogrel and aspirin prior to surgery. This may be a result of an
increased volume of transfusion, an increase in bleeding itself, or an independent effect. These drugs
(thienopyridine agents) act by non-competitive antagonism at one of the platelet ADP receptors, the P2Y12 receptor.
The P2Y12 receptor inhibits cyclic AMP production and potentiates platelet aggregation. The duration of anti-
platelet activity is the life-span of the platelet because the P2Y12 receptor is permanently altered. The effects of
clopidogrel plus aspirin are not just additive, they are synergistic and this may explain why cardiac surgical patients
having received this combination of drugs seem to have excessive postoperative bleeding. Ticagrelor, a new anti-
thrombotic agent in the cyclo-pentyl-triazolo-pyrimidine class which works as a direct-acting inhibitor of platelet
P2Y12 inhibitor. Unlike the thienopyridine agents this drugs antagonistic effects on the receptor is reversible
making it a more attractive alternative for patients who may be at high risk for requiring a surgical procedure.
Specific monitoring of the platelet defect induced by these anti-thrombotic drugs would be advantageous for a
number of reasons. For therapeutic efficacy, the degree to which patients are protected from thrombotic events is
related to the degree of platelet inhibition. Thus platelet function monitoring can be used for titrating drug effect. In
a large cardiovascular medicine trial, the TRILOGY trial, a substudy evaluated the effects of Prasugrel versus
Clopidogrel on anti-platelet efficacy relative to outcomes. Although prasugrel resulted in significantly greater
degrees of platelet inhibition, this did not result in a reduced incidence of the endpoint of a composite cardiovascular
morbidity which was the primary outcome. Also greater levels of platelet inhibition were not correlated with the
incidence of cardiovascular events or the composite endpoint
XIX
. However, when patients present for surgery after
discontinuation of clopidogrel, specific platelet function testing is useful in order to determine the risk of bleeding
need for transfusion. A number of point-of-care platelet function assays have been developed that utilize ADP and
can assess the degree of platelet inhibition with some degree of accuracy as compared with standard aggregometry.
Platelet function tests are listed in theTable.
Many of the POC tests listed can also be used in transfusion algorithms used to treat bleeding patients in the
perioperative period. Updated guidelines were published in 2011 in The Annals of Thoracic Surgery
iv
that include
POC testing for platelet reactivity as a new recommendation for preoperative patient assessment. These platelet
function assays are useful to detect patients who have residual anti-thrombotic therapy on board and those that have
CPB-induced bleeding.
Transfusion algorithms that include thrombelastography or thrombelastometry to measure platelet function
have proven helpful in reducing transfusion requirements in cardiac surgical patients, as reported in small
prospective studies.
XX,XXI,XXII
These algorithms can be further specified to qualify a coagulation defect so that the
amount of transfused blood product needed can be predicted by the algorithm. Other tests have been less well
studied but have shown benefit for identifying bleeding patients and for directing appropriate treatment. Some of the
studies that show a reduction in transfusions demonstrate no significant effect on blood loss. Thus it is unclear
whether or not the transfusion algorithm itself is responsible for the lower transfusion requirements, or if the change
in behaviour represents a bias, causing these studies to show benefit. Depending on the conduct of CPB and the
particular haemostasis abnormalities that are expected, some investigations have shown that point-of-care
coagulation tests have the strongest correlation with bleeding, and should be included early in a transfusion
algorithm.

420
Page 5

Instrument Mechanism/Agonist Clinical Utility
Thromboelastograph Viscoelastic/ Thrombin (native),
ADP, aracidonic acid (AA)
Post-CPB, liver transplant,
pediatric, obstetrics, drug
efficacy
ROTEM Viscoelastic/ Thrombin Post-CPB, drug efficacy
Sonoclot Viscoelastic/ Thrombin Post-CPB, liver transplant
PlateletWorks Plt count ratio/ ADP, AA,
collagen
Post-CPB, drug therapy
PFA-100 In vitro bleeding time/ ADP,
epinephrine
17

vWD, congenital disorder,
aspirin therapy, post-CPB
VerifyNow Agglutination/TRAP, AA, ADP Drug therapy
Clot Signature Analyzer Shear-induced in vitro bleeding
time/Collagen
Post-CPB, drug effects
Whole blood aggregometry

Electrical impedance/Many Post-CPB, drug effects

Multiplate analyzer Electricl impedance/ADP,AA,
collagen, ristocetin, TRAP-6
Drug therapy, congenital
disorder, post-CPB

Recombinant Activated Factor VII and Coagulation Factors
Recombinant Factor VIIa ([rVIIa] Novo Seven, Novo Nordisk (Denmark)) has been reported to be effective in
restoring hemostasis that results from severe hemorrhagic complications after CPB. Originally this drug was
prescribed for patients with specific factor deficiencies such as Hemophilia A with inhibitors. rVIIa induces
hemostasis directly at the site of bleeding by binding to locally expressed tissue factor.
XXIII
This activated Factor VII
then activates Factor X of the common coagulation pathway and Factor IX of the intrinsic coagulation pathway.
Thrombin generation is enhanced but without systemic activation of coagulation. Occasional case reports indicate
that in severe uncontrolled hemorrhage, after other possible therapeutic modalities were exhausted, recombinant
factor VIIa was effective in attenuating bleeding after CPB and in other surgical settings. Observational data indicate
a higher incidence of adverse events who receive rVIIa late rather than early in the course of hemorrhage.
XXIV
A
multicenter trial of rVIIa in cardiac surgery revealed that patients who received rVIIa versus placebo had a higher
incidence of adverse events, including stroke, but this difference was not statistically significant.
XXV

Mechanistically, rVIIa may reduce the bleeding due to platelet inhibitor therapy.
XXVI
The thrombin burst that is
created during the propagation phase of coagulation may augment platelet function to a degree that is clinically
acceptable and restores hemostasis. In addition to rVIIa, prothrombin complex concentrates (PCCs) and fibrinogen
concentrate are being used to replace clotting factors depleted or consumed during cardiopulmonary bypass. PCCs
are considered to be either 3-factor or 4-factor complexes of the vitamin-K dependent clotting factors II, IX, X.
Four-factor PCCs contain factor VII in active form. A few of these concentrates have been available commercially
for years and are used in hemophilia(FEIBA). Some newer PCCs such as Beriplex and Octoplex are available
and labeled for urgent warfarin reversal. Since PCCs have been approved for use in warfarin reversal and
hemophilia, their use in post-cardiac surgical bleeding algorithms is off-label. These pharmacologic complexes are
usually quantified by the amount of Factor IX contained within. Anticoagulant proteins are also included in these
complexes to guard against possible thrombotic complications. For example, Beriplex(CSL Behring, Marburg,
Germany), a 4-factor PCC, contains proteins C and S, anti-thrombin, and heparin. Since these products are not
blood products, but are pharmacologic preparations, their use early in transfusion algorithms has dramatically
reduced the transfusion of fresh frozen plasma, platelets, and using fibrinogen and PCCs led to significantly lower
transfusion requirements and fewer adverse events compared with a control group receiving standard transfusion
management
XXVII
.

Summary
The hematologic abnormalities of CPB result from contact with extracorporeal surfaces and the resultant
abnormalities of coagulation, fibrinolysis, and inflammation. These abnormalities are not solely due to CPB as they
exist in off-pump cardiac surgical patients as well. Concomitant anti-thrombotic drug therapy has increased
bleeding in cardiac surgery and further underscores the need for point of care testing of the hemostatic system.
Combinations of therapies (antifibrinolytic therapy plus rVIIa) require further investigation in cardiac surgery to
assess the benefit and risks.

420
Page 6
References:

I
Ranucci M, Isgro G, Cazzaniga A, Ditta A, Boncilli A, Cotza M, Carboni G, Brozzi S: Different patterns
of heparin resistance: therapeutic implications. Perfusion 2002; 17: 199-204
II
Pleym H, Videm V, Wahba A, Asberg A, Amundsen T, Bjella L, Dale O, Stenseth R: Heparin resistance
and increased platelet activation in coronary surgery patients treated with enoxaparin preoperatively. Eur J
Cardiothorac Surg 2006; 29: 933-40
III
Ranucci M, Frigiola A, Menicanti L, Ditta A, Boncilli A, Brozzi S: Postoperative antithrombin levels and
outcome in cardiac operations. Crit Care Med 2005; 33: 355-60
IV
Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER, Shore-
Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J, Baker RA, Dickinson
TA, Fitzgerald DJ, Likosky DS, Shann KG. 2011 Update to the Society of Thoracic Surgeons and the
Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac
Surg. 2011 Mar;91(3):944-82.
V
Nicholson SC, Keeling DM, Sinclair ME, Evans RD: Heparin pretreatment does not alter heparin
requirements during cardiopulmonary bypass. Br J Anaesth 2001; 87: 844-7
VI
Shore-Lesserson L, Manspeizer HE, Bolastig M, Harrington D, Vela-Cantos F, DePerio M:
Anticoagulation for cardiac surgery in patients receiving preoperative heparin: use of the high-dose
thrombin time. Anesth Analg 2000; 90: 813-8
VII
Lobato RL, Despotis GJ, Levy JH, Shore-Lesserson LJ, Carlson MO, Bennet-Guerrero E.
Anticoagulation management during cardiopulmonary bypass: a survey of 54 North American institutions>
J Thorac Cardiovasc Surg 2010;139:1665-6.
VIII
Garvin S, Muehlschlegel JD, Perry TE, et al: Postoperative activity, but not preoperative activity,
of antithrombin is associated with major adverse cardiac events after coronary artery bypass graft surgery.
Anesth Analg 2010;111:862-869
IX
Ranucci M, Baryshnikova E, Crapelli GB, et al: Preoperative antithrombin supplementation in cardiac
surgery:
A randomized controlled trirevadan
al. J Thorac Cardiovasc Surg 2013;145:1393-9
X
Avidan MS, Levy JH, van Aken H, et al. Recombinant human antithrombin III restores heparin
responsiveness and decreases activation of coagulation in heparin-resistant patients during
cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005;130:107-13
XI
Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced
thrombocytopenia:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Ed). Chest 2008; 133: 340S80S.
XII
Warkentin TE, Kelton JG: Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med.
2001;344:1286-92.
XIII
Warkentin TE: An overview of the heparin-induced thrombocytopenia syndrome. Semin Thromb
Hemost 2004; 30: 273-83
XIV
Koster A, Chew D, Grundel M, Bauer M, Kuppe H, Spiess BD: Bivalirudin monitored with the ecarin
clotting time for anticoagulation during cardiopulmonary bypass. Anesth Analg 2003; 96: 383-6
XV
Merry AF: Bivalirudin, blood loss, and graft patency in coronary artery bypass surgery. Semin Thromb
Hemost 2004; 30: 337-46
XVI
Dyke CM, Smedira NG, Koster A, Aronson S, McCarthy HL II, Kirshner R, Lincoff AM, Spiess BD: A
comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with
cardiopulmonary bypass: the EVOLUTION-ON study. J Thorac Cardiovasc Surg 2006; 131: 533-9
XVII
King SB 3rd, Smith SC Jr, Hirshfeld JW Jr, et al: 2007 focused update of the ACC/AHA/SCAI 2005
guideline update for percutaneous coronary intervention: a report of the American College of
Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol.
2008;51:172-209.
XVIII
Purkayastha S, Athanasiou T, Malinovski V, Tekkis P, Foale R, Casula R, Glenville B, Darzi A: Does
clopidogrel affect outcome after coronary artery bypass grafting? A meta-analysis. Heart 2006; 92: 531-2
XIX
Gurbel PA, Erlinge D, Ohman EM, et al: Platelet Function During Extended Prasugrel and Clopidogrel
Therapy for Patients with ACS Treated Without Revascularization. JAMA 2012;308:1785-94

420
Page 7

XX
Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA:
Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.
Anesth Analg 1999, 88(2):312-319
XXI
Nuttall GA, Oliver WC, Santrach PJ, Bryant S, Dearani JA, Schaff HV, Ereth MH: Efficacy of a simple
intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary
bypass. Anesthesiology 2001, 94(5):773-781
XXII
Weber CF, Gorlinger K, Meininger, et al: A Prospective, Randomized Clinical Trial of Efficacy in
Coagulopathic Cardiac Surgery Patients. Anesthesiology 2012;117:531-47
XXIII
Hoffman M: A cell-based model of coagulation and the role of factor VIIa. Blood Rev 2003; 17 Suppl
1: S1-5
XXIV
Karkouti K, Yau TM, Riazi S, Dattilo KM, Wasowicz M, Meineri M, McCluskey SA, Wijeysundera
DN, van Rensburg A, Beattie WS: Determinants of complications with recombinant factor VIIa for
refractory blood loss in cardiac surgery. Can J Anaesth 2006; 53: 802-9
XXV
Gill R, Herbertson M, Vuylsteke A, et al: Safety and efficacy of recombinant activated factor VII: a
randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation 2009
;120:21-7
XXVI
Szlam F, Tanaka KA, Rumph B, et al: In vitro effects of recombinant activated factor VIIa
(NovoSeven) on clopidogrel-induced platelet inhibition. Thromb Haemost. 2010 ;103:863-5
XXVII
Gorlinger K, Dirkmann D, Hanke AA, et al: First-line Therapy with Coagulation Factor Concentrates
Combined with Point-of-Care Coagulation Testing Is Associated with Decreased Allogeneic Blood
Transfusion in Cardiovascular Surgery. Anesthesiology 2011;115:1179-91

Disclosure
Elcam Medical, Self, Consulting Fees; AstraZeneca, Self, Consulting Fees
429
Page 1
New Era of Off-site Catheter Based Procedures and Anesthesia
Nathaen Weitzel M.D. Denver, Colorado
Description:
This refresher course lecture will highlight the anesthetic considerations for a variety of interventional cardiology
procedure. The concept of the Hybrid OR is a reality in many centers now, and a basic understanding of the types of
procedures being done is necessary to provide anesthetic care. This syllabus will provide the background
information for the lecture, which will focus on clinical application of anesthesia in these challenging locations.
Introduction:
Interventional Cardiac techniques have evolved well beyond the initial Percutaneous Cardiac interventions
done in the late 1970s published by Gruntzig and colleagues
1
. Percutaneous therapy now exists to treat brady or
tachyarrhythmias via pacemaker / defibrillator insertion, tachyarrythmias requiring ablative procedures, septal
defects amenable to percutaneous device closure, and mitral regurgitation amenable to percutaneous clipping.
Additional procedures that are becoming commonplace include lead extractions using a variety of lead extraction
techniques and the LARIAT procedure to isolate the atrial appendage in atrial fibrillation. Obviously there are
recent advances in percutaneous valve implantation as well, but this will not be covered in this lecture. This
summary will break these topics into three main sections: Procedures in the Electrophysiology suite; Procedures in
the hybrid OR (Lariat, Laser Lead), and those performed in the Interventional Catheterization Suite (MV clipping,
septal defect closure); Anesthetic management recommendations will be presented throughout, with a summary
table at the end.
Regardless of the type of intervention being performed, more and more of these patients have significant
co-morbid medical conditions warranting close evaluation by the anesthesiologist before the procedure. Many times
these patients have incomplete medical records, pending labs, or are actually emergent cases thus the
anesthesiologist may have to deal with a very sick patient, in the setting of limited pre-operative information.
Patients may present with intra-aortic balloon pumps or percutaneous ventricular assist devices, or have multiple
vasopressor infusions in place for hemodynamic support. A general comfort level with these modalities and
medications is needed for the anesthesiologist to safely manage and direct the care of these patients.
In general, procedures carried out in off site locations or hybrid suites introduce a unique challenge for the
anesthesiologist compared to the standard OR setup. The large amount of imaging equipment such as C-arm
fluoroscopy and viewing screens, echocardiography, and unique imaging specific tables creates a setup that is less
than ideal for the anesthesiologist. Limited access to the head / airway, along with various layouts to the room adds
an additional challenge to these cases. Assessment of each individual location should be considered in planning your
anesthetic and airway management strategy so appropriate access can be obtained when the need arrives.
Electrophysiology Suite (EP)
Cardiac Arrhythmias account for >800,000 hospitalizations and > 40,000 deaths annually
2
. To treat these
patients, nearly 15,000 pacemaker (PM) devices and 10,000 Implantable Cardioverter Defibrillator (ICD) devices
are implanted in the United States each month
3
. However, for more complex tachyarrhythmias, catheter ablation
techniques have evolved to allow for improved outcomes for many patients. Catheter ablation procedures are
possible for Atrial Fibrillation, Atrial flutter, and Ventricular tachycardia; allowing for better use of cardiac
resynchronization therapy
4
.
The diagnostic EP study is the cornerstone that all the ablative procedures are based upon. Initially an
electroanatomic map (EAM) is created using a 3D reconstruction of the heart combined with color mapping
representing electrical conduction pathways. EAMs are reliant on patient positioning and the patient remaining still
to allow for accurate guidance of catheters during the ablation procedure
5
. The technique of EAM is well described
by Kwak in 2013
4
. Color coding is used on the map to show the origin and pattern of signal propagation. Pace

429
Page 2
mapping involves pacing at a particular site and recording the resultant 12-lead ECG. The goal is to find a pacing
site that results in QRS complexes that are identical to those found on a previously obtained 12-lead ECG showing
the arrhythmia. Entrainment mapping is used to identify sites within the circuit of reentrant tachycardia such as atrial
flutter, atrioventricular nodal reentrant tachycardia, and VT. Information is collected during overdrive pacing at a
rate faster than the arrhythmia to find sites within the reentry circuit. Substrate mapping creates a 3D
electroanatomic map using ECG amplitude, which corresponds to voltage. Low voltage areas are typically scars or
areas of fibrosis from infarction, surgery, or previous ablation
4
.
The Electrophysiologist obtains vascular access and various catheters are positioned in atria or ventricular
chambers, typically via femoral veins, but occasionally via internal jugular or subclavian veins, or even the femoral
artery. Programmed pacing is carried out allowing study of the intrinsic conduction system, as well as induction of
the pathologic arrhythmia. Right-sided catheters and coronary sinus catheters are done without systemic
anticoagulation, but should access to the left side be required for mapping or ablation, then systemic heparinization
is needed to prevent embolization. Left sided structures are either accessed using atrial septal puncture or via
retrograde aortic access. Mapping is the critical stage of arrhythmia ablation providing the road map for subsequent
intervention. Due to the sensitivity of the conduction system to various sedative agents, mapping is often done
under light or even no sedation. Ventricular arrhythmias have a high sensitivity to local anesthetics as well, and
thus for these patients, local anesthetic use is minimized as well.
5

The ablation procedure itself was initially done with high energy current, but is now typically carried out
using radio-frequency ablation or cyro-ablative techniques. Success depends on stable catheter contact with the wall
of the heart, thus excessive heart motion tends to impede good contact, and slow the ablative process. Importantly,
RF ablations generate significant amounts of heat, and the catheter tip is cooled using saline infusions. This can lead
to fluid overload of patients over the course of long ablative procedures, a key point to consider for all ablations.

SVT Ablations:
The most common supraventricular lesions amenable to ablation are AV nodal re-entrant tachycardia, AV
re-entrant tachycardia, atrial flutter, and atrial tachycardia. Atrial Fibrillation is also amenable to ablation and will be
discussed separately. SVT lesions should be mapped out with minimal sedation. Once the EAM is established, more
attention should be placed on patient comfort as the ablation procedure often takes multiple hours. Various levels of
sedation may be needed on case-by-case basis, but SVT arrhythmias are induced in part by intrinsic adrenergic tone,
thus elimination of this response via anesthetic sedation can make identification and ablation of these lesions
difficult. For patients with normal airway anatomy amenable to light conscious sedation, this is the recommended
technique for the duration of the ablation. A key point in SVT ablations is that these tend to be fairly
hemodynamically stable (in contrast to VT ablations), and thus additional invasive monitors by the anesthesiologist
are generally not needed unless the patient has severe concomitant heart disease. General anesthesia may become
necessary for patients who have sleep apnea, are morbidly obese, or have other impediments to sedation, but this
should be done after the initial mapping. It is critical to avoid patient motion however during the sedation process,
as this changes the catheter positions and makes the initial mapping studies less accurate. General anesthetics do
appear to impact nodal conduction and ventricular repolarization however the mechanism is not entirely clear
4
.
Sevoflurane has been postulated to prolong the QT interval as well as prolonging the action potential duration of
accessory pathways thus complicating mapping / ablation of these lesions
6
.

Atrial Fibrillation (AFIB):
Ablation is now considered the standard of care for patients with AFIB resistant to medical therapy.
Catheter ablation for AFIB attempts to create electrical isolation of the pulmonary veins either with Cryoablation or
radiofrequency (RF) ablation and success depends on creating transmural lesions. While conscious sedation has
been employed for years, recent studies have indicated improved success rates for patients undergoing ablation with
general anesthesia
7
. Reduction in catheter motion is the postulated reason for improvements in results with GA due
to less respiratory variation. Reducing catheter motion due to respiratory variation has become a hot topic and some
centers have moved toward employing high frequency jet ventilation (HFJV) during the ablation period with some
success.
Initially reported for AFIB ablation in 2006, HFJV has seen steady increase in use over the past 5 years at
various centers. Goode et al reported results from a retrospective analysis comparing standard ventilation to HFJV in
72 patients (36 each group), and demonstrated reductions in number of required ablation lesions and reduced
procedure time. Direct comparison demonstrated that HFJV produced less variation in LA volume, pressure,
pulmonary vein blood flow velocity, and posterior LA position than standard ventilation
8
. Recently, Hutchinson and
colleagues performed a randomized trial looking at use of integrated 3D EAM, steerable introducers, and HFJV.

429
Page 3
They reported improvements in one-year freedom from AFIB with the use of all three of these techniques, but
improved even more with HFJV
9
. Elkassabany and colleagues reported retrospective results on anesthetic
management of 188 patients for pulmonary vein isolation using HFJV
10
. 175 cases were completed using HFJV,
while 13 cases were converted to standard ventilation due to either hypoxia or hypercarbia. These values were
followed by ABG analysis. Reported airway complications in this study related to difficulty with intubation, and not
the HFJV itself. Not every anesthesiologist is comfortable using HFJV for an ablation procedure due to concern for
barotrauma. Hu et al recently reported outcomes of >800 consecutive cases using HFJV for laryngeal surgery.
Complication rates due to HFJV were reported in 5.8% of cases (57 events in 49 cases). Complications were
hypoxia (SPO2 <90%, n = 30, 3.6%), hypercarbia (end tidal CO2 of >60 mm Hg, n = 17, 2.0%), airway obstruction
(n = 4, 0.5%), barotrauma (n = 2, 0.2%), seeding of blood into trachea (n = 2, 0.2%), submucosal injection of air (n
= 1, 0.1%), and mucosal damage (n = 1, 0.1%)
11
. Fernandez-Bustamante et al reported similar results in 2006 in
HFJV use during rigid bronchoscopy with the complications being hypercapnia, hypoxemia, and hemodynamic
instability, but just one case of barotrauma in the retrospective group
12
.
The take home message for AFIB ablations at this time is that general anesthesia is preferred technique,
although deep sedation may be appropriate in certain patients. HFJV can be considered, but use of HFJV probably
is an indication for invasive arterial access to follow oxygenation and carbon dioxide levels.

Ventricular Tachycardia (VT):
Ablation procedures are seeing increasing success and use in VT. Patients who present for VT ablations
generally fall into two categories: relatively healthy patients with symptomatic PVCs or idiopathic VT (no
structural heart disease), or patients with structural heart disease (ischemic or non-ischemic cardiomyopathy). The
second group tends to carry significant comorbid disease with various degrees of systolic or diastolic heart failure.
Patients with idiopathic VT often undergo EAM / ablation initially with little sedation and often avoidance of local
anesthetics to allow for spontaneous ventricular ectopy development and accurate mapping. Occasionally the
arrhythmia requires induction either using vasoactive infusions (isoproterenol / epinephrine) vs electric stimulation,
or burst pacing
4
. For ventricular arrhythmias that are hemodynamically stable, complete EAM may be carried out
followed by ablation, and this is frequently accomplished for idiopathic VT.
Patients with structural heart disease (group 2) are much more challenging to manage from both the
anesthesiologist and electrophysiologist standpoint. EAM in these patients is often done with minimal sedation as
above, however triggering VT or sustained VT in patients with severe heart failure is often not tolerated and many
times requires cardioversion / defibrillation. For this reason, invasive arterial line monitoring should be employed
for patients with reduced EF having VT ablations. Due to the hemodynamic challenges of EAM in these cases, this
period often requires vasopressor support and occasionally even ventricular assist device support of the LV
(Impella)
5
. VT ablations in this category are now being approached both from the endocardial surface and
epicardial surface. Obviously epicardial ablations require accessing the epicardial space, and add an additional level
of complexity and risk, in addition to the need for additional anesthesia due to patient discomfort. A key aspect to
success in VT ablations is direct communication with the EP team and anesthesiology team. Need for vasopressors
can signal a change that can be due to procedural concerns or due to intrinsic heart problems, but this needs to be
discussed immediately to rule our pericardial effusions or other procedure related complications (see below).

Complications of Ablations:
Vascular access complications are frequent but manageable and are well described by Price et al
5
.
Pericardial effusions, tamponade, myocardial ischemia, and stroke are all procedure related complications that
should be considered. Myocardial perforation occurs roughly 1% of the time and is monitored by fluoroscopy or
ICE (intra-cardiac echocardiography). Onset of new unexplained hypotension should trigger concern for pericardial
effusion / tamponade and should be immediately ruled out. Transient or permanent heart block can occur due to
ablations, and occasionally temporary or permanent pacemakers need to be employed. Left sided ablations require
anticoagulation to prevent stroke and thus ACT levels of 250-300 are often targeted. Phrenic nerve injury is also
possible in various ablation approaches. Pacing and identifying the nerve during the procedure enables the
electrophysiologist to monitor the phrenic nerve, thus use of neuromuscular blockade should be avoided. A rare
complication during ablation procedures (0.04% in AFIB ablations) using RF is development of atrio-esophageal
fistula due to heat injury, and thus esophageal temperature monitoring is often employed. Finally, fluid
administration is employed during the ablation procedures to cool the probes, thus large amounts of fluid may be
given over these lengthy procedures and is critical to monitor for patients with heart failure.

429
Page 4
Hybrid OR / Catheterization Lab:
Lead Extractions:
Pacemaker insertion is now a well-established practice performed routinely in the US. The standard is for
this to be done under sedation and local anesthesia, and patients generally do well. However with the large number
of pacemakers and leads implanted annually, more leads become defective, fracture, or become infected requiring
removal. Lead removal can be accomplished via manual traction, specialized traction devices that clamp or snare the
lead, mechanical sheaths that are advanced over existing leads and specialized sheaths. Specialized sheaths include:
laser sheaths, electrosurgical sheaths, rotating tip sheaths, and telescoping sheaths. The Heart Rhythm Society has
put out suggested guidelines for management of lead extractions from a system wide view (ie. not specific to
anesthesiology)
13
. The following discussion will focus on the use of laser lead excision, but the concepts apply to all
techniques.
The PLEXES (Pacing Lead Extraction With the Excimer Sheath) trial was the first large prospective,
randomized report of laser extraction techniques. This trial, which included 301 patients, showed 94% success using
laser extraction vs 64% success using non-laser extraction techniques
14
. Subsequently, Byrd et al. reported 2,561
laser-assisted pacing and defibrillator lead extractions from 1,684 patients at 89 sites with a procedural success rate
of 90% and a major complication rate of 1.9%
15
. Interestingly, this complication rate was similar to a previously
reported non-laser technique major complication rate of 1.96%
14
. Hence, even with excimer laser lead extraction
catastrophic complications remain possible, with mortality rates as high as 50% in the event of accidental rupture of
a large vein or of the heart itself
16
.
The removal of chronically implanted leads is impeded by dense fibrotic attachments that entrap the leads
within the veins and cardiac chambers
16
. Reports of major complications from laser extraction of chronically
implanted leads range from 1.9% to 3.4%
15,17-19
. Major complications include major venous injury, myocardial
tear, arrhythmia, arteriovenous fistula, pneumothorax, hemothorax, tricuspid valve injury, and pulmonary
embolus
20,21
. Because of the potential need for immediate surgical intervention including the institution of
cardiopulmonary bypass, many institutions now elect to adhere to the Heart Rhythm Society recommendations
which is to perform these procedures with immediate access to open-chest -surgery including cardiopulmonary
bypass
13
.
Based on the experience at University of Colorado Denver (UCD), a protocol using general anesthesia
under the direction a cardiothoracic anesthesiologist has been adopted. Arterial catheters are placed in all patients to
permit rapid evaluation of hemodynamic stability. It is not necessary to monitor central venous or pulmonary arterial
pressures in all patients. The procedure itself involves central venous cannulation for emergency temporary
transvenous pacing access, so this access can also be used for either monitoring or for infusion of vasoactive drugs.
For patients with significant pulmonary hypertension (mean pulmonary artery pressure >30mmHg) it may be
beneficial to have a pulmonary artery (PA) catheter in place, though this may not be needed given availability of
TEE monitoring. At UCD, a protocol is used for TEE monitoring for lead extractions. All patients receive a standard
comprehensive TEE examination under general anesthesia immediately prior to the lead extraction procedure as
described in ASE/SCA guidelines
22
. Special attention is given to assessing for the presence of a patent foramen
ovale (PFO) before use of the laser, since the laser generates gas bubbles that may embolize into the systemic
circulation in the presence of a right-to-left shunt. Efforts are also made to identify thick fibrinous sheaths on leads,
infective endocarditis with vegetations, and lead thrombi, all of which may embolize during extraction and increase
the chance for ischemic stroke. Commonly, the first obstruction point is at the junction of the superior vena cava
(SVC) and right atrium (RA). Trauma to the SVC at this location may predispose to laceration or tearing and lead to
either right-sided hemothorax or pericardial effusion, depending upon the specific location of the tear. The presence
of a high (cephalad) SVC laceration is not usually detectable with TEE; therefore a strong index of suspicion as well
as surveillance of the right pleural space should be undertaken.
Leads commonly adhere to the tricuspid valvular apparatus and extraction of fibrosed leads can further
damage TV leaflets. The TV is best seen in the ME 4-chamber and ME RV inflow-outflow views. All 3 leaflets can
also be seen in the transgastric window, commonly found between 20 to 50 (TV SAX view). RV leads are usually
implanted along the RV septum in order to minimize the chances of the lead causing RV free wall damage.
Extraction of RV leads at their distal insertion point should also be closely monitored. Traction on the RV can cause
significant hemodynamic compromise as a result of RV distortion or inversion. If observed, it should be
communicated to avoid potential papillary muscle injury or ventricular rupture.
Perforation of the either the atrial or the ventricular wall can occur during extraction procedures and the
presence of new or growing pericardial effusion should be vigilantly monitored during the procedure. The ME 4-
chamber view or the transgastric left ventricle SAX view are ideal views for diagnosing and monitoring this
complication. The presence of trivial to small pericardial effusions is common and seen in up to 14.5% of cases
23
,

429
Page 5
the majority of which can be managed conservatively and monitored with post-operative transthoracic
echocardiography; however clinically / hemodynamically significant effusions may require immediate
pericardiocentesis or even sternotomy and direct surgical repair with or without cardiopulmonary bypass. Finally,
these procedures typically will finish with placement of new pacemaker leads, either temporary in cases of infection,
or permanent. Guidance of placement of these leads is done using fluoroscopy and TEE imaging. TEE images are
useful to confirm that the leads are placed in the appropriate location, ie on the RV septum and not the RV free wall.

Lariat Procedure:
A new approach to management of AFIB has recently come to clinical practice, the so-called Lariat Snare
device
24-26
. AFIB affects > 2 million patients currently, and is expected to increase up to 12 million by 2050
24
.
While anticoagulation therapy is effective in reducing stroke risk for many patients, a certain subset are unable to be
adequately maintained on this due to excessive bleeding risk. Interventional exclusion of the left atrial appendage
has been developed using a snare device. The procedure is done under general anesthesia with TEE guidance
throughout along with fluoroscopy. Two access points are needed: L. atrium via femoral venous sheath / transeptal
puncture from the R. atrium to L. Atrium, and the pericardial space approached through the chest wall. The
procedure involves 4 basic steps: 1) pericardial and transseptal access; 2) placement of the endocardial magnet-
tipped guidewire in the apex of the LAA with balloon identification of the LAA os; 3) connection of the epicardial
and endocardial magnet-tipped guidewires for stabilization of the LAA; and 4) snare capture of the LAA with
closure confirmation and release of the pre-tied suture for LAA ligation
26
. The main procedural risks include:
including right ventricular puncture, epicardial vessel injury, sheath-related trauma, and post-procedure pericarditis,
laceration of the LAA, trauma to the epicardial surface of the myocardium, and incomplete closure due to the
inability to reposition the snare
26
.
As expected in any new interventional procedure, there is a learning curve for the interventionalist, as well
as for the team management of these cases. While this procedure does not fall under the same recommendations as
lead extractions, due to the risks outlined above, availability of CT surgery teams, cardiac anesthesia, and perfusion
teams / equipment should be readily available should significant injury to cardiac structures occur requiring open
surgery. Due to these risks, the anesthesia team should consider invasive blood pressure monitoring along with the
TEE monitoring.

Percutaneous Mitral Valve Repair:
Dr. Alfieri introduced the edge-to-edge repair for mitral lesions in 1991 as a simplified solution to open
surgical MV repair techniques
27
. Various companies have developed percutaneous techniques for mitral repair based
on this concept. The FDA approved the Mitra-clip by Abbot in the US for use as of 2013, largely based on results of
the EVEREST II trial (Endovascular Valve Edge-to-Edge Repair) High Risk Study (HRS)
28
, which looked at high
surgical risk patients (>12% estimated mortality) with grade III/IV MR. Device repair was achieved in in 96% of the
76 patients. Outcomes at 12 months were compared to the control group identified with similar risk and severity of
MR, but deemed not to be appropriate candidates. Standard management was employed for the control group with
86% managed medically and 14% managed with open surgical repair. 12-month survival rate was 76% for
intervention group and 55% for control group. The intervention group also demonstrated reduction in MR severity.
LV volume, improvement in NYHA classification, and improved quality of life indicators
28
.
Percutaneous MV clipping is performed in the hybrid suite or catheterization lab under a combination of
TEE and fluoroscopy guidance. Anesthetic planning should include consideration of heart failure due to severe MR
and appropriate induction agents should be employed. Invasive arterial access should be considered, as there can be
hemodynamic changes during device placement. General anesthesia is typically utilized due to prolonged procedure
times and need for TEE guidance. Trans-septal puncture is initially carried out to access the left atrium, followed by
identification of the appropriate MV segments by imaging. The device is placed and once secured, follow up
imaging confirms appropriate placement. Overall risks of the procedure include vascular access concerns, residual
septal defect, stroke, and potential embolization of the device.

Percutaneous Septal Defect Repair:
Atrial septal defects account for roughly 10% of congenital heart disease in adults, and if left untreated can
result in RV overload, increased RV volumes, pulmonary hypertension, elevated risk of embolism, and atrial
arrhythmias
29
. Initial attempts at device closure of septal defects dates back to 1974, with multiple versions and
attempts made at device employment. In 199,1 the Amplatzer device was released; a nickel and titanium self-
expanding device that is used in many cases currently. Data from the Nationwide Inpatient Sample identified 15,482
secundum ASD/patent foramen ovale closures between 1988 and 2005. Roughly 1/3 of these were managed with

429
Page 6
percutaneous therapy. Currently, both the Amplatzer septal occluder (ASO), and the Helex septal occluder (HSO)
are FDA approved for use in the US
29
.
ASO devices are indicated for closure of secundum ASD with Qp:Qs ratio of 1.5 : 1, or fenestration
following Fontan repair. Available sizes are from 3mm -38mm. Reported complications include: device
embolization, erosion into adjacent cardiac structures, arrhythmias, fracture of device, stroke, and device thrombus.
The procedure itself includes access of the femoral vein, and access to the right atrium with the guidewire. Balloon
sizing of the ASD is done under TEE / fluoroscopy guidance, with specific attention paid to the amount of ASD rim
tissue. Anesthetic management is typically to use GA. Planning with the cardiology team prior to the procedure is
important, specifically regarding need to measure Qp:Qs ratios. The cardiology team may want to obtain access and
measure RA and PA pressures under spontaneous respiration on room air prior to induction of anesthesia. In this
case, GA is typically induced following these measurements. Hemodynamic changes are relatively minor in this
procedure, so in the absence of significant heart failure symptoms, invasive arterial monitoring is often not
employed.
Table 1: Summary of key anesthesia management points:
Intervention / Procedure: Anesthetic Management Points*:
AFIB Ablation General Anesthesia preferred
Consider HFJV (+ Arterial line if HFJV)
Esophageal Temp monitoring
Typically stable hemodynamics throughout
Avoid Neuromuscular blockade during ablation
SVT Ablation Sedation preferred over General Anesthesia
Invasive Arterial monitor not indicated
Typically stable hemodynamics throughout
VT Ablation EAM initially done without sedation and minimal local anesthesia
General Anesthesia / deep sedation once mapping completed
+ Arterial line due to risk of hemodynamically unstable VT
Patients with EF < 30% may not tolerate arrhythmia induction / ablation
Plan for Inotropic support and consider mechanical support in extreme
cases (ie Impella Ventricular Support device)
Lead Extraction / Laser Lead General Anesthesia but possible with local / sedation
Arterial line + TEE monitoring.
Adequate IV access required, consider central access
Type and Crossmatch with products immediately available
CT surgery / Perfusion standby
Cardiac Anesthesiologist**
Lariat General Anesthesia
Arterial line + TEE monitoring.
Adequate IV access required, consider central access
Type and Crossmatch with products immediately available
CT surgery / perfusion standby
Percutaneous MV repair General Anesthesia
TEE guidance + Arterial line
Percutaneous ASD closure May start with local / spontaneous ventilation on Room Air
General Anesthesia once Qp:Qs measurements taken
TEE guidance
*All cases should have standard ASA monitoring in place. Specific anesthesia planning should be based on
individual medical conditions and may be altered from recommendations in table 1.
**Current debate surrounding whether CT Anesthesiologists should staff these cases, and may depend on whether
cardiology vs anesthesiology is performing TEE.

429
Page 7

References:
1. Gruntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis:
percutaneous transluminal coronary angioplasty. N Engl J Med 1979;301:61-8.
2. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: a report from
the American Heart Association. Circulation 2011;123:e18-e209.
3. Hammill SC, Stevenson LW, Kadish AH, et al. Review of the registry's first year, data collected, and future
plans. Heart Rhythm 2007;4:1260-3.
4. Kwak J. Anesthesia for Electrophysiology Studies and Catheter Ablations. Semin Cardiothorac Vasc
Anesth 2012.
5. Price A, Santucci, P. Electrophysiology Procedures: Weighing the Factors Affecting Choice of Anesthesia.
Semin Cardiothorac Vasc Anesth 2013;EPUB.
6. Gallagher JD. Electrophysiological mechanisms for ventricular arrhythmias in patients with myocardial
ischemia: anesthesiologic considerations, Pt II. J Cardiothorac Vasc Anesth 1997;11:641-56.
7. Di Biase L, Conti S, Mohanty P, et al. General anesthesia reduces the prevalence of pulmonary vein
reconnection during repeat ablation when compared with conscious sedation: results from a randomized study. Heart
Rhythm 2011;8:368-72.
8. Goode JS, Jr., Taylor RL, Buffington CW, Klain MM, Schwartzman D. High-frequency jet ventilation:
utility in posterior left atrial catheter ablation. Heart Rhythm 2006;3:13-9.
9. Hutchinson MD, Garcia FC, Mandel JE, et al. Efforts to enhance catheter stability improve atrial
fibrillation ablation outcome. Heart Rhythm 2013;10:347-53.
10. Elkassabany N, Garcia F, Tschabrunn C, et al. Anesthetic management of patients undergoing pulmonary
vein isolation for treatment of atrial fibrillation using high-frequency jet ventilation. J Cardiothorac Vasc Anesth
2012;26:433-8.
11. Hu A, Weissbrod PA, Maronian NC, et al. Hunsaker Mon-Jet tube ventilation: a 15-year experience.
Laryngoscope 2012;122:2234-9.
12. Fernandez-Bustamante A, Ibanez V, Alfaro JJ, et al. High-frequency jet ventilation in interventional
bronchoscopy: factors with predictive value on high-frequency jet ventilation complications. J Clin Anesth
2006;18:349-56.
13. Crossley GH, Poole JE, Rozner MA, et al. The Heart Rhythm Society (HRS)/American Society of
Anesthesiologists (ASA) Expert Consensus Statement on the Perioperative Management of Patients with
Implantable Defibrillators, Pacemakers and Arrhythmia Monitors: Facilities and Patient Management. Heart Rhythm
2011;8:1114-54.
14. Wilkoff BL, Byrd CL, Love CJ, et al. Pacemaker lead extraction with the laser sheath: results of the pacing
lead extraction with the excimer sheath (PLEXES) trial. J Am Coll Cardiol 1999;33:1671-6.
15. Byrd CL, Wilkoff BL, Love CJ, Sellers TD, Reiser C. Clinical study of the laser sheath for lead extraction:
the total experience in the United States. Pacing Clin Electrophysiol 2002;25:804-8.
16. Gaca JG, Lima B, Milano CA, et al. Laser-assisted extraction of pacemaker and defibrillator leads: the role
of the cardiac surgeon. Ann Thorac Surg 2009;87:1446-50; discussion 50-1.
17. Moon MR, Camillo CJ, Gleva MJ. Laser-assist during extraction of chronically implanted pacemaker and
defibrillator leads. Ann Thorac Surg 2002;73:1893-6.
18. Roux JF, Page P, Dubuc M, et al. Laser lead extraction: predictors of success and complications. Pacing
Clin Electrophysiol 2007;30:214-20.
19. Smith HJ, Fearnot NE, Byrd CL, Wilkoff BL, Love CJ, Sellers TD. Five-years experience with
intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin Electrophysiol 1994;17:2016-20.
20. Lawton JS, Moon MR, Curci JA, et al. Management of arterial injuries caused by laser extraction of
indwelling venous pacemaker and defibrillator leads. Pacing Clin Electrophysiol 2006;29:917-20.
21. Jones SOt, Eckart RE, Albert CM, Epstein LM. Large, single-center, single-operator experience with
transvenous lead extraction: outcomes and changing indications. Heart Rhythm 2008;5:520-5.
22. Shanewise JS, Cheung AT, Aronson S, et al. ASE/SCA guidelines for performing a comprehensive
intraoperative multiplane transesophageal echocardiography examination: recommendations of the American
Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular
Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography. Anesth Analg
1999;89:870-84.
23. Glover BM, Watkins S, Mariani JA, et al. Prevalence of tricuspid regurgitation and pericardial effusions
following pacemaker and defibrillator lead extraction. Int J Cardiol 2010;145:593-4.

429
Page 8
24. Massumi A, Chelu MG, Nazeri A, et al. Initial experience with a novel percutaneous left atrial appendage
exclusion device in patients with atrial fibrillation, increased stroke risk, and contraindications to anticoagulation.
Am J Cardiol 2013;111:869-73.
25. Shetty R, Leitner JP, Zhang M. Percutaneous catheter-based left atrial appendage ligation and management
of periprocedural left atrial appendage perforation with the LARIAT suture delivery system. J Invasive Cardiol
2012;24:E289-93.
26. Bartus K, Han FT, Bednarek J, et al. Percutaneous Left Atrial Appendage Suture Ligation Using the
LARIAT Device in Patients With Atrial Fibrillation: Initial Clinical Experience. J Am Coll Cardiol 2012.
27. Alfieri O, Maisano F, De Bonis M. The edge-to-edge repair. Multimedia Manual of Cardio-Thoracic
Surgery 2005;2005.
28. Whitlow PL, Feldman T, Pedersen WR, et al. Acute and 12-month results with catheter-based mitral valve
leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol
2012;59:130-9.
29. Moore J, Hegde S, El-Said H, et al. Transcatheter device closure of atrial septal defects: a safety review.
JACC Cardiovasc Interv 2013;6:433-42.

Disclosure
Sage Publications, Self, Consulting Fees
503
Page 1
Figure 1: Trends in acute renal failure (ARF) and a subset requiring
concurrent dialysis (ARF-D). Unadjusted values over an estimated US
population of 7.4 million CABG cases over 16 years from 1988-2003.
(Swaminathan, M, et al. Crit Care Med. 2007 Oct;35(10):2286-91)
Postoperative Acute Kidney Injury in Cardiac Surgery
Madhav Swaminathan, M.D., FASE, FAHA Durham, North Carolina
Introduction
Acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalized patients, especially
in the postoperative setting. In addition, it remains a significant complication of cardiac surgery throughout the
world.
1-5
Consequences of AKI include an increase in mortality risk which can exceed 60% among patients
requiring dialysis.
3
Even when serum creatinine values remain within the normal range, modest increases from
baseline values are associated with increased odds of death and end-stage renal disease, as well as longer hospital
stays and increased costs.
2,5,6
In general, there have neither been any associated improvements in incidence nor
mortality despite many recent advances in our understanding of the etiology and pathophysiology of AKI.
7

Incidence
Nearly 500,000 coronary artery
bypass graft (CABG) surgeries are
performed each year in the US.
8
AKI
is a common complication following
cardiac surgery that appears to be
increasing in frequency independent
of increasing severity of patient case-
mix, perhaps related to changing
diagnostic criteria (Figure 1).
9

Common risk factors include age,
diabetes, hypertension, and metabolic
syndrome, and chronic kidney disease.
In addition to the substantial increase
in short-term mortality associated with
AKI following cardiac surgery, long-
term mortality may be mediated by
persistent chronic kidney disease
among AKI survivors.
10

Pathophysiology
Perioperative AKI is the net result of
several possible insults. Common to
all AKI though, are tubular and vascular cell dysfunction, necrosis, and apoptosis. Although details of the trigger
mechanisms for AKI are unclear, there is better understanding of some insults specific to cardiac surgery, the field
in which it has been comprehensively studied. Cardiac surgery is an ideal model for studying the AKI phenomenon
a non-physiological insult and exposure to a pro-inflammatory, frequently hypothermic and ischemic
cardiopulmonary bypass (CPB) circulation in a patient with cardiovascular disease already at risk for renal injury.
Inflammation
Circulating proinflammatory cytokines are part of the systemic inflammatory response to surgical trauma and CPB.
Additionally, local release of cytokines related to renal ischemia/reperfusion is mediated by nuclear factor kappa B
(NF-!B) activation. Renal dysfunction also influences the inflammatory responses since filtration is a primary
clearance mechanism for many cytokines.
Ischemia Reperfusion

503
Page 2
Figure 2: The difference between a creatinine-based biomarker and novel
early biomarker-based diagnostic approach for postoperative AKI. (Hudson,
C et al. Semin Cardiothorac Vasc Anesth. 2008 Dec;12(4):320-30.)
Embolism, low-output syndrome, and exogenous catecholamines can all contribute to renal ischemia/reperfusion
during cardiac surgery, leading to phosphate depletion, calcium accumulation, oxygen free radical generation, local
leukocyte activation, and NF-!B activation. These changes cause necrosis, and apoptotic cell death through caspase
activation. Experimentally, caspase or NF-!B inhibition attenuates ischemia-reperfusion mediated AKI.
11

Embolism
Renal atheroembolism can be a major cause of postoperative AKI. Aortic atheroma burden and intraoperative
emboli counts predict AKI. Aortic plaque disruption due to intra-aortic balloon pump counterpulsation is likely also
a significant contributor to AKI. Anti-atheroembolism strategies have been widely adopted into the conduct of
cardiac surgery, including aortic avoidance and use of devices that limit aortic manipulation, but none have proved
effective tools at preventing postoperative AKI.
Nephrotoxins
Nephrotoxic agents blamed in the pathogenesis of AKI include pigments and drugs such as antifibrinolytics.
Myoglobin and hemoglobin avidly bind nitric oxide, causing AKI through direct cytotoxicity, vasoconstrictor
effects, and tubular obstruction. Leg ischemia from femoral artery cannulation has been blamed for myoglobinuric
AKI. Although statins have been associated with myopathy, they have not been associated with increased renal risk
in vascular and major non-cardiac surgery patients.
While both aprotinin and the lysine analogues (tranexamic acid, epsilon aminocaproic acid) are freely filtered by the
glomerulus and attach to the same brush border receptors in the proximal tubule (megalin/cubilin), understanding of
subsequent metabolism of these agents is incomplete. Aprotinin is taken up into proximal tubular cells, where it
remains for many hours. In contrast, epsilon aminocaproic acid and tranexamic acid, both of which resemble amino
acids in size, block these same receptors, causing minor tubular proteinuria. While proteinuria would normally be
evidence of tubular injury, this type can also be elicited by doses of lysine or arginine, and completely resolves 15
minutes after the agent is discontinued.
A single retrospective analysis of epsilon aminocaproic acid in 1502 patients did not find an increase in AKI.
12

Controversial retrospective studies comparing renal and other consequences of aprotinin, tranexamic acid, and
epsilon aminocaproic acid in large cardiac surgery populations found increased AKI and mortality with
aprotinin.
13,14
Concerns persist that a bias towards sicker patients receiving aprotinin cannot be adequately
addressed by statistical methods in these studies. Other studies on AKI have also used exposure to aprotinin as
models of investigating better creatinine profiles for AKI prediction.
15

Biomarkers
Given the limitations of using serum
creatinine and urine output for detecting
AKI, there is a need for better biomarkers
that can more reliably help diagnose AKI
that is specifically caused by acute
tubular necrosis, the most common renal
injury among post-cardiac surgery
patients. If such a diagnosis could be
accurately detected early after the injury,
then the window of opportunity for
effective therapies may shift dramatically
(figure 2). In addition, earlier and more
reliable detection of AKI would facilitate
better risk stratification. Examples of
outcomes that could be estimated include
the degree of AKI including dialysis
requirement, duration of AKI, subsequent
chronic kidney disease, or mortality.
Several new biomarkers have been identified while those previously known have been more intensely studied.
Although there have been over 20 unique biomarkers of AKI identified or under investigation, most of the current

503
Page 3

Figure 3: The association between early recovery of renal function as
characterized by the percentage decrease in creatinine 24 hours after its
peak value (PD24) and long-term adverse outcome. Significant
differences exist in event-free survival among patients grouped according
to magnitude of early recovery, with superior survival among those with a
higher PD24. (Swaminathan, M et al. Ann Thorac Surg. 2010)
Apr;89(4):1098-104.)
interest has focused on a handful of promising biomarkers: neutrophil gelatinase-associated lipocalin, cystatin C,
interleukin-18, and kidney injury molecule1.
16

In the setting of cardiac surgery, NGAL has been demonstrated to be a highly sensitive and specific biomarker of
postoperative AKI. Its gene is one of the earliest and the most upregulated in the kidney after ischemic injury.
17
In
a study of 81 adult cardiac patients, 20% of the patients developed postoperative AKI. NGAL was higher in patients
with AKI at 1 hour, 3 hours, and 18 hours post-CPB when compared with their non-AKI counterparts. A more
recent study found that the use of aprotinin versus epsilon amino-caproic acid in patients undergoing cardiac surgery
resulted in a two-fold incidence of AKI in the aprotinin group. Urinary NGAL was significantly higher at both 0 and
3 hours post CPB in patients receiving aprotinin.
18

Interleukin-18 (IL-18) is a proinflammatory cytokine that belongs to the IL-1 superfamily, and has been shown to be
both a mediator and biomarker of ischemic AKI. Kidney injury molecule-1 (KIM-1) is an immunoglobulin
superfamily transmembrane protein normally present at low levels in proximal renal tubular cells that dramatically
increases in expression following acute ischemic or nephrotoxic insult. Several studies among non-cardiac patients
have demonstrated that KIM-1 is a very sensitive indicator of AKI. However, fewer studies exist in the cardiac
surgery literature.
It has been suggested that cystatin C is an ideal molecule for measuring GFR because it is freely filtrated by the
glomerulus, completely reabsorbed by the proximal convoluted tubules, and is not secreted. Unlike creatinine, it is
not affected by age, gender, sex, or body mass. There have only been a few studies to date that have explored
cystatin C as a biomarker for AKI post-cardiac surgery. In one prospective study, both serum cystatin C and NGAL
were measured in 129 pediatric patients following CPB for corrective congenital heart surgery.
19
Both cystatin C
and NGAL were very strong independent predictors of AKI when compared to creatinine. In the 41 patients who
developed AKI, NGAL levels were elevated 2 hours postoperatively while cystatin C levels were elevated at 12
hours postoperatively.
In the largest cardiac surgery AKI biomarker study performed so far, the Translational Research Investigating
Biomarker Endpoints (TRIBE) AKI consortium gathered detailed plasma and urinary biomarker data in 1,219 adults
undergoing cardiac surgery at high risk for postoperative AKI.
20
These investigators found that the highest quintiles
of plasma NGAL and urinary IL-18 were associated with 6.8 and 5 fold greater odds of developing AKI, in addition
to being at higher risk for dialysis, longer hospital stay and overall mortality. The addition of these novel biomarkers
significantly improved the AKI risk
predictive capability of conventional models
inclusive of only clinical variables.
20

Renal Protective Strategies
Advances in identifying individuals at-risk for
AKI early are of limited value if they cannot
be used to meaningfully improve patient
outcomes. To date, attempts to prevent and
attenuate renal injury have met with limited
success. Current renal protective strategies
involve optimization of renal perfusion,
avoidance of nephrotoxic agents, and the use
of several pharmaceutical agents. Despite
decades of trying to mitigate the severity of
renal injury, none of these strategies have
shown a consistent benefit in improving
outcomes such as reduced incidence of AKI
requiring dialysis or death.
Although these biomarkers are still early in
the process of being validated, several are
likely to be used in clinical trials. Some
current trials are revisiting previously tested
renal protective agents while others are

503
Page 4

Figure 4: A suggested strategy for post-AKI targeted intervention
stratified using a combination of biomarkers and genomic methods
to stratify those at risk of adverse outcome. (Hudson, C et al. Semin
Cardiothorac Vasc Anesth. 2008 Dec;12(4):320-30.)
testing newer ones. Nonetheless, there are several exciting trials under way in post-cardiac surgical AKI. For
example, erythropoeitin has been shown to have diverse effects on nonhematopoeitic tissues that may be beneficial
in the prevention of AKI. Another promising treatment currently under investigation for the prevention of AKI is
minocyline. A second generation tetracycline, this antibiotic has both anti-inflammatory and antiapoptotic
properties. It has been shown in rat models to reduce nephrogenic inflammation and cell death. Currently, there is a
randomized, double-blind placebo control study under way to evaluate its efficacy preoperatively in patients with
pre-existing renal insufficiency undergoing cardiac surgery.
21

Intrarenal infusion of medication is another emerging therapy proposed to improve efficacy and decrease the
systemic effects of renal protective therapies. For instance, while systemic administration of a vasodilator may be
detrimental in a hypotensive post-surgical patient, selective renal vasodilation via intrarenal catheter infusion may be
beneficial in preventing AKI. Other therapies being investigated or revisited in AKI post cardiac surgery are sodium
bicarbonate, N-acetylcysteine, and tight glucose control.
Another phenomenon that is appears promising for management of AKI is recovery of renal function.
22
We have
recently shown that patients that recover renal function early after AKI may have reduced risk of mortality
compared to those who do not recover as well, given the same magnitude of injury (figure 3).
22
The repair and
regenerative potential of the kidneys may therefore be crucial to overall survival. With our failure to significantly
prevent postoperative AKI, salvage of renal function by targeting regenerative potential may the interventional
strategy that should be assessed next.

Summary
Acute kidney injury in the postoperative cardiac surgery population remains a significant cause of perioperative
morbidity and mortality. Despite extensive research in the prediction and treatment of this disease, there has been
limited success in altering patient outcomes. With advances in our understanding of underlying clinical and genetic
risk, as well as the development of more sensitive and specific biomarkers, we may be on the cusp of a new era of
AKI treatment. Once promising therapies are identified, customized approaches would harness information from
individuals own genetic profiles and biomarker
responses following cardiac surgery in order to
identify specific personalized interventions. For
example, preoperative evaluation may include a
genetic panel that stratifies patients into
categories of risk and targets them for
preventive therapies. For some high-risk
patients, this may also assist with the decision
whether to proceed with surgery or to use more
conservative medical management for their
cardiovascular disease. During the
perioperative period, urinary and serum
biomarkers could be used to detect AKI in the
earliest stages, confirm the appropriate
phenotype warranting intervention, and discern
anticipated responses to available agents in
order to deliver tailored therapy to each
individual patient (figure 4). Targeting renal
salvage to reduce mortality risk may offer hope
in those already affected by AKI. Although such a future hinges on many advances from the current state, we
believe that this multifaceted, individualized approach will finally lead to meaningful improvements in postoperative
AKI.
References
1. Conlon PJ, Stafford-Smith M, White WD, et al. Acute renal failure following cardiac surgery. Nephrol Dial
Transplant. 1999;14(5):1158-1162.
2. Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT. Renal
dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource

503
Page 5
utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med.
1998;128(3):194-203.
3. Chertow GM, Lazarus JM, Christiansen CL, et al. Preoperative renal risk stratification. Circulation.
1997;95(4):878-884.
4. Loef BG, Epema AH, Smilde TD, et al. Immediate postoperative renal function deterioration in cardiac
surgical patients predicts in-hospital mortality and long-term survival. J Am Soc Nephrol. Jan
2005;16(1):195-200.
5. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of
stay, and costs in hospitalized patients. J Am Soc Nephrol. Nov 2005;16(11):3365-3370.
6. Praught ML, Shlipak MG. Are small changes in serum creatinine an important risk factor? Current opinion
in nephrology and hypertension. May 2005;14(3):265-270.
7. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. May 2002;39(5):930-
936.
8. Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics--2006 update: a report from the
American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. Feb 14
2006;113(6):e85-151.
9. Swaminathan M, Shaw AD, Phillips-Bute BG, et al. Trends in acute renal failure associated with coronary
artery bypass graft surgery in the United States. Crit Care Med. Oct 2007;35(10):2286-2291.
10. Bhandari S, Turney JH. Survivors of acute renal failure who do not recover renal function. QJM. Jun
1996;89(6):415-421.
11. Daemen MA, van de Ven MW, Heineman E, Buurman WA. Involvement of endogenous interleukin-10
and tumor necrosis factor-alpha in renal ischemia-reperfusion injury. Transplantation. Mar 27
1999;67(6):792-800.
12. Stafford-Smith M, Phillips-Bute B, Reddan DN, Black J, Newman MF. The association of epsilon-
aminocaproic acid with postoperative decrease in creatinine clearance in 1502 coronary bypass patients.
Anesth Analg. 2000;91(5):1085-1090.
13. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med. Jan
26 2006;354(4):353-365.
14. Shaw AD, Stafford-Smith M, White WD, et al. The effect of aprotinin on outcome after coronary-artery
bypass grafting. N Engl J Med. Feb 21 2008;358(8):784-793.
15. Brown JR, Kramer RS, Coca SG, Parikh CR. The prognostic value of using the duration of acute kidney
injury in cardiac surgery: an example using two antifibrinolytics. The Journal of extra-corporeal
technology. Dec 2011;43(4):227-231.
16. Edelstein CL. Biomarkers of acute kidney injury. Adv Chronic Kidney Dis. Jul 2008;15(3):222-234.
17. Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for
acute renal injury after cardiac surgery. Lancet. Apr 2-8 2005;365(9466):1231-1238.
18. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Increased incidence of acute kidney
injury with aprotinin use during cardiac surgery detected with urinary NGAL. Am J Nephrol.
2008;28(4):576-582.
19. VandeVoorde RG, Katlman TI, Ma Q, et al. Serum NGAL and cystatin C as predictive biomarkers for
acute kidney injury. J Am Soc Nephrol. 2006;17:404A.
20. Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and
poor outcomes after adult cardiac surgery. J Am Soc Nephrol. Sep 2011;22(9):1748-1757.
21. http://clinicaltrials.gov/ct2/show/NCT00556491. Minocycline to Prevent Acute Kidney Injury After
Cardiac Surgery. Clinicaltrials.gov 2008; http://clinicaltrials.gov/ct2/show/NCT00556491, 2008.
22. Swaminathan M, Hudson CC, Phillips-Bute BG, et al. Impact of early renal recovery on survival after
cardiac surgery-associated acute kidney injury. Ann Thorac Surg. Apr 2010;89(4):1098-1104.

Disclosure

507
Page 1
Congenital Heart Disease in the Adult Presenting for Non-Cardiac Surgery
Susan S. Eagle, M.D. Nashville, Tennessee
Introduction: Advancement of surgical techniques and medical management patients with congenital heart lesions
has allowed this patient population to survive into adulthood, even with the most complex congenital lesions. As a
result, patients with patients with congenital heart lesions are increasingly encountered in the adult perioperative
setting for laparoscopic, obstetric, plastic, spine, and other non-cardiac procedures.
In the adult population, repaired or chronic non-palliated congenital heart lesions offer unique challenges. Therefore,
adult anesthesiologists must be familiar with the anatomy, long-term manifestations, and unique perioperative
management of adults with congenial heart disease.
Shunting Lesions: Intracardiac shunts, or communications between atria (atrial septal defects, ASD), ventricles
(ventricular septal defects (VSD), or great vessels (patent ductus arteriosus, e.g.) are the most common type of
congenital heart lesions. These communications allow shunting of blood from areas of high to low pressure,
typically left to right. While many are repaired surgically, these lesions may go unrecognized until adulthood. The
common consideration for shunting lesions is structural changes in the pulmonary vasculature resulting in
pulmonary hypertension with subsequent right ventricular failure. Chronic severe pulmonary hypertension in the
context of shunting lesions may result in
Eisenmenger syndrome with reversal of shunt
(right to left) and hypoxemia.
Preoperative evaluation should include a
thorough history and physical, with particular
attention to pulmonary hypertension and right ventricular failure. Right ventricular failure is heralded by elevated
jugular venous pressure, hepatomegaly, hepatic dysfunction, or peripheral edema. 12-lead electrocardiogram is
useful to detect atrial fibrillation or flutter, common with atrial enlargement in these patients. Patients with previous
VSD repair may have heart block from surgical patching proximal to or within the conduction system. These
patients may have a permanent pacemaker, which requires interrogation and proper programming in the
perioperative setting. Right heart catheterization is an invaluable tool for determining preoperative pulmonary artery
pressures.
The primary goals for the anesthesiologist caring for these patients include meticulous de-airing of vascular lines,
decreasing pulmonary vascular resistance, maintaining adequate right ventricular function, and increasing systemic
vascular resistance. Adequate ventilation and oxygenation is paramount to the care of these patients. Hypercarbia
secondary to excessive premedication with midazolam or narcotics can result in right ventricular failure and
Figure 1: Sinus venosus ASD, an
example of a shunting lesion.
Large defects as shown cause
significant RV volume overload
and pulmonary hypertension.
SVASD is also associated with
anomalous pulmonary venous
return (not shown).
507
Page 2
cardiovascular collapse in patients with severe pulmonary hypertension. Similar effects may be seen with induction-
induced apnea. Avoidance of sympathetic-induced pulmonary vasoconstriction with adequate anesthesia, analgesia,
and normothermia is recommended. Inhaled prostaglandins or nitric oxide are useful for reversible pulmonary
hypertension. Right ventricular dysfunction in this setting may require inodilator drugs, such as milrinone or
dobutamine. Increasing systemic vascular resistance with vasopressin, e.g. will offset decreased LV filling caused
by right ventricular dilation.
Complex lesions of the great vessels: Lesions of the great vessels include transposition of the great arteries (TGA)
and truncus arteriosus (TA). Critical for survival, these lesions require intracardiac shunting for mixing of blood
and adequate oxygenation. Left unrepaired, these lesions typically result in severe pulmonary hypertension and are
usually fatal.
TGA is a discordance of the ventricles and great vessels. Early repair includes the Mustard or Sennig procedures
involving an intra-atrial baffle or tunnel that redirects blood to the anatomically correct side. In these patients, the
right ventricle is remains the systemic ventricle. Considerations for these patients are right ventricular failure and
atrial arrhythmias from the baffle suture lines.
Similarly, repair of truncus arteriosus involves separation of the great vessels to their respective ventricles and VSD
repair. Considerations are anastamotic strictures, aortic valve insufficiency, persistent VSD, and ventricular
arrhythmias. Cardiac MRI is a useful tool for delineating the anatomy and identification of conduit or vessel
abnormalities. Repair of TGA since the mid-1980s is via the arterial switch procedure, where the pulmonary artery
and aorta are surgically reversed. Unique considerations include stenosis at the anastamotic sites (PA or aorta) and
pulmonic or aortic insufficiency.
Tetralogy of Fallot: TOF is one of the most commonly encountered adult congenital heart lesions. TOF is defined
by the presence of a VSD, overriding aorta, right ventricular outflow tract obstruction (or pulmonary valve stenosis),
and right ventricular hypertrophy. Most patients encountered have received a definitive repair of this lesion, though
there exists a rare population of unrepaired TOF. Unrepaired lesions, unlike our previous categories, obstruction to
pulmonary flow is protective against pulmonary overload and pulmonary hypertension. However, right ventricular
failure secondary to RVOT obstruction is common. Further, bidirectional or right to left shunting through the VSD
may result in profound hypoxemia. This is treated by intravascular volume expansion, beta blockade, and
Figure 2: Treatment for
pulmonary hypertension in
the perioperative setting.

507
Page 3
phenylephrine. These maneuvers decrease RVOT obstruction and increase systemic vascular resistance, promoting
left to right shunting.
More commonly encountered is the patient with repaired TOF with a VSD patch and augmentation of the RVOT or
pulmonic valve. A common surgical method to augment the RVOT is transannular patching. These repairs have
resulted in severe pulmonary valve insufficiency, RV volume overload, and right ventricular failure. The
combination of RV enlargement and RV scarring at the ventriculotomy site causes localized slowing of the
conduction system and malignant ventricular arrhythmias. A QRS interval > 180 ms is predictive of re-entrant
monomorphic ventricular tachycardia. It is not uncommon for patients with repaired TOF to have an implantable
cardioverter defibrillator (ICD). In addition, the overriding aorta may result in aortic insufficiency over time. VSD
patch leak is also a consideration. Intravascular air should always be avoided in congenital heart patients, even with
repaired lesions.

B.

Figure 3: Sequelae of TOF repair. A. TEE modified RV outflow
tract view with dilated right ventricle, RVOT and pulmonic valve.
B. Same TEE view with severe pulmonic insufficiency by color
Doppler. C. Left ventricular outflow tract TEE view with dilated
RV, VSD patch, and overriding aorta.
A.
B
.

507
Page 4

Complex congenital cardiac lesions: Several
types of complex congenital heart lesions exist
where preservation of biventricular function is
not feasible. These lesions include hypoplastic
left heart syndrome, tricuspid atresia,
unbalanced atrio-ventricular septal defects,
double inlet left ventricle, double outlet right
ventricle, and some forms of heterotaxy
syndrome.

While the initial anatomy of complex congenital heart lesions is rather variable, surgical treatment often results in
the common endpoint, Fontan palliation. Independent of the initial congenital lesion, there are two essential
components of Fontan physiology. First is the presence of a single ventricle (SV) dedicated to pumping oxygenated
blood to the systemic system via the aorta. The SV may be an anatomical right or left ventricle, depending on the
initial defect. Second, the entire systemic venous return reaches the pulmonary arterial system via a total
cavopulmonary connection (TCPC). Creation of a TCPC involves surgical anastamosis of the superior vena cava
(SVC) and the inferior vena cava (IVC) to the pulmonary artery in a staged fashion. As a result, pulmonary blood
flow is dependent upon an adequate trans-pulmonary gradient--a 5 to 8 mmHg gradient between the central venous
system and the left atrium. Decreases in trans-pulmonary gradient in the setting of inadequate preload, depressed
ventricular function, or increases in PVR manifest as systemic hypotension and decreased perfusion.
Figure 4: A variety of complex
congenital defects that often
lead to Fontan palliation
C.

507
Page 5

Evaluation of the adult with Fontan physiology involves a thorough history and physical examination using a multi-
system approach with attention to the unique characteristics of this patient population. Medical records, most recent
catheterization, cardiac MRI, and laboratory data are invaluable to elucidate cardiac anatomy, oxygen saturation,
pressure data, and SV function. A thorough history should focus on changes in health status, exercise capacity,
hospital admissions, pharmacology, and allergies.
Physical examination of a well-functioning Fontan patient should be relatively unremarkable, in spite of
univentricular pathology. Fontan patients are expected to be normothermic and acyanotic. Peripheral arterial
pulses are palpable and precordial auscultation is devoid of murmurs. Normal oxygen saturation by pulse oximetry
is typically between 90 to 95% in patients with a well-functioning Fontan. Oxygen saturations exceeding 95%
percent are not expected due to shunting of blood via the coronary sinus. Normal-sized cardiac silhouette and
absence of pleural effusions on chest radiography and normal sinus rhythm by electrocardiography (ECG) are
expected.
Standard intraoperative monitoring is adequate for patients with a well-functioning Fontan, particularly for
procedures where minimal hemodynamic derangements or fluid shifts are expected. Upper extremity blood pressure
measurements should be taken on the opposite side of a previous Blalock-Taussig (subclavian artery to pulmonary
artery) shunt to avoid an artificially low blood pressure.
Induction of anesthesia may be heralded by hypotension and hypoxemia. NPO status results in decreased preload,
the primary driving force for pulmonary blood flow in Fontan patients. Conservative administration of intravenous
fluids or colloids prior to induction of anesthesia may be prudent.
Achieving adequate pulmonary blood flow and cardiac output is the mainstay of anesthetic management of patients
with Fontan physiology. While there is predilection of volatile anesthetics and positive pressure ventilation to cause
hypotension in Fontan patients, general anesthesia must be adequate to prevent sympathetic stimulation leading to
detrimental increases in pulmonary vascular resistance. Similarly, inadequate tidal volumes lead to atelectasis,
hypoxemia, and hypercarbia. Since the majority of venous return with IPPV occurs during expiration, inspiratory
time should be shortened accordingly.
Caution must be taken with monitored anesthesia care (MAC) since hypoventilation leads to increased PVR.
Epidurals have been used successfully in the perioperative management of Fontan patients. Epidural dosing is
progressively titrated to minimize sympatholytic effects, venodilation, and decreased pulmonary return.
Endocarditis prophylaxis is recommended Fontan patients, due to increased endocarditis risk with palliative shunts
and conduits.
In spite of excellent survival rates, Fontan patients are at progressive risk for failing palliation. Preoperative
findings indicative of a failing Fontan include fatigue, decreased activity level, weight gain or volume retention,
palpitations, syncopal or pre-syncopal episodes, oxygen saturation below 90%, and dyspnea. Physical findings are
often secondary to SV failure, atrial arrhythmias or sinus node dysfunction, AV valve dysfunction, infectious
processes, protein-losing enteropathy and systemic-to-pulmonary artery collaterals. Abnormalities on chest
radiography consistent with failing Fontan include cardiomegaly, pulmonary edema, and pleural effusions.

Figure 5: Fontan schematic in patient
with hypoplastic left heart syndrome:
Salient features are total cavopulmonary
return, atrial communication, and right
ventricle as systemic ventricle.

507
Page 6

The incidence of arrhythmias, particularly atrial tachyarrhythmias, increases with time. A prevalent rhythm in the
Fontan patient is intra-atrial reentrant tachycardia (IART), or slow atrial flutter. IART is characterized by 2:1 AV
conduction with the second p wave buried in the QRS complex or the T-wave, making the diagnosis elusive.
Protein-losing enteropathy (PLE) is an enigmatic problem with a significant mortality and no clear treatment
modality. Pleural effusions, decreased, SpO2, peripheral edema, and ascites are consistent findings in patients with
PLE. Decreased levels of albumin and total protein, and stool positive for alpha-1 antitrypsin confirm the diagnosis
of PLE.
Hepatic cirrhosis is a commonly associated with failing Fontan palliation. Coagulopathy and esophageal varices
may be associated.
Thromboembolic events, including pulmonary embolism and cerebral vascular accidents, occur in up to 25% of
patients, and are a source of significant morbidity and mortality for patients with Fontan physiology. Prior to
elective cardioversion, intracardiac thrombi should be excluded by TEE.
Plastic bronchitis, a late finding after Fontan palliation, consists of obstructive bronchial casts within the
tracheobronchial tree. Once new-onset or worsening failed Fontan physiology is evident, elective surgery should be
postponed for further investigation.

Disclosure

Figure 6: Multi-organ
dysfunction associated
with failing Fontan
palliation.
21
513
Page 1
Hypoxia During Thoracic Surgery: Practical Advice for the Anesthesiologist
Javier Campos, M.D. Iowa City, Iowa
Learning Objectives:
As a result of completing this activity, the participant will be able to
List the factors that predict hypoxia during one-lung ventilation
Describe the different ventilation maneuvers to restore or improve arterial oxygenation
Describe the effects of anesthetics on hypoxia and inflammation, as well as their protective effects on the lung
Double-lumen tubes or bronchial blockers are used to provide one-lung ventilation (OLV) in patients undergoing
lung, esophageal, thoracic vascular, minimally invasive cardiac, and occasionally mediastinal surgery.1,2 During
OLV, an intrapulmonary shunt may result in hypoxemia related in part to collapse of the nondependent lung and
increased atelectatic areas in the dependent lung.3 Hypoxemia by definition is a decrease in oxygen saturation
(SpO2) to less than 90%4 or an arterial oxygen tension (PaO2) <60 mm Hg when the patient is being ventilated at
an inspired oxygen fraction (FiO2) of 1.0.5 The incidence of hypoxemia during OLV has been reported to be 1
10%. This relative infrequency is related in part to advances with routine use of a fiberoptic bronchoscope for
optimal placement of lung isolation devices. It is also attributable to the introduction of newer volatile anesthetics
that cause less inhibition of hypoxic pulmonary vasoconstriction (HPV) in a dose-dependent fashion and less venous
admixture during OLV.69
This review focuses on the predictors of hypoxia during OLV, the pathophysiology of HPV, protective
ventilation maneuvers to restore or improve arterial oxygenation, the effects of anesthetics on hypoxia and
inflammation, and cerebral desaturation episodes and hypoxia during OLV.
PATIENTS AT RISK OF DEVELOPING HYPOXIA DURING OLV
Slinger et al,10 using a regression analysis model in 80 patients undergoing OLV, showed that the three most
significant predictors for PaO2 were (1) side of operation (because the right lung is approximately 10% larger than
the left lung, there is better oxygenation during left than right thoracotomy), (2) the percentage of forced expiratory
volume in one second (FEV1), and (3) reduced intraoperative PaO2 during two-lung ventilation when patients were
breathing spontaneously in a lateral decubitus position. Others11,12 have shown better oxygenation during left-sided
thoracic procedures as compared to right-sided surgeries when an FiO2 of 1.0 is used.
Schwarzkopf et al.11 reported that patients undergoing lobectomy and pneumonectomy had better
oxygenation during OLV than patients undergoing video thoracoscopic metastasectomy. Lung perfusion studies in
these patients showed that perfusion of the nonventilated lung was more impaired in patients presenting for
pneumonectomy.
Another group of patients identified to be at risk of developing hypoxia are the morbidly obese. One study reported
that patients with a body mass index >30 kg!m2 undergoing thoracic surgical procedures with OLV developed
more intraoperative hypoxemia and increased alveolar oxygen difference than nonobese patients.13 Also, patients
with previous lobectomy requiring a second procedure in the contralateral lung may be at risk of developing
hypoxemia during total lung collapse because 25% of the lung function was compromised in the previous
lobectomy.14
The effects of the supine or lateral decubitus position on arterial oxygen tension will vary depending on
whether or not the lung is exposed to OLV. In general, surgeons who perform thoracic surgery with OLV most
commonly operate with the patient in a lateral decubitus position. Therefore, gravity is a major determinant of shunt
fraction and perfusion.15 Recent studies16,17 have examined the changes in PaO2 during procedures requiring
OLV. In a study by Watanabe et al,16 patients undergoing OLV were ventilated with an FiO2 of 1.0 and divided
into three groups. One group was placed in the supine position, another group in a left semilateral position, and the

513
Page 2
third group in left full-lateral position. In the supine position, 9 out of 11 patients had arterial oxyhemoglobin
saturations <90% while receiving OLV. Only one patient each in the other two groups developed hypoxemia.
A study by Bardoczky et al17 compared the positional effects and the inspired fraction of oxygen during
OLV. Patients were randomly assigned and received different concentrations of oxygen (FiO2 of 0.4, 0.6, or 1.0)
during two-lung ventilation and thereafter OLV in the supine and lateral positions. PaO2 decreased more during
OLV compared to two-lung ventilation regardless of the position. However, in all three groups, PaO2 was
significantly higher during OLV in patients in the lateral compared to the supine position.
These studies clearly demonstrate that during OLV in a lateral decubitus position, gravity augments the
redistribution of perfusion to the ventilated (dependent) lung, improving V/Q matching. Therefore, supine patients
requiring OLV will likely experience more transient episodes of hypoxemia. Figure 1 displays PaO2 values during
OLV in the supine or lateral decubitus position in patients with normal lung function16 or with chronic obstructive
pulmonary disease.17 Table 1 lists risk factors that will play a role in desaturation and hypoxemia.18

Figure 1:

This figure displays the PaO2 values over time during one-lung ventilation (OLV) in supine-lateral and semi-lateral
position.
Normal pulmonary function test (PFT) patients (Modified from reference #16)
Chronic obstructive pulmonary disease (COPD) patients (modified from reference #17)
(Modified with permission from reference #18)

Table 1: Factors That Will Increase the Risk of Desaturation during OLV
High percentage of ventilation or perfusion to the operative lung on preoperative V/Q scan
Poor PaO2 during two-lung ventilation in the lateral decubitus position
Right-sided thoracotomy
Normal preoperative spirometry (FEV1 or FVC)
Supine position during OLV
Morbidly obese patient during OLV
Previous lobectomy and contralateral lung collapse surgery
(Modified with permission from reference #18)

PATHOPHYSIOLOGY OF HYPOXIA DURING OLV
Hypoxemia during OLV is caused by venous admixture through shunts and areas of low V/Q gas exchanging units.
During OLV, the collapsed, nondependent lung is an obligate shunt while the dependent lung also causes a venous
admixture through the shunt and areas of low V/Q. V/Q mismatch is a consequence of atelectasis and is perhaps
increased with the patient in the lateral decubitus position by the weight of the mediastinum, abdominal organs,
retraction, and low compliance of the chest wall.19
The determinants of arterial oxygen content include hemoglobin concentration, hemoglobin dissociation
curve (P50), oxygen consumption, total cardiac output, FiO2, arterial carbon dioxide level (PaCO2), blood flow
through the nonventilated (nondependent) lung, and unventilated or low V/Q areas of the ventilated lung (dependent
lung). The last two factors are often associated together as shunt (Q) or shunt fraction (Qs/Qt).20

513
Page 3
In a lateral decubitus position when both lungs are being ventilated, the proportion of the pulmonary blood
flow is distributed as follows: the dependent (or down) lung receives approximately 60% of the pulmonary blood
flow (more perfusion) while the nondependent lung receives 40% of the total pulmonary blood flow. When OLV is
instituted, the nondependent lung becomes atelectatic. Because the alveolar arterial oxygen tension decreases, there
is a response to hypoxia, HPV, in which increased pulmonary vascular resistance diverts blood flow toward the
dependent lung. Figure 2A shows the redistribution of pulmonary blood flow in the lateral decubitus position while
both lungs are being ventilated. Figure 2B displays the atelectatic nonventilated lung along with the percentage of
HPV response.
Figure 2:

Figure 2A. The lungs of a patient positioned in the lateral decubitus position. The dependent, or down, lung receives
approximately 60% of the total pulmonary blood flow (PBF). The non-dependent but ventilated lung receives
approximately 40% of the total PBF.

Figure 2B. A non-dependent (collapsed) lung. This leads to a 50% response of HPV as blood flow is being diverted
to the dependent lung. In general, the Qs/Qt fraction seen during general anesthesia and OLV ranges from 20 to 40%
(this is the amount of blood not being oxygenated).

During OLV, the nondependent (operated) lung remains atelectatic and hypoperfused because of HPV.
Thus, the HPV in the nondependent lung ameliorates the pulmonary ventilation/perfusion relationship, preserving
systemic oxygenation by constricting pulmonary vessels in poorly ventilated or atelectatic hypoxic lung regions to
divert the pulmonary blood flow to better aerated areas.21 Although HPV decreases the shunt fraction and attempts
to resolve hypoxemia,22 there are associated factors to consider when ventilation is restored because pulmonary
reexpansion to correct hypoxemic episodes promotes reentry of oxygen through the airways, causing the release of
excessive oxidative radicals.23

MANAGEMENT OF INTRAOPERATIVE HYPOXEMIA DURING OLV
During the management of OLV, if the patients oxygen saturation as measured by pulse oximetry falls below 90%
or the PaO2 is <60 mm Hg, any nonurgent surgical procedure must be stopped. FiO2 should be increased to 1.0%
and two-lung ventilation restored. One should reassess the lung isolation device to ensure that the double-lumen tube
or bronchial blocker is in the correct position.24 During a pneumonectomy, hypoxemia can often be eliminated by
surgical clamping of the pulmonary artery feeding the operated lung (Table 2).

513
Page 4
Table 2. Treatment of Hypoxia during OLV
Increase the fraction of inspired oxygen to 100%
Convert to two-lung ventilation
Re-expand the collapsed lung
Confirm optimal position of lung isolation device with a flexible fiberoptic bronchoscope. After SpO2 has been
improved (i.e., SpO2 >98%), convert to OLV and apply CPAP 5 cm H2O to the non-dependent lung.
Unless counterproductive (i.e., auto PEEP >10 cm H2O), use PEEP 5 cm H2O to the dependent lung
Adjust ventilation according to the patients needs to maintain a PaCO2 3540 mm Hg and peek pressure of
<35 cm H2O
Use pressure-controlled ventilation in patients with severe emphysema or who are morbid obese
Perform ventilatory maneuvers prior to or during OLV if the patient is at risk for hypoxia during OLV
If a DLT is being used in video thoracoscopic surgery, consider selective O2 insufflation to the non-ventilated
lung with a fiberoptic bronchoscope
If a bronchial blocker is used, consider selective lobar blockade in patients with previous contra-lateral
lobectomy
Use intermittent O2 insufflation with 2 L/min for short intervals to the non-dependent lung
To reduce the shunt fraction, clamping pulmonary vessel by the surgeon during pneumonectomy cases will
improve oxygenation

Malposition of lung isolation devices is a common cause of hypoxemia. A study by Inoue et al5 showed
that patients who experience malposition of the double-lumen tube after being turned into the lateral decubitus
position had more malpositions during OLV and more hypoxemic episodes that required intervention to treat the
hypoxemia. A study by Campos et al25 showed that anesthesiologists with limited thoracic surgery experience
reported a frequent incidence of malposition (38%) of lung isolation devices. If hypoxemia occurs during OLV, the
first step is to ventilate the patients lung with FiO2 1.0%. After the device is correctly positioned, fiberoptic
bronchoscopy can determine whether all lobar bronchi and segmental branches are patent and free of secretions. In
addition, it is important that the patient under OLV be maintained normocapnic, normotensive, and normothermic.
Any extreme alteration of these factors will also contribute to the development of hypoxemia by modifying HPV.
Hemodynamic parameters must be checked to ensure that the desaturation episodes are not related to profound
hypotension caused by compression of the vena cava or direct compression of the aorta or pulmonary vessels.

VENTILATORY MANEUVERS TO IMPROVE ARTERIAL OXYGENATION
Alveolar recruitment maneuvers, continuous positive airway pressure (CPAP), positive end-expiratory pressure
(PEEP), fiberoptic oxygen insufflation, and selective lobar ventilation during hypoxia and OLV may be used to
improve arterial oxygenation.

Alveolar Recruitment Maneuvers
Lung recruitment is a ventilator maneuver aimed to reverse atelectasis by means of a brief, controlled increase in the
airway with expansion of the lungs. Clinical studies involving thoracic surgical patients undergoing OLV have
shown that employing lung recruitment prior to OLV or in the minute thereafter reduces atelectasis, improves
arterial oxygenation, and decreases pulmonary shunt and dead space with an adequate level of PEEP.26-28 One
study28 showed that recruitment of both lungs before instituting OLVby giving 10 consecutive breaths at a
plateau pressure of 40 and incremental levels of 510 up to 20 cm H2O of PEEPimproved arterial oxygenation.
Mean PaO2 values for the control group (no recruitment maneuvers) during OLV were 182 79 mm Hg; in
contrast, the group that received alveolar recruitment maneuvers had a mean PaO2 value of 251 69 mm Hg during
OLV. In some cases, increasing the PaO2 value to a safer level during OLV might eliminate the need for additional
therapeutic intervention such as CPAP. Although alveolar recruitment maneuvers improve oxygenation, they may
cause transient hypotension because the excessive intrathoracic pressure interferes with blood venous return.

CPAP
CPAP has traditionally been used to treat hypoxemia because of the obligatory shunt developed by the
nondependent (collapsed) lung. Application of CPAP has been suggested in the deflation phase of tidal volume (VT)
breath. CPAP is thought to improve oxygenation by a passive mechanism (uptake of oxygen by the alveoli with
continuous oxygen administration). It is recommended to start with 5 cm H2O of CPAP and progressively increase
to no more than 10 cm H2O. For CPAP to work, it must be applied to an at least partially reexpanded lung before it

513
Page 5
is adjusted to the desired value. Of the new CPAP devices, the easiest to use is the Mallinckrodt (Covidien,
Mansfield, MA) that can be attached to a lumen of the double-lumen tube or the center channel of a bronchial
blocker. Figure 3 shows the CPAP circuit attached to the center channel of a bronchial blocker.

Figure 3:

Figure 3 shows the Mallinckrodt continuous positive airway
pressure (CPAP) circuit attached to the center channel of a bronchial
blocker.

Oxygen insufflation by CPAP of up to 10 cm H2O into the
nondependent lung, along with no PEEP to the dependent lung during OLV,
has improved oxygenation to an average mean PaO2 value of 286 49 mm
Hg and a Qs/Qt fraction of 28 2.5% in thoracic surgical patients.29 The beneficial effects of CPAP are primarily
due to oxygen uptake from the nonventilated lung, not to blood flow diversion to the ventilated lung.
CPAP, even when properly administered, is not completely reliable for improving oxygenation during OLV
when the bronchus of the nonventilated lung is obstructed or open to the atmosphere, as in a patient with a
bronchopleural fistula or during endobronchial surgery. Also, in some situations such as thoracoscopic surgery,
CPAP may prevent adequate surgical exposure because of the partial expansion of the lung.

PEEP
Should PEEP be used routinely in all patients undergoing OLV? Resistance to blood flow through the lung is related
to lung volume in a biphasic pattern and is lowest when the lung is at its functional residual capacity (FRC).
Keeping the ventilated lung as close as possible to its normal FRC encourages pulmonary blood flow to the lung. In
select patients, the application of PEEP to the dependent (ventilated) lung is beneficial because it restores FRC to
close to normal values.30 This ventilatory maneuver will prevent atelectasis when its value is titrated along the static
compliance curve of the flow/volume curves.31 Many patients do not reach their end-expiratory equilibrium FRC
lung volume as they try to exhale a relatively large VT through one lumen of the double-lumen tube during OLV.
These patients develop dynamic hyperinflation and a positive end-expiratory pressure (auto-PEEP).32
Auto-PEEP occurs more often in patients with decreased lung elastic recoil, such as in the severely
emphysematous patient, and the estimated auto-PEEP averages 46 cm H2O in most lung cancer patients with
chronic obstructive pulmonary disease (COPD). The effects of applying external PEEP through the ventilator circuit
to the lung in the presence of auto-PEEP are complex. Slinger et al31 have shown that patients with a very low auto-
PEEP (i.e., <2 cm H2O) will have a greater increase in total PEEP from moderate (5 cm H2O) external PEEP than
those with a high level of the already present auto-PEEP (>10 cm H2O). The same study31 showed that if the
application of PEEP shifts the expiratory equilibrium position on the compliance curve toward the lower inflection
point of the curve, then the external PEEP will be beneficial.
A study by Yokota et al33 showed that auto-PEEP becomes more evident during OLV and is worst in
patients who have poor FEV1/forced vital capacity ratios. Also, this study showed no correlation with the
intraoperative PaO2 and auto-PEEP. Auto-PEEP is difficult to detect and measure intraoperatively with our
anesthesia machines. The application of PEEP during OLV to improve oxygenation depends on the individual
patients lung mechanics. Patients with normal lung parenchyma or those with restrictive lung disease tend to fall
below their FRC at the end-expiration during OLV and may benefit from the application of PEEP to the dependent
lung.34
When should PEEP be applied during OLV? A study by Ren et al35 in patients requiring OLV examined
the best time to apply PEEP and the ideal level of PEEP application. In their study, 30 patients undergoing thoracic
surgery were divided into three groups. No PEEP application or 510 cm H2O PEEP was applied at different
intervals. In one group, 5 cm H2O of PEEP was maintained during the entire time of OLV. The authors reported that
PEEP applied at the initial time of OLV improves oxygenation. Also, they reported that 5 cm H2O of PEEP may
produce a beneficial effect without the increase in airway pressure associated with 10 cm H2O of PEEP.
Another study, this one by Hoftman et al,36 reported that a VT of 6.6 mLkg plus 510 cm H2O of PEEP
in patients undergoing OLV improved oxygenation >20% from baseline in only 29% (12 of 41 patients); in contrast,
71% (29 patients) had no improvement of oxygenation. This study clearly confirms that the response to PEEP is
related to the lung mechanics of each individual patient. Another alternative to treat hypoxia during OLV is by

513
Page 6
intermittent positive airway pressure to the nonventilated lung. Russell37 managed 10 patients whose desaturated
SpO2 was <90% during OLV. They received slow inflation of 2L/min O2 in the nonventilated lung from 2 to 10
seconds for 5 min. In all 10 patients, the SpO2 rose to an average of 96% and PaO2 improved from a mean value of
67 13 to 99 20 mm Hg.

Selective Lobar Ventilation
Campos et al38 reported improved arterial oxygenation in thoracic surgical patients undergoing OLV when they
used selective lobar blockade with a bronchial blocker to block only the surgical lobe while ventilating the rest of
the lobes in the ipsilateral side, and with 5 cm H2O of CPAP delivered to the nondependent lung. Therefore, for
patients who have a history of previous contralateral lobectomy and years later require a surgical procedure on the
opposite lung, a selective lobar blockade should be considered in order to ventilate the remaining lobe on the
surgical side and to preserve or improve arterial oxygenation.14,38

Fiberoptic Oxygen Insufflation
An alternative method to treat hypoxemia during OLV for thoracoscopic surgery is by selective insufflation of
oxygen using the fiberoptic bronchoscope (with the suction channel connected to the O2 source), where the tip of
the bronchoscope is selectively positioned into the basilar segments of the nondependent lung and positioned in the
distal (nonsurgical) lobe. Apneic oxygenation with 5 L/min has been shown to improve oxygenation with this
technique.39 When applying CPAP or oxygen insufflation to the nondependent lung, it is always advisable to
observe the direct distention of the collapsed lung and make necessary adjustments to avoid overdistention of the
nonventilated lung.

EFFECTS OF ANESTHETIC TECHNIQUE ON HYPOXIA AND INFLAMMATORY RESPONSE
DURING ONE-LUNG VENTILATION
In the 1980s, special attention was given to the effects of anesthetics and HPV during OLV.40 One study40
reported that, in the canine model, the effect of isoflurane on HPV was dose-dependent inhibition. Others,9 using the
pig model, compared the effects of different minimal alveolar concentration (MAC) concentrations of desflurane
and isoflurane on lung perfusion, Qs/Qt fraction, and oxygenation during OLV. This study reported that pulmonary
venous oxygen, mixed venous oxygen saturation, and Qs/Qt fraction decreased in a dose-dependent fashion (i.e.,
MAC of 0.5, 1.0, and 1.5, respectively) without affecting arterial oxygenation. In addition, the influence of thoracic
epidural analgesia plus 0.5% MAC of isoflurane has been studied in patients undergoing OLV and compared with
total intravenous anesthesia with propofol.41 This study showed that, based on PaO2, arterial oxygenation was
better in the group who received general anesthesia with volatile agents plus thoracic epidural analgesia. Thus, the
effects of inhaled anesthetics on HPV are dose-dependent and thoracic epidural analgesia has no influence on HPV
as long as arterial blood pressure is maintained.
OLV increases a proinflammatory response, including cytokine release and leukocyte recruitment in the
ventilated lung. In the past 10 years, special interest has been focused on the effects of anesthetics and ventilation on
the inflammatory response by measurement of interleukinsinterleukin (IL), interleukin I" (I"), tumor necrosis
factor (TNF#), and IL1-6-8from bronchoalveolar lavage or systemic circulation, as well as the potential
effect/complications after OLV, including the development of acute lung injury, which has a reported incidence of
4.2% after thoracic surgery.42 Some have recommended the use of low levels of VT (i.e., 5 mL!kg) during OLV to
reduce the risk of lung injury. One study43 showed that 5 mL!kg of VT during OLV was associated with lower
levels of interleukin (IL6-8-10, IL18, and TNF#) when compared to a high VT of 10 mL!kg. However, the use of
small VT might predispose patients to atelectasis during general anesthesia.44 As a result, other investigators have
used different ventilatory strategies to maintain or improve oxygenation during OLV. Michelet et al45 reported that
protective ventilation with VT of 5 mL!kg plus 5 cm H2O of PEEP to the dependent lung in esophagectomy
patients has lower plasmatic levels of interleukins (IL, I", IL6-8, and TNF#) when compared to conventional
ventilation of 9 mL!kg during OLV. These same studies reported a lower extravascular lung water index and
intrathoracic blood volume ratio. The patients in the Michelet study had improved lung function, their tracheas were
extubated earlier, and they had a decreased proinflammatory systemic response compared with the group who
received conventional ventilation of a large VT.
The anesthetic technique plays an important role in the proinflammatory response during OLV. Schilling et
al46 reported an immunomodulatory effect with the use of a volatile anesthetic, desflurane, in the dependent
ventilated lung when compared to intravenous propofol anesthesia. This study reported an induced proinflammatory
response in the dependent lung during OLV while it was ventilated with a decidedly nonphysiological VT of 10
mL!kg. The study also showed that the immune response was attenuated by desflurane, and the administration of

513
Page 7
propofol resulted in a relative increase of alveolar granulocyte fraction. DeConno et al47 showed potential lung
protection with the use of sevoflurane (vs. propofol) in thoracic surgical patients undergoing OLV. Bronchoalveolar
lavage was performed before and after OLV on the nondependent lung, showing a marked reduction of
inflammatory mediators and a significantly better outcome in the group that received sevoflurane anesthesia. In
contrast, a similar study48 evaluated the effects of propofol, desflurane, and sevoflurane and the relationship
between pulmonary and systemic inflammation in patients undergoing thoracic surgery who required OLV. That
study showed that desflurane and sevoflurane suppressed the local alveolar response (lower cytokines) when
compared to propofol; however, the systemic inflammatory response was not evident with the three anesthetics
studied. All the studies discussed in this paragraph appear to support the beneficial effects of using volatile
anesthetics to suppress pulmonary cytokines as well as their potential protective effects against inflammation.
During OLV, it is not uncommon to switch from volume-controlled ventilation to pressure-controlled ventilation in
order to improve oxygenation. One study involving thoracic surgical patients demonstrated that better oxygenation
was achieved when pressure-controlled ventilation was used during OLV.49 Another study50 used a crossover
design involving thoracic surgical patients requiring OLV who had relatively normal lung function. Arterial
oxygenation was similar in the groups who received volume-controlled ventilation (PaO2 mean value 206 62 mm
Hg) when compared to pressure-controlled ventilation (PaO2 202 56 mm Hg). In addition, this study reported a
decrease in peak pressure in the group who received pressure-controlled vs. volume-controlled ventilation (24 3
cm H2O vs 34 5 cm H2O). Pressure-controlled ventilation appears more beneficial for the morbidly obese patient
or the severely emphysematous patient undergoing OLV.
Pharmacological interventions have been used to control pulmonary blood flow, prevent decreases of PaO2
during OLV, or improve oxygenation.5153 Some studies have shown that the use of a respiratory stimulant such as
almitrine intravenously improved oxygenation during OLV, probably due to the molecular mechanism of action on
the pulmonary vessels combined with direct stimulation of chemoreceptors and direct pulmonary vasoconstrictor
action.51 Another study showed no effect on oxygenation with inhaled nitric oxide (NO) in patients undergoing
OLV.52 However, the combination of NO and almitrine showed an improvement in PaO2 values during OLV in
two studies.53,54 Almitrine is not FDA approved and is unavailable in the United States.
Others have reported improved arterial oxygenation with inhaled epoprostenol plus intravenous
phenylephrine infusion during OLV in a patient with interstitial lung disease undergoing video-assisted
thoracoscopic surgery.55 Doering et al56 reported improved arterial oxygenation with phenylephrine and NO in
patients with adult respiratory distress syndrome. The mechanism by which vasoconstrictors such as phenylephrine
may improve oxygenation is unclear, but could result from enhancing HPV.

CEREBRAL DESATURATION DURING OLV
Another area that deserves special attention is the effect of hypoxia during OLV in relationship to a decrease in
regional cerebral oxygen saturation (SctO2) in thoracic surgical patients. There are different monitors that measure
SctO2, such as the FORE-SIGHT Cerebral Oximeter (CAS Medical Systems, Branford, CT) or the INVOS
Cerebral/Somatic Oximeter (Covidien, Boulder, CO). These devices have been used in patients undergoing OLV
with mixed results. A study by Hemmerling et al57 showed that an absolute value of SctO2 of 80% was recorded
while the patients were awake; during OLV this value decreased to an average of 63%, and during extubation it rose
to 71%. Overall in the 20 patients studied, cerebral desaturation >20% was recorded from baseline values.
Interesting in this study was the lack of correlation with SpO2 and PaO2. Also, no neurobehavioral testing was
performed to evaluate the neuropsychological outcome in these patients. In another study58 involving 40 patients
undergoing OLV, a SctO2 monitor detected cerebral desaturation in 28 patients; the minimum SctO2 during OLV
was lower than baseline value. The percentage of change was negatively correlated with preoperative respiratory
function. Another study59 showed that the duration of cerebral desaturation time during OLV correlates with the
Mini-Mental State Examination (MMSE); of the 69 patients studied, only 17 developed desaturation (SctO2 <80%
of the baseline value) and MMSE scores decreased significantly in this group. Overall, although measuring SctO2
values is interesting technology, further studies are needed to demonstrate the changes in SctO2 during OLV and
their association with hypoxemic events measured by SpO2.

RESTORATION OF TWO-LUNG VENTILATION
During OLV, the collapsed lung remains atelectatic and hypoperfused. After restoration of two-lung ventilation,
reentry of oxygen through the airways and alveoli produces a reactive pulmonary vascular dilation due in part to the
phenomenon of reperfusion as subsequent free oxygen radicals are released. The reoxygenation injury is the
structural damage caused by the excessive production of free radicals. The free radicals interact with cellular
structural molecules, producing dysfunction to the endothelial cells. One study23 has shown that switching from

513
Page 8
OLV to two-lung ventilation during video-assisted thoracoscopic surgery induces a massive production of reactive
oxygen species, but with minimal lung injuries. In this study, extravascular lung water index, intrathoracic blood
volume, and permeability index were insignificantly changed after resuming two-lung ventilation. Also, this study
showed that the amount of total antioxidants was adequate to counteract the reactive oxygen species. However, these
values may be different in patients with extensive lung tumors or pulmonary trauma. Another study59 showed that
OLV lasting longer than1 hour can cause cardiovascular complications (i.e., cardiac arrhythmias) through the
generation of severe oxidative stress during reexpansion and conversion to two-lung ventilation. Further studies are
needed to validate these results as a potential cause/effect.

SUMMARY
Hypoxemia usually does not occur during OLV. When it does, one should use fiberoptic bronchoscopy to rule out a
malposition of the isolation device, then institute ventilatory maneuvers (as necessary) to optimize and improve
oxygenation. Alveolar recruitment maneuvers during two-lung ventilation prior to conversion to OLV may serve to
prevent the problem. Compared with propofol anesthesia, desflurane and sevoflurane appear to attenuate the
inflammatory response to OLV. Smaller VT plus 5 cm H2O of PEEP to the dependent lung along with CPAP in the
nondependent lung should be considered while treating hypoxemic episodes during OLV. Further studies are needed
to determine whether monitoring cerebral oxygen saturation is beneficial to thoracic surgical patients requiring
OLV.

REFERENCES
1. Campos JH. Progress in lung separation. Thorac Surg Clin 2005; 15:71-83
2. Campos J: Lung Isolation. Chapter 16 in Principles and Practice of Anesthesia for Thoracic Surgery, 2011 pp
227-246. Ed Slinger P. Springer Publisher.
3. Roz H, Lafargue M, Ouattara A. Case scenario: Management of intraoperative hypoxemia during one-lung
ventilation. Anesthesiology 2011; 114:167-74
4. Karzai W, Schwarzkopf K. Hypoxemia during one-lung ventilation: prediction, prevention, and treatment.
Anesthesiology 2009; 110:1402-11.
5. Inoue S, Nishimine N, Kitaguchi K, et al. Double lumen tube location predicts tube malposition and
hypoxaemia during one lung ventilation. Br J Anaesth 2004; 92:195-201.
6. Slinger P. Pro: low tidal volume is indicated during one-lung ventilation. Anesth Analg 2006; 103:268-70.
7. Klein U, Karzai W, Bloos F, et al. Role of fiberoptic bronchoscopy in conjunction with the use of double-
lumen tubes for thoracic anesthesia: a prospective study. Anesthesiology 1998; 88:346-50.
8. Campos JH. Current techniques for perioperative lung isolation in adults. Anesthesiology 2002; 97:1295-1301
9. Schwarzkopf K, Schreiber T, Bauer R, et al. The effects of increasing concentrations of isoflurane and
desflurane on pulmonary perfusion and systemic oxygenation during one-lung ventilation in pigs. Anesth Analg
2001; 93:1434-1438
10. Slinger P, Suissa S, Triolet W. Predicting arterial oxygenation during one-lung anaesthesia. Can J Anaesth
1992; 39:1030-35.
11. Schwarzkopf K, Klein U, Schreiber T, et al. Oxygenation during one-lung ventilation: the effects of inhaled
nitric oxide and increasing levels of inspired fraction of oxygen. Anesth Analg 2001; 92:842-7.
12. Lewis JW Jr, Serwin JP, Gabriel FS, et al. The utility of a double-lumen tube for one-lung ventilation in a
variety of noncardiac thoracic surgical procedures. J Cardiothorac Vasc Anesth 1992; 6:705-10
13. Suemitsu R, Sakoguchi T, Morikawa K, et al. Effect of body mass index on perioperative complications in
thoracic surgery. Asian Cardiovasc Thorac Ann 2008; 16:463-7
14. Campos JH, Ledet C, Moyers JR. Improvement of arterial oxygen saturation with selective lobar bronchial
block during hemorrhage in a patient with previous contralateral lobectomy. Anesth Analg 1995; 81:1095-6.
15. Brodsky JB. Approaches to hypoxemia during single-lung ventilation. Curr Opin Anaesthesiol 2001; 14:71-6.
16. Watanabe S, Noguchi E, Yamada S, et al. Sequential changes of arterial oxygen tension in the supine position
during one-lung ventilation. Anesth Analg 2000; 90:28-34.
17. Bardoczky GI, Szegedi LL, d'Hollander AA, et al. Two-lung and one-lung ventilation in patients with chronic
obstructive pulmonary disease: the effects of position and FiO2. Anesth Analg 2000; 90:35-41.
18. Slinger P, Campos J. Anesthesia for Thoracic Surgery. Chapter 59 in Millers Anesthesia, 7th edition, 2009, pp
1219-1287
19. Larsson A, Malmkvist G, Werner O. Variations in lung volume and compliance during pulmonary surgery. Br
J Anaesth 1987; 59:585-91.

513
Page 9
20. Ward DS. Intra-operative ventilation strategies for thoracic surgery. Chapter 21 in Principles and Practice of
Anesthesia for Thoracic Surgery, 2011 pp 297-305. Ed Slinger P Springer Publisher.
21. Leite CF, Calixto MC, Toro IF, et al. Characterization of Pulmonary and Systemic Inflammatory Responses
Produced by Lung Re-expansion After One-Lung Ventilation. Cardiothorac Vasc Anesth 2012; 26:427-32
22. Lohser J. Evidence-based management of one-lung ventilation. Anesthesiol Clin 2008; 26:241-72
23. Cheng YJ, Chan KC, Chien CT, et al. Oxidative stress during 1-lung ventilation. J Thorac Cardiovasc Surg
2006; 132:513-8.
24. Campos JH, Update on Tracheobronchial Anatomy and Flexible Fiberoptic Bronchoscopy in Thoracic
Anesthesia, Curr Opin Anaesthesiol 2009; 22: 4-10
25. Campos JH, Hallam EA, Van Natta T and Kernstine KH: Devices for lung isolation used by anesthesiologists
with limited thoracic experience: comparison of double-lumen endotracheal tube, Univent torque control
blocker, and Arndt wire-guided endobronchial blocker. Anesthesiology 2006; 104:261-266
26. Tusman G, Bhm SH, Melkum F, et al: Alveolar recruitment strategy increases arterial oxygenation during
one-lung ventilation Ann Thorac Surg 2002;73:1204-1209
27. Tusman G, Bhm SH, Sipmann FS, et al. Lung recruitment improves the efficiency of ventilation and gas
exchange during one-lung ventilation anesthesia. Anesth Analg 2004; 98:1604-9
28. Unzueta C, Tusman G, Suarez-Sipmann F, et al: Alveolar recruitment improves ventilation during thoracic
surgery: a randomized controlled trial. Br J Anaesth 2012;108:517-24.
29. Capan LM, Turndorf H, Patel C, et al. Optimization of arterial oxygenation during one-lung anesthesia. Anesth
Analg 1980;59:847-51.
30. Cohen E, Eisenkraft JB. Positive end-expiratory pressure during one-lung ventilation improves oxygenation in
patients with low arterial oxygen tensions. J Cardiothorac Vasc Anesth 1996; 10:578-582.
31. Slinger PD, Kruger M, McRae K, et al. Relation of the static compliance curve and positive end-expiratory
pressure to oxygenation during one-lung ventilation. Anesthesiology 2001; 95:1096-102.
32. Ducros L, Moutafis M, Castelain MH, et al. Pulmonary air trapping during two-lung and one-lung ventilation.
J Cardiothorac Vasc Anesth 1999;13:35-39.
33. Yokota K, Toriumi T, Sari A, et al. Auto-positive end-expiratory pressure during one-lung ventilation using a
double-lumen endobronchial tube. Anesth Analg 1996;82:1007-1010.
34. Slinger PD, Hickey DR. The interaction between applied PEEP and auto-PEEP during one-lung ventilation. J
Cardiothorac Vasc Anesth 1998; 12:133-136.
35. Ren Y, Peng ZL, Xue QS, et al. The effect of timing of application of positive end-expiratory pressure on
oxygenation during one-lung ventilation. Anaesth Intensive Care 2008;36:544-548.
36. Hoftman N, Canales C, Leduc M, et al. Positive end expiratory pressure during one-lung ventilation: selecting
ideal patients and ventilator settings with the aim of improving arterial oxygenation. Ann Card Anaesth
2011;14:183-187.
37. Russell WJ. Intermittent positive airway pressure to manage hypoxia during one-lung anaesthesia. Anaesth
Intensive Care 2009;37:432-434.
38. Campos JH. Effects of oxygenation during selective lobar versus total lung collapse with or without continuous
positive airway pressure. Anesth Analg 1997; 85:583-586.
39. Ku CM, Slinger P, Waddell TK. A novel method of treating hypoxemia during one-lung ventilation for
thoracoscopic surgery. J Cardiothorac Vasc Anesth 2009; 23:850-852
40. Domino KB, Borowec L, Alexander CM, et al. Influence of isoflurane on hypoxic pulmonary vasoconstriction
in dogs. Anesthesiology. 1986;64:423-429.
41. Von Dossow V, Welte M, Zaune U, et al. Thoracic epidural anesthesia combined with general anesthesia: the
preferred anesthetic technique for thoracic surgery. Anesth Analg 2001;92:848-854.
42. Licker M, de Perrot M, Spiliopoulos A, et al. Risk factors for acute lung injury after thoracic surgery for lung
cancer. Anesth Analg. 2003;97:1558-1565.
43. Schilling T, Kozian A, Huth C, et al. e pulmonary immune effects of mechanical ventilation in patients
undergoing thoracic surgery. Anesth Analg. 2005;101:957-965
44. Duggan M, Kavanagh BP. Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology
2005;102:838-854.
45. Michelet P, D'Journo XB, Roch A, et al. Protective ventilation influences systemic inflammation after
esophagectomy: a randomized controlled study. Anesthesiology 2006;105:911-919.
46. Schilling T, Kozian A, Kretzschmar M, et al. Effects of propofol and desflurane anaesthesia on the alveolar
inflammatory response to one-lung ventilation. Br J Anaesth 2007;99:368-375

513
Page 10
47. De Conno E, Steurer MP, Wittlinger M, et al. Anesthetic-induced improvement of the inflammatory response
to one-lung ventilation. Anesthesiology 2009;110:1316-1326.
48. Schilling T, Kozian A, Senturk M, et al. Effects of volatile and intravenous anesthesia on the alveolar and
systemic inflammatory response in thoracic surgical patients. Anesthesiology 2011;115:65-74.
49. Tu$rul M, Camci E, Karadeniz H, et al. Comparison of volume controlled with pressure controlled ventilation
during one-lung anaesthesia. J Anaesth 1997;79:306-310.
50. Unzueta MC, Casas JI, Moral MV. Pressure-controlled versus volume-controlled ventilation during one-lung
ventilation for thoracic surgery. Anesth Analg 2007;104:1029-1033
51. Dalibon N, Moutafis M, Liu N, et al. Treatment of hypoxemia during one-lung ventilation using intravenous
almitrine. Anesth Analg 2004;98:590-594
52. Rocca GD, Passariello M, Coccia C, et al. Inhaled nitric oxide administration during one-lung ventilation in
patients undergoing thoracic surgery. J Cardiothorac Vasc Anesth 2001;15:218-223.
53. Moutafis M, Liu N, Dalibon N, et al. The effects of inhaled nitric oxide and its combination with intravenous
almitrine on PaO2 during one-lung ventilation in patients undergoing thoracoscopic procedures. Anesth Analg
1997;85:1130-1135.
54. Silva-Costa-Gomes T, Gallart L, Valls J, et al. Low- vs high-dose almitrine combined with nitric oxide to
prevent hypoxia during open-chest one-lung ventilation. Br J Anaesth 2005;95:410-416.
55. Raghunathan K, Connelly NR, Robbins LD, et al. Inhaled epoprostenol during one-lung ventilation. Ann
Thorac Surg 2010;89:981-983.
56. Doering EB, Hanson CW 3rd, Reily DJ, et al. Improvement in oxygenation by phenylephrine and nitric oxide
in patients with adult respiratory distress syndrome. Anesthesiology 1997;87:18-25.
57. Hemmerling TM, Bluteau MC, Kazan R, et al. Significant decrease of cerebral oxygen saturation during single-
lung ventilation measured using absolute oximetry. Br J Anaesth. 2008;101:870-875.
58. Suehiro K, Okutai R. Cerebral desaturation during single-lung ventilation is negatively correlated with
preoperative respiratory functions. J Cardiothorac Vasc Anesth 2011;25:127-130
59. Misthos P, Katsaragakis S, Theodorou D, et al. The degree of oxidative stress is associated with major adverse
effects after lung resection: a prospective study. Eur J Cardiothorac Surg 2006;29:591-595

Disclosure

517
Page 1
Wellness in Anesthesiologists
John E. Ellis, M.D. Philadelphia, Pennsylvania
Slides available after the presentation at vascularanesthesia.com
This review will examine wellness in anesthesia providers. Specifically, The specific objectives are to describe risk
factors for "burn out" in medical practice; describe anesthesiology-specific risk factors; and to provide safe and
effective stress reduction and lifestyle modification programs to promote self wellness.
Scholarship and personal experience
Stress and burnout in health care professionals
Causes of mortality in anesthesiologists
Occupational risks of anesthesia practice
drug dependence
ergonomic risks
radiation risks
infection risks
Tools to combat stress and reduce chronic disease
Stress and burnout in health care professionals
Sources of stress
Production pressure
Lack of control
Periop catastrophes / lawsuits
Financial
Personal
Circadian rhythms (call)
Predictors of burnout
Production pressure
A survey by Gaba et al. looked at the internal and external pressures on anesthesiologists, and reported that
respondents placed the highest pressures on themselves to avoid delays to surgery, avoid litigation, and get along
with surgeons. The survey reported that anesthesiologists faced relatively high pressure from surgeons to proceed
with a case rather than cancel it; and from administrators to reduce turnover time. An alarming 63% of respondents
suggested that they had made errors because of workload.
What is burnout?
Maslachs definition of burnout: Increased levels of emotional exhaustion, and depersonalization. Low levels of
personal accomplishment.

517
Page 2

Depersonalization
I feel I treat some patients as if they were impersonal objects.
I do not really care what happens to some patients.
Patients blame me for some of their problems.

Emotional exhaustion
I still feel tired when I wake up on workday mornings.

Personal accomplishment
I can easily understand how my patients feel about things
I deal effectively with my patients problems
I can easily create a relaxed atmosphere for my patients
I feel exhilarated after working closely with my patients

6 prime correlates of burnout
job
occupational
organizational
demographic
personality characteristics

At-risk negative job characteristics
Workload (overwork; boredom)
Conflict
Diminished resources or social support
Lack of input or feedback

Classical at-risk organizational profile
Steep hierarchy
More demanded of employees
Less is given by the employer, such as that seen with downsizing or mergers

At-risk demographics
At-risk demographics include younger adults with more education and busy unmarried people, especially those who
have never been married.

At-risk personality characteristics
Low hardiness
-without involvement in daily activities, a sense of control over events, and openness to change
Poor self-esteem
External locus of control
-the victim mentality

517
Page 3
Consequences of Physician Stress and Burnout
The personal consequences of physician stress and burnout include: depression; anxiety; suicide; broken
relationships with family, friends and colleagues; addiction to alcohol and/or drug; marital dysfunction and divorce;
and early retirement.

The professional consequences of physician stress and burnout include: disengagement; poor judgment in patient
care decision-making; hostility towards patients; medical errors; adverse patient events; diminished commitment and
dedication to optimal patient care; and difficult relationships with co-workers.

Residents have more burnout?
Physicians (particularly residents) had the largest global burnout scores, implying increased risk of burnout.
Improving overall health, increasing personal support, and improving work satisfaction may decrease burnout
among perioperative team members.

Predictors of Burnout
Spending < 20% time on most meaningful activity
Age < 55 y
Generalist
Total hrs worked/wk

High incidence of Burnout in Academic Chairpersons
In a survey of academic anesthesiology chairpersons, a majority reported moderate-high burnout. In a survey of 15
non-US anesthesiologists, majority believed that burnout among academic chairs is an important issue in their
country; that the department budget is a significant problem in their practice; and that the turnover of anesthesiology
chairs in their countries wasnt high. 7 responded that faculty retention was a significant problem in their practice,
while 8 didnt believe so.

Burnout among US Physicians relative to the general US population
A study reported 37.5% physician burnout vs. 27.6% in general population. US Physicians more burned out than
general population.

Implications of burnout
An at-risk job attitude is when people have unrealistically high expectations for their job. It is prudent to identify
those who are risk for burnout because it can contribute to:
worsening job performance i.e.,
-absenteeism
-job turnover
-decreased productivity, and
-negative effect on coworkers
health issues i.e.,
-substance abuse and
-mental and physical problems).

Burnout and complications
"In a multivariate model controlling for patient severity and nurse and hospital characteristics, only nurse burnout
remained significantly associated with urinary tract infection (0.82; P = .03) and surgical site
infection (1.56; P <.01) infection."

517
Page 4
Perioperative catastrophes
Respondents of a study by Gazoni et al. chose death, cardiac arrest, myocardial infarction, stroke or other brain
injury, perioperative visual loss, and wrong site/wrong patient as events that qualify most as perioperative
catastrophes.

Anesthesiologists who experience perioperative catastrophes undergo deep emotional trauma that may affect their
ability to provide subsequent patient care. Most respondents of the Gazoni et al. study required time to recover
emotionally from perioperative catastrophes. 21% of respondents required a week to recover and 19% never fully
recovered.4 67% of respondents felt that their ability was compromised when they provided care 4 hours after the
periop catastrophe, and 16% felt their ability was comprised more than a week after.

Financial Stress
Financial stress is among the top 5 sources of stress for anesthesiologists. Financial stress persists before residency,
through residency and in practice. Impatience (years of training = shorter working time), faith (physicians are
marks), and (over) confidence are the common factors that result in physicians financial mistakes.

Circadian rhythms (call): Sleep deprivation
Sleep deprivation is one of the most impactful consequences of physician call schedules. It elevates stress hormones
and promotes over eating. Studies of sleep deprivation have shown that long distance pilots have smaller temporal
lobes.

US Anesthesiologists over 50
50% of older anesthesiologists vs 38% of other older physicians contemplated retiring due to on call
responsibilities.
P < 0.001

Causes of mortality in anesthesiologists
Overall statistics
Suicide
Drug addiction
Exposure to anesthetic gases?
Infectious risks

Mortality in Anesthesiologists:
Death rates for anesthesiologists decreased between 1957-1976 after the introduction of fluorinated anesthetic
agents, but are similar to rates between 1930-1946 and 1947-1956. This suggests that fluorinated agents do not
adversely affect the health of anesthesiologists.

The main health problem among American anesthesiologists is the high suicide rate at ages <55 years.
Anesthesiologists have higher rates of suicide and drug-related deaths than internists. Male anesthesiologists had a
higher death rate from HIV and viral hepatitis, which may be explained by lifestyle.

Research by Kain et al. concluded that only minor acute physiological stress occurs in anesthesiology during the
perioperative process.

The incidence of coronary artery disease among anesthesiologists is not alarming in context to the general male
population or in comparison to a similar socioeconomic group. This may be, in part, because smoking is rare,
except in anesthesiologists who are also opiate addicts; physicians with opioid addiction have the higher rates of
tobacco and marijuana use than physicians in general, as well as the general population.

517
Page 5

Anesthesiologists vs. internists mortality
Cancer was not increased
Anesthesiologists had an increased risk of death from suicide, particularly suicide by drug overdose, and drug-
related death
Male anesthesiologists had a higher risk of death from HIV and viral hepatitis, which may be related to lifestyle.

Occupational risks of anesthesia practice
Occupational risks include drug dependence; and ergonomic, radiation, and infection risks.

Drug dependence
Anesthesiologists are over-represented in Florida drug treatment programs. Some have suggested that this may be, in
part, due to drug exposures in operating room. Second-hand exposure to drugs like fentayl and propofol in the
operating room may influence drug dependence on opioids. This environmental exposure may be a more reasonable
explanation - than mere access - for the high drug dependence among anesthesiologists.

Drug/Chemical dependence recovery among anesthesiologists
Anesthesiologists who received treatment from PHPs with strict regulations and guidelines for return to workplace
had similar recovery results as other physicians.

The Disabled Anesthesiologist
Three general categories of questions related to disability: 1) an anesthesiologist who has suffered an injury or
illness and wants to return to practice; 2) an anesthesiologist with an established impairment who is seeking support
in his/her attempt to receive disability insurance benefits; or 3) colleagues who are questioning whether an
anesthesiologist with particular limitations should be permitted to continue practicing.

Ergonomic risks: musculoskeletal disorders
A study of professional nurses in Mainland China reported a 70% prevalence of musculoskeletal disorders, with the
following breakdown: lower back (56.7%), neck (42.8%), shoulders (38.9%) and upper back (38.9%). A study
showed that anesthesia trainees often have poor ergonomics. Body posture and work clothing (lead apron, foot
wear, etc - clothing that causes physical discomfort) are among the factors that affect ergonomics for
anesthesiologists.

Radiation exposure
Radiation exposure to anesthesiologists face was six times greater during an angiography and three times greater
than that of a radiologist according to Anastasian et al. study. A recommendation for anesthesiologists who spend
significant time performing such procedures is to wear protective eyewear.

Infectious risks
Researchers from Robin Medical Center and Tel Aviv University conducted a study during a 3-month strike of
anesthesiologists. They measured induced cytokine production and lymphocytes proliferative responses in the blood
samples of 10 anesthesiologists before and after the strike. Proliferative responses were much lower at the end of the
strike, and the study concluded that anesthesiologist work environments correlate to certain immune changes.

Steps to promote personal well-being
Identify personal values and priorities
Enhance areas of work that are personally meaningful
Identify and nurture wellness strategies
Relationships
Spiritual
Hobbies
Rest and reflection
Self care

517
Page 6

References

Leedal JM, Smith AF. Methodological approaches to anaesthetists' workload in the operating theatre. Br J
Anaesth. 2005 Jun;94(6):702-9.

Hyman SA, Michaels DR, Berry JM, Schildcrout JS, Mercaldo ND, Weinger MB: Risk of burnout in perioperative
clinicians: A survey study and literature review. Anesthesiology 2011; 114:194204.

Balch CM, Shanafelt T. Combating stress and burnout in surgical practice: a review. Adv Surg. 2010;44:29-47.

Shanafelt TD, West CP, Sloan JA, Novotny PJ, Poland GA, Menaker R, Rummans TA, Dyrbye LN.
Career fit and burnout among academic faculty. Arch Intern Med. 2009 May 25;169(10):990-5.

De Oliveira Jr GS, Ahmad S, Stock MC, Harter RL, Almeida MD, Fitzgerald PC, McCarthy RJ: High incidence of
burnout in academic chairpersons of anesthesiology: Should we be taking better care of our leaders?
ANESTHESIOLOGY 2011; 114:18193.

Shanafelt TD, Boone S, Tan L, et al. Burnout and Satisfaction With Work-Life Balance Among US Physicians
Relative to the General US Population. Arch Intern Med. 2012;172(18):1377-1385.

Cimiotti JP, Aiken LH, Sloane DM, Wu ES (2012) Nurse staffing, burnout, and health care-associated infection. Am
J Infect Control 40: 48690.

Gazoni FM, Amato PE, Malik ZM, Durieux ME. The impact of perioperative catastrophes on anesthesiologists:
results of a national survey. Anesth Analg. 2012 Mar;114(3):596-603.

Lutsky I, Hopwood M, Abram SE, Jacobson GR, Haddox JD, Kampine JP. Psychoactive substance use among
American anesthesiologists: a 30-year retrospective study. Can J Anaesth. 1993 Oct;40(10):915-21.

Ron Lieber. Investment Advice for Doctors: First, Do No Harm. New York Times. Online. August 26, 2011.
http://goo.gl/AVGDc

Orkin FK, McGinnis SL, Forte GJ, Peterson MD, Schubert A, Katz JD, Berry AJ, Cohen NA, Holzman RS, Jackson
SH, Martin DE, Garfield JM.United States Anesthesiologists over 50: Retirement Decision Making and Workforce
Implications. Anesthesiology. 117(5):953-963

Linde HW, Mesnick PS, Smith NJ. Causes of Death among Anesthesiologists: 1930-1946. Anesthesia and
Analgesia 60:1-7, 1981.

Edward AL. Mortality Experience among Anesthesiologists, 1954-1976. Anesthesiology 51:195-199, 1979.

Bruce DL, Eide KA, Linde HW, Eckenhoff JE. Causes of Death among Anesthesiologists: A 20-Year Survey.
Anesthesiology May/June 1968 Volujme 29 Issue 3.

Merlo LJ, Goldberger BA, Kolodner D, Fitzgerald K, Gold MS. Fentanyl and propofol exposure in the operating
room: sensitization hypotheses and further data. J Addict Dis. 2008;27(3):67-76.

Kain ZN, Chan KM, Katz JD, Nigam A, Fleisher L, Dolev J, Rosenfeld LE. Anesthesiologists and acute
perioperative stress: a cohort study. Anesth Analg. 2002 Jul;95(1):177-83

Alexander BH, Checkoway H, Nagahama SI, Domino KB. Cause-specific mortality risks of anesthesiologists.
Anesthesiology. 2000 Oct;93(4):922-30.

517
Page 7
Gold MS, Graham NA, Goldberger BA. Second-hand and third-hand drug exposures in the operating room: a factor
in anesthesiologists' dependency on fentanyl. J Addict Dis. 2010 Jul;29(3):280-1.

Gold MS, Melker RJ, et al. Fentanyl Abuse and Dependence. Journal of Addictive Diseases, Vol. 25 (1) 2006.

Merlo LJ, Goldberger BA, Kolodner D, Fitzgerald K, Gold MS. Fentanyl and propofol exposure in the operating
room: sensitization hypotheses and further data. J Addict Dis. 2008;27(3):67-76.

Wilson C, Canning P, Caravati EM. The abuse potential of propofol. Clin Toxicol (Phila). 2010 Mar;48(3):165-70.

Oreskovich MR, Caldeiro RM. Anesthesiologists recovering from chemical dependency: can they safely return to
the operating room? Mayo Clin Proc. 2009 Jul;84(7):576-80. doi: 10.1016/S0025-6196(11)60745-3.

Bryson EO, Silverstein JH. Addiction and substance abuse in anesthesiology. Anesthesiology. 2008
Nov;109(5):905-17.

Bryson EO, Levine A. One approach to the return to residency for anesthesia residents recovering from opioid
addiction. J Clin Anesth. 2008 Aug;20(5):397-400.

May JA, Warltier DC, Pagel PS. Attitudes of anesthesiologists about addiction and its treatment: a survey of Illinois
and Wisconsin members of the American Society of Anesthesiologists. J Clin Anesth. 2002 Jun;14(4):284-9.

Rose GL, Brown RE Jr. The impaired anesthesiologist: not just about drugs and alcohol anymore. J Clin Anesth.
2010 Aug;22(5):379-84.

Jonathan D. Katz. The Disabled Anesthesiologist. ASA Volume 71, Number 5, May 2007.
http://old.asahq.org/Newsletters/2007/05-07/katz05_07.html

Smith DR, Wei N, Kang L, Wang RS. Musculoskeletal disorders among professional nurses in mainland China. J
Prof Nurs. 2004 Nov-Dec;20(6):390-5.

Ajmal M, Power S, Smith T, Shorten GD.Ergonomic task analysis of ultrasound-guided femoral nerve block: a pilot
study. J Clin Anesth. 2011 Feb;23(1):35-41.

Matthews AJ, Johnson CJ, Goodman NW. Body posture during simulated tracheal intubation. Anaesthesia. 1998
Apr;53(4):331-4.

Walker JD. Posture used by anaesthetists during laryngoscopy. Br J Anaesth. 2002 Nov;89(5):772-4.

Esser AC, Koshy JG, Randle HW. Ergonomics in office-based surgery: a survey-guided observational study.
Dermatol Surg. 2007 Nov;33(11):1304-13; discussion 1313-4.

Veelen MA, et al. Ergonomic problems encountered by the medical team related to products used for minimally
invasive surgery. Surg Endosc (2003) 17: 10771081

Dagal A. Radiation safety for anesthesiologists. Curr Opin Anaesthesiol. 2011 Aug;24(4):445-50.

Anastasian ZH, Strozyk D, Meyers PM, Wang S, Berman MF. Radiation exposure of the anesthesiologist in the
neurointerventional suite. Anesthesiology. 2011 Mar;114(3):512-20.

Ismail S, Khan F, Sultan N, Naqvi M. Radiation exposure to anaesthetists during interventional radiology.
Anaesthesia. 2010 Jan;65(1):54-60.

Beilin B, Greenfeld K, Abiri N, Yardeni IZ, Bessler H, Ben-Eliyahu S. Anesthesiologists at work: an increase in
pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responses. Acta
Anaesthesiol Scand. 2006 Nov;50(10):1223-8.

517
Page 8

Balch CM, Shanafelt T. Combating stress and burnout in surgical practice: a review. Adv Surg. 2010;44:29-47.

Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL. The global obesity
pandemic: shaped by global drivers and local environments. Lancet. 2011 Aug 27;378(9793):804-14.

Fernandez ID, Su H, Winters PC, Liang H. Association of workplace chronic and acute stressors with employee
weight status: data from worksites in turmoil. J Occup Environ Med. 2010 Jan;52 Suppl 1:S34-41.

Disclosure
BAXTER, Consulting Fees, Honoraria

103
Page 1
Transfusion Therapy: Optimal Use of Blood Products
Stephen Surgenor, M.D. Lebanon, New Hampshire
Introduction
Despite decades of effort, transfusion therapy practice remains suboptimal. This review will examine the
risks and benefits of red blood cell (RBC), platelet, and fresh frozen plasma (FFP) transfusions, as well as strategies
to optimize transfusion practice for each of these components. The American Association of Blood Bankers 2009
Nationwide Blood Collection and Utilization Survey Report describes the current status of blood utilization in the
United States. Key findings include that collection of autologous and directed blood is decreasing and now
represents less than 2 percent of total donation. Second the use of leukocyte reduction continues to increase and
now 80 percent of RBC units are treated. Figure 1 describes the collection and transfusion of blood nationally.
Demand for blood transfusions continues to rise.
Figure 1. Allogeneic whole blood and red blood cell collections and transfusions: 1989 2008.
Source: American Association of Blood Bankers 2009 Nationwide Blood Collection and Utilization Survey Report.
Variation in Transfusion Practice
Tremendous variation in the indications for and timing of transfusions exists. Large variations in the
indications for and timing of RBC transfusion have been documented for many years among coronary artery bypass
graft (CABG) surgery patients
1

2
. Importantly, this variation is not explained by patient or surgical variables, but
rather by differences in provider and institutional preferences
3
. More recently, another observational study
demonstrates that variation continues across institutions in Canada despite new knowledge about the benefits and
risks of RBC transfusions
4
. Such variation is not limited to just RBC transfusions. Similar observations have been
made for use of platelets and plasma during CABG surgery in Veterans Administration hospitals
5
. The presence of
significant variation in transfusion rates implies that the best practice has yet to be identified, and that indications for
transfusions are not consistent among providers.

103
Page 2
Guidelines
This variation persists despite the availability of practice guidelines. One of the oldest guidelines for RBC
transfusion is the 10/30 rule which originated from comments made by Adams and Lundy in 1942
6
. Several RBC
transfusion guidelines have been published based on best available evidence by the National Institute of Health
(1988), the American College of Physicians (1992), the Blood Management Practice Guidelines Conference (1995),
as well as the American Society of Anesthesiologists. Most recently, a comprehensive guideline has been developed
by the Society of Cardiovascular Anesthesiologists for the cardiac surgery population
7
. There has been less activity
to develop guidelines for platelet and plasma therapies; the only one was developed by the College of American
Pathologists in 1994
8
. The American Society of Clinical Oncology has developed guidelines for platelet therapy
among the oncology population, which are not easily generalized to either peri-operative or critically ill patients
9
.

While medical guidelines are believed to be an efficacious method to improve medical care, they have been
relatively ineffective in reducing unwarranted transfusions for several reasons. Specific to RBC transfusion, one
prescribed trigger is not appropriate for all patients and clinical settings, because a consistent physiologic
deterioration in is not observed among all patients at the same hemoglobin level. Second many physicians remain
unaware of available transfusion guidelines.

This past year, Dartmouth Hitchcock Health system implemented a transfusion decision support tool in our
electronic health record that is based on the current evidence yet allows clinicians flexibility to use blood for
appropriate indications. The results of this effort are presented in Figures 2 & 3. This type of approach likely
generalizable to other institutions, and represents one approach to effectively implement evidence based medicine in
general, but specifically for transfusion medicine as well.

Figure 2 Results of an Electronic Health Record Transfusion Decision Support Tool.
Source: Unpublished Data from Dartmouth Hitchcock Health

103
Page 3

Figure 3 Results of an Electronic Health Record Transfusion Decision Support Tool.
Source: Unpublished Data from Dartmouth Hitchcock Health

Red Blood Cell Transfusions
Risks of Anemia
There are numerous reports of severe anemia being well tolerated in healthy subjects. Acute normovolemic
hemodilutional anemia has been safely performed with animal models with dogs and baboons, as well as with
human subjects with and without surgery. Data from patients who decline RBC transfusion for religious reasons
suggests that mortality is more related to substantial blood loss than a low preoperative hematocrit per se.
Importantly this effect was significantly more pronounced among patients with cardiovascular disease
10
.

Studies from several prospective observational cardiac surgical databases have reported associations of
hemodilutional anemia during cardiopulmonary bypass (CPB) with increased risk of renal failure, stroke, and
mortality during coronary artery bypass graft (CABG) surgery. Plausible explanations for these observations
include direct injury as a result of exposure to hemodilutional anemia or alternatively that these associations a a
marker for another unmeasured process. One such process could be exposure to intra-operative RBC transfusions
administered as treatment for anemia.

A report by the Northern New England Cardiovascular Disease Study Group observed that among patients
managed without intra-operative RBC transfusion, exposure to hemodilutional anemia during CPB was associated
with Low Output Failure (increased need for prolonged inotropes, post-CPB intra-aortic balloon pumps, and return
to CPB after initial separation) (Figure 4)
11
. These observations support the concept that intraoperative anemia
reduces the oxygen supply available to the tissues to adequately meet demand, leading to ischemic tissue injury and
subsequent adverse outcomes.

103
Page 4

Figure 4. Crude risk of Low Output Failure by quartiles of lowest hematocrit during cardiopulmonary bypass
stratified by RBC transfusion.

Benefits of RBC Transfusion to treat Anemia
The long standing belief for RBC transfusion is that giving back blood will reverse the ill effects of anemia.
We now have three prospective trials comparing liberal and restrictive transfusion strategies among critically ill and
peri-operative patients.

The first prospective trial of RBC transfusion therapy in critically ill patients without active bleeding was
published in 1999
12
. The Canadian Transfusion Requirements in Critical Care, or TRICC trial, evaluated a
restrictive strategy of maintaining hemoglobin between 7 and 9 g/dL versus a liberal strategy of maintaining
hemoglobin between 10 and 12 g/dL. Inclusion criteria included anemic euvolemic patients who were not actively
bleeding. Patients with chronic anemia of following cardiac surgery were excluded, and a large number of patients
with significant coronary artery disease were not enrolled in the study at the discretion of the attending physician.
This study showed that the restrictive strategy was at least as effective as and possibly superior to a liberal
transfusion strategy. Furthermore, subgroup analysis showed an association of improved 30 day survival in
patients younger than 55 years old or those with APACHE II scores lower than 20 managed with the restrictive
strategy.

A more recent prospective trial of RBC transfusion during cardiac surgery was completed in Brazil
13
.
Among 500 patients undergoing cardiac surgery with CPB, a restrictive transfusion strategy of tolerating anemia to a
hematocrit of 24% was just as efficacious as a more liberal goal of maintaining hematocrit above 30%. The rate of
RBC transfusion was 78 percent vs. 47 percent in the liberal versus restrictive groups. These finding are consistent
with the TRICC trial conclusions.

Finally there is a prospective trial of liberal (greater than 10 g/dL) vs. restrictive (less than 8.0 g/dL)
strategies among high risk patients after hip surgery
14
. Similar to the previously mentioned trials, there was no
outcome benefit, as measured by death or inability to walk without assistance, to patients from a more liberal
approach to transfusion. Nearly 97 percent of patients in the liberal group were transfused withRBCs. In the
restrictive group, far less blood was administered, and only 40 percent of these patients were exposed to RBC
transfusions.

There is one other randomized trial that provides some evidence regarding the role of RBC transfusion as
part of early goal directed fluid therapy for treatment of sepsis or septic shock. Rivers et al. randomized septic
patients to either standard resuscitation or an explicit goal-directed protocol
15
. RBC transfusions were indicated in
the goal-directed protocol to maintain central venous oxygen saturation greater than 70 percent, if the hematocrit
was less than 30 percent. Patients in the early goal directed group experienced superior hospital, 28-day, and 60 day

103
Page 5
mortality compared to patients managed with standard resuscitation. Because there were multiple interventions used
in this protocol, it is not possible to separate the relative importance of RBC transfusion to the survival benefit.

Risks of RBC Transfusion
During the 1990s, the risks of RBC transfusion seemed to be well characterized. For example, there are
well defined risks of viral transmission for cytomegalovirus, hepatitis C, hepatitis B, HIV and HTLV via
transfusions
16
. Currently, for these viral risks, sophisticated patient screening, combined with laboratory detection
methods have become quite effective. As a result, the risks for these viral transmissions have decreased
dramatically over time (Figure 5). Transfusion has been estimated to be as safe as anesthetizing ASA I patients
17
.
However, screening tests are costly, and contribute to the rising costs of blood therapy. There are emerging
infectious risks that will require attention going forward, including Chagas disease, West Nile virus, Malaria, and
Creutzfeldt-Jakob disease.

Figure 5. Evolution of Viral Risks Related to Transfusion over Time.

For current management of peri-operative or critically ill patient, the risk of viral infections is not among
the major concerns. One issue that is of more consequence for the critically ill patient is the accumulating evidence
that blood transfusion may have profound negative effects on the immune system. Clearly in an environment like
the operating room or the intensive care units, where much of the morbidity and mortality is directly related to
infection, if blood transfusion does in fact increase the risk for infection it is of major concern. In the late 1970's, it
was observed that renal transplant outcome was improved among patients receiving blood transfusions before the
transplant surgery. There have been a large number of observational studies regarding the association of RBC
transfusions with infection, immunosuppression, and mortality.

Several studies have suggested that exposure to RBC transfusion increases the risk of postoperative
infection. Taylor et al recently observed that patients in a medical-surgical combined ICU experienced nearly a ten
percent increased risk of nosocomial infection with each unit of transfused RBCs
18
. Chelemer et al made similar
observations among patients undergoing CABG surgery
19
. There is also observational data that suggest decreased
long-term survival after exposure to RBC transfusion during CABG surgery
20
.

Other studies support the concept that transfusions induce immunomodulation in recipients. Fransen et al
observed that intra-operative allogeneic blood transfusions were associated with increased concentrations of
inflammatory mediators as well as increased postoperative morbidity
21
. Moore et al. reported the results of a
prospective cohort study of trauma patients
22
. They found that there was a dose response relationship between early
blood transfusion and later development of multiple organ failure. This was independent of other measures of
shock. The mechanism for these associations remains unclear, but mediation by allogeneic white blood cells is the
most likely etiology. These donor white blood cells may directly impact the recipients immune function, or cause
the release of mediators of immunomodulation into the stored RBC unit
23
.

T
r
a
n
s
m
i
s
s
i
o
n

r
i
s
k
,
T
r
a
n
s
m
i
s
s
i
o
n

r
i
s
k
,

p
e
r

u
n
i
t
p
e
r

u
n
i
t

1: 1 1: 10 0
0 0
1: 100 1: 100
0 0
1: 10 1: 10
000 000
1: 100 1: 100
000 000
1: 1 000 1: 1 000
000 000
199 199
6 6
199 199
4 4
199 199
2 2
199 199
0 0
198 198
8 8
198 198
6 6
198 198
4 4
199 199
8 8
200 200
0 0
200 200
2 2
200 200
4 4

HIV
HBC
HCV

103
Page 6
There are also observational data that suggest an association of RBC transfusions and increased risk of
acute respiratory distress syndrome
24
. This observation is of interest when considered together with transfusion
related acute lung injury (TRALI). TRALI is a non-specific constellation of dyspnea, hypotension, non-cardiogenic
pulmonary edema, and fever, which has large potential overlap with ARDs, which is defined clinically as dyspnea,
bilateral infiltrates, hypoxemia, and non-cardiogenic edema. Importantly, the mortality rate from TRALI is likely
low, in contrast with ARDs. The predominant hypothesis is that donor anti-leukocyte antibodies react with white
blood cells within the recipient
25
. A recent analysis of healthy volunteers receiving autologous RBC transfusions
demonstrates consistent impaired gas exchange after transfusion
26
. This suggests that RBC transfusions have
important immune effects on the respiratory system in the majority of recipients, not just those with obvious TRALI
events. More discussion regarding TRALI can be found in the sections regarding plasma blood products.

The association of decreased long term survival and exposure to red blood cell transfusion after cardiac surgery has
been reported by several investigators
27

28
. The mechanism for this decreased survivorship is not well understood,
and is likely not explained by infectious events alone. Transfusion exposure may merely be a marker for conditions
that limit survival, such as peri-operative hemorrhage. Alternatively, RBC transfusions may exert a long-lasting
alteration of a recipients immune function, thereby impacting long-term survival. The Northern New England
Cardiovascular Disease Study Group recently compared long-term survival for patients who were exposed to
smaller quantities of RBC transfusions (1 or 2 units) to those who were never exposed to RBC transfusion during
their index CABG admission. As a result, this analysis includes patients who were more likely transfused as
treatment for stable peri-operative anemia, thereby reducing the potentially confounding factor of substantial blood
loss or other hemorrhagic complications. Exposure to small doses of RBC transfusions (1 or 2 units) during
admission for cardiac surgery was associated with a 16 percent increased adjusted risk of 5 year mortality in this
regional cohort of cardiac surgical patients. The impact on survival was most pronounced in the first 6 months
following surgery, with an adjusted hazard ratio of 44 percent (Figure 4). This adverse impact on survival after
exposure to RBC transfusion was not explained by differences among patients who received blood nor by
procedural characteristics. This was confirmed using propensity score analysis.

Figure 4. Adjusted Survival by Red Blood Cell Exposure among 9,079 Cardiac Surgical Patients.

Leukoreduction
Because of the concern that donor white blood cells are problematic when administered to the donor during
RBC transfusion, strategies to reduce the presence of these unwanted white blood cells have been considered.
Leukoreduction has been hypothesized to be capable of reducing the previously described morbidity and mortality
related to RBC transfusion. However, meta-analyses of randomized controlled trials on this topic fail to justify
universal application of this therapy beyond previously accepted situations
25
. It is important to note that this meta-
analysis supported a benefit of leukoreduction in the cardiac surgical population, based on 4 randomized controlled
trials. While some have questioned whether the available data at this point supports the considerable expense
associated with the universal adoption of this change in transfusion practice, leukoreduction has recently been
adapted in Europe and Canada, and is being increasingly adopted in the US
29

30
.

103
Page 7

Storage of RBCs
A final consideration with RBC transfusions is the Storage Lesion. This concept considers the
predictable changes to red blood cells during storage
31
. There are emerging data that question the efficacy of stored
RBCs because of these changes. The goal of administering a RBC transfusion is to increase the hemoglobin
concentration and therefore improve oxygen delivery to the tissues. Normal RBCs have a biconcave shape and are
quite capable of deforming as they pass through capillaries. During storage, RBCs lose their biconcave shape and
become irregular in shape. As a result of these morphologic changes, stored RBCs are less deformable, and more
adherent to endothelium
32
. Stored RBCs also become depleted of ATP and 2,3-DPG and these changes may
contribute to decreased function. The clinical significance of the storage lesion is not certain.

Platelet Transfusions
A recent review of evidence based indications for platelet and plasma has been completed for the critically
ill patient
33
. Stored units of platelets are can be collected by two methods. Regardless of collection technique, units
of platelets must be stored at room temperature, kept in constant motion, which results in a short shelf life. They are
stored in a special permeable plastic, as they continue to respire during storage. If respiration were not to occur, the
platelets would become anaerobic, produce lactate which may not be able to be buffered by the small quantity of
plasma in the stored unit, become acidotic and ultimately die.

Transmission of bacterial infection is a significant risk of platelet therapy, and is several orders of
magnitude more frequent than transmission of viral infections, as mentioned previously
34
. In addition, the fatality
rate due to bacterial contamination of platelets is several orders of magnitude greater than the transmission rate of
viral infections, such as HIV or hepatitis C. For the peri-operative or critically ill patient, transmission of bacterial
infections via platelet administration is a serious concern.

Potential sources of bacterial contamination of platelet units include the skin of the donor at the time of
collection. Less likely sources are bacteremia of the donor, contamination of the collection bag, or contamination
during processing of the unit. The risk of bacterial transmission is greater with platelet units compared to other
blood products which are stored at cold temperatures. Currently the risk of bacterial contamination is estimated at
1:2000 to 1:3000. Blood banks currently culture stored platelet units to detect units that are contaminated with
bacteria. While this is helpful for reducing the risk of bacterial infection, there are ongoing concerns about both
false positive and false negative results. A recent observational study from the American Red Cross reported a
confirmed positive contamination rate of 1:5,399, from a pool of all positive cultures (crude rate of all positive
cultures was 1:1,641)
35
. In other words, only 30% of all positive cultures from these aphereis platelet units were
ultimately confirmed positive. This illustrates the limitation of this screening methodology.

Other risks related to platelet transfusions include TRALI, febrile reactions, and transfusion associated
circulatory overload. There are also observational data from CABG surgery patients that describe an association of
platelet transfusion with increased risk of stroke, inotrope use, pulmonary dysfunction, as well as death. These
associations were significant after adjustment for patient and disease characteristics
36
.

Interpreting these risks of platelet transfusions is challenging, because the data to support a benefit for
platelet transfusion is lacking. What limited data there is derives from the management of non critically ill
hematology and oncology patients who develop thrombocytopenia as a result of chemotherapy. A recent review
regarding platelet therapy summarizes the available literature
37
. This review suggests generalizing those guidelines
developed for the oncology patients does not make sense. Therefore the decision to use prophylactic transfusions
(i.e, keep the platelet count above a certain threshold) or therapeutic transfusions (i.e., transfuse only for active
bleeding or immediately prior to a procedure) in the operating room or intensive care unit is not currently clear. In
addition what dose of platelets is necessary is not well characterized either.

Fresh Frozen Plasma & Cryoprecipitate

Fresh frozen plasma (FFP) is often administered to patients with elevated prothrombin time (PT) or
activated partial thromboplastin time (PTT). FFP does contain fibrinogen, so this product can also be administered
to patients with a low fibrinogen. Cryoprecipitate is made from FFP, and contains higher concentrations of
fibrinogen, von Willebrand factor, and factor VIII. As such cryoprecipitate is indicated to replete deficiency of

103
Page 8
these factors. These indications based on abnormal laboratory coagulation studies are most appropriate prior to an
invasive procedure that is associated with bleeding risks or during an episode of active hemorrhage. These
indications are most often viewed as inappropriate when used to prevent spontaneous bleeding. Also use of FFP as
a volume expander is viewed as inappropriate. Unfortunately, none of these indications are evidence-based.
Furthermore, there is incomplete evidence that first, the correction of abnormal coagulation studies with FFP is
transient in nature (i.e., lasts only 2 to 4 hours), and second that abnormal coagulation studies do not necessarily
predict bleeding risk during procedures
32
.

While the indications for and benefits of these plasma blood products remain uncertain, some risks related
to their use are more clearly understood. Like all the blood products discussed in this review, use of plasma carries
risks of infection, allergic reactions, hemolysis, and circulatory volume overload. Data from the United Kingdom
(Serious Hazards of Transfusion) Hemovigilance Systems (SHOT) document that allergic reactions are more
common with plasma units compared to RBC units
38
. Hemolysis from ABO incompatibility is also possible,
because plasma may contain anti-A and anti-B antibiodies that react within the recipient. The universal donor is
AB type plasma. Recent data from the French and the United Kingdom (Serious Hazards of Transfusion)
Hemovigilance Systems document that the risk of transfusion related acute lung injury (TRALI) is also much higher
with plasma-rich blood components, such as fresh frozen plasma and platelets, compared to RBC transfusions
36
.
SHOT data suggests a risk of 1 in 60,000 per unit for plasma transfusion. Interestingly, these data found a strong
association of TRALI and female gender of the donor. It is hypothesized that pregnancy may induce human
leukocyte or human neutrophil antibodies among these female donors. This has led to the preferential use of male
derived plasma for fresh frozen plasma products in some countries.

Massive Transfusion

Observational evidence from Operation Iraqi Freedom and Trauma Centers is informing changes to
Massive Transfusion Protocols at many trauma centers
39
. One major change has been the suggested ratio of red
blood cell to fresh frozen plasma (FFP) transfusions during resuscitation of the most severely injured and
uncontrollably hemorrhaging trauma patients. An association between red cell to FFP ratios and mortality has led to
the recommendation of administering a ratio o f 1:1 or 1:2 for these patients
40
. A randomized trial of these ratios is
clearly needed to further investigate whether these observations are indeed valid. Other important considerations
during management of these patients include vigilance for and management of hypothermia, acidosis, and
hypotension.

General Considerations

Currently, there are three predominate risks to consider when deciding to use blood products: 1.
transfusion related acute lung injury (TRALI); 2, bacterial contamination of platelets; and 3. ABO incompatibility.
TRALI and bacterial contamination of platelets have been described above. Administration of an incompatible unit
of blood is not a new problem, but remains a significant risk today. For example, errors with blood specimens and
samples labeled with the wrong patient information are not rare
41
. ABO incompatibility is most frequently related to
transfusion of RBCs, but can also occur with platelets and plasma products. Sixty percent of the transfusion related
deaths reported to the FDA during 1990-1998 were hemolytic reactions. Every year one to two dozen patients will
die simply from getting the wrong blood in the United States. Of note, transfusion of ABO incompatible blood
products has recently been introduced as a one of the mistakes that will prohibit payment for hospital care of patients
in some states.

Today we are better positioned to optimize our use of transfusions than we have been in the past. This is
possible because of a rapid growth in our understanding of not only the risks of anemia, but the risks and benefits of
RBC unit storage and transfusion over the last decade. By understanding the current evidence regarding the
treatment of anemia with RBC transfusion, we can significantly decrease the local, regional, and national variation
currently witnessed for transfusions. Specific to the use of fresh frozen plasma (FFP) and platelets, the risks and
benefits of transfusion are less certain. However, there is growing evidence regarding the risks of transfusing FFP
and platelets that are relevant when making decisions to administer these products.

In conclusion despite significant advances in the safety of blood therapy, there remain significant risks
related to their use. Variation in the utilization of blood products that are not explained by differences in patient and

103
Page 9
disease characteristics suggest that provider behavior is driving at least some of our national use of blood products.
Given the risks to patients that still exist when they are transfused, careful and judicious use of blood products is
appropriate.

REFERENCES

1
Stover EP, Seigel LC, Parks R, Levin J, Body SC, Speiss, DAmbra MN. Variability in transfusion pratice for
coronary artery bypass surgery despite national consensus guidelines. Anesth (Abstract) 1994;81:1224A.
2
Goodnough LT, Johnston MFM, Toy PT: The variability of transfusion practice in coronary artery bypass surgery.
JAMA 1991;265:86-90.
3
Surgenor DM, Churcill EL, Wallace WH, et al. Determinants of red cell, platelet, plasma and cryoprecipitate
transfusions during coronary artery bypass graft surgery: the Collaborative Hospital Transfusion Study. Transfusion
1996;36:521-32.
4
Hutton B, Fergusson D, Tinmouth A, et al. Transfusion rates vary significantly amongst Canadian medical
centres. Can J Anesth 2005; 52: 581-90.
5
Covin R, OBrien M, Grunwald G, et al. Factors affecting transfusion of fresh frozen plasma, platelets, and red
blood cells during elective coronary artery bypass graft surgery. Arch Pathol Lab Med. 2003; 127: 415-23.
6
Adams RC, Lundy JS. Anesthesia in cases of poor risk. Some suggestions for decreasing the risk. Surg Gynecol
Obstet 1942;74:1011-101.
7
Ferrarris VA et al. 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular
Anesthesiologists Blood Conservation Clinical Practice Guidelines Ann Thorac Surg 2011;91:94482.
8
Fresh-frozen plasma, cryoprecipitate, and platelet administration practice guidelines development task force of the
College of American Pathologists. JAMA 1994; 271: 777-81.
9
Schiffer CA, Anderson KC, Bennet CL, et al. Platelet transfusion for patients with cancer: Clinical practice
guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19: 1519-38.
10
Carson JL, Spence RK, Poses RM: Severity of anaemia and operative mortality and morbidity. Lancet
1988;1:727-729
11
Surgenor SD, DeFoe GR, Fillinger Likosky DS, et al. Intraoperative red blood cell transfusion during CABG
surgery increases the risk of post-operative low output heart failure. Circulation 2006; 114[suppI]:I 43 -48.
12
Hbert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion
requirements in critical care. N Engl J Med 1999;340:409-417
13
Hajjar LA, Vincent JL, Galas FR et al. TRACS Randomized Controlled Trial JAMA. 2010;304(14):1559-1567
14
Carson JL, Terrin ML, Noveck H. et al. Liberal or Restrictive Transfusion in High-Risk Patients after Hip
Surgery. NEJM 2011; 365: 2453-62.
15
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic
shock. NEJM 2001; 345:1368-77.
16
Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP: Transfusion medicine: Blood transfusion. N Engl J
Med 1999;340:438-447.
17
Amalberti R, Auroy Y, Berwick D, Barach P. Five System Barriers to Achieving Ultrasafe Health Care. Ann
Intern Med 2005; 142: 756-64.
18
Taylor RW, OBrien J, Trottier J, et al. Red blood cell transfusions and nosocomial infections in critically ill
patients. Crit Care Med 2006; 34: 2302-8.
19
Chelemer SB, Prato S, Cox PM er al. Asssociation of bacterial infection and RBC transfusion after coronary
artery bypass surgery. Ann Thor Surg 2002; 73: 138-42.
20
Engoren MC, Habib RH, Zacharias A. Effect of blood transfusion on long term survival after cardiac operation.
Ann Thorac Surg 2002; 74:1180-6.
21
Fransen E, Maessen J, Dentener M, Senden N, Buurman W: Impact of blood transfusions on Inflammatory
Mediator Release in patients undergoing cardiac surgery. Chest (In Press).
22
Moore FA, Moore EE, Sauaia A: Blood transfusion: An independent risk factor for postinjury multiple organ
failure. Arch Surg 1997;132:620-625.
23
Vamvakas EC. White blood cell containing allogeneic blood transfusion and postoperative infection or mortality:
an updated meta-analysis. Vox Sang 2007; 92: 224-32.

103
Page 10

24
Gong MN, Thompson BT, Williams P et al. Clinical predictors of and mortality in acute respiratory distress
syndrome: the potential role of red blood cell transfusion. Crit Care Med 2005; 33: 1191-8.
25
Curtis BR, McFarland JG. Mechanisms of transfusion related acute lung injury (TRALI): anti leukocyte
antibodies. Crit Care Med 2006; 34: s118-23.
26
Weiskopf RB, Feiner J, Toy P, et al. Fresh and Stored Red Blood Cell Transfusion Equivalently Induce
Subclinical Pulmonary Gas Exchange Deficit in Normal Humans. Anesth Analg 2012; 114: 511-9.
27
Engoren MC, Habib RH, Zacharias A, et al. Effect of blood transfusion on long-term survival after cardiac
operation. Ann Thorac Surg 2002; 74:1180-1186.
28
Koch CG, Li L, Duncan AI, et al. Transfusion in coronary artery bypass grafting is associated with reduced long
term survival. Ann Thorac Surg 2006; 81:1650-1657.
29
Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP: Transfusion medicine: Blood transfusion. N Engl J
Med 1999;340:438-447.
30
Sharma AD, Sreeram G, Erb T, Grocott HP, Skaughter TF. Leukocyte-Reduced Blood Transfusions:
Perioperative Indications, Adverse Effects, and Cost Analysis Anesth Analg 2000; 90: 1315-23.
31
Tinmouth A, Fergusson D, Yee IC, Hebert PC. Clinical consequences of red cell storage in the critically ill.
Transfusion 2006; 46: 2014-27.
32
Chin-Lee I, Statchuk L, Milkovich S, et al. Transfusion of red blood cells under shock conditions in the rat
microvasculature. Blood 2004; 104: 2713A.
33
Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intesive
care unit: benefit or harm? Crit Care Med 2006; 34: S170-3.
34
Schrezenneier H, Walther-Wenke G, Muller TH, et al. Bacterial contamination of platelet concentrates: results of
a prospective multicenter study comparing pooled whole blood-derived platelets and apheresis platelets.
Transfusion 2007;47:644-52.
35
Eder AF, Kennedy JM, Dy BA, et al. Bacterial screening of apheresis platelets and the residual risk of septic
transfusion reactions: the American Red Cross experience (2004-2006). Transfusion 2007; 47: 1134-42.
36
Spiess BD, Royston D, Levy JH, et al. Platelet transfusionduring coronary artery bypass surgery are associated
with seious adverse outcomes. Transfusion 2004; 44: 1143-8.
37
Ongjen G, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the
intensive care unit. Crit Care Med 2006; 34[suppl]: 170-3.
38
Serious hazards of transfusion steering committee. Serious harzards of transfusion: annual report 2004.
http:/shotuk.orgshot%20report%2001-02.pdf
39
Damage control resuscitation: a sensible approach to the exsanguinating surgical patient. Beekley AC. CCM
2008; 36: S267-74.
40
Maegele M, Lefering R, Paffrath T, Tjardes T, Simanski C, et al. Red Blood Cell to plasma ratios during massive
transfusion are associated with mortality in severe multiply injury: a restrospective analysis for the Trauma Registry
of the Deutch Gesellschaft fur Unfallchirurgue. Vox Sanguinis 2008; 95: 112-19.
41
Lumadue J, Boyd J, Ness P. Adherence to a strict specimen-labeling policy decreases the incidence of erroneous
blood grouping of blood bank specimens
Transfusion 1997; 37: 11691172.

Disclosure

holders.
109
Page 1
ACLS in the Perioperative Period (AACLS)
Geral d Macci ol i , M. D. Ral ei gh, North Carol i na
This refresher course is based on the monograph: Anesthesiology Centric ACLS by Andrea Gabrielli, Michael
F. OConnor, and Gerald A. Maccioli. It is an approved work product of the ASAs Committee on Critical
Care, and available at:
http://www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf
The epidemiology of cardiac arrest in the anesthesia world is unique and special. In fact hypoxemic or
dysrhythmic cardiac arrest is rarely observed when sedation, regional or general anesthetics are provided. This
can be attributed to the development of better monitoring, safer medications, adoption of clinical standards and
advances in training. With detailed knowledge of the patients medical history, there is an intuitive difference in
a patients chance of survival. When cardiac arrest during anesthesia does occur, prompt recognition, and
diagnosis can lead to successful management.
The most recent data of cardiac arrest during anesthesia comes from the Mayo Clinic in Rochester (See Sprung
J, et al. 2002). In this study, cardiac arrest was defined as the requirement for resuscitation with either closed
chest compression or open cardiac message, after the onset of anesthesia in 518,294 patients. Cardiac arrests
after transport to the ICU were not included. The two outcome variables were survival of at least one hour after
initial resuscitation and survival to discharge from the hospital. All probable causes of cardiac arrest were
grouped into three categories: 1) intraoperative hemorrhage, 2) pre-existent cardiac pathology and 3) hypoxia,
both at intubation or extubation. Overall 24 cardiac arrests were determined to be secondary to anesthesia
(0.5/10,000 anesthetics). If one extrapolates this number to the 20 million anesthetics performed annually in the
United States, it translates to at least 1000 patients/year, or about three patients a day going from "sleep" to
cardiac arrest! This number is probably a gross underestimation since the many prestigious academic
institutions in the US and abroad that report their experiences do not necessarily reflect the incidence of this
problem in the real world, i.e. outside academic boundaries or abroad.
The impact on favorable outcome of having an anesthesiologist present or immediately available during a
surgical procedure is clear. In a large retrospective review, the adjusted alteration for death and failure to rescue
were greater when care was not directed by a physician anesthesiologist (alteration for death = 1.08, p< 0.04;
alteration for failure to rescue = 1.10, P < 0.01), suggesting that anesthesiologist-directed anesthesia care has a
significant positive effect on the outcome for complications in the OR, and long term mortality (see Silber, et al
2000). Appropriate vigilance and monitoring is often the key to recognition and timely response to such a crisis.
For example, in the late 80s the ASA Closed Claims study reported that 57% of hypoxiarelated deaths could
have probably been avoided simply by improved awareness of life threatening respiratory complications during
anesthesia and the use of pulse oximetry and capnography.
In the perioperative setting, patients typically deteriorate into a pulseless arrest over a period of minutes or
hours, under circumstances wholly dissimilar to other in-hospital or out-of-hospital settings. Consequently,
aggressive measures taken to support patient physiology can avert, avoid, or forestall the need for ACLS.
Additionally, patients in the perioperative period have a different milieu of pathophysiology. For example,
hypovolemia, as a cause of myocardial ischemia, is far more common than transmural infarction from plaque
rupture. Intraoperative myocardial ischemia resulting from an imbalance in O2 delivery and consumption rarely
holders.
109
Page 2
evolves to full pump failure or ventricular fibrillation in the operating room. The result is a different spectrum
of dysrhythmias in the operating room than in the ED. The most common cardiac dysrrythmia during general
and neuraxial anesthesia is bradycardia followed by asystole (45%). The other life threatening cardiac rhythms
are severe tachydysrrhythmias including ventricular tachycardia,ventricular fibrillation (14%), and pulseless
electrical activity (7%). Remarkably, in 33% of the cases the heart rhythm is not fully assessed or documented
Changes i n ACLS
Animal models of circulatory crisis and of CPR demonstrate that hyperventilation is almost invariably
associated with worsened survival. Ventilation at 20 breaths a minute is associated with significantly lower
survival than ventilation at 12 breaths/minute. As a whole, these studies emphasize the principle: in a low flow
state the duration of increased intrathoracic pressure is proportional to the ventilation rate and inversely
proportional to blood pressure, coronary and cerebral perfusion. Recent versions of the ACLS guidelines have
recommended lower levels of ventilatory support. This is the rationale driving the development of technologies
to ventilate patients using negative pressure.
Cardi oversi on: Speci al Considerations
Immediate cardioversion is indicated for a patient with serious signs & symptoms related to the tachycardia or
if ventricular rate is > 150 bpm (Table 2)
Always be prepared to externally pace patients who are being cardioverted, as some will convert into a very
bradycardic rhythm.
Biphasic defibrillators are more effective and utilize less energy than monophasic defibrillators. Thus biphasic
defibrillators have almost completely replaced the monophasic defibrillators discussed in older versions of
ACLS.
Rhythm Energy Sequence Monophasic Energy Sequence Biphasic PSVT 50 J, 100 J, 200 J, 300 J, 360 J 100 j
A Flutter 50 J, 100 J 50 J Atrial Fibrillation 200 J, 300 J, 360 J 50 J, 100 J Over the past two decades, there has
been increased interest in preserving vital organ perfusion during CPR and restoring it as quickly as possible
after there is a return of spontaneous circulation (ROSC). There are multiple animal studies and case series that
have suggested that vasopressin or higher doses of epinephrine may be superior to the standard doses of
epinephrine recommended in ACLS. Larger clinical studies have failed to demonstrate any consistent benefit
to either alternative, but have also not documented worsening of outcome associated with their use. Several of
the algorithms in the work product incorporate vasopressin in addition to epinephrine, as it is the opinion of the
authors that the combination of the two drugs is likely superior to either alone in those clinical settings.
Avoiding ACLS is as important as performing it well. The monograph offers the algorithms below as
reasonable approaches to the management of patients with LV shock and RV shock. Cardiac arrest in
perioperative patients typically occurs as a consequence of either hypoxemia or the progression of a circulatory
process. Avoiding cardiac arrest requires successfully managing acute anemia, hypoxemia, and all contributing
factors to cardiac output: preload, contractility, and afterload. Anesthesiologists are masters of recognizing and
treating hypoxemia. Consequently the focus of the remainder of this document will be on the management of
cardiopulmonary interactions and the circulation in the rapidly decompensating patient. Traditional ACLS is
intended for caregivers summoned to aid a patient who has suddenly collapsed. In the perioperative setting, the
list of causes is substantially larger, and ACLS needs to be managed concurrently with the anesthetic and
operation.
holders.
109
Page 3
Common Causes of ACLS events i n the peri operati ve setti ng Anesthetic
o Intravenous anesthetic overdose
o Inhalation anesthetic overdose
o Neuraxial block with high level sympathectomy
o Local anesthetic systemic toxicity
o Malignant hyperthermia
o Drug administration errors
Respiratory
o Hypoxemia
o Auto PEEP
o Acute Bronchospasm
Cardiovascular
o Vasovagal reflex
o Hypovolemic and/or hemorrhagic shock
o Tension Pneumothorax
o AnaphylacticReaction
o Transfusion Reaction
o Acute Electrolyte Imbalance (high K)
o Severe Pulmonary Hypertension
o Increased intraabdominal pressure
o Pacemaker failure
o Prolonged Q-T syndrome
o Acute Coronary Syndrome
o Pulmonary Embolism
o Gas embolism
o Oculocardiac reflexes
o Electroconvulsive therapy
Recogni zi ng cardi ac arrest i n the OR
- EKG with pulseless rhythm (V-tach, V-fib)
- Loss of pulse X 10 seconds
- Loss of end-tidal CO2
- Loss of plethysmograph
BLS/ ACLS i n the OR Some key poi nts to remember . . .
- CPR for patients under general anesthesia need not be preceded by Annie! Annie! Are you okay?
- Instruct appropriate personnel to start effective CPR.
- Discontinue the anesthetic and surgery
- Call for help, defibrillator
- Bag mask ventilation if ETT not in place followed by immediate
endotracheal intubation if feasible FiO2 = 1.0
- Don't stop CPR unnecessarily! Capnography is a more reliable indicator of ROSC than carotid
or femoral arterial pulse palpation.
- Capnograph to confirm advance airway positioning and effective CPR
- Hand ventilate rate 8 -10, VT to chest rise, TI one second with 100% oxygen assess for
obstruction, if none, institute mechanical ventilation. If obstruction, suction, fiberoptic bronchoscopy,
consider exchanging the airway. Continue CPR.
- Open all IVs to wide open
holders.
109
Page 4
Anaphylaxis
Anaphylaxis is a rare but important cause of circulatory collapse in the perioperative period. While
there is a wide range of minor allergic reactions, hypotension, tachycardia and bronchospasm can be
more easily followed by vasogenic shock when the offending agent is administered as a rapid
intravenous bolus, the most common route of drug administration during anesthesia. The
preponderance of anaphylaxis in perioperative patients is caused by a small number of drugs.
Anaphylactic shock has been identified as a coexisting or major indeterminate factor for dysrhythmic
cardiac arrest during anesthesia occurring in 2.2 to 22.4 per 10,000 anesthetics with 3% to 4% of them
being life threatening.
Neuroaxi al Anesthesia
Cardiac arrest in association with neuraxial (spinal or subarachnoid block) anesthesia remains the most
mysterious cause of morbidity and mortality in the perioperative period. Its existence would be controversial,
except that is has been well documented as an occurrence in younger, otherwise healthy patients undergoing a
variety of clinical procedures. Its pathophysiology remains a mystery. Clinically, the only unifying feature of
this syndrome is the degree of surprise among the caregivers of these patients. Various hypotheses have been
put forward over the years, invoking unrecognized respiratory depression, excessive sedation concurrent with
high block, under appreciation of both the direct and indirect circulatory consequences of a high spinal
anesthetic, and failure to rescue with airway management and drugs. Hypoxemia from hypoventilation does
not appear to be the cause, as there are case reports documenting adequate saturation in these patients. Thus
there is a substantial amount of basic science and clinical interest in the effects of high spinal anesthesia on the
sympathetic innervation of the heart and the circulation.
The most recent North American review of the epidemiology of cardiac arrest during neuraxial
anesthesia indicates the prevalence of cardiac arrest at 1.8 per 10,000 patients (neuraxial), with more
arrests occurring in patients with spinal anesthesia versus epidural (2.9 vs. 0.9 per 10,000 ; P = 0.041)
(Anesth Analg 2005;100:855-
865). In 46% (12/46) of the cases cardiac arrest was associated with recurrent specific surgical events
(cementing of joint components, spermatic cord manipulation, manipulation of a broken femur, and rupture of
amniotic membranes). In 54% (14/26), the anesthetic technique, i.e. subarachnoid block contributed directly to
the arrest. The choice of vasopressors during neuraxial anesthesia is still being debated.
Treatment of Cardi ac Arrest Associ ated wi th Neuraxi al Anesthesia
- Discontinue anesthetic or sedation infusion
- Ventilate with 100% Oxygen, intubate trachea
- Begin CPR if patient has significant bradycardia or is pulseless >10sec
- Treat bradycardia with 1mg Atropine
- Treat with at least 1 mg epinephrine IV (up to 0.1mg/kg)
- Consider concurrent treatment with 40 u vasopressin
N.B. the full monograph covers a variety of other scenarios, which are not
holders.
109
Page 5
included in this handout due to space limitations. These include:
o Local Anesthetic Overdose
o Gas embolism
o Tachycardia
o Bradycardia
o Obstretric Patients
http://www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf
Di fferenti al Di agnosi s for peri operati ve PEA or
Asystol e: 8H & 8T
Hypoxia Trauma/hypovolemia
Hypovolemia Tension Pneumothorax
Hyper-vagal Thrombosis of Coronary
Hydrogen Ion Tamponade
Hyperkalemia Thrombus in Pulmonary Artery
Malignant Hyperthermia Long QT syndrome
Hypothermia Toxins (anaphylaxis)
Hypoglycemia Pulmonary HTN
REFERENCES
www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf - 2008-02-19
2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular
care. Part 4: Adult Basic Life Support. Circulation 2005;112:IV-18-IV-34. Lagasse RS: Anesthesia safety:
Model or myth? A review of the published literature and analysis of current original data. Anesthesiology 2002;
97:1609-1617
Biboulet P, Aubas P, Dubourdieu J, Rubenovitch J, Capdevila X, d'Athis F. Fatal and non-fatal cardiac arrests
related to anesthesia. Can J Anesth 2001; 48:326-332 .
Olsson GL, Hallen B. Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics. Acta
Anaesthesiol Scand 1988; 32:653-664
Newland MC, Ellis SJ, Lydiatt CA, et al. Anesthetic-related cardiac arrest and its mortality. A report covering
72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology 2002;97:108-115
Runciman WB, Morris RW, Watterson LM et al. Crisis management during anaesthesia: Cardiac arrest. Qual
Saf Health Care 2005; 14:e14
Silber JH, Kennedy SK, Even-Shoshan O, et al. Anesthesiologist direction and patient outcomes.
Tinker JH, Dull DL, Caplan RA, Ward RJ, Cheney FW. Role of monitoring devices in prevention of anesthetic
mishaps: a closed claims analysis. Anesthesiology 1989;71:541-546
Sprung J, Warner ME, Contreras MG, et al. Predictors of survival following cardiac arrest in patients
undergoing non-cardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology 2002;
99:259-269
Kopp SL, Horlocker TT, Warner ME, et al. Cardiac arrest during neuraxial anesthesia: frequency and
predisposing factors with survival. Anesth Analg 2005;100:855-865
Keenan RL, Shaprio JH, Dawson K. Frequency of anesthetic cardiac arrest in infants: effect of pediatric
anesthesiologists. J Clin Anesth 1991;3:433-7
Flick RP, Sprung J, Harrison TE, et al. Perioperative cardiac arrests in children between 1988 and 2005 at a
tertiary referral center: a study of 92,881 patients. Anesthesiology 2007;106:226-37
DISCLOSURE
112
Page 1
Leading Responses to Medical Accidents In and Out of the Operating Room:
Priorities and Approaches
Richard Cook, M.D. Stockholm, Sweden
Outline not available
118
Page 1
Understanding Clinical Hemodynamics
Micharel F. OConnor, M.D. FCCM Chicago, Illinois
The physiologic paradigm that clinicians reference in their attempts to explain and understand the biology
of both healthy and critically ill patients has been in evolution for more than 100 years. Interestingly, our
understanding of the clinical circulation has always been thought of as complete, with creative clinicians invoking
a variety of reasons to explain away apparent discrepancies between commonly used mental models and the realities
of clinical medicine.
The most primitive formulation of the circulation entails simple conservation of matter:
Cardiac Output = Stroke Volume x Heart Rate = Qt = SV x HR
This statement, while obviously always true, offers sapient practitioners little insight into why the
circulation in a particular patient might be unacceptable, and how they might rationally intervene. During the mid-
20th century, a relatively complete paradigm for understanding the role of the venous return in controlling the
cardiac output was refined by Guyton and his co-workers, and has been repetitively validated since it was first
described (refs Jacobsohn, Magder, Guyton, Sylvester). Although not complete, this theory was powerful in the
hands of those who understood it.
The balloon-tipped, flow directed, thermistor equipped pulmonary artery catheter heralded the subsequent
era of the understanding of the clinical circulation. This device, coupled with a deep understanding of the
mechanics of left ventricular function heralded the era in which the circulation and all of its pathology were
understood from the perspective of the left-ventricle which some now refer to as the LV centered view of the
circulation (Sagawa). For those who trained in that paradigm, preload, afterload, and contractility were the
determinants of cardiac output:
Cardiac Output = CO = MAP-RAP
SVR
(Where MAP = Mean Arterial Pressure, RAP = Right Atrial Pressure and SVR = Systemic Vascular
Resistance)
Some patients have a right heart limited circulation, which can be formulated using a very similar equation:
__
CO = PA - LAP
__ PVR
(Where PA = Mean Pulmonary Artery Pressure, LAP = Left Atrial Pressure, and PVR = Pulmonary
Vascular Resistance).
Nevertheless, the LV centered view of the circulation focused on preload, afterload, and contractility, and
was frustrated by a variety of obstacles. The most important was the poor correlation between measured filling
pressures and left ventricular end-diastolic volumes as assessed by echocardiography (refs Kumar,Hofer, Kramer).
Echocardiography has documented that LV compliance is far more dynamic than anyone believed prior to its
widespread clinical use (Coriat). The other, more insidious problem with the LV centered world-view is that
adherents tend to regard RAP almost exclusively as an index of circulatory volume, forgetting that it is the
downstream hydrostatic resistance to venous return in the model of Guyton:
VR = CO = Pms RAP
RVR
(Where VR = Venous Return, RAP = Right Atrial Pressure, and RVR = Resistance to Venous Return)
118
Page 2
The circulation in any patient at any moment in time is the product of the interaction of the venous circuit
with the heart (the pump). The RAP is a product of that interaction. Theoretically, Pms should be the best
assessment of the circulatory volume and the best predictor of response to volume administration. There is an
evolving clinical literature that explores its measurement and utility under general anesthesia (Maas).
All of this has produced the present understanding of clinical hemodynamics, which is predicated on a
synthesis of venous return and cardiac physiology (Sylvester, Jacobsohn). This model can be used to generate a
series of questions that can guide the assessment of a patient in shock.
What is Shock? Shock is globally inadequate perfusion of tissues sufficient to produce both tissue hypoxia and
organ dysfunction. While shock is classically associated with hypotension, there is increasing acceptance of the
contention that hypotension is a relatively late indicator of shock, and that clinicians should be more attuned to
organ system dysfunction as evidence of shock.
Signs of Shock:
- altered mentation
- oliguria
- decreased mixed venous or central venous saturation
- hypotension, abnormal heart rate
- lactic acidosis
- peripheral cyanosis (variable)
In both the critical care and trauma literature, the endpoints for resuscitation have also evolved. While
traditional endpoints such as mean arterial pressure and central venous pressure are still regarded as important,
increasing emphasis is being placed on the mixed/central venous oxygen saturation (Ladakis) and lactate levels in
the blood. The combination of inexpensive and readily available serum lactates and increasing appreciation of the
prevalence of hyperchloremic acidosis in the setting of large volume resuscitation has led to the near abandonment
of the base excess/deficit as a guide to the adequacy of resuscitation. Several publications over the past several
years have dampened enthusiasm for the use of central venous oxygenation (Chawla, Sander, Varpula), but it
nevertheless remains a very useful indicator of the adequacy of oxygen delivery.
It is helpful to understand the modern incarnation of the Fick Equation of the relationship between oxygen
consumption, cardiac output, arterial oxygen content, and mixed venous oxygen content. This algebraic
rearrangement emphasizes that the mixed venous saturation is adequate only when the delivery of oxygen to the
peripheral tissues is well matched to their needs:
SvO2 (CvO2) = CaO2 VO2
Qt
(Where SvO2 is the mixed venous oxygen saturation, CvO2 is the mixed venous oxygen content, CaO2 is the
arterial oxygen content, VO2 is the oxygen consumption, and Qt is the cardiac output)
Importantly, as oxygen delivery to the tissues falls, oxygen extraction rises, and continues until the tissues are no
longer able to extract more oxygen. When this happens, crisis ensues.
118
Page 3
In the above figure, oxygen extraction increases as oxygen delivery decreases. When the tissues reach the limits of their ability
to extract oxygen (the critical extraction ratio ERc), the critical oxygen delivery has been reached (Qo2c), and further decreases
in oxygen delivery will be associated with a decline in oxygen consumption.
Arterial hypoxemia, anemia, hyper-metabolism, and a low cardiac output all lower the mixed venous and central
venous saturation. Increasingly, practitioners are utilizing protocols which include as one of their endpoints a
central venous oxygen saturation above a certain level (Ladakis, Rivers). This strategy of forward defense is in
part based on the increasing recognition that hypotension is a relatively late indicator of shock, and that resuscitating
a patient to a marginal blood pressure may leave them with an inadequate physiologic reserve.
__
From Physics : V = I x R Substituting produces: BP Pra = Qt x SVR
Hypoperfusion (shock) can arise from:
- low cardiac output
- low SVR
- the combination of a low cardiac output and high SVR
118
Page 4
We can represent the circulation by superimposing the Starling curve and the venous return curves. Examples of
this are below:
As demonstrated by the above figure, we can superimpose the Starling curve from above left upon the venous return curve from
the above right and generate a graphical representation of the state of the circulation. The cardiac output is represented by the
Y projection of the intersection of these curves, and the CVP we measure clinically is represented by the X projection of the
intersection of these curves.
Diastolic dysfunction is a generally underappreciated and very important contributor or cause of shock
states.
In animal models of hemorrhagic shock, even small reductions in pleural pressures from reduced levels of
PEEP or reduced respiratory rates can produce dramatic improvements in survival (Herff). This data, coupled with
similar data from animal models of CPR, are generating increased interest in ventilation strategies associated with
the lowest possible airway pressures in patients with shock.
Causes of Diastolic Dysfunction:
Extrinsic Intrinsic Luminal
PEEP, iPEEP Ischemia RV failure/septal shift
tPTX LVH Tumor (e.g. myxoma)
Pericardial fluid Infiltration Clot
Massive ascites Fibrosis
In the above table, those causes listed in italics may be responsive to the infusion of volume. The other causes are minimally
responsive to volume infusion, or not at all.
118
Page 5
Bedside Assessment of the patient with shock
The following questions constitute an orderly way to assess the patient with inadequate circulation:
1. Is the Cardiac Output Reduced?
2. Is the heart too full?
3. What doesnt fit?
Is the cardiac output reduced?
No ! Vasodilated Shock
Yes ! Hypovolemic shock, Cardiogenic Shock, or Obstruction to Venous Return
The above figure demonstrates the sentinel feature of vasodilated or high cardiac output shock: the wide pulse
pressure. Patients with vasodilated shock almost invariably have a pulse pressure which is greater than half of their
systolic pressure, whereas patients with low cardiac output shock typically have a pulse pressure which is
substantially lower than normal. A patient with a blood pressure of 80/30 almost certainly has vasodilated shock,
whereas a patient with a blood pressure of 80/60 will have one of the causes of low cardiac output. On examination,
patients with vasodilated shock will have brisk capillary refill while patients with low cardiac output shock will have
delayed capillary refill.
Differential Diagnosis of Vasodilated Shock:
- Sepsis, Sepsis, Sepsis
- Systemic Inflammatory Response Syndrome (SIRS) (e.g. pancreatitis)
- Hepatic failure
- Anaphylaxis
- Adrenal insufficiency
- AV fistula
- Others
118
Page 6
Is the heart too full?
If the cardiac output is low, the differentiation of hypovolemic and cardiogenic shock is accomplished
through the review of pertinent historical, physical examination, and laboratory data. Historical information is often
compelling in its support for the conclusion that hypovolemia is the cause of an unacceptable circulation.
Causes of Hypovolemia: Supportive of Cardiogenic Shock:
- Hemorrhage - jugular venous distention
- insensible losses - extra heart sounds
- redistribution to extravascular space - pulmonary edema in association with narrow PP
- GI losses - signs or symptoms of myocardial ischemia
- renal losses - new heart murmurs
- vasodilation (venodilation) - cardiomyopathy or myocarditis
Cardiogenic shock is most readily assessed with echocardiography. The differential diagnosis of
cardiogenic shock includes acute LV infarction, acute on chronic LV failure, RV infarction, RV failure from some
cause of increased pulmonary vascular resistance, and previously undiagnosed valvular lesions such as aortic
stenosis, mitral stenosis, and mitral regurgitation.
Echocardiography has supplanted the Swan-Ganz catheter as the method of choice for assessing the patient
with suspected cardiogenic shock. Reasons for this include increasing recognition that practitioner understanding of
how to utilize data from a Swan-Ganz catheter is generally poor (Iberti), difficulty demonstrating that these catheters
improve outcomes (Sandham), and increasing acceptance that central venous gases correlate well with mixed venous
gases. Perhaps most importantly, echocardiographic studies have documented surprisingly poor correlation between
filling pressures as measured by invasive monitors and left ventricular end-diastolic volume (Osman). Evidence
impeaching the use of central venous pressure measurements continues to accumulate, and is now being
summarized in colorful review articles(Marik).
As a consequence of these insights, experts are increasingly advocating the use of arterial pulse pressure
variation as a guide to administering fluid, with a difference of >10-15% with respiration strongly associated with a
favorable response to fluid administration (Michard, 2005). The two most commonly used metrics are Systolic
Pressure Variation (SPV) and Delta Pulse Pressure (!PP). Systolic Pressure Variation is easier to estimate from
conventional monitors, but is slightly inferior to delta Pulse Pressure (also referred to as Pulse Pressure Variation
PPV). SPV and/or PPV outperform both CVP and Pcwp as predictors of volume responsiveness in septic patients
and cardiac patients, including patients undergoing OPCAB and post-op CABGs (Auler, Hofer, Kramer). Newer
monitors intended for use in either the ICU or the OR incorporate software that facilitates the evaluation of these
parameters. Other technologies, including Stroke Volume Variation (SVV)(Lahner, Machare-Delgado), and the
PICCO derived Intrathoracic Blood Volume Index (ITBV)) are being explored as alternatives to the CVP in
predicting volume responsiveness (Muller), but do not yet match the performance of either PPV or SPV. There is a
growing literature regarding the use of pulse-oximeter derived plethysmography as a less-invasive alternative to
SPV or PPV(e.g. Pizov)
Systolic pressure variation is useful as a guide to the management of the patient in shock in another way:
patients with minimal or no variation in the blood pressure and pulse pressure are very unlikely to respond to volume
administration. The initial efforts to resuscitate such patients should therefore be directed at pharmacologic or
mechanical interventions, which are much more likely to be effective. Because this strategy minimizes the
unnecessary administration of fluid to critically ill patients, it may improve outcomes.
What doesnt fit?
Most patients with hypovolemic shock, LV shock, and sepsis respond to appropriate therapy. Failure to
respond should raise red flags, and drive an evaluation for obstructive shock. Obstructive shock is shock caused by
an obstruction to venous return. Obstructions to venous return are often insidious. While volume resuscitation and
therapy with vasoactives might produce a transient minor improvement in the circulation, the definitive treatment
consists of relieving the obstruction if this is possible.
Interestingly, as a group, obstructions to venous return produce the kinds of variations in pulse
pressure described above (Magder 2004, 2005). More recent clinical studies have reported that right ventricular
shock can also produce an increase in SPV or PPV that is not responsive to fluid administration (Mahjoud). Hence,
when a patient with significant pulse pressure variation (and a higher CVP) fails to respond to fluid administration,
the sapient practitioner should entertain the possibility of right ventricular shock or an obstruction to venous return
as the explanation. The expeditious evaluation of such patients includes a physical exam with careful attention to
118
Page 7
the character of the heart tones, chest wall symmetry and excursion, and abdominal wall tension. In patients with
tense or distended abdominal walls, transducing a bladder pressure is very helpful in completing the evaluation for
abdominal tamponade. In mechanically ventilated patients, the expiratory flow waveform should be evaluated for
auto-PEEP. In most instances, a stat portable chest radiograph, trans-thoracic echocardiogram, and the measurement
of a bladder pressure will be sufficient to complete the evaluation of a patient with refractory shock
Causes of Obstructive Shock (Obstructions to Venous Return)
- pericardial effusion
- restrictive pericardium
- tension pneumothorax
- high levels of PEEP or intrinsic PEEP
- massive pleural effusion
- abdominal tamponade
- venous occlusion (clot, air, tumor, pregnancy)
- atrial occlusion (clot, air, tumor)
Reconciliation of Central Venous Pressures and Dynamic Indicators
The following 2x2 table is intended to aid practitioners in their assessment of patients with hypotension:
Studies using strategies similar to this are beginning to be reported in the literature (Benes).
References:
- Maas JJ, et al: Bedside Assessment of Total Systemic Vascular Compliance, Stressed Volume,
and Cardiac Function Curves in Intensive Care Unit Patients Anesth Analg 2012; 115:880 7
- Magder S: Hemodynamic monitoring in the mechanically ventilated patient. Curr Op Crit Care 2011; 17:36-42
- Machare-Delgado E, Decaro M, Marik PE: Inferior Vena Cava Variation Compared to Pulse Contour Analysis as
Predictors of Fluid Responsiveness: A Prospective Cohort Study Journal of Intensive Care Medicine 26(2) 116-124,
2011
- Jansen TC et al: Early Lactate-Guided Therapy in Intensive Care Unit Patients
Am J Respir Crit Care Med Vol 182. pp 752761, 2010
- Benes J, Chytra I, Altmann P, et al: Intraoperative fluid optimization using stroke volume variation in high risk
surgical patients: results of prospective randomized study Critical Care 2010, 14:R118
- Pizov R, Eden A, Bystritski D, et al: Arterial and Plethysmographic Waveform Analysis in Anesthetized Patients
with Hypovolemia. Anesthesiology 2010;113:83-91
118
Page 8
- Marik PE: Techniques for Assessment of Intravascular Volume in Critically Ill Patient J Intensive Care Med 2009
24: 329-37
- Mahjoud Y, Pila C, Friggeri A, et al: Assessing fluid responsiveness in critically ill patients: False-positive pulse
pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle Crit Care Med 2009;
37:2570-75
- Marik PE, Cavallazzi R, Vasu T, et al: Dynamic changes in arterial waveform derived variables and fluid
responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care Med 2009;
37:26422647
- Lahner D, KabonB, Marschalek C, et al: Evaluation of stroke volume variation obtained by arterial pulse contour
analysis to predict fluid responsiveness intraoperatively. Br J Anaesth 2009; 103: 34651
- Marik PE, Baram M, Vahid B: Does Central Venous Pressure Predict Fluid Responsiveness? A Systematic Review
of the Literature and the Tale of Seven Mares. Chest 2008; 134:172178
- Muller L, Louart G, Bengler C, et al: The Intrathoracic Blood Volume Index as an Indicator of Fluid
Responsiveness in Critically Ill Patients with Acute Circulatory Failure: A Comparison with Central Venous
Pressure. Anesth Analg 2008;107:60713
- Herff H, Paal P, von Goedecke A, et al: In!uence of ventilation strategies on survival in severe controlled
hemorrhagic shock. Crit Care Med 2008; 36:26132620
- Gelman S: Venous Function and Central Venous Pressure. Anesthesiology 2008; 108:735 48
- Durairaj L, Schmidt GA: Fluid Therapy in Resuscitated Sepsis: Less is More. Chest 2008; 133:252263
- Buettner M, Schummer W, Huettemann, E et al: In!uence of systolic-pressure-variation-guided intraoperative !uid
management on organ function and oxygen transport. British Journal of Anaesthesia 2008;101 (2): 194 9
- Auler JO, Galas F, Hajjar L, et al: Online Monitoring of Pulse Pressure Variation to Guide Fluid Therapy After
Cardiac Surgery. Anesth Analg 2008;106:12016
- Osman D, Ridel C, Ray P, et al: Cardiac filling pressures are not appropriate to predict hemodynamic response to
volume challenge. Crit Care Med 2007; 35:6468
- Sander M, Spies CD, Foer A, et al: Agreement of central venous saturation and mixed venous saturation in cardiac
surgery patients. Intensive Care Med 2007; 33:17191725
- ARDSnet: Comparison of Two Fluid-Management Strategies in Acute Lung Injury N Engl J Med 2006;354:2564-
75.
- Varpula M, Karlsson S, Ruokonen E, et al: Mixed venous oxygen saturation cannot be estimated by central venous
oxygen saturation in septic shock. Intensive Care Med 2006; 32:13361343
- Magder S: Central venous pressure: A useful but not so simple measurement. Crit Care Med 2006; 34:22242227
- Michard F: Changes in Arterial Pressure during Mechanical Ventilation Anesthesiology 2005; 103: 419-28
- Preisman S, Kogan S, Burkenstadt H et al: Predicting !uid responsiveness in patients undergoing cardiac surgery:
functional haemodynamic parameters including the Respiratory Systolic Variation Test and static preload indicators
British Journal of Anaesthesia 2005; 95: 74655
- Magder S: How to use central venous pressure measurements. Curr Opin Crit Care 2005; 11:264-70
- Hofer CK, Muller SM, Furrer L, et al: Stroke Volume and Pulse Pressure Variation for Prediction of Fluid
Responsiveness in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting Chest 2005; 128:848-54
- Kramer S, Zygun D, Hawes H, et al: Pulse Pressure Variation Predicts Fluid Responsiveness following CABG.
Chest 2004; 126:1263-68
- Chawla LS, ZIa H,Gutierrez G, et al: Lack of Equivalence Between Central and Mixed Venous Oxygen Saturation
Chest 2004; 126:18911896
- Magder S. Clinical usefulness of respiratory variations in arterial pressure. Am J Resp Crit Care Med 2004;
169:151-5
- Holmes CL, Walley KR: The evaluation and management of shock. Clin Chest Med 24 (2003) 775789
- Rivers E, Nguyen B, Havstad, S, et al: Early Goal-Directed Therapy in the treatment of Severe Sepsis and Septic
Shock. NEJM 2001;345:1368-77
- Magder S, Scharf SM. Venous return. In: Scharf S, Pinsky M, Magder S, editors. Respiratory-circulatory
interactions in health and disease, 2nd ed. New York: Marcel Dekker; 2001. p. 93112.
- Munis JR, Bhatia S, Lozada L: Peripheral Venous Pressure as a Hemodynamic Variable in Neurosurgical Patients.
Anesth & Analg 92:172-179, 2001
- Massumi RA, Mason DT, Zakauddin V, et al. Reversed pulsus paradoxus. N Eng J Med 1973; 289:1272-5
- Robotham JL, Lixfield W, Holland L, MacGregor D, Bryan AC, Rabson S. Effect of respiration on cardiac
performance. J Appl Physiol 1978; 44:703.
118
Page 9
- Robotham JL, Cherry D, Mitzner W, et al.: A re-evaluation of the hemodynamic consequences on intermittent
positive pressure ventilation. Crit Care Med 1983; 11:783-93
- Magder SA, Lichtenstein S, Adelman AG. Effects of negative pleural pressure on left ventricular hemodynamics
Am J Cardiol 1983; 52:588593
-Brower R, Wise RA, Hassapoyannes C, et al. Effect of lung inflation on lung blood volume and pulmonary venous
flow. J Appl Physiol 1985; 58:954-63
-Perel A, Pizov R, Cotev C. The systolic blood pressure variation is a sensitive indicator of hypovolemia in
ventilated dogs subjected to graded hemorrhage. Anesthesiology 1987; 67:498-502
- Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest
2002; 121:2000-08
- Bendjelid K, Romand JA. Fluid responsiveness in mechanically ventilated patients: a review of indices used in
intensive care. Intensive Care Med 2003; 29:352-60
- Michard F, Boussat S, Chemla D, et al. Relation between respiratory changes in arterial pulse pressure and fluid
responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000; 162:134-8
- Tavernier B, Makhotine, O, Lebuffe G, et al: Systolic Pressure Variation as a guide to fluid therapy in patients with
sepsis induced hypotension. Anesthesiology 1998; 89:1313-21
- Berkenstadt H, Margalit N, Hadani M, et al. Stroke volume variation as a predictor of fluid responsiveness in
patients undergoing brain surgery. Anesth Analg 2001; 92:984-9
- Reuter DA, Kirchner A, Felbinger TW, et al. Usefulness of left ventricular stroke volume variation to assess fluid
responsiveness in patients with reduced cardiac function. Crit Care Med 2003;31:13991404
- Guyton AC. Determination of cardiac output by equating venous return curves with cardiac response curves.
Physiol Rev 1955; 35:123129.
- Sylvester JT, Goldberg HS, Permutt S.: The role of the vasculature in the regulation of cardiac output. Clin Chest
Med 1983; 4:111125
- Jacobsohn E, Chorn R, OConnor M: The role of the vasculature in regulating venous return and cardiac output:
historical and graphical approach. Can J Anaesth 1997; 44:849-867
- Sagawa K.: The ventricular pressure-volume diagram revisited. Circ Res 1978; 43:677687.
- Coriat P, Vrillon M, Perel A, et al. A comparison of systolic blood pressure variations and echocardiographic
estimates of end-diastolic left ventricular size in patients after aortic surgery. Anest Analg 1994; 78:46-53
- Ladakis C, Myrianthefs P, Karabinis A, et al: Central Venous and Mixed Venous Oxygen Saturation in Critically
Ill Patients. Respiration 2001; 68:279285
- Kumar A, Anel R, Bunnell E, et al. Pulmonary artery occlusion pressure and central venous pressure fail to predict
ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Crit Care
Med 2004;32:691-9.
- Iberti TJ, Fischer EP, Lebowitz AB, et al: A multicenter study of physicians knowledge of the PA catheter. JAMA
1990;264:2928-32
- Sandham JD. Hull RD. Brant RF. et al: A randomized, controlled trial of the use of pulmonary-artery catheters in
high-risk surgical patients. New England Journal of Medicine. 2003; 348(1):5-14
Disclosure
Page 1
Central Line Insertion: State-of-the-Art in 2013
Avery Tung, M.D. Wilmette, Illinois
Introduction:
Although central line insertion has been performed in hospitals for decades, only recently has attention
been paid to optimizing the process by which such lines are inserted. Driven by a decreasing number of clinical
opportunities for teaching line insertion, a rising awareness of the role of medical error in patient outcomes, and a
desire to minimize preventable complications, clinicians have begun to measure and report the incidences of central
line complications including failed insertion, catheter related bloodstream infections, pneumothorax, air embolism,
and retained guide wire. As an example, the Pubmed search term central venous catheter complications returned
108 entries in 1990 vs 278 in 2012. Armed with these data and with new technologies, clinicians have developed
new strategies for safer central line insertion.
Within the last 15 years, three strategies stand out as significant. The first is the ready availability and
widespread adoption of high fidelity 2 dimensional ultrasound devices. These devices have allowed clinicians to
define central vein anatomy with far greater accuracy than by using landmarks, and provided inserters with real time
guidance during actual line insertion. Accumulating data from studies of ultrasound use suggest not only that
classical landmark strategies for line insertion are frequently inaccurate (2), but that use of ultrasound for vein
identification and needle guidance during insertion can greatly facilitate both the identification of relevant venous
anatomy and the actual process of cannulation (3-5).
The second strategy for improving the safety and reducing the complication rate of central line insertion
has been the introduction of an organized, start-to-finish systematic process for placing central lines. Symbolized by
the central line checklist, this conceptual shift has caused the technical process of line placement to evolve from
just another clinical chore to a highly technical, complex task. Considerable evidence suggests that viewing line
insertion in this way, and using a central line checklist, can meaningfully reduce the incidence of central line
bloodstream infections. In addition to the seminal 2006 report of reduced central line infections with checklist use
(6), other subsequent studies have found reduced infection rates, even in hospitals without preexisting safety
infrastructures (7,8). That many elements of commonly used checklists are seemingly mundane (handwashing),
further suggests that an organized, systematic focus on the technical process of line placement may be as important
as operator skill and experience.
The third advance is an increased focus on technical training for line insertion. In many large teaching
hospitals, historic see one do one approaches have largely been supplanted by structured curricula that include
video and computer based training, and hands-on simulation. With these advanced educational approaches, novices
can become familiar with the insertion hardware, refine their sterile technique, practice the required tasks, and
rehearse rescue or troubleshooting strategies all without adverse effects on actual patients. Existing evidence
suggests an effect of simulation on reducing the number of needle passes (9), complications (10), and overall
success (11).
In addition to the above, medical specialty societies have responded to this increased focus on central line
safety and evolution in insertion techniques by creating guidelines. The American Society of Anesthesiologists
(ASA) (12), American College of Surgeons (13), British National Institute of Clinical Excellence (14), Australian
Clinical Excellence Commission (CEC) (15), and the Centers for Disease Control (16) have all issued
recommendations regarding best practice for some aspect of central line insertion. This talk will review existing
124
124
Page 2
literature (including these guidelines where appropriate) with respect to central line insertion, identify best practice
where applicable, and briefly address specific complications of line insertion.
Pre-insertion
a. Indications
A full discussion of indications (and contraindications) for central line placement are beyond the scope of this talk.
Two trends in clinical practice are worth noting. The first is a decreasing emphasis on central venous access for
hemodynamic monitoring purposes. Neither central venous pressure measurement nor Swan Ganz catheterization,
for example, have clear evidence-based benefit for hemodynamic monitoring (17,18). The second is the rising
acceptance of peripherally inserted central access (PICC) lines for intravenous infusions. Placed in the same
anatomic location as peripheral IVs, these devices can sometimes obviate the need for central access altogether.
b. Location and resource preparation:
Surveying the anticipated site of central line insertion with ultrasound can identify anatomical issues that may
complicate placement. Such pre-scanning can be particularly useful in complex patients with other central venous
hardware, previous central lines, a history of prior neck surgery and/or venous thrombosis. Unanticipated
abnormalities in the size/location of the target vein, hematomae or clot, and/or foreign bodies can all be identified
with ultrasound. In one study of ultrasound surveillance, the internal jugular vein could not be visualized in up to
2.5% of patients (2). Recognizing these issues may affect site selection or even the decision to place a line itself.
For the internal jugular site, prescanning may permit positioning the head to maximize lateral separation of the
carotid and internal jugular vein. Increased head rotation generally increases carotid/internal jugular overlap, raising
the risk of inadvertent carotid puncture (19).
Although not explicitly evidence based, Both ASA and CEC guidelines recommend basic levels of ancillary support
for central line insertion. An environment that permits use of aseptic techniques, a trained assistant, adequate space
and lighting, access to a handwashing sink, monitoring equipment for ECG, BP, and pulse oximetry, and immediate
access to resuscitation equipment and drugs are all considered basic support requirements for line insertion.
c. Site Selection:
In principle, identifying the insertion site (femoral, subclavian, internal jugular) with the lowest incidence of
complications should be easy to do. Existing evidence, however, is surprisingly variable with respect to site-specific
risks.
Historically, femoral access sites have been considered at higher risk for infection than either intrathoracic site.
However, more recent data suggest that any difference in infectious risk is narrowing with more modern usage
patterns. In a 2012 Cochrane review examining the relationship between insertion site and infection risk (20), the
authors found no randomized controlled trials comparing all three sites, and only 4 trials with a total of 1,513
patients meeting inclusion criteria. When femoral and subclavian line sites were compared, femoral routes had a
higher risk of catheter colonization (relative risk 6.43, 95% CI 1.95 to 21.21). However, no difference in catheter-
related blood stream infections or colonization was found between femoral and internal jugular line sites. The
Cochrane review also found no overall differences in catheter-related complications between the subclavian and
internal jugular sites (20).
When mechanical and thrombotic complications were considered, the Cochrane review found more thrombotic and
mechanical complications with the femoral (vs subclavian) site (RR 11.53 for thrombotic complications), but fewer
mechanical complications than the internal jugular site (relative risk 0.51). Cochrane found no evidence
differentiating subclavian from internal jugular insertion sites with respect to mechanical or thrombotic
complications. A more recent study (21), however, found greater thrombotic risk in the internal jugular than the
femoral position, highlighting the variability in the literature.
With respect to other aspects of line site selection, current evidence favors the right vs the left internal jugular
insertion site, citing the larger diameter and straighter course of the right IJ, the lower right pleural dome, absence of
the thoracic duct, and ease of access for the right handed operator (22,23). Although existing comparative evidence
does not favor internal jugular over subclavian approaches, multiple case reports describe aortic injury, hemothorax,
and tamponade with subclavian central venous catheterization. In addition, literature reviews suggest slightly higher
risk for arterial puncture with the right subclavian approach, possibly due to kinking of the guidewire during vessel
124
Page 3
dilation (24). One (pre-ultrasound) 2002 meta-analysis (25) assessed 6 comparative trials with >2000 internal
jugular and subclavian catheters and found more arterial punctures with the jugular approach, more malpositions
with the subclavian approach, and no difference in hemo or pneumothoraces.
Changes in clinical practice may also affect line site selection. Most prominent among these is the use of
ultrasound. Because of anatomical considerations, ultrasound is a better guide to insertion in the internal jugular
than the subclavian position. This slight advantage to internal jugular line placement may affect clinical decision
making, particularly when patients are anticoagulated or have a history of difficult line insertion. In addition, the
proclivity for subclavian vein stenosis with large bore subclavian lines (26) has resulted in current CDC guidelines
issuing a Category 1A contraindication for subclavian dialysis access (27). The National Kidney Foundation also
recommends against the subclavian site for placement of dialysis access .
Taken together, these data and guidelines dictate the following best practice approach to line site selection:
1. Identify available sites. Avoid sites with prior surgery, known thrombotic complications, broken/infected
skin, or existing hardware (such as transvenous pacemakers). Be aware that case reports identify the left IJ site as
more complication prone than the right IJ, suggest a higher likelihood of aortic injury/tamponade with subclavian
than internal jugular approaches, and imply that the more tortuous path of the right subclavian approach may
predispose to aortic injury due to guidewire kinking.
2. Prioritize the femoral site LAST for thrombosis and infectious control reasons, particularly if the duration
of the line is expected to be long. Although existing data find no increased infectious risk in the femoral position,
these results may be due to shorter line durations and greater use of PICC strategies.
3. Scan available sites to identify potential barriers to site insertion
4. If placing a cordis or large-bore introducer, consider the smaller size and more variable location of the left
IJ, and risk of subclavian stenosis with large bore indwelling catheters as potential decision factors.
e. Aseptic technique
How should the central line inserter prepare himself/herself to minimize central line associated infection? While
existing literature is unable to quantify the contribution to reducing central line infections from specific aseptic
activities, bundles of activities performed together have been extensively and empirically tested. Elements of such
bundles include cap, mask, sterile gown and gloves, and handwashing prior to performing the procedure. The most
prominent of these bundles is that used in the Michigan Keystone project, which combined inserter aseptic
strategies (cap, mask, handwashing, sterile gown and gloves) with specific patient preparation activities
(chlorhexidine skin prep and full body sterile drape (6). Using a before/after study design, this approach, reinforced
by use of a checklist, produced a sustained, significant reduction in central line infections.
Much of the bundle lacks comparative evidence of efficacy. As a result, attribution of benefit to inserter elements
(rather than patient elements) is not possible. Some inserter elements (such as sterile gloves and gown) are self-
evident. Others (cap, full body drape) are less so. These data may suggest that cognitively regarding line insertion
as a technically complex task may itself have benefit and that the specific elements of a line insertion bundle may
not be as important as whether a bundle exists at all.
With respect to skin preparation, a combination of chlorhexidine and alcohol has largely supplanted Povidine-Iodine
due to a combination of incomplete data and guideline pressure. The Centers for Disease Control, the Michigan
checklist, and ASA guidelines all recommend 2% Chlorhexidine, with or without 70% alcohol as a first line agent,
with Povidine Iodine with 70% alcohol for patients allergic to Chlorhexidine. The combination of alcohol and
Chlorhexidine is recommended because alcohol alone does not provide long lasting antimicrobial activity. Note that
the package insert for chlorhexidine/alcohol recommends a, back and forth scrubbing application pattern rather
than the inside to outside circular pattern used for Povidine Iodine. This scrubbing strategy is advocated to
penetrate the first 5 cell layers where 80% of skin flora reside (28)
With respect to antibiotic-impregnated central lines, a 2013 Cochrane review (29) found a reduction in catheter
colonization and related bloodstream infections, but that benefit was significant only in the ICU and that no effect on
mortality was apparent. As a result, few centers routinely use antibiotic impregnated lines. CDC guidelines
recommend use of impregnated catheters only for prolonged use, or if a comprehensive strategy to reduce infection
rates does not work.
124
Page 4
Insertion
a. Patient position
Existing evidence suggests that abdominal compression, increased intrathoracic pressure, and Trendelenburg
position increase internal jugular vein size (30). Effects of similar maneuvers on subclavian vein size are unclear
(31). Nevertheless, using the Trendelenburg position where clinically feasible for both access sites reduces the risk
of air embolism. If targeting the internal jugular site, current evidence suggests that head rotation should be limited
as increasing head rotation increases overlap between the internal jugular vein and carotid artery (19). Evidence
suggests modest improvements in subclavian vein size with the head in the neutral position (31).
No comparative data exist to differentiate the Seldinger from the modified technique. In the Seldinger technique,
the inserter cannulates the vein using a thin walled, hollow needle. Once blood return is obtained, a wire is placed
through the needle and into the vein. In the modified Seldinger technique, the inserter cannulates the vein using a
hollow needle which is threaded through a plastic catheter. Once blood return is obtained, the plastic catheter is
threaded into the vein. The guide wire is then passed through the plastic catheter into the vein and the plastic
catheter is removed. Arguments for the Seldinger technique include speed and simplicity. Arguments for the
modified technique include ease of use of manometry for venous confirmation, and ease of use for the novice. It is
easy to see that local preferences, operator skill, and equipment availability likely have a greater effect on
cannulation success than intrinsic aspects of each technique.
Several observational studies find that central venous access complication rates increase with the number of needle
passes (32), and that more experienced operators have higher success rates (33). Based on these data, best practice
should include changing operators or techniques if multiple passes by a single operator are unsuccessful.
Considerable controversy exists among practitioners regarding the use of ultrasound for locating the vein and for
guiding the actual cannulation (34). Comparisons between the anatomical landmark approach and an ultrasound
guided approach routinely find that real time ultrasound use increases success rates, decreases carotid puncture rates,
and reduces access time. Existing literature is less robust for ultrasound use for the subclavian site, and equivocal
for the femoral site.
Numerous specialty societies and guidelines recommend the use of ultrasound to facilitate central line insertion.
These include the American Society of Anesthesiologists, the American College of Surgeons, the British National
Health Service, the Australian Clinical Excellence Commission, and the US Agency for Healthcare Research and
Quality. Arguments against routine use of ultrasound include time, availability of equipment during emergencies,
inadequate training cost, and adverse effects of improper use. Because imaging the internal jugular vein for line
insertion is best done in short axis view to rule out carotid cannulation, the tip and shaft of the needle will have the
same appearance on ultrasound. Inexperienced operators may fail to identify the location of the tip, leading to
carotid puncture, pneumothorax, and other complications. Also, a tendency to focus on the ultrasound image instead
of the patient during insertion may lead to overadvancing the needle. Ultrasound training is considered so important
that CDC guidelines for prevention of central line infections consider training a category 1B recommendation and
CEC guidelines explicitly state that previous training or experience is required to use this technology effectively.
Although no direct evidence exists to specify how deep the wire should be inserted into the vein, reported
complications from deep insertion of the wire have included dislodgement and ensnarement of vena caval filters
(35), entanglement in the tricuspid valve (36), and complete heart block (37) Taken together, the above anecdotal
and case report-based literature suggest that best practice should involve some surface assessment of how deep the
wire must be inserted to facilitate free passage of the dilator and catheter. Once the wire is inserted into the vessel, a
verification step is strongly recommended to verify whether the wire is in the target vein. However, few verification
strategies are validated by high quality current evidence and no comparative trials exist. Strategies to distinguish
venous from arterial location with equivocal evidence include pressure waveform analysis, color of blood, blood gas
analysis, or absence of pulsatile flow. Because hypoxemia, tricuspid regurgitation, and/or hypotension may
confound these strategies, they are not recommended by ASA guidelines. Other strategies such as fluoroscopy,
continuous electrocardiography, transesophageal echo, or chest XRay have slightly stronger supporting evidence.
If ultrasound is used to guide insertion, it can also be used to verify wire location by tracking the guide wire from
where it enters the skin to where it enters the relevant vessel. This approach, however, is not foolproof. If an error
is made in identifying the vessel then verification using ultrasound will likely fail to catch that original error. In
124
Page 5
addition, ultrasound may not be able to track more than 5cm into the thoracic cavity. Guidewires that pass
completely through the vein and end up in the artery may escape ultrasound-based verification.
The strongest published evidence for verifying wire location in the vein is manometry. With this technique, a length
of IV tubing is attached to an IV catheter or needle located inside the vessel in question. The pressure in the vessel
is then measured either by holding the tubing vertically and visualizing the height of the column, or by connecting
the tubing to a pressure transducer. In a 2009 retrospective review, 9,348 central venous catheters placed during a
15 year period using manometry to verify venous location of the wire (38). No cases of dilator placement into
adjacent arteries were noted, and the authors calculated that use of manometry prevented up to 56 possible arterial
dilations.
In part, the choice of verification technique depends on cannulation technique. Whether the Seldinger or modified
Seldinger technique is used to cannulate the vein can significantly affect the ease of using either manometry or
ultrasound for verification. With the Seldinger technique, use of manometry to verify wire placement must be
performed with the needle tip manually stabilized while in the vein or by inserting the wire and switching over to a
plastic catheter. It is easy to see that this approach requires a high degree of manual dexterity, and may result in loss
of access or air embolism, particularly when access is difficult or the patient is breathing spontaneously or moving.
In contrast, with the modified Seldinger technique the inserter threads a plastic catheter over the hollow needle into
the vein. Manometry can then be performed via this hollow plastic catheter, with less difficulty in maintaining
venous access. Although this strategy assumes that a wire passed through the plastic catheter terminates in the vein,
this assumption seems reasonable and no case reports have observed successful manometry with the plastic catheter,
and subsequent malposition of a wire inserted through that catheter.
Overall, existing evidence is insufficient to dictate a best practice. Nevertheless, the combination of case reports,
observational trials, clinical experience, and expert opinion can be integrated to recommend a reasonable practice
with respect to verifying wire placement in the target vein:
1. Because the consequences of arterial puncture are significant, verification that the target vein has been cannulated
(vs the artery) is strongly recommended by ASA and CEC guidelines
2. Blood color, waveform analysis, and/or pulsatility are not recommended due to the high likelihood of
confounding states
3. If fluoroscopy, catheter tip electrocardiography, or transesophageal echocardiography are available, case reports
and observational trials support their use for verification purposes
4. The two verification strategies with the greatest degree of overall support are pressure transduction of the target
vessel (manometry) and ultrasound imaging of the catheter inside the target vessel.
5. Choice of verification technique should depend on operator experience and technical issues. Because use of
manometry with the Seldinger wire through needle technique is technically more difficult than with the modified
catheter over needle Seldinger approach, consider using ultrasound verification with the Seldinger technique.
Once inserted, the line tip should remain in the superior vena cava and not extend into the right atrium to prevent
arrhythmias and right atrial perforation. Strategies for localizing the tip include insertion markings at the skin,
topographical markings of the chest, or chest radiography, transesophageal echocardiography, and right atrial
electrocardiography. No comparative trials exist. One (non-evidence-based) useful rule of thumb is to verify that
the tip of the line does not protrude below the bottom border of the right mainstem bronchus. Although ASA
guidelines are silent, CEC guidelines provide a table to specify insertion depth as a function of patient height and
insertion site.
Complications and aftercare
The list of complications referable to central line insertion is large. These include arterial puncture, hematoma,
hemothorax, pneumothorax, aortic injury, vena caval or atrial perforation, tamponade, thoracic duct damage,
arrhythmia, and catheter-related infection. Because of rapid changes in insertion technique/training, incidences of
these complications are difficult to assess accurately. A 2003 New England Journal review estimated the incidence
of arterial puncture as 6-9% for the IJ site and 3-5% for the subclavian site, and the incidence of pneumothorax as
0.1-0.2% for IJ and 6 to 11% for subclavian sites (39). In the era of ultrasound, these numbers are likely lower for
the IJ site, and may also be falling for subclavian use.
124
Page 6
The ASA closed claims database provides another window into the landscape of central line complications. A 1970-
2004 analysis of malpractice claims for central line complications found 110 claims for injuries related to central
lines (40). The most common were wire/catheter embolus (N=20), followed by tamponade, carotid artery
puncture/cannulation, and hemothorax/pneumothorax. While it is likely that most of these events also predated the
routine use of ultrasound, their presence as a closed claim suggests that they are considered at least partly
preventable. Post-insertion best practice should thus include maintaining a high degree of suspicion for the
possibility of injury due to line insertion.
Other elements of central line aftercare includes attention to infection prevention. Daily attention to the ongoing
need for central access, and prompt removal if the line isno longer necessary can clearly shorten line duration and
reduce infectious complications. Existing literature recommends against routine replacement of central venous
catheters (41), against routine use of antibiotic ointments (42), and against routine wire guided line exchange (41).
ASA guidelines, citing low quality literature and expert opinion, recommend transparent bio-occlusive dressings,
wiping catheter access ports with antiseptic before use, keeping ports capped when not used, and daily inspection of
the line site for redness, drainage, or other signs of infection. CEC guidelines further suggest weekly changes of
sterile occlusive dressings unless there is evidence of inflammation, and allows for the use of chlorhexidine
impregnated sponges.
Summary
Recent advances in central line insertion techniques, increased attention to preventing central line, and improved
training strategies have dramatically improved the process of central line insertion. For many aspects of line
insertion, best practices are beginning to emerge. These include an organized, systematic approach to inserter
training and line insertion, consistent, specific aseptic preparation of the patient and inserter, use of static and
dynamic ultrasound when feasible, evidence based site selection, verification of wire position, localization of the
catheter tip, and post-insertion maintenance.
The results of these recent advances are clear: a dramatic, widespread, and persistent fall in the rate of central line-
associated bloodstream infections. With further implementation of bundled line insertion strategies, advances in
training, and increasing ultrasound use, it is possible that other central line complications my also decrease in
incidence.
References
1. Tung A. Best practices for central line insertion. Int Anesthesiol Clin. 2013;51(1):62-78
2. Denys BG, Uretsky BF. Anatomical variations of internal jugular vein location: impact on central venous access.
Crit Care Med. 1991;19:1516-9.
3. Karakitsos D, Labropoulos N, De Groot E, Patrianakos AP, Kouraklis G, Poularas J, Samonis G, Tsoutsos DA,
Konstadoulakis MM, Karabinis A: Real-time ultrasound-guided catheterisation of the internal jugular vein: a
prospective comparison with the landmark technique in critical care patients. Crit Care 2006; 10:R162.
4. Mallory DL, McGee WT, Shawker TH: Ultrasound guidance improves the success rate of internal jugular vein
cannulation: a prospective randomized trial. Chest 1990; 98:157-160
5. Slama M, Novara A, Safavian A, Ossart M, Safar M, Fagon JY: Improvement of internal jugular vein cannulation
using an ultrasound-guided technique. Intensive Care Med 1997; 23:916-919
6. Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G,
Bander J, Kepros J, Goeschel C. An intervention to decrease catheter-related bloodstream infections in the ICU. N
Engl J Med. 2006;355:2725-32
7. Lin DM, Weeks K, Bauer L, Combes JR, George CT, Goeschel CA, Lubomski LH, Mathews SC, Sawyer MD,
central line-associated bloodstream infections statewide: the Hawaii experience. Am J Med Qual. 2012;27:124-9
124
Page 7
8. Centers for Disease Control and Prevention (CDC). Vital signs: central line-associated blood stream infections--
United States, 2001, 2008, and 2009. MMWR 2011;60:243-8.
9. Barsuk JH, McGaghie WC, Cohen ER, Balachandran JS, Wayne DB. Use of simulation-based mastery learning
to improve the quality of central venous catheter placement in a medical intensive care unit. J Hosp Med.
2009;4:397-403
10. Barsuk JH, McGaghie WC, Cohen ER, O'Leary KJ, Wayne DB. Simulation-based mastery learning reduces
complications during central venous catheter insertion in a medical intensive care unit. Crit Care Med.
2009;37(:2697-701.
11. Evans LV, Dodge KL, Shah TD, Kaplan LJ, Siegel MD, Moore CL, Hamann CJ, Lin Z, D'Onofrio G.
Simulation training in central venous catheter insertion: improved performance in clinical practice. Acad Med.
2010;85:1462-9.
12. ASA Task Force on Central Venous Access. Practice Guidelines for Central Venous Access. Anesthesiology
2012; 116:53973
13. American College of Surgeons Revised statement on recommendations for use of real-time ultrasound guidance
for placement of central venous catheters. http://www.facs.org/fellows_info/statements/st-60.html, accessed June 2,
2012
14. http://www.nice.org.uk/nicemedia/pdf/Ultrasound_49_GUIDANCE.pdf, accessed June 2, 2012
15. http://www.cec.health.nsw.gov.au/programs/clab-icu, accessed June 2, 2012
16. OGrady NP et al. Guidelines for the Prevention of Intravascular Catheter-related Infections. Clinical Infectious
Diseases 2011;52:e162e193
17. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review
of the literature and the tale of seven mares. Chest. 2008;134:172-8.
18. Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, Laporta DP, Viner S, Passerini L, Devitt H,
Kirby A, Jacka M; Canadian Critical Care Clinical Trials Group. A randomized, controlled trial of the use of
pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;348:5-14.
19. Sulek CA, Gravenstein N, Blackshear RH, Weiss L Head rotation during internal jugular vein cannulation and
the risk of carotid artery puncture. Anesth Analg. 1996;82:125-8.
20. Ge X, Cavallazzi R, Li C, Pan SM, Wang YW, Wang FL. Central venous access sites for the prevention of
venous thrombosis, stenosis and infection. Cochrane Database Syst Rev. 2012 Mar 14;3:CD004084.
21. Malinoski D, Ewing T, Bhakta A, Schutz R, Imayanagita B, Casas T, Woo N, Margulies D, Barrios C, Lekawa
M, Chung R, Bukur M, Kong A. Which central venous catheters have the highest rate of catheter-associated deep
venous thrombosis: a prospective analysis of 2,128 catheter days in the surgical intensive care unit. J Trauma Acute
Care Surg. 2013;74(2):454-60
22. Sulek CA, Blas ML, Lobato EB. A randomized study of left versus right internal jugular vein cannulation in
adults. J Clin Anesth 2000; 12:142-5
23. Muralidhar K. Left internal versus right internal jugular vein access to central venous circulation using the
Seldinger technique. J Cardiothorac Vasc Anesth 1995; 9:115-6.
24. Robinson JF, Robinson WA, Cohn A, Garg K, Armstrong JD 2nd. Perforation of the great vessels during
central venous line placement. Arch Intern Med. 1995;155(11):1225-8
124
Page 8
25. Ruesch S, Walder B, Tramr MR. Complications of central venous catheters: internal jugular versus subclavian
access--a systematic review. Crit Care Med. 2002 Feb;30(2):454-60.
26. Spinowitz BS, Galler M, Golden RA, Rascoff JH, Schechter L, Held B, Charytan C. Subclavian vein stenosis as
a complication of subclavian catheterization for hemodialysis. Arch Intern Med. 1987;147:305-7.
27. OGrady NP et al. Guidelines for the Prevention of Intravascular Catheter-related Infections. Clinical Infectious
Diseases 2011;52:e162e193
28. Brown E, Wenzel RP, Hendley JO. Exploration of the microbial anatomy of normal human skin by using
plasmid profiles of coagulase-negative staphylococci: search for the reservoir of resident skin flora. J Infect Dis.
1989;160:644-50.
29. Lai NM, Chaiyakunapruk N, Lai NA, O'Riordan E, Pau WS, Saint S. Catheter impregnation, coating or bonding
for reducing central venous catheter-related infections in adults. Cochrane Database Syst Rev. 2013;6:CD007878
30. Lobato EB, Florete OG Jr, Paige GB, Morey TE. Cross-sectional area and intravascular pressure of the right
internal jugular vein during anesthesia: effects of Trendelenburg position, positive intrathoracic pressure, and
hepatic compression. J Clin Anesth. 1998;10:1-5.
31. Fortune JB, Feustel P. Effect of patient position on size and location of the subclavian vein for percutaneous
puncture. Arch Surg. 2003;138(9):996-1000.
32. Mansfield PF, Hohn DC, Fornage BD, Gregurich MA, Ota DM. Complications and failures of subclavian-vein
catheterization. N Engl J Med. 1994;331:1735-8.
33. Sznajder JI, Zveibil FR, Bitterman H, Weiner P, Bursztein S. Central vein catheterization. Failure and
complication rates by three percutaneous approaches. Arch Intern Med. 1986;146:259-61.
34. Ultrasound guided vascular access: efficacy and safety. Kumar A, Chuan A. Best Pract Res Clin Anaesthesiol.
2009;23(3):299-311.
35. Chattar-Cora D, Tutela RR Jr, Tulsyan N, Patel R, Cudjoe EA, Onime GD. Inferior vena cava filter
ensnarement by central line guide wires--a report of 4 cases and brief review. Angiology. 2004;55:463-8.
36. Hoda MQ, Das G, Mamsa KA, Salimullah H. Unusual site of guide-wire entrapment during central venous
catheterization. J Pak Med Assoc. 2006;56:139-41.
37 Chhabra L, Spodick DH. Complete heart block--an underappreciated serious complication of central venous
catheter placement. J Electrocardiol. 2012;45:790-2.
38. Ezaru CS, Mangione MP, Oravitz TM, Ibinson JW, Bjerke RJ. Eliminating arterial injury during central venous
catheterization using manometry. Anesth Analg. 2009;109:130-4.
39. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med.
2003;348:1123-33.
40. Domino KB, Bowdle TA, Posner KL, Spitellie PH, Lee LA, Cheney FW. Injuries and liability related to central
vascular catheters: a closed claims analysis. Anesthesiology. 2004;100:1411-8.
41. Cook D, Randolph A, Kernerman P, Cupido C, King D, Soukup C, Brun-Buisson C. Central venous catheter
replacement strategies: a systematic review of the literature. Crit Care Med. 1997;25:1417-24.
42. Maki DG, Band JD. A comparative study of polyantibiotic and iodophor ointments in prevention of vascular
catheter-related infection. Am J Med. 1981;70:739-44.
124
Page 9
Disclosure
201
Page 1
Perioperative Coagulation and Coagulopathy
Linda L. Liu, M.D. San Francisco, California
Back decades ago, the coagulation cascade was taught in terms of 2 pathways, the intrinsic versus the extrinsic.
Figure 1 shows a very simplified version of the proposed waterfall/ cascade model of the coagulation system.
Unfortunately, as we started to understand more about the coagulation system, it became more and more complex.
Many of the enzymes were found to be cofactors or were precursors to the active form. We also found that the 2
pathways were not completely separate in function. They appeared to be an intertwined system where modulation
of one arm may or may not affect the second arm. The modern view of coagulation is to actually look at the
coagulation system as a series of steps, 1) initiation, 2) amplification, and 3) propagation, as opposed to distinct
pathways, (1) but the old 2 pathway model is still beneficial in terms of helping us understand what abnormal
coagulation tests mean. This chapter will exam some causes of abnormal coagulation in the perioperative period and
discusses agents that are used to modulate the coagulation system.
Figure 1: Waterfall/ Cascade Model of the Coagulation System
Pre-operative causes of abnormal coagulation
Most patients with congenital coagulation abnormalities present in early life and come to surgery with a known
diagnosis. Patients with hemophilia, von Willebrand disease (vWD), and platelet disorders usually need treatment
before, during, and after surgery. For the patient without a diagnosis of a prior coagulation abnormality, the best
means of detecting a hemorrhagic diathesis is a properly taken history. Some screening pre-operative questions that
201
Page 2
may help flush out a bleeding history are:
1) Is there a history of bleeding in the family?
2) Is there a history of bleeding after procedures (such as biopsy, tooth extraction, surgery)?
3) Do you experience recurrent nosebleeds?
4) Do you experience recurrent gum bleeding?
5) Do you experience bruising routinely?
6) And for females, do you have heavy periods (10 pads/d x 4 days)?
Equally important is a detailed history of drug ingestion and herbal remedy use.
Pre-op abnormalities are best classified based on the abnormal laboratory value platelet count, fibrinogen level,
prothrombin time (PT) or activated partial thromboplastin time (aPTT). PT abnormalities are associated with
deficiencies or inhibitors of FII, FV, FVII, FX, or fibrinogen, which are often associated with liver disease, vitamin
K deficiency, or warfarin effect. Activated PTT abnormalities can be associated with deficiencies or inhibitors of
FII, FV, FVIII, FIX, FX, FXI, FXII or fibrinogen. Diseases often associated with these deficiencies include:
hemophilia A (VIII), hemophilia B (IX), lupus anti-coagulant, and heparin or thrombin inhibitor effect.
An algorithm for further pre-operative work-up for an abnormal PT or aPTT and a positive bleeding history is
shown in figure 2. Patients with a positive bleeding history, but normal PT and aPTT, should be sent for
hematology consultation for more extensive work-up. In this instance, low or dysfunctional platelets, mild
deficiency of von Willebrand factor, vascular disorders, and, rarely, factor XIII deficiency should be considered.
Figure 2: Algorithm for work-up of an abnormal pre-operative PT or aPTT
Intra-operative causes of abnormal coagulation
There are really only 2 main causes of perioperative bleeding. The first and most common is surgical bleeding,
which will not be discussed here. The second is non-surgical bleeding, or failure of the hemostatic pathways.
Causes for this failure include: massive blood transfusion (leading to thrombocytopenia, low fibrinogen, and
coagulopathy), fibrinolysis (induced by the surgical procedure such as prostatectomy, orthotopic liver transplant, or
201
Page 3
exposure to a foreign graft material), disseminated intravascular coagulation (from sepsis, cardiopulmonary bypass,
or transfusion reactions), an undetected pre-existing bleeding disorder or a combination of the above possibilities.
The mainstays of massive blood loss management basically include replacement of red cells, platelets, clotting
factors and fibrinogen. The patient needs to be kept warm and frequent labs are necessary to help guide transfusions
and electrolyte replacements. A basic laboratory profile in the operating room should include hematocrit, platelet
count, PT, aPTT, and fibrinogen level. Antifibrinolytics like tranexamic acid and epsilon-aminocaproic acid can be
given if fibrinogen levels remain low and a mechanism for primary fibrinolysis seems likely. Disseminated
intravascular coagulation (DIC) is difficult to diagnose during surgery since there is no one pathognomonic
laboratory test. Surgical bleeding alone can cause an elevated PT, low fibrinogen levels, and low platelet count.
Distinguishing between primary fibrinolysis and DIC by laboratory values intra-operatively is also very difficult.
The diagnosis may sometimes have to depend on the clinical scenario. D-dimers can be sent, but the results will not
be available quickly. The first goal for treatment of DIC is to correct the primary disorder if possible and then
replace fibrinogen, platelets, and coagulation factors as necessary. In some patients, the correction of the primary
disorder may not be readily possible. Heparin therapy is not universally accepted in the treatment of DIC, and the
decision to use heparin, especially intra-operatively, should be discussed with the surgical team and the
hematologists.
Recombinant factor VIIa (rFVIIa)
One drug that may help during massive hemorrhage is recombinant factor VIIa. A growing number of case reports
suggest that this agent may be effective in various off-label indications. It has been used in controlling intractable
bleeding in trauma, obstetrical, and surgical patients where all other efforts to correct the bleeding have failed to
work. Because this drug has seemed to be the magical pill, its use has progressed from rescue therapy to
preventative therapy in surgical situations such as complex cardiac surgery or liver transplantation where heavy
blood loss is expected. When rFVIIa is administered, hemostasis is enhanced because of the additional generation of
thrombin. In the tissue factor dependent or extrinsic system, rFVIIa binds to tissue factor at the site of vessel injury,
causing activation of factor X. In the tissue factor independent or intrinsic system, rFVIIa binds to the surface of the
activated platelet, activating factor X. Both mechanisms result in a burst of thrombin and fibrin generation, which
leads to clot formation (Figure 3).
201
Page 4
Figure 3: Mechanism of action of rFVIIa
In a randomized controlled trial conducted in 36 patients undergoing radical prostatectomy, patients were
randomized to placebo, rFVIIa at 20 mcg/kg or 40 mcg/kg. (2) Patients receiving rFVIIa had a mean blood loss that
was statistically significantly lower than the control group. In trauma patients, the use of rFVIIa reduced the need for
massive blood transfusions (defined as > 20 units) from 33% in the control group down to 14% in the treatment
group. (3) While the results for penetrating trauma are just as promising, the results did not reach statistical
significance.
During orthotopic liver transplant (OLT), where there is dilution of coagulation factors and platelets, level 3 or 4
evidence (ie case reports) have been published, but no randomized controlled trials. A few reported studies have
actually been unable to show decreased transfusion requirements with the prophylactic use of rFVIIa in OLT. There
are several reasons why rFVIIa may not work as well during OLT. 1) Recombinant FVIIa has no effect against
heparin or heparin-like substances, which may have been released by the reperfused liver. 2) Recombinant FVIIa
has no direct anti-fibrinolytic effect. Anti-fibrinolytics may be necessary since fibrinolysis may occur after
reperfusion. 3) Because of the fibrinolysis and low fibrinogen levels, rFVIIa may not be as effective. FFP or
cryoprecipitate may still be required since fibrinogen is required for the thrombin burst to produce the fibrin clot.
In all, 2 meta-analyses and 1 Cochrane report have been published. (4-6) Depending on the inclusion criteria, most
included only 7 to 13 trials. Approximately 700 patients have been enrolled in trials involving the prophylactic use
of rFVIIa during OLT, liver resection, prostatectomy, repair of pelvic trauma, and cardiac surgery. Approximately
1200 patients have been enrolled in the therapeutic use of rFVIIa. The underlying etiologies for the use of rFVIIa
have been quite varied, and include stem-cell transplant, dengue fever, trauma, upper GI bleeding, and intracranial
hemorrhage. If all trials are analyzed together, there is a slight reduction in the number of patients that need PRBC
transfusions with the prophylactic use of rFVIIa. The effect is mostly from the use of high dose rFVIIa (>50
mcg/kg) and not low dose. In the studies that looked at the use of rFVIIa therapeutically, there is no statistically
significant difference between the 2 groups in terms of the number of patients that needed a blood transfusion.
One other end-point of interest other than PRBC transfusions is mortality. The question is: can the use of rFVIIa
improve mortality? With only 14 deaths out of 507 patients, the results give a wide confidence interval that crosses
1, so mortality does not seem to be improved from the meta-analyses.
201
Page 5
As the use of rFVIIa increases, there are now more reports of thrombosis. OConnell et. al. look at the FDA adverse
event database, which is a voluntary reporting system. Pooling all reported cases in which rFVIIa was used in non-
hemophillac patients resulted in 168 cases of thrombosis attributable to the drug. The rate of complication is
uncertain because no one really knows what the denominator is. (7) Patients with procoagulant diseases (cancer,
infections, h/o thromboembolic events, and receiving procoagulant drugs) were usually excluded from the studies,
so the real risk of thromboembolic events may be much higher when we start using the drug more in the general
surgical population or in critically ill patients.
As researchers gain experience with the use of rFVIIa in intracranial hemorrhages, the data show that the drug
decreases the size of the hemorrhage, but increases the incidence of thrombosis to 7%. (8) The study was repeated in
a phase 3 trial. (9) There was decreased growth in the volume of the intracranial hemorrhage, but there was no
significant difference among the groups in terms of mortality. Also, the incidence of severe disability was not
improved in the treatment groups. In the second study, frequency of venous complications were the same in the
groups, but there remained an increase frequency of arterial events, defined as myocardial infarctions and
cerebrovascular accidents, in the rFVIIa group that received the higher dose of 80 mcg/kg.
At this point, the data does not favor the prophylactic use of rFVIIa, but also cant show definitive harm from its
use. Considering that no RCT has been able to demonstrate a significant benefit in terms of ICU stay, hospital stay
or mortality, the financial burden of this drug needs to be weighed against the cost benefit of transfusing fewer
products. Each clinician will have to weigh the risk of thromboembolic events against the benefit of clotting for the
individual patient. More randomized controlled trials are necessary before a definitive statement can be made about
the safety of rFVIIa.
Post-operative causes of abnormal coagulation
In the post-operative period, usually the deficiency of clotting factors, platelets, and red cells begin to resolve unless
there is ongoing surgical blood loss. Now, the imbalance of procoagulant and anticoagulant agents increases the risk
for prothrombotic complications. Standard of care is to institute thomboembolic prophylaxis in surgical patients
(Figure 4). Heparin is usually the drug that comes to mind, but heparin does have its drawbacks. There is wide
inter-individual variability when administering the drug. It is an indirect thrombin inhibitor and therefore, is
effective on free thrombin only, and has limited inhibition of clot bound thrombin. It requires anti-thrombin as a
cofactor, and it induces platelet activation. The most devastating side effect of heparin is its ability to form a
complex with PF4 (platelet factor 4) that then can generate formation of heparin/PF4 antibodies.
201
Page 6
Figure 4: Site of action of anticoagulants
Direct Thrombin Inhibitors
Direct thrombin inhibitors (DTI), initially isolated from the saliva of
leeches, have been developed for use as anticoagulants in patients with
HIT. There are now lots of direct thrombin inhibitors on the market that
an anesthesiologist needs to be familiar with (Table 1). Most direct
thrombin inhibitors are relatively short acting, inhibit free and clot-
bound thrombin, and are indicated for prophylaxis and treatment of
patients with HIT. One DTI, melagatran, and its oral formulation,
ximelagatran, were removed from the market due to hepatotoxicity.
The drawback for these drugs is that there are no specific reversal
agents. Dialysis may be somewhat effective, and rFVIIa has shown
some efficacy in animals and in healthy volunteers ex vivo. (10)
Argatroban
Argatroban has a 45-minute half-life, and it is cleared by the liver, so no dose adjustments are needed in patients
with low glomerular filtration rate (GFR). It is less immunogenic than lepirudin, but it does increase the
international normalized ratio (INR), which may be a factor when initiating coumadin. Like all direct thrombin
inhibitors, dose should be titrated to aPTT (1.5-3x normal) or activated clotting time (ACT). The FDA approved
this drug as an anticoagulant for prophylaxis or treatment of thrombosis in patients with HIT and for percutaneous
coronary intervention (PCI) in patients with or at risk for HIT. Two prospective, multi-center trials studied 754
patients with HIT versus 193 historical controls. They found a significant decrease in the primary endpoint of death,
amputation, and new thrombosis (34% vs. 43%). (11, 12) Safety trials for patients with HIT undergoing PCI showed
that argatroban was as safe in terms of procedural success (lack of death, need for emergent CABG, or increased
Table 1: Direct Thrombin
Inhibitors
Hirudin
Lepirudin
Desirudin
Argatroban
Bivalirudin
Ximelagatran/
melagatran
Dabigatran
201
Page 7
incidence of Q-wave MI) as historical controls receiving heparin (98.2% vs. 94.3%). There are also a few reports of
the successful use of argatroban in ischemic stroke, hemodialysis, CRRT, and peripheral vascular surgery.
Bivalirudin
Bivalirudin has a 25-minute half-life, and it is 80% cleared by proteolysis and 20% renally cleared. Unlike
argatroban, it needs to be dosed for GFR, and it only causes a slight increase in INR. The dose should be titrated to
aPTT (1.5-3x normal) or ACT. The FDA approved this drug as an anticoagulant for PTCA in patients with unstable
angina (13) and for PCI. Multiple RCTs have studied the use of bivalirudin for PCI versus heparin. (14, 15) Most
show similar ischemic outcomes in both groups with less major bleeding in the bivalirudin group. Other studied
uses of bivalirudin include cardiopulmonary bypass and vascular surgery. Table 2 summarizes a comparison
between the different direct thrombin inhibitors.
Table 2: DTI comparisons
Lepirudin Argatroban Bivalirudin
FDA indications HIT HIT/ PCI PCI
Half-life 1.3 hours 40-50 minutes 25 minutes
Elimination Renal Hepatic Plasma/ Renal
Monitoring INR + INR +++ INR +
Cost $700 $1500 $800
New Oral DTI Dabigatran
The US FDA approved dabigatran, an oral direct thrombin inhibitor, for the management of patients with atrial
fibrillation in 2010. Because of its predictable pharmacokinetics and few drug or food interactions, dagibatran can
be given as a fixed daily dose without the need for coagulation monitoring. The new oral DTIs show promise in
reducing the complexity of current anticoagulants. (16)
Fondaparinux
One new anticoagulant is fondaparinux, a synthetic five saccharide molecule that is functionally and structurally like
heparin. It binds and activates antithrombin, but unlike heparin, it only inhibits FXa and not thrombin. The drug has
not been extensively studied for HIT, but successful use of fondaparinux in patients with HIT has been reported.
One multicenter in vitro study demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies.
(17) Recently, case reports of thrombocytopenia without thromboembolic complications while receiving
fondaparinux have been described. (18, 19) At this time, the American College of Chest Physicians continues to
recommend the use of direct thrombin inhibitors as the first-line agents in the setting of HIT. (20) Further clinical
trials should be conducted before fondaparinux becomes the therapy of choice for HIT.
Rivaroxaban and Apixaban
Direct Xa inhibitors are new agents whose activity is directed against the active site of Factor Xa. These agents are
being approved for use in prophylaxis of DVT, PE, and stroke in patients with atrial fibrillation. Like dabigatran,
these agents also have minimal drug interactions and predictable pharmacokinetics. For the majority of patients,
coagulation monitoring is unnecessary.
Use with Regional Anesthesia
There is not a lot of data on the use of these new anticoagulants with regional anesthesia. The broad clinical
experience with these drugs and neuraxial techniques does not exist. Most recommendations are based exclusively
on the pharmacokinetics. (21)
201
Page 8
Drug Reversal
A major disadvantage of the new oral anticoagulants is the lack of a reversal agent in case of serious bleeding. One
study looked at 12 healthy male volunteers in a cross-over study. They received rivaroxaban or dabigatran followed
by a bolus of a prothrombin complex concentrate (PCC). Laboratory values were then followed. It appears that the
PCC was able to reverse the laboratory anticoagulant effect of rivaroxaban but not dabigatran. Of course, it is
unclear whether the chosen laboratory values are good surrogate markers for the actual clinical bleeding potential.
More studies are clearly needed. (22)
Given the lack of data, current recommendations in the face of serious bleeding are to provide support care with
fluid resuscitation, site compression, and transfusion, discontinue the drug, consider activated charcoal for recent
ingestions, and possibly start hemodialysis for dabigatran. (23) There is not enough data to make recommendations
about FFP, PCC, and rFVIIa.
Summary
The modern view of coagulation is of a highly complex system with multiple cofactors and enzymes divided into the
initiation, amplification, and propagation phase of clot formation. The older view of an intrinsic and extrinsic
pathway, although greatly simplified, is still useful because it illustrates what the coagulation tests are measuring.
Analyzing the PT or aPTT can help diagnose the coagulation defect. Bleeding diatheses in the perioperative period
are easier to discuss when we divide the differential into the pre-, intra-, or post-op periods. Several new drugs that
either increase clotting or increase anticoagulation have been introduced, and many more are due on the market. It
is the anesthesiologists job to understand their mechanisms of action, how to manipulate the drugs in the
perioperative period, and how the drugs will affect the anesthetic plan.
References
1. Hoffman M, Monroe D: Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin N Am 21:1-
11, 2007.
2. Friederich P, Henny C, Messelink E, et al.: Effect of recombinant activated factor VII on perioperative
blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomized trial.
Lancet 361:201-5, 2003.
3. Boffard K, Riou B, Warren B, et al.: Recombinant factor VIIa as adjunctive therapy for bleeding control in
severely injured trauma patients: two parallel randomized placebo-controlled double blind clinical trials. J Trauma
59, 2005.
4. Hsia CC, Chin-Yee IH, McAlister VC: Use of recombinant activated factor VII in patients without
hemophilia: a meta-analysis of randomized control trials. Ann Surg 248:61-8, 2008.
5. Ranucci M, Giuseppe I, Soro G, et al.: Efficacy and safety of recombinant activated factor VII in major
surgical procedures. Arch Surg 143:296-304, 2008.
6. Stanworth SJ, Birchall J, Doree CJ, et al.: Recombinant factor VIIa for the prevention and treatment of
bleeding in patients without haemophilia. Cochrane Database Syst Rev:CD005011, 2007.
7. O'Connell K, Wood J, Wise R, et al.: Thromboembolic adverse events after use of recombinant human
coagulation factor VIIa. JAMA 295:293-8, 2006.
8. Mayer SA, Brun NC, Begtrup K, et al.: Recombinant activated factor VII for acute intracerebral
hemorrhage. N Engl J Med 352:777-85, 2005.
9. Mayer SA, Brun NC, Begtrup K, et al.: Efficacy and safety of recombinant activated factor VII for acute
intracerebral hemorrhage. N Engl J Med 358:2127-37, 2008.
10. Crowther M, Warkentin T: Bleeding risk and the management of bleeding complications in patients
undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood 111: 4871-4879, 2008.
11. Lewis B, Wallis D, Berkowitz S, et al.: Argatroban anticoagulation therapy in patients with heparin-
induced thrombocytopenia. Circulation 103:1838-43, 2001.
12. Lewis B, Wallis D, Leya F, et al.: Argatroban anticoagulant in patients with heparin-induced
thrombocytopenia. Arch Intern Med 163:1849-56, 2003.
13. Weitz J, Buller H: Direct thrombin inhibitors in acute coronary syndromes: Present and Future. Circulation
105:1004-11, 2002.
201
Page 9
14. Lincoff, AM, Bittl J, Harrington R, et al.: Bivalirudin and provisional glycoprotein IIb/IIIa blockade
compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention.
REPLACE-2 randomized trial. JAMA 289:853-63, 2003.
15. Stone G, Ware J, Bertrand M, et al.: Antithrombotic strategies in patients with acute coronary syndromes
undergoing early invasive management: one-year results from the ACUITY trial. JAMA 298:2497-607, 2007.
16. Lee C, Badhwar G, Ansell J: Oral IIa inhibitors. Hematol Oncol Clin N Am 24:739-753, 2010.
17. Savi P, Chong B, Greinacher A, et al.: Effect of fondaparinux on platelet activation in the presence of
heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 105:139-
44, 2005.
18. Rota E, Bazzan M, Fantino G: Fondaparinux-related thrombocytopenia in a previous low-molecular-weight
heparin (LMWH)-induced heparin-induced thrombocytopenia (HIT). Throm Haemost 99:779-81, 2008.
19. Warkentin T, Maurer B, Aster R: Heparin-induced thrombocytopenia associated with fondaparinux. J Engl
J Med 356:2653-5, 2007.
20. Warkentin TE, Greinacher A, Koster A, et al.: Treatment and prevention of heparin-induced
thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Edition). Chest 133(6 Suppl):340S-380S, 2008.
21. Horlocker T, Wedel D, Rowlingson J et al: Regional anesthesia in the patient receiving antithrombotic or
thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines
(third edition). Reg Anesth Pain Med 35: 64-101, 2010.
22. Eerenberg ES, Kamphuisen PW, Sijpkens MK et al.: Reversal of rivaroxaban and dabigatran by
prothrombin complex concentrate. Circulation 124: 1573-1579, 2011.
23. Kaatz S, Kouides PA, Garcia DA, et al.: Guidance on the emergent reversal of oral thrombin and factor Xa
inhibitors. Am J Hematol. 87 Suppl 1:S141-5, 2012
Disclosure
213
Page 1
Protecting the Kidney from Perioperative Injury
Robert N. Sladen, MBChB, FCCM New York, New York
CLINICAL DEFINITIONS AND PATHOGENESIS OF ACUTE KIDNEY INJURY (AKI)
Defining and Diagnosing Acute Kidney Injury (AKI)
For many years the ability to quantitate renal protection was hampered by the lack of a clear clinical definition
of acute kidney injury (AKI). In 2000 a group of experts (the Acute Dialysis Quality Initiative) met and defined
AKI by five criteria they called RIFLE (Risk, Injury, Failure, Loss, End-stage)
1
. The first 3 stages (R,I,F) reflect
progressively more severe increases in serum creatinine (SCr), decreases in estimated glomerular filtration rate
(eGFR) and duration and severity of oliguria within a 7-day period; the last two (L,E) reflect longer term renal
outcome. Subsequently, the group coalesced into the Acute Kidney Injury Network (AKIN)
2
, and simplified the
definition into three stages evaluated over 24 hrs. These AKIN Criteria acknowledge the adverse implications of
even small increases in SCr (Table 1):
Limitations of RIFLE and AKIN Criteria
Both the RIFLE and AKIN definitions of AKI identify an increasing severity of renal insult and show good
correlation with renal outcome. There is actually poor correlation between oliguria alone and AKI unless there is
hemodynamic instability
3
, so many studies use the AKIN SCr criteria alone. It may be days before the SCr reaches
its peak postoperative value that reflects the nadir GFR
4
, which is unhelpful for real-time diagnosis. A more
meaningful indicator of actual GFR is obtained by a short (< 2 hr), timed creatinine clearance
5
. The RIFLE and
AKIN criteria factor in the common postoperative entity of non-oliguric renal failure (NORF) or prerenal oliguria;
nor do they offer any insight into the etiology of AKI.
Renal Biomarkers
More than 50 biomarkers have been studied as indicators of renal injury
6
. Cystatin C, a cysteine proteinase
inhibitor released by all nucleated cells and completely filtered by the glomerulus, is advocated as a more stable
indicator of GFR than SCr
7
. A number of proteins that are released into the urine within hours of ischemia could
serve as biomarkers of acute tubular injury: these include neutrophil-gelatinase associated lipocalin (NGAL)
8,9
,
interleukin-18 (IL-18)
10
, and kidney injury molecule-1 (KIM-1)
11
. Another promising biomarker is liver-type fatty
acid-binding protein (L-FABP), whose urinary concentrations increase earlier and more specifically than NGAL
12
.
It is conceivable that a reliable renal biomarker or panel of biomarkers
13
- for AKI may render the RIFLE and
AKIN criteria obsolete, but we are not there yet. In the interim, renal biomarkers do provide surrogate end-points
for randomized controlled trials (RCTs), and allow stratification based upon the severity of injury.
Table 1: AKIN Criteria for AKI
2

Stage Serum Creatinine (SCr) Urine Output (UO)
1
Increase by 1.5-2 x baseline,
or by > 0.3 mg/dL
< 0.5 mL/kg/hr x 6 hr
2 Increase by 2-3 x baseline < 0.5 mL/kg/hr x 12 hr
3
Increase by 3 x baseline,
or by 0.5 mg/dL if SCr > 4 mg/dL
< 0.3 mL/kg/hr x 24 hr
or anuria > 12 hr

213
Page 2
Renal Autoregulation and Urine Output
Renal autoregulation maintains RBF and GFR through a broad range of perfusion pressure, but does not
preserve urine flow, which is very pressure dependent
14
. Blood pressure (BP) invariably decreases during
anesthesia, and urine flow declines accordingly; when BP returns to normal at emergence, so does urine flow.
An important endogenous mechanism to preserve GFR in the face of decreased RBF or arterial pressure is
preferential efferent arteriolar constriction induced by local release of norepinephrine (NE), angiotensin II and
arginine vasopressin (AVP). This explains the loss of GFR when a patient under stress is given an angiotensin
converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
In patients with chronic hypertension autoregulatory responses are reset, so a higher BP may be required to
maintain RBF and GFR. In certain states, including AKI, sepsis and possibly cardiopulmonary bypass (CPB), renal
autoregulation may be impaired or lost, so RBF becomes much more pressure dependent
15
.

Perioperative Oliguria and the Prerenal Syndrome
The etiology of oliguria traditionally has been defined as postrenal, prerenal or intrarenal. Postrenal oliguria
implies urinary tract obstruction (renal pelvis, ureters, bladder, urethra or urinary catheter) and typically manifests as
anuria if the obstruction is complete.
If postrenal obstruction has been excluded, perioperative oliguria should be interpreted as a prerenal
(physiologic) response to intravascular hypovolemia. The latter may be absolute (acute hemorrhage, severe
diarrhea, vomiting, fluid restriction), or relative (congestive heart failure, sepsis, liver failure).
Hypovolemia and hypotension trigger osmoreceptor, volume receptor and baroreceptor reflexes that include the
sympathoadrenal and renin-angiotensin systems, aldosterone and AVP (formerly called antidiuretic hormone,
ADH). The net effect is avid reabsorption of water and sodium (Na), resulting in oliguria with high urine osmolality
(UOsm) and low urine Na (UNa). When normal renal hemodynamics are restored, the stimulus to the tubules abates
and normal urinary flow resumes. If hypovolemia is severe and/or combined with nephrotoxic insults, frank AKI
may ensue (intrarenal oliguria).
In sepsis and liver failure, circulating endotoxin disrupts the renal circulation and induces a prerenal vasomotor
nephropathy characterized by oliguria and Na retention (UNa < 10 mEq/L). It is generally refractory to fluid
replacement and responds only to treatment of the underlying condition.
In sum, perioperative oliguria is common, but rarely implies AKI
16
. It is a sign of intravascular hypovolemia
and should be treated as prerenal until otherwise proven. In contrast, the absence of oliguria does not exclude AKI,
because about 75% is non-oliguric (urine flow rate 15-80 mL/hr)
17
, a reflection of incremental smaller insults in a
protected milieu. Until the role of renal biomarkers becomes established, the most reliable early clinical indicator of
AKI and diminished GFR remains a serial decline in measured creatinine clearance.
The Interface between Prerenal Syndrome and AKI
In the classic animal model of ischemic acute tubular necrosis (ATN), the nature of the injury depends on the
duration of infusion of NE into the renal artery. A brief infusion (< 60 min) results in reversible oliguria; the intact
renal tubules avidly conserve Na and water so UNa is low and UOsm high; and oliguria resolves when the NE
infusion stops. This is a typical prerenal syndrome.
A longer infusion (60 120 min) results in persistent oliguria and subsequent azotemia after NE is stopped:
this is ATN. The renal tubules lose their ability to conserve salt and water, so urine sodium is high and osmolality
low. When normal renal hemodynamics are restored, GFR remains < 10% of baseline because of tubular
obstruction by necrotic cells in the proximal tubule; loss of glomerular-tubular gradient; and back leak of tubular
fluid into the interstitial tissue
18
.
The implication of this model is that the physiologic, reversible prerenal syndrome may deteriorate into frank
ATN if the ischemic insult persists long enough. A prerenal (dehydrated) state also sensitizes the kidney to
nephrotoxic insults from non-steroidal anti-inflammatory drugs (NSAIDs), aminoglycoside antibiotics, radiocontrast
dyes and calcineurin inhibitors. Also in this model, administration of renal protective agents (saline, mannitol,
vasodilators) prior to NE infusion ameliorates the severity of ATN, akin to the clinical syndrome of non-oliguric
acute renal failure (NORF)
19
.
Nephrotoxic Pathways to AKI
An isolated nephrotoxic insult in a normal milieu almost never induces AKI, but risk increases exponentially
when multiple agents are administered in an adverse milieu that may be acute (shock, hypovolemia, CHF) or chronic
(advanced age, diabetes, chronic renal insufficiency)
20
. The reasons are explained below.

213
Page 3
Nephrotoxic agents directly injure target cells but also cause harm by disrupting renal oxygen balance in the
medullary thick ascending loop of Henle (mTAL). The hypertonic medulla provides renal concentrating ability, but
to do so, RBF must remain very slow (<10% of total RBF) and the tissue PaO
2
is accordingly very low (<10
mmHg). The mTAL is at risk when dehydration further compromises available RBF, and/or there is any disruption
to the formation of local nitric oxide or prostacyclin that maintains medullary vasodilation. Nephrotoxic AKI is
usually non-oliguric and SCr increases quite slowly.
Aminoglycosides are absorbed into intracellular lysosomes where they inhibit oxidative phosphorylation and
ATP synthesis
21
. Nephrotoxicity is related to sustained high trough serum levels
22
, and can be ameliorated by
hydration, monitoring of serum levels and creatinine clearance, and once-daily administration
23
.
Non-steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-1 (COX-1) inhibition by NSAIDs (e.g.
indomethacin, meclofenamate or ketorolac) impairs medullary vasodilator prostaglandin synthesis. During stress,
this results in decreased RBF and GFR, diuretic unresponsiveness and hyperkalemia
24
.
Calcineurin Antagonists. Cyclosporine A and tacrolimus induce sympathetic hyperreactivity and renal
vasoconstriction. This is counteracted by calcium channel blockers, which provide renoprotection after cadaveric
renal transplantation
25
.
Radiocontrast Agents. Hyperosmolar radiocontrast agents induce osmotic diuresis that may exacerbate
hypovolemia; RBC crenation that obstructs the microcirculation; and release free oxygen radicals that injure renal
tubules. The risk of radiocontrast nephropathy (RCN) is increased by hypovolemia, diabetes, and CHF
26
, and may
be ameliorated by hydration, low-osmolar radiocontrast agents, bicarbonate or N-acetylcysteine
27
.
A CLINICAL APPROACH TO OLIGURIA
Table 2. Oliguria Algorithm
1. Assume that oliguria is prerenal
28

2. Evaluate, monitor and treat intravascular volume deficits
3. Maximize renal blood flow by optimizing hemodynamic function
4. Maintain renal perfusion pressure with vasoconstrictor therapy (NE AVP)
5. Consider diuretic therapy
6. Counteract diuretic resistance (Table 3)
Diuretic Therapy
Therapeutic
Diuretic therapy should be reserved for oliguria that persists despite optimization of intravascular volume,
hemodynamic status and renal perfusion pressure
29
. Administration of diuretic agents to make urine or relieve
edema in the face of intravascular hypovolemia or hypotension will likely exacerbate volume depletion and increase
the risk of AKI.
Prophylactic
Diuretic agents induce renal cortical vasodilation (dopaminergic agents, loop diuretics), prevent tubular
obstruction (osmotic, loop diuretics), suppress reflex vasoconstriction (dopaminergic agents, natriuretic peptides),
and decrease tubular VO
2
(dopaminergic agents, loop diuretics)
30
. Prophylactic mannitol is commonly used in aortic
cross clamping, CPB, and pigment nephropathy (rhabdomyolysis, intravascular hemolysis, jaundice)
31
. There is
little evidence that diuretic therapy is more effective in maintaining GFR than fluid volume loading alone
32-34
.
Diuretic Resistance
Acute Tolerance
Acute tolerance or the braking phenomenon refers to diuretic tachyphylaxis that occurs with hypovolemia, or
when repeated doses contract the ECF and activate Na retention; it is counteracted by fluid repletion
35
. Caveat: a
diuretic agent or low dose dopamine is no substitute for rehydration!
Chronic tolerance
Chronic tolerance refers to the situation that arises when long term administration of loop diuretics triggers
compensatory hypertrophy of the distal tubule
36
.
Generalized edema refractory to diuretic therapy is encountered in acute and chronic kidney disease (CKD),
renal insufficiency, CHF, cirrhosis and the nephrotic syndrome. The pharmacokinetic handling and
pharmacodynamic effects of diuretics are markedly altered. In uremia, endogenous organic acids compete with loop
diuretics for active transport sites at the proximal tubule
37
. Renal clearance of furosemide is inversely proportional

213
Page 4
to the BUN and GFR
38
. Depleted intravascular volume markedly increases proximal Na reabsorption, restricting Na
available for diuretic action at the mTAL
39
.
Table 3. Strategies for Overcoming Diuretic Resistance
36, 37

1. Restore normal hemodynamics
2. Administer higher doses of diuretic agent
3. Concomitant administration of human albumin
40

4. Continuous diuretic infusion (furosemide 1-10 mg/hr or bumetanide 0.5-2 mg/hr)
41

5. Dual segment nephron blockade with combination diuretic therapy (Table 4)
39

Table 4. Combination Diuretic Therapy (Loop + Thiazide)
Loop Diuretic Thiazide Diuretic
furosemide 20-40 mg IV chlorothiazide 125-250 mg IV
bumetanide 1-5 mg IV metolazone 2.5 mg PO bid
torsemide 10 mg IV
ethacrynic acid 25-50 mg IV
PHARMACOLOGIC INTERVENTIONS TO PREVENT AND REVERSE AKI
Mannitol
Mannitol is an inert sugar that may provide renal prophylaxis by expanding the intravascular volume, which
increases preload, cardiac output and atrial natriuretic peptide (ANP) release. It also induces an osmotic diuresis
that may prevent tubular obstruction; releases intrarenal prostaglandins; and attenuates reperfusion injury by
scavenging of free radicals. For the greatest effect mannitol should be present at the time of the renal insult
42
.
Mannitols benefit is well established in animal models of AKI but there are few human RCTs that confirm this.
Loop diuretics
Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) inhibit Na reabsorption at the mTAL, and
can attenuate AKI if administered prior to a renal ischemic or nephrotoxic insult
43
. However, inappropriate diuresis
to make urine or relieve anasarca may induce a severe prerenal syndrome and exacerbate nephrotoxic insults.
High-dose (2-10 mg/kg) IV furosemide used to convert oliguric to non-oliguric AKI does not alter outcome
44,45
.
Dopaminergic agonists
Stimulation of DA
1
receptors causes renal vasodilation as well as inhibition of active Na transport in the
proximal tubule, leading to natriuresis and diuresis
46
. Stimulation of presynaptic DA
2
receptors inhibits NE release
and promotes peripheral vasodilation but appears to attenuate the beneficial effects of DA
1
effectors on RBF.
Dopamine
Despite the lack of definitive evidence
47
, low dose dopamine (0.53.0 !g/kg/min) has been widely used as a
renal protective agent. Biotransformation is extremely variable and plasma dopamine levels vary up to 10-fold
between individuals
48
. It is likely that in many cases dopamine benefits the kidney by its beta-adrenergic actions
(increased cardiac output, renal blood flow and perfusion pressure)
49, 50
.
There is little if any evidence that prophylactic administration of low dose dopamine has a positive impact on
renal outcome
51
. The use of low-dose dopamine is often limited by unpredictable tachycardia, supraventricular and
ventricular arrhythmias
52
, which likely reflects the inter-individual variability of plasma dopamine levels.
Fenoldopam
Fenoldopam is a phenol-dopamine analog that is a selective DA
1
-receptor agonist
53
. It has no beta- or alpha-
adrenergic effects, a relatively rapid onset and offset, an elimination half-life of 10 min, and little if any inter-
individual variability in metabolism. At infusion rates of 0.03-0.3 !g/kg/min it induces dose-dependent increases in
RBF, and there has been considerable interest in low dose (< 0.05 mcg/kg/min) fenoldopam for renal protection.
A meta-analysis of 16 studies representing 1290 ICU or perioperative patients concluded that fenoldopam
consistently and significantly reduced the risk for AKI, need for dialysis, ICU length of stay and in-hospital
mortality
54
. In cardiac surgery (6 studies, 440 patients), fenoldopam provided significant benefit on the risk of AKI
only, and increased the need for vasopressor therapy
55
. A large study of prophylaxis in RCN showed no benefit
56
,
although a small retrospective study in which fenoldopam was directly infused into the renal arteries suggested
amelioration of nephrotoxicity
57
.
N-Acetylcysteine

213
Page 5
N-Acetylcysteine (NAC) is an antioxidant long used as an antidote to acetaminophen toxicity. Initial studies
indicated efficacy in the amelioration of RCN in high-risk patients undergoing contrast radiography
58
, with
decreased AKI and mortality in patients undergoing percutaneous coronary intervention
59
. However, a recent large
(2308 patients) prospective RCT could not confirm this benefit
60
. NAC has not been shown to be effective in
preventing AKI during cardiac surgery with CPB
61
.
Sodium Bicarbonate
Through free radical scavenging, alkalinization of the urine (pH > 6.5) with sodium bicarbonate (NaHCO
3
) or
acetazolamide may theoretically ameliorate renal tubular injury.

There are conflicting data on the protective effects of NaHCO
3
versus normal saline for protection against RCN.
A large meta-analysis (12 trials, 1854 subjects) concluded that although hydration with NaHCO
3
decreases RCN by
SCr criteria, it has no impact on the need for dialysis or in-hospital mortality
62
. In an RCT on 100 patients, a 24-hr
infusion of NaHCO
3
during high-risk cardiac surgery decreased the incidence of a >25% rise in postoperative SCr,
without any other benefit
63
. Large RCTs are needed to clarify the risk-benefit ratio of urinary alkalinization on the
incidence and outcome of AKI.
The natriuretic peptides (22-32 amino acids) oppose the sympathoadrenal, renin-angiotensin, aldosterone, and
AVP systems
64
; counteract the vasoconstrictor and anti-natriuretic responses induced by hypovolemia; and induce
vasodilation and natriuresis that protect against hypervolemia and hypertension. Their vasodilator and renal effects
are mediated by cyclic guanosine monophosphate (cGMP), which increases glomerular filtration fraction by afferent
arteriolar vasodilation.
Atrial (A-type) natriuretic peptide (ANP) is synthesized by modified atrial myocytes and released by atrial
stretch and increased CVP
65
. Brain (B-type) natriuretic peptide (BNP) is synthesized in the cardiac right and left
ventricles, and is released by ventricular dilation. Assay of BNP (and its precursor, N-terminal-pro-BNP) is used as
an ER diagnostic tool for acute CHF, and BNP levels correlate with outcome in acute myocardial ischemia as well
as heart failure. C-type natriuretic peptide (CNP) is synthesized in the endothelium of the great vessels. Urodilatin
is a renal 22-amino acid peptide that has less vasodilator activity than ANP.
Anaritide is the human recombinant formulation of ANP. Parenteral administration decreases systemic BP by
arterial and venodilation, increases GFR, induces natriuresis, and reverses renovascular hypertension. In animal
models of ischemic
66
or nephrotoxic
67
ATN anaritide demonstrated great promise as a rescue agent. However a 504
patient RCT showed improved dialysis-free survival in oliguric (urine output < 400 mL/day) patients only, and
outcome was actually worse in patients with non-oliguric ARF
17
. A follow up study on 222 patients with oliguric
ARF found no difference in renal outcome between anaritide and placebo
68
. The lack of benefit of anaritide appears
to be related to hypotension induced by its vasodilator effect, and attests to the importance of maintenance of renal
perfusion pressure when renal autoregulation is impaired
69
.
Nesiritide is the human recombinant formulation of BNP, approved by the FDA for the parenteral treatment of
patients with advanced decompensated CHF. In these patients it provides preload and afterload reduction, enhances
cardiac function, and also can promote a sustained diuresis with improvement in pulmonary congestion, edema and
anasarca
70
. The major adverse effect is dose-related hypotension, which can impair renal function
71
.
In an RCT of 279 patients with impaired ventricular function (EF <40%) undergoing CPB for coronary
revascularization or mitral valve surgery, patients who received low dose nesiritide had increased urine output, an
attenuated postoperative increase in SCr, and improved survival six months after surgery
72
.
Vasopressor Therapy
Renal autoregulation maintains RBF and GFR over a wide range of renal arterial pressure. In certain situations,
notably ATN itself
69
, severe sepsis
15
, and possibly during cardiopulmonary bypass
73
, autoregulation appears to be
lost or attenuated. Moreover, in these situations systolic BP may fall below the normal autoregulatory limit.
Hypotension results in strikingly decreased RBF, which is restored by normalization of renal perfusion pressure -
even if this is achieved by vasoconstrictor therapy.
Established Acute Renal Failure
In established acute renal failure (stage 3 AKI) there is an almost complete loss of renal autoregulation
69
, so that
hypotension during intermittent hemodialysis (HD) provides a repetitive ischemic insult to the kidney that delays or
prevents renal recovery from ATN. In animal models of ischemic ATN, the renal vasculature develops a smooth
muscle injury that renders it relatively unresponsive to the vasoconstrictor effect of NE
74
. This suggests that during

213
Page 6
intermittent HD, BP should be supported with fluids or even pressor therapy, and that continuous venovenous
hemodialysis (CVVHD), which provides greater hemodynamic stability, should be used in the ICU.
Vasodilatory Shock
In severe sepsis with vasodilatory shock, impaired autoregulation is implicated by the dramatic improvement in
renal function that is observed when BP is normalized by the use of vasopressor therapy. This response has been
observed with infusions of NE
15
and low dose (1-4 u/hr) AVP
75
. As well as restoring overall renal perfusion
pressure, AVP preferentially constricts the efferent arteriole, thereby improving glomerular filtration pressure,
filtration fraction and GFR
76
.
REFERENCES
1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures,
animal models, fluid therapy and information technology needs: the Second International Consensus
Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204-12.
2. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve
outcomes in acute kidney injury. Crit Care 2007;11:R31.
3. Prowle JR, Liu YL, Licari E, et al. Oliguria as predictive biomarker of acute kidney injury in critically ill
patients. Crit Care 2011;15:R172.
4. Swaminathan M, Hudson CC, Phillips-Bute BG, et al. Impact of early renal recovery on survival after cardiac
surgery-associated acute kidney injury. Ann Thorac Surg 2010;89:1098-104.
5. Sladen RN, Endo E, Harrison T. Two-hour versus 22-hour creatinine clearance in critically ill patients.
6. McIlroy DR, Wagener G, Lee HT. Biomarkers of acute kidney injury: an evolving domain. Anesthesiology
2010;112:998-1004.
7. Zahran A, Qureshi M, Shoker A. Comparison between creatinine and cystatin C-based GFR equations in renal
transplantation. Nephrology, Dialysis, Transplantation 2007;22:2659-68.
8. Haase M, Bellomo R, Devarajan P, et al. Novel biomarkers early predict the severity of acute kidney injury
after cardiac surgery in adults. Annals of Thoracic Surgery 2009;88:124-30.
9. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated
lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 2008;52:425-33.
10. Haase M, Bellomo R, Story D, Davenport P, Haase-Fielitz A. Urinary interleukin-18 does not predict acute
kidney injury after adult cardiac surgery: a prospective observational cohort study. Crit Care 2008;12:R96.
11. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel
biomarker for human renal proximal tubule injury. Kidney International 2002;62:237-44.
12. Matsui K, Kamijo-Ikemori A, Sugaya T, Yasuda T, Kimura K. Usefulness of urinary biomarkers in early
detection of acute kidney injury after cardiac surgery in adults. Circ J 2012;76:213-20.
13. Parikh SV, de Lemos JA. Biomarkers in cardiovascular disease: integrating pathophysiology into clinical
practice. Am J Med Sci 2006;332:186-97.
14. Sladen RN, Landry D. Renal blood flow regulation, autoregulation, and vasomotor nephropathy. Anesthesiol
Clin North America 2000;18:791-807, ix.
15. Desjars PH, Pinaud M, Bugnon D, et al. Norepinephrine has no deleterious renal effects in human septic shock.
Critical Care Medicine 1989;17:426-9.
16. Alpert RA, Roizen MF, Hamilton WK, et al. Intraoperative urinary output does not predict postoperative renal
function in patients undergoing abdominal aortic revascularization. Surgery 1984;95:707.
17. Allgren RL, Marbury TC, Rahman SN, al e. Anaritide in acute tubular necrosis. New England Journal of
Medicine 1997;336:828-34.
18. Myers B, Chui F, Hilberman M, Michaels A. Transtubular leakage of glomerular filtrate in human acute renal
failure. Am J Physiol 1979;237(4):F319-F25.
19. Gorfinkel HJ, Szidon JP, Hirsch LJ, et al. Renal performance in experimental cardiogenic shock. American
Journal of Physiology 1972;222:1260-8.
20. Brezis M, Rosen S. Hypoxia of the renal medulla - its implications for disease. New England Journal of
Medicine 1995;332:647-55.
21. Wardle N. Acute renal failure in the 1980s: the importance of septic shock and of endotoxemia. Nephron
1982;30:193-200.
22. Zager RA. Endotoxemia, renal hypoperfusion, and fever: interactive risk factors for aminoglycoside and sepsis-
associated acute renal failure. American Journal of Kidney Diseases 1992;20:223-30.

213
Page 7
23. Wetzels JF, Burke TJ, Schrier RW. Prevention and attenuation of acute renal failure. Current Opinion in
Nephrology & Hypertension 1992;1:133-40.
24. Clive D, Stoff J. Renal syndromes associated with nonsteroidal antiinflammatory drugs. New England Journal
of Medicine 1984;310:563-72.
25. Kunzendorf U, Walz G, Brockmoeller J, et al. Effects of diltiazem upon metabolism and immunosuppressive
action of cyclosporine in kidney graft recipients. Transplantation 1991;52:280-4.
26. Parfrey PS, Griffiths SM, Barrett BJ, et al. Contrast material-induced renal failure in patients with diabetes
mellitus, renal insufficiency or both. New England Journal of Medicine 1989;320:143.
27. Eisenberg RL, Bank WO, Hedgecock MW. Renal failure after major angiography can be avoided with
hydration. American Journal of Radiology 1981;136:859.
28. Sladen RN. Perioperative Renal Protection. In: Murray MJ, Coursin DB, Pearl RG, Prough DS, eds. Critical
Care Medicine: Perioperative Management. New York: Raven Press; 1996:551-64.
29. Dishart MK, Kellum JA. An evaluation of pharmacological strategies for the prevention and treatment of acute
renal failure. Drugs 2000;59:79-91.
30. Brezis M, Rosen S, Epstein F. The pathophysiologic implications of medullary hypoxia. American Journal of
Kidney Disease 1989;13:253-8.
31. Ron D, Taitelman U, Michaelson M, Bar-Joseph G, Burzstein S, Better OS. Prevention of acute renal failure in
traumatic rhabdomyolysis. Archives of Internal Medicine 1984;144:277.
32. Paul MD, Mazer CD, Byrick RJ, Rose DK, Goldstein MB. Influence of mannitol and dopamine on renal
function during elective infrarenal aortic cross-clamping in man. Amer J Nephrol 1986;6:427-34.
33. Parks RW, Diamond T, McCrory DC, Johnston GW, Rowlands BJ. Prospective study of postoperative renal
function in obstructive jaundice and the effect of perioperative dopamine. Br J Surg 1994;81:437-9.
34. Plusa SM, Clark NW. Prevention of postoperative renal dysfunction in patients with obstructive jaundice: a
comparison of mannitol-induced diuresis and oral sodium taurocholate. Journal of the Royal College of
Surgeons of Edinburgh 1991;36:303-5.
35. Bryan AG, Bolsin SN, Vianna PTG, Haloush H. Modification of the diuretic and natriuretic effects of a
dopamine infusion by fluid loading in preoperative cardiac surgical patients. Journal of Cardiothoracic and
Vascular Anesthesia 1995;9:158-63.
36. Sica DA, Gehr TW. Diuretic combinations in refractory oedema states: pharmacokinetic-pharmacodynamic
relationships. Clin Pharmacokinet 1996;30:229-49.
37. Brater DC. Diuretic resistance: mechanisms and therapeutic strategies. Cardiology 1994;84(suppl 2):57-67.
38. Rose HJ, O'Malley K, Pruitt AW. Depression of renal clearance of furosemide in man by azotemia. Clinical
Pharmacology and Therapeutics 1976;21:141-6.
39. Knauf H, Mutschler E. Functional state of the nephron and diuretic dose-response - rationale for low-dose
combination therapy. Cardiology 1994;84(suppl 2):18-26.
40. Inoue M, Okajima K, Itoh K, et al. Mechanism of furosemide resistance in analbuminemic rats and
hypoalbuminemic patients. Kidney International 1987;32:198-203.
41. van Meyel JJ, Smits P, Russel FG, Gerlag PG, Tan Y, Gribnau FW. Diuretic efficiency of furosemide during
continuous administration versus bolus injection in healthy volunteers. Clin Pharmacol Ther 1992;51:440-4.
42. Behnia R, Koushanpour E, Brunner EA. Effects of hyperosmotic mannitol infusion on hemodynamics of dog
kidney. Anesthesia and Analgesia 1996;82:902.
43. Brezis M, Rosen S, Silva P, et al. Transport activity modifies thick ascending limb damage in the isolated
perfused kidney. Kidney International 1984;25:65.
44. Kleinknecht D, Ganeval D, Gonzalez-Duque LA, al e. Furosemide in acute oliguric renal failure. A controlled
trial. Nephron 1976;17:51.
45. Brown C, Ogg C, Cameron J. High dose furosemide in acute renal failure: a controlled trial. Clinical
Nephrology 1981;15:90-6.
46. Lokhandwala MF, Amenta F. Anatomical distribution and function of dopamine receptors in the kidney.
FASEB Journal 1991;5:3023-30.
47. Burton CJ, Tomson CR. Can the use of low-dose dopamine for treatment of acute renal failure be justified?
Postgraduate Medical Journal 1999;75:269-74.
48. MacGregor DA, Smith TE, Prielipp RC, Butterworth JF, James RL, Scuderi PE. Pharmacokinetics of dopamine
in healthy male subjects. Anesthesiology 2000;92:338-46.
49. Bailey JM. Dopamine: One size does not fit all. Anesthesiology 2000;92:303-5.
50. Davis RF, Lappas DG, Kirklin JK, Buckley MJ, Lowenstein E. Acute oliguria after cardiopulmonary bypass:
renal functional improvement with low-dose dopamine infusion. Critical Care Medicine 1982;10:852-6.

213
Page 8
51. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal
dysfunction: a placebo- controlled randomised trial. Lancet 2000;356:2139-43.
52. Chiolero R, Borgeta A, Fisher A. Postoperative arrhythmias and risk factors after open heart surgery. Thoracic
and Cardiovascular Surgeon 1991;39:81-4.
53. Murphy MB, McCoy CE, Weber RR, Frederickson ED, Douglas FL, Goldberg LI. Augmentation of renal blood
flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous
administration of the dopamine-1 agonist fenoldopam. Circulation 1987;76:1312-8.
54. Landoni G, Biondi-Zoccai GG, Tumlin JA, et al. Beneficial impact of fenoldopam in critically ill patients with
or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Am J Kidney Dis 2007;49:56-68.
55. Zangrillo A, Biondi-Zoccai GG, Frati E, et al. Fenoldopam and acute renal failure in cardiac surgery: a meta-
analysis of randomized placebo-controlled trials. J Cardiothorac Vasc Anesth 2012;26:407-13.
56. Stone GW, McCullough PA, Tumlin JA, et al. Fenoldopam mesylate for the prevention of contrast-induced
nephropathy: a randomized controlled trial. Jama 2003;290:2284-91.
57. Talati S, Kirtane AJ, Hassanin A, et al. Direct Infusion of Fenoldopam into the Renal Arteries to Protect from
Contrast-Induced Nephropathy in Patients at Increased Risk. Clin Exp Pharmacol Physiol 2012.
58. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-
agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343:180-4.
59. Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary
angioplasty. N Engl J Med 2006;354:2773-82.
60. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular
angiography: Acetylcysteine for Contrast-induced nephropathy Trial (ACT). Circulation 2011;124:1250-9.
61. Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R. Cardiopulmonary bypass-associated acute
kidney injury: a pigment nephropathy? Contributions to Nephrology 2007;156:340-53.
62. Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR. Sodium bicarbonate therapy for prevention of
contrast-induced nephropathy: a systematic review and meta-analysis. Am J Kidney Dis 2009;53:617-27.
63. Haase M, Haase-Fielitz A, Bellomo R, et al. Sodium bicarbonate to prevent increases in serum creatinine after
cardiac surgery: a pilot double-blind, randomized controlled trial. Critical Care Medicine 2009;37:39-47.
64. Laragh J. Atrial natriuretic hormone, the renin-angiotensin axis, and blood-pressure electrolyte homeostasis.
New England Journal of Medicine 1985;313:1330-40.
65. Maack T, Camargo MJF, Kleinert HD, Laragh JH, Atlas SA. Atrial natriuretic factor: structure and functional
properties. Kidney International 1985;27:607-15.
66. Atanasova I, Girchev R, Dimitrov D, et al. Atrial natriuretic peptide and dopamine in a dog model of acute renal
ischemia. Acta Physiologica Hungarica 1994;82:75-85.
67. Seki G, Suzuki K, Nonaka T, et al. Effects of atrial natriuretic peptide on glycerol induced acute renal failure in
the rat. Japanese Heart Journal 1992;33:383-93.
68. Lewis J, Salem MM, Chertow GM, et al. Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute
Renal Failure Study Group. Am J Kidney Dis 2000;36:767-74.
69. Kelleher SP, Robinette JB, Miller F, Conger JD. Effect of hemorrhagic reduction in blood pressure on recovery
from acute renal failure. Kidney International 1987;31:725-30.
70. Mills RM, LeJemtel TH, Horton DP, et al. Sustained hemodynamic effects of an infusion of nesiritide (human
b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial.
Natrecor Study Group. J Am Coll Cardiol 1999;34:155-62.
71. Colucci WS. Nesiritide for the treatment of decompensated heart failure. J Card Fail 2001;7:92-100.
72. Mentzer RM, Jr., Oz MC, Sladen RN, et al. Effects of perioperative nesiritide in patients with left ventricular
dysfunction undergoing cardiac surgery:the NAPA Trial. J Am Coll Cardiol 2007;49:716-26.
73. Mackay JH, Feerick AE, Woodson LC, et al. Increasing organ blood flow during cardiopulmonary bypass in
pigs: comparison of dopamine and perfusion pressure. Crit Care Med 1995;23:1090-8.
74. Conger JD, Hammond WS. Renal vasculature and ischemic injury. Renal Failure 1992;14:307-10.
75. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during
severe septic shock. Anesthesiology 2002;96:576-82.
76. Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists.
Am J Physiol 1989;256:F274-8.

Disclosure
Orion Pharma Finland, Honoraria

222
Page 1
Perioperative Delirium and Cognitive Dysfunction
William E. Hurford, M.D. Cincinnati, Ohio
Perioperative cognitive changes are often overlooked until a patient presents with an agitated delirium several days
after surgery. These acute changes in cognitive function, while sometimes dramatic, often are relegated to
emergence delirium or ICU psychosis and are simply permitted to run their course. Delirium, however, is not a
benign disease. Rather, it is associated with a significant increase in postoperative morbidity, disability, and
death.
1,2
Recently attention has focused on a broader set of disorders of postoperative cognitive dysfunction
(POCD), which may represent a spectrum of organ system dysfunction of varying severity, duration, and
reversibility. Disorders of perioperative cognitive function are often complicated by pain and anxiety, and, while
guidelines for their diagnosis, prevention, and treatment exist, most recommendations are preliminary.
3

Definitions
Agitation, which is simply excessive motor activity, is quite common in the postoperative period. It is a nonspecific
symptom resulting from any type of internal discomfort including pain, anxiety, fear of death, etc. Agitation
resulting from pain or anxiety is relatively easily treated with reassurance and the appropriate use of analgesics and
benzodiazepines. Delirium, however, is more difficult to prevent, diagnose, and treat, and the clinical outcome of
patients with delirium is much different.
4

Anxiety specifically describes an unpleasant alteration of mood and emotions that is not accompanied by cognitive
dysfunction. The patient continues to think and comprehend normally. There appears to be no relationship between
perioperative anxiety and the occurrence of delirium.
5,6

Delirium, like anxiety, is characterized by an unpleasant alteration of mood. Unlike anxiety, delirium is an acute
confusional state accompanied by cognitive impairment. Accordingly, delirium has been described as acute
cognitive dysfunction or acute brain failure. The distinction of cognitive impairment is critical to making the
proper diagnosis and prescribing appropriate therapy. The DSM-IV-TR diagnostic criteria include: 1) a disturbance
of consciousness with reduced ability to focus, sustain, or shift attention; 2) a change in cognition or the
development of a perceptual disturbance that is not better accounted for by a pre-existing or evolving dementia; 3)
development of the disturbance over a short period of time (hours to days) and a fluctuating course over the day.
7

Clinical features of delirium are summarized in Table 1. Patients may be hyperactive and agitated, or hypoactive
and lethargic. Hypoactive delirium may be difficult to appreciate, often remains undiagnosed, and may have a
poorer long-term outcome than agitated delirium.
1

Table 1. Clinical Features of Delirium
Prodromal phase
Fluctuating course with lucid intervals
Altered arousal and psychomotor abnormalities
Decreased attentiveness
Disturbed sleep-wake cycle
Impaired memory
Disorganized thinking and speech
Altered perceptions
Disorientation
Dysgraphia

222
Page 2
Etiology and Risk Factors

As many as one to two-thirds of older patients admitted to intensive care units will have an episode of delirium
during their stay. The precise etiology is entirely unclear. Of course, organic causes of an altered mental status
must always be considered and include drug and alcohol withdrawal, Wernicke's encephalopathy, hypertensive
encephalopathy, hypoglycemia, hypoperfusion, hypoxemia, intracranial bleed, meningitis/encephalitis, and side
effects of medications (all designated by the mnemonic WHHHHIMP).
8
Some hypothesize that delirium results
from vulnerability on the part of the patient (e.g., cognitive impairment, severe illness, visual impairment, etc.) and
hospital-related insults (e.g., medications and procedures).
9
Others suggest that acute brain dysfunction occurs
secondary to a perioperative systemic inflammatory response, similar to other organ failures.
7,10-12
Inouye and
Charpentier developed a predictive model for the occurrence of delirium in hospitalized general medical patients
greater than 70 years of age.
13
Risk factors included the use of physical restraints, the presence of malnutrition, the
addition of more than three medications over the last 24 hours, the use of a bladder catheter, and the occurrence of
any iatrogenic event. A greater number of factors was associated with an increased incidence of new-onset delirium
(0 factors, 4%; 1 to 2 factors, 20%; > 3 factors 35%).

Subtle pre-existing attentional and cognitive deficits, decreased executive function, and depression are associated
with an increased risk of postoperative delirium.
14-20
Other pre-existing factors that have been correlated with the
occurrence of perioperative delirium include: age 70 years or older; self-reported alcohol abuse; poor functional
status; markedly abnormal preoperative serum sodium, potassium, or glucose levels; hypoalbuminemia; surgery for
hip fracture; noncardiac thoracic surgery; and aortic aneurysm surgery.
21-26
Overall, vascular surgical patients are
about twice as likely as other elective surgical patients to experience delirium.
27
Intraoperative factors include
prolonged operative time, large blood losses, and anemia.
7,19,24,28,29
A recent prospective study of 563 cardiac
surgery patients reported a 16% incidence of delirium. Independently associated with delirium were advanced age,
preoperative cognitive impairment, major depression, anemia, atrial fibrillation, prolonged intubation and
postoperative hypoxia.
30

Assessment

Many rating scales have been developed to communicate a patients level of agitation and/or delirium more easily.
Among them, one of the most common scales, the Ramsay scale, simply rates the patients degree of arousal from
anxious or agitated (level 1), to deeply sedated (levels 4 and 5), to anesthetized (level 6).
31
Perhaps a more useful
scale for assessment of agitation is the Richmond Agitation-Sedation Scale (Table 2), which rates a patients level of
agitation or sedation on a 10-point scale, ranging from -5 (unarousable to vigorous stimulation) to +4 (physically
combative).
32-34

Delirium in postoperative and ICU patients commonly is assessed using the Confusion Assessment Method
(CAM),
35-37
which has been modified for ICU patients (CAM-ICU). The CAM-ICU briefly examines four key
features of delirium: (1) acute onset or fluctuating course; (2) inattention; (3) disorganized thinking; and (4) altered
level of consciousness. Diagnosis of delirium is made if the patient displays the first two features along with either
disorganized thinking or altered level of consciousness. Testing with the CAM-ICU has been highly standardized,
and the assessment is quick, repeatable, and reliable.
38,39
A pediatric version of the scale has been recently
validated.
40

Table 2. The Richmond Agitation-Sedation Scale (RASS)
33,34

Score Term Description
+4 Combative Combative, violent, immediate danger to staff
+3 Very agitated Pulls or removes tubes or catheters; aggressive
+2 Agitated Frequent nonpurposeful movement; dyssynchrony with ventilator
+1 Restless Anxious, but movements not aggressive or vigorous
0 Alert and calm
-1 Drowsy Sustained awakening (>10 sec) with eye contact to voice
-2 Light sedation Briefly awakens (<10 sec) with eye contract to voice
-3 Moderate sedation Movement or eye opening to voice, but no eye contact
-4 Deep sedation No response to voice; responds to physical stimulation
-5 Unarousable No response to voice or physical stimulation

222
Page 3
Therapy

Postoperative delirium usually develops between postoperative days 2 to 7.
41
This time-course correlates with the
typical progression of postoperative systemic inflammatory response. One hypothesis for the etiology of delirium is
that the postoperative increase in inflammatory, oxidative, and psychosocial stress stimulates the production of pro-
inflammatory cytokines and the production of delirium-potentiating neurotoxins.
7,42,43
Disruption of vulnerable
neurons may lead to a hyperdopaminergic and hypocholinergic state and potentiation of the neurotransmitter
glutamate.
44

Clinically, however, delirium remains a diagnosis of exclusion. Identification and treatment of other causes of acute
brain dysfunction, correction of electrolytes, and avoidance of benzodiazepines and other medications sometimes
can be curative.

Prevention

Evidence for the efficacy of preventative measures for delirium is sparse, but conservative measures, such as prompt
treatment of infections, maintenance of a normal sleep-wake cycle, avoidance of physical restraints, early
mobilization, involvement of family members, and frequent reorientation have been suggested and appear
reasonable on face value (Table 3).
7,9,45
The presence of an endotracheal tube, urinary catheter or surgical drains,
urinary retention, and pain are common triggers for acute confusion and agitation, especially in the post-anesthesia
care unit (PACU), and the occurrence of delirium in the PACU appears predictive of continued postoperative
delirium.
46
Postoperative pain and increased pain severity have been correlated with the occurrence of delirium.
47

In a study of hip fracture patients, cognitively intact patients with undertreated pain were nine times more likely to
develop delirium than patients whose pain was adequately treated.
48
Elderly patients who received oral opioid
analgesics, compared with intravenous or neuraxial analgesia, had a decreased incidence of delirium.
49

Minimization of tubes and drains and anticipatory treatment of pain are reasonable approaches to reducing the
chance of delirium. A proactive geriatric consultation, or treatment within a specialized hospital program, may
reduce delirium incidence and severity in elderly patients.
9,50-54

Table 3. Risk Factors and Interventions for Delirium
9

Risk Factor Example of Intervention
Cognitive impairment Frequent reorientation; provide stimulating activities
Sleep deprivation Noise reduction strategies; schedule adjustments
Immobility Early mobilization; ambulation; active range of motion;
minimize catheters and physical restraints
Visual impairment Provide glasses and adaptive equipment
Hearing impairment Provide hearing aids; special communication techniques
Dehydration Encourage oral intake of fluids

Few studies suggest any efficacy for prophylactic pharmacologic treatment. A recent study of 457 elderly patients
following noncardiac surgery reported a reduced incidence of delirium in patients receiving prophylaxis with low-
dose intravenous haloperidol.
55
The use of ketamine during anesthetic induction for cardiac surgery has also been
reported to reduce the incidence of postoperative delirium compared to placebo-treated patients.
56
Some have
suggested that preoperative administration of statins may reduce the risk of postoperative delirium following cardiac
surgery,
57
but others have reported that statin use is associated with increased risk.
58

Most anesthetic agents, with the exception of ketamine, antagonize GABA receptors and can produce confusion and
delirium. Many common perioperative medications can contribute to the occurrence of delirium, including
meperidine
59
, anticholinergic medications such as atropine, first generation antihistamines (diphenhydramine),
promethazine benzodiazepines, and tricyclic antidepressants.
60,61
With the exception of meperidine, neither opioid
administration, nor the total dose administered, appears to correlate with the occurrence of delirium.
62
Use of
regional anesthetic techniques instead of general anesthesia does not appear to reduce the incidence of delirium,
probably because the variable depth of accompanying sedation.
63-65
In a study of elderly patients receiving a spinal
anesthetic for hip fracture repair, a lighter level of propofol sedation (bispectral index > 80 compared with an index
of 50) was associated with a 50% reduction in the incidence of delirium.
66
A secondary analysis of 526 elderly

222
Page 4
patients undergoing hip surgery found no significant harm or benefit from general or regional anesthesia, or the use
of benzodiazepines, narcotics or anticholinergic agents.
67
Postoperatively, there is no evidence that pain
management with neuraxial techniques is superior to management with opioids.
68,69

Benzodiazepines

Benzodiazepines are often used for the treatment of anxiety. Their duration of action in critically ill and elderly
patients is unpredictable. While these drugs often are used to treat delirium and withdrawal, no adequately
controlled trials support their use in the treatment of delirium unrelated to alcohol withdrawal.
70
Elderly patients
may become further disinhibited with the administration of benzodiazepines. Their use should be minimized in such
patients and may be associated with an increased risk for delirium
59,71-73
and prolongation of its duration in elderly
patients.
74

Haloperidol

There is insufficient evidence to strongly recommend a particular pharmacologic treatment for delirium, but
haloperidol often is used for this purpose and has been recommended in guidelines of the American Psychiatric
Association (APA).
75
Low-dose haloperidol may reduce the severity and duration of delirium, and the length of
hospital stay in delirious elderly patients.
76,77
Haloperidol is a butyrophenone with strong dopamine D
2
receptor
binding activity, which atypical antipsychotics lack.
7
Although it is an alpha-1 adrenergic antagonist, it has few
hypotensive side effects. It has little meaningful effect on ventilation. Extrapyramidal side effects are relatively
uncommon in the critically ill patient, perhaps because of concurrent use of benzodiazepines or beta-blockers.
Prolongation of the Q-T interval and serious ventricular arrhythmias, notably torsade-de-pointes, following
haloperidol administration have been described in a black box warning by the Food and Drug Administration
(FDA).
78
Monitoring the Q-T interval of the electrocardiogram and correction of serum potassium and magnesium
levels, if necessary, are advisable when high doses of haloperidol are used. APA guidelines suggest that a QTc
interval greater than 450 msec or more than 25% over baseline may warrant discontinuation of the drug.
7

Haloperidol also has been associated with neuroleptic malignant syndrome. The drug can decrease the threshold for
seizures and should be used cautiously in patients with delirium tremens. Although not approved by the FDA, the
intravenous route appears preferable in the critically ill patient, since absorption is assured. Side effects may be
reduced with intravenous administration.
79

Other options

Pharmacologic options that may be useful for treatment of delirium include the atypical antipsychotics olanzapine,
risperidone,
80,81
and quetiapine.
82-84
Prophylaxis with olanzapine has been reported to reduce the incidence of
delirium, but not its duration or severity, following joint replacement.
85
For treatment of delirium, the atypical
antipsychotics appear to have similar efficacy as haloperidol, but additional studies will be necessary before such
drugs can be strongly recommended. Short-term treatment with dexmedetomidine has been demonstrated to be
effective for the treatment of delirium in several prospective studies.
86-89
Cholinesterase inhibitors, such as
physostigmine
90
have been suggested for treatment, but a recent large study of the cholinesterase inhibitor
rivastigmine did not demonstrate efficacy and the drug was associated with increased mortality.
91
Interestingly,
maintaining a body temperature < 36
o
C during total knee replacement under spinal anesthesia was reported to be
associated with a lower incidence of cognitive dysfunction (delirium was not specifically assessed) following
surgery.
92

Outcome

The occurrence of delirium is far from benign, and is associated with an increased risk of death and disability.
93-97

In the postoperative period, the occurrence of delirium has been associated with prolonged ICU and hospital length
of stay, greater use of sedatives and physical restraints, increased unintended decannulations and extubations,
increased hospital costs, prolonged cognitive dysfunction, and higher mortality rates.
21,98-102
Elderly patients who
experienced delirium during their stay in a surgical ICU were more likely to be discharged to a place other than
home, and have a greater functional decline than nondelirious patients.
103,104
In hospitalized patients with Alzheimer
disease, those with hospital-acquired delirium had an increased rate of cognitive deterioration that continued for up
to 5 years following hospitalization.
105
While the simple occurrence of postoperative delirium does not appear to be

222
Page 5
an independent predictor of mortality,
106
persistence of delirium appears to be a predictor of increased 1-year
mortality.
107
One-quarter of delirious elderly patients die within 6 months.
108

The Spectrum of Postoperative Cognitive Dysfunction (POCD)

Delirium represents a profound manifestation of cognitive dysfunction. The current definition is binary (yes/no) and
neglects differences in the severity and duration of brain dysfunction. Undoubtedly, there is a spectrum of organ
dysfunction that falls short of a diagnosis of delirium, and can sometimes be diagnosed only by special testing. The
definition of POCD is informal; it refers to any difficulty with memory, cognition, or attention following surgery
and anesthesia. Variable definitions of POCD, the presence of preoperative cognitive impairment, and inconsistent
inclusion of appropriate control groups complicate analysis of studies in this field.
109
The incidence of POCD
appears relatively common following cardiac and non-cardiac surgery, especially in the elderly. Its occurrence is
associated with prolonged hospital stays, decreased likelihood of returning to the workforce, and increased
mortality.
110-112
Just as the etiology of delirium is unclear, so is the etiology of postoperative cognitive dysfunction
and its potential relationship to anesthetic exposure. Other perioperative organ system dysfunctions, such as renal
failure, have diverse causes. It is likely that there are multiple important causes of postoperative cerebral
dysfunction. The hypothesis that anesthetic exposure may exacerbate neurodegenerative diseases such as Alzheimer
disease, is receiving intense examination. Current studies, however, are inadequate to confirm or refute such a
relationship. At best, the controversy remains in equipoise: we dont have the scientific evidence that any particular
anesthetic agent or technique, at clinically relevant doses and durations, causes or will prevent long-lasting cognitive
dysfunction.
113,114
In a study of cardiac surgery patients, the presence of postoperative delirium was associated with
a more rapid decline and prolonged impairment in cognitive ability during the year following surgery. Patients
without delirium returned to their preoperative level of function within one month, while those with delirium had not
returned to their preoperative level of function by 1 year postoperatively.
115
Neuroanatomic abnormalities may, at
least in part, play an important role. Elderly patients have been reported to have an increased rate of brain atrophy 5
to 9 months following surgery.
116
Duration of delirium appears correlated with long-term POCD, which have both
been correlated with smaller brain volumes and disruption of white matter integrity, as assessed by MRI.
117,118

In the absence of definitive recommendations, it seems reasonable to apply those recommendations found useful in
reducing the incidence and severity of delirium, as discussed above, to an empiric effort to minimize the incidence
and severity of postoperative cognitive dysfunction.

References

1. Pun BT, Ely EW: Chest 2007; 132: 624-36
2. Witlox J, Eurelings LS, de Jonghe JF, et al.: JAMA 2010; 304: 443-51
3. Barr J, Fraser GL, Puntillo K, et al.: Crit Care Med 2013; 41: 263-306
4. Rudolph JL, Marcantonio ER: Anesth Analg 2011; 112: 1202-11
5. Lepouse C, Lautner CA, Liu L, et al.: Br J Anaesth 2006; 96: 747-53
6. Detroyer E, Dobbels F, Verfaillie E, et al.: J Am Geriatr Soc 2008; 56: 2278-84
7. Fricchione GL, Nejad SH, Esses JA, et al.: Am J Psychiatry 2008; 165: 803-12
8. Cassem NH, Murray GB, Lafayette JM, et al.: Delirious patients, The MGH Handbook of General Hospital
Psychiatry, 5th Edition. Edited by Stern TA, Fricchione GL, Cassem NH, et al. St. Louis, Mosby, 2004, pp
119-134
9. Inouye SK, Bogardus ST, Jr., Charpentier PA, et al.: N Engl J Med 1999; 340: 669-76
10. Hala M: Med Hypotheses 2007; 68: 194-6
11. de Rooij SE, van Munster BC, Korevaar JC, et al.: J Psychosom Res 2007; 62: 521-5
12. McGrane S, Girard TD, Thompson JL, et al.: Crit Care 2011; 15: R78
13. Inouye SK, Charpentier PA: JAMA 1996; 275: 852-7
14. Leung JM, Sands LP, Mullen EA, et al.: J Gerontol A Biol Sci Med Sci 2005; 60: 1563-8
15. Kalisvaart KJ, Vreeswijk R, de Jonghe JF, et al.: J Am Geriatr Soc 2006; 54: 817-22
16. Lowery DP, Wesnes K, Ballard CG: Dement Geriatr Cogn Disord 2007; 23: 390-4
17. Smith PJ, Attix DK, Weldon BC, et al.: Anesthesiology 2009; 110: 781-7
18. Greene NH, Attix DK, Weldon BC, et al.: Anesthesiology 2009; 110: 788-95
19. Rudolph JL, Jones RN, Levkoff SE, et al.: Circulation 2009; 119: 229-36
20. Jankowski CJ, Trenerry MR, Cook DJ, et al.: Anesth Analg 2011; 112: 1186-93
21. Marcantonio ER, Goldman L, Mangione CM, et al.: JAMA 1994; 271: 134-9

222
Page 6
22. Litaker D, Locala J, Franco K, et al.: Gen Hosp Psychiatry 2001; 23: 84-9
23. Galanakis P, Bickel H, Gradinger R, et al.: Int J Geriatr Psychiatry 2001; 16: 349-55
24. Yildizeli B, Ozyurtkan MO, Batirel HF, et al.: Ann Thorac Surg 2005; 79: 1004-9
25. Dasgupta M, Dumbrell AC: J Am Geriatr Soc 2006; 54: 1578-89
26. Veliz-Reissmuller G, Aguero Torres H, van der Linden J, et al.: Aging Clin Exp Res 2007; 19: 172-7
27. Rudolph JL, Jones RN, Rasmussen LS, et al.: Am J Med 2007; 120: 807-13
28. Marcantonio ER, Goldman L, Orav EJ, et al.: Am J Med 1998; 105: 380-4
29. Bohner H, Hummel TC, Habel U, et al.: Ann Surg 2003; 238: 149-56
30. Kazmierski J, Kowman M, Banach M, et al.: J Psychosom Res 2010; 69: 179-85
31. Ramsay MA, Savege TM, Simpson BR, et al.: Brit Med J 1974; 2: 656-659
32. Riker RR, Picard JT, Fraser GL: Crit Care Med 1999; 27: 1325-9
33. Sessler CN, Gosnell MS, Grap MJ, et al.: Am J Respir Crit Care Med 2002; 166: 1338-44
34. Ely EW, Truman B, Shintani A, et al.: JAMA 2003; 289: 2983-91
35. Inouye SK, van Dyck CH, Alessi CA, et al.: Ann Intern Med 1990; 113: 941-8
36. Wei LA, Fearing MA, Sternberg EJ, et al.: J Am Geriatr Soc 2008; 56: 823-30
37. Wong CL, Holroyd-Leduc J, Simel DL, et al.: JAMA 2010; 304: 779-86
38. Ely EW, Inouye SK, Bernard GR, et al.: JAMA 2001; 286: 2703-10
39. Ely EW, Margolin R, Francis J, et al.: Crit Care Med 2001; 29: 1370-9
40. Smith HA, Boyd J, Fuchs DC, et al.: Crit Care Med 2011; 39: 150-7
41. Ely EW, Gautam S, Margolin R, et al.: Intensive Care Med 2001; 27: 1892-900
42. van Munster BC, Korevaar JC, Zwinderman AH, et al.: J Am Geriatr Soc 2008; 56: 1704-9
43. Rudolph JL, Ramlawi B, Kuchel GA, et al.: J Gerontol A Biol Sci Med Sci 2008; 63: 184-9
44. Caplan JP: Crit Care Med 2012; 40: 982-3
45. Siddiqi N, Stockdale R, Britton AM, et al.: Cochrane Database Syst Rev 2007: CD005563
46. Sharma PT, Sieber FE, Zakriya KJ, et al.: Anesth Analg 2005; 101: 1215-20, table of contents
47. Leung JM, Sands LP, Lim E, et al.: Am J Geriatr Psychiatry 2013
48. Morrison RS, Magaziner J, Gilbert M, et al.: J Gerontol A Biol Sci Med Sci 2003; 58: 76-81
49. Vaurio LE, Sands LP, Wang Y, et al.: Anesth Analg 2006; 102: 1267-73
50. Marcantonio ER, Flacker JM, Wright RJ, et al.: J Am Geriatr Soc 2001; 49: 516-22
51. Lundstrom M, Edlund A, Karlsson S, et al.: J Am Geriatr Soc 2005; 53: 622-8
52. Lundstrom M, Olofsson B, Stenvall M, et al.: Aging Clin Exp Res 2007; 19: 178-86
53. Schweickert WD, Pohlman MC, Pohlman AS, et al.: Lancet 2009; 373: 1874-82
54. Bjorkelund KB, Hommel A, Thorngren KG, et al.: Acta Anaesthesiol Scand 2010; 54: 678-88
55. Wang W, Li HL, Wang DX, et al.: Crit Care Med 2012; 40: 731-9
56. Hudetz JA, Patterson KM, Iqbal Z, et al.: J Cardiothorac Vasc Anesth 2009
57. Katznelson R, Djaiani GN, Borger MA, et al.: Anesthesiology 2009; 110: 67-73
58. Redelmeier DA, Thiruchelvam D, Daneman N: CMAJ 2008; 179: 645-52
59. Marcantonio ER, Juarez G, Goldman L, et al.: JAMA 1994; 272: 1518-22
60. Tannenbaum C, Paquette A, Hilmer S, et al.: Drugs Aging 2012; 29: 639-58
61. Rothberg MB, Herzig SJ, Pekow PS, et al.: J Am Geriatr Soc 2013
62. Lynch EP, Lazor MA, Gellis JE, et al.: Anesth Analg 1998; 86: 781-5
63. Williams-Russo P, Sharrock NE, Mattis S, et al.: JAMA 1995; 274: 44-50
64. Beaussier M, Weickmans H, Parc Y, et al.: Reg Anesth Pain Med 2006; 31: 531-8
65. Fong HK, Sands LP, Leung JM: Anesth Analg 2006; 102: 1255-66
66. Sieber FE, Zakriya KJ, Gottschalk A, et al.: Mayo Clin Proc 2010; 85: 18-26
67. Slor CJ, de Jonghe JF, Vreeswijk R, et al.: J Am Geriatr Soc 2011; 59: 1313-9
68. Williams-Russo P, Urquhart BL, Sharrock NE, et al.: J Am Geriatr Soc 1992; 40: 759-67
69. Mann C, Pouzeratte Y, Boccara G, et al.: Anesthesiology 2000; 92: 433-41
70. Lonergan E, Luxenberg J, Areosa Sastre A, et al.: Cochrane Database Syst Rev 2009: CD006379
71. Milstein A, Pollack A, Kleinman G, et al.: Int Psychogeriatr 2002; 14: 301-6
72. Pandharipande P, Shintani A, Peterson J, et al.: Anesthesiology 2006; 104: 21-6
73. Pandharipande P, Cotton BA, Shintani A, et al.: J Trauma 2008; 65: 34-41
74. Pisani MA, Murphy TE, Araujo KL, et al.: Crit Care Med 2009; 37: 177-83
75. Am J Psychiatry 1999; 156: 1-20
76. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al.: J Am Geriatr Soc 2005; 53: 1658-66
77. Schrader SL, Wellik KE, Demaerschalk BM, et al.: Neurologist 2008; 14: 134-7

222
Page 7
78. Perrault LP, Denault AY, Carrier M, et al.: Can J Anaesth 2000; 47: 251-4
79. Menza M, Murray G, Holmes V, et al.: J Clin Psychiatry 1987; 48: 278-280
80. Bourgeois JA, Hilty DM: Psychosomatics 2005; 46: 90-1
81. Lonergan E, Britton AM, Luxenberg J, et al.: Cochrane Database Syst Rev 2007: CD005594
82. Devlin JW, Roberts RJ, Fong JJ, et al.: Crit Care Med 2010; 38: 419-27
83. Tahir TA, Eeles E, Karapareddy V, et al.: J Psychosom Res 2010; 69: 485-90
84. Gilchrist NA, Asoh I, Greenberg B: J Intensive Care Med 2011
85. Larsen KA, Kelly SE, Stern TA, et al.: Psychosomatics 2010; 51: 409-18
86. Pandharipande PP, Pun BT, Herr DL, et al.: JAMA 2007; 298: 2644-53
87. Szumita PM, Baroletti SA, Anger KE, et al.: Am J Health Syst Pharm 2007; 64: 37-44
88. Riker RR, Shehabi Y, Bokesch PM, et al.: JAMA 2009; 301: 489-99
89. Shehabi Y, Grant P, Wolfenden H, et al.: Anesthesiology 2009; 111: 1075-84
90. Madi-Jebara S, Yazigi A, Haddad F, et al.: J Cardiothorac Vasc Anesth 2002; 16: 665-6
91. van Eijk MM, Roes KC, Honing ML, et al.: Lancet 2010; 376: 1829-37
92. Salazar F, Donate M, Boget T, et al.: Acta Anaesthesiol Scand 2011; 55: 216-22
93. Bickel H, Gradinger R, Kochs E, et al.: Dement Geriatr Cogn Disord 2008; 26: 26-31
94. Kat MG, Vreeswijk R, de Jonghe JF, et al.: Dement Geriatr Cogn Disord 2008; 26: 1-8
95. Robinson TN, Raeburn CD, Tran ZV, et al.: Ann Surg 2009; 249: 173-8
96. Gottesman RF, Grega MA, Bailey MM, et al.: Ann Neurol 2010; 67: 338-44
97. Shehabi Y, Riker RR, Bokesch PM, et al.: Crit Care Med 2010; 38: 2311-8
98. Dolan MM, Hawkes WG, Zimmerman SI, et al.: J Gerontol A Biol Sci Med Sci 2000; 55: M527-34
99. Franco K, Litaker D, Locala J, et al.: Psychosomatics 2001; 42: 68-73
100. Milbrandt EB, Deppen S, Harrison PL, et al.: Crit Care Med 2004; 32: 955-62
101. Ely EW, Shintani A, Truman B, et al.: JAMA 2004; 291: 1753-62
102. Girard TD, Jackson JC, Pandharipande PP, et al.: Crit Care Med 2010; 38: 1513-20
103. Balas MC, Happ MB, Yang W, et al.: Chest 2009; 135: 18-25
104. Rudolph JL, Inouye SK, Jones RN, et al.: J Am Geriatr Soc 2010; 58: 643-9
105. Gross AL, Jones RN, Habtemariam DA, et al.: Arch Intern Med 2012; 172: 1324-31
106. Kat MG, de Jonghe JF, Vreeswijk R, et al.: Age Ageing 2011; 40: 312-8
107. Kiely DK, Marcantonio ER, Inouye SK, et al.: J Am Geriatr Soc 2009; 57: 55-61
108. Fann JR: Semin Clin Neuropsychiatry 2000; 5: 64-74
109. Selnes OA, Gottesman RF, Grega MA, et al.: N Engl J Med 2012; 366: 250-7
110. Newman S, Stygall J, Hirani S, et al.: Anesthesiology 2007; 106: 572-90
111. Monk TG, Weldon BC, Garvan CW, et al.: Anesthesiology 2008; 108: 18-30
112. Steinmetz J, Christensen KB, Lund T, et al.: Anesthesiology 2009; 110: 548-55
113. Bittner EA, Yue Y, Xie Z: Can J Anaesth 2011; 58: 216-23
114. Terrando N, Brzezinski M, Degos V, et al.: Mayo Clin Proc 2011; 86: 885-93
115. Saczynski JS, Marcantonio ER, Quach L, et al.: N Engl J Med 2012; 367: 30-9
116. Kline RP, Pirraglia E, Cheng H, et al.: Anesthesiology 2012; 116: 603-12
117. Gunther ML, Morandi A, Krauskopf E, et al.: Crit Care Med 2012; 40: 2022-2032
118. Morandi A, Rogers BP, Gunther ML, et al.: Crit Care Med 2012; 40: 2182-2189

Disclosure

228
Page 1
Pulmonary Hypertension and Management of Perioperative
Right Ventricular Failure.
Eric Jacobsohn, MBChB, MHPE, FRCPC Winnipeg, Manitoba, Canada
Pulmonary hypertension (PH) and the associated right ventricular (RV) dysfunction are increasingly being
encountered in the perioperative period. Managing these patients is challenging, but a thorough understanding of the
pathophysiology of PH and the related RV dysfunction allows the practitioner to anticipate, prevent, and
successfully manage many of the perioperative risks. Normal systolic, diastolic, and mean pulmonary artery
pressures are 25, 10, and 15 mmHg, respectively; the normal range for pulmonary vascular resistance (PVR) is 0.9
1.4 Wood units or 90120 dynes s cm5. PVR = (!P)/flow, where !P represents the mean pulmonary artery
pressure (mPAP) minus the left atrial pressure (LAP), and flow equals cardiac output (CO). The gradient between
mPAP and LAP is commonly referred to as the transpulmonary gradient. If the gradient is elevated, there is an
increase in PVR; on the contrary, if the transpulmonary gradient is not elevated, the increase in mPAP is caused by
an elevation in LAP resulting from left heart pathology (left ventricular [LV] systolic/diastolic dysfunction, mitral
and/or aortic valve abnormality). Thus, PVR = (mPAP LAP) CO, or mPAP = LAP + (CO " PVR). Therefore,
only three physiological factors could lead to a rise in mPAP: (1) an increase in LAP (due to left heart pathology),
(2) an increase in cardiac output (resulting from congenital heart disease with left-to-right shunt, fluid overload, or
hyperdynamic states), and (3) an increase in PVR (caused by pulmonary parenchymal/airway disease, hypoxia,
interstitial lung disease, thromboembolic disease, or idiopathic pulmonary artery hypertension).
1
Because of
pulmonary vascular remodeling, even factors 1 and 2 could eventually lead to an increased PVR, and the associated
rise in mPAP will reflect both an increase in LAP as well as an eventual elevation in PVR over time. For example,
patients with mitral valve stenosis who have an increased mPAP solely because of elevated LAP (without increased
PVR, i.e., early or reversible PH) usually have an uncomplicated mitral valve replacement with little risk of RV
failure after cardiopulmonary bypass. In comparison, patients with mitral valve stenosis associated with a
preoperative increase in LAP, mPAP, and PVR (secondary to pulmonary vascular remodeling, i.e., fixed PH) may
have severe RV failure after mitral valve replacement, which could lead to difficulty in weaning from
cardiopulmonary bypass. Acute-on-chronic increases in PVR are common in the perioperative period and can lead
to acute decompensation in RV function. Some of the factors responsible for acute exacerbations in PVR are
hypoxia, hypercapnia, acidosis, hypothermia (shivering), increased sympathetic tone (pain, anxiety), and exogenous
or endogenous pulmonary vasoconstrictors such as catecholamines, serotonin, thromboxane, and endothelin. Early
recognition and reversal of these causes of acute deterioration could be lifesaving.
Pulmonary Hypertension
Definition and Classification Normal mPAP at rest is 14
3 mmHg with an upper limit of 20 mmHg. The
significance of mPAP between 2124 mmHg is unclear.
The European Society of Cardiology and the European
Respiratory Society define precapillary PH as a persistent
increase in mPAP # 25 mmHg at rest as assessed by right
heart catheterization in the setting of a normal pulmonary
capillary wedge pressure (PCWP) of $15 mmHg, PVR #3
Wood units, and normal or reduced cardiac output. They
define postcapillary PH as a persistent increase in mPAP
#25 mmHg at rest as assessed by right heart
catheterization in the setting of an increased PCWP #15
mmHg, PVR #3 Wood units, and normal or reduced
Fig. 1

228
Page 2
cardiac output.
2
The definition of PH according to the American College of Cardiology/American Heart Association
2009 Expert Consensus Document on Pulmonary Hypertension is a measurement, by right heart catheterization, of a
resting mPAP #25 mmHg, PCWP/LAP $15 mmHg, and PVR #3 Wood units.3 PH has undergone several
reclassifications over the past 20 years. The most recent, the Dana Point Classification, is shown schematically in
Figure 1.
4
There are five major categories: (1) pulmonary arterial disease, (2) left heart disease, (3) lung disease
with hypoxemia (4) chronic thromboembolic disease, (5) unclear and/or multifactorial causes. Because the WHO
classification is not based on a physiological approach, classification into precapillary, postcapillary, and mixed PH
may more useful in the periop period (Figure 2).

Pathogenesis
PH is a syndrome resulting from a pathological increase in PVR that leads to restricted flow through the pulmonary
arterial circulation and, ultimately, RV failure. The loss of vascular cross-section due to remodeling is the
predominant reason for the rise in PVR; however, excessive vasoconstriction may be a significant contributing
factor in about 20% of patients.
5
The vasculopathy, which predominantly affects small resistance pulmonary
arteries, consists of intimal hyperplasia, medial hypertrophy, adventitial proliferation, thrombus in situ, and varying
degrees of inflammation. Mutations in three genes in the transforming growth factor % superfamily receptor pathway
are part of the pathogenesis of hereditary PH. These include BMPR-2,
activin receptor-like kinase-1, and endoglin. The lack of penetrance in
families with PH suggests that some form of second insult is required, in
addition to the mutation, for PH to be manifested. Environmental factors
associated with the development of pulmonary hypertension (PH) include
hypoxia, anorexigenics, and central nervous system stimulants. Hypoxia
causes vasodilatation of systemic vessels but vasoconstriction of the
pulmonary vasculature, in part through the action of endothelin and
serotonin. Acute hypoxia further inhibits the function of voltage-gated K+-
ATP channels of the pulmonary artery smooth muscle cells, resulting in
membrane depolarization, an increase in cytoplasmic calcium
concentration, vasoconstriction, and eventually PH. Endothelial
dysfunction contributing to PH involves increased production of vasoconstrictor and mitogenic compounds such as
endothelin-1, angiotensin II, serotonin, thromboxane A2, VIP, and deficient production of vasodilators including
prostacyclin and nitric oxide.
6
Prostacyclin, normally a potent local vasodilator, inhibits platelet activation and has
antiproliferative properties. These mechanisms are thought to be associated with PH that complicates the use of
appetite suppressants and, in PH of the newborn, the use of SSRIs in pregnancy.
Diagnosis and Investigations
The most common presenting
symptoms are fatigue, dyspnea
on exertion, chest pain,
presyncopy, syncope,
palpitations, and lower extremity
swelling. Syncopy is an ominous
sign that usually predicts a poor
prognosis. Signs of PH and RV
failure include tachypnea,
tachycardia, distended neck
veins, left parasternal lift, an
audible tricuspid regurgitation
murmur, RV S3 gallop,
hepatomegaly, ascites, and lower
extremity edema. The AHA
divides the investigations into
pivotal and contingency tests,
and these are shown in Figure
3.
3
A ECG, chest x-ray, and
echocardiogram may display
signs suggestive of PH. An
echocardiogram should be
Fig. 2
Fig. 3

228
Page 3
considered once PH is suspected by history, clinical examination, and risk factors. Possible causes of PH that can be
excluded or confirmed by echocardiography are congenital and acquired valvular disease, LV systolic and diastolic
dysfunction, large pulmonary embolus, dilated RV, and congenital disease with shunts. It is important to rule out
chronic thromboembolic pulmonary hypertension (CTEPH), as 50% of patients with a diagnosis of CTEPH have no
prior history of acute pulmonary embolism. The screening test of choice is radionuclide perfusion scanning. A
normal or very low probability scan essentially excludes CTEPH, whereas a high probability scan warrants further
evaluation with a pulmonary angiogram. A spiral CT scan, although excellent in ruling out an acute pulmonary
embolus, is less sensitive than perfusion scanning in excluding CTEPH. Generally, right heart catheterization should
be performed in patients with unexplained preoperative dyspnea or confirmatory findings on echocardiography (RV
systolic pressure >40 mmHg, right atrial enlargement, RV hypertrophy/dilatation, or flattening of the inter-
ventricular septum) to better delineate the hemodynamic profile and assess the response to vasodilator therapy.
Medical Therapy
A treatment algorithm for PH
is shown in Figure 4. General
treatment goals include the
improvement of symptoms
and functional capacity (6-
minute walk test and
cardiopulmonary exercise
testing), lowering mPAP,
normalizing cardiac output,
slowing the rate of
progression of the underlying
disease, and ultimately,
improvement in survival.
3
Low-level aerobic exercise
(walking) is encouraged.
Avoidance of high altitudes
and oxygen supplementation
on commercial aircraft for
patients with room air
saturations <92% is advised.
Oxygen therapy is indicated if
oxygen saturation is less than
90% on room air. Ideally, pregnancy should be avoided. Routine anticoagulation with warfarin may improve
survival. Diuretics and a sodium-restricted diet are indicated in RV dysfunction or overt failure. Digoxin is often
added, although outcome studies are lacking. Calcium channel blockers are indicated in a small, select group of
patients with idiopathic pulmonary arterial hypertension who show acute vasodilator responsiveness on right heart
catheterization. Patients with chronic obstructive pulmonary disease may benefit from the addition of oxygen,
bronchodilators, steroids, and antibiotics if indicated. Use of BIPAP (biphasic positive airway pressure) may
improve PVR and RV function among patients with obstructive sleep apnea. Prostanoids are the mainstay therapy
for many patients. The three available for treatment of PH include intravenous epoprostenol (i.e., prostacyclin, or
PGI2), subcutaneous treprostinil, and inhaled iloprost. Several studies have shown improvement in symptoms,
exercise tolerance, hemodynamics, quality of life, and survival with prostanoid therapy. Although tachyphylaxis
with the need for frequent dose adjustments occurs, the beneficial effects of prostanoids can be sustained for years;
as a result, many patients have been removed from heart-lung transplantation lists. Many patients eligible for
prostanoid therapy do not receive it, partly due to the cost and the delivery methods. Oral prostanoid therapy is
currently under investigation and preliminary results are promising. Activation of endothelin A (ET-A) receptors
causes pulmonary vasoconstriction, and activation of endothelin B (ET-B) receptors, pulmonary vasodilatation. The
endothelin receptor antagonists bosentan and sitaxsentan are increasingly used as first-line oral therapy. Bosentan is
a nonselective, competitive ET-A and -B receptor antagonist that promotes pulmonary vasodilatation. Sitaxsentan is
a selective ET-A receptor blocker that preserves ET-B receptor dependent nitric oxidemediated vasodilatation. The
phosphodiesterases are another important class of agents. PDE-3 and -5 are enzymes that inactivate cyclic adenosine
monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), respectively, the principal second
messengers of prostacyclins and nitric oxide. The phosphodiesterases augment cAMP- and cGMP-mediated
Fig. 4

228
Page 4
intracellular signaling respectively, leading to vasodilation and decreased PVR. The phosphodiesterase class of
agents have an increasing role in acute PH crises in the perioperative period (discussed in a later section).
Invasive Therapy
Patients whose PH is associated with Eisenmenger syndrome (R-to-L shunting through an ASD or VSD) generally
have superior survival rates compared to patients with idiopathic PH, mainly because of decompression of a
pressure-overloaded RV, improved LV filling, and a resulting increase in cardiac output.8 Atrial septostomy is
considered a palliative procedure and may be a bridge to lung or heart-lung transplantation in patients with
intractable RV failure.
8
The shunt causes a decrease in systemic arterial oxygen saturation that is compensated for
by increases in cardiac output and systemic oxygen delivery. Pulmonary endarterectomy is indicated for patients
with a positive perfusion scan or positive pulmonary angiogram who have surgically accessible disease and an
acceptable surgical risk. The goal is to remove sufficient material to lower PVR and increase cardiac output. The
underlying abnormality in CTEPH includes initial thrombus obstruction, thrombus organization, fibrous obstruction
of proximal arteries, and vascular remodeling in patent distal arteries. Therefore, it is a disease with a proximal
mechanical component (amenable to surgery) and a variable degree of distal small vessel arteriopathy (amenable to
medical therapy). Identification of these patients is important, since CTEPH is generally underdiagnosed as a cause
of PH and has a poor prognosis if untreated.
9
Bilateral lung transplantation (and occasionally heart-lung
transplanation) is the final option for a minority of patients in whom medical therapy has failed. Although effective
medical therapy has reduced the rate of transplantation, death rates on waiting lists are high because of a global
shortage of donor organs. Only approximately 4% of lung and combined heart/lung transplants performed annually
worldwide are for patients with PH.
10
Extracorporeal support may occasionally be a rescue option for acute RV
failure and hypoxemia caused by massive pulmonary embolus. It is also used as a bridge to lung transplantation, for
support after lung transplant, in the treatment of severe reperfusion pulmonary edema after pulmonary
endarterectomy, and for RV failure unresponsive to conventional medical therapy.
11,12
Patients with end-stage RV
failure due to idiopathic PH have traditionally done poorly with RV assist devices, as the increased flow (high dP/dT
ratio) potentially damages the pulmonary microcirculation, causing even greater increases in mPAP and PVR.
Prognosis
Predictors of poor prognosis include advanced NYHA Functional Class 3 or 4, rapid symptom progression, poor
exercise capacity, significant RV dysfunction, low cardiac output, elevated brain natriuretic peptide, and an
associated diagnosis of scleroderma. The best survival rates are seen in patients with congenital heart disease
associated with PH. The natural history of idiopathic PH reveals a median survival of 2.8 years with 1-, 3-, and 5-
year survival rates of 68%, 48%, and 34% respectively.
13
Perioperative RV failure in patients with PH
Although often preventable, acute decompensation of patients
with PH during the periop. period is relatively common, is
frequently fatal, and occurs as a result of acute RV failure. In
2002, patients with Eisenmenger syndrome undergoing
cesarean section were reported to have a perioperative
mortality in the range of 70%.
14
In 2005, patients with PH
undergoing liver transplantation had a reported mortality as
high as 80%.
15
However, it is noteworthy that the periop risks
associated with PH have improved steadily over the past
decade, likely as a result of better understanding and
management of these patients (Figure 5). Emergency
procedures, ASA class >2, intermediate- or high-risk surgery,
longer duration of surgery and anesthesia (>3 hours),
coronary artery disease, chronic renal insufficiency, history of
pulmonary embolism, and NYHA Functional Class of 2 or
greater have all been identified as independent predictors of
morbidity and mortality in patients with PH undergoing
noncardiac surgery. High-risk surgical procedures include
those that could cause significant perioperative systemic
inflammatory response (cardiac surgery), rapid blood loss,
high possibility of venous air or CO2 emboli (laparoscopic
surgery), fat or cement emboli (orthopedic surgery), and loss
of lung blood vessels (lung resection). Serious consideration
should be given to cancelling or delaying surgery if the PVR
Fig. 5

228
Page 5
is largely fixed on vasodilator testing with inhaled NO, if moderate to severe PH with significant RV dysfunction is
present, and if high-risk surgery is planned. Some of the important factors that impact these decisions are shown in
Figure 5. All attempts must be made to optimize PVR before surgery, including maximizing medical therapy and
preventing conditions that may cause acute deterioration. Patients on chronic therapy for PH ideally should continue
their regimen throughout the perioperative period, as discontinuation can precipitate an acute pulmonary
hypertensive crisis. Intravenous prostacyclin has potent antiplatelet properties and changing to inhaled therapy
preoperatively should be considered, especially if increased blood loss is anticipated. In selected patients not on PH-
specific therapies, a preoperative right heart catheterization, vasodilator trial, and PH-specific therapy may be
indicated. Acute periop. decompensation and the subsequent rapid, potentially lethal RV failure are frequently
under-recognized or misdiagnosed. Shock caused by acute RV failure is schematically presented in Figure 6 A, B
and has a poorer prognosis as compared to LV with the same blood pressure.
RV failure (low end-organ inflow
pressure due to reduced LV
stroke volume and high end-
organ outflow pressure due to
elevated right atrial pressure) has
a worse prognosis than shock due
to acute LV failure (only low
end-organ inflow pressure)
because of the double-hit on
end-organs, leading to rapid
multiorgan failure. In addition,
elevation in right atrial pressure
may cause hypoxemia by right-
to-left shunting across a patent
foramen ovale. It is important to
note that tricuspid regurgitation is
common in acute and chronic RV
failure; hence, thermodilution
cardiac output measurements
may be misleading. However,
pulmonary artery pressure
measurements may still be useful
to monitor the effect of
pulmonary artery vasodilators or
systemic vasopressors. Many
issues in the perioperative period,
some of them minor by
themselves, can critically affect
the outcome of these patients.
These include, among others, the
timing of extubation, meticulous management of mechanical ventilation, the surgical acumen and outcome, fluid and
electrolyte shifts, balancing the positive vs. negative effects of transfusion, intravascular volume optimization, acid-
base optimization (pH >7.4, PaCO2 3035 mmHg, PaO2 >100 mmHg), temperature control, optimized analgesia,
and early restarting of noninvasive ventilation.
Prevention and Treatment
1. Optimize heart rate and rhythm
Restoring and maintaining sinus rhythm is important for optimal filling of a hypertrophied/dilated RV. Because of
the association of RV failure with tricuspid valve regurgitation, higher heart rates (80100 bpm) may be desirable to
reduce end-diastolic volume. Furthermore, because an increase in RV stroke volume is limited by the increase in RV
afterload, it is best to avoid bradycardia as the RV cardiac output becomes rate dependent. Where appropriate, early
synchronized cardioversion should be considered, as loss of sinus rhythm may lead to acute hemodynamic
decompensation. If cardiac pacing is possible, atrial or atrioventricular sequential pacing leads to improved RV
diastolic filling compared with ventricular pacing alone. Serum potassium and magnesium levels must be optimized
to prevent arrhythmias and efforts made to mitigate mechanical irritation of the cardiac chambers by central lines
Fig. 6

228
Page 6
(i.e., make certain the distal end of the central venous catheter does not enter the right atrium, and ensure early
removal of the pulmonary artery catheter in case of ventricular irritability or dysrhythmias).

2. Optimize RV filling
Perioperative central venous pressure (CVP) monitoring is important; in general, when the CVP is low, the RV must
be coping even if the pulmonary artery pressure and PVR are elevated (ie, the RV must have been primed
[hypertrophied] and exposed to a progressively higher pulmonary artery pressure and PVR over time, or it is truly
under filled). On the other hand, progressive elevation in CVP may imply a failing RV, especially when
accompanied by increasing size of V waves (worsening tricuspid regurgitation) and decrease in pulmonary artery
pressure and cardiac output. The compromised RV will tolerate neither hypovolemia nor overfilling; therefore, an
optimal position has to be determined and maintained on the (compromised) RV Frank-Starling curve. Because the
RV is mainly a volume chamber, it is less dependent on preload than the LV. Thus, for a given increase in
preload, a smaller increase in stroke volume is expected. However, because it is thin walled, the RV is much more
afterload dependent than the LV, and RV cardiac output decreases significantly with an acute increase in mPAP.
Past teachings have often suggested that the RV be filled aggressively to passively increase pulmonary blood flow
and cardiac output. This may hold true when the PVR is normal (Fontan physiology), but not when it is high. Excess
volume loading in these circumstances will result in acute RV distention, increased tricuspid regurgitation, right-to-
left shift of the interventricular septum, and impaired LV end-diastolic filling, leading to a decrease in stroke volume
and cardiac output (diastolic ventricular interdependence). The resultant drop in systemic blood pressure causes
decreased right coronary artery perfusion as well as a decline in the transseptal pressure gradient (TSG), and
eventually hemodynamic collapse. This is especially true once the CVP reaches values of 1520 mmHg. Assessment
of optimal RV filling can be very difficult. Options include a fluid bolus (250 mL of Lactated Ringers solution) or
autotransfusion (by elevation of the patients legs). Ongoing fluid boluses are indicated if leg elevation causes a
modest (25 mmHg) increase in CVP and corresponding increase in PCWP, cardiac output, and/or blood pressure;
an increase in only the CVP (with minimal or no change in PCWP, cardiac output, or mean arterial pressure) likely
indicates RV distention and precludes further fluid boluses. A relatively
underfilled RV is likely the lesser of the two evils. Repeated bedside
echocardiographic assessments could prove invaluable. In patients with a
pulmonary artery catheter, monitoring RV filling pressures through
continuous transducing of the RV pressure tracing is an underused but
invaluable tool (Figure 7).16

3. Maintain RV myocardial performance
This includes maintenance of RV coronary perfusion pressure and RV
inotropic therapy. Normally, RV coronary perfusion occurs during systole
and diastole. However, as the PVR and RV systolic pressure rise, flow
through the right coronary artery occurs mainly in diastole, similar to left
coronary artery perfusion. RV subendocardial ischemia caused by
myocardial oxygen supply-demand imbalance is common in PH.
Therefore, systemic hypotension and excessive increases in RV systolic
pressure, contractility, and heart rate must be avoided. When acute RV
failure is suspected, the systemic blood pressure must be increased
immediately to ensure adequate right coronary artery perfusion pressure
and restoration of TSG. This can be achieved by optimizing volume status
and with early use of norepinephrine with or without vasopressin.
Accumulating clinical experience as well as animal data suggest that
vasopressin causes less of an increase in PVR than does norepinephrine,
and reduces the dose of norepinephrine required to maintain an adequate
systemic blood pressure. Vasopressin binds to peripheral V1 receptors and
causes systemic vasoconstriction while stimulating nitric oxide release and
vasodilation in the pulmonary circulation. The choice of anesthetic
technique (general versus regional) and the anesthetic agents used are
much less important than understanding the possible physiological
perturbations that may result from their use. All anesthetic agents cause
varying degrees of myocardial and autonomic nervous system depression.
In this regard, volatile agents, propofol, thiopental, narcotics, ketamine,

228
Page 7
and etomidate can all be used in the appropriate manner. Contractility may need to be enhanced in the acutely failing
RV with either a %-adrenoreceptor agonist (dobutamine), PDE-3 inhibitor (milrinone), or calcium sensitizer
(levosimendan), which all also reduce pulmonary and systemic vascular resistance. Thus, if the increase in RV
cardiac output does not offset the reduction in systemic vascular resistance, the systemic blood pressure will
decrease with resultant decline in right coronary artery perfusion pressure and TSG. The combination of low-dose
dobutamine and low-dose milrinone is synergistic in inotropy and has fewer negative effects on systemic vascular
resistance. Levosimendan is a cardiac inotrope that binds to troponin C and sensitizes the cell to calcium, leading to
increased contractility without raising intracellular calcium levels. Monitoring overall RV function with continuous
RV pressure transduction through the RV port of the pulmonary artery catheter is invaluable (see Figure 7), which
shows progression form a flat (A) diastolic pressure relationship (i.e. a normal, compliant RV), to the non-compliant
square-root type waveform in the failing, pressure-overloaded RV.

4. Maintain the TSG and RV geometry
At normal systolic pressure (RV 25 mmHg, LV 125 mmHg), there is a large TSG (TSG = 100 mmHg) that is
responsible for the normal configuration of the interventricular septum; this provides a buttress for the free wall to
contract against (bellows effect). The septal contraction (septal twist) accounts for more than 50% of overall RV
systolic function, and the maximum RV developed pressure is reduced by 30% with septal inactivation. Therefore,
conditions that reduce LV systolic pressure (systemic hypotension) or increase RV systolic pressure will reverse the
TSG and severely compromise RV function: not only will septal function be compromised because of misalignment
of the obliquely oriented septal myofibrils to a transverse configuration, resulting in less contractile force, but the
free wall loses its buttress as the distance between the free wall and the septum increases (the result of leftward
septal bowing). In order to restore the TSG, the PVR needs to be reduced and LV systolic pressure needs to be
aggressively maintained or increased.

5. Reduce PVR
Perioperative hypoxemia, hypercapnia, atelectasis, pleural effusions,
hypothermia, fluid overload, pain, and anxiety all cause acute rises
in PVR with resultant RV decompensation. Patients on chronic
therapy for PH should continue their established treatment during
the perioperative period. The combination of nitrous oxide and
protamine increases PVR and should be avoided. Functional
residual capacity (FRC) must be carefully maintained, as both
hyperinflation and atelectasis can lead to an increase in PVR. The
important relationship between lung volume and FRC during
mechanical ventilation is U -shaped with PVR the lowest at FRC
(Figure 8). At low lung volumes, hypoxia and hypercapnia cause
hypoxic pulmonary vasoconstriction; on the other hand,
hyperinflation causes compression of intraalveolar vessels with a
resultant increase in PVR in both circumstances. Positive end-
expiratory pressure >15 mmHg also leads to an increase in PVR. In
contrast to systemic arteries, pulmonary vessels constrict with
hypoxia (Euler-Liljestrand reflex) and dilate with hyperoxia.
Therefore, perioperative ventilation strategies for patients with PH should incorporate high concentrations of
oxygen, low tidal volumes (6 mL/kg of predicted body weight), a respiratory rate sufficient to achieve mild
hypocapnia, and optimum levels of positive end-expiratory pressure (510 cmH2O). Early drainage of pleural
effusions and recruitment maneuvers should be considered. Intravenous air or particulate material (precipitated
drugs) should be avoided because of the potential for right-to-left embolization through an open foramen ovale.
Apart from the aforementioned physiological considerations, the PVR can be reduced by selective pulmonary artery
vasodilators. Unfortunately, none of the intravenously administered agents are selective enough not to cause
accompanying systemic vasodilation; these agents could also potentially worsen hypoxia by inhibiting hypoxic
pulmonary vasoconstriction. The PDE-3 inhibitor milrinone lowers the PVR and has positive inotropic effects
(inodilator). Pulmonary artery vasodilation with intravenous nitroglycerin, sodium nitroprusside, or citrulline (all
metabolized to nitric oxide) can be useful provided simultaneous systemic hypotension is anticipated and treated.
Intravenous epoprostenol (PGI2) has been successfully used to treat protamine-induced PH and to facilitate weaning
patients with PH from cardiopulmonary bypass. It is, however, a powerful antiplatelet agent and must be used
Fig. 8

228
Page 8
cautiously in the face of surgical bleeding. Inhaled pulmonary artery vasodilators improve V/Q matching and arterial
oxygen saturation, which in itself decreases PVR. An algorithm for their use is shown in Figure 9.

Unlike the intravenous pulmonary artery
vasodilators, these agents have little effect
on systemic vascular resistance. Inhaled
nitric oxide (iNO) is a selective pulmonary
artery vasodilator (increases cGMP
production) that is almost immediately
inactivated by binding to hemoglobin;
inhaled epoprostenol (iPGI2) promotes
pulmonary artery vasodilation by
increasing cAMP in smooth muscle cells.
iNO and iPGI2 are equally effective in
decreasing mPAP and PVR, and overly fast
weaning of both can lead to rebound PH.
Inhaled iloprost is a water-soluble analog
of prostacyclin with a longer half-life that makes it suitable for intermittent nebulization. Inhaled milrinone is
associated with less systemic hypotension but a smaller decrease in PVR when compared with intravenous
administration. The PDE-5 inhibitor sildenafil, administered sublingually or orally, has been used to manage acute
RV dysfunction in heart transplant recipients, wean patients from iNO, reduce the duration of mechanical
ventilation, and prevent pulmonary endothelial cell dysfunction after prolonged cardiopulmonary bypass. It also
extends and potentiates the effects of iNO. The sublingual route, although not specifically studied in the
perioperative period, is potentially an excellent ancillary in conjunction with the inhaled agents.

Conclusion
The perioperative management of patients with PH and associated RV dysfunction is complex and requires a
thorough understanding of the pathophysiology involved. Failure to make an early diagnosis of RV failure and
institute the correct therapy will lead to high perioperative morbidity and mortality. The anesthesiologist must be
aware of the potential treatment strategies including optimizing physiological parameters, use of selective
pulmonary artery vasodilators, inotropic support, and systemic blood pressure maintenance. Wherever possible,
these patients should be cared for in specialty centers.

References
This ASA2013 refresher course is similar in content to the same refresher course delivered by Dr Jacobsohn in 2012
and available from the 2012 ASA Refresher Course Lecture Series.
1. Strumpher J, Jacobsohn E: Pulmonary hypertension and Right Ventricular Dysfunction: Physiology and
perioperative management; J Cardiovasc Thorac Anesth Vol 25:687-704, 2011
2. Galie N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: ESC/ERS GUIDELINES.
Eur Heart J 30:2493-2537, 2009
3. McLaughlin V, et al. et al for the Writing Committee: CCF/AHA 2009 Expert Consensus Document on
Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on Expert
Consensus Documents and the American Heart Association Developed in Collaboration with the American College
of Chest Physicians; American Thoracic Society, and the Pulmonary Hypertension Association. J Am Coll Cardiol
53: 1573-1619, 2009
4.Simonneau G, et al. Updated clinical classification of PH. J Am Coll Cardiol 54:S43-S53, 2009
5. Herget J, et al. A possible role of the oxidant tissue injury in the development of hypoxic pulmonary hypertension.
Physiol Res 49:493-501, 2000
6. Christman BW, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in
pulmonary hypertension. N Engl J Med 327:70-75, 1992
7. Gomberg-Maitland M, et al. Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am
J Cardiol 96:1334-1336, 2005
8. Doyle RL, et al. Surgical treatments/Interventions for pulmonary arterial hypertension: ACCP evidence based
clinical practice guidelines. Chest 126:63S-71S, 2004
9. Lewczuk J, et al. Prognostic factors in medically treated patients with chronic PE. Chest 119:818-823, 2001
Fig. 9

228
Page 9
10. Toyoda Y, et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial
hypertension. Ann Thorac Surg 86:1116-1122, 2008
11. Vlasselaers D, et al. Femoral venoarterial extracorporeal membrane oxygenation for severe reimplantation
response after lung transplantation. Chest 118:559-561, 2000
12. Thistlethwaite PA, et al. Venovenous extracorporeal life support after pulmonary endarterectomy: indications,
techniques and outcomes. Ann Thorac Surg 82:2139-2145, 2006
13. DAlonzo GE, et al. Survival in patients with primary pulmonary hypertension. Results from a national
prospective registry. Ann Intern Med 115:343-349, 1991
14. Martin JT, et al. JF: Safety of regional anesthesia in Eisenmengers syndrome. Reg Anesth Pain Med 27:509-
513, 2002
15. Krowka MJ, et al. Hepatopulmonary syndrome and portopulmonary hypertension: A report of the multicenter
liver transplant database. Liver Transpl 10:174-182, 2004
16. Denault AY, Haddad F, Jacobsohn E, Deschamps A. Perioperative right ventricular dysfunction. Curr Opin
Anaesthesiol. 2013 Feb;26(1):71-81.

Disclosure

234
Page 1
Current Controversies in Critical Care Anesthesiology
Brenda G. Fahy, M.D. Gainesville, Florida
INTRODUCTION
EVIDENCE BASED MEDICINE (EBM)
Current controversies in anesthesiology continue and applying the best evidence helps guide care. Evidence based
medicine (EBM) involves the application of the scientific method to medical practice and clinical decisions
replacing the traditional authority based medical paradigm. A common definition and explanation of evidence based
medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the
care of individual patients. The practice of EBM means integrating individual clinical expertise with the best
available external clinical evidence from systematic research. Individual clinical expertise is the proficiency and
judgment that individual clinicians acquire through clinical experience and clinical practice.
50
This approach
involves incorporating the best available scientific literature to substantiate clinical decision making with the hopes
that this will reduce inherent bias that may be present when recent experiences unduly influence scientifically
unsubstantiated care decisions. EBM strives to integrate the physicians clinical experience (including cumulative
clinical experience, education, and skills), the best scientific evidence for the particular clinical decision, and patient
preferences and values. However, the evidence by itself does NOT determine the clinical decision; EBM represents
one part of the process. The health care provider must examine the risk(s) and benefit(s) of a data based clinical
decision while incorporating individual patient factors. These individual patient factors include personal
experiences, expectations, and values that can impact and at times limit clinical decision making for those unique
circumstances.
What does best evidence entail?
The best evidence is often found when well designed investigational methodology has been used to generate
clinically relevant research. A properly randomized prospective (and ideally blinded) double placebo controlled
clinical trial is a powerful tool to evaluate the effectiveness of one therapy compared to another. However, the
quality and design of the trial can impact the validity and application of the results. For example, a trial with
prohibitively narrow inclusion criteria may not be valid for extrapolation and application to a general population.
Some clinically relevant questions may be more appropriately answered by a carefully designed observation study
than a randomized controlled trial. Certain patient populations, such as the critically ill patients, also may present
logistical and ethical difficulties for research.
What advantages might EBM confer?
Patient encounters generate clinical decision process questions that would be appropriate to apply to EBM. When
studied, only 30% of the physicians informational needs for these clinical questions were met during the patient
visit. The majority of questions generated by those physicians were answered by utilizing another colleague.
12

Further direct observational study revealed an average of 5 physician generated questions per patient encounter;
52% of these questions could be answered by medical record review or hospital information system query while
25% required review of published information in a textbook or Medline.
46
Evidence based medicine removes the
bias of my experience care, which can result in therapy that is based on personal experience rather than the best
available evidence. According to studies, American healthcare gets it right 54.9% of the time.
42

234
Page 2
Does EBM application lead to change?
The literature says yes. Using an evidence based cart on hospital rounds led to new therapy or diagnostic tests 25%
of the time and corrected a previous plan 16% of the time.
51
EBM requires critical evaluation of the literature so that
decisions may be based on the strongest applicable evidence. This critical evaluation entails assessing study
validity and design while evaluating the applicability of the final results to this unique patients circumstance.
Why is EBM important for perioperative care?
More than thirty million major operations are performed yearly in the United States.
5
Despite continued medical
advances in both anesthesia and surgery, and improvements in perioperative care, there still remain variations in
outcome for patients undergoing similar procedures and interventions. Postoperative complications are a major
cause of mortality and excess length of hospital stay and hospital costs.
16
Independent of preoperative patient risk,
the occurrence of a complication within the first 30 days of the postoperative period reduced median patient survival
by 61%.
33
Many of these complications are potentially preventable.
APPLICATION OF EBM TO PERIOPERATIVE GLUCOSE MANAGEMENT
This handout focuses on one specific controversial globally pertinent perioperative issue - glycemic control. The
discussion reviews current evidence and outlines advantages and limitations of application of evidence based
medicine in perioperative glucose management.
Scope of the problem and implications of hyperglycemia
Approximately 20 million adults (8-10% of the adult population) in the United States have diabetes mellitus.
44
Over
90% have type 2 diabetes with deficient insulin production, insulin responsiveness, excessive gluconeogenesis or a
combination of these factors. Diabetes is the 6th most common cause of death in the United States
4
with the risk of
death amongst diabetics approximately double that of non-diabetics for the same age.
44
Hyperglycemia, even
without the diagnosis of diabetes, is an independent risk factor for sudden cardiac death, myocardial infarction,
cerebral vascular accident, or poor outcome after ICU admission.
8, 9, 35, 49
Given the significant morbidity and
mortality
11
associated with diabetes and concerns over stress hyperglycemia, various regulatory organizations and
learned societies drafted guidelines on management of perioperative hyperglycemia.
3
The following focuses on the
current evidence supporting such recommendations, the need for additional data, particularly regarding the incidence
of intraoperative hypoglycemia, and outlines on-going efforts to address unresolved management issues in
optimizing care of patients with perioperative hyperglycemia.
Hyperglycemia has been shown to impair leukocyte functions,
64, 65
resulting in compromised wound healing and
exacerbating other complications (e.g., ischemia). Hyperglycemia also results in increased cytokine levels and
inflammation.
34, 56
Particularly noteworthy, is that potent pro-inflammatory signals are generated by an interaction
between advanced glycation end products and various receptor agonists.
65
These signals in turn amplify the
expression of the receptor for advanced glycation which can lead to a positive feedback mechanism that potentially
may permit acute inflammation to transition to a chronic state.
32

Hospitalized patients and elective surgery patients
Hyperglycemia occurs frequently in hospitalized patients. In a study of 1034 screened hospitalized patients with no
prior history of diabetes, 33% of surgical patients and 38% of medical patients had at least one serum glucose of
greater than 200 mg/dl with two-thirds of these patients having two or more serum glucose levels of greater than 200
mg/dl.
40
Hyperglycemia in another study occurs in 38% of hospitalized patients: 26% with a prior history of
diabetes but 12% with no prior history of diabetes.
57
Newly discovered hyperglycemia has been linked to adverse
outcome with an 18 fold increase in hospital mortality, longer length of stay, and a higher risk of infection.
49

Diabetics are conservatively estimated to represent approximately a quarter of hospitalized patients,
10
and are more
likely than non-diabetics to undergo surgery. In diabetic patients undergoing elective surgery,
48
a blood glucose
level > 220 mg/dl resulted in a 5.8 fold increase in nosocomial infections on the first postoperative day compared to
those with lower glucose levels.
Cardiac surgery patients
Cardiac surgery glucose levels of greater than 200 mg/dl within the first 48 hours postoperatively doubled the risk of
surgical site infections.
36
Hyperglycemic events occurred in patients without a prior history of diabetes 47% of the
234
Page 3
time in this study. In diabetic patients during cardiac surgery, four consecutive intraoperative glucose levels of
greater than 200 mg/dl worsened hospital outcome.
47
Recent studies further examining the impact of long term
glucose control in diabetics revealed in a single academic medical center that diabetics undergoing primary, elective
coronary artery bypass grafting with an elevated hemoglobin A1c had an increased risk of adverse events including
hospital mortality and deep sternal wound infections compared to diabetics with lower hemoglobin A1c reflecting
better long term glucose control.
31
Further studies with noncardiac surgery have shown diabetics with a better
glucose control preoperatively with lower hemoglobin A1c levels have improved outcomes.
66-67

In the Portland Diabetic Project, the outcome of 5,510 consecutive diabetic cardiac surgery patients over an 18 year
period revealed that an average glucose of >150 mg/dl for the first three postoperative days was an independent
predictor of mortality, deep sternal wound infection, and increased length of stay.
25
Continuous intravenous insulin
infusions were shown to independently reduce the risk of death and deep sternal wound infection. Each deep sternal
wound infection increased care costs and extended hospitalization 16 days.
26
Although glucose was controlled
intraoperatively, there was no standardization. Tight glycemic control resulted in no significant higher risk of death
and stroke. In a prospective randomized controlled study,
28
patients undergoing cardiac surgery were randomized to
maintain intraoperative glucose with insulin therapy in the range of 80 to 110 mg/dl compared to treatment of
glucose only if >200 mg/dl. Both groups received postoperative insulin infusions. The intensive insulin therapy had
lower glucoses on arrival to the ICU, however, with more deaths and strokes after surgery although this was not
statistically significant. There was no difference in length of ICU or hospital stay between the two groups. A
subsequent systematic review and meta-analysis of perioperative glycemic control in patients undergoing any
surgery showed a trend toward lower mortality with intensive insulin therapy with a higher incidence of
hypoglycemia.
29
The authors advocated the collection of additional data.
29

Anesthesia and Glucose Homeostasis
The magnitude of surgical trauma in part determines the degree of insulin resistance and thus may impact anesthetic
management. Minimally invasive surgical techniques have less endogenous glucose release and production of
oxidized lipids compared to open procedures.
55
Inhaled volatile anesthesia can inhibit insulin secretion and increase
hepatic glucose production
37
while regional anesthesia can decrease both intra-and postoperative glucose
production.
17, 37, 38
Techniques for perioperative pain management may also have an effect on perioperative glucose
as insulin resistance is decreased in orthopedic patients with perioperative regional anesthesia techniques compared
to patient controlled analgesia
17, 38.
Administration of an oral carbohydrate beverage several hours preoperatively
can decrease whole body insulin sensitivity
52
and require less inotropic support weaning from cardiopulmonary
bypass.
6
Additional benefits may be derived from improved glucose control including in patients who received a
preoperative carbohydrate beverage had a decrease expression of a marker for immunocompetence, Human
Leukocyte Antigen (HLA)-DR compared to controls.
43

Intensive Care Unit (ICU) patients
In 2001, Van den Berghe and colleagues performed the first large, major study in a surgical intensive care unit
(SICU) with intensive insulin infusion therapy. This prospective controlled randomized trial enrolled 1548 patients,
all surgical patients, with two-thirds having undergone cardiac surgery. Patients were randomized to receive insulin
for glucose levels above 215 mg/dl versus intensive insulin therapy to maintain glucose between 80 to 110 mg/dl.
All patients on admission received 300 gram of intravenous glucose over a 24 hour period. Overall hospital
mortality rates were 37% lower with tight glucose control with the mortality advantage occurring in patients without
a prior history of diabetes.
59

The Stamford Project used a before and after design for a 14-bed mixed medical/surgical/cardiac ICU. Following
development of an insulin protocol, 800 consecutive patients were followed. Their outcomes were compared to a
control group of 800 consecutive patients cared for during the period immediately prior to initiation of an insulin
protocol targeting a blood glucose of < 140 mg/dl.
35
Compared to controls, the insulin protocol resulted in
significant improvement in mortality, shorter ICU stay, and better glycemic control.
In a second randomized controlled trial by Van den Berghe in 2006 in 1200 medical ICU (MICU) patients, intensive
insulin infusion therapy to achieve goal glucoses of 80 to 110 mg/dl was compared to the conventional therapy with
goals of 180 to 200 mg/dl.
60
Intensive insulin therapy significantly reduced morbidity but not mortality in the MICU
patients who required three or more days in the ICU; but increased mortality in MICU patients who required less
234
Page 4
than three days in the ICU. There was a higher incidence of hypoglycemia with the intensive insulin therapy which
raised warnings on potential long term impact
41
but was not shown to be associated with mortality.
Due to safety concerns triggered by Van den Berghes trials, her group performed a pooled analysis of 2748 patients
enrolled in both randomized controlled trials in the ICU.
61
Intensive insulin therapy reduced mortality in these
populations without increasing mortality in patients with short ICU lengths of stay. The incidence of one or more
hypoglycemic episodes was more common during intensive insulin therapy yet death within 24 hours after a
hypoglycemic episode was more frequent in the conventional treatment group. Following a hypoglycemic episode,
there was no increase in delayed mortality or neurological sequelae, although these were not specifically sought data
in the study. When analyzed further there was no survival benefit for BG < 110 mg/dl for patients with a history of
diabetes and there appeared to be a trend toward increased mortality in the diabetic population..
To address the same issue in a nested-case control study
62
using a mixed medical-surgical ICU population, 156
consecutive patients with hypoglycemia during intensive insulin therapy were matched with 155 patients at risk for
hypoglycemia. Three patients had possible hypoglycemic induced coma and/or general seizures although there was
no overall risk of increased mortality caused by hypoglycemia. Risk factors that were independent predictors of
hypoglycemic episodes were a decrease in the rate of nutritional supplementation with the same insulin infusion
rate, use of bicarbonate substitution fluids during hemofiltration, preexisting diabetes, sepsis, and inotropic
support.
63

A multicenter German trial (VISEP trial)
7
was recently halted following enrollment of 537 medical or surgical
patients with severe sepsis comparing conventional versus intensive insulin therapy because of frequent
hypoglycemic episodes associated with intensive insulin therapy (17% with intensive insulin versus 4% with
conventional therapy) mortality. In Europe the Glucontrol trial investigators, examined titration of insulin therapy
to achieve blood glucose levels of 80-110 versus 140-180 mg/dl. It was stopped prematurely
15
after inclusion of only
1100 patients of a planned 3500 due to a higher rate of hypoglycemia (< 40 mg/dl) and associated higher mortality
with one episode of hypoglycemia in the tight glucose control (80-110 mg/dl) group. A meta-analysis of 29
randomized controlled trial with over 8,000 patients found no difference in hospital mortality if glucose goals were
! 110 mg/dl versus < 150 mg/dl or based on ICU setting (surgical, medical, or combined surgical-medical).
However, there was a significant increase in hypoglycemia with intensive insulin therapy.
53

The NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm
Regulation) trial conducted by the Australian and New Zealand Intensive Care Society and the Canadian Critical
Care trial group and involving U.S. sites as well enrolled 6104 medical and surgical ICU patients titrating insulin
therapy to achieve blood glucose levels of 80-108 versus 144-180 mg/dl.
45
There was a higher 90-day mortality with
intensive insulin therapy compared to controls with no difference in median days in the hospital or ICU, mechanical
ventilation, or renal replacement. A meta-analysis
30
included NICE-SUGAR involving 26 trials with 13,000
patients showed no overall effect on 90-day mortality with intensive insulin versus conventional therapy. There was
a pooled relative risk of 6.0 for intensive insulin versus conventional therapy in 14 trials involving over 12,000
patients. When contributing factors were examined there was a benefit of intensive insulin versus conventional
therapy from 5 trials in surgical ICUs with the majority of patients being cardiac surgery patients; no benefit was
observed in medical ICUs or mixed medical-surgical ICUs.
Since the NICE-SUGAR trial, further analyses have raised concerns about the risks of hypoglycemia. In a
retrospective analysis of almost 5,000 ICU patients, 22% had experienced at least one episode of hypoglycemia
(defined as glucose < 81 mg/dl)
18
Mortality increased significantly and increased further the lower the glucose the
hypoglycemic episode. After adjustment for insulin therapy or timing of hypoglycemic episodes, the risk of death
was increased the lower the glucose level with the hypoglycemic episode.
Perioperative Glycemic Control for Diabetics
Diabetes remains a risk factor for perioperative complications compared to the general population However, much
of the current literature with glycemic control during the perioperative period entails patients with previously
diagnosed diabetes as a small subpopulation of those studied. A recent metanalysis evaluated RCT of more
intensive control of perioperative glucose compared to conventional care in patients with previously diagnosed
diabetes. Twelve studies were included with 694 patients randomized to intensive glucose control and 704 to
conventional therapy. Eight of these studies involved cardiovascular or cardiac surgery and 3 focused on patients in
the ICU. Blood glucose targets varied from less than 120 to 200 mg/dl for intensive therapy. Although the blood
glucose concentrations were lower in the intensive control group, this did not significantly reduce mortality,
234
Page 5
cardiovascular or infectious complications or length of stay (ICU or hospital). There was evidence of increased
hypoglycemia during intensive control however further studies are required to confirm.
68

So what does the evidence say?
The optimal target for blood glucose remains unclear and is a key clinical question.
23
The evidence is conflicting
with benefits of tight glucose control in certain populations with specific target blood glucose levels; while other
patient populations failed to reap significant benefits and had significant risks of hypoglycemia. Some trials have
been halted because of concerns related to higher mortality following a hypoglycemic episode(s) associated with
achieving target glucoses of 80-110 mg/dl. Hypoglycemia episodes have associated morbidity including coma and
seizures with long-term sequelae including cognitive dysfunction with more recent data further supporting these
concerns and further study is required. In addition, delineation as to whether the risks of a hypoglycemic episode
and whether the definition of symptomatic hypoglycemia are the same or higher for a newly diagnosed
hyperglycemic patient without a history of diabetes versus long standing diabetes remain to be clarified. Whether
the glucose thresholds for treatment and acceptable ranges should differ for those with preexisting diabetes versus
newly diagnosed hyperglycemia has yet to be answered. The variability of blood glucose concentration
19
may be as
deleterious as hypoglycemia and is currently a topic undergoing further investigation. When is the ideal time to
begin glucose management? The studies differ on when glucose management was instituted. In the first
randomized control trial in the ICU, therapy was initiated immediately postoperatively in a SICU population before
complications were evident; whereas in the same institution a subsequent MICU study initiated insulin therapy after
there were complications of multiorgan failure. This latter study failed to show an improvement in outcome but
raised safety concerns with hypoglycemia. With the potential for the hyperglycemic complications including
surgical site infections and release of proinflammatory mediators, early intervention to prevent hyperglycemia
would seem reasonable. But, strong evidence is currently lacking and at the current time there exist no large data
base for intraoperative glucose management or hypoglycemia. Intraoperative hypoglycemia is more worrisome due
to lack of the early warning signs. Continuous monitoring of glucose
13
may be a future option to limit these
complications but the data is sparse.
21
There are numerous factors that can impact reliability of point-of-care blood
glucose measurements
22
which must be taken into account. Circumstances such as anemia or peripheral
hypoperfusion due to dehydration or shock may exist in the intraoperative and perioperative periods and reduce
inaccurate glucose measurements. Is there an ideal level of glucose which might confer benefit and avoid risk?
Three large retrospective trials
24, 27, 35
have found that glucose levels below 140 mg/dl compared to higher levels
resulted in improved outcomes. Another study
16
found poor intraoperative glucose control (defined as a failure to
achieve glucose levels below 144 mg/dl) resulted in significantly more postoperative morbidity and a higher
adjusted odds ratio for severe postoperative morbidity among those with poor intraoperative glucose control
compared to those with intraoperative glucoses below 144 mg/dl. The largest randomized study in the ICUs found
glucose levels of 144-180 mg/dl had a lower 90-day mortality rate than glucose levels of 80-108 mg/dl.
45
Questions
remain as to the appropriate range(s) of glucose levels for control. Whether this data can be extrapolated to all
patients who become hyperglycemic during the perioperative period remains unknown. The mortality curve with
glucose appears to be a J-shaped curve with mortality the lowest when glucose is normal for age and highest with
hyperglycemia.
58
There is also an increased mortality with hypoglycemia.
Recent recommendations by organizations have recognized the risks of hypoglycemia with the Society of Thoracic
Surgeons published practice guidelines recommending during adult cardiac surgery blood glucose should be
maintained less than 180 mg/dl intraoperatively and at least 24 hours postoperatively.
39
However, this guideline does
not adequately address many of the risks of treatment of hyperglycemia including hypoglycemia and limitations of
glucose monitoring techniques.
1,14, 20, 22, 54

Recognizing recent concerns, the American Diabetes association is now recommending that a starting threshold for
treatment of glucose in critically ill patients should be 180 mg/dl with glucose maintained 140-180 mg/dl.
2
This
guideline recognizes that additional benefits may be achieved at the lower end of the range but cannot recommend
targets <110 mg/dl.
The Society of Critical Care Medicine has also published guidelines for the use of insulin infusion to manage
hyperglycemia in critically ill patients. This guideline acknowledges that the majority of literature for insulin
infusion in critically ill patients cannot support more than weak recommentations. This guideline suggests a blood
glucose level (greater than or equal to) 150 mg/dL should trigger interventions to maintain the blood glucose level
<180 mg/dL.
69

234
Page 6
What is the ideal regime? The ideal method and frequency of glucose monitoring in the perioperative period has not
undergone rigorous study nor has there been identification of the true incidence of intraoperative hypoglycemia.
Tight glucose control also costs resources including personnel costs to monitor glucoses and regulate the insulin
infusion.
SUMMARY
The application of the scientific method to medical practice and clinical decision making to provide improved
outcome in perioperative care can present a significant challenge. The evidence for prevention of
venothromboembolism in the perioperative period has been much more rigorously evaluated in high-risk patient
populations then perioperative glycemic control. Although EBM involves the use of the scientific method to
medical practice and clinical decision making, the evidence requires critical evaluation and appropriate
application. Glucose control in the perioperative period includes guidelines that have been developed by reputed
societies with limitations of extrapolating to all patients in the perioperative period. In fact, with some of the
current trials failing to show benefit and reporting a risk of hypoglycemic episodes, these current recommendations
may need further scrutiny and will require further scientific evaluation. There are many unanswered questions
concerning glycemic control. However, first do no harm and maintaining the safety of surgical patients throughout
the perioperative course remains of prime importance. More data is needed particularly for intraoperative
management of glucose and will hopefully be forthcoming with appropriate interpretation and incorporation into
various current protocols and guidelines.
REFERENCES
1. Akhtar S, Barash PG, Inzucchi SE. Scientific principles and clinical implications of perioperative glucose
regulation and control. Anesth Analg 110:478-497, 2010
2. American Diabetes Association. Standards of medical care in diabetes 2013. Diabetes Care 2013; 36:S11-
66.
3. American College of Endocrinology, Position Statement on Inpatient Diabetes and Metabolic Control.
Endocr Pract. 2004;10(1): 77-82.
4. Anderson RN, Smith BL, Deaths: Leading Causes for 2002 National Vital Statistics Report. NVSS CDC,
2005; 53(17): 1-89, 92.
5. Bratzler DW, Hunt DR., The surgical infection prevention and surgical care improvement projects: national
initiatives to improve outcomes for patients having surgery. Clin Infect Dis. 2006; 43(3):322-30.
6. Breuer JP, von Dossow V, von Heymann C, et al. Preoperative oral carbohydrate administration to ASA III-
IV patients undergoing elective cardiac surgery. Anesth Analg. 2006; 103(5):1099-108.
7. Brunkhorst FM, Engel C, Bloos F, et al. German Competence Network Sepsis (SepNet). Intensive insulin
therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008; 358(2): 125-39.
8. Capes SE, Hunt D, Malmberg K,Gerstein HC. Stress hyperglycaemia and increased risk of death after
myocardial infarction in patients with and without diabetes: A systematic overview. Lancet. 2000; 355: 773
778.
9. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in
nondiabetic and diabetic patients: A systematic overview. Stroke. 2001; 32:24262432.
10. Clement S, Braithwaite SS, Magee MF, et al. Management of Diabetes and Hyperglycemia in Hospitals.
Diabetes Care. 2004; 27(2): 553-91.
11. Coursin DB,Connery LE, Ketzler JT. Perioperative diabetic and hypergylycemic management issues. Crit
Care Med. 2004; 32(Suppl 4): S116-25.
12. Covell DG, Uman GC, Manning PR, Information needs in office practice: are they being met? Ann Int
Med. 1985; 103: 596-599.
13. De Block C, Manuel-Y-Keenoy B, Van Gaal L, Rogiers P. Intensive insulin therapy in the intensive care
unit: assessment by continuous glucose monitoring. Diabetes Care. 2006; 29(8): 17501756.
14. Desachy A, Vuagnat AC, Ghazali AD, et al: Accuracy of bedside glucometry in critically ill patients:
influence of clinical characteristics and perfusion index. Mayo Clin Proc 83:400-405, 2008
234
Page 7
15. Devos P, Preiser JC. Current controversies around tight glucose control in critically ill patients. Curr Opin
Clin Nutr Metab Care. 2007; 10(2): 206-9.
16. Dimick JB, Chen SL, Taheri PA, et al. Hospital costs associated with surgical complications: a report from
the private-sector National Surgical Quality Improvement Program., J Am Coll Surg. 2004; 199(4): 531-7.
17. Donatelli F, Vavassori A, Bonfanti S, et al. Epidural anesthesia and analgesia decrease the postoperative
incidence of insulin resistance in preoperative insulin-resistant subjects only. Anesth Analg. 2007;
104(6):1587-93.
18. Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Taori G, Hegarty C, Bailey M. Hypoglycemia and
outcome in critically ill patients. Mayo Clin Proc. 2010 Mar; 85:215-6.
19. Egi M, Bellomo R, Stachowski E, et al. Variability of blood glucose concentration and short-term mortality
in critically ill patients. Anesthesiology. 2006; 105(2):244-52.
20. Facchinetti A, Sparacino G, Cobelli C: Modeling the error of continuous glucose monitoring sensor data:
critical aspects discussed through simulation studies. J Diabetes Sci Technol 4:4-14, 2010
21. Fahy BG, Coursin DB. An Analysis: Hyperglycemic Intensive Care Unit Patients Need Continuous Glucose
Monitoring - Easier Said Than Done. J Diabetes Sci Technol 2008, 2(2): 201-204.
22. Fahy BG, Coursin DB. Critical Glucose Control the Devil is in the Details. Mayo Clin Proc 2008, 83 (4):
394-397.
23. Fahy BG, Sheehy AM, Coursin DB. Perioperative glucose control: what is enough? Anesthesiology. 2009
Feb; 110(2):204-6.
24. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. JAMA.
2003; 290(15): 20412047.
25. Furnary AP, Wu Y. Clinical effects of hyperglycemia in the cardiac surgery population: the Portland
Diabetic Project. Endocr Pract. 2006; 12(Suppl 3): 22-6.
26. Furnary AP, Postoperative hyperglycemia prolongs length of stay in diabetic CABG patients. Circulation.
2000; 102 (Suppl 2): 556.
27. Gabbanelli V, Pantanetti S, Donati A, et al. Correlation between hyperglycemia and mortality in a medical
and surgical intensive care unit. Minerva Anestesiol. 2005; 71: 717725.
28. Gandhi GY, Nuttall GA, Abel MD, et al. Intensive intraoperative insulin therapy versus conventional
glucose management during cardiac surgery: a randomized trial. Ann Intern Med. 2007; 146(4): 233-43.
29. Gandhi GY, Murad MH, Flynn DN, et al. Effect of perioperative insulin infusion on surgical morbidity and
mortality: systematic review and meta-analysis of randomized trials. Mayo Clin Proc. 2008; 83(4):418-30.
30. Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR,
Chittock DR, Finfer S, Talmor D. Intensive insulin therapy and mortality among critically ill patients: a
meta-analysis including NICE-SUGAR study data. CMAJ. 2009 Apr 14; 180(8):821-7.
31. Halkos ME, Lattouf OM, Puskas JD, Kilgo P, Cooper WA, Morris CD, Guyton RA, Thourani VH. Elevated
preoperative hemoglobin A1c level is predictive of adverse events after coronary artery bypass surgery. J
Thorac Cardiovasc Surg. 2008; 136:631-40.
32. Hofmann MA, Drury S, Fu C, et al. RAGE mediates a novel proinflammatory axis: a central cell surface
receptor for S100/calgranulin polypeptides. Cell. 1999; 97: 889-901.
33. Khuri SF, Henderson WG, DePalma RG, Mosca C, et al. Participants in the VA National Surgical Quality
Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of
postoperative complications. Ann Surg. 2005; 242(3): 326-41; discussion 341-3.
34. Kjersem H, Hilsted J, Madsbad S, et al. Polymorphonuclear leucocyte dysfunction during short term
metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients. Infection.
1988; 16(4): 215-21.
35. Krinsly JS, Effect of an intensive glucose management protocol on the mortality of critically ill adult
patients. Mayo Clin Proc. 2004; 79(8): 992-1000.
36. Latham R, Lancaster AD, Covington JF, et al. The association of diabetes and glucose control with surgical-
site infections among cardiothoracic surgery patients. Inf Contr Hosp Epidemiol. 2001; 22(10): 607-12.
37. Lattermann R, Schricker T, Wachter U, et al. Understanding the mechanisms by which isoflurane modifies
the hyperglycemic response to surgery. Anesth Analg. 2001; 93(1):121-7.
38. Lattermann R, Belohlavek G, Wittmann S, et al. The anticatabolic effect of neuraxial blockade after hip
surgery. Anesth Analg. 2005; 101(4):1202-8
234
Page 8
39. Lazar HL, McDonnell M, Chipkin SR, et al: The Society of Thoracic Surgeons practice guideline series:
Blood glucose management during adult cardiac surgery. Ann Thorac Surg 87:663-669, 2009
40. Levetan CS, Passaro M, Jablonski K, et al. Unrecognized diabetes among hospitalized patients. Diabetes
Care. 1998; 21(2): 246-9.
41. Malhotra A: Intensive insulin in intensive care. N Engl J Med 2006; 354(5): 516-518.
42. McGlynn EA, Asch SM, Adams J, et al. The quality of healthcare delivered to adults in the United States.
N Engl J Med. 2003; 348(26): 2635-45.
43. Melis GC, van Leeuwen PA, von Blomberg-van der Flier BM, Goedhart-Hiddinga AC, Uitdehaag BM,
Strack van Schijndel RJ, Wuisman PI, van Bokhorst-de van der Schueren MA. A carbohydrate-rich
beverage prior to surgery prevents surgery-induced immunodepression: a randomized, controlled, clinical
trial. JPEN J Parenter Enteral Nutr. 2006; 30:21-6.
44. National Center for Disease Prevention and Health Promotion. Diabetes Fact Sheet available at
http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2005.pdf [accessed June 12,2009].
45. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo
R, Cook D, Dodek P, Henderson WR, Hbert PC, Heritier S, Heyland DK, McArthur C, McDonald E,
Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose
control in critically ill patients. N Engl J Med. 2009 Mar 26; 360(13):1283-97.
46. Osheroff JA, Forsythe DE, Buchanan BG, et al. Physicians information needs: analysis of questions posed
during clinical teaching. Ann Intern Med. 1991; 114(7): 576-81.
47. Ouattara A, Lecomte P, Le Manach Y, et al. Poor intraoperative blood glucose control is associated with a
worsened hospital outcome after cardiac surgery in diabetic patients. Anesthesiology. 2005; 103:687694.
48. Pomposelli JJ, Baxter JK 3rd, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial
infection rate in diabetic patients. JPEN 1998; 22(2):77-81.
49. Rady MY, Johnson DJ, Patel BM, et al. Influence of individual characteristics on outcome of glycemic
control in intensive care unit patients with or without diabetes mellitus. Mayo Clin Proc. 2005; 80(12):
1558-67.
50. Sackett DL, Rosenberg WM, et al. Evidence based medicine: what it is and what it isnt. BMJ. 1996; 312
(7023): 71-2.
51. Sackett D, Straus SE, Finding and applying evidence during clinical rounds: the "evidence cart". JAMA.
1998 Oct; 280(15): 1336-8.
52. Soop M, Nygren J, Myrenfors P, et al. Preoperative oral carbohydrate treatment attenuates immediate
postoperative insulin resistance. Am J Physiol Endocrinol Metab. 2001; 280(4):E576-83.
53. Soylemez Wiener R, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill
adults: a meta-analysis. JAMA 2008; 300: 933-44.
54. Steil GM, Deiss D, Shih J, et al: Intensive care unit insulin delivery algorithms: Why so many? How to
choose? J Diabetes Sci Technol 3:125-140, 2009
55. Thorell A, Nygren J, Essen P, et al. The metabolic response to cholecystectomy: insulin resistance after open
compared with laproscopic operation. Eur J Surg. 1996; 162:187-91.
56. Turina M, Fry DE, Polk HC Jr, Acute hyperglycemia and the innate immune system: clinical, cellular, and
molecular aspects. Crit Care Med. 2005; 33(7): 1624-33.
57. Umpierrez GE, Isaacs SD, Bazargan N, et al. Hyperglycemia: an independent marker of in-hospital
mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002; 87(3): 978-82.
58. Van den Berghe G, Schetz M, Vlasselaers D, et al. Intensive insulin therapy in critically ill patients: NICE-
SUGAR or Leuven blood glucose target? J Clin Endocrinol Metab. 2009; 94: 3163-3170.
59. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J
Med. 2001; 345(19): 13591367.
60. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J
Med. 2006; 354(5): 449-461.
61. Van den Berghe G, Wilmer A, Milants I, et al. Intensive insulin therapy in mixed medical/surgical intensive
care units: benefit versus harm. Diabetes. 2006; 55: 31513159.
62. Vriesendorp TM, DeVries JH, van Santen S, et al. Evaluation of short-term consequences of hypoglycemia
in an intensive care unit. Crit Care Med. 2006; 34(11): 27142718.
63. Vriesendorp TM, van Santen S, DeVries JH, et al. Predisposing factors for hypoglycemia in the intensive
care unit. Crit Care Med. 2006; 34(1): 96-101.
234
Page 9
64. Walrand S, Guillet C, Boirie Y, Vasson MP In vivo evidences that insulin regulates human
polymorphonuclear neutrophil functions. J Leukoc Biol. 2004; 76(6): 1104-10.
65. Yan SF, Ramasamy R, Naka Y, et al. Glycation, inflammation, and RAGE: a scaffold for the
macrovascular complications of diabetes and beyond. Circ Res. 2003; 93: 1159-1169.
66. Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C et al. Prevalence and clinical outcome of
hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care 2010: 33: 1783-1788
67. Dronge AS, Perkal MF, Kancir S, Concato J, Aslan M, Rosenthal RA. Long-term glycemic control and
postoperative infectious complications. Arch Surg. 2006 Apr;141(4):375-80; discussion 380.
68. Buchleitner AM, Martnez-Alonso M, Hernndez M, Sol I, Mauricio D. Perioperative glycaemic control
for diabetic patients undergoing surgery. Cochrane Database Syst Rev. 2012 Sep 12;9:CD007315. doi:
10.1002/14651858.CD007315.pub2.
69. Jacobi J, Bircher N, Krinsley J, Agus M, Braithwaite SS, Deutschman C, Freire AX, Geehan D, Kohl B,
Nasraway SA, Rigby M, Sands K, Schallom L, Taylor B, Umpierrez G, Mazuski J, Schunemann H.
Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.
Crit Care Med. 2012 Dec;40(12):3251-76. doi: 10.1097/CCM.0b013e3182653269.
Disclosure
317
Page 1
Emergent Airway Management: Tips, Tricks, and Evidence
Aaron Joffe, M.D. Seattle, Washington
319
Page 1
Sepsis: Current Concepts and Perioperative Management
Mark E. Nunnally, M.D., FCCM Chicago, Illinois
Introduction
Sepsis continues to be a high-impact syndrome. In the U.S., about 250,000 people die of sepsis annually. Sepsis
kills more people than breast cancer, prostate cancer and AIDS combined (1). Sepsis is a comorbidity in many
major surgeries, is often responsible for an emergency designation. The increased morbidity and mortality of E
status patients can be attributed to sepsis physiology.
In an era of powerful antibiotics and a better understanding of how to use them, the primacy of sepsis should
confuse us as clinicians. In simple terms, our patients are dying of the same illness (infection) that other patients did
100 years ago. The details may be different, but sepsis still persists and perseveres. In recognition of this
phenomenon, basic science research, translational clinical trials and guidelines production continue at a fast pace.
Sepsis is a spectrum of disease, requiring aggressive and timely management. The topic for speculative discussion
is the bodys common response to illness. Finally, sepsis is ideal for examining the way clinical care is delivered
and directed at institutional, societal and governmental levels.
The sepsis syndrome: common themes
Sepsis has been defined by a loose set of criteria (2), among which are signs of inflammation. These signs are linked
to known or suspected infection. Another system for describing the syndrome is the PIRO model (predisposition,
infection, response, and organ dysfunction) (3). The criteria for defining and characterizing sepsis are nonspecific.
For example, urosepsis is clinically different from sepsis with influenza, even though many factors are common to
both.
Table: Broad diagnostic criteria for sepsis (Modified from reference 2):
Infection: documented or suspected
General variables: T > 38.3 or < 36C, HR > 90/min, ! RR, encephalopathy, edema or
positive fluid balance, hyperglycemia
Inflammatory variables: WBC > 12,000 or < 4000/mcL, > 10% immature forms, ! C-reactive
protein, procalcitonin
Hemodynamic variables: SBP < 90, MAP < 70 mmHg or " > 40 mmHg, SvO
2
> 70%, Cardiac
Index > 3.5 L/min
Organ dysfunction variables: hypoxemia, oliguria, ! creatinine, coagulopathy, ileus, " platelet
count, ! bilirubin
Tissue perfusion variables: ! lactate, " capillary refill, mottling
319
Page 2
Central to sepsis is inflammation. Systemic responses to infection range from elevated white blood cell counts to
fever to hyperglycemia to changes in intercellular mediators. Inflammation has been the main focus of sepsis
research for over 40 years. Patients dont usually die from inflammation, however; they die from organ dysfunction.
Organ dysfunction in sepsis takes many forms and affects every organ system. Renal (e.g., acute kidney injury),
vascular (vasoplegic shock) and respiratory failure (acute lung injury/acute respiratory distress syndrome) are well
recognized sequelae of severe sepsis, but endocrine (hyperglycemia), neurologic (encephalopathy), and
gastrointestinal (ileus) dysfunctions often presage severe sepsis and are signals to intervene before the syndrome
worsens.
Why do patients become septic?
Infection drives the septic response, consistent with the original definition of sepsis. Yet many systemic changes
during the sepsis syndrome are common to noninfectious causes of inflammatory responses. The systemic
inflammatory response syndrome (SIRS) criteria recognize this fact. SIRS criteria describe a sepsis-like syndrome
without a known or suspected infection.
Components of SIRS are conserved across animal species, and in multiple animal models these components protect
an organism from ongoing damage and allow it to heal. The overlap of inflammation, coagulation, metabolism,
immunologic function, neurologic function, and tissue growth is the result of a complicated network of signals and
activities that correct derangements and repair damage. In a case of modern sepsis, these responses can seem
appropriate or inappropriate, although it is not always clear which is the case. With intensive care, patients survive
previously fatal injuries, changing the natural history of the syndrome. Modern critically ill patients are unique and
their illness has progressed to physiology that would never be seen in the wild. Many feel that the acute responses
of the sepsis syndrome are adaptive, but that in later phases (i.e., chronic sepsis) dysfunction becomes prominent. It
is in the later phases when many patients die.
Sepsis management: key interventions
The Surviving Sepsis Campaign, first launched in 2002, details the evidence in support of sepsis therapy, translating
the large body of sepsis literature into guidelines (4). Timely diagnosis, antibiotic therapy and goal-directed fluid
resuscitation are key components of sepsis management. Several of the suggestions and recommendations directly
influence management in the operating room. The anesthesia care team contributes to care by managing shock
resuscitation with physiologic goals such as mixed-venous oxygen saturation and lactate clearance; by drawing
blood, urine and sputum cultures to confirm diagnoses; and by facilitating the timely administration of antibiotics
(ideally after cultures are drawn, but as quickly as possible). Central venous and arterial access helps with
resuscitation and management. Support of failing organs is ideally suited to anesthesiologists and should be viewed
as akin to management in the intensive care unit. With surgical sources of sepsis, the locale of the intervention
(intensive care unit versus operating room) should make no difference in the goals of resuscitation and antibiotic
therapy. Facilitating timely surgical intervention, however, can make a major difference in outcomes.
What sort of a difference can these interventions have? Absolute mortality from sepsis decreased more than 6% as
compliance with Surviving Sepsis Campaign recommendation bundles increased (5). Curiously, compliance in one
study increased from 18.4 to 36.1%, suggesting that the recommendations are neither easily nor frequently adopted.
Both evidence and rationale support timely intervention. Anesthesiologists can and should strive to facilitate
cultures, antibiotics and resuscitation for septic and suspected-septic patients in their care.
An evolving understanding
Any improvements have to be viewed in light of limited progress and continuing mortality. What has been
accomplished in sepsis research in the last 40 years? Goal-directed resuscitation and antibiotics reduce morbidity
and mortality. In fact, indirect evidence suggests that exposure to a septic source over time increases the collateral
physiologic damage and overall organ dysfunction burden. At the same time, the goals of resuscitation and timing
of antibiotic therapy remain controversial. One may speculate about whether a fixed goal such as a mixed venous
saturation greater than 60% is as important as attention to other clinical signs in an unstable patient. Aggressive
319
Page 3
early antibiotic administration can lead to improper use of antibiotics when a diagnosis of sepsis is unclear, as during
an exacerbation of congestive heart failure.
Investigations document multiple failed therapies. Many of the studies were of inflammatory mediators because of
the theory that the inflammatory response to infection leads to organ dysfunction in sepsis. A long list of failed
therapies, including anti-TNF alpha, ibuprofen, anti-IL-2, branch-chain amino acids and, most famously, drotrecogin
alfa (activated protein C), suggests that not only is a single magic bullet for sepsis unlikely, but that the model for
therapeutic intervention may be wrong. Although inflammation is a key component of sepsis syndromes, immune
suppression, altered endocrine activity and decreased autonomic signaling appear to influence disease progression.
Since the septic patient who dies does so in a state of chronic critical illness after multiorgan failure, a new model of
disease and therapy is necessary. Sepsis patients manifest neuroendocrine exhaustion, immune dysfunction and
energy failure. These findings may provide an opportunity for intervention. In the future, therapies targeting the
central nervous system, hormones, or inflammatory cell apoptosis may improve outcomes more than therapies
targeting inflammation.
An administrative issue
Given the substantial impact that sepsis has on morbidity and mortality, the case has been made for aggressive
management and research investment. The successes of the Surviving Sepsis Campaign argue that recommendation
bundles directed at evidence-based and standardized care make a substantial difference. There is, however, a caveat.
The failures in sepsis management, best documented by the long list of failed anti-inflammatory therapies, suggest
that simple, single solutions will not be common. Controversy continues around resuscitation and antibiotic therapy.
Many adjunctive therapies, such as glucocorticoids, tight glycemic control and pulmonary artery catheter-directed
resuscitation have not fulfilled the promise they had 10 years ago- a warning. Are we too easily tempted to throw
ineffective therapies at a largely insoluble problem? Clinicians who treat disease may be willing to embrace a
therapy just to be able to do something. They want to be optimistic.
At an administrative level, problems like sepsis are an opportunity for regulation, standardization and general
control. Pundits argue eloquently that care variability is the problem and that standardization lets more patients get
better care. Guidelines that are useful tools to help clinicians manage complex problems also restrict their ability to
respond uniquely to unique circumstances. There is a tradeoff. In the case of sepsis, the tradeoff has some benefit
in improving outcomes but should not be taken for granted. The failures in sepsis tell a story about a quest for an
easy solution that sometimes misses the important elements altogether. Re-thinking the problem might reveal elusive
opportunities.
Conclusions
As anesthesia providers, we must be prepared to deliver the best care to patients with sepsis, participate in the
discussions about its causes and treatments, investigate new ideas, and generate and promote measures that can
improve outcomes. Our unique skills in critical care and resuscitation make us ideally suited to these tasks. At the
same time, we understand as well as any physician the complex nature of medical therapies, the assets and liabilities
of guidelines, and the need to think critically about them during care and consultation. We can continue to care for
septic patients with fluids, vasopressors, inotropes, cultures, monitoring and antibiotic therapy while supporting
organ function. But as clinical experts in neurosciences, anesthesiologists have an opportunity to investigate new
means of treating sepsis. Finally, as experts in safety and guidelines management, anesthesiologists can offer
valuable expertise to future guidelines efforts.
References:
1. NIH Sepsis Fact Sheet. Available from: http://www.nigms.nih.gov/Publications/factsheet_sepsis.htm. Accessed
May 23, 2012
2. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition
Conference. Crit Care Med 2003;31(4):1250-6
3. Rubulotta F, Marshall JC, Ramsay G, et al. Predisposition, insult/infection, response, and organ dysfunction: A
new model for staging severe sepsis. Crit Care Med 2009; 37(4):1329-35

319
Page 4
4. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management
of severe sepsis and septic shock. Crit Care Med 2008; 36(1):296-327
5. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international
guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38(2):367-74

Disclosure

502
Page 1
Protocols and Guidelines for the Practitioner
Brian P. Kavanagh MB FRCPC Toronto, Canada
Guidelines and protocols are an integral aspect of acute care. Characteristics of guidelines are such that they help
clinicians to help patients and need to be simple, clear, available and widely supported by relevant expert opinion.
There are many sources of guidelines, some commercial, some from professional bodies and there are standardized
approaches for guideline development including those by the Institute of Medicine.
Of course, guidelines are not infallible. There are clear-cut situations where guidelines were developed which were
thought to reduce mortality, for example the surviving sepsis guidelines instituted as part of an educational program
in Spain in a before and after study were associated with a hospital mortality of 44% before institution and 39.7%
after institution of the guideline. In the surviving sepsis campaign there were two components: resuscitation and
management components and careful analysis of these data revealed that many of the management components (i.e.
low dose steroids, activated protein C, tight glucose control) were subsequently proven either not to work, or be
harmful; indeed the resuscitation component consisting of broad resuscitation measures, with which most physicians
would naturally agree, did not account for better outcome either.
Many guidelines enjoy the support of key professional organizations. This is important as it conveys a sense of
credibility that is necessary for the broad acceptance of the guideline. However, support may not always be
unanimous. For example, the same set of sepsis guidelines received broad support by many professional bodies, but
were not adopted by the Australia and New Zealand Intensive Care Society; this was understandable as sepsis
outcomes in ICUs in Australia and New Zealand is associated with superior outcomes compared with much of
Europe and North America and thus adopting such guidelines that are not based in local practice could conceivably
worsen outcomes in Australia and New Zealand.
The preoperative surgical checklist is another example of a type of guideline. This is supported by most
professional bodies including the World Health Organization and involves elements to be checked before induction
of anesthesia, before skin incision and before the patient leaves the operating room. Its important to note that all of
these are intuitive and common sense interventions. The study that supported the institution of the surgical safety
checklist was done on a global population. Overall, an aggregate across taking into account eight separate
institutions, the instance of surgical site infection on planned return to the operating room, death or any complication
was significantly reduced after versus before institution of the checklist. Because the interventions are common
sense and because their objective data that support their use, it would seem logical that this be good practice.
However, its possible in this paper to examine the implementation of key process measures as they are presented
and when the outcome at each site is correlated with the degree of implementation at each site, in fact there is
largely disagreement between the compliance of the safety indicators and the reduction of complications. This is
counter-intuitive and it does not mean that the checklist should not be used but it does mean that the specific
elements of the checklist are not likely to explain the associated improvement in outcome. If a checklist is used
therefore and the clinicians concentrate only on the checklist (to the exclusion of other measures that they may take
and observations they may make that are not included in the checklist), then it is possible that the use of a checklist
could result in harm. This has not been proven.
Protocols are somewhat different. They are inherently simple, they contain knowledge that is explicit and they are
ideal when there is a need to minimize variability. In certain situations such as titrating neuromuscular blockade or
setting up a hemodialysis circuit, a protocol is ideal. Where the practices required are uniform, minimization of
variability of care is also ideal. In particular, in performance of research, protocols should ideally not be flexible,
thus allowing the reader clear knowledge of what was done during the research project. In research, the most
important aim is not to be able to reproduce the protocol used in this study but rather to be able to understand what

502
Page 2
was done in the study. In clinical practice, processes that are simple (e.g. heparin titration, potassium replacement)
or for which variation is definitely not desired (e.g. assembling a circuit for cardiopulmonary bypass) are ideally
suited to protocolization.

While eliminating variability is often desirable, especially where one knows what the best approach truly is, there
are many situations where variability turns out to be beneficial. Virtually all health services research requires
variability in a database because of course if everybody was treated exactly the same way, there would be no
comparisons possible among different types of care that could point to which was superior.

There are situations when use of protocol might not be a good idea. One example may be where tacit knowledge is
a key element. Tacit knowledge is less amenable to explicit description; for example the rudiments of skills required
in auscultation of the chest, history taking or physical examination may be taught explicitly; however, mastery of
these elements requires practice. Another example might be where scenarios are extremely complex. For example, a
protocol may be used for aspects of ventilator management or septic shock or traumatic head injury, but in a
situation where all three are combined, it is unlikely that all three protocols will converge in a meaningful or helpful
manner.

In some situations there can definitely be unintended consequences. For example, a guideline designed to
rationalize the care for acute immunity acquired pneumonia resulted in an outbreak of clostridium difficile infection
which had the unintended consequences of a large increase in cephalosporin use, prolonged length of hospital stay,
and increased risk of death.

The use of guidelines is thought to perhaps require more subtlety than was previously considered. Lessons from
mammography and prostate surgery suggest that instead of binary risk benefit assessments, that we often operate in
a grey zone which requires more consideration, discussion and review rather than a binary yes/no assessment or
decision.

A particular concern might be legislation mandating clinical practice guidelines; it is generally felt that such
mandates can be dangerous with unintended consequences and are best left in the realm of medical practice.

Finally, trust in guidelines is an important concern. For example, while industry would naturally favour guidelines
that augmented product sales, clinicians and of course, patients- will always want to be reassured that the most
important driver of guidelines is patient wellbeing and affordability. To maximize trust (and confidence) in
guidelines, the Institute of Medicine has issued a series of criteria that are thought to maximize guideline validity.
Unfortunately almost no guidelines fulfill the majority of these criteria, a concern that has not abated over recent
years.

In the end, we must be careful to utilize guidelines carefully, to participate in guideline development and recognize
that guidelines can perform very useful prompts but would never replace expertise. Indeed, there is a suggestion
that relying on simplistic guidelines as a substitute for in-depth reading of textbooks can result in a very different
approach to thinking. This talk will review the differences between protocols and guidelines where they are most
useful and where caution should be exercised.

REFERENCES

The Australasian Resuscitation in Sepsis Evaluation (ARISE) Investigators and the Australian and New Zealand
Intensive Care Society (ANZICS) Adult Patient Database (APD) Management Committee. Crit Care Resus 9: 8,
2007

Dellinger RP et al, Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic
shock: 2008. Intens Care Med 34:17, 2008

Ferrer R et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in
Spain. JAMA 299: 2294, 2008

502
Page 3
Groopman J, Hartzband P. Why quality care is dangerous The growing number of rigid protocols meant to guide
doctors have perverse consequences. The Wall Street Journal April 08, 2009.

Haynes AB et al. A surgical safety checklist to reduce morbidity and mortality in a global population. N Engl J Med
360: 491, 2009

Hicks P, Cooper DJ et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and
septic shock: 2008. An assessment by the Australian and New Zealand Intensive Care Society. Anaesth Intensive
Care 36: 149, 2008

Institute of Medicine. Clinical practice guidelines we can trust. Washington DC: National Academies Press, 2001

Morris AH. Clinical trial of a weaning protocol (commentary). Crit Care 8:2007, 2004

Quanstrum KH, Hayward RA. Lessons from the mammography wars. N Engl J Med 363: 1076, 2010

Shaneyfelt TM. In guidelines we cannot trust. Arch Int Med 172:1633, 2012

Tobin MJ. Of principles and protocols and weaning (editorial). Am J Respir Crit Care Med 169: 661, 2004

Tonelli MR et al. An official multi-society statement: The role of clinical research in the practice of critical care
medicine. Am J Respir Crit Care Med 185: 1117, 2012

Disclosure

514
Page 1
Respiratory Physiology: Gas Exchange and Respiratory Mechanics
Luca M. Bigatello, M.D. Boston, Massachusets
Respiration provides oxygen (O
2
) and removes carbon dioxide (CO
2
) for the body. An extraordinary anatomic
arrangement of functional units (the alveoli) delimited by extra-thin walls (epithelium and endothelium) creates the
interface for gas exchange between air and blood. Repetitive expansion and collapse of the chest wall facilitates
movement of gas in and out of the lungs. This review focuses on the mechanical events that regulate the exchange
of O
2
and CO
2
between the body and the outside environment.
Gas exchange.
How much O
2
gets from the atmosphere to the arterial blood- the alveolar air equation. Oxygen constitutes
approximately 21% of the air. At sea level, air exerts a pressure of 760 mmHg; once inside the airways, it is
saturated by water vapor (47 mmHg) and the partial pressure of O
2
in the inspired air (PiO
2
) can be calculated:
PiO
2
= (760 - 47) mmHg x 0.21 ! 150 mmHg
In the alveoli, one volume of O
2
is exchanged for 1.2 volumes of CO
2
(at a normal respiratory quotient [RQ] of 0.8).
Hence, with a normal PaCO
2
of 40 mmHg, the alveolar PO
2
(PAO
2
) will be:
PAO
2
= PiO
2
- PaCO
2
x 1.2 ! 100 mmHg
Past the pulmonary capillaries, the arterial blood receives a small
amount of non- oxygenated blood (e.g., from the bronchial
circulation), and the PaO
2
decreases slightly below 100 mmHg.
Causes of hypoxemia. Understanding how oxygen moves from the air
to the arterial blood (Figure 1) provides a convenient framework to
classify the various causes of hypoxemia. From top to bottom these
include:
Low PiO
2
. The most common cause of a low PiO
2
is breathing at high
altitude. As a reference, breathing air at 5,300 feet in Denver lowers
the PiO
2
from 150 to approximately 120 mmHg, and breathing air at
30,000 feet on the summit of Mount Everest lowers the PiO
2
to 40
mmHg. Although rare, causes of low PiO
2
at sea level are generally
related to the accidental administration of a hypoxic mixture.
Low PAO
2
- hypoventilation. The alveolar air equation explains how
hypoventilation, in addition to hypercarbia, can cause hypoxemia. While a normal PaCO
2
and RQ will result in a
PACO
2
of 48 mmHg and a PAO
2
of 100 mmHg, an increased PaCO
2
, e.g., 80 mmHg, will decrease the PAO
2
to 150
- 80 x 1.2 = 54 mm Hg. This scenario underlies the importance of immediately administering O
2
to the patient that
seems to be hypoventilating, as supplemental O
2
will rapidly increase PiO
2
and offset the effects of a high PaCO
2
in
the alveolus. Common causes of hypoventilation include: a) a decrease of the central drive to breathe, as it occurs
with the administration of hypnotics and opiates; b) respiratory muscle weakness, in syndromes such as Guillain-
Barre and polineuropathy of critical illness; and c) high resistive or elastic ventilatory loads (see below), as it
occurs in severe asthma and abdominal distention.
Impaired diffusion across the alveolo- capillary membrane is rare. Although this seems to contradict the observation
that the diffusing capacity of carbon monoxide for the lung (DLCO) is a sensitive test to quantify impairment of
lung function, the DLCO is primarily affected by abnormality in ventilation / perfusion ratio rather than of gas
diffusion per se.
Low PaO
2
. Under normal circumstances, the PaO
2
is slightly lower than the PAO
2
(see above). Additional increase
in this gradient occurs in physiological conditions such as aging, the sitting and supine positions, and with the
514
Page 2
induction of general anesthesia. The decrease of PaO
2
under these circumstances is due to the absence or decrease
of ventilation to variable areas of the lung, which results in shunt and low ventilation / perfusion (V/Q) ratio
respectively. These two phenomena are part of the same physiological continuum, but may have different clinical
implications.
1. Shunt occurs when there is no ventilation at all to alveoli that receive blood flow. Under these circumstances,
the PaO
2
is equal to the PvO
2
. The fraction of total pulmonary blood flow (Qt) that is shunted away from
unventilated alveoli (Qs) can be calculated from the difference in content of O
2
between the pulmonary capillary
(CcO
2
) and the arterial (CaO
2
) and venous (CvO
2
) blood, as:
Qs/ Qt = (CcO
2
- CaO
2
) / (CcO
2
- CvO
2
)
where the CcO
2
is calculated using the PAO
2
as a surrogate for the PO
2
in the capillary blood. Clinically, true shunt
occurs in the presence of intracardiac right- to- left flow, and in diverse pulmonary pathology such as atelectasis,
pneumonia, and acute lung injury / acute respiratory distress syndrome (ALI/ARDS). An important feature that
differentiates shunt from a low V/Q ration is that with shunt, increasing the PiO
2
through the administration of
supplemental O
2
will not correct the hypoxemia. The appropriate intervention to increase PaO
2
under these
circumstances is to recruit the collapsed alveoli through, e.g., the application of positive end-expiratory pressure
(PEEP).
2. Low V/Q. A low PaO
2
is due more commonly to combinations of low and high V/Q than to shunt (see below).
As V/Q decreases, the arterial blood gas tensions will approach those of the mixed venous gas (Figure 1). Two
corollaries are important. First, although the PaCO
2
should also increase towards its venous value, the extent of it is
unpredictable in the spontaneously breathing patient, as a higher PaCO
2
will rapidly stimulate alveolar ventilation
and restores normocarbia. Second, coexisting and opposite V/Q abnormalities do not average out but result in
hypoxemia. Figure 2 illustrates this phenomenon. While the O
2
content leaving the alveolus with a low V/Q
approximates the content of venous blood (16 and 14 ml O
2
/100 ml respectively in this example), the O
2
content
leaving the alveolus with a high V/Q is barely higher than in the normal alveolus (20 and 19 ml O
2
/100 ml of blood
respectively). This is due to the shape of the hemoglobin- O
2
dissociation curve: once the hemoglobin is fully
saturated, further increase in PaO
2
will dissolve in plasma, adding very little to the total content of O
2
.
Low PvO
2
. A decreased PO
2
in the mixed
venous blood (PvO
2
) will feed venous blood
with a lower PO
2
through areas of low V/Q
and shunt, further decreasing the PaO
2
. The
extent of the resulting hypoxemia is difficult
to predict, because it is affected by the
magnitude of the underlying V / Q
abnormality and because a low PvO
2
elicits
local vasoconstriction that counteracts the
low V / Q to a certain extent. However, it is
important to think of this as a cause of
hypoxemia in at least two common
circumstances in anesthesia and critical
care. First, during shivering the PvO
2
may
decrease significantly and cause hypoxemia,
which is corrected by the administration of
supplemental oxygen. Second, a low PvO
2
may result from a low cardiac output and consequent increase in O
2

extraction by the periphery; hence, hypotension from low blood flow can cause hypoxemia!
The PaCO
2
. Carbon dioxide and water are the end- products of aerobic metabolism. Carbon dioxide is stored in
tissues, and transported in blood as carbamino compounds, bicarbonate, and dissolved CO
2
. The latter determines
the PCO
2
, and is eliminated as a gas from the lungs. At steady state, the PaCO
2
results from the equilibrium
between production of CO
2
by cellular metabolism (VCO
2
) and its elimination by the lungs through alveolar
ventilation (VA):
PaCO
2
= VCO
2
/ VA
It is also important to note that the VA is linearly correlated with the PaCO
2
. In other words, if the PaCO
2
rises (see
below) the VA increases nearly instantly and steeply. Albeit with some variability, an increase of the PaCO
2
of 1
mm Hg results in an average increase of VA of 1 - 2 l/min. Of course, we know that many of the drugs that we use
in anesthesia (chiefly hypnotic and opiates) blunt this response.
Causes of hypercarbia.
Fig. 2
514
Page 3
High CO
2
production occurs with fever, shivering, excessive caloric / carbohydrate intake, and, to its maximum
extent, in malignant hyperthermia (MH) and neuroleptic malignant syndrome (NMS). However, except for MH and
NMS, the increase of VCO
2
is generally transient, and may or may not cause hypercarbia depending upon the ability
of the respiratory system to increase the VA in response to the hypercarbia. Such response may be limited in the
anesthesia practice by the administration of anesthetics, hypnotics and opiates.
Low CO
2
elimination is the most common cause of hypercarbia in anesthesia and critical care practice, and it
includes two main causes: hypoventilation and dead space ventilation.
1. Hypoventilation increases PaCO
2
by hindering the elimination of the CO
2
produced metabolically. As
discussed earlier, hypoventilation may also causes hypoxemia. Immediate treatment of hypoventilation includes
supplemental O
2
and ventilatory support.
2. High V/Q and dead space. Similarly to low V/Q and shunt, high V/Q and dead space are a continuum of the
same phenomenon. As perfusion to an alveolus decreases, the gases dissolved in the venous blood fail to reach the
alveolus; less CO
2
is eliminated, the exhaled PCO
2
decreases and, at a constant VCO
2
, the PaCO
2
will rise. These
phenomena are at the basis of the measurement of the physiological dead space fraction, which is the fraction of
unperfused (or dead) ventilatory space (Vd) over the tidal volume (Vt):
Vd/Vt phys = (PaCO
2
- PECO
2
) / PaCO
2

This definition of physiological dead space (Vd/Vt phys) includes the anatomical (proximal airways) and the
alveolar dead space (Vd/Vt alv). The Vd/Vt phys is calculated using the mean exhaled CO
2
(PECO
2
), which is
measured as the exhaled PCO
2
averaged over several breaths. While the anatomical dead space is for the most part
fixed (approximately 25% of the total ventilation) the Vd/Vt alv is the most useful of these parameters, because it is
close to 0 in normal lungs, and it increases with the inefficiency of ventilation due to disease. The Vd/Vt alv can be
calculated:
Vd/Vt alv = (PaCO
2
- PetCO
2
) / PaCO
2

where PetCO
2
is the PCO
2
at end- expiration, or end- tidal. When the expiratory flow reaches a plateau, the
PetCO
2
is highly representative of the PACO
2
. A normal PECO
2
is approximately 30 mmHg, and a normal PetCO
2

is 38 - 40 mmHg (nearly the same as PaCO
2
).
Respiratory mechanics.
Moving air in and out of the lungs- the law of motion of the respiratory system. When we breathe, we generate a
negative pressure with the respiratory muscles (Pmus) that that causes a flow (V) of gas in the airways and an
increase of volume of the lungs (Vt). Exhalation occurs by passive elastic recoil. This rhythmic movement is
opposed by the impedance of lung and chest wall (the respiratory system) composed by the resistance to flow
through the airways (Raw) and the elastance (E) or stiffness of the respiratory system. When a patient is
mechanically ventilated, the pressure to generate flow is applied from the exterior, generally a positive pressure
from a ventilator (Pvent); when a patient is partially ventilated (e.g., on pressure support ventilation) the pressure
will be a combination of negative (Pmus) and positive (Pvent) pressure. These phenomena describe the law of
motion of the respiratory system:
Paw = Pmus + Pvent = V x Raw = Vt x E
where Paw is the pressure at the airway. This relationship has important corollaries:
1. Ventilation works the same whether spontaneous, mechanical, or a combination of the two.
2. The mechanical characteristics of the respiratory system, i.e., resistance and compliance (C, the reciprocal
value of elastance), are important determinants of the effects of ventilation.
3. If we set a variable on a ventilator (e.g., Vt) and measure another (e.g., Paw) we can then calculate the third
one, Raw or C.
Bedside measurement of respiratory mechanics. Modern ventilators (included anesthesia ventilators) have the
capability to measure with acceptable precision pressure, flow and volume. A practical way to assess respiratory
mechanics during anesthesia and intensive care includes:
1. Setting the ventilator on volume- limited, constant (square- wave) flow.
2. Verifying that the patient is adequately relaxed and is not taking spontaneous breaths.
3. Performing an end- inspiratory pause (inspiratory hold), which separates the dynamic component of the
Paw (peak inspiratory pressure [PiP]) from the static component or plateau pressure (Pplat) and allows to
calculate Raw and C.
4. Performing an end- expiratory maneuver (rarely available in anesthesia ventilators) to measure the intrinsic
positive end-expiratory pressure (PEEPi).
514
Page 4
Figure 3 shows an airway pressure trace obtained as described, with the respective measurements of mechanics-
compliance and resistance:
C = Vt / Pplat PEEP
Raw = (PiP - Pplat) / V
The volume- limited mode provides the value of Vt; the end- inspiratory pause creates a semi- static condition
(Pplat) that takes away the pressure component due to airway resistance (PiP - Pplat). Normal values of C of the
respiratory system (Crs, sum of C of the lung [Cl] and of the chest wall [Ccw]) is 80 - 100 mls / cm H
2
O.
The volume- limited mode also provides a convenient
way to calculate Raw by setting the inspiratory flow
rate at 60 l/min (1 l/sec), which will allows to divide the
PiP - Pplat difference by 1. Normal Raw is 1- 3
cmH
2
O/l/sec.
Finally, it is important to understand the concept of
intrinsic PEEP (PEEPi), or auto- PEEP. During
normal ventilation (spontaneous and mechanical), at
end- expiration the lung returns to functional residual
capacity (FRC), and the alveolar pressure (estimated by
the Paw) equals atmospheric pressure (zero). When
there is expiratory flow limitation, as in asthma,
emphysema, and upper airway obstruction, the lung
volume may not reach FRC before the next breath. In
these conditions, the lung volume at end- expiration is
larger than FRC, and the alveolar pressure higher than
0. PEEPi has similar effects of externally applied
PEEP: it can increase PaO
2
and decrease cardiac output.
However, differently from applied PEEP, the PEEPi has to be overcome by the patients effort in order to start each
breath. This wasted effort (wasted because it does not generate any volume) can be taxing on subjects with
borderline respiratory function and contribute to failure. Additional complexities of respiratory mechanics relevant
to our practice include the effect of lung volume and the effect of the chest wall.
Compliance over a range of lung volumes (Figure 4). The bedside measurement of compliance described above is
carried out at the Vt set on the ventilator. Although an acceptable approximation in normal circumstances, in
conditions that decrease (ALI/ARDS) or increase (emphysema) lung volume, the relationship between alveolar
volume and pressure is no longer linear additional measurements at various lung volumes may be of value. A more
comprehensive measurement of compliance includes constructing a semi- static pressure / volume curve by
delivering a series of lung volumes, possibly from FRC to total lung capacity (TLC), with respective measurements
of Pplat. The compliance is the slope of the pressure / volume line. Under normal circumstances, this relationship is
almost linear, flattening as it nears TLC (25 - 30
cmH
2
O). In situations characterized by a low lung
compliance, such as ALI/ARDS, the shape of this
relationship changes. Here, the curve is not only
moved to the right (lower compliance) but also
assumes a sigmoid shape, indicating that at the two
extremes of lung volume (near FRC and near TLC),
compliance is much lower. This finding has potential
clinical implications:
1. Breathing over the steep part of the line is most
efficient, because it causes the least increase in
pressure for a given volume.
2. Recruiting collapsed alveoli will increase FRC
and reduce the initial flat segment of the curve. This
may be accomplished by a level of PEEP at or above
the flat segment.
3. Setting end- inspiratory pressure below the value
of the high flat segment may avoid lung overdistention
514
Page 5
In clinical practice, this kind of measurement is cumbersome and requires a high degree of expertise. Nevertheless,
the physiological principles behind it are useful to select the level of PEEP and of Pplat to set on a ventilator.
The lung, the chest wall, and the transpulmonary pressure. While we generally use the term compliance referring
to the compliance of the lungs, what we are actually measuring with the method described above is the overall
compliance of the respiratory system (Crs), which includes in equal parts the compliance of the lung (Cl) and of the
chest wall (Ccw). In many cases, changes of C
RS
are a reasonable estimate of changes of Cl. However, in certain
situations, our measurements of Pplat may not accurately estimate pressures exerted by the lung, and our use of Crs
as a surrogate of Cl may lead to incorrect decisions. To better understand these phenomena, we need to review the
concept of transpulmonary pressure (Ptp):
Ptp = Pplat - Ppl
Where Pplat is the surrogate for alveolar
pressure, and Ppl is the intrapleural pressure.
Since normal Cl and Ccw in humans are equal, if
we apply 10 cmH
2
O PEEP to the airway of a
normal subject, half of this pressure will be
transmitted across the lung, resulting in a Ppl of 5
cmH
2
O and a Ptp of 5 cmH
2
O (Table 1). If the
subject has stiff lungs (e.g., ALI/ARDS) less
PEEP is transmitted, and the Ptp will be higher; if
the subject has a stiff chest wall (e.g.,
laparoscopic surgery) more PEEP will be
transmitted and the Ptp will be lower.
Consider the circumstance of an acutely injured
lung (e.g., ALI/ARDS) that can be damaged by a
high ventilating pressures (ventilator- induced
lung injury), the Pplat. However, the pressure
that hurts the lung is not the Pplat but the Ptp.
Hence, in the ALI/ARDS lung we have to be
concerned when we reach a high Pplat (e.g., 30 cmH
2
O) because with a stiff lung the Pplat is a good estimate of the
Ptp. On the contrary, during laparoscopic surgery or during ALI/ARDS with abdominal distention, a high Pplat is
due also to a low Ccw and thus overestimates the Ptp Reducing the VT out of concern of a high Pplat under these
circumstances may lead to alveolar derecruitment and hypoventilation. The most common way to measure Ppl is via
an esophageal balloon (esophageal pressure). Unfortunately, measuring Ppl is imprecise and somewhat
cumbersome, requiring specialized equipment and significant expertise.
Another situation where the pressure measured at the airway may not correctly estimate the pressure in the alveoli
occurs when a patient is adding spontaneous breathing efforts to a set level of mechanical support, typically during
pressure support ventilation.
Here, the VT results from the combination of the pressure applied by the ventilator and the pressure generated by the
patient. Unfortunately, the latter cannot be
measured by the ventilator, and the displayed Paw
is not a reliable surrogate of the Ptp. For
example, a patient generating a VT of 700 mls on
10 cmH
2
O of pressure support may give the
impression to have an excellent Cl (C
RS
= 700
mls/10 cmH
2
O = 70 ml/cmH
2
O). However, we
do not know how much additional pressure the
patient is generating to get to that 700 mls VT.
An example of this situation is shown in Figure
5, where the proper calculation of the distending
pressure (through the use of an esophageal
balloon) shows that the patients compliance was
significantly lower that one would have estimated
just by looking at the set Paw during pressure
support ventilation.
514
Page 6
Suggested reading
1. JB West. Respiratory Physiology- The Essentials. Seventh edition. Lippincott Williams and Wilkins,
Philadelphia, 2005.
2. A Lumb. Nunns Applied Respiratory Physiology. Sixth edition. Elsevier, Philadelphia, 2005.
3. AC Guyton, JH Hall. Textbook of Medical Physiology, Eleventh edition. Elsevier, 2006.
4. West, JB. Ventilation- perfusion relationships. Am Rev Respir Dis 1977;116:919-943.
5. Mancini M, Zavala E, Mancebo J, et al. Mechanisms of pulmonary gas exchange improvement during a
protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med
2001;164:1448-145.
6. Lucangelo U, Blanch L. Dead space. Intensive Care Med 2004;30:576-579.
7. Rossi A., Gottfried SB, Zocchi L, et al. Measurement of static compliance of the total respiratory system in
patients with acute respiratory failure during mechanical ventilation. Am Rev Respir Dis 1985;131:672-677
8. Ninane V, Yernault J-C, De Troyer A. Intrinsic PEEP in patients with chronic obstructive pulmonary disease.
Am Rev Respir Dis 1993;148:1037-1042
9. Lucangelo U, Bernab F, Blanch L. Respiratory mechanics derived from signals in the ventilator circuit. Respir
Care 2005;50:55-67.
10. Hess DR, Bigatello LM. The chest wall in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit
Care 2008;14:94-102.
11. Hess DR. Ventilator waveforms and the physiology of pressure support ventilation. Respir Care 2005;50:166.
12. Dhand R. Ventilator graphics and respiratory mechanics in the patient with obstructive lung disease. Respir
Care 2005;50:246-261.
13. Bigatello LM, Davignon KR, Stelfox HT. Respiratory mechanics and ventilator waveforms in patients with
acute lung injury. Respir Care 2005; 50:235-244
14. Harris RS, Hess DR, Venegas JG. An objective analysis of the pressure- volume curve in the acute respiratory
distress syndrome. Am J Respir Crit Care Med 2000;161:432-439.
15. Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung
injury. N Engl J Med 2008;359:2095-2104.
Disclosure

508
Page 1
Mechanical Ventilatory Support: What Every Anesthesia Provider Should Know
Michael A. Gropper, MD, PhD. San Francisco, California
Introduction:
Respiratory failure is the leading cause for admission to most intensive care units (ICUs). Providing mechanical
ventilation is a core competency for every anesthesia provider, whether in the operating room or ICU. Mortality
from respiratory failure continues to fall, in part due to the recognition that the technique of mechanical ventilation
may result in propagation of injury. A number of recent advances have identified superior techniques for the
management of patients with acute respiratory failure and the acute respiratory distress syndrome (ALI/ARDS).
Importantly, new definitions for Acute Respiratory Distress Syndrome have been developed that take into account
ventilator settings and simplify identification of these patients.
1
Figure 1. describes the new definitions. In order for
the clinician to develop an understanding of modern mechanical ventilation, this lecture will review new
understanding of the pathophysiology of ventilator associated lung injury (VALI) and new techniques for the
management of patients requiring mechanical ventilation. In the last year, three clinical trials focused on
management of severe respiratory failure have informed current practice.
Pathophysiology
Ventilator Associated Lung Injury
Patients with ALI/ARDS usually require mechanical ventilation, yet the process of mechanical ventilation itself can
induce or worsen lung injury.
2,3
To understand the rationale behind the various modes of mechanical ventilation, we
must first examine how the interactions between the ventilator and the lung. The mechanisms for VALI are
multifactorial, and include:
1. Volutrauma: Direct injury to alveoli from over-distention of the lung.
2. Barotrauma: Injury resulting from high intra-pulmonary air pressures.
3. Biotrauma: Lung and distant organ injury resulting from the release of inflammatory mediators into the
airspaces and into the systemic circulation.
4. Atelectrauma: Injury to alveoli resulting from the cyclic collapse and opening of atelectatic alveoli.
Volutrauma: Mechanical ventilation with large tidal volumes causes both physiologic and histologic injury to the
lung. This phenomenon can be separated from barotrauma, since when thoracic expansion is prevented, high
inspiratory pressures without lung expansion do not cause injury.
4
In patients with ALI/ARDS, the lung
parenchyma tends to be heterogeneous, with atelectasis in dependent areas of the lung, and relative over-expansion
in the non-dependent areas. When a mechanical ventilatory breath is delivered, it will distribute according to
regional compliance. Heterogeneity in compliance may result with large tidal volumes being delivered to normal or
already overdistended lung regions. Limitation of tidal volume can prevent regional overdistention, and was the
basis of the successful ARDSnet trial.
5
It is likely that the most important determinant of volutrauma is end-
inspiratory volume, rather than the tidal volume delivered. There is no convincing evidence that volutrauma occurs
in normal lungs until tidal volumes are very large.
Barotrauma: It can be difficult to separate the effects of high inspiratory pressure from those of high tidal volume.
In patients with ALI/ARDS, edema, infiltration of inflammatory cells, and formation of hyaline membranes all
contribute to worsened pulmonary compliance.
6
Regardless of the mode of mechanical ventilation used, inspiratory
pressures are increased. Peak inspiratory pressures (PIPs) are increased from a combination of decreased static and
dynamic lung compliance, and large and small airway secretions. As opposed to PIP, it is likely that the most
important determinant of barotrauma is the inspiratory plateau pressure. It is this pressure that most accurately
reflects end-inspiratory volume, and therefore lung injury. Keeping plateau pressure below 35 cmH
2
O is a
reasonable target to minimize barotraumas, and has been associated with improved outcomes.

508
Page 2
Biotrauma: Mechanical ventilation, especially with large tidal volumes, results in inflammatory mediator release
into the alveolar space and systemic circulation.
7-10
When lung epithelial cells are stretched, they are stimulated to
produce these inflammatory mediators. These mediators have local and systemic effects identical to those seen in
severe sepsis. It is in this manner that patients presenting with primary pulmonary pathology, such as pneumonia,
can progress to multiple organ dysfunction syndrome (MODS). A large number of mediators have been implicated,
including TNF!, IL-1, IL-6, and metalloproteinases.
11
There are no specific strategies to prevent biotrauma, other
than targeting prevention of VALI.

Atelectrauma: The cyclic opening and closing of atelectatic alveoli results in the phenomenon of atelectrauma.
ALI/ARDS results in pulmonary edema, and the inflammatory mediators and proteases released into the alveolar
space can disrupt the functioning of surfactant.
6
These patients often have pleural effusions, and the combination of
these factors result in significant atelectasis, best appreciated on CT scan.
12
When the atelectatic lung is inflated,
there is thought to be transmission of high shear pressures to the delicate alveolar wall. At very low tidal volumes,
lung compliance is low, up to what is termed Pflex, where atelectatic alveoli start to be recruited, and lung
compliance improves. To avoid this region of low lung compliance, and avoid atelectrauma, positive end-expiratory
pressure (PEEP) can be set to a level higher than Pflex. Alternatively, alveolar recruitment maneuvers can be
employed. The efficacy of these maneuvers is discussed in the section on protective mechanical ventilation.

Protective Mechanical Ventilation

Protective mechanical ventilation refers to the practice of setting the mechanical ventilator with the goal of
minimizing lung injury.
13
There is no single, agreed upon approach to protective ventilation, yet most strategies
share the basic components of low tidal volumes and permissive hypercapnea. This section will review the rationale
for this practice, along with the major clinical trials demonstrating its efficacy.

Traditionally, patients with ALI/ARDS were mechanically ventilated with large tidal volumes. A 1996 survey by
Carmichael et al found that tidal volumes greater than 10 ml/kg were routinely used.
14
Clinicians used these larger
tidal volumes because in general, when tidal volume and therefore mean airway pressure are increased, oxygenation
improves. With recent understanding of the detrimental effects of mechanical ventilation, a number of studies have
been carried out in order to identify the most efficacious (least injurious) method to support patients with
ALI/ARDS. After identification of volutrauma as a probable mediator of VALI, the first study to prospectively test
low tidal volumes was that by Hickling et al, who used low tidal volume and permissive hypercapnea in patients
with ARDS.
15
Following this landmark study, a number of prospective clinical trials were performed testing
protective ventilation, culminating in the ARDSnet trial.
5

The ARDSnet trial was a randomized, prospective trial comparing traditional tidal volume (12 ml/kg ideal body
weight) to low tidal volume (6 ml/kg IBW). All patients received assist-control ventilation, and were weaned by
protocol. Specific targets were set for all ventilator parameters, including rate, PEEP, FiO2, and management of
acidosis. A total of 861 patients were enrolled, and the trial was halted early by the data safety monitoring board
because of efficacy in the low tidal volume group. The important outcomes in this study included a reduction in
mortality from 40% to 31%, an increase in the number of ventilator-free days, and a decrease in non-pulmonary
organ system failures. There was a considerable amount of controversy regarding this study, focused primarily on
the use of 12 ml/kg in the control group.
16
Subsequent investigation fully supported the results of the trial, and at
this time, ventilation of patients with ALI/ARDS should be according to the ARDSnet protocol. This study
contained an important surrogate outcome: patients in the high tidal volume group had significantly improved
oxygenation in the first two study days, yet increased mortality. This finding suggests that biotrauma, with remote
organ injury, is a critical component of the efficacy of protective mechanical ventilation.

An important component of the ARDSnet trial was the selection of PEEP and FiO
2
parameters. As stated
previously, levels of PEEP that exceed Pflex were thought to protect against atelectrauma, and possibly improve
outcomes. Adverse effects of high levels of PEEP include increased risk of barotrauma and decreased venous
return. The ARDSnet group examined the effect of higher levels of PEEP compared to traditional levels of PEEP,
when used in conjunction with 6 ml/kg IBW tidal volume. They were unable to demonstrate additional benefit
when higher levels of PEEP were used, and therefore the same PEEP/FiO2 parameters employed in the ARDSnet
trial are recommended. Similarly, recruitment maneuvers, where the lung is subjected to prolonged periods of
continuous positive airway pressure, have been attempted to try to recruit atelectatic lung. Recruitment maneuvers

508
Page 3
in patients with severe ALI/ARDS can be dangerous, as venous return may decrease significantly, causing
hypotension, and alveolar ventilation is decreased, which may result in respiratory acidosis. In general, recruitment
maneuvers have been found to only transiently increase oxygenation, without changing outcome.
17
At this time,
routine use of recruitment maneuvers cannot be recommended. Figure 2 demonstrates pressure-volume curves
derived when normal and injured lungs are mechanically ventilated with either normal tidal volumes or with
protective ventilation.

More recently, lung protective mechanical ventilation has been validated in a prospective cohort study. Needham et
al demonstrated an 8% reduction in overall mortality when there was 100% adherence to a lung protective
strategy.
28

Prone Mechanical Ventilation

Patients with ALI/ARDS develop dependent atelectasis. Atelectatic areas of the lung cause intrapulmonary shunting
and ventilation/perfusion mismatching, both of which lead to hypoxemia. In addition, dependent atelectasis results
in regional compliance differences, and may contribute to volutrauma in normal lung segments. Computerized
tomography of patients with ARDS clearly shows this relationship.
12
If these changes are gravity dependent, then it
is logical to assume that if the patient is turned from the supine to the prone position, that they would dissipate,
resulting in improved gas exchange. Although there are other, theoretical advantages to prone positioning such as
higher functional residual capacity and improved secretion drainage, it is improved oxygenation that has spurred the
enthusiasm for this technique. The mechanisms whereby prone mechanical ventilation might improve oxygenation
are shown in Figure 3. There are substantial logistical problems to prone positioning, including accidental
extubation, line or chest tube removal, and padding of the facial area. Gattinoni et al performed a multicenter,
prospective, randomized trial in patients with ALI/ARDS comparing supine positioning to placing patients in the
prone position for six or more hours per day for 10 days.
18
They studied 304 patients, and did not identify a
difference in mortality. They did find a significant improvement in oxygenation, but as the ARDSnet trial taught us,
this is not a valid outcome parameter in patients with ALI/ARDS. Recently, Guerin et al published a randomized,
prospective trial of prone positioning in patients with ARDS. 446 patients were randomized to protective ventilation
or prone positioning for at least 16 hours a day. Unlike Gattinoni, Geurin et al found significantly reduced 28-day
(16% prone, 33% supine) and 90-day mortality (24% prone, 41% supine) with prone positioning.
31

High Frequency Ventilation

High frequency osciallatory ventilation (HFOV) employs small tidal volumes and a high respiratory rate in an effort
to minimize inspiratory pressures in the injured lung.
19
Whereas traditional mechanical ventilation uses respiratory
rates from approximately 2-40 breaths/minute, HFV uses rates up to 100 breaths/minute, and high frequency
oscillation (HFOV) uses rates as high as 2,400 breaths/minute. In general, HFV results in increased mean airway
pressure without increasing PIP, but also is less efficacious for CO2 removal than traditional ventilation. This
technique is frequently used in neonatal respiratory failure, but remains controversial.
20
The trials that have been
conducted in adults, similar to those trials of prone positioning, have been able to demonstrate improved
oxygenation, but not reduced mortality.
21
HFOV has recently been reviewed, including its role in lung protection
during mechanical ventilation.
22
Earlier this year, two randomized, prospective, controlled trials of HFOV were
published. In the OSCILLATE trial performed in Canada, patients were randomized to HFOV or conventional
ventilation.
29
The trial was stopped after enrollment of 548 patients due to increased mortality in the treatment
group. There was no benefit from HFOV, and the HFOV patients required more pressors and neuromuscular
blockade. The OSCAR trial had similar enrollment criteria, and also did not find benefit from HFOV.
30

Dual Control Modes of Mechanical Ventilation

Traditional mechanical ventilation tends to be volume-cycled (synchronized intermittent mandatory ventilation and
assist control ventilation) with the thought that critically ill patients should have guaranteed minute ventilation.
Pressure limited mechanical ventilation may limit inspiratory pressures, but does so at the expense of guaranteed
minute ventilation; a rapid decrease in lung compliance may result in significant alveolar hypoventilation. Dual
control modes of mechanical ventilation try to exploit the advantages of both these methods: limiting inspiratory
pressure while ensuring adequate minute ventilation. A theoretical advantage is improved patient comfort, as the

508
Page 4
ventilator can respond instantaneously to increased flow demand. There are a large number of proprietary dual
control modes, depending on the ventilator manufacturer. This fact alone dampens the enthusiasm for this
technique, as a clinician may not be familiar with the modes if multiple ventilators are used in an ICU.
Microprocessor technology now allows a ventilator to change pressure and flow variables both between breaths
(Pressure Regulated Volume Control {PRVC}) and within a breath (Adaptive Support Ventilation).

For example, with PRVC (Siemens), the clinician chooses a minimum respiratory rate, target tidal volume, and
upper pressure limit. The ventilator continuously monitors tidal volume and minute ventilation, and if minute
ventilation falls behind, can increase inspiratory pressures up to the limit in order to catch up. None of the dual
control modes have been demonstrated to improve outcomes, including mortality, length of ICU stay, or duration of
mechanical ventilation.

Continuous Positive Airway Pressure for Postoperative Respiratory Failure

Hypoxemia is a common postoperative complication in patients undergoing abdominal surgery, and a portion of
those patients will go on to requiring reintubation.
23
Postoperative care of these patients should include lung re-
expansion therapies such as incentive spirometry and intermittent positive pressure breathing (IPPB). A recent
prospective trial examined the efficacy of continuous positive airway pressure (CPAP) in preventing postoperative
hypoxemia and decreasing the incidence of reintubation in patients who had undergone abdominal surgery
24
.
Squadrone et al compared 6 hours of oxygen therapy by facemask to CPAP at 7 cmH
2
O in 209 patients. They
measured the need for intubation in the first seven days after surgery. Ten percent of the control group required
intubation, whereas only 1% of the CPAP group required intubation. The event rates for pneumonia, infection, and
sepsis were lower in the CPAP group as well. Criticisms of the study include the large number of patients excluded
(1332 patients were enrolled, but only 209 were randomized), and the fact that the control group received only
supplemental oxygen, without other postoperative respiratory therapy maneuvers. A recent meta-analysis of nine
clinical trials has confirmed the benefit of CPAP in preventing postoperative pulmonary complications.
24

Recruitment Maneuvers in ARDS

ARDS is characterized by alveolar flooding and abnormalities in surfactant function. This results in alveolar
collapse, ventilation-perfusion mismatching, and hypoxemia. Use of positive end-expiratory pressure (PEEP) will
recruit collapsed lung units, allowing them to participate in oxygenation and ventilation. One solution to recruiting
collapsed lung is to turn patients prone, whereas another technique is to use high levels of CPAP repeated at regular
intervals. This results in opening of collapsed alveoli, improved oxygenation, and decreased airway pressures.
There is little data, however, that these benefits are more than transient. Gattinoni et al studied the amount of
potentially recruitable lung using CT scanning in patients with ARDS.
26
Using airway pressures of 5, 15, and 45
cmH
2
0, they found wide variability in the amount of recruitable lung. They also found that the proportion of
potentially recruitable lung was correlated with the physiologic response to PEEP. This suggests that PEEP should
be chosen based on the potential recruitability of the lung parenchyma.

How Much PEEP Should We Use?

Although it has been demonstrated that PEEP can improve oxygenation, as can be seen from the literature on prone
mechanical ventilation and recruitment maneuvers that transient improvement in oxygenation doesnt mean that
patients will show improved outcomes. A recent meta-analysis examined 2299 patients in 3 large trials comparing
lower to higher PEEP levels in patients with ALI and ARDS. Overall, there was no improvement in outcome in the
patients with ALI treated with higher PEEP. However, higher PEEP levels were associated with improved survival
in the subset of patients with ARDS. There were no differences in vasopressor use or in the incidence of
pneumothorax.
27

Performance of Newer Generation Anesthesia Ventilators

Earlier models of anesthesia ventilators suffered from poor performance when ventilation demands were high. The
combination of poor lung compliance and high minute ventilation demand require that the ventilator deliver
effective minute ventilation in order to avoid hypercapnea and respiratory acidosis. Maximum ventilatory capacity
can be calculated for a specific ventilator by using the mean inspiratory flow versus airway pressure curves, and the

508
Page 5
maximum allowable inspiratory duty cycle (the ratio of inspiratory time to total breathing cycle duration). This
approach permits prediction of ventilator performance for patients with high minute ventilation requirements. With
low lung compliance, inspiratory flow rate falls as airway pressure increases. The clinical implication of this finding
is that alveolar ventilation will fall. Recognition of the limitations of anesthesia ventilators is critical as patients
that are acidotic may not tolerate the respiratory acidosis associated with hypoventilation. In addition, the ventilator
tubing used with ICU ventilators tends to be much less compliant than the tubing used with anesthesia ventilators.
This means that in patients with high airway pressures, a larger fraction of the tidal volume will be wasted in
tubing expansion when anesthesia ventilator tubing is used. When a patient with severe respiratory failure requires
mechanical ventilation in the operating room, consider using an ICU ventilator for transport and in the OR if peak
inspiratory pressures are greater than 50 cmH
2
O and minute ventilation is greater than 15 liters/minute.
Summary:

Although mechanical ventilation can be life saving, the way in which it is employed can have significant impact on
the propagation of further lung injury. This article describes the various types of VALI and identifies strategies to
avoid further injury. The most robust of these strategies is tidal volume limitation, with a target of 6 mL/kg ideal
body weight. Other adjuncts such as prone mechanical ventilation and recruitment maneuvers have not significantly
lowered mortality. The most recent data on oscillatory ventilation suggests that this strategy is also no more
effective than the use of low tidal volume.
29,30
The newer generation of ventilators that allow dual control hold the
promise of better synchrony with the patient, but data is lacking regarding whether they can offer real outcomes
improvement.

References

1. ARDS Definition Task Force: Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan
E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun
20;307(23):2526-33.
2. Hudson LD: Progress in understanding ventilator-induced lung injury. Jama 1999; 282: 77-8
3. Pinhu L, Whitehead T, Evans T, Griffiths M: Ventilator-associated lung injury. Lancet 2003; 361: 332-40
4. Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of
high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988;
137: 1159-64
5. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and
the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med
2000; 342: 1301-8
6. Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334-49
7. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of
mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a
randomized controlled trial. Jama 1999; 282: 54-61
8. Ranieri VM, Giunta F, Suter PM, Slutsky AS: Mechanical ventilation as a mediator of multisystem organ
failure in acute respiratory distress syndrome. Jama 2000; 284: 43-4
9. Shimabukuro DW, Sawa T, Gropper MA: Injury and repair in lung and airways. Crit Care Med 2003; 31:
S524-31
10. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatory strategies increase cytokines
and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997; 99: 944-52
11. Pittet JF, Mackersie RC, Martin TR, Matthay MA: Biological markers of acute lung injury: prognostic and
pathogenetic significance. Am J Respir Crit Care Med 1997; 155: 1187-205
12. Goodman LR, Fumagalli R, Tagliabue P, Tagliabue M, Ferrario M, Gattinoni L, Pesenti A: Adult
respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical, and functional
correlations. Radiology 1999; 213: 545-52
13. Moloney ED, Griffiths MJ: Protective ventilation of patients with acute respiratory distress syndrome. Br J
Anaesth 2004; 92: 261-70
14. Carmichael LC, Dorinsky PM, Higgins SB, Bernard GR, Dupont WD, Swindell B, Wheeler AP: Diagnosis
and therapy of acute respiratory distress syndrome in adults: an international survey. J Crit Care 1996; 11:
9-18

508
Page 6
15. Hickling KG, Henderson SJ, Jackson R: Low mortality associated with low volume pressure limited
ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med
1990; 16: 372-7
16. Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C: Meta-analysis of acute lung injury and
acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002; 166:
1510-4
17. Grasso S, Mascia L, Del Turco M, Malacarne P, Giunta F, Brochard L, Slutsky AS, Marco Ranieri V:
Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with
protective ventilatory strategy. Anesthesiology 2002; 96: 795-802
18. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P,
Fumagalli R, Pelosi P, Brazzi L, Latini R: Effect of prone positioning on the survival of patients with acute
respiratory failure. N Engl J Med 2001; 345: 568-73
19. Krishnan JA, Brower RG: High-frequency ventilation for acute lung injury and ARDS. Chest 2000; 118:
795-807
20. Courtney SE, Durand DJ, Asselin JM, Eichenwald EC, Stark AR: Pro/con clinical debate: High-frequency
oscillatory ventilation is better than conventional ventilation for premature infants. Crit Care 2003; 7: 423-6
21. Fort P, Farmer C, Westerman J, Johannigman J, Beninati W, Dolan S, Derdak S: High-frequency
oscillatory ventilation for adult respiratory distress syndrome--a pilot study. Crit Care Med 1997; 25: 937-
47
22. Derdak S: High-frequency oscillatory ventilation for adult acute respiratory distress syndrome: a decade of
progress. Crit Care Med 2005; 33: S113-4
23. Thompson JS, Baxter BT, Allison JG, Johnson FE, Lee KK, Park WY: Temporal patterns of postoperative
complications. Arch Surg 2003; 138: 596-602; discussion 602-3
24. Squadrone V, Coha M, Cerutti E, Schellino MM, Biolino P, Occella P, Belloni G, Vilianis G, Fiore G,
Cavallo F, Ranieri VM: Continuous positive airway pressure for treatment of postoperative hypoxemia: a
randomized controlled trial. Jama 2005; 293: 589-95
25. Ferreyra GP, Baussano I, Squadrone V, et al: Continuous Positive Airway Pressure for treatment of
respiratory complications after abdominal surgery. Ann Surg 2008;247:617-626.
26. Gattinoni, L, Cairoini P, Cressoni M, et al: Lung Recruitment in Patients with the Acute Respiratory
Distress Syndrome. NEJM 2006;354:1775-86
27. Briel M, Meade M, Mercat A, et al. Higher vs Lower Positive End-Expiratory Pressure in Patients with
Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA 2010:303:865-873
28. Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, Dennison Himmelfarb CR,
Desai SV, Shanholtz C, Brower RG, Pronovost PJ. Lung protective mechanical ventilation and two year
survival in patients with acute lung injury: prospective cohort study. BMJ. 2012 Apr 5;344:e2124
29. Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD,
Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; the
OSCILLATE Trial Investigators and the Canadian Critical Care Trials Group. High-Frequency Oscillation
in Early Acute Respiratory Distress Syndrome. N Engl J Med. 2013;368:795-805
30. Young D, Lamb SE, Shah S, Mackenzie I, Tunnicliffe W, Lall R, Rowan K, Cuthbertson BH; the OSCAR
Study Group. High-Frequency Oscillation for Acute Respiratory Distress Syndrome. N Engl J Med. 2013;
368:808-813.
31. Guerin et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med.
2013:368:2159-68.

508
Page 7
Multiple Choice Questions

1. Which of the following mechanisms associated with the development of ventilator-associated lung injury
(VALI) explains injury to other organs such as the kidney?
a. Biotrauma (correct answer)
b. Barotrauma
c. Volutrauma
d. Atelectrauma
2. Which of the following statements regarding prone positioning for mechanical ventilation are true?
Prone positioning results in:
a. Transiently improved ventilation
b. A significant reduction in mortality
c. Transiently improved oxygenation (correct answer)
d. A significant increase in mortality
3. In characterizing mechanical ventilator performance, the term duty cycle refers to:
a. The product of peak inspiratory pressure and minute ventilation
b. The ratio of mean inspiratory pressure and tidal volume
c. The ratio of inspiratory time to total breathing cycle duration (correct answer)
d. The product of minute ventilation and inspiratory time

Disclosure

113
Page 1
Intraoperative Awareness: From Neurobiology to Clinical Practice
Michael S. Avidan, M.D.
St. Louis, Missouri
Learning Objectives: Learner will be able to:
1) Describe how awareness might be generated and memories might be formed; 2) Describe evidence-based
decision pathways to prevent intraoperative awareness;
3) Understand the controversies surrounding over- and under-dosing of anesthesia;
4)
Discuss key features and limitations of depth of anesthesia monitors.
Description: This Refresher Course Lecture will provide an overview of the neurobiology of awareness and
memory. Evidence-based decision pathways for preventing intraoperative awareness will be described. The
complexity of targeting the appropriate anesthetic depth will be discussed. Difficulties, advances and challenges in
monitoring depth of anesthesia will be covered.
Keywords: Intraoperative awareness, depth of anesthesia, monitoring, neurobiology of awareness, neurobiology of
memory
Neurobiology of Awareness and Memory
Consensus is lacking among anesthesiologists regarding what is required for general anesthesia. Some argue that as
long as patients do not remember the surgery, operating conditions are good, and patients are kept safe, all the
necessary requirements for general anesthesia are met. Others believe that unpleasant conscious experiences, even if
not remembered, are unacceptable and need to be prevented with general anesthesia. Yet another perspective is that
preventing or mitigating pain is the major goal of anesthesia, although it would be hard to argue that analgesia alone
could be sufficient for general anesthesia. My perspective is that the minimum requirement for general anesthesia is
safely rendering a patient perceptively unaware, otherwise stated as safely preventing external sensory perceptions.
With unconsciousness, episodic memory formation, which depends on conscious experience, is theoretically
impossible. However, consciousness without episodic memory formation can and does occur. In order for a person
to be conscious, it is likely that they need to be aroused and key brain regions need to be networked. How arousal
and networking of brain regions could generate consciousness is unknown, however credible theories, such as
information integration, provide intriguing models. Different general anesthetic agents inhibit various arousal-
promoting nuclei in the cortex and brainstem (e.g., pontine reticular formation, latero-dorsal tegmentum /
pedunculopontine tegmentum, locus coeruleus, dorsal raphe, tuberomamilary nuclei, orexinergic nuclei, basal
forebrain, prefrontal cortex), and could additionally potentiate sleep-promoting nuclei in the venrolateral preoptic
area and other areas.
1
General anesthetics also appear to disrupt cortico-cortico and cortico-thalamic networks; in
particular communication from the frontal cortex to the parietal cortex might be interrupted with all currently used
general anesthetics.
1
Different brain regions appear to be required for explicit memory, including the hippocampus,
medial temporal lobe, parahippacampal gyrus, prefrontal cortex and other neocortical regions.
1
Yet other brain
regions, including the amygdala, the insular cortex and the anterior cingulate cortex are involed in traumatic
memory formation.
1
Given that there are non-overlapping brain regions involved in consciousness and memory
consolidation, it is unsurprising that they are dissociable processes.
Most general anesthetic agents, such as propofol and potent inhaled anesthetics, have powerful amnesic actions even
at sub-hypnotic concentrations.
2
The clinical implication of this is that patients might have episodes of awareness
during surgery without explicit memory. When arousals during surgery are very brief, explicit memory formation
might be unlikely. Usually a much higher concentration of anesthetic is required to achieve unawareness than to
achieve amnesia. In clinical practice, patients appear to lose responsiveness at higher concentrations of anesthetic
agents than the concentrations at which they regain responsiveness. Recent experimental work suggests that this

113
Page 2
might reflect a neurobiological hysteresis.
3
The clinical implication of this hysteresis is that there is a margin of
safety for the majority of patients; once rendered unconscious by an anesthetic agent at a particular concentration,
they typically regain consciousness at a much lower concentration of the agent. It is important to mention that some
patients might be resistant to the hypnotic or amnesic actions of anesthetic agents, and some patients might have
near collapse of the hypnotic hysteresis - the concentration of anesthetic at which they regain consciousness is
very close to the concentration at which they lose consciousness. Patients who have such atypical neurobiological
responses to anesthetics could potentially be at increased risk for intraoperative awareness or consciousnesses during
surgery with postoperative explicit recall.
Prevention of Awareness
There are three general approaches that are likely to be effective in preventing (many cases of) intraoperative
awareness:
4

1. Target adequate anesthetic concentration.
2. Assess purposeful patient movement.
3. Monitor the brain.
Adequate Dose
The difficulty with targeting an adequate concentration or dose is that this dose may be quite different for various
patients. In this respect potent volatile anesthetic agents currently have two distinct advantages over propofol total
intravenous anesthesia (TIVA).
5
Firstly, there is probably less inter-patient variability in hypnotic concentrations for
volatile anesthetics than there is for propofol.
6
Secondly, exhaled volatile anesthetic concentrations are routinely
monitored in real time in operating rooms around the world. The concentration of propofol is only estimated using
pharmacokinetic models. It is therefore unsurprising that the risk of awareness is higher with TIVA than with
volatile-based anesthesia. The risk of awareness with volatile anesthetics could probably be reduced even further if
alarms were set routinely for low volatile concentration. The default treatment for hypotension should perhaps be a
pressor agent, like phenylephrine, rather than aggressive lightening of anesthesia. As there is no specific
anesthetic concentration that guarantees unconsciousness in all patients (unless one were to administer an
unacceptably high dose across the board), it is important to adopt optimal analgesic strategies to limit distress if
unintended awareness does occur. Unnecessary pharmacological paralysis should also be avoided for two reasons.
First, an awake patient can move to register wakefulness and second, being awake and unable to move is frequently
very distressing.
Purposeful Patient Movement
It is difficult to distinguish purposeful movement from reflex movement in response to a noxious stimulus. When
patients move during surgery, they are usually not awake and distressed, or at least are not forming explicit
memories. In such circumstances, distress is sometimes felt by the anesthesia team, which is subjected to predictable
sarcastic comments. The knee-jerk initial response is often to administer a muscle relaxant, which could be
absolutely the inappropriate action when patients truly are awake. The anesthetic concentration required to prevent
movement is generally much higher than the concentration required to achieve unresponsiveness (and possibly
unconsciousness). This difference is especially pronounced with pure propofol anesthesia. Furthermore, volatile
agent-induced immobility is mediated largely at the spinal cord,
7,8
whereas the targets of hypnotic actions are higher
brain centers. If a patient who is not pharmacologically paralyzed does not move in response to a noxious stimulus,
it is likely that the patient is unaware. The caveat is that with various dissociated states, there might be awareness
without movement, or some patients might be unable to initiate movement when exposed to certain drugs, even
when they are awake.
9
Nonetheless, given the uncertainties regarding adequate dose and in view of the fact that no
brain monitor can reliably detect consciousness, avoiding or minimizing muscle relaxants is a worth contemplating.
When patients are pharmacologically paralyzed, one might consider increasing rather than decreasing anesthetic
concentration.
Monitor the Brain
Since the 1930s there have been staunch advocates of brain monitoring during anesthesia.
10
After all the brain is the
target organ of general anesthesia. There are several reasons why brain monitors have not yet become standard of

113
Page 3
care during anesthesia, including lack of reliability and complexity. Despite the limitations, electroencephalogram
(EEG)-based brain monitors can frequently distinguish conscious from unconscious states, especially with propofol
and potent volatile anesthetic agents. Furthermore rigorous clinical trials have found that for TIVA and compared
with routine care, clinician support incorporating EEG-based monitors is likely to decrease the incidence of
intraoperative awareness.
11-13
Ongoing research continues to yield fresh insights into the EEG changes that occur
during general anesthesia.
14
Preliminary findings suggest that an approach based on monitoring effective
connectivity between the frontal cortex and the parietal cortex could detect anesthetic-induced unconsciousness with
propofol, potent volatile agents and ketamine.
15
I believe that brain monitoring will become standard of care in
future, although improvements in monitors and diagnostic algorithms might have to occur first. Currently,
acceptable alternatives to brain monitoring include avoidance of muscle relaxants and use of a potent volatile
anesthetic agent, preferably with a low agent alarm.
16,17

Overdosing Anesthesia
A major motivation for brain monitors, other than the prevention of awareness, is to allow practitioners safely to
minimize the amount of anesthetic administered. There are different perspectives on this. Some argue that modern
anesthetic agents like desflurane are safe, and even with higher concentrations (e.g., 1 MAC) for long periods of
time, patients wake up quickly and with clear heads. Others suggest that higher anesthetic concentrations are
associated with clinically meaningful side effects, including nausea and prolonged postoperative recovery.
18,19
Even
if it were true that higher anesthetic concentrations were injurious, from various studies, especially with volatile
anesthetic agents, it does not seem that current brain monitors decrease anesthetic dose or postoperative
complications.
11,12,16,17,20
Recent concerns have arisen that higher administered anesthetic concentrations, especially
to vulnerable patients, could increase postoperative delirium and even mortality.
21-23
In particular, one large
randomized study showed that bispectral index-guided anesthesia was associated with decreased anesthetic
administration and decreased postoperative complications, including delirium.
24
The data are conflicting
25,26
and
further rigorous studies must be conducted before we can conclude that anesthetic dose should be minimized within
a clinically relevant range for vulnerable patients. Nonetheless, concerns about relative anesthetic overdose and the
potential of brain monitors to mitigate this are gaining traction, including with regulatory bodies such as the UKs
National Institute for Health and Care Excellence (NICE). Despite the fact that only 2% of anesthetists in the UK
currently routinely use EEG-based brain monitors,
27
NICE has proposed that consideration should be given to their
use not just for awareness prevention, but also for patients who might be especially vulnerable to neurological injury
during general anesthesia. This recommendation has stirred controversy and has encountered resistance.
28

Features and Limitations of Depth of Anesthesia Monitors
There are certain key criteria that should be fulfilled by an ideal depth of anesthesia (DOA) monitor.
29
The current
generation of candidate DOA monitors have many deficiencies and future monitors will probably address several of
these weaknesses. Ideally, a DOA index should meet most of the following requisites:
1. It should be founded on neurobiological principles.
2. It should discriminate accurately between consciousness and unconsciousness (or responsiveness and
unresponsiveness).
3. The index should change predictably in response to increasing and decreasing anesthetic concentrations.
4. There should be a strong correlation between the index and anesthetic drug concentrations.
5. It should have intra- and inter-patient reliability.
6. It should have a rapid response time.
7. It should e reliable with all general anesthetic agents.
8. It should be resistant to interference and should filter artifacts efficiently.
Conclusion
Our field has made major advances in the provision of general anesthesia with safe and predictable agents. The
incidence of intraoperative awareness has declined steadily over the decades and evidence-based approaches have
emerged, which, if applied, are likely to decrease the incidence even further. Two priorities facing our specialty are
to clarify whether or not anesthesia within a clinically relevant range is independently injurious and to improve on
the current generation of candidate DOA monitors so that brain monitoring is incorporated as a standard of care for
general anesthesia.

113
Page 4
References:
1. Mashour GA, Orser BA, Avidan MS. Intraoperative awareness: from neurobiology to clinical practice.
2. Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. The New England
journal of medicine 2003;348:2110-24.
3. Kelz MB, Sun Y, Chen J, et al. An essential role for orexins in emergence from general anesthesia.
Proceedings of the National Academy of Sciences of the United States of America 2008;105:1309-14.
4. Avidan MS, Mashour GA. Prevention of intraoperative awareness with explicit recall: making sense of the
evidence. Anesthesiology 2013;118:449-56.
5. Aranake A, Mashour GA, Avidan MS. Minimum alveolar concentration: ongoing relevance and clinical
utility. Anaesthesia 2013;68:512-22.
6. Smith C, McEwan AI, Jhaveri R, et al. The interaction of fentanyl on the Cp50 of propofol for loss of
consciousness and skin incision. Anesthesiology 1994;81:820-8; discussion 26A.
7. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat.
8. Zhou HH, Jin TT, Qin B, Turndorf H. Suppression of spinal cord motoneuron excitability correlates with
surgical immobility during isoflurane anesthesia. Anesthesiology 1998;88:955-61.
9. Sanders RD, Tononi G, Laureys S, Sleigh JW. Unresponsiveness not equal unconsciousness.
10. Gibbs FA, Gibbs EL, Lennox WG. Effect on the electroencephalogram of certain drugs which influence
nervous activity. Arch Intern Med 1937;60:154-66.
11. Mashour GA, Shanks A, Tremper KT, Kheterpal S, Turner CR, Ramachandran SK, Picton P, Schueller C,
Morris M, Vandervest JC, Lin N, Avidan MS. Prevention of Intraoperative Awareness in an Unselected Surgical
Population: A Randomized Comparative Effectiveness Trial. Anesthesiology 2012.
12. Myles PS, Leslie K, McNeil J, Forbes A, Chan MT. Bispectral index monitoring to prevent awareness
during anaesthesia: the B-Aware randomised controlled trial. Lancet 2004;363:1757-63.
13. Zhang C, Xu L, Ma YQ, et al. Bispectral index monitoring prevent awareness during total intravenous
anesthesia: a prospective, randomized, double-blinded, multi-center controlled trial. Chinese medical journal
2011;124:3664-9.
14. Purdon PL, Pierce ET, Mukamel EA, et al. Electroencephalogram signatures of loss and recovery of
consciousness from propofol. Proceedings of the National Academy of Sciences of the United States of America
2013;110:E1142-51.
15. Lee U, Ku S, Noh G, Baek S, Choi B, Mashour GA. Disruption of Frontal-Parietal Communication by
Ketamine, Propofol, and Sevoflurane. Anesthesiology 2013;118:1264-75.
16. Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness and the bispectral index. N Engl J Med
2008;358:1097-108.
17. Avidan MS, Jacobsohn E, Glick D, et al. Prevention of intraoperative awareness in a high-risk surgical
population. N Engl J Med 2011;365:591-600.
18. Bruhn J, Myles PS, Sneyd R, Struys MM. Depth of anaesthesia monitoring: what's available, what's
validated and what's next? Br J Anaesth 2006;97:85-94.
19. Klopman MA, Sebel PS. Cost-effectiveness of bispectral index monitoring. Curr Opin Anaesthesiol
2011;24:177-81.
20. Fritz BA, Rao P, Mashour GA, et al. Postoperative Recovery with Bispectral Index versus Anesthetic
Concentration-guided Protocols. Anesthesiology 2013;118:1113-22.
21. Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and the development of
postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clinic proceedings Mayo Clinic
2010;85:18-26.
22. Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac
surgery. Anesth Analg 2005;100:4-10.
23. Leslie K, Myles PS, Forbes A, Chan MT. The effect of bispectral index monitoring on long-term survival
in the B-aware trial. Anesth Analg 2010;110:816-22.
24. Chan MT, Cheng BC, Lee TM, Gin T. BIS-guided anesthesia decreases postoperative delirium and
cognitive decline. Journal of neurosurgical anesthesiology 2013;25:33-42.

113
Page 5
25. Kertai MD, Pal N, Palanca BJ, et al. Association of perioperative risk factors and cumulative duration of
low bispectral index with intermediate-term mortality after cardiac surgery in the B-Unaware Trial. Anesthesiology
2010;112:1116-27.
26. Lindholm ML, Traff S, Granath F, et al. Mortality within 2 years after surgery in relation to low
intraoperative bispectral index values and preexisting malignant disease. Anesth Analg 2009;108:508-12.
27. Pandit JJ, Cook TM, Jonker WR, O'Sullivan E. A national survey of anaesthetists (NAP5 baseline) to
estimate an annual incidence of accidental awareness during general anaesthesia in the UK. British journal of
anaesthesia 2013;110:501-9.
28. Pandit JJ, Cook TM. National Institute for Clinical Excellence guidance on measuring depth of anaesthesia:
limitations of EEG-based technology. British journal of anaesthesia 2013;110:325-8.
29. Whitlock EL, Villafranca AJ, Lin N, et al. Relationship between bispectral index values and volatile
anesthetic concentrations during the maintenance phase of anesthesia in the B-Unaware trial. Anesthesiology
2011;115:1209-18.
Disclosure

114
Page 1
Anesthesia For Major Orthopedic Surgery
Andrew D. Rosenberg, M.D. New York, New York
Peripheral Nerve Blocks
Issues currently being considered in regional anesthesia include: 1. Choice of technique: ultrasound (US),
peripheral nerve stimulator (PNS), or paresthesia. 2. The appropriate milliamperage (mA) and nerve response to
accept when performing regional techniques with a PNS (Can we be going too low?); 3. Superficial stimulation as a
guide to nerve location; 4. Choice of regional blocks for procedures below the elbow; 5. Choice of regional blocks
for postoperative pain relief; 6. Whether to perform blocks in anesthetized patients; and 7.Treatment of local
anesthetic systemic toxicity (LAST).
Ultrasound Guided Regional Anesthesia-
The ultrasound approach to performing regional techniques has gained popularity with advocates favoring
the ability to visualize the needle, nerves, and adjacent vascular structures and muscles in real time during
performance of the block. (1-3) When using ultrasound it is important to know the anatomy of the patient, the
terminology involved, and the pitfalls that one can encounter. Reflection of ultrasound waves back to the probe
indicates the characteristic of the substance that is being scanned. Fluid filled vessels and cysts do not reflect the
ultrasound wave, are seen as black objects on the screen and referred to as anechoic structures. Some reflection, as
from nerves and soft tissue are noted as grey structures and are referred to as hypoechoic, and strong reflection of
ultrasound waves from objects such as bones and needles are noted as white structures and referred to as
hyperechoic. The more parallel or less steep of an angle the needle is to the probe as it is advanced, the greater the
reflection of sound waves back to the probe and the better visualization of the needle. As the angle of needle
insertion increases, some sound waves from the needle are not reflected back to the probe and the ultrasound image
is not as hyperechoic. To avoid too steep an insertion angle, the object to be blocked should be in the middle of
the screen. If the needle is advanced along the long axis of the ultrasound probe, the block is being performed in-
plane and the whole shaft of the needle should be visualized. With this technique, as with all techniques, it is
important to note the needletip, and in the in-plane approach the whole needle, especially the tip should be seen. If
the needle crosses the probes long axis, by being advanced perpendicular to it, the technique is called the out of
plane approach. The important needle reflection to be noted is the point at which the reflection starts to be seen as
the needle is advanced as this is the needletip. If the needle is advanced further, a reflection is frequently still noted
as the shaft of the needle will also reflect sound waves, but the exact location of the needletip cannot be verified and
one cannot be certain where the injection is occurring. The ultrasound approach to the infraclavicular area is
performed at a point just medial to the coracoid process. The pulsating axillary artery and surrounding cords of the
brachial plexus can be visualized. Figure A-1 demonstrates the plane that the ultrasound probe cuts and figure A-2
shows the path that the needle takes to the plexus from its insertion point just below the clavicle (from Popovic et al
ref 1). The needle is advanced into the area of the lateral cord, and as local anesthetic is injected, the medication can

114
Page 2
be seen to surround the vessel. Additional injections can be made either near the medial or the posterior cords.

Figure A-1 Figure- A-2

The ultrasound view of the interscalene area (B-1 and B-2) demonstrates the circular trunks of the brachial plexus
as structures with hyperechoic rims and hypoechoic centers surrounded by the anterior and middle scalene muscles.
The carotid and internal jugular can also be noted. If the probe is moved further in a caudad direction, the brachial
plexus divisions can be seen in the supraclavicular area near the subclavian artery. Some physicians have been
performing ultrasound-guided blocks in this area. There is a concern that since the block is being performed near the
lung that a pneumothorax can occur. However, those performing the block in this location believe that the real time
visualization afforded by ultrasound guidance helps prevent against this complication.

Figure B-1 Figure B-2
For lower extremity surgery, lumbar plexus blocks can be used for procedures in the distribution of the
femoral, obturator, and lateral femoral cutaneous nerves. Fractured hip repair, femoral shaft surgery, and other
anterior femur surgery are amenable to this block. Femoral nerve and lateral femoral cutaneous nerve blocks can be
used for femoral neck fractures requiring cannulated pinning. Combined femoral and sciatic nerve blocks are
effective for procedures on the knee or distal to the knee. Postoperative pain relief after knee surgery can be
obtained with a femoral nerve block or a fascia iliaca block. In addition to single injection nerve blocks, catheters
may be used to provide postoperative pain relief by a continuous infusion of local anesthetic.
One block that does not utilize the nerve stimulator technique is the fascia iliaca block.(4) This block is
performed in a location that is between the femoral nerve and the lateral femoral cutaneous nerve so the chance of
nerve damage or inadvertent arterial or venous puncture is diminished. The block is performed in the following
manner. A line is drawn from the anterior superior iliac spine to the pubic tubercle and divided into thirds. A point is
located 2-3 cm (1) caudad to the junction of the lateral and middle thirds of the line. After a sterile prep, a local
anesthetic wheal is raised at this point. A small entry hole is made in the skin with a sharp sterile needle and then a
blunt-tip spinal needle is advanced at a 45 degree angle to the skin in a cephalad direction. A distinct pop is felt as
the fascia lata is pierced. As the needle is advanced a more subtle pop is felt as the fascia iliaca is traversed. After
obtaining the second pop, the needle is then advanced another millimeter to be certain that the side port of the blunt
tip needle, the site from which the local anesthetic is injected, is in the correct space. After initial aspiration, local
anesthetic is injected with intermittent aspiration. The local anesthetic then travels medially anesthetizing the
femoral nerve and laterally anesthetizing the lateral femoral cutaneous nerve. (4)

114
Page 3

Figure C-1 Figure C-2

Ultrasound can be used to perform a femoral nerve block for perioperative pain relief. The long axis of
the ultrasound probe is placed in the inguinal crease below the inguinal ligament in a plane, which is approximately
perpendicular to the long axis of the femur or leg. The femoral nerve is visualized next to the femoral artery and
vein. Pulsations of the femoral artery help in its identification. Ultrasound also allows visualization of the fascial
planes surrounding the nerve and veins. As the needle is advanced toward the femoral nerve from lateral to medial a
popping sensation can be appreciated. When the needle is next to the nerve local anesthetic is injected and it
surrounds the nerve. (Figure C-1 and Fig C-2, from Popovic et al ref 1)
The sciatic nerve can be visualized under ultrasound as it courses down the leg and divides in the popliteal area
(Figure D). Sciatic and popliteal US guided blocks, with and without catheters, are becoming popular.
Figure D

The question has been raised as to whether the ultrasound guided technique is safer than paresthesia or nerve
stimulator techniques. An evidence based medicine review of the topic reported that there is no evidence that UGRA
results in less injury than historic controls. (5)

114
Page 4

Nerve Stimulation and Paresthesia Techniques
In choosing between PNS or paresthesia techniques, the PNS method is preferred because of its clear
endpoint (a twitch response in the muscle group innervated by the target nerve), its high success rate (frequently >
90%), its ability to minimize paresthesias (and thus theoretically reduce the incidence of traumatic nerve injury
because the needle has come as close to the nerve as possible without actually contacting it), and its proven track
record of a long history with minimal significant complications.(6-12)
When utilizing the nerve stimulator technique, success rate is increased with knowledge of anatomy. Use
proper equipment such as an insulated needle, which localizes the source of the electric current to the tip of the
needle, and a nerve stimulator that has a digital readout in 0.1 mA increments, can be easily adjusted, and provides a
stimulus at a fixed rate. The initial stimulating current should be set low, at 1-1.5mA, depending on the nerve to be
blocked.(13,14) Searching for a twitch response at this level is usually not painful, as it takes less current to
stimulate the motor fibers (A alpha fibers) of a mixed motor and sensory nerve than the sensory or pain fibers (A
delta or C fibers). (6) The initial search mode current setting (1.0-1.5 mA) is used to localize the nerves to be
blocked. Once a twitch is obtained the stimulating current can be decreased. During this next phase or the fine tune
mode the needle is optimally positioned to obtain a twitch response in the distribution of the nerves to be blocked at
the appropriately low mA needed to produce a successful block. Try to maintain a twitch response as you dial down
the nerve stimulator. If the twitch diminishes on advancing or withdrawing the needle, maximize the twitch response
again by increasing the current or returning the needle to its prior location, change direction if necessary, then
proceed. Injection of local anesthetic should be performed when the best twitch is obtained at the lowest mA
possible (0.2-0.3 mA range). Two ml of local anesthetic is injected after negative aspiration. Loss of twitch confirms
proximity of the needle to the nerves to be blocked. After this, the remainder of the local anesthetic is injected with
intermittent aspiration. (6,7,12-15)
Some controversy exists about the proper mA to attain prior to injecting local anesthetic. With the use of
insulated needles and close attention to success rates, the mA sought prior to injection of local anesthetic has been
decreased to 0.2-0.3 mA for a number of blocks by some practitioners. Concern has been raised by others that
obtaining "too low" a current can result in nerve damage as the needle may be impaling the nerve and they suggest
levels of 0.5mA as the low point (16,17) There is no strong evidence to demonstrate that a low mA (0.2mA) current
at the time of injection is associated with the needle being intraneuronal. Accepting a twitch response as high as 0.5
mA for infraclavicular, interscalene, or axillary blocks will result in some failed blocks. High success rates without
complications have been obtained at 0.2-0.3 mA in blocks of the upper and lower extremity. (6,7,11,14,19) Higher
currents risk obtaining a twitch response when the needle and nerves to be blocked are on opposite sides of a fascial
plane. To facilitate the PNS technique, patients can receive anxiolysis but blocks should not be performed in adult
patients under general anesthesia as intraneuronal injections and even injection of the cervical spinal cord can occur
without the operator's knowledge.(18) The block should not be performed with the patient asleep and injection
should be stopped if there is unusual resistance or if the patient exhibits significant pain on injection.(18)
Superficial stimulation is a technique in which nerves are located superficially on the skin with a PNS.
(19,20) Superficial mapping facilitates performance of a block since the nerves to be blocked are located prior to
beginning the block, the entry point for the needle is determined before the patient receives a needlestick, the
number of needlesticks to which the patient is subjected is decreased, and the anesthesiologist performing the block
looks more adept. The technique can be performed with the metal component of an ECG electrode.(20) Using an
axillary brachial plexus block as an example, the brachial plexus can be located with superficial stimulation in the
axilla. The metal component of an ECG is connected to the negative lead of the nerve stimulator, and with the
current at approximately 5 mA, twitches of the brachial plexus are sought as proximal in the axilla as possible. Once
an acceptable twitch is obtained, the area is marked and becomes the needle entry location site for performing the
block.
The block should be chosen based upon the site of surgery. An interscalene block is utilized for surgery on
the shoulder down to the mid-shaft of the humerus. If a regional technique is not used for the operative procedure it
can be performed to provide pain relief after the patient is awake in the PACU and is well accepted and appreciated
by both inpatient and ambulatory patients. Infraclavicular nerve blocks are utilized for surgical procedures below the
mid-shaft of the humerus including the elbow, forearm and hand. Axillary blocks can be used for procedures on the
ulnar side of the hand. (13) Intermittent blocks or continuous catheters can be used for postoperative pain relief after
surgery.
The infraclavicular block is a very useful block. When performing the block as described by Raj, the head
is turned away from the side to be blocked and the arm is abducted 90 degrees. An insulated needle is passed at a
45-degree angle from a point 1 below the midpoint of the clavicle, drawn perpendicular to the plane of the clavicle,

114
Page 5
to the pulsation of the axillary artery in the axilla (Figures E-1 and E-2). (15) Instead of palpating for the axillary
artery, superficial stimulation can be used to locate the brachial plexus as proximal in the axilla as possible. The
needle is then passed at a 45-degree angle from a point 1 below the clavicle, perpendicular to the clavicle, to the
point determined by superficial stimulation. The endpoint is a twitch in the distribution of the median, ulnar, or
radial nerves (a twitch in the forearm, wrist, or hand) at 0.2-0.4 mA. The advantage of the infraclavicular block is
that at this level the musculocutaneous nerve is still part of the brachial plexus and there is no need for a separate
block of the musculocutaneous nerve in the coracobrachialis muscle. (12,13,15) However, the musculocutaneous
nerve is the most superficial nerve in the brachial plexus at this level (Figure E-2) and it is possible that a twitch
obtained in its distribution, a biceps twitch, may be occurring across a fascial plane or after the nerve has exited
from the sheath. The biceps twitch is not a reliable endpoint to use when performing an infraclavicular nerve block
and other twitches, those in the hand or forearm, which are generated from the median, ulnar, or radial nerve, should
be used as the endpoint. (10,22). Therefore, use the biceps twitch from musculocutaneous nerve stimulation as an
indication that you are in the correct anatomical region but need to adjust the needle.

Figure E-1 Figure E-2

Although needle direction is away from the lung when performing an infraclavicular nerve block some
prefer to perform the block more laterally. Sims modified the original Raj approach by utilizing an approach that is
slightly more lateral, but care must be taken not to increase the needle angle. (23) While we use either of the two
techniques described above, an even more lateral approach, a vertical approach, in which the needle is advanced at a
90 degree angle in the area of the coracoid process is gaining popularity. (11,24)
Local Anesthetic Systemic Toxicity (LAST)
20% intralipid has been demonstrated to be effective in reversing the cardiotoxic effects of bupivacaine
and other local anesthetics. (25,26) It should be made available for use where local anesthetic is injected in sufficient
doses to cause LAST. Remember to institute ACLS protocols as well with special attention to current
recommendations concerning use of epinephrine and vasopressin. (26,27) Recommended dosing is initial bolus of
1.5ml/kg IV followed by infusion of 0.25 mL/kg/min continued for 10 min after hemodynamic stability is attained.
Failure to achieve stability should prompt an additional bolus and increase of infusion rate to 0.5ml/kg/min.
Approximately 10mL/kg lipid emulsion for 30min is recommended as an upper limit for initial administration.
(26,27)
Spine Surgery
Current issues in patients undergoing spine surgery include understanding the degree of cervical spine
pathology as it affects endotracheal intubation and neck movement, caring for patients undergoing prolonged
surgical procedures (combined anterior-posterior spinal fusions), use of lung isolation techniques, loss of vision, and
the effect of non-steroidal anti-inflammatory medications (NSAIDS) on bone healing.
Patients presenting for spine surgery or other orthopedic procedures may be suffering from rheumatoid
arthritis (RA), ankylosing spondylitis, and other rheumatologic disorders. Difficulty in intubating patients with RA
can result from temperomandibular joint arthritis, a hypoplastic mandible, an overbite, and effects of RA on the
cervical spine.(12,13) Cervical spine pathology occurs in 80% of patients with RA and may manifest itself in a
number of ways- 1) atlantoaxial subluxation- the anterior arch of C1 and the dens or odontoid move more than 4 mm
apart from each other on flexion and extension 2) subaxial subluxation- greater than a 15% displacement of one
vertebrae on another 3) and superior migration of the odontoid in which collapse of some of the cervical vertebrae
results in displacement of the odontoid into the base of the skull through the foramen magnum. (12,13,28) Patients
with ankylosing spondylitis may present with fused cervical spines fixed in a flexed position. Forced movements can
result in cervical spinal cord damage. An organized approach to the patient with cervical spine disease, whether as a

114
Page 6
result of a rheumatologic disorder or other medical conditions, includes proper preoperative evaluation including
range of motion, consideration of x-rays in flexion and extension, and appropriate use of intubation aides such as a
fiberoptic bronchoscope or other airway assistance device to facilitate intubation.
Major spine surgery in the thorax and lumbar areas may involve anterior, posterior, or combined
procedures in one setting. The anterior component can include thoracic exposure and involve lung isolation
techniques. These procedures can take many hours and result in major blood loss and fluid shifts. Considerations
include controlling blood pressure, monitoring spinal cord function, treating blood loss, and positioning concerns.
Lung isolation techniques for open thoracic or thorascopic procedures can be obtained with a double lumen
tube or a bronchial blocker. One option is to use a Univent tube, a single lumen tube with the bronchial blocker
attached alongside. The blocker is advanced and inflated at the time of occlusion of the mainstem bronchus and then
the blocker is retracted into the casing, and the tube functions as a single lumen tube. Therefore, you do not have to
change the tube between anterior and posterior portions of the surgery. Additionally the Univent tube can be left in
place if controlled ventilation is necessary in the postoperative period. A fiberoptic bronchoscope is utilized to
position the bronchial blocker into the mainstem bronchus to be occluded. One drawback is that the external
diameter of the Univent tube is large since it encompasses both the endotracheal and the separate bronchial
blocker components. It is important to inform the postoperative care team about the type of tube you left in place.
The prone position is associated with alterations in pulmonary function, increases in venous pressure,
pressure and stretch on nerves, and visual loss. Postoperative vision loss (POVL) has become a recent concern (29-
32). A combination of factors including perioperative anemia, hypotension, prolonged surgery and resistance to
blood flow may be causal factors. (29-33) However, the etiology remains unclear. While direct pressure on the eye
can cause problems this does not appear to be the cause for the majority of cases. Ischemic optic neuropathy (ION),
a common diagnosis in postoperative visual loss may result from decreases in ocular perfusion pressure (OPP)
causing decreased blood supply to the optic nerve. Another possible etiology is a compartment syndrome within the
orbit. OPP is a function of mean arterial pressure (MAP) and intraocular pressure (IOP) and can be determined from
the formula OPP=MAP-IOP such that decreases in MAP or increases in IOP will decrease OPP. (26-33) ION may
result from decreased blood flow through the posterior ciliary arteries which are end arteries. The areas receiving
watershed blood supply from these arteries may be compromised resulting in ischemia. Cheng et al. demonstrated an
increase in intraocular pressure over time in the prone position. (31) Prone position, especially if the patient is in a
slight head down tilt, can result in edema and venous engorgement, increasing IOP. Since the etiology of vision loss
was unclear, a postoperative visual loss national database was established to identify risk factors associated with
postoperative visual loss. A report from the registry included 93 cases and pinpoints ION as the most common cause
with blood loss over 1 liter and anesthesia duration over 6 hours being present in 96% of cases. (34) An
accompanying editorial suggested staging long procedures (35). A practice advisory on POVL has recently been
updated. (36). In 2012, an analysis of cases having POVL with matched patients who did not suffer vision loss was
published and noted that male gender, obesity, use of a Wilson frame, longer cases, greater estimated blood loss and
decrease use of colloid were associated with POVL. (37)
Attempts to decrease blood loss during spine surgery include use of antifibrinolytics such as aprotinin as
well as tranexamic acid (TXA) and epsilon aminocaproic acid. (38-40) These medications do tend to decrease blood
loss in orthopedic surgical procedures. Aprotinin is no longer used do to the side effects of renal, cardiac, and
neurologic complications, the increased mortality in some patient populations, warnings circulated by the FDA
about the medication, and that the manufacturer is no longer marketing or supplying the medication. (41) With all
three medications there is a theoretical concern of increased thrombosis.
Non-specific NSAIDS such as ketorolac have been identified as interfering with bone fusion after spine
surgery. Therefore, many surgeons avoid using ketorolac in this setting. (42) Research is being conducted on the
specific COX-2 inhibitors. While studies have been performed on animal models, the recommendation for use of
COX-2 inhibitors in humans where bone fusion is desired needs further clarification. The issue of using these
medications and their effect on bone fusion is now clouded by controversy.
Intraoperative monitoring of spinal cord function may include somatosensory evoked potentials (SSEPs),
motor evoked potentials (MEPs), including transcranial motor evoked potentials, EMGs, or a wakeup test. A
nitrous oxide/oxygen, narcotic technique with an infusion of propofol and muscle relaxant is frequently utilized.
Dexmetadomidine is also used by some, as is ketamine. Benzodiazepines are avoided and only a low concentration,
a small percent of 1 MAC of inhalation agent is used, if any is used at all, so as to not effect SSEP or TCMEP
monitoring. If EMGs are monitored to assess pedicle screw placement, muscle relaxants need to be discontinued
early enough to allow for proper testing. When transcranial motor evoked potentials (TCMEPs) are employed
muscle relaxant cannot be used as well. Be careful to adequately protect the tongue and endotracheal tube in patients
having TCMEPs performed as there is a strong contraction of the masseter muscles and other muscles of mastication

114
Page 7
when the potentials are generated. These contractions can cause lacerations in the tongue and even damage the
endotracheal tube. Alterations in SSEPs and MEPs may take time, as long as half an hour, to occur after distraction
or rotation of the spine. Changes in SSEPs or MEPs may require modifications in the distraction or rotation of the
surgical correction. Be prepared to perform a wake up test if the surgeon requests it.
Since combined anterior-posterior spine procedures can be prolonged, the patient must be carefully
assessed at the end of the procedure. The degree of swelling is an important consideration prior to deciding on
extubation of the patient as significant facial swelling would be an indication to leave the endotracheal tube in place.
Hematocrit, body temperature, pulmonary function, including the effect of the thoracic procedure on respiratory
capability, and reversal of neuromuscular blockade are additional important factors to be considered.

The Beach Chair Position
Shoulder surgery is often performed in the beach chair (BC) position with the pt elevated from 30-90!. In
addition, some surgeons request hypotension. Rare reports of severe neurologic complications including stroke,
ischemic brain injury and vegetative state have occurred.(43,44) A decrease in cerebral perfusion pressure (CPP) is
present in the BC position as compared to supine due to a gradient between the level of the heart and the head. The
location of the BP cuff must be considered when figuring the actual BP at the level of the brain. An adjustment and
decrease of 0.77mm Hg for each cm of height above the level of the BP cuff should be calculated to understand the
perfusion pressure present at the Circle of Willis (COW)-which is roughly at the level of the external auditory
meatus. (43,44) Remember, there is additional brain tissue above the level of the Circle of Willis. Caution should be
used to avoid significant hypotension and decreased CPP when patients are in the BC position. (43,44)

Anticoagulation and the Orthopedic Patient
The Second Consensus Conference on Neuraxial Anesthesia and Anticoagulation (available at the ASRA
website). (45) described the issues of caring for patients with anticoagulation and provided recommendations. Other
anticoagulants or antiplatelet medications should be avoided when LMWH are used, an appropriate length of time
(10 12 hours) should elapse after the last dose of LMWH thromboprophylaxis before performing neuraxial
anesthesia, and appropriate timing of the first dose of LMWH in the postoperative period needs to be considered to
decrease the chance of spinal hematoma. (45). Another issue is the use of spinal and regional anesthesia in the
presence of clopidogrel, a potent antiplatelet medication, and how long a patient should have discontinued the
medicine before a neuraxial block is performed.. The recently published guidelines on Regional Anesthesia in the
Patient Receiving Antithrombotic or Thrombolytic therapy (Third Edition) reiterate the 7 day period that has been
suggested in the past but also include the suggestion that if neuraxial block is indicated between 5 and 7 days of
discontinuation of clopidogrel, normalization of platelet function should be documented. (46,47) Others suggest
less time and that patients can be off of clopidogrel for 5 days before surgery. As experience grows, it is expected
that these guidelines will be modified and practitioners should make themselves aware of the latest suggestions
when balancing the time a patient is off this medication with the risks of bleeding.
References:
1. Popovic J, Morimoto M, Wambold D, Blanck TJJ, Rosenberg AD. Current Practice of Ultrasound-Assisted
Regional Anesthesia. Pain Practice 2006;6:127-134
2. Sandhu NS, Capan L. Ultrasound guided infraclavicular brachial plexus block BJA 2002;89:254-9
3. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anesthesia. Br J Anaesth 2005 94(1): 7-17
4. Wambold D, Carter C, Rosenberg AD. Pain Practice 2001;1:274-277
5. Neal, Brull, Chan et al ASRA Evidence Based Medicine Assessment of Ultrasound Guided Regional Anesthesia
RAPM 2010;35:S1-S9
6. De Andres J, Sala-Blanch X. Peripheral nerve stimulation in the practice of brachial plexus anesthesia. A
review. Reg Anes Pain Med 2001;26:478-48
7. Kaiser H, Niesel HC, Klimpel L et al. Prilocaine in lumbosacral plexus block: General efficacy and comparison
of nerve stimulation amplitude. Acta Anes Scand 1992;36:692-697
8. Davies MJ, McGlade DP. One hundred sciatic nerve blocks: Aneasth Intens Care 1993;21:76-78
9. Fanelli G, Casati A, Garaneini P et al. Nerve stimulator and multiple injection technique for upper and lower
limb blockade Anesth Analg 1999;88:847-852
10. Albert DB, Bernstein RL, Rosenberg AD et al. Anesth Analg 78: S3, 1994
11. Wilson JL, Brown DL, Wong GY et al. Infraclavicular brachial plexus block AnesthAnalg 1998;87:870-3
12. Rosenberg AD Anesthesia for major orthopedic surgery. ASA Refresher Courses Chap 15 2004;32:169-178.
13.Bernstein RL, Rosenberg AD. Manual of orthopedic anesthesia and related pain syndromes NY Churchill
Livingstone, 1993

114
Page 8
14. Pither CE, Raj P, Ford DJ. The use of the peripheral nerve stimulator. Reg Anes 1985;10:49-58
15.Raj PP, Montgomery SJ, Nettles et al. Infraclavicular brachial plexus block. Anes Analg1973;52:897-902
16.Choyce A, Chan V, MiddletonW, Knight P, et al. What is the relationship between paresthesia and nerve
stimulation for axillary brachial plexus block. Reg Anes Pain Med 2001;26:100-4
17. Neal JM. How close is close enough? Defining the paresthesia chad Reg An Pain Med 2001;26:97-99
18. Benumof JL. Permanent loss of cervical spine cord function associate with interscalene block performed under
general anesthesia. Anesth 2000;93:1541-4
19. Keschner MT, Michelsen H, Rosenberg AD, Wambold D, Albert DB, Altman R, Green S, Posner M, Safety and
Efficacy of the Infraclavicular Nerve Block Performed at Low Current. Pain Practice 2006;6:107-111
20. Ganta R, Cajee RA, Henthorn RW. Letter to ed: Use of transcutaneous nerve stimulation to assist interscalene
block Anesth Analg 1993;76:914-5
21. Albert DB, Dudarevitch D, Bloom K, Rosenberg AD. Surface Stimulation to Determine Needle Direction and
Angle When Performing an Infraclavicular Brachial Plexus Block. Pain Practice 2006;6:104-106
22. Fitzgibbon DR, Debs AD, Erjavec MK. Selective musculocutaneous nerve block.. Reg Anes 1995;20:239-241
23. Sims JK. Clarification of landmarks for infraclavicular approach. Anes Analg 1977;56:554
24. Jandard C, Gentili ME, Girard F, et al. Infraclavicular block with lateral approach and nerve stimulation: extent
of anesthesia and adverse effects Reg Anesth and Pain Med 2002;27:37-42
25. Rosenblatt MA et al Successful use of a 20% lipid emulsion to resusitate a patient after presumed bupivacaine-
related cardiac arrest. Anesth 2006;105;217-18
26. Weinberg G Treatment of local anesthetic systemic toxicity RAPM 2010;35:188-193
27. ASRA Practice Advisory on Local Anesthetic Toxicity RAPM2010;35(2): 152-161
28. Skues MA, Welchew EA. Anesthesia and rheumatoid arthritis. Anaesthesia 1993;48:989
29. Roth S Perioperative Visual Loss: What do we know, what can we do? BJA 103; BJA/PGA suppl 131-140, 2009
30. Williams EL. Postoperative Blindness. Anes Clin N Am 2002;20:367-384
31. Cheng MA, et al. The effect of prone positioning on IOP in anesthetized patients. Anesth 2001;95:1351-5
32. Lee L, Lam A. Unilateral blindness after prone position lumbar spine surgery. Anesth 2001;95:793-5
33. Roth S, Barach P. Postoperative visual loss: still no answers-yet. Anesthesiology 2001;95:575-7
34. Lee L, Roth S, Posner K et al The ASA Postoperative Visual Loss Registry: Analysis of 93 Spine Surgery
Cases with Postoperative Visual Loss Anesth2006;105:652-659
35. Warner M. Postoperative Visual Loss Experts Data and Practice Anesthesiology 2006 105:641-642
36. Practice Advisory for Perioperative Visual Loss Associated With Spine Surgery Anesth 2012;116:274-85
37. Risk Factors Associated with Ischemic Optic Neuropathy after Spine Surgery Anesthesiology 2012; 116:15-24
38. Neilipovitz DT et al. A Randomized Trial Of TXE to Reduce Blood Transfusion Anes Anal 2001;93;82-87
39. Urban MK et al The Efficacy of Antifibrinolytics in the Reduction of Blood Loss During Complex Adult
Reconstructive Spine Surgery Spine 2001;26;1152-1157
40. ZuffreyP et al. Do Antifibrinolytics Reduce Allogeneic Blood Transfusion in Orthop Surg Anes 2006;105:1034
41. Mangano DT et al. The Risk Associated with Aprotinin in Cardiac Surgery NEJM 2006;354:353-65
42. Glassman SD, Rose SM, Dimar JR, et al. The effect of Postoperative Nonsteroidal Anti-inflammatory Drug
Administration on Spinal Fusion. Spine 1998;23:834-838.
43. Pohl A, Cullen DJ Cerebral Ischemia during shoulder surgery in the upright position: a case series J Clin
Anesth 2005;17:463-469
44. Cullen DJ, Kirby RB. Beach Chair Position May Decrease Cerebral Perfusion Pressure Catastrophic Outcomes
Have Occurred APSF Newsletter 22:2,25 Summer 2007
45. 2nd Consensus Conference on Neuraxial Anesthesia & Anticoagulation2002, R Anes Pain Med 2003;28:172
46. Horlocker TTet al Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy
(Third Edition) RAPM 2010;35:64-101
47. Horlocker TT et al Executive Summary: Regional Anesthesia in the Patient Receiving Antithrombotic or
Thrombolytic Therapy (Third Edition) RAPM 2010; 35:102-105

Disclosure

121
Page 1
Top 10 Respiratory Anesthesia Practices That Drive Me Crazy
David O. Warner, M.D. Rochester, Minnesota
As ever-more sophisticated ventilators are incorporated into anesthesia machines, there is increasing confusion
regarding both the physiological principles pertinent to perioperative respiratory management and their clinical
implications. Many of the practices commonly employed have little or no evidence to support them, nor are they
supported by a convincing physiological rationale. This lecture is an opportunity to vent about some of our
irrational or sloppy practices, and is designed to be deliberatively provocative. The conclusions may be open to
debate, but hopefully any such debate will help you consider your practice on the basis of evidence and physiology,
rather than on the basis of thats how weve always done it. Here are my personal top 10 (in no particular order).
1. Wimpy preoxygenation
Preoxygenation prior to anesthesia induction is a time-honored procedure applied routinely in anesthesia practice.
When properly performed, it prolongs the duration that apnea can be maintained without arterial oxygen
desaturation, a useful outcome if unanticipated airway difficulties arise. However, proper technique is often not
applied. For example, the facemask is lightly placed on the patients face, such that there is significant entrainment
of room air around the edges of the mask. The facemask seal must be sufficient so that all the inspired gas comes
from the anesthesia circuit and bag, rather than via room air entrainment. .Because peak airflow during inspiration
may approach 60 L/min, with typical fresh gas flows of 6 L/min the effective inspired oxygen fraction is
approximately 40% if a proper seal is not obtained. This will significantly reduce the apneic time prior to
desaturation. Many ventilatory maneuvers during preoxygenation have been described, ranging from normal tidal
breathing to vital capacity inspiration, most of them equally efficacious, but all depend on an adequate mask fit.
One way to objectively evaluate the quality of preoxygenation is to monitor the end-tidal oxygen fraction aim for
at least 80% prior to proceeding.
So take the time to do it right, every time and monitor the efficacy of your technique.
2. Routine ventilator settings
Many anesthesiologists were taught in training to use the following ventilator settings intraoperatively: tidal volume
= 10 ml/kg and rate = 10-12/min. These settings will routinely produce significant hyperventilation. The rationale
for these settings includes:
1) higher tidal volumes will prevent atelectasis and improve oxygenation;
2) respiratory rates of 10-12 are physiologic, and;
3) hypocarbia is good, hypercarbia is bad.
121
Page 2

However..
1) High tidal volumes, at least in the ranges used to maintain ventilation in modern practice, do not prevent or
reverse atelectasis and do not consistently improve gas exchange. Resolution of intraoperative atelectasis requires
recruitment maneuvers (prolonged, high airway pressures), not higher tidal volumes as we will see in point #5
below. Indeed, higher tidal volumes certainly hurt lungs that are already injured, and may have deleterious effects in
even normal lungs;

2) Because metabolic demands are decreased during anesthesia, it is not necessary to maintain an awake
respiratory ratewhich in any event widely varies among individuals;

3) Other than for some neurosurgical cases, hypocapnia is not beneficial. Indeed, there is some evidence that
hypercarbia may be beneficial. For example, hypercarbia causes peripheral vasodilation and increases tissue
oxygenation, which could help prevent wound infection (although this remains to be shown). There is also
fascinating study (which to my knowledge has not been repeated) suggesting that intraoperative hypocapnia delays
emergence.

So consider using lower tidal volumes (in the 5-6 ml/kg range) and lower breathing frequencies that will maintain at
least normocarbia.

3. Routine use of mechanical ventilation and paralysis
Anesthesiologists in the US frequently employ pharmacologic paralysis and mechanical ventilation, even for cases
in which neuromuscular blockade is not required to accomplish the procedure, or cases in which patients could
easily maintain spontaneous breathing. Indeed, when patients move after the induction of anesthesia, the first
response is often to administer a neuromuscular blocking drug. After all, the surgeons will be happier and wont
yell if the patients dont move, I can use less anesthetic drugs which avoids hypotension and hastens emergence, and
in fact we always do it that way. And if I just turn on the ventilator, I dont have to worry about whether the patient
will be adequately ventilated its a ventilator, right? Plus, succinylcholine is now persona non grata at many
institutions, committing patients to extended paralysis if nondepolarizing neuromuscular blocking drugs are used to
facilitate endotracheal intubation.

Here are a few reasons to reconsider routine mechanical ventilation/paralysis:

1) Positive pressure ventilation requires a more-or-less secure airway. Endotracheal intubation is not a benign
intervention; if the only indication for an endotracheal tube is to provide mechanical ventilation, consider whether
you really need mechanical ventilation. Many use positive pressure ventilation with supraglottic airways such as the
LMA, but remember that unless properly seated, the gas may be delivered to locations you do not wish to receive it
(e.g., the stomach).

2) When patients move, they are generally telling you give me more anesthesia rather than please paralyze me.
Use of neuromuscular blocking drugs is a risk factor for intraoperative awareness, which is rare (but not unheard of)
in a patient who is not paralyzed. There are many other risks associated with neuromuscular blocking drugs,
including anaphylactic and anaphylactoid reactions and postoperative respiratory complications associated with
incomplete reversal of block.

3) Just like our anesthetic forefathers (and foremothers), you can learn a lot by watching patients breathe. For
example, parameters such as end-tidal CO
2
maintained during spontaneous breathing depend on anesthetic depths,
such that central respiratory control mechanisms can serve as an excellent integrated neurophysiology monitor for
overall anesthetic effects. This can be a useful tool to help administer anesthesia, for example to titrate opioid
supplementation at the end of cases to facilitate smooth, painless emergence. There also may be situations in which
gas exchange is better maintained if physiologic diaphragmatic contraction is also maintained, as spontaneous
breathing can be associated with improved ventilation-perfusion matching during anesthesia.

So use mechanical ventilation/paralysis because it is specifically indicated for a patient, not as a matter of
routine.or as a substitute for adequate anesthesia

121
Page 3


4. Assisted ventilation
Patients breathing spontaneously under anesthesia often receive assistance a squeeze on the bag every now and
then to augment tidal volume, or in todays world one of numerous modes of pressure support, again designed to
augment tidal volumes. The rationales behind this practice are that increased tidal volumes will improve atelectasis,
and that this practice will augment minute ventilation and improve hypercapnia.

However, there are inconvenient truths that make this reasoning suspect. We have already discussed that increasing
tidal volumes, at least to the relatively modest degree used in assisted ventilation, does not improve atelectasis or
oxygenation. And is it possible to significantly augment minute ventilation during spontaneous breathing under
anesthesia, and still maintain spontaneous ventilatory effort? When patients are breathing spontaneously under
volatile anesthesia, there is an apneic threshold a value of arterial PCO
2
below which ventilatory effort (i.e.,
respiratory muscle activity) ceases. This threshold is 4-5 cm below the arterial PCO
2
maintained during spontaneous
breathing, largely independent of anesthetic or the depth of anesthesia. So if you want to maintain your patients
respiratory effort, you can only achieve modest decreases in PCO
2
with assisted ventilation.

So although assisted ventilation may keep your hand (or your anesthesia ventilator) busy and make you feel like
you are doing something useful, the reasoning supporting its use is questionable at best.

5. PEEPed out
General anesthesia nearly always causes atelectasis in dependent areas of the lung, which represents a major (but not
the only) source of gas exchange abnormalities during anesthesia. When combined with other abnormalities of chest
wall mechanics such as obesity, intraoperative hypoxemia may occur. A frequent response is to simply dial in 5-10
cm H
2
O of positive end-expiratory pressure (PEEP) which sometimes seems to help in ICU patients, right?
Unfortunately, the isolated application of PEEP is unlikely to reverse intraoperative atelectasis. Rather,
recruitment maneuvers are required, involving sustained (30-40 seconds), high (approximately 40 cm H
2
O) airway
pressures. PEEP applied after recruitment maneuvers can help prevent the reformation of atelectasis. Also, a high
inspired fraction of O
2
can accelerate the reoccurrence of atelectasis so keep the F
I
O
2
below 80% if possible.
Intraoperative atelectasis can also persist into the postoperative period and cause impairment of gas exchange, so it
is worth considering recruitment maneuvers prior to extubation at the end of the case.

So intraoperative hypoxemia is often caused by dependent lung atelectasis, which is best treated by recruitment
maneuvers followed by PEEP dont just turn on the PEEP.

6. Mode madness
Newer generations of anesthesia machines are equipped with sophisticated ventilators that provide many of the same
features of those ventilators utilized in intensive care units. These are touted by their manufacturers as major
advances in anesthesia technology, and it is indeed fun to play with the dials (or rather the touchscreen) for those
who are mechanically inclined.
However, keep three things in mind.
1) There is little to no evidence that any mode of intraoperative ventilation has any effect on outcomes, despite
multiple attempts to prove benefits of the latest mode-of-the-month. This has largely been true even in the
intensive care unit all we really know is that high tidal volumes are bad.

2) The multiple modes of ventilation available on modern anesthesia machines provide multiple opportunities for
confusion and misuse. Anecdotal experience suggests that many providers do not really understand how the
ventilators operate, and this lack of knowledge can have consequences. For example, providers may assume that the
patient is breathing spontaneously with a pressure-support mode, and not recognize the absence of spontaneous
ventilatory effort. This can make for an interesting extubation experience.

3) In their zeal to optimize the performance of their ventilators, manufacturers have compromised abilities basic to
the functioning of the anesthesia machine (in my opinion). For example, allowing pediatric patients to breathe
spontaneously with some modern machines results in significant rebreathing of CO
2.

121
Page 4

So if you choose to indulge in mode madness, please recognize that it is for your benefit, generally not for the benefit
of your patients, and make sure you understand how that fancy ventilator works.

7. Why is my vaporizer broken?
Now that the monitoring of inhaled and exhaled gases is widespread, anesthesia personnel have noted apparent
discrepancies between the set volatile anesthetic concentration and the actual inspired anesthetic concentration,
sometimes prompting concerns that there is a malfunction of the machine.

However.remember that anesthesia circle systems allow rebreathing of exhaled gas, with the amount of
rebreathing dependent on the balance between fresh gas flow into the circuit and minute ventilation. With lower
flows, more rebreathing occurs. If this happens say early in induction, the rebreathed gas will be relatively poor in
anesthetic, and the inhaled anesthetic concentration will be less than the set anesthetic concentration. The opposite
consideration applies during emergence. This phenomenon is as old as the use of volatile agents but only recently
have we had the technology to see it routinely!

So remember that if you wish to rapidly change the inspired concentration of a volatile anesthetic (or to wash out
agent at the end of the case), you need to use high fresh gas flows and dont worry, the vaporizer is fine..

8. What, no pediatric circuit?
For smaller children, we often use anesthesia circuits with small diameters, and smaller anesthesia bags. Do we
really need to use smaller circuit equipment for smaller people? When asked why, people often mumble something
about dead space.

However.remember that the dead space in a circle system extends only distal to the Y-junction the diameter of
the tubing leading to and from the Y-junction makes no difference to dead space. There is the concept of
compression volume that applies during positive pressure ventilation. This represents ventilation that is lost due
to the increase in pressure that occurs in the limbs of the ventilator circuit. The lower the volume of each limb of the
circuit, the lower the compression volume. However, the magnitude of this effect is trivial for normal airway
pressures used during intraoperative ventilation, only about 2% of the delivered volume is lost. So this is not
much of a reason to use smaller circuit equipment. It is true that with a smaller anesthesia bag, it is easier for the
educated hand to detect changes in compliance, tidal volume, etc.

So use whatever circuit you wish for your smaller patients but dont panic if the pediatric circuits are not
available.

9. Two puffs is enough
When patients develop intraoperative bronchospasm, they are often treated using aerosolized drugs such as
albuterol. However, it can be quite challenging to administer aerosols to anesthetized patients via an endotracheal
tube. Even under the best of conditions in ambulatory patients, only a minority of the total amount of drug
administered by a metered dose inhaler actually reaches the small airways. Even less is delivered when
administered via an endotracheal tube, with only 5-10% of an administered dose being delivered to the airways.
Thus, simply attaching a metered dose inhaler to the elbow of the breathing circuit and administered two puffs
(hopefully at the right portion of the respiratory cycle) is unlikely to produce an adequate therapeutic effect.
Suggestions to improve drug delivery include: 1) consider using nebulizers rather than metered dose inhalers if
available in a timely fashion; 2) use a spacer device in the inspiratory limb of the circuit, and; 3) increase the
number of puffs to account for decreased efficiency of delivery.

Usually two puffs is not enough so dont be afraid to administer more puffs to obtain the necessary therapeutic
effect.

10. Dont stop smoking!
One of the most pernicious and persistent myths in perioperative medicine is that quitting smoking shortly before
surgery will actually increase the risk of pulmonary complications, supposedly because of increased cough and
sputum production. Multiple studies have now shown that this is absolutely not true quitting smoking at any time
121
Page 5

prior to surgery will not increase the rate of any complication. Anesthesiologists are in a unique position to help
their patients quit smoking, and should take every opportunity to help them do so. Surgery serves as a teachable
moment for smoking cessation, as having major surgery can double the chances that patients can quit successfully.
This will improve both immediate perioperative outcomes and long term health.

So any time is the right time for patients to quit smoking even shortly before surgery.

In summary
You may or may not agree with all these points, but hopefully this presentation will help you consider the evidence
and the physiology that underlies these and other practices in perioperative respiratory management so that you can
make your own rational choices.

Highly selected references (#s refer to which point is addressed)

McGowan P, Skinner A: Preoxygenation--the importance of a good face mask seal. Br J Anaesth 1995; 75: 777-8
(#1)

Cai H, Gong H, Zhang L, Wang Y, Tian Y: Effect of low tidal volume ventilation on atelectasis in patients during
general anesthesia: a computed tomographic scan. J Clin Anesth 2007; 19: 125-9 (#2)

Fleischmann E, Herbst F, Kugener A, Kabon B, Niedermayr M, Sessler DI, Kurz A: Mild hypercapnia increases
subcutaneous and colonic oxygen tension in patients given 80% inspired oxygen during abdominal surgery.
Anesthesiology 2006; 104: 944-9 (#2)

121
Page 6

Hovorka J: Carbon dioxide homeostasis and recovery after general anaesthesia. Acta Anaesth Scand 1982; 26: 498-
504 (#2)
Plaud B, Debaene B, Donati F, Marty J: Residual paralysis after emergence from anesthesia. Anesthesiology 2010;
112: 1013-22 (#3)

Mahour G, Orser BA, Avidan MS: Intraoperative awareness: from neurobiology to clinical practice. Anesthsiology
2011; 114: 1218-1233 (#3)

Hickey RF, Fourcade HE, Eger EI, 2nd, Larson CP, Jr., Bahlman SH, Stevens WC, Gregory GA, Smith NT: The
effects of ether, halothane, and Forane on apneic thresholds in man. Anesthesiology 1971; 35: 32-7 (#4)

Duggan M, Kavanagh BP: Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology 2005; 102: 838-
54 (#5)

Warner DO, Warner MA, Ritman EL: Atelectasis and chest wall shape during halothane anesthesia. Anesthesiology
1996; 85: 49-59 (#5)

Benoit Z, Wicky S, Fischer JF, Frascarolo P, Chapuis C, Spahn DR, Magnusson L: The effect of increased FIO(2)
before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95: 1777-81 (#5)

Tusman G, Belda JF: Treatment of anesthesia-induced lung collapse with lung recruitment maneuvers. Curr
Anaesth Crit Care 2010; 21: 244-249 (#5)

Aldenkortt M, Lysakowski C, Elia N, Brochard L, Tramer MR: Ventilation strategies in obese patients undergoing
surgery: a quantitative systematic review and meta-analysis. Br J Anaesth 2012; 109: 493-502 (#6)

Crogan SJ, Bishop MJ: Delivery efficiency of metered dose aerosols given via endotracheal tubes. Anesthesiology
1989; 70: 1008-10 (#9)

Shi Y, Warner DO: Brief preoperative smoking abstinence: is there a dilemma? Anesth Analg 2001; 113:1348-1351
(#10)

Warner, DO: Helping surgical patients quit smoking: why, when, and how. Anesth. Analg.2005; 101: 481-487
(#10)

Disclosure

126
Page 1
Perioperative Glycemic Management: Anesthesiologists Manual
Basem B. Abdelmalak, M.D. Cleveland, Ohio
Introduction: Every day anesthesiologists are faced with new and often conflicting research results regarding
perioperative glycemic management. This review will outline a practical and comprehensive plan for perioperative
glycemic management based on the available evidence. Topics discussed include: the prevalence of pre-operative
hyperglycemia and the decision making process for proceeding with or delaying surgery, intraoperative
hyperglycemic surgical stress response and the added effect of perioperative steroid, risks associated with hyper and
hypoglycemia, a recommended target for perioperative glucose concentration, principles and strategies for safe
intraoperative insulin dosing, postoperative glycemic management and a proposed algorithm for managing diabetic
patients on continuous insulin pump therapy perioperatively.
The Prevalence of Preoperative Hyperglycemia and Undiagnosed Diabetes: Diabetes mellitus (DM) affects
8.3% of the US population.
1
Fifty percent of diabetics will require surgery during their lifetime. A third to half of
patients with type 2 DM do not know they are diabetic at the time of surgery.
2
Abdelmalak et al, retrospectively
reviewed the records of 35,000 noncardiac surgery patients and found that 21% of the patients without a diagnosis of
diabetes are hyperglycemic and more than half of those have undiagnosed diabetes.
3
Similar findings have been
reported by Hatzakorzian and colleagues who prospectively studied 500 noncardiac surgery patients.
4
Among the
nondiabetics, patients who are older, male,
3,4
with higher BMI, and higher ASA-PS,
3
are more likely to have
hyperglycemia.
The Clinical Practice Guidelines from The Endocrine Society 2012 recommend blood glucose (BG) testing in all
patients on admission to the hospital (including admissions for surgery) regardless of their diabetic status and further
monitoring of admitted nondiabetics with BG > 140 mg/dL for 24-48 hours with appropriate therapeutic
intervention. They also recommend Hb A1c testing for inpatient nondiabetics whose BG concentration is >140
mg/dL, and all diabetics if it has not been done in the prior 2-3 month period.
5
These recommendations are on the
basis of high prevalence of inpatient hyperglycemia, and its associated poor outcomes and the opportunity to
diagnose diabetes.
5
Identifying the undiagnosed diabetics and directing them to the appropriate care has the potential
to impact these patients beyond the perioperative period, but rather their overall life-long well-being. Early diagnosis
and treatment of type 2 diabetes might well reduce its burden and its complications.
6,7

Pre-op Hyperglycemia and Outcomes in Noncardiac Surgery: Retrospective data is supporting the notion that
pre-operative hyperglycemia is harmful in the perioperative setting. A case-control study in the Netherlands
examined preoperative blood glucose levels and mortality in noncardiac, non-vascular surgery patients and found
that preoperative BG levels greater than 200 mg/dL were associated with a 2.1-fold increased risk in overall
mortality and a 4-fold increased cardiovascular mortality risk.
8

Another study in Canada showed a direct relationship between glucose concentration and the risk of pulmonary
embolism (PE) with up to a 4-fold increased risk in patients undergoing total joint replacement with preoperative
levels greater than 200 mg/dL.
9
In cardiac surgery patients, pre-operative BG > 110 mg/dL has been associated with
a longer hospital stay and increased mortality.
10
Abdelmalak, et al, examined data on 62,000 relatively high risk
patients who underwent elective noncardiac surgery. One-year mortality but not composite outcome of in-hospital
morbidity including cardiopulmonary and infectious complications, was independently associated with preoperative
blood glucose concentration.
11
Additionally, hyperglycemia is associated with increased production and/or impaired
scavenging of reactive oxygen species,
12
polymorphonuclear neutrophil dysfunction,
13
and decreased intracellular
killing.
14,15
It is thus unsurprising that poor wound healing and increased infection risk are established detrimental
effects of hyperglycemia.
16
Now, that the association of hyperglycemia with poor outcomes has been established,
the question then arises, should we cancel surgery for any identified hyperglycemia?

126
Page 2
Cancelling Surgery for Pre-operative
Hyperglycemia: Unfortunately current data offer no
concrete guidance on whether an elective procedure
should be cancelled in light of a given level of
hyperglycemia. Furthermore, if the surgery gets
cancelled, there is no data to support that if a specific
optimal target glucose concentration is achieved and
maintained for a given optimal duration of time
preoperatively, that it would in fact result in
improvement in surgical outcomes.
Patients scheduled for surgery (and family and loved
ones) have already re-planned their lives, and took time
away from work to be available for this surgery and
psychologically prepared for it. Cancelling their surgery
would constitute a major inconvenience with potential
financial implications to the patient/family and the
hospital to say the least. Therefore, the decision should
be an individualized one, depending on the surgery,
patient characteristics including chronic glycemic state,
clinicians experience with glucose management, etc.
That said, many clinicians do not end up cancelling
elective surgery for mild to moderate hyperglycemia but
rather treat it, and the associated osmotic diuresis
induced hypovolemia. On the other hand, many believe
that it might be prudent to cancel elective surgery. when
faced with glucose concentrations >350 mg/dL and /or
any concentration associated with diabetic ketoacidosis
(DKA) and/or hyperosmolar state;
17,18
DKA can easily
be diagnosed based on the clinical presentation and when certain simple laboratory criteria are met; the triad of
Hyperglycemia > 250 mg/dL, acidosis (arterial pH <7.3, serum bicarb < 18 mEq/l, and anion gap of >10) and
ketonemia, urine and serum ketones are positive.
19

To avoid hyper and hypoglycemia preoperatively in patients diagnosed with diabetes and treated with oral
hypoglycemics and/or insulin,
several plans have been recommended for scheduling their medications and doses preoperatively. Table 1, presents
one of these popular algorithms that is currently being used at the authors institution.
Diabetics and nondiabetics, who should we monitor, and/or treat?: Abdelmalak and colleagues have shown that
patients without a diagnosis of diabetes and with preoperative hyperglycemia had higher one-year mortality than
patients with diabetes with the same level of preoperative hyperglycemia. Patients with diagnosed diabetes and
preoperative glucose concentrations in the lower euglycemic range had higher one-year mortality than patients
without diabetes with the same levels of preoperative euglycemia.
11
Such findings highlight the complex
relationship between glucose metabolism and outcomes and corroborates with the evidence from the ICU as well.
Hyperglycemia upon admission to the ICU has been shown to be an independent risk factor for in-hospital mortality
only in patients without diabetes.
20
By the same token, Krinsley and colleagues showed that diabetics had better
outcomes at higher targets than nondiabetics in the ICU.
21

Collectively, both diabetics and nondiabetics, should be monitored and treated, and emerging evidence suggests that
treating hyperglycemia may be more beneficial for nondiabetics compared to diabetics.
Hyperglycemic surgical stress response: Major surgical procedure ! release of catecholamines, glucagon,
cortisol, and growth hormone ! insulin resistance, glycogenolysis, gluconeogenesis ! hyperglycemia. Recently,
Abdelmalak et al have described the magnitude of intraoperative hyperglycemic response to surgical stress during
major noncardiac surgery that is inversely proportional to the starting pre-operative glucose concentration, and the
intraoperative pattern of that response in patients with and without diabetes diagnosis (figure 1-A).
22
As noted, all
patients had a sizable intraoperative hyperglycemic response, albeit those who did not have the diagnosis of diabetes
had a more pronounced steeping rise compared to those diagnosed. Most of that rise was from incision to the mid
surgery time point.
The same investigators,
22
have also described the hyperglycemic effects of a small dose of steroids (8 mg of
dexamethasone IV) on glucose concentrations in patients with and without diabetes (figure 1-B). Surprisingly,
patients with diabetes who received steroids, compared to those who received placebo, did not have significantly

126
Page 3
different glucose concentrations. However, those without diabetes who received dexamethasone showed a small
increase (approximately 30 mg/dL) compared to those who received placebo.

Fig. 1: Pattern of intraoperative hyperglycemic stress response over time in diabetics and nondiabetics ( A), and the
added effects of 8 mg of IV dexamethasone given preoperatively in all patients (B).
22
Reprinted with permission
from Anesthesia and Analgesia.

Such factors indicate that whatever methodology or algorithm one would use intraoperatively to manage
hyperglycemia ought to be a dynamic one, i.e. adjusts to the above mentioned factors that may impact the
intraoperative glucose concentration such as the one the author utilized in a prior study,
23
and currently uses a
modified version.
24
(figure 2)
Intraoperative Management:
Intraoperative management is aimed at treating hyperglycemia, and avoiding hypoglycemia. Prevention and
treatment of hyperglycemia has been shown to improve outcomes, on the other hand, tight glucose control did not.
In the ICU, a retrospective study by Krinsley et al showed that insulin treatment reduced mortality, prevented lethal
sepsis, reduced severe infections and multi-organ failure, and protected the central and the peripheral nervous
systems.
25
In a landmark paper, Van den Berghe and colleagues showed in a prospective randomized trial that
intensive insulin therapy to maintain blood glucose at or below 110 mg/dL substantially improved ICU outcomes.
26

However a more recent trial aimed at treating hyperglycemia targeting tight glycemic control (80-110 mg/dL) did
not improve outcomes.
27
Furthermore, some investigations of intensive insulin therapy in the ICU report a higher
risk of hypoglycemia without a mortality benefit.
27-30

In the perioperative period, a prospective study of 2,467 cardiac surgical patients revealed that continuous IV insulin
infusion reduced the incidence of deep sternal wound infection in diabetic patients after cardiac surgery.
Subsequently, the same authors found that continuous insulin infusion reduced mortality in patients with diabetes
undergoing coronary artery bypass grafting.
31,32
However, A single center randomized trial by Gandhi et al where
they randomly assigned 400 cardiac surgery patients to tight glycemic control (80-100 mg/dL) intraoperatively or
usual care (no insulin during surgery unless BG levels were > 200 mg/ dL) did not show difference in outcomes
between the two groups.
33
Carvalho et al studied the effects of a glucose, insulin, potassium (GIK) regimen while
maintaining normoglycemia (the so-called GIN therapy) during cardiac surgery and showed that such a strategy
confers more cardioprotection than standard care which utilized the same GIK but did not maintain
normoglycemia.
34
.

The hyperinsulinemic clamp technique remains under investigation.
35

Duncan and colleagues, in their retrospective study, reported that in cardiac surgery, intraoperative glucose
concentrations > 200, and < 140 mg/dL were associated with increased morbidity and mortality, and 141-170 mg/dL
was a safer range.
36
In a recent randomized trial, Abdelmalak et al, reported that intraoperative tight glucose control
did not improve surgical outcomes in patients undergoing major noncardiac surgery.
37
Finfer and colleagues in their
randomized trial in ICU patients, showed that a range of 140-180 mg/dL was associated with improved outcomes
compared to a higher target of 180-200.
27
Thus, current recommendations favor more moderate targets in the
range of 140-180 mg/dL.5
,
27
,
38
Route of insulin administration perioperatively: While the subcutaneous route is being viewed as a safe route by
many clinicians and may have a role in managing moderate hyperglycemia in ambulatory surgery patients,
39
, it has
the disadvantages of a very slow onset compared to IV as well as longer duration of action, that makes titratability a
challenging task to say the least, and would not allow for timely management of dangerously severe hyperglycemia
and thus the risk of stacking doses and the resulting hypoglycemia.
39
In addition, the change in the subcutaneous

126
Page 4
circulation, due to fluid shifts and change of temperature from exposure to cold operating rooms, to forced air skin
warming devices application make SQ absorption variable and not very reliable.

Fig. 2 An example of an intraoperative insulin infusion titration algorithm targeting moderate glucose control 140-
180 mg/dL. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography 2013. All rights
reserved.

Another important point to discuss is that if the SQ route is the route used perioperatively, an insulin regimen in the
form of a long acting basal, with boluses (preprandial, and to treat episodic hyperglycemia) is preferred over the
traditional sliding scale of insulin (SSI).
5
SSI is based on repeated responses to hyperglycemia resulting in glucose
variability that has been found to correlate with poor outcomes in various populations. Glycemic variability is an
independent risk factor for mortality in the ICU.
40,41
and in septic patients.
42
This may explain why the use of
insulin infusion with boluses, presumably with better glucose management and low variability, results in less all-

126
Page 5
cause mortality and fewer poor cardiac outcomes than intermittent IV bolusing of short-acting insulin despite the
same glycemic control target.
43

Thus the intravenous infusion approach is recommended whenever feasible especially in long surgery. The
intravenous algorithm used will need to be a dynamic one adjusting for variability in individual patients response,
the stage of surgery and other factors affecting intraoperative glucose concentrations (see above discussion on
hyperglycemic surgical stress response, and the added effects of steroid administration), such algorithm should also
dictate when glucose measurements should be performed, and an intervention plan for detected hypoglycemia. An
example of such protocol is presented in Fig. 2.
24
In all cases, no one algorithm will replace a physicians judgement
which is essential in making decisions in dosing and titrating insulin perioperatively.
Intraoperative Insulin Sensitivity: Some insulin dosing algorithms include patient-related factors such as weight,
5

and diabetic status,
44,45
while others do not.
27-29
There is no consensus about which baseline factors should be
included, although insulin sensitivity has been related to various factors in non-operative settings. In noncardiac
surgery, it appears as if the diabetic status , and body weight contribute little if any (contrary to the common belief)
to the response to a given insulin bolus.
46
Regardless of the insulin sensitivity, the use of a dynamic insulin
algorithm like the one presented (fig.2) in which insulin dosing does not depend only on the measured glucose
concentration but also on the delta change from the prior measurement which should account for differences in
insulin sensitivity resulting from identified or unidentified factors as well as other factors influencing glucose
concentrations like the administration of glucose containing solutions, and glucose containing cardioplegic solutions
in cardiac surgery.
Safety of Glycemic Control: While hyperglycemia is detrimental, hypoglycemia is not without risk. Hypoglycemia
per se can increase mortality and morbidity and results in increased neurological damage. Severe hypoglycemia was
shown to result in somnolence, unconsciousness, seizures,
47
and when sustained sufficiently irreversible
neurologic sequelae and/or death.
48
Not only severe but also moderate hypoglycemia was found to be associated
with mortality in ICU patients.
49
Clinicians understandably are concerned about tightly controlling glucose
perioperatively due to the high incidence of hypoglycemia in association with intensive glucose control;
27-29,50
whose
symptoms are masked by general anesthesia and sedation,
51
and no proven benefit.
27-29
Even when we were able to
tightly control glucose without inducing severe hypoglycemia in noncardiac surgery patients,
23
no benefit was
shown.
37
that is why a moderate control target has been proposed especially since they have been proven beneficial
at least in the ICU population.
27

Management of diabetic patients with insulin pumps: Fig 3 outlines a proposed plan for perioperative
management of insulin pump patients that is being utilized currently at the authors institution. The reader is referred
to reference number 24 for a comprehensive discussion of this topic, and rationale for every proposed step in this
algorithm.
24

Postoperative Glycemic Management: In noncardiac surgery patients, Ramos et al,
52
in their retrospective study of
995 patients, concluded that postoperative hyperglycemia increased the risk of postoperative infections irrespective
of diabetic status. A larger study by Frisch et al
53
retrospectively studied the records of over 3000 noncardiac
surgery patients and found that hyperglycemia resulted in worse outcomes (postoperative infections, acute renal
failure, and acute myocardial infarction, 30-day mortality), as well as longer ICU and hospital stays. In both cardiac
and noncardiac surgery, postoperative hyperglycemia increased the infectious complication risk,
54
thus avoiding
hyperglycemia is recommended postoperatively, and moderate targets are preferred.
5
In doing so, the so called basal
bolus regimen has been found to be superior to the SSI approach.
55
And more recently, both basal bolus and basal
plus regimens have both been more effective compared to SSI.
56
It is thought that compared to SSI, the latter two
techniques provide less glycemic variability which has been linked to poor outcomes as discussed above.
Glucose Measurement: The central laboratorys measurement of blood glucose remains the gold standard however
it is costly, and takes time. Point of care testing (POCT) devices while they tend to overestimate the actual glucose
concentration value,
57
they are cheap, readily available and fast; providing a good resource for implementing
effective glucose management strategy.
5
The continuous interstitial fluid glucometer, although it is convenient and
provides frequent readings, has the disadvantage of a lag period between blood and tissue glucose concentrations.
When one methodology is used (such as POCT), the sampling site and the methodology should remain consistent
throughout the procedure.

126
Page 6

Fig. 3: Perioperative Glycemic Management in Insulin Pump Patients Undergoing Noncardiac Surgery. Reprinted
with permission, Cleveland Clinic Center for Medical Art & Photography 2013. All rights reserved.

Summary: An alarming proportion of our surgical patients are hyperglycemic and many are undiagnosed diabetics.
Hyperglycemic surgical stress response is real, and is not linear throughout surgery. Perioperative steroids induce a
small hyperglycemic response. Close monitoring of blood glucose levels intraoperatively is of prime importance
especially if treatment has been initiated. Symptoms and signs of hypo and hyperglycemia are for the most part
masked by general anesthesia. Consequences of untreated hypoglycemia are grave. Current evidence supports IV
insulin infusion for BG management intraoperatively. Insulin pump patients should be managed very carefully
according to a standard protocol.

126
Page 7
Conclusions: Glucose control should be implemented to some degree for hyperglycemic patients. Intra-op tight
glucose control is not beneficial neither in cardiac nor in noncardiac surgery. It is pre-mature to mandate certain
glucose values in light of insufficient evidence. Current recommendations call for moderate control.
References

1. Center for Disease Control: National Diabetes Fact Sheet, 2011
2. Center for Disease Control and Prevention: Prevalence of diabetes and impaired fasting glucose in adults-
United States,1999-2000. Morb Mortal Wkly Rep 2003; 52: 833-7
3. Abdelmalak B, Abdelmalak JB, Knittel J, Christiansen E, Mascha E, Zimmerman R, Argalious M, Foss J:
The prevalence of undiagnosed diabetes in non-cardiac surgery patients, an observational study. Can J
Anaesth 2010; 57: 1058-64
4. Hatzakorzian R, Bui H, Carvalho G, Shan WL, Sidhu S, Schricker T: Fasting blood glucose levels in
patients presenting for elective surgery. Nutrition 2011; 27: 298-301
5. Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, Van den
Berghe G: Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine
society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 16-38
6. The effect of intensive treatment of diabetes on the development and progression of long-term
complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial
Research Group. N Engl J Med 1993; 329: 977-86
7. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care
2003; 26 Suppl 1: S5-20
8. Noordzij PG, Boersma E, Schreiner F, Kertai MD, Feringa HH, Dunkelgrun M, Bax JJ, Klein J,
Poldermans D: Increased preoperative glucose levels are associated with perioperative mortality in patients
undergoing noncardiac, nonvascular surgery. Eur J Endocrinol 2007; 156: 137-42
9. Mraovic B, Hipszer BR, Epstein RH, Pequignot EC, Parvizi J, Joseph JI: Preadmission hyperglycemia is an
independent risk factor for in-hospital symptomatic pulmonary embolism after major orthopedic surgery. J
Arthroplasty; 25: 64-70
10. Cammu G, Lecomte P, Casselman F, Demeyer I, Coddens J, Morias K, Deloof T, Nobels F, Van
Crombrugge P, Foubert L: Preinduction glycemia and body mass index are important predictors of
perioperative insulin management in patients undergoing cardiac surgery. J Clin Anesth 2007; 19: 37-43
11. Abdelmalak B, Knittel J, Abdelmalak J, Dalton J, Christiansen E, Foss J, Argalious M, Zimmerman R, Van
den Berghe G: Preoperative Blood Glucose Concentrations and Postoperative Outcomes Following
Elective Noncardiac Surgery. Br J Anaesth 2013: In Press
12. Van den Berghe G: How does blood glucose control with insulin save lives in intensive care? J Clin Invest
2004; 114: 1187-95
13. Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP: Insulin infusion improves neutrophil
function in diabetic cardiac surgery patients. Anesth Analg 1999; 88: 1011-6
14. Nielson CP, Hindson DA: Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose
concentrations in vitro. Diabetes 1989; 38: 1031-5
15. Perner A, Nielsen SE, Rask-Madsen J: High glucose impairs superoxide production from isolated blood
neutrophils. Intensive Care Med 2003; 29: 642-5
16. McMurry JF, Jr.: Wound healing with diabetes mellitus. Better glucose control for better wound healing in
diabetes. Surg Clin North Am 1984; 64: 769-78
17. Fasanmade OA, Odeniyi IA, Ogbera AO: Diabetic ketoacidosis: diagnosis and management. Afr J Med
Med Sci 2008; 37: 99-105
18. Akhtar S, Barash PG, Inzucchi SE: Scientific principles and clinical implications of perioperative glucose
regulation and control. Anesth Analg; 110: 478-97
19. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM: Management of
hyperglycemic crises in patients with diabetes. Diabetes Care 2001; 24: 131-53
20. Whitcomb BW, Pradhan EK, Pittas AG, Roghmann MC, Perencevich EN: Impact of admission
hyperglycemia on hospital mortality in various intensive care unit populations. Crit Care Med 2005; 33:
2772-7
21. Krinsley JS, Egi M, Kiss A, Devendra AN, Schuetz P, Maurer PM, Schultz MJ, van Hooijdonk RT,
Kiyoshi M, Mackenzie IM, Annane D, Stow P, Nasraway SA, Holewinski S, Holzinger U, Preiser JC,
Vincent JL, Bellomo R: Diabetic status and the relation of the three domains of glycemic control to
mortality in critically ill patients: an international multicenter cohort study. Crit Care 2013; 17: R37

126
Page 8
22. Abdelmalak BB, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, Sessler DI: The
hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in
patients with and without diabetes. Anesth Analg 2013; 116: 1116-22
23. Abdelmalak B, Maheshwari A, Kovaci B, Mascha EJ, Cywinski JB, Kurz A, Kashyap VS, Sessler DI:
Validation of the DeLiT Trial intravenous insulin infusion algorithm for intraoperative glucose control in
noncardiac surgery: a randomized controlled trial. Can J Anaesth 2011; 58: 606-16
24. Abdelmalak B, Ibrahim M, Yared JP, Modic MB, Nasr C: Perioperative glycemic management in insulin
pump patients undergoing noncardiac surgery. Curr Pharm Des 2012; 18: 6204-14
25. Krinsley JS: Effect of an intensive glucose management protocol on the mortality of critically ill adult
patients. Mayo Clin Proc 2004; 79: 992-1000
26. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D,
Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in the surgical intensive care unit. N Engl J
Med 2001; 345: 1359-67.
27. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson
WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R,
Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill patients. N
Engl J Med 2009; 360: 1283-97
28. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M,
Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E,
Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K: Intensive insulin therapy and pentastarch
resuscitation in severe sepsis. N Engl J Med 2008; 358: 125-39
29. Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, Groeneveld J, Iapichino G, Leverve X,
Nitenberg G, Singer P, Wernerman J, Joannidis M, Stecher A, Chiolero R: A prospective randomised
multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care
units: the Glucontrol study. Intensive Care Med 2009; 35: 1738-48
30. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, Inzucchi SE, Ismail-Beigi
F, Kirkman MS, Umpierrez GE: American Association of Clinical Endocrinologists and American
Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract 2009; 15: 353-69
31. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A: Continuous intravenous insulin infusion reduces the
incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures [see
comments]. Ann Thorac Surg 1999; 67: 352-60; discussion 360-2
32. Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A: Continuous insulin
infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac
Cardiovasc Surg 2003; 125: 1007-21
33. Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, O'Brien PC, Johnson MG, Williams AR,
Cutshall SM, Mundy LM, Rizza RA, McMahon MM: Intensive intraoperative insulin therapy versus
conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med 2007; 146:
233-43
34. Carvalho G, Pelletier P, Albacker T, Lachapelle K, Joanisse DR, Hatzakorzian R, Lattermann R, Sato H,
Marette A, Schricker T: Cardioprotective Effects of Glucose and Insulin Administration While Maintaining
Normoglycemia (GIN Therapy) in Patients Undergoing Coronary Artery Bypass Grafting. J Clin
Endocrinol Metab 2011; 96: 1469-77
35. Sato H, Hatzakorzian R, Carvalho G, Sato T, Lattermann R, Matsukawa T, Schricker T: High-dose insulin
administration improves left ventricular function after coronary artery bypass graft surgery. J Cardiothorac
Vasc Anesth 2011; 25: 1086-91
36. Duncan AE, Abd-Elsayed A, Maheshwari A, Xu M, Soltesz E, Koch CG: Role of intraoperative and
postoperative blood glucose concentrations in predicting outcomes after cardiac surgery. Anesthesiology
2010; 112: 860-71
37. Abdelmalak B Bonilla A, Mascha E, Maheshwari A, Tang WHW, You J, Ramachandran M, Kirkova Y,
Clair D, Walsh M, Kurz A, Sessler DI: The Dexamethasone, Light Anaesthesia, and Tight Glucose Control
(DeLiT) randomized controlled trial. Br J Anaesth 2013 Mar 28; . [Epub ahead of print]

38. Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu AR, Bridges CR, Haan CK,
Svedjeholm R, Taegtmeyer H, Shemin RJ: The Society of Thoracic Surgeons practice guideline series:
Blood glucose management during adult cardiac surgery. Ann Thorac Surg 2009; 87: 663-9

126
Page 9
39. Joshi GP, Chung F, Vann MA, Ahmad S, Gan TJ, Goulson DT, Merrill DG, Twersky R: Society for
Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic
patients undergoing ambulatory surgery. Anesth Analg 2010; 111: 1378-87
40. Egi M, Bellomo R, Stachowski E, French CJ, Hart G: Variability of blood glucose concentration and short-
term mortality in critically ill patients. ASA A-578 2006; 105: 244-52
41. Krinsley JS: Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill
patients before and during the era of intensive glycemic management: six and one-half years experience at
a university-affiliated community hospital. Semin Thorac Cardiovasc Surg 2006; 18: 317-25
42. Ali NA, O'Brien JM, Jr., Dungan K, Phillips G, Marsh CB, Lemeshow S, Connors AF, Jr., Preiser JC:
Glucose variability and mortality in patients with sepsis. Crit Care Med 2008; 36: 2316-21
43. Subramaniam B, Panzica PJ, Novack V, Mahmood F, Matyal R, Mitchell JD, Sundar E, Bose R,
Pomposelli F, Kersten JR, Talmor DS: Continuous perioperative insulin infusion decreases major
cardiovascular events in patients undergoing vascular surgery: a prospective, randomized trial.
44. Zimmerman CR, Mlynarek ME, Jordan JA, Rajda CA, Horst HM: An insulin infusion protocol in critically
ill cardiothoracic surgery patients. Ann Pharmacother 2004; 38: 1123-9
45. Furnary AP, Cheek DB, Holmes SC, Howell WL, Kelly SP: Achieving tight glycemic control in the
operating room: lessons learned from 12 years in the trenches of a paradigm shift in anesthetic care. Semin
Thorac Cardiovasc Surg 2006; 18: 339-45
46. Maheshwari A, Abdelmalak B, Mascha EJ, Kurz A, Sessler DI: Effects of Intraoperative Dosing of IV
Insulin Bolus on Diabetics Vs Non-Diabetics. Anesthesiology. Anesthesiology 2008; 109:A1459 (
Abstract)
47. Kagansky N, Levy S, Rimon E, Cojocaru L, Fridman A, Ozer Z, Knobler H: Hypoglycemia as a predictor
of mortality in hospitalized elderly patients. Arch Intern Med 2003; 163: 1825-9
48. Ketzler JT AG, Coursin DB,: Perioperative care of the diabetic ASA Refresher courses in Anesthesiology
Edited by Ketzler JT AG, Coursin DB, 2001, pp 1-9
49. Finfer S, Liu B, Chittock DR, Norton R, Myburgh JA, McArthur C, Mitchell I, Foster D, Dhingra V,
Henderson WR, Ronco JJ, Bellomo R, Cook D, McDonald E, Dodek P, Hebert PC, Heyland DK, Robinson
BG: Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012; 367: 1108-18
50. Arabi YM, Dabbagh OC, Tamim HM, Al-Shimemeri AA, Memish ZA, Haddad SH, Syed SJ, Giridhar HR,
Rishu AH, Al-Daker MO, Kahoul SH, Britts RJ, Sakkijha MH: Intensive versus conventional insulin
therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 2008;
36: 3190-7
51. Fahy BG, Sheehy AM, Coursin DB: Perioperative glucose control: what is enough? Anesthesiology 2009;
110: 204-6
52. Ramos M, Khalpey Z, Lipsitz S, Steinberg J, Panizales MT, Zinner M, Rogers SO: Relationship of
perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular
surgery. Ann Surg 2008; 248: 585-91
53. Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C, Hudson M, Mendoza J, Johnson R, Lin E,
Umpierrez GE: Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac
surgery. Diabetes Care 2010; 33: 1783-8
54. Pomposelli JJ, Baxter JK, 3rd, Babineau TJ, Pomfret EA, Driscoll DF, Forse RA, Bistrian BR: Early
postoperative glucose control predicts nosocomial infection rate in diabetic patients. JPEN J Parenter
Enteral Nutr 1998; 22: 77-81
55. Umpierrez GE, Smiley D, Jacobs S, Peng L, Temponi A, Mulligan P, Umpierrez D, Newton C, Olson D,
Rizzo M: Randomized study of basal-bolus insulin therapy in the inpatient management of patients with
type 2 diabetes undergoing general surgery (RABBIT 2 surgery). Diabetes Care 2011; 34: 256-61
56. Umpierrez GE, Smiley D, Hermayer K, Khan A, Olson DE, Newton C, Jacobs S, Rizzo M, Peng L, Reyes
D, Pinzon I, Fereira ME, Hunt V, Gore A, Toyoshima MT, Fonseca VA: Randomized Study Comparing a
Basal Bolus With a Basal Plus Correction Insulin Regimen for the Hospital Management of Medical and
Surgical patients With Type 2 Diabetes: Basal Plus Trial. Diabetes Care 2013
57. Desachy A, Vuagnat AC, Ghazali AD, Baudin OT, Longuet OH, Calvat SN, Gissot V: Accuracy of bedside
glucometry in critically ill patients: influence of clinical characteristics and perfusion index. Mayo Clin
Proc 2008; 83: 400-5

Disclosure

126
Page 10

219
Page 1
Obstructive Sleep ApneaWhat an Anesthesiologist Should Know?
Frances Chung, MBBS, FRCPC Toronto, Canada
Obstructive Sleep Apnea (OSA) syndrome is a disease characterized by recurrent episodic cessation of
breathing lasting ! 10s during sleep. In this condition, there is exaggerated depression of pharyngeal muscle
tone during sleep and anesthesia, resulting in a cyclical pattern of partial or complete upper airway obstruction
with impaired respiration.
1
Clinically, this manifests as repeated nocturnal arousals and increased sympathetic
output, daytime hypersomnolence, memory loss, and executive and psychomotor dysfunction.
2
. Its estimated
prevalence are 1 in 4 males and 1 in 10 females for mild OSA
3,4
, and 1 in 9 males and 1 in 20 females for
moderate OSA.
5,6
The economic cost of OSA is considerable.
7
A significant number of patients with OSA are
undiagnosed when they present for elective surgery.
8
Approximately 24% of surgical patients were found to be
at high risk based on screening, of whom 81% had not been previously diagnosed with OSA.
9,10

OSA Diagnostic Criteria Classically, the gold standard for the definitive diagnosis of OSA requires an
overnight polysomnography or sleep study. The Apnea Hypopnea Index (AHI), defined as the average number
of abnormal breathing events per hour of sleep, is used to determine the presence of and the severity of OSA.
An apneic event refers to cessation of airflow for 10s, while hypopnea occurs with reduced airflow with
desaturation !4%.
11
The American Academy of Sleep Medicine (AASM) diagnostic criteria for OSA requires
either an AHI !15, or AHI !5 with symptoms, such as daytime sleepiness, loud snoring, or observed obstruction
during sleep.
12
The Canadian Thoracic Society guidelines for the diagnosis of OSA specifies the presence of an
AHI !5 on polysomnography, and either of (1) daytime sleepiness or (2) at least 2 other symptoms of OSA (e.g.
choking or gasping during sleep, recurrent awakenings, unrefreshing sleep, daytime fatigue).
13
OSA severity is
mild for AHI !5 to15, moderate for AHI 15 to 30, and severe for AHI >30.
12

Comorbidities Associated with OSA OSA is associated with multiple comorbidities such as myocardial
ischemia, heart failure, hypertension, arrhythmias, cerebrovascular disease, metabolic syndrome, insulin
resistance, gastroesophageal reflux, and obesity. The prevalence of OSA was 78% in morbidly obese patients
planned for bariatric surgery.
14
Various pathophysiological, demographic and lifestyle factors also predispose to
OSA. These include anatomical abnormalities which cause a mechanical reduction in airway lumen diameter
(e.g. craniofacial deformities, macroglossia, retrognathia), endocrine diseases (e.g. Cushing disease,
hypothyroidism), connective tissue diseases (e.g. Marfan Syndrome), male gender, age above 50 years, neck
circumference >40 cm, and lifestyle factors of smoking and alcohol consumption.
15

Postoperative Complications in Patients with OSA Chronic untreated OSA leads to multisystemic adverse
consequences and is an independent risk factor for increased all-cause mortality in the general population.
16, 17

The anatomical inherent collapsibility of the airway and the systemic effects of the disease also place the
surgical OSA patients at increased risk of serious complications. Memtsoudis et al found a 2X higher risk of
pulmonary complications in OSA patients after non-cardiac surgery vs non-OSA.
18
In bariatric surgical patients,
the presence of OSA was found to be an independent risk factor for adverse postoperative events.
19
Flink et al
reported a 53% incidence of postoperative delirium in OSA patients vs 20% in non-OSA patients.
20
A meta-
analysis by Kaw et al showed that the presence of OSA increased the odds of postoperative cardiac events
including myocardial infarction, cardiac arrest and arrhythmias (OR 2.1), respiratory failure (OR2.4),
desaturation (OR 2.3), ICU transfers (OR 2.8), and reintubations (OR2.1).
21
However, a recent study found that
neither an OSA diagnosis nor suspected OSA was associated with increased 30-day or 1-year postoperative
mortality.
22
Also, Mokhlesi et al examinated large nationally representative cohorts in elective orthopedic,
prostate, abdominal and CV surgery in 1 million patients.
23
and 90,000 patients undergoing bariatric surgery.
24

Both studies showed increased complications but not an increase in mortality. Given the body of evidence
associating a diagnosis of OSA with adverse perioperative outcomes, precautions should be taken
perioperatively to reduce complications in this vulnerable group of patients.
Clinical Pathways and Perioperative Management Principles In an attempt to improve the perioperative
care for OSA patients, various authors have constructed guidelines or clinical pathways.
25-30

219
Page 2
Preoperative Evaluation of the Patient with Diagnosed OSA (Figure 1) A thorough history and physical
examination are essential. Focused questions regarding OSA symptoms should be asked. Polysomnography
results should be reviewed to confirm the diagnosis of OSA and evaluate the severity of the disease. Patients
with long standing OSA may manifest a myriad of signs and symptoms suggesting the development of systemic
complications, such as hypoxemia, hypercarbia, polycythemia and cor pulmonale. The patient should also be
assessed for significant comorbidities including morbid obesity, uncontrolled hypertension, arrhythmias,
cerebrovascular disease, heart failure and metabolic syndrome. Obesity hypoventilaton syndrome occurs in 0.15
-0.3 of the general population.
31
Pulmonary arterial hypertension is a fairly common long term complication of
OSA, occurring in 15-20% of patients.
32
Its significance lies in the fact that certain physiological derangements
may raise pulmonary artery pressures further and should be avoided intraoperatively. The American College of
Chest Physicians does not recommend routine evaluation for pulmonary arterial hypertension in patients with
known OSA.
33
However, should there be anticipated intraoperative triggers for acute elevations in pulmonary
arterial pressures, for example, high risk surgical procedures of long duration, a preoperative transthoracic
echocardiography may be considered.
27
Simple bedside investigations may be performed in the preoperative
clinic to screen for OSA related complications. In the absence of other attributable causes for hypoxemia, a
baseline oximetry reading of " 94% on room air suggests severe long standing OSA, and may be a red flag
signaling postoperative adverse outcome.
34

Frequently, OSA patients may be on PAP devices for treatment, for example the continuous positive
airway pressure (CPAP), bilevel positive airway pressure (BiPAP), and automatically adjusting positive airway
pressure (APAP) machines. Automatically adjusting PAP devices provide respiratory assistance based on
airflow measurements, fluctuations in pressure or airway resistance.
35
The compliance of OSA patients to such
treatment should be evaluated. The patients updated PAP therapy settings should be obtained. Reassessment by
a sleep medicine physician may be indicated in patients who have defaulted follow up, have been non-compliant
to treatment, have had recent exacerbation of symptoms, or have undergone upper airway surgery to relieve
OSA symptoms. Patients who default PAP use should be advised to resume therapy.
Interestingly, there is to date insufficient evidence to prove conclusively the benefit of PAP therapy in
the preoperative setting; and the duration of therapy required to effectively reduce perioperative risks has not
been delineated. A retrospective matched cohort study by Liao et al suggested that preoperative PAP therapy
may possibly be beneficial based on the observation that OSA patients who did not use home PAP devices prior
to surgery but required PAP therapy after surgery had increased complication rate.
36
Perioperative auto-titrated
continuous positive airway pressure treatment was shown to significantly reduce postoperative apnea hypopnea
index and improved oxygen saturation in surgical patients with moderate and severe obstructive sleep apnea.
37

However, one study did not show benefit for APAP applied postoperatively to PAP nave patients at high-risk
for sleep apnea.
38
A recent study showed that the preoperative patients identi#ed to have OSA and treated with
CPAP have long term health bene#ts in terms of improved snoring, sleep quality, daytime sleepiness and
reduction of medications for comorbidites.
39
However, adherence to prescribed CPAP therapy during the
perioperative period was extremely low.
40

Current guidelines recommend that patients with moderate or severe OSA already on PAP therapy
should continue PAP use prior to surgery.
26
The anesthesia team should be informed early to allow for
advanced intraoperative management planning and risk mitigation. Mild OSA may not be a significant disease
entity for patients undergoing surgery and anesthesia. From the published results of the Busselton Health Cohort
Study, mild OSA was not an independent risk factor for higher mortality in the general population.
17
Based on
expert opinion and symptomatology of OSA patients, preoperative PAP use may not be indicated in patients
with mild OSA. Figure 1 suggests an algorithm for the preoperative evaluation and management of the patient
already diagnosed with OSA.
28,41

Methods for Perioperative Screening for OSA An overnight polysomnography is the gold standard
diagnostic test for OSA. However, routine screening with polysomnography is costly and resource-intensive,
due to equipment constraints and the requirement for special technical expertise. As a result, several tools have
been developed to meet this need for simple, economical and sensitive screening tests for the detection of
patients with suspected OSA. These include questionnaire-based methods such as the Epworth Sleepiness
Scale,
42
the Berlin Questionnaire,
43
the ASA checklist,
26
the Sleep Apnea Clinical Score,
25
the P-SAP score
44

and the STOP-Bang questionnaire.
45
The STOP-Bang questionnaire was originally developed in the surgical
population but has been validated in various patient populations (Table 1).
45-47
Patients with STOP-Bang scores
0-2 may be considered low risk, 3-4 intermediate risk, and 5-8 high risk of OSA.
47
Apnea/hypopnea during
sleep can lead to intermittent hypercapnia and result in serum bicarbonate retention. The addition of serum
bicarbonate level to the STOP-Bang questionnaire may improve its specificity.
48
The STOP-Bang questionnaire
is useful in the preoperative setting to predict OSA severity, triage patients for further confirmatory testing, and
exclude those without disease.
46

219
Page 3
Preoperative Evaluation of the Patient with Suspected OSA (Figure 1) In patients suspected of OSA, a
thorough clinical examination should be performed with emphasis on pertinent symptoms and signs of OSA.
The subsequent management is determined by the urgency of surgery. In emergency situations, the patient
should proceed for surgery. Extensive testing for OSA will result in a delay of vital surgery. Perioperative
precautions should be taken based on the clinical suspicion of OSA. A clinical algorithm is suggested in the
elective setting (Figure 1).
28
Where non-urgent elective surgery is planned, the decision for further evaluation
rests on (1) the risk of surgery, and (2) the presence of other significant comorbidities suggestive of chronic
OSA, such as uncontrolled hypertension, heart failure, arrhythmias, pulmonary hypertension, cerebrovascular
disease, morbid obesity and metabolic syndrome. For patients with STOP-Bang score 5-8, scheduled for major
elective surgery, and have comorbid disease(s) associated with long standing OSA, a preoperative assessment
by the sleep physician and a polysomnography should be considered for diagnosis and treatment.
26
Sometimes,
major elective surgery may have to be deferred to allow adequate evaluation and optimization of suspected
severe OSA. The eventual decision to evaluate a patient preoperatively should ultimately be made based on the
clinical judgment of the attending physician, after taking into account patient-related and logistical factors. We
suggest that patients scored as high risk but without significant comorbidities be considered for further
evaluation with portable monitoring devices, or proceed with surgery with a presumed diagnosis of moderate
OSA and with perioperative OSA precautions. These patients can be referred after surgery.
Patients with an intermediate risk of OSA based on STOP-Bang may proceed for surgery without
further testing with perioperative OSA precautions. This subset of patients may have previously undergone
anesthesia uneventfully, and represent false positives on screening, or may have less severe OSA. Nonetheless,
increased vigilance is prudent in managing these at risk patients. If the subsequent perioperative course
suggests a higher likelihood of OSA, for example difficult airway,
49
or recurrent postoperative respiratory
events such as desaturation, hypoventilation or apnea,
50
a subsequent sleep physician referral and
polysomnography may be indicated. Patients deemed to be low risk on screening with score 0-2 on STOP-Bang
are unlikely to have OSA. These patients may proceed for surgery with routine perioperative care.

Portable Polysomnography and Overnight Oximetry Home sleep testing may be a viable alternative to
standard polysomnography for the diagnosis of OSA in certain subsets of patients.
51
Such monitoring
equipment are classified into level 2 (full unattended polysomnography with !7 channels), level 3 (devices
limited to 4-7 channels), and level 4 (1-2 channels including nocturnal oximetry) devices. In particular, the level
2 portable polysomnography has been shown to have a diagnostic accuracy similar to standard
polysomnography,
52
while nocturnal oximetry is both sensitive and specific for detecting OSA in STOP-Bang
positive surgical patients.
53
The oxygen desaturation index derived from nocturnal oximetry correlates well
with the AHI obtained from polysomnography.
53
Furthermore, patients with mean preoperative overnight SpO2
<93% or ODI > 28.5 events/h are at higher risk for postoperative adverse events.
34

The Portable Monitoring Task Force of the American Academy of Sleep Medicine (AASM) suggests
that portable devices may be considered when there is high pretest likelihood for moderate to severe OSA
without other substantial comorbidities.
54
Following the AASM 2007 guidelines, the Canadian Thoracic
Society 2011 update on the diagnosis and treatment of sleep disordered breathing recommended that level 2, 3
and 4 portable monitoring devices including nocturnal oximetry may be used as confirmatory tests for the
diagnosis of OSA, provided that proper standards for conducting the test and interpretation of results are met.
55

Intraoperative Risk Reduction Strategies for OSA Patients (Table 2) Various strategies can be employed
to mitigate the risks and avert adverse outcomes in OSA patients perioperatively (Table 2). Preoperatively,
sedative premedication should be avoided.
56
Pain adjuvants such as the alpha-2 agonists (dexmedetomidine)
have an opioid sparing effect and also reduce anesthetic requirement.
57
A history of OSA may be associated
with difficult mask ventilation
58
as well as 8 times more likely of difficult intubation.
59
Adequately skilled
personnel and appropriate equipment, including a range of airway adjuncts, should be available prior to
induction of anesthesia.
60
The entire anesthesia team should be familiar with a specific difficult airway
algorithm, such as the ASA Guidelines for the management of difficult airway.
61
Preoxygenation using 100%
oxygen with continuous PAP of 10 cmH
2
O for 3-5 min with a 25 degree head-up tilt has been reported to
achieve higher end-tidal concentrations of O2.
62,63
Triple airway maneuvers and two-handed mask ventilation
may be needed to attain adequate ventilation. Gastroesophageal reflux disease secondary to hypotonia of the
lower esophageal sphincter is common among patients with OSA.
64
Measures to decrease the risk of gastric
acid aspiration should be considered, and include preoperative proton pump inhibitors, antacids, and rapid
sequence induction and cricoid pressure. Notably, use of cricoid pressure may further impede mask ventilation
and tracheal intubation.
65

Many of the anesthetic agents, for example, volatile agents, anxiolytics and opioids, cause respiratory
depression. OSA patients have a heightened sensitivity to the respiratory depressant effects of these drugs due to
their increased susceptibility for airway collapse, chronic sleep deprivation, and blunted response to hypercarbia

219
Page 4
and hypoxia. Nocturnal hypoxemia in patients at high risk for OSA was associated with an increased potency of
opioid analgesia.
66
Short acting agents such as propofol, remifentanil and desflurane are preferred while long
acting agents should be avoided or their use minimized. Pulmonary hypertension is a known complication of
chronic OSA. Intraoperative triggers for elevation of pulmonary artery pressures namely hypercarbia,
hypoxemia, hypothermia and acidosis should be avoided.
Intraoperative use of opioid sparing agents like NSAIDs, COX-2 inhibitors, paracetamol, tramadol, and
adjuvants such as the anticonvulsants pregabalin and gabapentin are helpful with reducing postoperative opioid
requirements. Previous studies showed that desaturation was 12 to 14 times more common in OSA patients who
received opioids postoperatively.
67
Other novel opioid sparing adjuvants being investigated include
corticosteroids like dexamethasone, NMDA receptor antagonist ketamine,
68
alpha 2 agonists clonidine and
dexmedetomidine,
69
and melatonin.
70
A recent study investigating the beneficial effects of intraoperative
intravenous doxapram found that post anesthetic recovery and outcomes of OSA patients undergoing bariatric
surgery were improved with the use of central respiratory stimulants.
71
The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an
increased risk of respiratory adverse events.
72
Even minute amounts of residual neuromuscular blockade can
result in greater postoperative morbidity with increased risks of aspiration, airway obstruction, hypoventilation,
hypoxia and reintubation.
73
Patients should be extubated only when awake fully conscious, obeying
commands and airway patency confirmed. Purposeful movements must be distinguished from involuntary
actions such as coughing and reflex reaching for the endotracheal tube. Post extubation, patients should be
nursed in a semi-upright or lateral position.
26

A recent study utilizing nationwide data of 40,316 patients with sleep apnea diagnosis who underwent
hip and knee arthroplasty, the use of neuraxial anesthesia vs general anesthesia was associated with decreased
odds for the need for mechanical ventilation, use of ICU, prolonged length of stay and cost.
74
Local and regional
anesthesia techniques may be preferable to general anesthesia as they avoid manipulation of the airway and
reduce postoperative requirement for analgesic.
26
Patients receiving sedation for surgical procedures under
monitored anesthetic care should be monitored for adequacy of ventilation by capnography. Patients previously
on PAP therapy at home may require the use of their PAP devices during procedures under mild to moderate
sedation.
75
A secured airway is preferred to an unprotected one for procedures requiring deep sedation.
26
Pregnant patient with OSA will require special care.
76
Clinical practice guideline has been published on the
management of childhood OSA and the indication for polysomnography before tonsillectomy.
77,78

Postoperative Disposition of Known and Suspected OSA Patients after General Anesthesia (Figure 2)
The postoperative disposition of the OSA patient will depend on three main components: the
invasiveness of the surgery, the severity of OSA, and the requirement for postoperative opioids (Figure 2). To
illustrate, a patient with severe OSA who just had major surgery and receiving high dose opioids would be more
likely to require continuous monitoring than another patient with suspected OSA undergoing minor surgery. The
final decision regarding the level of monitoring is determined by the attending anesthesiologist, taking into
account all patient-related, logistical and circumstantial factors.
A practical algorithm (Figure 2) has been formulated based on the ASA 2006 guidelines on the
perioperative management of patients with OSA, and on evidence from recent research.
28,41
All patients with
known or suspected OSA who had received general anesthesia should have extended monitoring in PACU with
continuous oximetry. There are currently no evidence-based guidelines addressing the optimal length of
monitoring required in PACU. The ASA guidelines, which were based on expert opinion, recommended
prolonged observation for 7 hours in PACU if respiratory events such as apnea or airway obstruction occur.
Such recommendations are difficult to adhere to, especially in the context of community hospitals.
75
We
propose extended PACU observation for an additional 30-60 minutes in a quiet environment after the modified
Aldrete criteria for discharge has been met.
28, 41

The occurrence of recurrent respiratory events in PACU is another indication for continuous
postoperative monitoring.
50
PACU respiratory events are: (1) episodes of apnea ! 10 seconds, (2) bradypnea <8
breaths/min, (3) pain-sedation mismatch, or (4) repeated O2 desaturation <90%. Any of the above events
occurring repeatedly in separate 30-minute intervals may be considered recurrent PACU respiratory events.
Patients with suspected OSA and who develop recurrent PACU respiratory events are at increased risk of
postoperative respiratory complications.
50,79,80
Continuous monitoring with oximetry in a unit with ready access
to medical intervention is advocated. These would include ICU, step down units, or the surgical ward equipped
with remote telemetry and oximetry monitoring. These patients may require postoperative PAP therapy.
75
Advances incorporating smart technologies have been made with monitoring equipment. Multiple
parameters including heart rate, blood pressure, temperature, capnography and oxygen saturation can be tracked
continuously and the trends analysed according to pre-programmed algorithms. This will potentially improve
the sensitivity in detecting at risk patients during their recovery, while reducing false alarms, making the
postoperative care of OSA patients safer.
81,82

219
Page 5
One should consider discharging a patient with known OSA to a monitored environment if the patient
has severe OSA, is non-compliant to PAP therapy, or has recurrent PACU respiratory events (Figure 2).
Furthermore, monitoring with continuous oximetry is recommended with parenteral opioids due to possible drug
induced respiratory depression.
83
Patients with moderate OSA who require high dose oral opioids should be
managed in a surgical ward with continuous oximetry (Figure 2) regardless of the number of PACU respiratory
events.
Known OSA patients already on PAP devices should continue PAP therapy postoperatively. While
there is insufficient high level evidence demonstrating an improvement of outcomes with postoperative PAP
therapy in OSA patients, a recent retrospective review of 797 patients scheduled for bariatric surgery suggested
that timely recognition and management of OSA with perioperative continuous PAP may mitigate the risk of
postoperative complications.
84
Where possible, a multimodal approach to analgesia should be employed to
minimize the use of opioids postoperatively. Apart from oral or systemic administration of opioid sparing
agents, other effective techniques include local anesthetic wound infiltration, peripheral nerve block catheters
and neuraxial infusions of local anesthetic agents. If postoperative parenteral opioids are necessary,
consideration should be made for the use of patient controlled analgesia with no basal infusion and a strict
hourly dose limit, as this may help reduce the total amount of opioid used. OSA patients may have an
upregulation of the central opioid receptors secondary to recurrent hypoxemia, and are therefore more
susceptible to the respiratory depressant effects of opioids. As such, they may benefit from supplemental oxygen
while on parenteral opioids.
85
The Anesthesia Patient Safety Foundation advises that ventilation should be
monitored for the detection of hypoventilation when supplemental oxygen is delivered.
83

Recently, Swart et al published a PACU order-based approach to facilitate postoperative decision
making for patients with sleep apnea. The orders prompt anesthesiologists to consider the factors and events
associated with higher risk of complications from OSA, diagnostic follow-up and possible sleep medicine
consult.
86
A recent study found that patients had no significant increase in postoperative complications if
managed on the OSA risk management protocol. The authors indicated that it may be clinically safe to proceed
with elective surgery without delay for formal polysomnography confirmation.
87
For the perioperative
management, it is important to educate surgeons, nurses, patients, and their family. Pharmacy involvement to
prevent multiple drugs with potential to cause sedation and limiting the upper dose of opioids is essential. Nurse
training in detecting respiratory depression and in rapid administration of naloxone will prevent mortality and
morbidity.
We have found that the disturbances in sleep architecture were greatest on postoperative N1 and
breathing disturbances during sleep were greatest on postoperative N3.
88
Patients with a higher preoperative
AHI were predicted to have a higher postoperative AHI. Preoperative AHI, male gender and 72h opioid dose
were positively associated with postoperative AHI.
89
At present, deciding on the optimal level and duration of
monitoring for OSA patients remains a daunting challenge. The vulnerable OSA patient is at risk of serious
postoperative complications and even death. Granted, the incidence of postoperative OSA-related mortality is
low; however, it only takes one unnecessary death or one case of hypoxic encephalopathy to be the impetus for
closer postoperative monitoring.
90,91

Ambulatory Surgery for OSA Patients
The 2006 ASA guidelines on the perioperative management of OSA patients advised that superficial
surgery, minor orthopedic surgery under local anesthesia or regional anesthesia, and lithotripsy may be
performed as day cases.
26
The newly published Society for Ambulatory Anesthesia (SAMBA) consensus
statement addressed the selection of suitable OSA patients for ambulatory surgery. Despite a higher incidence of
desaturation and need for supplemental O2 among OSA patients, there was no significant difference in rates of
serious adverse outcomes such as reintubation, mechanical ventilation, surgical airway or death. The authors
recommend that known OSA patients with well controlled comorbid diseases and compliance with PAP therapy
may be considered for ambulatory surgery. Patients are advised to apply their PAP devices when sleeping even
in daytime for several days postoperatively. Diagnosed or suspected OSA patients without significant
comorbidities, recurrent PACU respiratory events or need for high dose oral opioids may be considered for
discharge home after minor surgery at the discretion of the attending physician (Figure 2).
28,92
Emphasis was
placed on advanced planning of the perioperative anesthetic and analgesic options, and timely education of
patients and caregivers regarding their post-discharge care. Patients with severe OSA and uncontrolled
comorbid diseases are not suitable for ambulatory surgery.
92,93
With regards to the type of procedures suitable
for day surgery, the SAMBA guidelines recommend that painful operations where postoperative non opioid
analgesia would be inadequate should not be performed on an outpatient basis.
All OSA patients should be escorted home by a reliable adult upon discharge. Caution should be
exercised if diagnosed or suspected OSA patients develop repeated respiratory events in the early postoperative
period; and there should be a lower threshold for unanticipated hospitalization. Ideally, ambulatory surgical

219
Page 6
centers that manage OSA patients should have transfer agreements with better equipped inpatient facilities and
should also have the capacity to handle the postoperative problems associated with OSA.
Retrospective observational studies have reported low (<0.5%) postoperative complication rates with
ambulatory or short stay surgery for OSA patients undergoing bariatric surgery.
94-96
Such approaches are still
deemed unconventional.
97
Importantly, a discriminating patient selection criteria, meticulous preoperative risk
stratification and optimization of OSA and related comorbidities, together with well-trained medical personnel,
experienced high volume facilities, and strict discharge criteria are all essential for the delivery of safe
ambulatory surgery for this subset of patients.

Conclusion
It is well known that OSA patients can suffer serious postoperative consequences. This has led to the
formulation of various screening methods for the detection and risk stratification of OSA patients. While every
patient deserves individualized care, practical algorithms to guide the perioperative management of such high
risk patients would be advantageous. We formulated clinical algorithms to guide the care of diagnosed and
suspected OSA patients in the preoperative, intraoperative and postoperative periods. To date, many care
pathways and recommendations are based on consensus or expert opinion rather than high level evidence.
Future research in these areas and collaboration between the fields of anesthesiology and sleep medicine will be
instrumental in shedding light on these lingering OSA-related perioperative care issues.
98

Adapted from Seet E, LH Tee, Chung F. Sleep Med Clin 2013; 8:105-120
References:
1. Isono S. Obstructive sleep apnea of obese adults: Pathophysiology and perioperative airway
management. Anesthesiology 2009; 110:908-21.
2. Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: Towards a comprehensive
model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep
Res 2002; 11:1-16.
3. Kryger MH. Diagnosis and management of sleep apnea syndrome. Clin Cornerstone 2000; 2:39-47.
4. Young T, Palta M, Dempsey J et al. The occurrence of sleep-disordered breathing among middle-aged
adults. N Engl J Med 1993; 328:1230-5.
5. Bixler EO, Vgontzas AN, Ten HT et al. Effect of age on sleep apnea in men: I. Prevalence and
severity. Am J Respir Crit Care Med 1998; 157:144-8.
6. Bixler EO, Vgontzas AN, Lin HM et al. Prevalence of sleep-disordered breathing in women. Am J
Respir Crit Care Med 2001; 163:608-13.
7. Hillman DR, Murphy AS, Antic R et al. The economic cost of sleep disorders. Sleep 2006; 29:299-305.
8. Singh M, Liao P, Kobah S et al. Proportion of surgical patients with undiagnosed obstructive sleep
apnoea. Br J Anaesth 2013; 110:629-636.
9. Finkel KJ, Searleman AC, Tymkew H et al. Prevalence of undiagnosed obstructive sleep apnea among
adult surgical patients in an academic medical center. Sleep Med 2009; 10:753-8.
10. Stierer TL, Wright C, George A et al. Risk assessment of obstructive sleep apnea in a population of
patients undergoing ambulatory surgery. J Clin Sleep Med 2010; 6:467-72.
11. Iber C, Ancoli-Israel S, Cheeson A et al. The AASM Manual for the Scoring of Sleep and Associated
Events, Rules, Terminology and Technical Specifications. Westchester, Illinois, American Academy of
Sleep Medicine, 2007.
12. Epstein LJ, Kristo D, Strollo PJ et al. Clinical guideline for the evaluation, management and long-term
care of obstructive sleep apnea in adults. J Clin Sleep Med 2009; 5:263-76
13. Fleetham J, Ayas N, Bradley D et al; CTS Sleep Disordered Breathing Committee. Canadian Thoracic
Society guidelines: Diagnosis and treatment of sleep disordered breathing in adults. Can Respir J 2006;
13:387-92.
14. Lopez PP, Stefan B, Schulman CI et al. Prevalence of sleep apnea in morbidly obese patients who
presented for weight loss surgery evaluation: more evidence for routine screening for obstructive sleep
apnea before weight loss surgery. Am Surg 2008; 74: 834-8.
15. Chung F, Elsaid H. Screening for obstructive sleep apnea before surgery: Why is it important? Curr
Opin Anesthesiol 2009; 22:405-411.
16. Young T, Finn L, Peppard PE et al. Sleep disordered breathing and mortality: Eighteen-year follow-up
of the Wisconsin sleep cohort. Sleep 2008; 31:1071-8.
17. Marshall NS, Wong KKH, Liu PY et al. Sleep apnea as an independent risk factor for all-cause
mortality: The Busselton Health Study. Sleep 2008; 31:1079-85.
18. Memtsoudis S, Liu SS, Ma Y et al. Perioperative pulmonary outcomes in patients with sleep apnea
after noncardiac surgery. Anesth Analg 2011; 112:113-21.

219
Page 7
19. Flum DR, Bella SH et al Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. N Engl J
Med 2009; 361:445-54.
20. Flink BJ, Rivelli SK, Cox EA et al. Obstructive sleep apnea and incidence of postoperative delirium
after elective knee replacement in the nondemented elderly. Anesthesiology 2012; 116:788-96.
21. Kaw R, Chung F, Pasupuleti V et al. Meta-Analysis of the Association between Obstructive Sleep
Apnoea and Postoperative Outcome. Br J Anaesth 2012; 109:897-906
22. Lockhart EM, Willingham MD, Abdallah AB et al Obstructive sleep apnea screening and postoperative
mortality in a large surgical cohort. Sleep Med. 2013 Mar 13. pii: S1389-9457(12)00396625.
23. Mokhlesi B, Hovda MD, Vekhter B et al Sleep-disordered breathing and postoperative outcomes after
elective surgery: analysis of the Nationwide Inpatient Sample. Chest 2013; Mar 28. doi:
10.1378/chest.12-2905
24. Mokhlesi B, Hovda MD, Vekhter B et al Sleep-Disordered Breathing and Postoperative Outcomes after
Bariatric Surgery: Analysis of the Nationwide Inpatient Sample. Obes Surg 2013, May 22 [Epub ahead
of print]
25. Flemons WW. Obstructive Sleep Apnea. N Engl J Med 2002; 347:498-504.
26. Gross JB, Bachenberg KL, Benumof JL et al. Practice guidelines for the perioperative management of
patients with obstructive sleep apnea: A report by the ASATask Force on perioperative management of
patients with obstructive sleep apnea. Anesthesiology 2006; 104:1081-93.
27. Adesanya AO, Lee W, Greilich NB et al. Perioperative management of obstructive sleep apnea. Chest
2010; 138:1489-98.
28. Seet E, Chung F. Management of sleep apnea in adults - Functional algorithms for the perioperative
period: Continuing Professional Development. Can J Anesth 2010; 57:849-64.
29. Porhomayon J, El-Solh A, Chhangani S et al. The management of surgical patients with obstructive
sleep apnea. Lung 2011; 189:359-67.
30. Meoli AL, Rosen CL, Kristo D et al. Upper airway management of the adult patient with obstructive
sleep apnea in the perioperative period - Avoiding complications. Sleep 2003; 26:10605.
31. Chau EH, Lam D, Wong J et al Obesity Hypoventilation Syndrome: A Review of Epidemiology,
Pathophysiology, and Perioperative Considerations. Anesthesiology 2012; 117:188-205
32. Bady E, Achkar A, Pascal S et al. Pulmonary hypertension in patients with sleep apnoea syndrome.
Thorax 2000; 55:934-9.
33. Atwood CW, McCrory D, Garcia JG et al. Pulmonary Artery Hypertension and Sleep-Disordered
Breathing: ACCP Evidence-Based Clinical Practice Guidelines. Chest 2004; 126:72S-77S.
34. Chung F, Zhou L, Liao P. Association of preoperative oximetry parameters with postoperative adverse
events. Anesthesiology 2012; Abstract 12-A-2312-ASAHQ.
35. Berry RB, Parish JM, Hartse KM. The use of auto-titrating continuous positive airway pressure for
treatment of adult obstructive sleep apnea. An American Academy of Sleep Medicine review. Sleep
2002; 25:148-73.
36. Liao P, Yegneswaran B, Vairavanathan S et al. Postoperative complications in patients with obstructive
sleep apnea: A retrospective matched cohort study. Can J Anesth 2009; 56:819-28.
37. Liao P, Luo Q, Elsaid H et al. Perioperative auto-titrated continuous positive airway pressure treatment
in surgical patients with obstructive sleep apnea: A RCT. Anesthesiology 2013 in press.
38. OGorman SM, Gay PC, Morgenthaler TI. Does auto-titrating positive airway pressure therapy
improve postoperative outcome in [atients at risk for obstructive sleep apnea syndrome? A randomized
controlled clinical trial. Chest 2013; Jan 3. doi: 10.1378/chest.120989
39. Mehta V, Subramanyam R, Shapiro CM et al Health effects of identifying patients with undiagnosed
obstructive sleep apnea in the preoperative clinic: A follow-up study. Can J Anesth 2012; 59:54455
40. Guralnick AS, Pant M, Minhaj M et al PAP adherence in patients with newly diagnosed obstructive
sleep apnea prior to elective surgery. J Clin Sleep Med 2012; 8:5016
41. Seet E, Chung F. Obstructive sleep apnea: preoperative assessment. Anesthesiology Clin 2010; 28:199-
215
42. Johns MW. A new method of measuring daytime sleepiness: The Epworth sleepiness scale. Sleep
1991; 14:540-5
43. Netzer NC, Hoegel JJ, Loube D, et al. Prevalence of symptoms and risk of sleep apnea in primary care.
Chest 2003; 124:1406-14.
44. Ramachandran SK, Kheterpal S, Consens F et al. Derivation and validation of a simple perioperative
sleep apnea prediction score. Anesth Analg 2010; 110:1007-15.
45. Chung F, Yegneswaran B, Liao P et al. STOP Questionnaire: A tool to screen patients for obstructive
sleep apnea. Anesthesiology 2008; 108:812-21.

219
Page 8
46. Farney RJ, Walker BS, Farney RM et al. The STOP-Bang equivalent model and prediction of severity
of obstructive sleep apnea: relation to polysomnographic measurements of the apnea/hypopnea index. J
Clin Sleep Med 2011; 7:459-65.
47. Chung F, Subramanyam R, Liao P et al. High STOP-Bang score indicates a high probability of
obstructive sleep apnoea. Br J Anaesth 2012; 108: 768-75.
48. Chung F, Chau E, Yang Y et al Serum bicarbonate level improves specificity of STOP-Bang screening
for obstructive sleep apnea. Chest 2013;143: 1284-83
49. Chung F, Yegneswaran B, Herrera F, et al. Patients with difficult intubation may need referral to sleep
clinics. Anesth Analg 2008; 107:915-20.
50. Gali B, Whalen FX, Schroeder D et al. Identification of patients at risk for postoperative respiratory
complications using a preoperative obstructive sleep apnea screening tool and postanesthesia care
assessment. Anesthesiology 2009; 110:869-77.
51. Collop NA. Home sleep testing: It is not about the test. Chest 2010; 138:245-6.
52. Chung F, Liao P, Sun Y et al. Perioperative practical experiences in using a level 2 portable
polysomnography. Sleep Breath 2011; 15:367-75.
53. Chung F, Liao P, Elsaid H et al. Oxygen desaturation index from nocturnal oximetry: A sensitive and
specific tool to detect sleep-disordered breathing in surgical patients. Anesth Analg 2012; 114:993-
1000.
54. Collop NA, Anderson WM, Boehlecke B et al. Clinical guidelines for the use of unattended portable
monitors in the diagnosis of obstructive sleep apnea in adult patients: Portable Monitoring Task Force
of the American Academy of Sleep Medicine. J Clin Sleep Med 2007; 3:737-747.
55. Fleetham J, Ayas N, Bradley D et al. Canadian Thoracic Society 2011 guideline update: Diagnosis and
treatment of sleep disordered breathing. Can Respir J 2011; 18: 2547.
56. Chung S, Yuan H, Chung F. A systematic review of obstructive sleep apnea and its implications for
anesthesiologists. Anesth Analg 2008; 107:1543-63.
57. Bamgbade OA, Alfa JA. Dexmedetomidine anaesthesia for patients with obstructive sleep apnoea
undergoing bariatric surgery. Eur J Anaesthesiol 2009; 26:176-7.
58. Kheterpal S, Martin L, Shanks AM et al. Prediction and outcomes of impossible mask ventilation: a
review of 50,000 anesthetics. Anesthesiology 2009; 110:891-7.
59. Siyam MA, Benhamou D. Difficult endotracheal intubation in patients with sleep apnea syndrome.
Anesth Analg 2002; 95:1098-102.
60. Cook TM, Woodall N, Harper J, et al; Fourth National Audit Project. Major complications of airway
management in the UK: Results of the fourth national audit project of the Royal College of
Anaesthetists and the Difficult Airway Society. Part 2: intensive care and emergency departments. Br J
Anaesth 2011; 106:632-42.
61. American Society of Anesthesiologists Task Force on Management of Difficult Airway. Practice
guidelines for management of the difficult airway: An updated report by the American Society of
Anesthesiologists task force on management of the difficult airway. Anesthesiology 2003; 98:1269-77.
62. Delay JM, Sebbane M, Jung B et al. The effectiveness of noninvasive positive pressure ventilation to
enhance preoxygenation in morbidly obese patients: A randomized controlled study. Anesth Analg
2008; 107:1707-13.
63. Dixon BJ, Dixon JB, Carden JR et al. Preoxygenation is more effective in the 25 degrees head-up
position than in the supine position in severely obese patients: a randomized controlled study.
64. Sabate JM, Jouet P, Merrouche M et al. Gastroesophaegeal reflux in patients with morbid obesity: A
role of obstructive sleep apnea syndrome? Obes Surg 2008; 18:1479-84.
65. Ovassapian A, Salem MR. Sellicks maneuver: To do or not do. Anesth Analg 2009; 109:1360-2.
66. Doufas AG, Tian L, Padrez KA et al Experimental pain and opioid analgesia in volunteers at high risk
for obstructive sleep apnea. PLoS One. 2013;8:e54807. doi: 10.1371/journal.pone.0054807
67. Bolden N, Smith CE, Auckley D et al. Perioperative complications during use of an obstructive sleep
apnea protocol following surgery and anesthesia. Anesth Analg 2008; 105:1869-70.
68. Eikermann M, Gross-Sundrup, Zaremba S et al. Ketamine activates breathing and abolishes the
coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology
2012; 116:35-46.
69. Ankichetty S, Wong J, Chung F. A systematic review of the effects of sedative and anesthetics in
patients with obstructive sleep apnea. J Anaesthesiol Clin Pharm 2011; 27:447-58.
70. Yousaf F, Seet E, Venkatraghavan L et al. Efficacy and safety of melatonin as an anxiolytic and
analgesic in the perioperative period: A qualitative systematic review of randomized trials.

219
Page 9
71. Bamgbade OA. Advantages of doxapram for post-anaesthesia recovery and outcomes in bariatric
surgery patients with obstructive sleep apnoea. Eur J Anaesthesiol 2011; 28:387-91.
72. Grosse-Sundrup M, Henneman JP, Sandberg WS et al Intermediate acting non-depolarizing
neuromuscular blocking agents and risk of postoperative respiratory complications: Prospective
propensity score matched cohort study. BMJ 2012; DOI: 10.1136/bmj.e6329
73. Murphy GS, Brull SJ. Residual neuromuscular block: Lessons unlearned part 1: Definitions, incidence,
and adverse physiologic effects of residual neuromuscular block. Anesth Analg 2010; 111:120-8.
74. Memtsoudis SG, Stundner O, Rasul R et al. Sleep apnea and total joint arthroplasty under various types
of anesthesia: A population-based study of perioperative outcomes. Reg Anesth Pain Med 2013; Apr 3
75. Sundar E, Chang J, Smetana GW. Perioperative screening for and management of patients with
obstructive sleep apnea. JCOM 2011; 18:399-411.
76. Louis J, Auckley D, Bolden N. Management of Obstructive Sleep Apnea in Pregnant Women. Obstet
Gynecol 2012; 119:8648.
77. Marcus CL, Brooks LJ, Ward SD et al. Clinical Practice Guideline: Diagnosis and Management of
Childhood Obstructive Sleep Apnea Syndrome. Pediatrics 2012; Aug 27
78. Roland PS, Rosenfeld RM, Brooks LJ et al. American Academy of Otolaryngology-Head and Neck
Surgery Foundation. Clinical practice guideline: Polysomnography for sleep-disordered breathing
prior to tonsillectomy in children. Otolaryngol Head Neck Surg 2011; 145(1 Suppl):S1-15.
79. Chung F, Yegneswaran B, Liao P et al. Validation of the Berlin questionnaire and American Society of
Anesthesiologists checklist as screening tools for obstructive sleep apnea in surgical patients.
80. Vasu TS, Doghramji K, Cavallazzi R et al. Obstructive sleep apnea syndrome and postoperative
complications: Clinical use of the STOP-Bang questionnaire. Arch Otolaryngol Head Neck Surg 2010;
136:1020-4.
81. Overdyk FJ, Carter R, Maddox RR et al. Continuous oximetry/capnography monitoring reveals
frequent desaturation and bradypnea during PCA. Anesth Analg 2007;105:412-8.
82. Lynn LA, Curry JP. Patterns of unexpected in-hospital deaths: A root cause analysis. Patient Safety in
Surgery 2011; 5:3. Doi:10.1186/1754-9493-5-3
83. Weinger MB, Lee LA. No patient shall be harmed by opioid-induced respiratory depression. In:
Proceedings of Essential monitoring strategies to detect clinically significant drug-induced respiratory
depression in the postoperative period conference. APSF Newsletter 2011; 26(2):21,26-28.
84. Weingarten TN, Flores AS, McKenzie JA, et al. Obstructive sleep apnoea and perioperative
complications in bariatric patients. Br J Anaesth 2011; 106:131-9.
85. Blake DW, Chia PH, Donnan G et al. Preoperative assessment for obstructive sleep apnoea and the
prediction of postoperative respiratory obstruction and hypoxaemia. Anaesth Intensive Care 2008;
36:379-84.
86. Swart PA, Chung F, Fleetham J. An order-based approach to facilitate postoperative decision-making
for patients with sleep apnea. Can J Anesth 2013; 60:3214
87. Chong CT, Tey J, Leow SL et al. Management plan to reduce risks in perioperative care of patients
with obstructive sleep apnoea averts the need for presurgical polysomnography. Ann Acad Med
Singapore. 2013; 42:1109.
88. Chung F, Liao P, Yegneswaran B et al Postoperative Changes in Sleep Disordered Breathing and Sleep
Architecture in Patients with Obstructive Sleep Apnea. Anesthesiology 2013 in press
89. Chung F, Liao P, Elsaid H et al. Factors Associated with Postoperative Exacerbation of Sleep
Disordered Breathing. Anesthesiology 2013 in press
90. Gay PC. The value of assessing risk of obstructive sleep apneain surgical patients: It only takes one. J
Clin Sleep Med 2010; 6:467-72.
91. Chung F, Liao P. Preoperative screening for obstructive sleep apnoea - One death is too many. Anaesth
Intensive Care 2010; 38:949-50.
92. Ankichetty S, Chung F. Consideration for patients with obstructive sleep apnea undergoing ambulatory
surgery. Curr Opin Anaesthesiol 2011; 24:605-11.
93. Joshi GP, Ankichetty SP, Gan TJ et al. Society for Ambulatory Anesthesia Consensus statement on
peroperative selection of adult patients with obstructive sleep apnea scheduled for ambulatory surgery.
Anesth Analg 2012; 115: 1060-8
94. Kurrek MM, Cobourn C, Wojtasik Z et al. Morbidity in patients with or at high risk for obstructive
sleep apnea after ambulatory laparoscopic gastric banding. Obes Surg 2011; 21:1494-8
95. Bergland A, Gaslason H, Raeder J. Fast-track surgery for bariatric laparoscopic gastric bypass with
focus on anaesthesia and peri-operative care. Experience with 500 cases. Acta Anaesthesiol Scand
2008; 52:1394-9

219
Page 10
96. Raeder J. Bariatric procedure as day/short stay surgery: is it possible and reasonable? Curr Opin
Anaesthesiol 2007; 20:508-12
97. Schumann R. Anaesthesia for bariatric surgery. Best Pract Res Clin Anaesthesiol 2011; 25:83-93.
98. Chung F, Hillman D, Lydic R. Sleep medicine and anesthesia - A new horizon for anesthesiologists.

Disclosure

219
Page 11
Table 1: Obstructive Sleep Apnea Screening Questionnaire STOP-Bang

S Snoring: Do you snore loudly (louder than talking or loud enough to be
heard through closed doors)?

Yes No
T Tired: Do you often feel tired, fatigued, or sleepy during daytime?

Yes No
O Observed: Has anyone observed you stop breathing during your sleep?

Yes No
P Blood Pressure: Do you have or are you being treated for high blood
pressure?

Yes No
B BMI: BMI more than 35 kg/m
2
?

Yes No
A Age: Age over 50 years old?

Yes No
N Neck circumference: Neck circumference greater than 40 cm?

Yes No
G Gender: Male?

Yes No

Low risk of OSA: Yes 0-2 At risk of OSA: Yes 3 or more questions High risk of OSA: Yes 5-8
Adapted from Chung F, et al Anesthesiology 2008; 108:812-21 and Chung F et al. Br J Anaesth 2012; 108: 768-75.

219
Page 12

Table 2: Perioperative Precautions and Risk Mitigation for OSA Patients

Anesthetic Concern Principles of Management

Premedication Avoid sedating premedication
56

Consider Alpha-2 adrenergic agonists (clonidine,
dexmedetomidine)
57

Potential difficult airway (difficult
mask ventilation and tracheal
intubation)
58, 59

Optimal positioning (Head Elevated Laryngoscopy Position) if
patient obese
Adequate preoxygenation
Consider CPAP preoxygenation
62

Two-handed triple airway maneuvers
Anticipate difficult airway. Personnel familiar with a specific
difficult airway algorithm
61

Gastroesophageal reflux disease
64

Consider proton pump inhibitors, antacids, rapid sequence induction
with cricoid pressure

Opioid-related respiratory
depression
56

Minimize opioid use
Use of short-acting agents (remifentanil)
Multimodal approach to analgesia (NSAIDs, acetaminophen,
tramadol, ketamine, gabapentin, pregabalin, dexmedetomidine,
clonidine, Dexamethasone, melatonin)
Consider local and regional anesthesia where appropriate

Carry-over sedation effects from
longer-acting intravenous and volatile
anesthetic agents
Use of propofol / remifentanil for maintenance of anesthesia

Use of insoluble potent anesthetic agents (desflurane)

Use of regional blocks as a sole anesthetic technique

Excessive sedation in monitored
anesthetic care

Use of intraoperative capnography for monitoring of ventilation
26

Post-extubation airway obstruction Verify full reversal of neuromuscular blockade
26

Extubate only when fully conscious and cooperative
26

Non-supine posture for extubation and recovery
26

Resume use of positive airway pressure device after surgery
26

Adapted from Seet E, Chung F Can J Anesth 2010; 57: 849-64

219
Page 13
Figure 1: Preoperative Evaluation of Suspected or Diagnosed OSA Patient in the Anesthesia Clinic

SuspecLed CSA
SLop 8ang quesLlonnalre
no, CSA
rlsk
mlLlgaLlon

Ma[or LlecLlve
Surgery &
SlgnlflcanL
ComorbldlLles

?es, conslder
referral and/or
SC or oxlmeLry
Low rlsk
Score 0-2
Plgh rlsk
Score >3
lnLermedlaLe
rlsk
Score 3-4
CSA rlsk
mlLlgaLlon
8ouLlne perloperaLlve
managemenL

ModeraLe/Severe CSA
APl > 13,
CxlmeLry < 94
Mlld CSA
APl 3 - 13
CxlmeLry > 94

CxlmeLry > 94

A Lherapy
CSA rlsk mlLlgaLlon

ulagnosed CSA
Px or sleep sLudy

219
Page 14

Figure 2 - Postoperative Management of the Diagnosed or Suspected OSA Patient after General Anesthesia

ACu exLra monlLorlng
30-60 mln afLer modlfled AldreLe crlLerla meL
SuspecLed CSA

ulagnosed CSA

! ModeraLe/Severe CSA (APl > 13) or
! non-compllance wlLh A Lherapy
or
! SlgnlflcanL comorbldlLles or
! osLoperaLlve parenLeral oplolds or
! 8ecurrenL ACu 8esplraLory LvenLs
?es: ConLlnuous oxlmeLry
monlLorlng and/or A Lherapy
ulscharge lf mlnor surgery noL
requlrlng oplolds

S1C-8ang > 3 wlLh
! osLoperaLlve parenLeral oplolds or
! 8ecurrenL ACu 8esplraLory LvenLs

no: ulscharge lf mlnor
surgery noL requlrlng
oplolds.
224
Page 1
Positioning Problems You Hope to Never Encounter
Mark A. Warner, M.D. Rochester, Minnesota
Perioperative neuropathies, soft tissue injuries, and other positioning-related problems have received increasing
attention from the lay press, plaintiffs lawyers, the anesthesiology community, and clinical researchers in recent
years. This lecture will provide an update of current findings and discuss possible mechanisms of injury for these
potentially devastating problems.
A relatively new finding in this field of study is the discovery that a generalized perioperative inflammatory
response is present in a number of patients who have sustained significant prolonged ulnar neuropathy. This is a
surprising, unexpected finding. A 2010 paper by Staff et al describes the remarkably successful treatment of
persistent perioperative ulnar neuropathy with very high doses of steroids (immunomodulation) over several months
after finding generalized microneuritis by sural nerve biopsy in affected patients. Let me repeat that microneuritis
of the sural nerve located far distant from the symptomatic ulnar nerve. It appears that there might be a diffuse
perioperative inflammatory response throughout the body that contributes to perioperative ulnar neuropathy.
Would a similar mechanism contribute to other perioperative neuropathies? Many perioperative factors have been
associated with acute immunosuppression and subsequent inflammatory responses (e.g., blood transfusions, volatile
anesthetics). It is not clear what role this mechanism might play, if any, in a number of perioperative neuropathies.
There clearly is much more yet to learn. However, the Staff study suggests that there may be factors beyond
anatomic positioning issues that are involved in some proportion of perioperative neuropathies.
Upper Extremity Neuropathies
Ulnar Neuropathy
Ulnar neuropathy is the most common perioperative neuropathy. There are a number of factors that may be
associated with ulnar neuropathy, including direct extrinsic nerve compression (often on the medial aspect of the
elbow), intrinsic nerve compression (associated with prolonged elbow flexion), and inflammation. Key points of
interest:
Timing of postoperative symptoms: Most develop during the postoperative, not the intraoperative, period.
There are good data that most surgical patients who develop ulnar neuropathy experience their first
symptoms at least 24 hours postoperatively, suggesting that the mechanism of acute injury occurs primarily
outside of the operating room setting. Parenthetically, medical patients also develop ulnar neuropathies
during hospitalization.
Impact of elbow flexion: The ulnar nerve is the only major peripheral nerve in the body that always passes
on the extensor side of a joint, in this case the elbow. All other major peripheral nerves primarily pass on
the flexion side of joints (e.g., median and femoral nerves). This anatomy difference may play a role in
some perioperative ulnar neuropathies. In general, peripheral nerves begin to lose function and develop
foci of ischemia when they are stretched > 5% of their resting lengths. Elbow flexion, particularly > 90
degrees, stretches the ulnar nerve. Prolonged elbow flexion and stretch of the ulnar nerve can result in
sufficient ischemic areas to cause symptoms in awake and sedated patients and potential long-lasting
damage in all patients.

224
Page 2
Anatomy and elbow flexion: Prolonged elbow flexion of > 90 degrees increases intrinsic pressure on the
nerve and may be as important an etiologic factor as prolonged extrinsic pressure. The ulnar nerve passes
behind the medial epicondyle and then runs under the aponeurosis that holds the two muscle bodies of the
flexor carpi ulnaris together. The proximal edge of this aponeurosis is sufficiently thick, especially in men,
to be separately named the cubital tunnel retinaculum. This retinaculum stretches from the medical
epicondyle to the olecranon. Flexion of the elbow stretches the retinaculum and generates high pressures
intrinsically on the nerve as it passes underneath (fig 1).
Forearm supination and ulnar neuropathy: Supination of the forearm and hand does not, by itself, reduce
the risk of ulnar neuropathy. The action of forearm supination occurs distal to the elbow. Supination is
typically used when positioning arms on arm boards or at patients sides because of the impact it has on
humerus rotation. That is, supination is uncomfortable for most patients, and they will externally rotate
their humerus to increase comfort. It is this external rotation of the humerus that lifts the medical aspect of
the elbow, including the ulnar nerve, from directly resting on the table or armboard surface. This rotation
helps reduce extrinsic pressure on the ulnar nerve.
Outcomes of ulnar neuropathy: Forty percent of sensory-only ulnar neuropathies resolve within 5 days;
80% resolve within 6 months. Few combined sensory/motor ulnar neuropathies resolve within 5 days; only
20% resolve within 6 months, and most result in permanent motor dysfunction and pain. The motor fibers
in the ulnar nerve are primarily located in its middle. Injury to those fibers likely is associated with a more
significant ischemia or pressure insult to all of the ulnar nerve fibers, and recovery may be prolonged or not
possible.

Brachial Plexopathies

Brachial plexopathies occur most often in patients undergoing sternotomies. The risk for this plexopathy in patients
undergoing sternotomy is particularly high in those with internal mammary artery mobilization. This finding is
presumed to be associated with excessive concentric retraction on the chest wall and potential compression of the
plexus between the clavicle and rib cage or stretch of the plexus. Otherwise, patients in prone and lateral positions
have a higher risk of developing this problem than those in supine positions. Key points of interest:

Brachial plexus entrapment: There are many problems that can occur to the plexus in prone and laterally-
positioned patients. For example, the brachial plexus can become entrapped between compressed clavicles
and the rib cage. Special attention should be given to altering positions that might exacerbate this potential
problem.
Prone positioning: In prone positioned patients, its prudent to tuck the arms at the side if at all possible;
many patients have somatosensory evoked potential changes when their arms are abducted (e.g., a
surrender position).
Anatomy of shoulder abduction: Abduction of a shoulder > 90 degrees places the distal plexus on the
extensor side of the joint and potentially stretches the plexus (fig 2). Therefore, it is best to avoid abduction
> 90 degrees, especially for extended periods.

Median Neuropathies

Median neuropathies primarily occur in men between the ages of 20-40 years of age. These men often have large
biceps and reduced flexibility (think weightlifters). The large biceps and reduced flexibility tend to prevent
complete extension at the elbow. This chronic limitation in range of motion results in shortening of the median
nerve over time. Median neuropathies typically involve motor dysfunction and do not resolve readily. In fact, up to
80% of median neuropathies with motor dysfunction are sustained 2 years after the initial onset. Key points of
interest:

Stretch of a nerve: As mentioned in the section on ulnar neuropathy, nerves become ischemic when
stretched more than 5% of their resting length. This amount of stretch tends to kink penetrating arterioles
and exiting venules, both of which decrease perfusion pressure.

224
Page 3
Arm support: When we subsequently anesthetize these men, we may fully extend their arms at the elbow
and place them on arm boards or at the patients sides. This full extension of the elbow stretches
chronically contracted median nerves and promotes ischemia, often at the level of the elbow. Thus, it is
important to support the forearm and hand to prevent full extension in men who have large, bulky biceps
and who cannot fully extend their elbows because of a lack of flexibility.

Radial Neuropathies

Radial neuropathies occur more often than median neuropathies. The radial nerve appears to be injured by direct
compression (in contrast to the median nerve being injured primarily by stretch). The important factor appears to be
compression of the nerve in the mid-humerus region where it wraps posteriorly around the bone (fig 3). Radial
neuropathies tend to have a better chance of recovery than ulnar or median neuropathies. Approximately half get
better within 6 months, and 70% appear to resolve completely within 2 years. Key points of interest:

Surgical retractors: A case series reported several radial neuropathies associated with compression of the
radial nerve by the vertical bars of upper abdominal retractor holders. The arms reportedly were impinged
by these vertical support bars (fig 3.a).
Lateral positions: The radial nerve may be impinged by overhead arm boards when they protrude into the
mid-humerus soft tissue (fig 3.d).
An unsupported arm: Anecdotal reports discuss compression on the nerve in the mid-humeral when the
elbow of a fixated arm (at side or on an arm board) slips, loses support, and the weight of the upper
extremity is supported by the mid-humerus (fig 3.e).

Lower Extremity Neuropathies

Although common peroneal and sciatic neuropathies have the most impact on ambulation, the most common
perioperative neuropathies in the lower extremities involved the obturator and lateral femoral cutaneous nerves.
Key points of interest:

Impact of hip abduction on the obturator nerve: Hip abduction > 30 degrees results in significant strain on
the obturator nerve. The nerve passes through the pelvis and out the obturator foramen. With hip
abduction, the superior and lateral rim of the foramen serves as a fulcrum (fig 4). The nerve stretches
along its full length and also is compressed at this fulcrum point. Thus, excessive hip abduction should be
avoided whenever possible. With obturator neuropathy, motor dysfunction is common. Thankfully, it is
usually not painful, but it can be crippling. Approximately 50% of patients who have motor dysfunction in
the perioperative period will continue to have it 2 years later.
Impact of hip flexion on the lateral femoral cutaneous nerve: Prolonged hip flexion > 90 degrees increases
ischemia on fibers of the lateral femoral cutaneous nerve. One-third of this nerves fibers pass through the
inguinal ligament as they pass into the thigh (fig 5). Hip flexion > 90 degrees results in lateral
displacement of the anterior superior iliac spine and stretch of the inguinal ligament. The penetrating nerve
fibers are compressed by this stretch and, with time, become ischemic and dysfunctional. The lateral
femoral cutaneous nerve carries only sensory fibers, so there is no motor disability when it is injured.
However, patients with this perioperative neuropathy can have disabling pain and dysthesias of the lateral
thigh. Approximately 40% of these patients have dysesthesias that last for more than one year.
Peroneal neuropathies and leg holders: It appears that most peroneal neuropathies are associated with
direct pressure of the lateral leg, just below the knee, where the peroneal nerve wraps around the head of
the fibula. Leg holders, ranging from candy cane leg holders to various leg holders or crutches that
hold the leg and foot, can impinge on the nerve as it wraps around the head of the fibula. The result can be
devastating, with prolonged foot drop and difficulty ambulating.

224
Page 4
Practical Considerations for Perioperative Peripheral Neuropathies

Use padding to distribute compressive forces. Although there are few studies that demonstrate padding to
impact the frequency or severity of perioperative neuropathies, it makes sense to distribute point pressure.
The use of padding also is found by juries to be positive in medicolegal actions.
Position joints to avoid excessive stretching, recognizing that stretch of any nerve > 5% of its resting
length over a prolonged period results in varying degrees of ischemia and dysfunction.
What to do if your patient develops a peripheral neuropathy:

! If the loss is sensory-only, it is reasonable to follow the patient daily for up to 5 days. Many
sensory deficits in the immediate postoperative period will resolve during this time. If the deficit
persists for longer than 5 days, it is likely that the neuropathy will have an extended impact. It is
appropriate at that point to get a family physician, internist, or neurologist involved to provide
long-term care.
! If the loss is motor-only or combined sensory/motor, it would be prudent to get a neurologist
involved early. These patients likely have a significant neuropathy and will need prolonged
postoperative care.

Unique Positioning Problems with Catastrophic Results

Spinal cord ischemia. This rare event occurs when patients undergoing pelvic procedures (e.g.,
prostatectomy) are placed in a hyperlordotic position, with greater than 15 degrees of hyperflexion at the
L
2
-L
3
interspace. This results in spinal cord ischemia and infarction. It is best detected with magnetic
resonance imaging. Operating room tables made in the U.S. are designed to limit hyperlordosis in supine
patients, even when the table is maximally retroflexed with the kidney-rest elevated. In almost all reported
cases, the table has been maximally retroflexed, the kidney-rest has been elevated, AND towels or blankets
have been placed under the lower back to promote further anterior or forward tilt of the pelvis (to improve
vision of deep pelvic structures). In general, anesthesia providers should not allow placement of materials
under the lower back for this purpose.
Thoracic outlet obstruction. This rare event occurs when patients with this syndrome are positioned prone
or, less commonly, laterally. In almost all reported cases, the shoulder has been abducted > 90 degrees. In
that position, the vasculature to the upper extremity is either compressed between the clavicle and rib cage
or between the anterior and middle scalene muscle bodies. This entrapment of the vasculature leads to
upper extremity ischemia. When prolonged, the results range from minor disability to severe tissue loss
that requires forequarter amputation. Simple preoperative questions such as Can you use your arms to
work above your head for more than a minute? can elicit a history of thoracic outlet obstruction and
reduce the risk of this potentially devastating complication.
Steep head-down positions. As surgeons gain experience with new technologies (e.g., robotics for pelvic
procedures), they often request steep head-down positions. These positions can be associated with
cephalad shifting of anesthetized patients on operating room tables. Patients often are fixated to these
tables with draw sheets and other retaining devices (e.g., shoulder braces). Cephalad shifting can lead to
cervical plexopathies from stretch and subclavian vessel obstruction from compression. Although
intracranial pressure also increases, it rarely results in a negative outcome. However, orofacial edema
requires careful airway attention. Recently, there are reports of patients sliding cephaladly off of operating
room tables when they are placed in steep head down positions and not secured to the beds. The resulting
cervical spine and cerebral injuries have been devastating to both patients and providers.
Steep head-up positions. While many of us think of sitting craniotomies for these positions, the most
common of the steep head-up positions is the beach chair position used for many shoulder surgeries.
These positions invoke considerable debate on hemodynamic issues, specifically systemic blood pressure
and cerebral blood pressure. The Anesthesia Patient Safety Foundation held a special workshop on this
issue and published an excellent summary in its Winter 2009-2010 Newsletter. In addition, a number of
severe brachial and cervical plexopathies have been reported. It appears that at least some of these
plexopathies have been associated with nerve stretch or compression when patients who often have their
heads fixated slide laterally or distally during procedures.

224
Page 5
Soft tissue problems. Skin and other soft tissues are particularly vulnerable to sustained pressure, resulting
in ischemia. While there are many examples, several related to prone positions deserve special mention.
Tissues in direct contact with rolls that extend from shoulder girdle across the chest and to the pelvis may
become ischemic with prolonged pressure (fig 6). There are multiple cases of women with large breasts
who developed severe ischemia of one or both breasts when they were pushed in between chest rolls. The
lateral pressure was sufficient to cause necrosis and sloughing. In most of these reported cases, the women
subsequently underwent mastectomies. Similarly, ostomies have developed ischemia from pressure when
they are placed in direct contact with these rolls.

Suggested References
American Society of Anesthesiologists Task Force on the Prevention of Perioperative Neuropathies. Practice
guidelines for the prevention of perioperative neuropathies. Anesthesiology 2000;92:1168-82.
Contreras MG, Warner MA, Charboneau WJ, et al. Anatomy of the ulnar nerve at the elbow: potential relationship
of acute ulnar neuropathy to gender differences. Clin Anat 1998;11:372-8.
Litwiller JP, Wells RE, Halliwill JR, et al. Effect of lithotomy positions on strain of the obturator and lateral
femoral cutaneous nerves. Clin Anat 2004;17:45-9.
Staff NP, Engelstad J, Klein CJ, et al. Post-surgical inflammatory neuropathy. Brain. 2010;133:2866-80.
Warner MA, Warner DO, Matsumoto JY, et al. Ulnar neuropathy in surgical patients. Anesthesiology 1999;90:54-9.
Warner MA. Patient positioning and related injuries. In: Barash PG, et al, editors. Clinical anesthesia. 6th Edition.
Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2009:793-814.

Disclosure

1a 1b
Figure 1: (a) The ulnar nerve of the right arm passes distally behind the medial epicondyle and underneath the aponeurosis that
holds the two heads of the flexor carpi ulnaris together. The proximal edge of the aponeurosis is
sufficiently thick in 80% of men and 20% of women to be distinct anatomically from the remainder of the tissue. It is commonly
called the cubital tunnel retinaculum. (b) Viewed from behind, the ulnar nerve is intrinsically compressed by the cubital tunnel
retinaculum when the elbow is progressively flexed beyond 90 and the distance between the olecranon and the medial
epicondyle increases.

224
Page 6

2a 2b
Figure 2: (a) The neurovascular bundle to the upper extremity passes on the flexion side of the shoulder joint when the arm is at
the side or abducted less than 90. (b) Abduction of the arm beyond 90 transitions the neurovascular bundle to where it now
lies on the extension side of the shoulder joint. Progressive abduction greater than 90 increases stretch on the nerves at the
shoulder joint.

224
Page 7

Figure 3: The anatomy of the radial nerve is shown in the upper left corner, illustrating how it wraps around the mid-humerus.
Reported mechanisms of perioperative injury include (a) compression by surgical retractor support bar; (b) direct needle trauma
at the wrist; (c) compressive tourniquet effect by a drawsheet at the wrist; (d) impingement by an overhead arm board; (e)
compression in the mid-humerus level as the arm supports much of the weight of the upper extremity.

224
Page 8

3a 3b
Figure 4: (a) The obturator nerve passes through the pelvis and exits out the superior and lateral corner of the obturator foramen
as it continues distally down the inner thigh. (b) Abduction of the hip stretches the obturator nerve and can provoke ischemia,
especially at the exit point of the obturator foramen. The point serves as a fulcrum for the nerve during hip abduction.

4a 4b

Figure 5: (a) Approximately one-third of the lateral femoral cutaneous nerve fibers penetrate the inguinal ligament as the nerve
passes out of the pelvis and distally into the lateral thigh. (b) Hip flexion, especially when greater than 90, leads to stretch of the
inguinal ligament as the ilium is displaced laterally. This stretch causes the intra-ligament pressure to increase and compresses
the nerve fibers as they pass through the ligament.

224
Page 9

Figure 6: Soft tissues can be compressed and even become ischemic if there is too much pressure on them for long periods of
time. This figure illustrates how chest rolls may compress the lateral aspects of large breasts or a stoma in prone positioned
patients.

226
Page 1
Anesthesia and the Patient with Thyroid, Parathyroid, or Adrenal Disease
William R. Furman, M.D. Nashville, Tennessee
Introduction
Management of a patient with adrenal, thyroid, or parathyroid disease is based on an understanding of the
pathophysiology of the specific hormonal system involved. This lecture will discuss current concepts and new
developments in the perioperative care of patients with adrenal cortical insufficiency, hyper- or hypothyroidism,
hyperparathyroidism, or pheochromocytoma.
Adrenal Insufficiency
Normal Hypothalamic-Pituitary-Adrenal (HPA Axis) Function (Fig 1). Adrenal production and secretion of cortisol
is controlled by blood levels of adrenocorticotropic hormone (ACTH). ACTH is secreted by the anterior pituitary
gland which is, in turn, stimulated by hypothalamic corticotropin releasing hormone (CRH) carried directly from the
hypothalamus to the pituitary by a specialized portal venous system. Stress of almost any variety stimulates the
hypothalamus to release CRH, and blood cortisol levels exert a negative feedback influence on the production of
both CRH and ACTH [1].
Figure 1: Normal HPA Axis Function
Cortisol is important because of its effects on the cardiovascular system, especially in the presence of stress. It
maintains vascular tone, endothelial integrity, vascular permeability, the distribution of total body water in the
vascular compartment, and it potentiates the constrictor effects of catecholamines on vascular tone. When cortisol
levels are deficient, systemic vascular resistance and myocardial contractility are decreased [2]. Conversely, patients
with an excess of cortisol have hypertension associated with an increased plasma volume and an increased systemic

226
Page 2
vascular resistance. They also develop left ventricular hypertrophy, and are at risk for coronary ischemia related to
abnormal lipid and glucose metabolism and an increased tendency toward thrombosis [3] (Table 1).

Table 1: Effects of Excess Cortisol

Humoral Structural
Hypertension Left Ventricular Hypertrophy
! Plasma Volume Vascular Remodeling
! Systemic Vascular Resistance
" Diastolic Relaxation
" HDL, !HDL
Prothrombotic Effects

Most of the symptoms experienced by patients with chronic adrenal insufficiency are non-specific. They include
fatigue, malaise, lethargy, weight loss, anorexia, arthralgias, myalgias, nausea, vomiting, abdominal pain, diarrhea,
and fever. When chronic adrenal insufficiency is due to non-function of the adrenal glands (primary adrenocortical
insufficiency), hyponatremia and hyperkalemia due to concomitant aldosterone deficiency may be seen. These
metabolic abnormalities are less likely when the adrenal insufficiency is due to pituitary or hypothalamic (secondary
or tertiary insufficiency) failure or to HPA Axis suppression by the prior administration of exogenous steroids.
Common etiologies of primary chronic adrenal insufficiency are immunologic (autoantibody), malignant (metastatic
cancer, commonly from lung or breast), or infectious (such as tuberculosis).

Adrenal (Addisonian) Crisis. The term acute adrenal failure, or Addisonian crisis, is applied to the condition of
circulatory shock due to cortisol deficiency, usually in the presence of primary adrenal failure. This generally occurs
because of acute stress such as trauma, surgery, or infection in a patient with underlying chronic adrenal
insufficiency. Another etiology is the Waterhouse-Friedricksen Syndrome of bilateral acute adrenal hemorrhage,
usually associated with fulminant sepsis from an endotoxin-producing bacterium such as N. meningitides.
Characteristic physiologic findings are hypovolemic shock with myocardial and vascular unresponsiveness to
catecholamines. Treatment usually requires several liters of isotonic saline plus corticosteroid administration. 100mg
of IV cortisol equivalent every 6-8 hours usually reverses the pathophysiology in the first day of treatment. Tapering
and conversion to an oral agent are usually possible in 1-4 days. The equivalent doses and corresponding relative
potencies of common corticosteroids are commonly expressed using hydrocortisone 100 mg as the standard for
comparison (Table 2). Hydrocortisone is the synthetic form of cortisol. It is worth noting that the commonly-used
dosage of dexamethasone 4 mg, intended for anti-emetic prophylaxis, is approximately equivalent to cortisol 100mg
and has a much longer duration of action.

Table 2: Relative Equivalent Potencies of Common Corticosteroid Drugs

Agent Equivalent Dose (mg) Relative Potency Duration (hr)
Hydrocortisone 100 1 8-12
Cortisone 125 0.8 8-12
Prednisone; Prednisolone 25 4 12-36
Methylprednisolone 20 5 12-36
Dexamethasone 4 25 >24

Relative Adrenal Insufficiency or Unresponsiveness
Relative adrenal insufficiency or Critical Illness Related Corticosteroid Insufficiency (CIRCI) is a term that has been
applied in retrospect to clinical situations where 100-300mg per day of IV hydrocortisone eliminates a pre-existing
need for vasopressors. The implication is that the HPA axis may not be abnormal, but the magnitude of the expected
response to stress is reduced. Prior steroid treatment is a potential cause of this condition. Features that have been
described include:

226
Page 3
Unexplained vasopressor-dependent refractory hypotension
Major discrepancies between the anticipated severity of the disease and the present state of the patient
High fever without apparent cause (negative blood cultures), or not responding to antibiotics
Hypoglycemia, hyponatremia, hyperkalemia, neutropenia, eosinophilia
Prompt resolution with steroid treatment
Vasopressin can be useful

What steroid management is required for a patient who has received exogenous steroids and may have relative
adrenal insufficiency? Steroid-induced adrenal suppression is highly variable and its duration is unpredictable (days
to perhaps years). The consequences of a short course of steroids are minimal, so anticipatory treatment is generally
safe. Pain, fever, hypovolemia, and surgery all normally cause increases in corticotropin and cortisol that persist for
2 days after surgery. Therefore, in suppressed patients, the recommended approach is 48-72 hours of tapered
replacement beginning with no more than 100-150mg of cortisol equivalent per day [4, 5]. Animal studies have
indicated that higher doses do not offer benefit [6]. The commonly-used dosage of dexamethasone 4mg, intended for
anti-emetic prophylaxis, is approximately equivalent to cortisol 100mg.

Etomidate and Adrenal Function. A single dose of etomidate 0.3mg/kg has been shown to suppress cortisol
production, but while the effect is seen at 4-6 hours, it does not appear to be present at 24 hours [7, 8].

Hyper- and Hypothyroidism
Thyroid hormone production. The thyroid gland is subject to feedback in a manner similar to the adrenal gland.
Thyroid releasing hormone (TRH) is made in the hypothalamus and reaches the anterior pituitary via the long portal
vessels. TRH stimulates pituitary production of thyroid stimulating hormone (TSH), which reaches the thyroid
through the blood stream. TSH stimulates the thyroid to incorporate iodide into thyroglobulin and release thyroid
hormone (~80% as T4 and 20% as the much more potent T3) into the blood stream. T4 is converted to T3 in the
periphery, where it exerts its effects. T3 and T4 exert negative feedback on the production of TRH and TSH [9].

Hyperthyroidism. Overproduction of thyroid hormones results in elevated levels of unbound T3 and T4 and
produces the clinical syndrome known as thyrotoxicosis. The principal manifestations are cardiac (Table 3),
neurologic, and constitutional [10]. Thyroid hormone decreases systemic vascular resistance, increases resting sinus
rate, and increases cardiac sensitivity to catecholamines, resulting in systolic (not diastolic) hypertension and
tachycardia. Atrial fibrillation is common, and may be the presenting sign of hyperthyroidism, as it was for
President George H. W. Bush in 1991. Other signs of marked hyperthyroidism include high-output congestive heart
failure or angina (even in the absence of coronary plaques) and pulmonary hypertension. Tremor, hyperreflexia, and
irritability are common neurologic manifestations. Periodic paralysis, characterized by hypokalemia and proximal
muscle weakness, may also occur. Fever and heat intolerance are common. Gastrointestinal symptoms include
nausea, vomiting, and diarrhea, as well as hepatic dysfunction and jaundice.

Table 3: Cardiovascular Effects of Hyperthyroidism

Humoral Structural
" Systemic Vascular Resistance Left Ventricular Hypertrophy
Sinus Tachycardia, SVT, AFib Cardiomyopathy
! Cardiac Contractility Pulmonary Hypertension
Improved Diastolic Relaxation
Coronary Spasm/Coronary Ischemia
! Erythropoietin/ ! Blood Volume
Systolic Hypertension - Widened Pulse Pressure

226
Page 4
The most common cause of thyrotoxicosis is Graves Disease; however it may also be caused by:
Struma ovarii, which is the presence of thyroid tissue in an ovarian teratoma
HCG-secreting hydatidiform mole [11]
The administration of iodinated contrast dye to a susceptible patient
Amiodarone

Thyroid Storm. All patients with thyrotoxicosis should be considered to be at risk of developing thyroid storm,
which is a life-threatening emergent clinical syndrome that has a ~30% mortality rate despite treatment. Thyroid
storm is characterized by worsening of the signs and symptoms of thyrotoxicosis, including cardiac dysfunction,
hyperglycemia, hypercalcemia, hyperbilirubinemia, altered mental status, seizures, and coma. It may be triggered in
a thyrotoxic patient by any one of several stresses, including:
Infection
Stroke
Trauma, especially to the Thyroid Gland [12]
Surgery
Diabetic Ketoacidosis
Drugs: Pseudoephedrine, Aspirin, Excess Iodine Intake, Contrast Dye, Amiodarone
Incorrect Anti-Thyroid Drug Discontinuation

Diagnosis of Thyroid Storm. The distinction between thyrotoxicosis and thyroid storm is one of degree. Clinical
scoring systems can be used as a guide. One example (Table 4) assigns points for temperature (up to 30), central
nervous system effects (up to 30), gastrointestinal dysfunction (up to 20), and cardiovascular signs and symptoms
(up to 50). The points are summed, and a total of 45 or above is considered suggestive of thyroid storm, while a
score between 25 and 44 indicates impending storm [10].

Table 4: Example of Scoring System for Thyroid Storm.
System Parameter Scoring Maximum
Thermoregulatory Temperature (F above 98.9) 5 points for T of 99-99.9 and
5 more for every degree higher
up to T !104
30
Central Nervous Altered Mental Status 10 points for agitation
20 points for delirium
30 points for seizures or coma
30
Gastrointestinal Nausea, Vomiting, Abdominal Pain
Hepatic Disease
10 points for symptoms
20 points for jaundice
20
Cardiovascular Congestive Heart Failure 5 points for pedal edema
5 for bibasilar rales
5 for pulmonary edema
15
Cardiovascular Rhythm 5 points for heart rate 90-109
and 5 more for every 10 bpm
up to HR !140 bpm
10 points for atrial fibrillation
35

45 points = probable thyroid storm; 25-44 points suggests impending thyroid storm

Treatment. The initial approach to treatment for thyrotoxicosis is to reduce thyroid hormone synthesis. Definitive
therapy with either surgery or radioactive iodine may follow after the patient has been made euthyroid[13]. Initial
control is accomplished by administration of propythiouracil (PTU) to inhibit thyroid peroxidase (TPO), the enzyme
that catalyzes the incorporation of iodide into thyroglobulin. At least an hour after giving PTU, large doses of stable
iodide are given. This takes advantage of a paradoxical effect, called the Wolfe-Chaikoff Effect. Rather than
catalyze additional incorporation of iodide into thyroglobulin, as might be expected, large amounts of iodide
suppress gene transcription of TPO, further reducing the glands capacity to produce and release hormone. This
benefit is temporary (~1 week), but is useful at the beginning of thyroid suppression.

226
Page 5
Treatment of thyroid storm incorporates the above, often at larger doses. In addition to PTU and iodide, it includes
beta adrenergic blockade and corticosteroids. The traditional beta blocker is propranolol, selected because it blocks
peripheral conversion of T4 to T3 in addition to its beneficial cardiovascular effects. Dosages of as much as 120mg
po or 3mg IV every 4 hours have been used. Other beta blockers such as atenolol, metoprolol, and esmolol have
been used and are not contraindicated.
Corticosteroids are recommended to treat the relative adrenal insufficiency that results from accelerated metabolism.
Cortisol levels tend to be in the normal range in thyrotoxic patients, but they ought to be higher to be appropriate to
the level of stress. The recommended approach is tapered replacement beginning with 100mg of cortisol equivalent
every 8 hours.
The general rule regarding surgery in the setting of thyrotoxicosis or thyroid storm is to only undertake that which
cannot be delayed until control of thyroid hormone secretion and effect has been accomplished. It is worth
reiterating that thyrotoxicosis can masquerade as coronary ischemia [14] and present a very difficult dilemma.
Sub-clinical hyperthyroidism. This is a clinical entity characterized by normal free thyroid hormones (FT3 and FT4)
and elevated TSH levels. Recent reviews have shown that this entity may cause cardiac function abnormalities that
can be demonstrated on surface cardiac echo. Reported echocardiographic findings are: increased LV wall mass,
increased volume of the cardiac chambers, increased diameter of the ascending aorta, and LV diastolic dysfunction.
LV systolic function appears to be preserved however a shortened ejection time is reported. These abnormalities are
reported to resolve with treatment of the hyperthyroidism[15].
Hypothyroidism. The cardiovascular effects of hypothyroidism (Table 5) typically do not pose an impediment to
anesthetic and surgical management. Hypothyroid patients are at increased risk of ischemic heart disease; however
the hypothyroid condition may be protective because it results in a reduced capacity for cardiac work. Thyroid
hormone replacement in hypothyroid patients with coronary artery disease must be undertaken carefully, as it may
provoke ischemia [16].
Table 5: Cardiovascular Effects of Hypothyroidism
Humoral Structural
! Systemic Vascular Resistance Ischemic Heart Disease
Sinus Bradycardia Pericardial Effusion (Rarely Significant in Volume)
" Cardiac Contractility
Diastolic Dysfunction
" Response to ! and " Adrenergic Agonists
Diastolic Hypertension - Narrowed Pulse Pressure
Hyperparathyroidism and Hypercalcemia
Serum calcium is regulated by parathyroid hormone (PTH), calcitonin, and the active form of Vitamin D. PTH
stimulates bone resorption, inhibits renal excretion of calcium, and promotes conversion of Vitamin D to its active
form. Calcitonin, which is produced by the medullary cells of the thyroid gland (also called C Cells), antagonizes the
effects of PTH. Vitamin D promotes gut absorption of calcium, phosphate and magnesium, and facilitates the effects
of PTH on bone.
Parathyroid cells have a calcium receptor (CaR) on their cell surface that senses ionized calcium levels. In the
presence of an elevated ionized calcium level, the CaR signals a decrease in PTH production. In primary
hyperparathyroidism, a single gland becomes enlarged and its CaR almost always becomes ineffective. As a result,
that gland overproduces PTH, resulting in hypercalcemia. Secondary hypercalcemia is a condition associated with
chronic kidney disease in which chronically low calcium levels lead to down-regulation of the CaR, ultimately and
paradoxically resulting in autonomous excessive PTH production [17]. Typically, this is associated with hyperplasia
of all 4 parathyroid glands.
226
Page 6
Calcium has an integral role in neuromuscular function, neurotransmitter signaling, cardiac conduction, energy
metabolism, enzymatic action, hormone secretion, and hemostasis. All of these functions may be disrupted by
hypercalcemia, however patients with mild hypercalcemia commonly have non-specific symptoms. There is,
however, a condition of hypercalcemic crisis, characterized by altered mental status and disturbances of cardiac,
renal, and gastrointestinal function. This condition is most often associated with primary hyperparathyroidism and a
serum calcium >14 mg/dL. The patients are typically dehydrated and the treatment is rehydration followed by
expeditious parathyroidectomy. Correction of the calcium to normal levels prior to surgery is not required [18].
In addition to surgical removal, options for treatment of hypercalcemia include hydration, diuretics to produce a
calciuresis, steroids if the hypercalcemia is related to a non-parathyroid malignant tumor, calcitonin, and cinacalcet.
Cinacalcet is a new calcimimetic agent that stimulates the CaR, resulting in decreased PTH production [19].
Pheochromocytoma
Tumor overproduction of the adrenal medullary hormones dopamine, norepinephrine, and/or epinephrine results in a
hypertension and tachycardia plus heart rate and blood pressure hyper-responsiveness to noxious stimulation. The
cells that produce these hormones are of neural crest origin. When the tumor arises in the adrenal medulla, it is
called a pheochromocytoma; when it arises elsewhere, it is called a paraganglioma. In either case, life-threatening
hypertensive crises are possible, especially during surgery on a previously undiagnosed patient. Pheochromocytoma
often goes unrecognized because its symptoms (headache, palpitations, sweating) are non-specific and as many as
8% are asymptomatic. Its prevalence in the general population may be as high as 1 in 2000 [20].
Cardiac function in the setting of pheochromocytoma. Most patients with pheochromocytoma have preserved
cardiac function or hyperfunction, but some develop a cardiomyopathy in the setting of catecholamine excess. A
recent review[21] of echocardiograms in 36 patients showed normal function in 90% (60% normal echo; 30%
normal function with concentric LVH). 3 patients had decreased LV ejection fraction below 50%. 2 of these had
inverted Takotsubo-type cardiomyopathy and 1 had diffuse hypokinesia. Catecholamine cardiomyopathy is widely
reported and noted to resolve with fluid administration and adrenergic blocking drugs.
Mechanism of hypertension. The conventional theory (unsupported by scientific evidence) is that hypertension
occurs because arteriolar smooth muscle is exposed to norepinephrine, since norepinephrine is the neurotransmitter
for sympathetic nervous system mediated vasoconstriction. According to this theory, exogenous norepinephrine
bathes the synapses directly. But if this were true, the sympathetic nervous system should be suppressed and should
not regulate blood pressure; instead the circulating hormones would do so[22]. This theory has prompted the
practice (also unsupported) of pre-operative alpha adrenergic blockade prior to tumor resection as well as the
mistaken beliefs that blood catecholamine levels correlate with blood pressure level and that hypertension occurs
when the surgeon manipulates the tumor because this squeezes hormones out of the tumor and into the blood stream.
Scientific data suggest contrary interpretations. Catecholamine levels do not correlate with the time or magnitude of
blood pressure levels [23], and in practice two weeks of preoperative non-selective alpha adrenergic blockade with
phenoxybenzamine is usually ineffective at preventing intraoperative hypertension. Published clinical experience
supports an approach in which hypertension, if present, is controlled prior to surgery with any of a variety of agents
[24]. Once the blood pressure is under reasonable control, the procedure is undertaken; however there is no basis to
expect that intraoperative hypertension will not occur.
In theory, the non-specific alpha blocker phenoxybenzamine would not be an agent of choice because it has alpha-2
blocking properties, and blocking the alpha-2 receptor would be expected to raise blood pressure and pulse [25]. It is
also very expensive, as it has no other clinical application. An alpha-1 selective blocker would seem more
appropriate, and all of them cost far less. In fact, calcium channel blockers, ACE inhibitors and receptor blockers,
beta blockers, and alpha-2 agonists have all been used effectively prior to surgery. During surgery, infusions of
vasodilators and esmolol still may be required to treat hypertension and tachycardia. Infusions of magnesium [26]
and the alpha-2 agonist dexmedetomidine [27] may be useful as well.
Why doesnt receptor blockade work? An alternate theory would be that chronic catecholamine excess amplifies the
sympathetic nervous systems responses to stress and trauma in general. Hypertension and tachycardia would be
caused by the substantial stress of laryngoscopy (not the induction of anesthesia) and the stress of surgical

226
Page 7
manipulations of any kind (not specifically tumor manipulation). This is true in any patient, but the effect appears to
be exaggerated under the influence of chronic catecholamine excess. Such a theory is supported by animal data
showing that the sympathetic nervous system in chronically catecholamine infused rats remains active and
influences blood pressure [28]. The failure of receptor blockade might be explained by the ability of the sympathetic
nervous system to overwhelm the competitive blockade with orders of magnitude greater release of norepinephrine
than normal.

Suggested guidelines for perioperative management prior to pheochromocytoma or paraganglioma removal:
1. Control BP prior to surgery. Use any effective regimen with which you or your colleagues have experience.
2. Aim for 120-160 systolic/65-85 diastolic, and then be prepared to operate. Anesthetic management
recommendations do not appear to be different for the various surgical techniques that have recently been
developed (open vs. laparoscopic; supine, flank, vs. prone position).
3. Cardiomyopathy associated with pheochromocytoma may be uniquely responsive to alpha-adrenergic
blocking agents. Catecholamine cardiomyopathy is an interesting phenomenon whose mechanism is not
fully understood [29-31].
4. No specific agent (volatile or intravenous anesthetic) has been shown to be superior in terms of outcomes.
5. Use what you know best for intraoperative control. For most of us, thats sodium nitroprusside and esmolol.
6. It is hard to support the notion that one should use phentolamine if one is not familiar with its use in any
other situation.
7. The common recommendation that antihypertensive therapy should be given for 2 weeks prior to the
operation has not been tested in properly conducted clinical trials, nor has the recommendation to treat until
orthostatic hypotension has developed. These are not evidence-based recommendations, and may be
entirely incorrect.
8. There probably is a limited role for phenoxybenzamine in modern perioperative medicine, although there
are physicians with many years of experience caring for pheochromocytoma patents who continue to use it
rather than the more selective alpha-1 blocking agents or other classes of antihypertensive drug. For the
patient with an unresectable malignant pheochromocytoma, phenoxybenzamine seems valuable because of
its long duration of action. It is, however, quite expensive.
9. If confronted with severe hypertension after induction and you suspect pheochromocytoma in a previously
undiagnosed patient, dont proceed with surgery unless it is urgent or emergent.
10. But if the surgery is urgent or emergent, see #4 above. Consider using local and regional anesthesia to
supplement your technique.

References
1. Lamberts, S.W., H.A. Bruining, and F.H. de Jong, Corticosteroid therapy in severe illness. N Engl J Med,
1997. 337(18): p. 1285-92.
2. de Herder, W.W. and A.J. van der Lely, Addisonian crisis and relative adrenal failure. Rev Endocr Metab
Disord, 2003. 4(2): p. 143-7.
3. Deegan, R.J. and W.R. Furman, Cardiovascular Manifestations of Endocrine Dysfunction. J Cardiothorac
Vasc Anesth, 2011.
4. Salem, M., et al., Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a
problem. Ann Surg, 1994. 219(4): p. 416-25.
5. Purnell, J.Q., et al., Association of 24-hour cortisol production rates, cortisol-binding globulin, and
plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin
Endocrinol Metab, 2004. 89(1): p. 281-7.
6. Udelsman, R., et al., Adaptation during surgical stress. A reevaluation of the role of glucocorticoids. J Clin
Invest, 1986. 77(4): p. 1377-81.
7. Schenarts, C.L., J.H. Burton, and R.R. Riker, Adrenocortical dysfunction following etomidate induction in
emergency department patients. Acad Emerg Med, 2001. 8(1): p. 1-7.
8. Zed, P.J., et al., Etomidate for rapid sequence intubation in the emergency department: is adrenal
suppression a concern? CJEM, 2006. 8(5): p. 347-50.
9. Pimentel, L. and K.N. Hansen, Thyroid disease in the emergency department: a clinical and laboratory
review. J Emerg Med, 2005. 28(2): p. 201-9.
10. Nayak, B. and K. Burman, Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am, 2006.
35(4): p. 663-86, vii.

226
Page 8
11. Chiniwala, N.U., et al., Thyroid storm caused by a partial hydatidiform mole. Thyroid, 2008. 18(4): p. 479-
81.
12. Delikoukos, S. and F. Mantzos, Thyroid storm induced by blunt thyroid gland trauma. Am Surg, 2007.
73(12): p. 1247-9.
13. Ross, D.S., Radioiodine therapy for hyperthyroidism. N Engl J Med, 2011. 364(6): p. 542-50.
14. Lee, S.M., et al., Thyrotoxicosis with coronary spasm that required coronary artery bypass surgery. Intern
Med, 2007. 46(23): p. 1915-8.
15. Kaminski, G., et al., Prospective echocardiographic evaluation of patients with endogenous subclinical
hyperthyroidism and after restoring euthyroidism. Clin Endocrinol (Oxf), 2011. 74(4): p. 501-7.
16. Toft, A.D., Thyroxine therapy. N Engl J Med, 1994. 331(3): p. 174-80.
17. Cunningham, J., F. Locatelli, and M. Rodriguez, Secondary hyperparathyroidism: pathogenesis, disease
progression, and therapeutic options. Clin J Am Soc Nephrol, 2011. 6(4): p. 913-21.
18. Cannon, J., J.I. Lew, and C.C. Solorzano, Parathyroidectomy for hypercalcemic crisis: 40 years'
experience and long-term outcomes. Surgery, 2010. 148(4): p. 807-12; discussion 812-3.
19. Duntas, L.H. and N. Stathatos, Cinacalcet as alternative treatment for primary hyperparathyroidism:
achievements and prospects. Endocrine, 2011.
20. McNeil, A.R., et al., Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and
Auckland. Aust N Z J Med, 2000. 30(6): p. 648-52.
21. Park, J.H., et al., Prevalence and patterns of left ventricular dysfunction in patients with
pheochromocytoma. J Cardiovasc Ultrasound, 2011. 19(2): p. 76-82.
22. Bravo, E.L., Pheochromocytoma: an approach to antihypertensive management. Ann N Y Acad Sci, 2002.
970: p. 1-10.
23. Bravo, E.L., et al., Circulating and urinary catecholamines in pheochromocytoma. Diagnostic and
pathophysiologic implications. N Engl J Med, 1979. 301(13): p. 682-6.
24. Ulchaker, J.C., et al., Successful outcomes in pheochromocytoma surgery in the modern era. J Urol, 1999.
161(3): p. 764-7.
25. Bravo, E.L. and R. Tagle, Pheochromocytoma: state-of-the-art and future prospects. Endocr Rev, 2003.
24(4): p. 539-53.
26. James, M.F. and L. Cronje, Pheochromocytoma crisis: the use of magnesium sulfate. Anesth Analg, 2004.
99(3): p. 680-6, table of contents.
27. Wong, A.Y. and C.W. Cheung, Dexmedetomidine for resection of a large phaeochromocytoma with
invasion into the inferior vena cava. Br J Anaesth, 2004. 93(6): p. 873.
28. Johnson, M.D., et al., Paradoxical elevation of sympathetic activity during catecholamine infusion in rats. J
Pharmacol Exp Ther, 1983. 227(1): p. 254-9.
29. Jindal, V., et al., Pheochromocytoma: presenting with regular cyclic blood pressure and inverted
Takotsubo cardiomyopathy. J Clin Hypertens (Greenwich), 2009. 11(2): p. 81-6.
30. Ganguly, A., et al., Rapid cyclic fluctuations of blood pressure associated with an adrenal
pheochromocytoma. Hypertension, 1984. 6(2 Pt 1): p. 281-4.
31. Ahn, J.T., J.U. Hibbard, and J.B. Chapa, Atypical presentation of pheochromocytoma as part of multiple
endocrine neoplasia IIa in pregnancy. Obstet Gynecol, 2003. 102(5 Pt 2): p. 1202-5.

Disclosure

232
Page 1
Anaphylaxis, Allergy, and Adverse Drug Reactions:
Important Considerations for Perioperative Management
Jerrold H Levy, M.D., FAHA, FCCM Durham, North Carolina
INTRODUCTION
Surgical patients are exposed to multiple foreign substances in the perioperative period including drugs, blood
products, or environmental antigens such as latex. Because any substance can produce an allergic or adverse
reaction, clinicians must be ready to manage patients in this perioperative environment. The most life-threatening
form of an allergic reaction is anaphylaxis, however, the clinical presentation of anaphylaxis may represent different
immune and nonimmune responses.
1
There is confusion in the literature about the term anaphylaxis, and multiple
terms have been reported to describe this reaction. In recent years, anaphylaxis has been redefined as a severe, life-
threatening, generalized or systemic hypersensitivity reaction, mainly mediated by immunoglobulin E (IgE)
antibodies.
2
Further, anaphylaxis represents a serious allergic reaction that is rapid in onset and may cause death.
3-6

The term anaphylactoid, often used to describe for non IgE-mediated reactions, is confusing and probably should no
longer be used. For the practicing clinician, anaphylaxis is best defined as a clinical syndrome characterized by
acute cardiopulmonary collapse following antigen (also called allergen) exposure. Much of the confusion about
anaphylaxis in the literature is because many older anesthetic agents (e.g., d-tubocurarine) could directly degranulate
mast cells. The incidence of immune-mediated anaphylaxis during anesthesia ranges from 1 in 10,000 to 1 in 20,000
based on recent reports.
7
This presentation will define the spectrum of life threatening anaphylactic and allergic
reactions an anesthesiologist may encounter.
ADVERSE DRUG REACTIONS
Adverse drug reactions (ADRs) are common in hospitalized patients. Reports suggest the overall incidence of
serious ADRs

was 6.7% and of fatal

ADRs was 0.32% from data evaluating 39 prospective studies

from US
hospitals.
8,9
A recent study noted fatal adverse drug reactions account for nearly 3% of all deaths in the general
population, and noted hemorrhage is responsible for ~2/3 of the fatal adverse drug reactions and antithrombotic
agents are involved in more than half of the suspected fatal adverse drug reactions.
10
Most serious predictable
adverse drug reactions are in fact not allergic mediated events and related to other causes that include the amount of
drug in the body (overdosage), unintended administration route, or known side effects (i.e., opioid related nausea).
However, some drugs have direct effects on inflammatory cells (i.e., heparin, histamine releasing agents).
Unfortunately, patients often refer to any adverse drug effects as being allergic in nature. Anesthetic drugs can also
produce hypotension via different mechanisms (e.g., propofol induced vasodilation) complicating the diagnosis of
perioperative adverse drug reactions. Allergic drug reactions are often differentiated from other adverse drugs
reactions because they are unpredictable and dose-independent (i.e., reactions due to latex allergy from latex
gloves).
ALLERGY AND ANAPHYLAXIS
Allergic reactions and anaphylaxis have the same pathophysiologic mechanisms, as both are immune mediated
and due to previous exposure to the antigen or a substance of similar structure. Richet and Portier first used the
word anaphylaxis (ana -against, prophylaxis - protection) to describe the marked shock and resulting death that
sometimes occurred in dogs immediately following a second challenge with a foreign antigen.
11
The term allergy
was introduced in 1906, but is now often used to describe IgE-mediated allergic disease.
6
The basis of acute allergic
reactions including anaphylaxis is the release of inflammatory mediators released by mast cells and basophils when
an allergen interacts with membrane-bound IgE.
5,6

232
Page 2
PATHOPHYSIOLOGY
Anaphylaxis and allergy result from the release of inflammatory mediators including membrane-derived lipids,
cytokines, and chemokines.
12
When the offending antigen and IgE bind on the surface of mast cells and basophils,
preformed storage granules are released that contain histamine and tryptase.
13
Other membrane derived lipid
mediators are released including leukotrienes, prostaglandins, and other factors.
13
These inflammatory substances
have a critical role in producing acute cardiopulmonary dysfunction, characterized by a symptom complex of
bronchospasm and upper airway edema in the respiratory system, vasodilation and increased capillary permeability
in the cardiovascular system, and urticaria in the cutaneus system.
14-16
Cardiovascular collapse during anaphylaxis
results from the effects of multiple mediators on the heart and vasculature.
17
The vasodilation seen clinically can
result from a spectrum of different mediators that interact with vascular endothelium and/or vascular smooth
muscle.
1,18
Why some individuals develop severe cardiopulmonary dysfunction instead of minor cutaneous
reactions is unknown, but may relate to systemic compared to local release of inflammatory mediators.
19

Interestingly, the original description of anaphylaxis from sea anemone toxin represents an IgG-mediated response.
IgG mechanisms will be further discussed in protamine reactions that follow.

VASODILATORY SHOCK AND ANAPHYLAXIS
Vasodilatory shock occurs in anaphylaxis because of multiple mechanisms that include: excessive activation of
vasodilators that increase nitric oxide synthesis to activate soluble guanylate cyclase and increase cGMP, and
increased prostacyclin synthesis that activates soluble adenylate cyclase and produces cAMP. Collectively, this
produces vasodilation and shock.
1,18
Nitric oxide and metabolic acidosis from shock also activate vascular
potassium channels to cause persistent vasodilatation despite catecholamine therapy.
1,18
Other mediators that are
released by non IgE mechanisms may also produce shock by different mechanisms (e.g., protamine induced acute
pulmonary vasoconstriction) and heparin will be discussed in non IgE mediated reactions.
1,18

RECOGNITION OF ANAPHYLAXIS
Because any parenterally administered agent can cause death from anaphylaxis, anesthesiologists must diagnose
and treat the acute cardiopulmonary changes that can occur. Studies from Europe suggest that perioperative drug
induced anaphylaxis may be increasing. The onset and severity of the reaction relate to the mediator's specific end
organ effects. Antigenic challenge in a sensitized individual usually produces immediate clinical manifestations, but
the onset may be delayed 2-20 minutes.
14,20,21
The manifestations and course of anaphylaxis are variable, ranging
from minor clinical changes including urticaria to cardiopulmonary collapse including severe bronchospasm,
vasodilatory shock, and pulmonary vascular injury in certain cases, leading to death. The enigma of anaphylaxis is
the unpredictability of the event, the severity of the attack, and the lack of a prior allergic history.
14,20,21

NON-IgE MEDIATED REACTIONS
Other immunologic and nonimmunologic mechanisms release inflammatory mediators independent of IgE,
creating a clinical syndrome identical with anaphylaxis. Polymorphonuclear leukocyte (neutrophil) activation can
occur following complement activation by immunologic (antibody mediated: IgM, IgG-antigen activation) or non-
immunologic (heparin, protamine, endotoxin, cardiopulmonary bypass) pathways.
22
,
23,24
Complement fragments of
C3 and C5 (C3a and C5a) release histamine from mast cells and basophils, contract smooth muscle, and increase
capillary permeability. In addition, C5a binds receptors on neutrophils and platelets, causing chemotaxis,
aggregation, and activation.
23,24
Aggregated leukocytes embolize to various organs producing microvascular
occlusion and liberation of inflammatory products including oxygen-free radicals, lysosomal enzymes and
arachidonic acid metabolites (i.e. prostaglandins and leukotrienes). IgG antibodies directed against antigenic
determinants or granulocyte surfaces can also activate leukocytes, and are thought to be responsible for the clinical
expressions of transfusion reactions, pulmonary vasoconstriction following protamine reactions, and transfusion
related acute lung injury (TRALI).
25-27

HEPARIN, HIT, AND KININ GENERATION
Following heparin administration, IgG antibody formation is common. These antibodies bind heparin-PF4
complexes on the platelet surface to form immune complexes that activate platelets to promote thrombin formation
and thrombosis.
22
This is the clinical manifestation of heparin induced thrombocytopenia (HIT). Nearly 7-50% of
heparin-treated patients form heparin-PF4 antibodies.
22
However, recent reports about allergic reactions to heparin
from China were because of an oversulfated chondroitin sulfate contaminant that directly activated the kinin-
kallikrein pathway to produce bradykinin, a potent vasoactive mediator. In addition, this contaminant induced

232
Page 3
generation of C3a and C5a.
28
Angiotensin converting enzyme inhibitors also may potentially increase bradykinin
levels, and this is the mechanism of vasodilation, angioedema, and cough that can occur with their use.
1

ANGIOEDEMA
Angioedema is the rapid swelling of skin, mucosa, and submucosal tissues most commonly produced by allergic
reactions, but also by ACE inhibitors as noted above.
29
Oral, laryngeal, and pharyngeal swelling can occur with
acute airway compromise needing urgent airway control. There are also inherited qualitative and quantitative
deficiencies of the complement C1 esterase inhibitor (C1-INH) called hereditary angioedema (HAE). Patients with

HAE also have recurrent episodes of gastrointestinal manifestations of the disease. Bradykinin plays a critical role
in angioedema as previously noted. Therapy of attacks includes symptomatic management and C1-INH from C1-

INH concentrates. Patients with this history and documented HAE need short-term prophylaxis before surgery or
dental treatment because tissue injury activates complement to increase C1-INH levels and also antifibrinolytics that
inhibit plasmin mediated activation. New therapies are also being studied in this life threatening disease. (16) A
C1-INH concentrate (Cinryze) is currently FDA-approved indicated for routine prophylaxis against angioedema
attacks in adolescent and adult patients with Hereditary Angioedema (HAE).
29

NONIMMUNOLOGIC RELEASE OF HISTAMINE
Many diverse molecular structures administered during the perioperative period degranulate mast cells to release
histamine in a dose-dependent, nonimmunologic fashion.
30-33
Intravenous administration of morphine, atracurium,
or vancomycin can release histamine, producing vasodilation and urticaria along the vein of administration.
Although the cardiovascular effects of histamine release can be treated effectively with intravascular volume
administration and/or catecholamines, the responses in different individuals may vary.
1
The newer neuromuscular
blocking agents (e.g., rocuronium and cisatracurium) lack histamine releasing effects but can produce direct
vasodilation and false-positive cutaneous responses that can confuse allergy testing and interpretation.
31,34
The
mechanisms involved in nonimmunologic histamine release represent degranulation of mast cells but not basophils
by cellular activation and stimulation of phospholipase activity in mast cells.
35

TREATMENT PLAN
Most anesthetic drugs and agents administered perioperatively have been reported to produce anaphylaxis.
1

Therefore, a plan for treating anaphylactic reactions must be established before the event.
1
Airway maintenance,
100% oxygen administration, intravascular volume expansion, and epinephrine are essential to treat the hypotension
and hypoxia that results from vasodilation, increased capillary permeability, and bronchospasm.
1
Table 2 lists a
protocol for management of anaphylaxis during general anesthesia, with representative doses for a 70-kilogram
adult. Therapy must be titrated to needed effects with careful monitoring. The route of administration of
epinephrine and the dose depends on the patient's condition. (1) Rapid and timely intervention with common sense
must be used to treat anaphylaxis effectively.

Reactions may be protracted with persistent hypotension, pulmonary hypertension and right ventricular
dysfunction, lower respiratory obstruction, or laryngeal obstruction that persist 5 to 32 hours despite vigorous
therapy.(24) Novel therapeutic approaches for shock and/or right ventricular failure are currently under
investigation.
35
During general anesthesia patients may have altered sympathoadrenergic responses to acute
anaphylactic shock. In addition, the patient during spinal or epidural anesthesia may be partially sympathectomized,
needing earlier intervention with even larger doses of epinephrine and other catecholamines.
36
Additional
hemodynamic monitoring including radial and pulmonary artery catheterization may be needed when hypotension
persists despite therapeutic interventions as listed. Following anaphylaxis, patients should be carefully monitored
for 24 hours as they may develop recurrence of manifestations following successful treatment and covered with
corticosteroids for the acute event.
1

After the initial resuscitation, norepinephrine is also an effective agent that should be considered for treating
shock and dopamine should be avoided.
37
Based on the efficacy of vasopressin in reversing vasodilatory shock, it
should also be considered in therapy of anaphylactic shock not responding to therapy.
1
,
18,38
There are increasing
laboratory and clinical reports supporting the use of vasopressin in anaphylactic shock.
39,40
When available, the use
of transesophageal echocardiography in an intubated patient, or potentially transthoracic echocardiography can be
useful in diagnosing the cause of acute or persistent cardiovascular dysfunction.
1

232
Page 4

PRETREATMENT FOR ALLERGIC REACTIONS
Hypersensitivity reactions are more likely to occur in patients with a history of allergy, atopy, or asthma.
However, this does not make it mandatory to pretreat these patients with antihistamines and/or corticosteroid
because there is no data in the literature to suggest that pretreatment is effective for true anaphylactic reactions.
Most of the literature on pretreatment is from studies evaluating patients with previous radiocontrast media reactions
that are non-immunologic mechanisms. Although attempts to pretreat patients for anaphylaxis to latex have been
used, there is no data to support this as an effective preventative measure and removal of latex from the

perioperative environment is important. In fact, pretreatment may lull physicians into a false sense of security.
Further, even when large doses of corticosteroids have been administered, life threatening anaphylactic reactions
have occurred.
41
Allergists have used immunospecific pretreatment therapies, but these are not practical for
perioperative use.

MANAGEMENT OF THE ALLERGIC PATIENT
Patients presenting with an allergic history need to be carefully evaluated. Patients may report allergy when the
reaction was a predictable adverse drug reaction. However, for practical and medico-legal purposes, that class of
drug should be avoided if possible when the history is consistent with an allergic reaction, and preservative free
alternatives should be chosen. The problem occurs whenever multiple drugs are simultaneously administered or
when patients present with muscle relaxant reactions because of the risk of cross reactivity to the biquarternary
ammonium ions in the molecule. In this situation, skin testing may be required to see what the patient is can safely
be administered.

EPIDEMIOLOGY OF ANAPHYLAXIS: AGENTS IMPLICATED
Although any molecule can produce anaphylaxis, the drugs typically associated with producing perioperative
anaphylaxis include antibiotics, blood products, neuromuscular blocking drugs (NMBDs), polypeptides (aprotinin,
latex, and protamine), and intravascular volume expanders.
1
During surgery, the risk of anaphylaxis is reported to
be between 1:3500 and 1:20,000, with a mortality rate of 4% and an additional 2% surviving with severe brain
damage.
1
,
7
More recent data suggest the incidence of perioperative anaphylaxis is 1 in 10,00020,000.
7
Patients
undergoing major surgery are an increased risk group, because of the multiple blood products, polypeptides, and
potential for impaired cardiovascular function. Mertes reported an epidemiological study from 99-01 of 789
reactions diagnosed by clinical history, skin tests, and/or specific IgE in 518 cases (66%) and nonimmune reactions
in 271 cases (34%).
42
The most common causes were NMBAs (58.2%), latex (16.7%), and antibiotics (15.1%), of
which rocuronium (43%) and succinylcholine (22.6%) were the most common NMBAs reported. The positive
predictive value of tryptase for the diagnosis of anaphylaxis in their study was 92.6%; the negative predictive value
was 54.3%.
42
The agents most often implicated will be discussed.

LATEX ALLERGY
Latex represents an environmental agent often associated as a cause of perioperative anaphylaxis. Health care
workers, children with spina bifida and urogenital abnormalities, and certain food allergies have also been
recognized as individuals at increased risk for anaphylaxis to latex.
43-45
Brown reported a 24% incidence of irritant
or contact dermatitis and a 12.5% incidence of latex-specific IgE positivity in Anesthesiologists.
46
Of this group,
10% were clinically asymptomatic although IgE positive. A history of atopy was also a significant risk factor for
latex sensitization. Brown suggests these individuals are in their early stages of sensitization and perhaps, by
avoiding latex exposure, their progression to symptomatic disease can be prevented.
46

Patients allergic to both tropical fruits (e.g., bananas, avocados, and kiwis) and stone fruits have also been
reported to have antibodies that cross-react with latex.
45,47
Multiple attempts are being made to reduce latex
exposure to both healthcare workers and patients. If latex allergy occurs, then strict avoidance of latex from gloves
and other sources needs to be considered, following recommendations as reported.
45
Because latex is such a
widespread environmental antigen, this represents a daunting task.

NEUROMUSCULAR BLOCKING AGENTS
Neuromuscular blocking agents (NMBAs) have several unique molecular features that make them potential
allergens. All neuromuscular blocking drugs are functionally divalent and are thus capable of cross-linking cell-
surface IgE and causing mediator release from mast cells and basophils without binding or haptenizing to larger

232
Page 5
carrier molecules.
1
NMBAs have also been implicated in epidemiological studies of anesthetic drug-induced
anaphylaxis. Epidemiological data from France suggest that NMBAs are responsible for 6281% of reactions,
depending on the time period evaluated.
42,48
Rocuronium is the NMBA most reported from France. We and others
have reported previously that aminosteroidal compounds as well as benzylisoquinoline-derived agents produce
positive weal and flare responses when injected intradermally.
31,49,50
Estimates of anaphylactic reactions in
anesthesia vary, but data suggests that false-positive skin tests may overestimate the incidence of rocuronium-
induced anaphylactic reactions.
31,49,50
The differences noted in the incidence of reactions may reflect the potential
for false-positive weal and flare responses.
31,49,50
NMBAs can also produce direct vasodilation by multiple
mechanisms, which include calcium channel blockade. The false-positive skin tests that were reported to be biopsy-
negative for mast cell degranulation clearly confound interpreting skin tests in patients who have had life-
threatening cardiopulmonary collapse. Dilute solutions of NMBAs need to be used when skin testing for potential
allergic reactions to these agents. However, the exact concentration that should be used is unclear. Since skin-testing
procedures are important in evaluating potential drug allergies, the threshold for direct vasodilating and false-
positive effects must be determined whenever subjects are skin-tested for a particular drug.

POLYPEPTIDES AND BLOOD PRODUCTS
Polypeptides are larger molecular weight molecules that pose greater potential to be antigenic, and include
aprotinin, latex, and protamine. Diabetic patients receiving protamine containing insulin as neutral protamine
Hagedorn (NPH) or protamine insulin have a 10-30 fold increased risk for anaphylactic reactions to protamine when
used for heparin reversal, with a risk of 0.6-2% in this patient population.
41,51
Because protamine is often given with
blood products, protamine is often implicated as the causative agent in adverse reactions, especially in cardiac
surgical patients. Platelet and other allogeneic blood transfusions can produce a series of adverse reactions by
multiple mechanisms, and blood products have a greater potential for allergic reactions including TRALI.
25

Although antigen avoidance is one of the most important considerations in preventing anaphylaxis, this is not always
possible, especially with certain agents where alternatives are not available. Protamine is an important example of
where alternatives are under investigation, but not currently available.

EVALUATING THE PATIENT FOLLOWING ANAPHYLAXIS
A detailed history is one of the most important considerations to evaluate a patient following anaphylaxis,
determining what agents were administered, and what the temporal sequence was.
52
Also, after resuscitation collect
a red top tube (serum) for mast cell tryptase, preferably within 1-2 hours of the reaction, and then repeat 24 hours
later. Serum can also be collected postmortem, which may be important for you medico-legally. Most hospital
laboratories will need to send this test to a reference laboratory. If tryptase is positive, sending the patient for an
allergy consultation may be useful if the temporal sequence is confusing, and the agent responsible needs further
investigation. Often, a positive mast cell tryptase usually represents an IgE mediated reaction (i.e., anaphylaxis) but
vancomycin and other histamine releasers can also increase tryptase.
35
Negative mast cell tryptase tests are rarely
associated with positive skin tests and antibody tests. IgG reactions due to protamine, or blood products are unlikely
to increase tryptase. Few laboratory based tests are available for determining immunologic testing, so skin testing is
required if better differentiation of the agent responsible is required.

CONCLUSIONS
Anaphylaxis represents an important potential problem and an important cause of life threatening events.
Clinicians must be able to recognize and treat these life threatening events if they occur. Clinicians should
remember that test doses may produce anaphylaxis. There are few in vitro tests available to assess patients at high
risk for reexposure anaphylaxis. Anaphylactic reactions represent a continuing challenge, but rapid diagnosis and
treatment are important in preventing adverse clinical outcomes.

SUGGESTED WEB SITES: AnaphylaxisWeb.com, FDA.gov

REFERENCES
1. Levy JH, Adkinson NF, Jr.: Anaphylaxis during cardiac surgery: implications for clinicians. Anesth Analg
2008; 106: 392-403
2. Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML,
Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wuthrich B: A revised nomenclature for allergy. An
EAACI position statement from the EAACI nomenclature task force. Allergy 2001; 56: 813-24

232
Page 6
3. Sampson HA, Munoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA, Decker WW, Furlong TJ,
Galli SJ, Golden DB, Gruchalla RS, Harlor AD, Jr., Hepner DL, Howarth M, Kaplan AP, Levy JH, Lewis LM,
Lieberman PL, Metcalfe DD, Murphy R, Pollart SM, Pumphrey RS, Rosenwasser LJ, Simons FE, Wood JP,
Camargo CA, Jr.: Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin
Immunol 2005; 115: 584-91
4. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, Branum A, Brown SG,
Camargo CA, Jr., Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD, Jr., Hepner DL, Lewis LM, Lieberman
PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP,
Decker WW: Second symposium on the definition and management of anaphylaxis: summary report--second
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann
Emerg Med 2006; 47: 373-80
5. Kay AB: Allergy and allergic diseases. Second of two parts. N Engl J Med 2001; 344: 109-13
6. Kay AB: Allergy and allergic diseases. First of two parts. N Engl J Med 2001; 344: 30-7
7. Mertes PM, Lambert M, Gueant-Rodriguez RM, Aimone-Gastin I, Mouton-Faivre C, Moneret-Vautrin DA,
Gueant JL, Malinovsky JM, Demoly P: Perioperative anaphylaxis. Immunol Allergy Clin North Am 2009; 29: 429-
51
8. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients: a meta-
analysis of prospective studies. Jama 1998; 279: 1200-5
9. Zimmerman CR, Chaffee BW, Lazarou J, Gingrich CA, Russell CL, Galbraith M, Khatlawala NK, Laing
TJ: Maintaining the enterprisewide continuity and interoperability of patient allergy data. Am J Health Syst Pharm
2009; 66: 671-9
10. Wester K, Jonsson AK, Spigset O, Druid H, Hagg S: Incidence of fatal adverse drug reactions: a population
based study. Br J Clin Pharmacol 2008; 65: 573-9
11. Portier MM RC: De l'action anaphylactique de certains venins. C R Soc Biol 1902; 54: 170-172
12. Stone SF, Cotterell C, Isbister GK, Holdgate A, Brown SG: Elevated serum cytokines during human
anaphylaxis: Identification of potential mediators of acute allergic reactions. J Allergy Clin Immunol 2009; 124:
786-92 e4
13. Metcalfe DD, Peavy RD, Gilfillan AM: Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin
Immunol 2009; 124: 639-46; quiz 647-8
14. Pumphrey RS: Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp 2004; 257: 116-28;
discussion 128-32, 157-60, 276-85
15. Pumphrey RS, Roberts IS: Postmortem findings after fatal anaphylactic reactions. J Clin Pathol 2000; 53:
273-6
16. Simons FE: Anaphylaxis: Recent advances in assessment and treatment. J Allergy Clin Immunol 2009;
124: 625-36
17. Levy JH: Biomarkers in the diagnosis of anaphylaxis: making nature disclose her mysteries. Clin Exp
Allergy 2009; 39: 5-7
18. Landry DW, Oliver JA: The pathogenesis of vasodilatory shock. N Engl J Med 2001; 345: 588-95
19. Prussin C, Metcalfe DD: IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2006; 117:
S450-6
20. Pumphrey R: Anaphylaxis: can we tell who is at risk of a fatal reaction? Curr Opin Allergy Clin Immunol
2004; 4: 285-90
21. Pumphrey RS: Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy
2000; 30: 1144-50
22. Levy JH, Hursting MJ: Heparin-induced thrombocytopenia, a prothrombotic disease. Hematol Oncol Clin
North Am 2007; 21: 65-88
23. Walport MJ: Complement. Second of two parts. N Engl J Med 2001; 344: 1140-4
24. Walport MJ: Complement. First of two parts. N Engl J Med 2001; 344: 1058-66
25. Silliman CC, Ambruso DR, Boshkov LK: Transfusion-related acute lung injury. Blood 2005; 105: 2266-73
26. Silliman CC, Kelher M: The role of endothelial activation in the pathogenesis of transfusion-related acute
lung injury. Transfusion 2005; 45: 109S-116S
27. Sheppard CA, Logdberg LE, Zimring JC, Hillyer CD: Transfusion-related Acute Lung Injury. Hematol
Oncol Clin North Am 2007; 21: 163-76
28. Kishimoto TK, Viswanathan K, Ganguly T, Elankumaran S, Smith S, Pelzer K, Lansing JC, Sriranganathan
N, Zhao G, Galcheva-Gargova Z, Al-Hakim A, Bailey GS, Fraser B, Roy S, Rogers-Cotrone T, Buhse L, Whary M,
Fox J, Nasr M, Dal Pan GJ, Shriver Z, Langer RS, Venkataraman G, Austen KF, Woodcock J, Sasisekharan R:

232
Page 7
Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med
2008; 358: 2457-67
29. Levy JH ea: Hereditary angioedema: current and emerging treatment options. Anesth Analg: In Press.
30. Levy JH, Kettlekamp N, Goertz P, Hermens J, Hirshman CA: Histamine release by vancomycin: a
mechanism for hypotension in man. Anesthesiology 1987; 67: 122-5
31. Levy JH, Gottge M, Szlam F, Zaffer R, McCall C: Weal and flare responses to intradermal rocuronium and
cisatracurium in humans. Br J Anaesth 2000; 85: 844-9
32. Levy JH, Brister NW, Shearin A, Ziegler J, Hug CC, Jr., Adelson DM, Walker BF: Wheal and flare
responses to opioids in humans. Anesthesiology 1989; 70: 756-60
33. Levy JH, Adelson D, Walker B: Wheal and flare responses to muscle relaxants in humans. Agents Actions
1991; 34: 302-8
34. Levy JH, Davis GK, Duggan J, Szlam F: Determination of the hemodynamics and histamine release of
rocuronium (Org 9426) when administered in increased doses under N2O/O2-sufentanil anesthesia. Anesth Analg
1994; 78: 318-21
35. Veien M, Szlam F, Holden JT, Yamaguchi K, Denson DD, Levy JH: Mechanisms of nonimmunological
histamine and tryptase release from human cutaneous mast cells. Anesthesiology 2000; 92: 1074-81
36. Caplan RA, Ward RJ, Posner K, Cheney FW: Unexpected cardiac arrest during spinal anesthesia: a closed
claims analysis of predisposing factors. Anesthesiology 1988; 68: 5-11
37. Levy JH: Treating shock: old drugs, new ideas. N Engl J Med: In Press.
38. Tsuda A, Tanaka KA, Huraux C, Szlam F, Sato N, Yamaguchi K, Levy JH: The in vitro reversal of
histamine-induced vasodilation in the human internal mammary artery. Anesth Analg 2001; 93: 1453-9
39. Dewachter P, Jouan-Hureaux V, Franck P, Menu P, de Talance N, Zannad F, Laxenaire MC, Longrois D,
Mertes PM: Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption.
40. Dewachter P, Mouton-Faivre C, Emala CW: Anaphylaxis and anesthesia: controversies and new insights.
41. Levy JH, Zaidan JR, Faraj B: Prospective evaluation of risk of protamine reactions in patients with NPH
insulin-dependent diabetes. Anesth Analg 1986; 65: 739-42
42. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid reactions occurring during anesthesia
in France in 1999-2000. Anesthesiology 2003; 99: 536-45
43. Holzman RS: Latex allergy: an emerging operating room problem. Anesth Analg 1993; 76: 635-41
44. Peixinho C, Tavares-Ratado P, Tomas MR, Taborda-Barata L, Tomaz CT: Latex allergy: new insights to
explain different sensitization profiles in different risk groups. Br J Dermatol 2008; 159: 132-6
45. Cullinan P, Brown R, Field A, Hourihane J, Jones M, Kekwick R, Rycroft R, Stenz R, Williams S,
Woodhouse C: Latex allergy. A position paper of the British Society of Allergy and Clinical Immunology. Clin Exp
Allergy 2003; 33: 1484-99
46. Brown RH, Schauble JF, Hamilton RG: Prevalence of latex allergy among anesthesiologists: identification
of sensitized but asymptomatic individuals. Anesthesiology 1998; 89: 292-9
47. Blanco C, Carrillo T, Castillo R, Quiralte J, Cuevas M: Latex allergy: clinical features and cross-reactivity
with fruits. Ann Allergy 1994; 73: 309-14
48. Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G: Epidemiology of life-threatening and
lethal anaphylaxis: a review. Allergy 2005; 60: 443-51
49. Levy JH: Anaphylactic reactions to neuromuscular blocking drugs: are we making the correct diagnosis?
Anesth Analg 2004; 98: 881-2
50. Dhonneur G, Combes X, Chassard D, Merle JC: Skin sensitivity to rocuronium and vecuronium: a
randomized controlled prick-testing study in healthy volunteers. Anesth Analg 2004; 98: 986-9, table of contents
51. Levy JH, Schwieger IM, Zaidan JR, Faraj BA, Weintraub WS: Evaluation of patients at risk for protamine
reactions. J Thorac Cardiovasc Surg 1989; 98: 200-4
52. Mertes PM, Laxenaire MC: Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol 2002; 19:
240-62

Disclosure
CSL Behring, Self, Consulting Fees; ViroPharma, Self, Funded Research ; Boehringer Ingelheim, Self, Consulting
Fees; Merck, Self, Consulting Fees; J&J, Self, Consulting Fees

236
Page 1
Strategies for Success in One-lung Anesthesia
Jerome Klafta, M.D. Western Springs, Illinois
Objectives:
1. Explain common and uncommon causes of lung separation failure and present strategies for success
2. Review evidence-based recommendations for management of one-lung ventilation
3. Discuss approaches to lung separation in patients with difficult airways
The big picture
Success in the context of one-lung anesthesia means that lung collapse is both complete and well tolerated
by the patient. Although the concept is simple, a number of clinical details frequently make the difference between
success and failure. Lung isolation (= functional lung separation) allows us to ventilate one lung independent of the
other (airtight seal) or to restrict passage of blood or fluids (watertight seal) from one lung to another. One-lung
anesthesia requires not only functional lung separation but also adequate one-lung ventilation (OLV) and
oxygenation. Figure 1 depicts the three clinical endpoints integral to one-lung anesthesia:
Optimal position of double-lumen tube or
blocker
Functional lung separation
Adequate one-lung ventilation and oxygenation
Various overlapping subsets of these conditions can
and do occur. For example, adequate position of the
double-lumen tube (DLT) or bronchial blocker (BB)
does not ensure functional lung separation (condition
A), and adequate OLV can sometimes be achieved
with suboptimal DLT position (condition C). Table
1 lists examples of causes and solutions for each
clinical condition in Figure 1. By identifying the
exact nature of the difficulties, the anesthesiologist
can implement appropriate therapy without wasting
time on maneuvers (DLT repositioning, cuff volume
manipulations, or ventilation changes) that are not
part of the problem.
Table 1: Clinical conditions during one-lung anesthesia
Area Example Situation Typical Solution
A No airtight cuff seal lungs not separated More air in cuff or larger DLT
B Left DLT in too far occluding LUL orifice Position DLT optimally
C Right DLT cuff occluding RUL orifice Position DLT optimally
D
Hypoxemia
Obstruction of the ventilating lumen of DLT
100% oxygen/CPAP/PEEP/TLV
Consider alternative lung separation technique
E No Problem!
LUL = left upper lobe; RUL = right upper lobe; TLV = two lung ventilation
Design characteristics of double lumen tubes and bronchial blockers
Common adult DLT sizes are 35, 37, 39, and 41 French (F). Some manufacturers also provide 26, 28 and 32
F sizes. The particular dimensions and design characteristics vary somewhat between manufacturers (Rusch, Portex,

236
Page 2
Sheridan, Mallinckrodt, and Fuji Systems). The resting bronchial cuff volume (defined as the smallest cuff volume
beyond which a 0.5 cc increase results in more than a 10 Torr increase in cuff pressure) can differ between sizes (35
F = 3.7 cc; 41 F = 2.0 cc) (1). Inflation of the bronchial cuff beyond its resting volume (or even less than its resting
volume if fitted tightly inside a bronchus) may result in dangerously high intracuff pressures and should be avoided
(1,2).

The Univent tube, an alternative device for providing OLV, underwent design modifications in 2001. This
Torque Control Blocker (TCB) Univent has a more flexible shaft that is easier to direct into the target bronchus and
a blocker made from a softer medical grade silicone material that is more compliant. Typical cuff inflation volume
is 5-6 cc.
The Arndt endobronchial blocker was the first of several additions to our armamentarium of lung separation
devices (3). This system minimizes some of the traditional difficulties associated with the use of Fogarty
embolectomy catheters as independent BBs and with Univent tubes. A patients lungs can be conveniently
ventilated while the blocker is fiberoptically positioned through the Arndt multiport airway adapter. The guide wire
loop that protrudes through the blockers tip is used to couple the blocker to the fiberoptic bronchoscope (FOB)
which can be directed fiberoptically to the desired location in the bronchial tree. The blockers 1.4 mm lumen can
be used to insufflate oxygen or suction gas from the blocked lung after the wire loop is removed. The smallest
single lumen tube (SLT) for use with this blocker coaxially (! 7.5 mm ID) has a corresponding outer diameter that
compares favorably with that of the typical DLTs and Univent tubes used for small adults.
Since its introduction in 1999, Cook Critical Care has made several design modifications. The elliptical cuffs
on the 9 F blocker were discontinued in 2011. A 5 F pediatric blocker has been available since 2001 and can be
used inside SLTs as small as 4.5 mm. A midsize 7 F catheter is also available to permit the use of a larger diameter
FOB or a smaller diameter SLT for coaxial use. Murphy eye side holes have been introduced into the distal end
of the 9 F adult catheter to circumvent suctioning difficulty if the end hole abuts the bronchial mucosa, and the guide
wire loop can now be reinserted if needed. Characteristics of available blockers are described in Table 2 below:
Table 2: Arndt Endobronchial Blockers
Size
(F)
Smallest SLT ID for
coaxial use (mm) *
Length
(cm)
Cuff shape
Average cuff inflation
volume (cc)

9

7.5

78

Spherical

4 8

7

6.5

65

Spherical

2 6

5

4.5

50

Spherical

0.5 2.0
ID = inner diameter * with 3.4 mm FOB (data from Cook Critical Care)

Cook Critical Care introduced the Cohen blocker in 2003. This device is similar to the Arndt blocker except
that its distal tip is directed by way of a proximal control mechanism instead of coupling to a bronchoscope. The
Uniblocker is an independent BB controlled similarly to the one integral to the Univent tube. The use of bronchial
blockers in adults for routine cases (4) and for selective lobar blockade (5) was recently reviewed. The Y-shaped,
dual-balloon EZ blocker is the newest BB design. Early reports of its functionality are encouraging (6).

Size selection of double-lumen tubes
Assuming that the main body of a DLT will fit through the glottic opening and the trachea, an appropriately
sized DLT is the largest tube that will fit in the mainstem bronchus with only a small air leak detectable when the
cuff is deflated (2). The presence of some air leak ensures that the tube is not tightly impacted in the bronchus.
Thus, the goal is to select a DLT with an outer bronchial diameter that is 1-2 mm smaller than the diameter of the
intubated bronchus to allow for the size of the deflated cuff (2). Although some practitioners use 35 F DLTs for all
patients (7), many select 41 F and 39 F DLTs for tall and short men, respectively, and 39 F and 37 or 35 F DLTs for
tall and short women, respectively. However, there is considerable variability in left mainstem diameters and
relatively weak predictive value of gender and height (2,8). Since prediction is imprecise, measurement of the left
mainstem diameter is most reliable. On chest x-ray (CXR), it is discernible only 50-69% of the time (2,9) but it is
reliably identified on chest CT (11). Brodsky et al measured the more readily obtainable tracheal diameter on CXR
at the level of the clavicles and used a previously described mean left bronchial to tracheal width ratio to calculate

236
Page 3
the left mainstem diameter (11). However, the confidence limits for this ratio may be too large to be useful
clinically (9). Checking the radiograph to identify unexpectedly large or small bronchi is probably most important.
One critically important assumption is that we clinicians know the dimensions of the differently sized
DLTs. Russell et al independently measured the dimensions of DLTs from 4 manufacturers and found marked
variations even within the same tube size for each manufacturer (12)! See Figure 2. Thus, any effort to predict
appropriate DLT size has this important limitation.

Figure 2 (from ref 12)

While attempting to select an appropriately sized DLT is important, it is equally important clinically to recognize
when a DLT is too large (bronchial lumen will not fit in bronchus or forms an airtight seal with no air in the cuff) or
too small (requires more than 3 cc of air in the bronchial cuff to create a seal) and adjust accordingly.
Right-sided double-lumen tubes
The perceived or real difficulty in achieving adequate OLV with right-sided DLTs is evidenced by the fact
that they are used much less frequently than are left-sided DLTs: 96% of Bronchocath sales are left-sided (Sherri
Cowan, personal communication, 2013). Use of left-sided DLTs is generally encouraged because of the greater
margin of safety in positioning them, but a recent retrospective analysis of 691 cases demonstrated indistinguishable
oxygenation, ventilation, and airway pressure performance between right- and left-sided DLTs (13). Moreover, in
the hands of infrequent users of DLTs, the 3 aforementioned performance criteria were less favorable using left-
sided tubes (14).
When right- and left-sided DLTs were compared for left-sided thoracic surgery in 40 patients, no right upper
lobes collapsed and the difference in the time to place the tubes was clinically insignificant (3.37 vs. 2.08 min) (15).
Although their routine use in thoracic surgery is controversial (15,16), right-sided DLTs are indicated when a patient
requires a DLT but also has an anatomic abnormality of the left mainstem bronchus such as an exophytic or stenotic
lesion or left tracheobronchial disruption. Regardless of the reasons for use, the right mainstem bronchial length
must be at least 10 mm to accommodate the lateral aspect of the bronchial cuff (17). This length can be determined
bronchoscopically or from a CXR or CT. Attempts to position a right-sided DLT in patients whose right mainstem
bronchi are too short are almost certainly doomed to failure.

Fiberoptic placement and positioning of double-lumen tubes
Precise positioning of a DLT is most reliably achieved with the benefit of a FOB. In comparisons of
fiberoptic positioning of DLTs with conventional methods, over one-third of left DLTs were malpositioned after
blind intubation and the inspection and auscultatory method (18). In a study of 200 patients, the incidence of
malposition (0.5 cm deviation from ideal position) was 39.5% with 14% of them critical (19). Critical
malpositions were those in which the left endobronchial limb allowed no clear view of the left upper or lower lobe
bronchus, the right endobronchial limb allowed no clear view of the RUL bronchus, or there was intratracheal
dislocation of more than one-half of the endobronchial cuff. Visually unassisted placement of left DLTs may result
in initial intubation of the wrong bronchus 7-30% of the time (19,20,21,22).
236
Page 4
Ovassapian described a reliable and reproducible method of placing left-sided tubes (and right-sided, with
slight modification) on the first attempt (21). This technique involves first inserting the DLT through the glottis
with direct laryngoscopy, rotating it 90 leftward, and advancing it only until the proximal edge of the tracheal cuff
is past the vocal cords. This limited advancement ensures that the tip of the bronchial lumen is supracarinal. After
the tracheal cuff is inflated, ventilation through both lungs is initiated. The FOB is then placed through the
bronchial lumen and advanced until the carina and mainstem bronchi are clearly identified. The posterior
membranous portion of the trachea, the 5 cm left mainstem bronchus, and the characteristic trifurcation of the RUL
bronchus are reliable anatomic landmarks to facilitate directional orientation. The FOB is then advanced into the
left mainstem bronchus to a position just proximal to the left upper and left lower lobe bronchi. After deflation of
the tracheal cuff, the entire DLT is slid over the FOB until its bronchial lumen comes into view beyond the tip of the
FOB. Confirmation of a patent left upper and left lower lobe bronchus ensures that the DLT is not in too far.
Finally, the FOB is passed through the tracheal lumen to check for a carinal or subcarinal position of the bronchial
cuff and ensure patency of the right mainstem bronchus.
When 50 thoracic surgical patients with left-sided DLTs were positioned from supine to lateral, the tubes
tended to move outward by an average of about 1 cm (23). Inflation of the endobronchial cuff before lateral
positioning did not decrease the incidence or the amount of overall distance change. Because of the tendency for
carinal shift and DLT movement upward with lateral positioning, there is an advantage to keeping the bronchial cuff
at least 1 cm inside the left mainstem bronchus before turning laterally. In another study of 61 patients, the
incidence of proximal repositioning was reduced significantly (43% vs. 16%) after turning from supine to lateral
when the left Bronchocath was initially inserted with the proximal edge of its bronchial cuff 5 mm beyond the
tracheal carina (24). Intraoperative use of a rigid neck collar to prevent head and neck movement will minimize but
still not prevent DLT movement while positioning supine to lateral (25). Initially positioning the DLT without a
headrest may minimize this displacement (26).
Confirming lung separation
Of the techniques described to achieve a minimum occlusive seal (17,27,28), I routinely use the positive
pressure test or bubble test depicted in Figure 3. There are a number of reasons to use a just seal technique to
inflate the bronchial cuff of a DLT or bronchial blocker (BB). First, a cuff that is inflated beyond a minimum
occlusive pressure may result in bronchial mucosal ischemia or even rupture (27,29). Second, an over-inflated
bronchial cuff or BB is more likely to herniate over the tracheal carina and interfere with contralateral ventilation.
Third is the ability to immediately and definitively
verify lung separation. That moment of truth when
the thoracoscopic port is inserted or the hemithorax is
opened is thoroughly predictable. If lung collapse is
slow or incomplete, documented lung separation
assures the anesthesiologist that manipulation of the
DLT or BB or their cuffs will not improve the
situation. Attention can be focused on other
maneuvers that will improve the surgical exposure:
manual compression, suction, additional time, or
intrahemithoracic CO
2
insufflation (30).
Ventilation management
Traditional teaching is that for most patients, tidal volumes during OLV are initiated at 10 cc/kg with a
respiratory rate adjusted to maintain normal pCO
2
(18). However, the use of smaller (6 cc/kg) or larger (15 cc/kg)
tidal volumes may be beneficial in some patients (31). In patients with COPD, the development of significant auto
PEEP or dynamic pulmonary hyperinflation is an ever-present risk (32). A growing body of evidence suggests that
lower tidal volumes (5-6 cc/kg) and their associated lower plateau pressures may protect against acute lung injury
during surgery for lung resection (33,34,35,36). A 2006 Pro/Con editorial summarized the low versus high tidal
volume debate for OLV (37, 38).
The use of pressure-controlled ventilation (PCV) during OLV results in lower airway pressures compared to
volume-controlled ventilation (VCV) and may improve oxygenation in select patients with preexisting lung
pathology (39,40). PCV with 4 cm H
2
O PEEP to the dependant lung provides lower airway pressures compared to
236
Page 5
VCV with no PEEP (41). Comparisons of desflurane (42) and sevoflurane (43) with isoflurane during OLV
demonstrated that the choice of volatile anesthetic does not significantly influence arterial oxygenation. Sevoflurane
and propofol for maintenance anesthesia also had similar effects of oxygenation during OLV (44). The addition of
dexmedetomidine to desflurane anesthesia did not alter oxygenation (45). Emerging evidence suggests that using
volatile anesthetics compared to propofol decreases the local alveolar inflammatory response to OLV (46).
Predicting which patients are at highest risk for intraoperative hypoxemia during OLV informs our decision
to institute prophylactic nondependent lung CPAP (47) or to even attempt OLV. CPAP is most effectively applied
to a fully inflated lung, since the opening pressure of atelectatic lung units may exceed 20 cm H
2
O. Factors
associated with the development of desaturation with OLV include poor PaO
2
during TLV in the lateral position,
normal preoperative spirometry, right-sided surgery, a significant proportion of ventilation or perfusion to the
operative lung on preoperative ventilation-perfusion testing (47) and supine positioning (48). Applying external
PEEP to the dependent, ventilated lung as the first intervention may benefit some patients (49, 50). A recruitment
maneuver to the ventilated lung at the beginning of OLV also improves oxygenation (51, 52) with only transient
decreases in blood pressure and cardiac index (52). Most recent data suggests recruitment of both lungs before OLV
decreases alveolar dead space and improves oxygenation (53).
The primary mechanism by which the lung fully collapses is absorption atelectasis. This is achieved most
rapidly with an N
2
O/O
2
mixture (FiO
2
=40%), then 100% O
2
, and then air/O
2
(FiO
2
=40%) (54,55). Lung collapse
will be most rapid if lung separation is initiated at end expiration (at FRC), especially when using a BB that has a
small or absent lumen (17). I highly recommend two recent reviews on hypoxemia and OLV (56,57).
Comparison of lung isolation techniques
Campos et al prospectively compared the effectiveness of lung isolation with a left Bronchocath, TCB
Univent tube, and the Arndt endobronchial blocker through a SLT in 64 elective right- and left-sided thoracic
surgical cases (58). There were no statistically significant differences among the 3 groups in frequency of tube
malpositions, number of required bronchoscopies, or overall quality of lung isolation as assessed by the surgeon
(blinded to technique) once lung isolation was achieved. The Arndt blocker took slightly longer to place (3 min, 34
sec) compared to the DLT (2 min, 8 sec) or Univent (2 min, 38 sec) groups, inclusive of time to place the SLT,
although 86- and 46-sec differences are hardly of clinical significance. Complete lung collapse took longer with the
Arndt blocker (26 min, 2 sec) than with the DLT (17 min, 54 sec) or Univent (19 min, 28 sec) and more frequently
required suction assistance.
More recently, Campos et al studied the success with which the occasional thoracic anesthesiologist (< 2
cases per month) correctly placed and positioned these same 3 devices in 66 patients with favorable airways (59).
He found an astonishing overall 38% failure rate with no differences between devices. When successful, placement
times averaged between 6 and 9 minutes regardless of the device used. Their observations suggested that
unfamiliarity with tracheobronchial anatomy and lack of skill in fiberoptic bronchoscopy were most responsible for
the difficulties. An excellent web-based resource for self-assessment and learning of tracheobronchial anatomy is
the Bronchoscopy Quiz and Simulator at www.thoracicanesthesia.com developed by Drs. Kanellakos, Dugas, and
Slinger.
Comparing a left Bronchocath DLT to the Arndt BB for port-access cardiac surgery, more laryngoscopy
attempts (2.3 vs. 1.1) and additional time (105 sec) to replace the DLT at the end of the case were trade offs for
slightly better right lung deflation with DLTs (60). Most recently, in comparing three different BBs to left DLTs for
left-sided surgery, all four devices provided equivalent surgical exposure at 10 and 20 minutes after pleural opening
(61). Postoperative hoarseness was prospectively found to be more common with DLTs (44%) than BBs (17%)
(62).
Lung separation and the difficult airway
In the patient with a difficult airway who requires lung separation, the concern for providing lung separation
is subordinate to securing the airway. Several options exist for achieving lung separation once a SLT has been
successfully placed. BBs are especially useful in these situations, particularly when a nasal intubation is required
(63). An algorithm for airway management options is presented in Figure 4.

236
Page 6
A. Upper and lower airway difficulties
Airway difficulties may arise from the upper airway (more common) or the lower airway. Upper airway
anatomic or pathologic features that render conventional rigid laryngoscopy difficult for placement of SLTs are even
more problematic for the placement of DLTs and Univent tubes because of their size and shape (64). Awake
fiberoptic intubation with a SLT or DLT may be the best option in cases of known or anticipated difficult intubation
(20,65,66).
Lower airway difficulties are encountered with anatomical variation or distortion of the tracheal or
bronchial anatomy. Distortion can occur with strictures, extraluminal compression, deviation, or intraluminal
masses. These will influence the selection of the bronchus to be targeted and the choice of a BB or DLT.
Lower airway difficulties can be detected or predicted by diagnostic bronchoscopy before intubation or by imaging
studies performed preoperatively.
B. Options for lung separation
Double-lumen tubes. The literature on videolaryngoscopy (VL) to facilitate DLT insertion has blossomed
and now contains more comparative trials rather than just case reports or series. One recent study randomly
allocated 60 patients with normal airways to intubation with a Glidescope or Macintosh direct layngoscope (DL).
Although duration of intubation was longer with DL (63 vs. 46 sec), the success of the first intubation attempt (87
vs. 100%) was not significantly different (67). Another 2012 study allocated 170 patients to intubation with a CEL-
100 VL or Macintosh DL (this VL has a 30 degree curve whereas the Glidescope's is 60 degrees). These authors
found similar intubation times but a higher first attempt intubation success (93% vs. 79%) with the CEL-100 (68).
Critical analysis of all such studies must consider both patient characteristics (e.g., average BMIs were all <24) and
design features of the particular VLs.
Oral fiberoptic intubation with a DLT is well described in both awake and asleep patients (66,69,70). A
patients mouth opening and oropharyngeal size must be large enough to accommodate a DLT for orotracheal
intubation. Awake placement requires good topical anesthesia, adequate conscious sedation, and assistance in
maintaining soft tissue support. Soaking a DLT in a warm water bath just before intubation and using sufficient
lubrication will minimize its rigidity. Concurrent direct laryngoscopy may be required to elevate the supraglottic
tissues to facilitate passage of a DLT through the glottic opening after the fiberoptic scope is in the trachea (70).
Videolaryngoscopy may add further benefit (71).
Univent tubes. Some anesthesiologists consider a Univent tube easier to place and position than a DLT (72),
particularly in patients with upper airway abnormalities (73). The internal diameter of the ventilating lumen in a
size 8.5 or 9.0 Univent tube will accommodate an adult 5.0 mm bronchoscope (72), which then precludes the need to
change tubes after diagnostic bronchoscopy. Although it is also suitable for fiberoptic intubation, the Univent tube
has several limitations. First, unlike the polyvinyl chloride of the SLT and DLT, the Univent tube is constructed of a
polymeric silicone material that will not soften in a warm water bath. As such, its curved shape is fixed, and this
may be a disadvantage when sliding it over a bronchoscope. Second, the fixed concavity often makes the leading
edge of the tube impinge upon the vocal cords, impeding its passage into the trachea. A successful nasal intubation
with a 7.0 Univent tube has been described, despite its size and rigidity (74).
Endobronchial blockers. See earlier discussion.
Single-lumen endotracheal tubes. Using a SLT to intubate a mainstem bronchus is another option for
achieving lung separation and is frequently the preferred technique for children who are too small for DLTs or
coaxial BBs (75). Advantages of this approach include its simplicity and the rapidity with which lung separation
236
Page 7
can often be achieved, particularly when the right lung must be ventilated. Blind advancement of a SLT will rarely
result in a left mainstem intubation, but rotating an in situ SLT 180 degrees while turning the patients head to the
right will improve the success rate of left mainstem intubation to about 92% (76). Fiberoptic guidance of a SLT into
the appropriate mainstem bronchus is probably the easiest and most reliable technique. If significant amounts of
blood or secretions preclude fiberoptic visualization, using fluoroscopy to visualize and direct the radiopaque
bronchoscope is another option (77).
Disadvantages of the use of a SLT for lung separation include frequent exclusion of RUL ventilation when a
SLT is in the right mainstem bronchus. Left upper lobe ventilation can also be excluded when the left mainstem
bronchus is relatively short (78). Regardless of which lung is ventilated, neither independent suctioning nor
application of CPAP to the nonventilated lung is possible. Lastly, if the nasotracheal route is used, most SLTs will
not be long enough to provide a reliable mainstem intubation.
C. The patient with a tracheostomy
Although the presence of a tracheostomy greatly simplifies airway management for most anesthetics, it presents an
interesting challenge when lung separation is required. As with orotracheal intubation, options include a DLT (21),
Univent tube (79), or BB through the tracheostomy stoma. Depending upon the details of a patients anatomy such
as stomal diameter, distance between the skin and the anterior tracheal wall, and stoma-to-carinal distance, DLTs
and Univent tubes may be difficult to place and position precisely and atraumatically.
Another way to achieve lung separation in a patient with a tracheostomy is using a BB, either coaxially or
alongside a SLT or tracheostomy tube through the stoma (80) or through the mouth (81). Blind or fiberoptically
directed mainstem intubation with a SLT inserted through the stoma is yet another option, although it has the usual
limitations associated with mainstem intubations.
D. Extubation and postoperative intubation
When the decision is made to leave a patient intubated after a procedure involving lung separation, some
special considerations need to be addressed. The possibility of the recurrent need for lung separation should be
considered a reason to leave a patient intubated. Occasionally, an airway that was not difficult initially may become
difficult after a lengthy procedure involving large fluids shifts that contribute to upper airway or head and neck
edema. An anticipated need for postoperative intubation should therefore inform the preoperative choice of lung
separation technique. If a SLT with a BB was used, then all that needs to be done at the end of the procedure is to
remove the BB. If a Univent was used, then its blocker should be fully retracted, and the Univent can function as a
SLT.
If a DLT was used for lung separation, then the risks and benefits of changing to a SLT must be carefully
weighed. The main advantage to leaving the tube in place is that the hazards associated with a tube change with a
difficult airway are avoided. In this case, one can leave the tube positioned and ventilate both lungs through both
lumens. Alternatively, the tube can be withdrawn to the point at which the tip of the bronchial lumen is just above
the carina, which will position the tracheal cuff below the vocal cords (82). Increased flow resistance leading to
obstructed expiratory flow or increased work of breathing is probably not clinically significant with 37 F or larger
Rusch or Sheridan DLTs (83).
If the DLT is to be changed, it should be done under direct vision if possible. If adequate laryngeal exposure
is not possible with a rigid laryngoscope, an airway exchange catheter (AEC) may be used to exchange a SLT for a
DLT preoperatively or DLT for a SLT postoperatively. Cook Critical Care manufactures AECs specifically
designed for DLT exchanges. These differ from conventional AECs in that they are longer (100 cm) and have
centimeter markings that extend to 50 cm. Eleven and 14 F sizes will fit inside small and large DLTs, respectively.
An extra firm variety colored green became available in 2002 to which a soft tip was added in 2006.
Keys to success in one-lung anesthesia
Understand the physical details of DLTs and BBs - select them appropriately
Use the FOB! optimize conditions (antisialagogue, suction), learn the tracheobronchial anatomy, and practice!
Employ a just seal test every time avoid trouble and identify problems early
References
1. Hannallah MS, et al. Anesth Analg 1993; 77:1222-1226 2. Hannallah MS, et al. J Cardiothorac Vasc Anesth
1995; 9:119-121 3. Arndt GA, et al. Anesthesiology 1999; 90:1484-1486 4. Campos JH. Anesth Analg 2003;
97:1266-1274 5. Campos JH. Curr Opin Anaesthesiol 2009; 22:18-22 6. Mourisse J, et al. Anesthesiology 2013;
118:550-61 7. Amar D, et al. Anesth Analg 2008; 106:379-83 8. Brodsky JB, et al. J Clin Anest 2005; 17:267-270

236
Page 8
9. Hampton T, et al. Anaesth Intensive Care 2000; 28:540-542 10. Chow MYH, et al. Anesth Analg 1999; 88:302-
305 11. Brodsky JB, et al. Anesth Analg 1996; 82:861-864 12. Russell WJ, et al. Anaesth Intensive Care 2003;
31:50-53 13. Erhenfeld JM, et al. Anesth Analg 2008; 106:1847-52 14. Ehrenfeld JM, et al. J Cardiothorac Vasc
Anesth 2010; 24:598-601 15. Campos JH, et al. J Cardiothorac Vasc Anesth 2002; 16:246-248 16. Cohen E. J
Cardiothorac Vasc Anesth 2002; 16:249-252 17. Benumof JL. Anesthesia for Thoracic Surgery, 2nd ed.
Philadelphia: WB Saunders, 1995: 330-89 18. Pennefather SH, et al. Br J Anaesth 2000; 84:308-310 19. Klein U,
et al. Anesthesiology 1998; 88:346-350 20. Brodsky JB et al. J Cardiothrac Vasc Anesth 2003; 17:289-298 21.
Ovassapian A. Fiberoptic Endoscopy and the Difficult Airway, 2nd ed. Philadelphia: Lippincott-Raven 1996: 117-
156 22. Brodsky JB, et al. Anaesth Intensive Care 1995: 23:583-586 23. Desiderio DP, et al. J Cardiothorac Vasc
Anesth 1997; 11:595-598 24. Fortier G, et al. Can J Anaesth 2001; 48:790-794 25. Yoon TG, et al. Can J Anesth
2005; 52:413-417 26. Seo J-H, et al. Can J Anesth/J Can Anesth 2012; 59:437-441 27. Guyton DC, et al. J
Cardiothorac Vasc Anesth 1997; 11:599-603 28. Hannallah MS, et al. Anesth Analg 1993; 77:990-994 29.
Fitzmaurice BG, et al. J Cardiothorac Vasc Anesth 1999; 13:322-329 30. Brock H, et al. Anaesthesia 2000; 55:10-
16 31. Szegedi LL, et al. Brit. J of Anaesth 2002; 88(1):56-60 32. Ducros L, et al. J Cardiothorac Vasc Anesth
1999; 13:35-39 33. Licker M, et al. Anesth Analg 2003; 97:1558-1565 34. Slinger P. Anesth Analg 2003;
97:1555-1557 35. Michelet P, et al. Anesthesiology 2006; 105:911-919 36. Choi G, et al. Anesthesiology 2006;
105:689-695 37. Slinger P. Anesth Analg 2006; 103:268-270 38. Gal TJ Anesth Analg 2006; 103:271-273 39.
Tugrul M, et al. Br J Anaesth 1997; 79:306-310 40. Unzueta MC, et al. Anesth Analg 2007; 104:1029-1033 41.
Senturk NM, et al. J Cardiothrac Vasc Anesth 2005; 19:71-75 42. Wang JY, et al. Anaesthesia 2000; 55:167-173
43. Abe K, et al. Anesth Analg 1998; 86:1266-1270 44. Pruszkowski O, et al. Br J Anaesth 2007; 98:539-544 45.
J Minim Access Surg 2011; 7:227-231 46. Schilling T, et al. Anesthesiology 2011; doi:
10.1097/ALN.0b013e318214b9de 47. Slinger PD, et al. J Cardiothorac Vasc Anesth 2000; 14:202-211 48.
Szegedi LL, et al. Acta Anaesthesiol Scand 2010; 54:744-50 49. Slinger PD, et al. Anesthesiology 2001; 95:1096-
1102 50. Valenza F, et al. European J Anaesth 2004; 21:938-943 51. Tusman, et al. Anesth Analg 2004; 98:1604-
9 52. Cinnella G, et al. Acta Anaesthesiol Scand 2008; 52:766-75 53. Br J Anaesth 2012; 108:517-524 54.
Nunn JF. Nunns Applied Respiratory Physiology, 4th ed. Oxford: Butterworth-Heinemann, 1993:496 55. Ko R,
et al. Anesth Analg 2009; 108:1092-6 56. Ng A, et al. Br J Anaesth 2011; 106:761-763 57. Losher J.
Anesthesiology Clin 2008; 26:241-72 58. Campos JH, et al. Anesth Analg 2003; 96:283-289 59. Campos JH, et
al. Anesthesiology 2006; 104:261-266 60. Grocott HP, et al. J Cardiothorac Vasc Anesth 2003; 17:725-727 61.
Narayanaswamy M, et al. Anesth Analg 2009; 1097-101 62. Knoll H, et al. Anesthesiology 2006; 105:471-477
63. Campos JH. Anesthesiology 2002; 97:1295-1301 64. Wilson RS. Chest Surg Clin N Am 1997; 7:735-751 65.
Klafta JM, et al. Probl Anesth. 2001; 13:69-77 66. Patane PS, et al. J Cardiothorac Anesth 1990; 4:229-231 67.
Hus H-T, et al. Anaesthesia 2012; 67:411-415 68. Lin W, et al. Anaesthesia 2012; doi:10.1111/j.1365-
2044.2012.07137.x 69. Ovassapian A. J Bronchol 1994; 1:1-8 70. Benumof JL. J Cardiothorac Vasc Anesth
1998; 12:131-132 71. Chen A, et al. J Cardiothorac Vasc Anesth 2008; 22:170-2 72. Gayes JM. J Cardiothorac
Vasc Anesth 1993; 7:103-107 73. Slinger P. J Cardiothorac Vasc Anesth 1993; 7:108-112 74. Gozal Y, et al.
Anesthesiology 1996; 84:477 75. Hammer GB, et al. Anesth Analg 1999; 89:1426-1429 76. Kubota H, et al.
Anesthesiology. 1987; 67:587-589 77. Klafta JM, et al. Anesthesiology 1997; 87:1248-1250 78. Lammers CR, et
al. Anesth Analg 1997; 85:946-947 79. Andros TG, et al. Anesthesiology 1993; 79:1127-1128 80. Dhamee MS. J
Cardiothorac Vasc Anesth 1997; 11:124-125 81. Veit AM, et al. Anesth Analg 1996; 82:1292-1293 82. Cohen E,
et al. Curr Opin Anesthesiol 1999; 12:29-35 83. Slinger PD, et al. J Cardiothorac Vasc Anesth 1998; 12:142-144

Disclosure
237
Page 1
Whats New in Airway Management
Lauren Berkow, M.D. Baltimore, Maryland
Introduction
As patients presenting for anesthesia and surgery continue to become more complex, so has
airway management. In addition, the number of patients requiring anesthesia and airway management
outside the operating room setting continues to increase. New airway devices continue to be introduced into
the market and clinical practice, making airway management decisions even more challenging. Claims
involving airway management, both inside as well as outside the operating room setting, according to the
ASA Closed Claims database, continue to be significant.
1,2
This lecture discusses some of the new
evaluation methods and reviews many of the newer airway devices available as well as many of the issues
surrounding airway competency, airway management outside the operating room setting, and the role of
simulation and standardization for airway education and airway management.
1. Airway evaluation
a. Conventional Methods
Routine pre-operative airway examination usually includes an assessment of mouth opening and
dentition, Mallampati classification, measurement of thyromental distance and evaluation of neck
mobility. These methods are quickly and easily performed at the bedside, but unfortunately, their
sensitivity and specificity for accurate prediction of difficulty with airway management is not very
robust.
b. Newer Methods
i. Pre-operative endoscopic airway examination (PEAE)
3
Pre-operative endoscopy of the airway can aid in identification of airway pathology that
could potentially alter the choice of airway plan. Conversely, in patients suspected of
airway difficulty, direct observation of airway structures can provide valuable
information. The procedure can be performed in the pre-operative area and requires only
topicalization of the nasal cavity.
ii. Ultrasound assessment of the Airway
4
Ultrasonography can also be used to identify airway pathology. It is non-invasive, safe,
portable, and easily repeatable, Ultrasound can also be used to confirm endotracheal tube
placement (or esophageal intubation), identify the cricothyroid membrane, or assist with
percutaneous tracheostomy placement.
237
Page 2
2. Predicting the difficult airway
Predicting which patients may be difficult to mask ventilate or intubate can be challenging,
however certain disease processes have been associated with difficult airway management.
5
(Table 1)

The best predictor of difficulty with airway management is a prior history of difficulty.
3. Predicting difficult mask ventilation
Predicting difficulty with mask ventilation is a very important factor when planning
airway management-the inability to ventilate carries a much higher risk to the patient than the
inability to intubate. Several patient risk factors have been associated with difficult mask
ventilation (Table 2).
6
Difficult mask ventilation has also been identified as a risk factor for
difficult intubation.
7
Table 2: Risk factors for difficult mask ventilation

4. Airway management of the obese patient
The prevalence of obesity continues to rise in both the United States and worldwide. Currently,
65% of Americans are classified as overweight, and all states in the U.S. have an obesity rate of 20% or
higher based on 2010 data from the Center for Disease Control.
8
The incidence of childhood obesity is also
increasing. Similarly, the World Health Organization reports that more than 1.4 billion adults worldwide
are overweight, and 10% of the worlds adult population is obese.
9
The current evidence in the literature is equivocal as to whether obesity is a clear risk factor for
difficult mask ventilation or intubation.
10,11
Several studies show that with proper ramp positioning,
airway management of the obese patient can be successful.
12,13
There are other studies, however, that do
demonstrate an association between obesity and increased difficulty with airway management.
Table 1: Disease states associated with difficult airway management
Congenital Acquired
Pierre-Robin syndrome Morbid obesity
Treacher-Collins syndrome Acromegaly
Goldenhar's syndrome Infections involving the airway (Ludwig's angina)
Mucopolysaccharidoses Rheumatoid arthritis
Achondroplasia Obstructive sleep apnea
Micrognathia Ankylosing Spondylitis
Down's syndrome Tumors involving the airway
Trauma (airway, cervical spine)
Increased Body Mask Index (BMI)
Snoring/Obstructive Sleep Apnea
Presence of Beard
Lack of dentition
Age > 55 years
Mallampati III or higher
Male Gender
Airway masses/tumors
237
Page 3
5. Alternate Airway devices
The ASA Practice Guidelines for management of the Difficult Airway were recently updated in
February 2013, and recommend the use of alternate airway devices when conventional methods fail.
The guidelines also recommend that alternate airway devices be readily available in the operating room
setting.
14
With the large number of airway devices now available, it is difficult to become proficient in
the use of every device. Individual providers should choose one or two devices from the variety of
classes of devices available to them and become comfortable with their use in difficult airway
management.
The use of the supraglottic airway was added to the current 2003 version of the ASA Difficult
Airway Algorithm as a rescue device in the cannot ventilate-cannot intubate scenario. A variety of
Supraglottic Airway Devices are now available, and many of these devices have been adapted to allow
intubation via the device as well as evacuation of the stomach (Table 3). Two of these devices, the Air-
Q and the i-gel, contain malleable cuffs that do not require insufflation.
Table 3: Supraglottic Airway Devices
Brand Device Offered Allows
decompression of
the stomach
Designed for
intubation
Disposable/Reusable
versions
Pediatric
sizes
LMA
America
Classic LMA
Proseal LMA
LMA Supreme
FastTrach LMA
No
Yes
Yes
No
No
No
No
Yes
Yes/Yes
No/Yes
Yes/No
Yes/Yes
Yes
Yes
Yes
Yes
Ambu AuraStraight
Aura40
AuraFlex
Aura-i
AuraOnce
No
No
No
No
No
No
No
No
No
No
All disposable Yes
Yes
Yes
Yes
Yes
Smiths
Medical
Portex LM
Portex Soft Seal
No
No
No
No
All disposable Yes
Intersurgical i-gel Yes No All disposable Yes
King King LT
King LT-S
No
Yes
No
No
Yes/Yes Yes
Teleflex Rusch Easy tube
Sure Seal LM
Yes
No
No All disposable No
Yes
Mercury
Medical
Air-Q No No All disposable Yes
SLIPA SLIPA No No Yes/No No
Flexicare LarySeal LM No No All disposable Yes
Fiberoptic Intubation Devices
Fiberoptic intubation remains one of the most versatile airway management techniques since it can be
performed via either the oral or nasal route and in both an awake or anesthetized patient. In the awake patient,
adequate airway topicalization is required. Fiberoptic intubation is a necessary skill for any anesthesia provider.
Most fiberoptic scopes allow for suctioning of the airway as well as delivery of lidocaine. Some are battery
operated, and all can be connected to a video system for better viewing as well as recording. A single use, battery
operated fiberoptic scope is also available (Ambu aScope) that can be attached to a portable video monitor.
237
Page 4
Videolaryngoscopes (Table 4)
Videolaryngoscopes now play a major role as an alternative to conventional laryngoscopy, and
were added to the recently updated 2013 version of the ASA difficult airway algorithm as an alternative initial
approach to intubation.. Both reusable and disposable devices not exist, and all allow more anterior exposure of the
larynx compared to conventional laryngoscopy as well as the ability to display the laryngeal structures on a video
screen.
Table 4: Videolaryngoscopes
Brand Disposable? Stylet needed Channel for
ETT
Battery
operated
Pediatric
sizes
Glidescope
(Verathon Medical)
Blades only
(Cobalt version)
Yes No No Yes
C-Mac/Video
Macintosh system
(Karl Storz)
No Yes No No Yes
Pentax AWS
(Pentax/Ambu)
Blades only No Yes Yes Adolescent
only
Mcgrath scope Blades only Yes No Yes No
King Vision Scope
(King Systems)
Blades only Only for
unchanneled
blade
Yes Yes No
Airtraq Entire device No Yes Single
use
Yes
CoPilot VL (Magaw
Medical)
No No Yes Yes No
Bullard No Built into
device
No No Yes
Truview (Truphatek) No Yes No Yes Yes
Venner (Venner
Capital)
Blades only No Yes Yes No
Clarus Video stylet
(Clarus Systems)
No No ETT loaded
directly
onto stylet
Yes No
RIFL stylet (AI
Medical Devices)
No No ETT loaded
directly
onto stylet
Yes No
Other Devices:
It is beyond the scope of this lecture to review all the available classes of airway management devices, so
only a short list of additional classes of devices are provided below.
a. Endotracheal tube introducers
i. Frova intubating catheter-available in pediatric and adult sizes
ii. Aintree Intubating Catheter-allows passage of a fiberoptic scope inside the catheter
iii. Cook Airway Exchange catheter-available in a variety of sizes
iv. Sun Med Tracheal Tube introducer-single size
v. Radlyn stylet
b. Lighted intubating stylets
i. Shikani optical stylet
ii. Flexible Airway Scope Tool (FAST)
iii. Levitan stylet
iv. Bonfils retromolar intubation fiberscope
v. Air-Vu Plus fiberoptic stylet
vi. Sensascope semirigid intuboscope
237
Page 5
6. Extubation
Extubation, especially in the difficult airway patient, can be just as challenging as
intubation. Recently extubated patients requiring re-intubation pose additional challenges. Often
the airway is edematous, hemodynamic instability may be present, and often the environment in
which the airway must be managed is small. According to the ASA Closed Claims database, 12%
of claims involving airway management are associated with extubation.
2

The Difficult Airway Society in the United Kingdom recently published guidelines for
tracheal extubation.
15
These guidelines suggest that planning for extubation begin prior to
induction of anesthesia, and propose two algorithms: a low-risk and high-risk pathway. Both
the DAS guidelines as well as other studies support the use of an airway exchange catheter as a
bridge to extubation.
15, 16
This technique has several advantages: the catheter can be left in place
for as long as needed, is well tolerated by patients, an provides a conduit for re-intubation.
7. Difficult airway reporting and tracking
Dissemination of difficult airway information among providers and between institutions continues to
be a challenge. Although many institutions and some countries maintain databases of patients identified as
a difficult airway, no system currently exists to share this information. In the United States, the Medic
Alert Registry provides a method to collect and disseminate critical information about a variety of medical
conditions including difficult airway but requires a subscription by the patient and encouragement by
medical providers to enroll.
17

Alert bracelets are widely used throughout hospitals for allergy alerts and can also be used for difficult
airway alerts, but these bracelets only function in an individual hospital environment.
Electronic patient records also provide an opportunity to document difficult airway information and
disseminate this information to all hospital providers.
8. Airway challenges outside the Operating Room
Despite the widespread availability of advanced airway devices, airway management continues to be
more challenging outside the operating room environment. Several studies as well as the ASA closed
claims database have demonstrated an increased incidence of complications associated with airway
management outside the operating room setting.
18
The Fourth National Audit Project (NAP4) was
published last year (Table 5) and reported that 60% of airway-related adverse events in the ICU resulted in
death or brain damage.
19

Table 5: Fourth National Audit Project (NAP4) Results
Prospective study of airway-related adverse events over 1 year period of 300 hospitals in UK
61% of airway events in the ICU resulted in death or brain damage
Common themes:
Almost 50% of cases obese
Large number of events occurred in off hours
Lack of capnography, lack of needed equipment
Lack of experienced personnel, inadequate training
Delayed recognition of high risk patients
Lack of back-up plans for management

237
Page 6
9. Role of standardization

Standardization is a common practice in Aviation and Industry to improve efficiency and
decrease errors and has recently been applied to health care and airway management.
Standardization of equipment and procedures as well as standardized training of personnel has
been shown to reduce adverse airway events.
20
The ASA also recommends the availability of
consistent airway equipment in the OR setting.

10. Airway Education

As additional airway devices continue to be introduced into practice, continuing education and
practice of these devices is essential for safe airway management. As important as competence in use
of these devices is the ability to create and implement a variety of intubation plans. Specific airway
rotations required during residency training can provide opportunities for exposure to and adequate
experience in a variety of airway techniques.
21,22

Simulation has long been used in Aviation for teamwork training and standardization of practice,
with documented reduction in errors.
23
Simulation has recently been introduced into the medical
environment, and is now widely used to teach decision making and teamwork. Simulation provides a
safe environment in which to teach airway skills, familiarity with new airway devices, as well as
teamwork and communication during complicated airway management scenarios. The additional
advantages of simulation are the opportunity to immediately review and debrief events as well as
simulate rare clinical events.
24-28

11. Airway competency-how do we define it?

A current area of controversy is airway competency: how is competency in airway management
defined, and should competency be assessed and documented during residency training? The number of
times an airway procedure must be performed before competency is obtained is currently unknown, and
most likely varies among providers and between airway devices. Formal airway rotations during residency
can help insure that the opportunity exists to obtain competency with a variety of airway techniques and
devices.

Conclusion

Management of the difficult airway, both inside and outside the operating room setting, requires a thorough
airway examination whenever possible to predict difficulty with both ventilation and intubation. Novel airway
evaluation methods such as endoscopy and ultrasound may assist in prediction of difficulty. A variety of airway
devices are available to assist with difficult airway management, and the anesthesia provider should be familiar with
several types of these devices in order to create back-up airway plans. The individual plan will depend on patient
disease, provider expertise, and the airway equipment available for use. Complex airway management outside the
operating room setting continues to be a challenge, and having the correct equipment and training to manage
patients outside the operating room can potentially reduce adverse events.

237
Page 7
References
1.Metzner L, Posner K, Lam MS, Domino KB. Closed claims analysis. Best Practice & Research Clinical
2.Domino KB, Posner KL, Caplan RA. Cheney FW. Airway injury during anesthesia-a closed claims analysis.
3.Rosenblatt W, Ianus AI, Sukhupragarn W, Fickenscher A, Sasaki C. Preoperative endoscopic airway examination
(PEAE) provides superior airway information and may reduce the use of unnecessary awake intubation. Anesth
Analg 2011; 112: 602-7.
4.Kristensen MS. Ultrasonography in the management of the airway. Acta Anaesthesiol Scand 2011;55: 1155-1173.
5.Benumofs Airway Management, 2
nd
Edition, C. Hagberg, editor, Mosby, 2007.
6. El-Orbany M, Woehlick HJ. Difficult mask ventilation. Anesth Analg 2009;109: 1870-80.
7.Langeron O, Masso E, Huraux C, Guggiari M, Blanchi A, Coriat P, Riou B.. Prediction of difficult mask
ventilation. Anesthesiology 2000;92: 1229-36..
8. Behavioral Risk factor Surveillance System, Center for Disease Control
9. World Health Organization www.who.org
10.Juvin P, Lavaut E, Dupont H, Lefevre P, Demetriou M, Dumolin JL, Desmonts JM. Difficult tracheal intubation
is more common in obese than lean patients. Anesth Analg 2003; 97: 595-600.
11. Lavi R, Segal D, Ziser A. Predicting difficult airways using the intubation difficulty scale: a study comparing
obese and non-obese patients. J Clin Anesth 2009;21: 264-7.
12. Rao SL, Kunselman AR, Schuler HG, DesHarnais S.. Laryngoscopy and tracheal intubation in the head-elevated
position in obese patents: a randomized, controlled, equivalence trial. Anesth Analg 2008;107:1912-8.
13.Cattano D, Melnikov V, Khalil Y, Sridhar S, Hagberg C.. An evaluation of the rapid airway management
positioner in obese patients undergoing gastric bypass or laparoscopic gastric banding surgery. Obes Surg
2010;20:1436-41.
14. Practice guidelines for management of the difficult airway: an updated report by the American Society of
Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 2013; 118: 251-70.
15. Popat M, Mitchell V, Dravid R, Patel A, Swampillai C, Higgs A. Difficult Airway Society guidelines for the
management of tracheal extubation. Anaesthesia 2012; 67: 318-340.
16.Mort TC. Continuous airway access for the difficult extubation: the efficacy of the airway exchange catheter.
Anesth Analg 2007;107: 1357-62.
17. www.medicalert.org
18.Mort TC. The incidence and risk factors for cardiac arrest during emergency tracheal intubation: a justification
for incorporating the ASA guidelines in the remote location. J Clin Anesth 2004; 16: 508-16.
19.Cook TM et al. Major complications of airway management in the UK: results of the Fourth National Audit
Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2: intensive care and emergency
departments. Br J Anaesth 2011; 106: 632-42.
20.Berkow et al. Need for emergency surgical airway reduced by a comprehensive difficult airway program. Anesth
Analg 2009; 109:1860-9.
21.Borovcanin Z, Shapiro JR. Design and implementation of an educational program in advanced airway
management for anesthesiology residents. Anesthesiol Res Pract 2012;epub Feb 28.
22. Baker PA, Weller JM, Greenland KB, Riley RH, Merry AF. Education in airway management. Anaesthesia
2011; 66: Suppl 2101-11.
23. Johnston N. Integrating human factors training into ab initio airline pilot curricula. ICAO J 1993;48: 14-17.
24.Sudikoff SN, Overly FL, Shapiro MJ. High-fidelity medical simulation as a technique to improve pediatric
residents emergency airway management and teamwork. Pediatr Emer Care 2009;25: 651-6.
25.Zirkle M, Blum R, Raemer DB, Healy G, Roberson DW. Teaching emergency airway management using
medical simulation: a pilot program. Laryngoscope 2005;115: 495-500.
26.Volk MS, Ward J, Irias N, Navedo A, Pollart J, Weinstock PH. Using medical simulation to teach crisis resource
management and decision making skills to Otolaryngology housestaff. Otolaryngol Head Neck Surg. 2011
27. Gaba DM, Howard SK, Fish KJ et al. Simulation-based training in anesthesia crisis resource management
(ACRM): a decade of experience. Simul Gaming 2001; 32: 175-93.
28.Capella et al. Teamwork training improves the clinical care of trauma patients. J Surg 2010;67: 439-43.
Disclosures
Masimo, Self, Consulting Fees, Honoraria ; Teleflex, Self, Consulting Fees, Honoraria ; Medtronic, Self, Consulting
Fees ; Ambu, Self, Consulting Fees
238
Page 1
Perioperative Management of the Patient with Cirrhosis
Randolph H. Steadman, M.D., M.S. Los Angeles, California
As many as 5-10% of patients with cirrhosis undergo non-transplant surgery during the last two years of
life.(Palmieri 2012) Some surgical conditions, such as gallstones, are more common in patients with
cirrhosis.(Poggio 2000) Importantly, the perioperative risk is increased for cirrhotic patients, and a number of risk
factors have been identified. This refresher course will outline those risk factors and help formulate plans for the
perioperative care of this challenging group of patients. We will start with a description of the preoperative
assessment of the cirrhotic patient.
Definition
Cirrhosis is defined by the presence of hepatic parenchymal necrosis, fibrosis and regeneration, which results in
portal hypertension. Decompensated cirrhosis is associated with ascites, encephalopathy, varices, hepatorenal
syndrome and hepatic synthetic dysfunction. In 2010 chronic liver disease was the twelfth most common cause of
death in the United States.(Murphy 2012)
Causes
The etiology of end stage liver disease (ESLD) includes developmental or genetic defects, metabolic abnormalities,
autoimmune diseases, infectious diseases, neoplasm, alcohol, environmental toxins, and drug toxicity. Chronic viral
infection due to hepatitis C, alcoholic liver disease and nonalcoholic steatohepatitis are the most common causes of
cirrhosis leading to liver transplantation in the U.S.(OPTN 2011) Fourteen million adults in the U.S. meet the
diagnostic criteria for alcohol dependence. Alcohol accounts for 40% of deaths due to chronic liver disease. Three to
four million people in the United States are infected with hepatitis C, and one million have hepatitis B.(CDC 2010)
About 20-30% of these chronically infected individuals develop cirrhosis over a 20-30 year period. Nonalcoholic
fatty liver disease (NAFLD), a consequence of the obesity epidemic, is increasingly recognized as a cause of
cirrhosis. The metabolic causes of cirrhosis include hemochromatosis, Wilsons disease, alpha-1 antitrypsin
deficiency and cystic fibrosis.
Pre-operative Assessment
Liver disease is common and frequently asymptomatic. History and physical examination may uncover risk factors,
symptoms and/or signs that require further evaluation. Risk factors include a history of blood transfusions, illicit
drug use, sexual promiscuity, excessive alcohol use, jaundice and exposure to hepatotoxic drugs. Symptoms include
pruritus and fatigue. Physical exam findings include icterus, palmar erythema, spider telangiectasias, hepatomegaly,
splenomegaly, ascites, testicular atrophy and/or gynecomastia.
Signs of liver disease should prompt a search for the underlying cause. A combination of serologic testing,
ultrasonography and computed tomography or magnetic resonance imaging will narrow the differential diagnosis
and guide further evaluation. Liver biopsy, the diagnostic gold standard, is necessary on occasion.
Cirrhosis affects nearly every organ system. Cardiac manifestations include a decreased systemic vascular resistance
and increased cardiac output, which result from the production of vasodilators in patients with portal
hypertension.(Moller 2008) Overproduction of vasodilators also accounts for a reduced responsiveness to
sympathetic stimulation.(Schepke 2001) Diastolic dysfunction has been described in cirrhotic patients. This renders
them sensitive to volume changes, making them vulnerable to heart failure and pre-renal insufficiency.
Ascites and hydrothorax can cause hypoxemia and restrictive pulmonary disease. Hepatopulmonary syndrome
(HPS), which results from dilatation of the pulmonary microcirculation, is found in up to a third of patients with
end-stage liver disease. It manifests as hypoxemia, which worsens in the upright position. The hypoxemia associated
238
Page 2
with HPS typically responds to supplemental oxygen; however, complications are frequent in patients with severe
disease (room air PaO2 less than 50 mmHg). Portopulmonary hypertension, pulmonary hypertension associated with
cirrhosis, occurs in up to 6% of ESLD patients.(Kawut 2008) Perioperative morality is increased in these patients,
particularly in those with more severe elevations in pulmonary pressure.(Krowka 2004)
Hepatic encephalopathy is a serious, albeit reversible, complication of cirrhosis that is associated with a sensitivity
to sedatives and a predisposition to pulmonary aspiration. Encephalopathy appears as a result of portal-systemic
shunting, and its onset is generally associated with signs of advanced hepatocellular dysfunction such as ascites,
hypoalbuminemia, and elevations of the prothrombin time. Ammonia elevations due to inadequate hepatic
metabolism are an important contributor to encephalopathy, but other factors are involved. These include gut-
derived neurotoxins, gamma-aminobutyric acid (GABA), GABA receptor agonists, oxidative stress, inflammatory
mediators and abnormal serotonin transmission.(Munoz 2008; Bass 2010)
About one third of patients have esophageal varices at the time the diagnosis of cirrhosis is made, and another 10%
develop varices each year. One third with varices develop bleeding. Prophylactic use of non-selective beta blockers
(propranolol or nadolol) and endoscopic band ligation are useful in preventing gastrointestinal bleeding.(Garcia-
Tsao 2007) Up to 30% of cirrhotics with ascites develop spontaneous bacterial peritonitis (SBP), which has a 25%
in-hospital mortality rate. About 10% of patients with cirrhosis develop hepatorenal syndrome (HRS). Refractory
ascites often precedes the onset of HRS. Treatment of HRS includes midodrine, an alpha-agonist, octreotide and
intravenous albumin.(Gines 2004) HRS is frequently a terminal event unless patients are successfully treated or
transplanted.
Nutritional deficiencies are manifested as muscle wasting, ascites and hypoalbuminemia. Enteral supplementation
improves immunocompetence and prognosis. Electrolyte disturbances, infection, an increased dietary protein load,
or sedatives can precipitate hepatic encephalopathy. The precipitating cause should be sought and treated prior to
elective surgery. Management includes lactulose, which is titrated to 2-3 soft stools per day, and oral antibiotics,
such as neomycin or rifaximin.
Coagulopathy occurs as a result of thrombocytopenia and a prolonged prothrombin time, secondary to splenic
sequestration and decreased hepatic synthesis of clotting factors, respectively. The surgical risk of severe
coagulopathy (INR > 1.5 and platelet count < 50,000/mm
3
) has not been studied. The decision to treat patients with
fresh frozen plasma, cryoprecipitate and/or platelets should be based upon the presence of intraoperative bleeding or,
in the event of prophylactic transfusions, based upon the risk of potential bleeding (e.g., during craniotomy).
Recombinant factor VII has not been shown to decrease transfusion requirements or to improve outcomes in liver
transplantation; however, it may be valuable in selected patients who cannot tolerate the volumes associated with
plasma transfusions. Maintenance of a low central venous pressure may decrease operative blood loss.(Alkozai
2009)
Risk Assessment
In a retrospective case series of 733 patients with cirrhosis, 30-day mortality was 12%.(Ziser 1999) Risk factors for
mortality included ASA physical status 4 or 5, CTP class B or C, preoperative infection, ascites, an etiology of
cirrhosis other than primary biliary cirrhosis, preoperative upper gastrointestinal bleeding, intraoperative
hypotension and surgical severity score. The presence of each additional risk factor added roughly 10% to the risk of
mortality. With 4 risk factors present the risk of mortality was greater than 50%; with 7 or more risk factors the
mortality approached 100%.
The severity of preoperative liver disease correlates with operative risk. (Friedman 1999) Both the Child-Turcotte-
Pugh (CTP) class and the Model for End-Stage Liver Disease (MELD) score are useful measures of the degree of
underlying liver disease. The CPT score is based on serum bilirubin and albumin levels, prothrombin time, and the
degree of encephalopathy and ascites. Childs class A patients have a perioperative mortality of 10%, while class B
patients have a 30% perioperative mortality, and class C patients mortality is as high as 80%. Emergency surgery is
associated with even higher mortality, and approaches 100% in class C patients. These risk rates are supported by
two large retrospective studies.(Garrison 1984; Mansour 1997) The general consensus is that the perioperative risk
in Childs class C patients precludes elective surgery.

238
Page 3
The MELD score, originally designed to predict mortality after transjugular intrahepatic portosystemic shunt
(TIPSS), is a predictor of ninety-day mortality for patients awaiting liver transplantation. It has been shown to be a
more sensitive indicator of perioperative risk in cirrhotic patients than the CTP score. The MELD score is derived
from a linear regression model that uses three predictor variables: bilirubin, creatinine and INR (International
Normalized Ratio). As opposed to the CTP score, ascites and encephalopathy are excluded from the MELD score,
making it a more objective, reliable predictor that relies solely on laboratory values. MELD also avoids the arbitrary
categorization of predictors found in the CTP. In cirrhotic patients a 1-point increase in MELD score between the
values of 5 and 20 is associated with a 1% increase in perioperative mortality. Each point increase in MELD over 20
is associated with a 2% increase in mortality.(Northup 2008) American Society of Anesthesiologists Physical Status
category has also been shown to predict risk. Physical Status IV equates to 5 MELD points, or 10% additional
perioperative risk.(Teh 2007)

The Hepatic Effects of Anesthesia and Surgery
Many surgical procedures are accompanied by mild elevations in liver enzymes, regardless of whether general
anesthesia or regional is performed. Usually these changes are insignificant, but in patients with cirrhosis hepatic
function can decompensate further, leading to significant morbidity and mortality. Preoperative efforts to improve
encephalopathy and coagulopathy, elevate albumin levels and reduce ascites (elements of the CTP score) are
recommended, as this approach appears to lower perioperative risk.(D'Albuquerque 1995) Coexisting morbidities,
such as anemia and infection, should be treated prior to surgery. In patients with portal hypertension placement of a
transjugular intrahepatic portosystemic shunt may lower perioperative risk.(Gil 2004)

The perioperative risk depends more on the operative site and the degree of liver impairment than the anesthetic
technique. Upper abdominal surgery (cholecystectomy), when compared to hysterectomy, was associated with liver
enzyme abnormalities, while the anesthetic technique (halothane, enflurane or fentanyl) was not.(Viegas 1979)
Although inhalational anesthetics cause reductions in hepatic blood flow over baseline, the newer agents isoflurane,
desflurane and sevoflurane appear similar in this regard, and cause less alteration than older volatile agents. Despite
this the selection of general versus regional anesthesia does not appear to affect surgical outcomes.(Nishiyama 2004)
Hemorrhage, hypotension, positive pressure ventilation and pneumoperitonium can further reduce hepatic blood
flow.

In patients with ESLD the volume of distribution is increased, particularly for neuromuscular blockers. This results
in the need for larger loading doses to achieve the desired clinical effect. Cisatracurium and atracurium are good
choices because their metabolism is unaffected by liver disease. The action of drugs can be prolonged due to
impaired metabolism and reduced levels of albumin. Propofol is a good choice in ESLD patients as its metabolism is
not significantly altered.

Narcotics and sedatives may precipitate or worsen encephalopathy, so dosage must be carefully titrated.
Benzodiazepines that undergo glucuronidation, such as oxazepam and lorazepam, are preferred as their elimination
is unaffected by liver disease.

Acute Liver Failure
Acute liver failure (ALF) is defined as the rapid development of jaundice, coagulopathy and encephalopathy in a
patient without preexisting liver disease. Such patients are critically ill and should not undergo surgery other than
those related to liver transplantation. It is important to establish the etiology of acute liver failure as the prognosis,
and need for liver transplantation, relates to the underlying cause.(Ostapowicz 2002) Transplant-free survival is
highest for patients with ALF due to acetaminophen overdose (roughly two-thirds recover without transplant), but is
less than 25% for ALF due to other causes.

Outcomes for Specific Surgeries
Patients with end stage liver disease frequently require procedures and surgery related to their disease. Biliary tract
obstruction is best managed using percutaneous techniques when possible. Endoscopic sphincterotomy may be
associated with increased rates of bleeding, yet mortality and morbidity is low.(Freeman 1999) The risk of
complications in biliary tract surgery is related to the degree of hepatic synthetic dysfunction as measured by the
INR; however, the risk of bleeding does not correlate with the INR.(Tripodi 2007) Laparoscopic cholecystectomy is

238
Page 4
preferred to open procedures for patients with less severe liver disease; open cholecystostomy is preferable in
patients with advanced (Childs class C) disease. Biliary tract surgery is associated with high infection rates due to
the translocation of bacteria and the absence of bile salts in the gastrointestinal tract, which increases absorption of
endotoxin.
The incidence of hepatocellular carcinoma (HCC) is 1-4% per year in patients with cirrhosis.(El-Serag 2004)
Hepatic resection for HCC carries a high risk in patients with cirrhosis. In a study of 82 HCC patients, those with
MELD scores greater than 9 had a perioperative mortality of 29%, while MELD scores less than 9 were associated
with no perioperative mortality.(Teh 2005)
Patients with Childs class B and C have high mortality and morbidity rates after cardiac surgery.(Hayashida 2004)
The least invasive option is preferred for the management of coronary artery disease. Bare metal stents may be
preferable to drug eluting stents due to the shorter duration of aspirin and clopidogrel after stent placement.
Summary
Patients with end stage liver disease can have associated abnormalities of nearly every organ system. A thorough
preoperative evaluation with optimization of coexisting problems is important in minimizing perioperative mortality
and morbidity. Patients with high MELD scores (or Childs class C) should not undergo elective surgery. Non-
elective surgery in patients with severe liver dysfunction is accompanied by a high mortality, and a high risk of liver
failure. Surgery in these patients is best coordinated with a regional liver transplant center to achieve optimal results.
References
Alkozai, E. M., T. Lisman, et al. (2009). "Bleeding in liver surgery: prevention and treatment." Clin Liver Dis 13(1):
145-154.
Bass, N. M., K. D. Mullen, et al. (2010). "Rifaximin treatment in hepatic encephalopathy." The New England
journal of medicine 362(12): 1071-1081.
CDC. (2010). "Viral Hepatitis Surveillance in the United States, 2010." National Notifiable Disease Surveillance
System, from http://www.cdc.gov/hepatitis/Statistics/2010Surveillance/.
D'Albuquerque, L. A., M. P. de Miranda, et al. (1995). "Laparoscopic cholecystectomy in cirrhotic patients." Surg
Laparosc Endosc 5(4): 272-276.
El-Serag, H. B. (2004). "Hepatocellular carcinoma: recent trends in the United States." Gastroenterology 127(5
Suppl 1): S27-34.
Freeman, M. L., D. B. Nelson, et al. (1999). "Same-day discharge after endoscopic biliary sphincterotomy:
observations from a prospective multicenter complication study. The Multicenter Endoscopic
Sphincterotomy (MESH) Study Group." Gastrointest Endosc 49(5): 580-586.
Friedman, L. S. (1999). "The risk of surgery in patients with liver disease." Hepatology 29(6): 1617-1623.
Garcia-Tsao, G., A. J. Sanyal, et al. (2007). "Prevention and management of gastroesophageal varices and variceal
hemorrhage in cirrhosis." Hepatology 46(3): 922-938.
Garrison, R. N., H. M. Cryer, et al. (1984). "Clarification of risk factors for abdominal operations in patients with
hepatic cirrhosis." Ann Surg 199(6): 648-655.
Gil, A., F. Martinez-Regueira, et al. (2004). "The role of transjugular intrahepatic portosystemic shunt prior to
abdominal tumoral surgery in cirrhotic patients with portal hypertension." Eur J Surg Oncol 30(1): 46-52.
Gines, P., A. Cardenas, et al. (2004). "Management of cirrhosis and ascites." The New England journal of medicine
350(16): 1646-1654.
Hayashida, N., T. Shoujima, et al. (2004). "Clinical outcome after cardiac operations in patients with cirrhosis." Ann
Thorac Surg 77(2): 500-505.
Kawut, S. M., M. J. Krowka, et al. (2008). "Clinical risk factors for portopulmonary hypertension." Hepatology
48(1): 196-203.
Krowka, M. J., M. S. Mandell, et al. (2004). "Hepatopulmonary syndrome and portopulmonary hypertension: a
report of the multicenter liver transplant database." Liver Transpl 10(2): 174-182.
Mansour, A., W. Watson, et al. (1997). "Abdominal operations in patients with cirrhosis: still a major surgical
challenge." Surgery 122(4): 730-735; discussion 735-736.
Moller, S. and J. H. Henriksen (2008). "Cardiovascular complications of cirrhosis." Gut 57(2): 268-278.
Munoz, S. J. (2008). "Hepatic encephalopathy." The Medical clinics of North America 92(4): 795-812, viii.

238
Page 5
Murphy, S. L., J. Xu, et al. (2012). "Deaths: Preliminary data for 2010." CDC National Vital Statistics Reports
60(4): 7.
Nishiyama, T., T. Fujimoto, et al. (2004). "A comparison of liver function after hepatectomy in cirrhotic patients
between sevoflurane and isoflurane in anesthesia with nitrous oxide and epidural block." Anesthesia and
Analgesia 98(4): 990-993.
Northup, P. G. (2008). "Hypercoagulation and thrombophilia in liver disease." Journal of Thrombosis and
Haemostatis 6: 2-9.
OPTN. (2011). "OPTN / SRTR 2010 Annual Data Report." Organ Procurement and Transplantation Network
(OPTN) and Scientific Registry of Transplant Recipients (SRTR), from
http://www.srtr.org/annual_reports/2010/flash/03_liver/index.html.
Ostapowicz, G., R. J. Fontana, et al. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care
centers in the United States." Ann Intern Med 137: 947-954.
Palmieri, K., Sladen R.L. (2012). "The Patient with Liver Disease for Non-hepatic Surgery." In Liver Anesthesiology
and Critical Care Medicine, ed. G. Wagener, pp333-351. New York: Springer.
Poggio, J. L., Rowland, C. M., et al. (2000). "A Comparision of Laparoscopic and Open Cholecystectomy in
Patients with Compensated Cirrhosis and Symptomatic Gallstone Disease." Surgery 127(4): 405-11.
Schepke, M., J. Heller, et al. (2001). "Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis:
evidence for a receptor-specific mechanism." Hepatology 34(5): 884-888.
Teh, S. H., J. Christein, et al. (2005). "Hepatic resection of hepatocellular carcinoma in patients with cirrhosis:
Model of End-Stage Liver Disease (MELD) score predicts perioperative mortality." J Gastrointest Surg
9(9): 1207-1215; discussion 1215.
Teh, S. H., D. M. Nagorney, et al. (2007). "Risk factors for mortality after surgery in patients with cirrhosis."
Gastroenterology 132(4): 1261-1269.
Tripodi, A., S. H. Caldwell, et al. (2007). "Review article: the prothrombin time test as a measure of bleeding risk
and prognosis in liver disease." Aliment Pharmacol Ther 26(2): 141-148.
Ziser, A., Plevak, D. J., et al. (1999) "Morbidity and Mortality in Cirrhotic Patients Undergoing Anesthesia and
Surgery." Anesthesiology 90: 42-53.

Disclosure

302
Page 1
Hazards of the Anesthesia Workstation
James B. Eisenkraft, M.D. New York, New York
The anesthesia delivery system comprises the anesthesia machine, vaporizers, ventilator, and waste gas
scavenging system. Failure of the delivery system is a rare cause of anesthesia-related injury to, or death of, a patient.
Much more commonly the delivery system is misused, the anesthesia caregiver makes an error, or the delivery system
fails while the user is unaware that a failure has occurred. This lecture will review failures and complications of
anesthesia gas delivery systems from the viewpoint of how they may arise, be detected and thereby harm to the patient
prevented.
PERSPECTIVE
The critical incident (CI) technique was first described by Flanagan in 1954
1
and was developed to reduce loss
of military pilots and aircrafts during training. It was modified and introduced into anesthesia by Cooper et al.
2
who
interviewed staff and resident anesthesiologists in a large metropolitan teaching hospital. They collected and analyzed
1089 descriptions of CIs during anesthesia.
3
A mishap was labeled a CI when it was clearly an occurrence that could
have led, if not discovered or corrected in time, or did lead to an undesirable outcome, ranging from increased length of
hospital stay to death or permanent disability. Other CI study inclusion criteria were: that each incident involve an error
by a member of the anesthesia team or a failure(s) of the anesthetists equipment to function properly; it occurred during
patient care; it could be clearly described; and the incident was clearly preventable.
3
Of the 1089 CIs, 70 represented
errors or failures that had contributed in some way to a substantive negative outcome (SNO) defined as mortality,
cardiac arrest, canceled operative procedure, or extended stay in the PACU, ICU or in the hospital. While 30% of all
CIs were related to equipment failures, including breathing circuit disconnections, misconnections, ventilator
malfunctions, and gas flow control errors, only 3 (4.3%) of SNO incidents involved equipment failure, suggesting that
human error was the dominant problem. Although equipment failures rarely cause death, CIs related to equipment are
common and have prompted improvements in equipment design, construction and in monitoring.
In 1993, the Australian Anaesthesia Patient Safety Foundation published results of the Australian Incident
Monitoring Study (AIMS) that had collected 2000 CIs.
4
Of these, 177 (9%) were due to equipment failure in general
and 107 (60%) involved the anesthesia delivery system.
5
Failures included problems due to unidirectional valves,
ventilator malfunctions, gas or electrical supply, circuit integrity, vaporizers, absorbers and pressure regulators.
Concerning the problems with ventilation, it was recommended that critical areas be doubly or triply monitored and that
monitoring equipment be self-activating.
6

The role of equipment failures leading to malpractice litigation in the United States has been studied by the
ASA Closed Claims Project (CCP). A 1997 analysis of 3791 claims,
7
of which 76% occurred during the period 1980-
1990, found that gas delivery equipment problems accounted for 72/3791 (2%). Of these 72, 39% were related to
the breathing circuit, 17% to ventilators, 21% to vaporizers, 11% to gas tanks or lines and 7% to the anesthesia machine.
Death or brain damage occurred in 76% of the 72 cases. Initiating events were circuit misconnects, disconnects and gas
delivery system errors. Misuse was judged to have occurred in 75% and equipment failure in only 24%. Anesthesia
caregivers were considered responsible in 70% of use error cases and ancillary staff (e.g., technicians) to have
contributed in 30%. Predominant mechanisms of injury were hypoxemia, excessive airway pressure and anesthetic agent
overdose. Overall, the reviewers deemed 78% of claims to have been preventable by the use or better use of monitoring.
As of May 2012, the Closed Claims Project database included 9536 claims of which 115 were related to
anesthesia gas delivery equipment.
8
The most recent gas delivery system claims were for an event in 2005. Thus far,
however, it appears that gas delivery equipment problems are decreasing as a proportion of surgical anesthesia claims.
Anesthesia gas delivery claims represented 4% of surgical anesthesia claims from the l970s, 3% from the 1980s, 1%
from the 1990s, and 1% from the period 2000-2010. There were only 39 anesthesia gas delivery system claims from
302
Page 2
1990-2010. These include 14 vaporizer problems, 10 breathing circuit problems, 8 oxygen tank and supplemental
oxygen line events, , , 5 ventilator problems, and2 anesthesia machine problems . The outcomes in anesthesia gas
delivery equipment claims from 1990-2010 seem to be less severe than earlier claims. In 1990-2010, 38% of anesthesia
gas delivery system claims resulted in severe injury or death compared to 80% in 1970-1989, p<0.001. Among the 39
claims from 1990-2010 were 10 deaths, 9 awareness claims , 6 pneumothorax claims, and5 permanent brain damage
claims. Payments reflect the lower severity of injury, with a median payment (in 2011 dollars) of $199,000 in the 1990-
2010 claims compared with $802,750 (adjusted to 2011 dollars) for earlier gas delivery equipment claims. Thirty-two
(82%) of the 39 post-1990 claims resulted in payment.
8

MONITORING THE ANESTHESIA BREATHING SYSTEM
The anesthesia breathing system (patient circuit) represents the interface between the patient and the anesthesia
delivery system.
9
While not all equipment failures are preventable, appropriate monitoring of the patient circuit should
lead to early detection of failures and enable prompt intervention before the patient suffers any harm. Aspects of the
patient circuit that can be routinely monitored include pressure, volume, capnography, respiratory gas composition and,
gas flows. Used correctly (i.e., appropriate monitors, alarm threshold limits, alarms enabled and functioning) such
monitoring should detect most errors or failures. Each monitoring modality will be briefly considered, together with its
applications and limitations.
Pressure Monitoring.
Many traditional anesthesia breathing systems incorporate an analogue pressure gauge, as well as an electronic pressure
monitoring and alarm system. The pressure gauge, if present, is usually mounted on the CO
2
absorber and may measure
the pressure at that site (Drger). In the Ohmeda GMS Absorber System, pressure is sensed on the patient side of the
inspiratory unidirectional valve and piloted to the pressure gauge and pressure monitoring system. Depending upon
breathing circuit configuration, the pressure monitor may fail to detect certain abnormal pressure situations. Thus
monitoring pressure at the absorber will not detect PEEP produced by a free-standing PEEP-valve that has been placed
between the expiratory limb of the circle system and the expiratory unidirectional valve. Ideally, pressure is monitored at
the patients airway. Some newer electronic anesthesia workstations use only electronic monitoring and display of
pressures, some on a virtual analog gauge displayed on the monitor screen.
Low Pressure Alarm. Because breathing system disconnects and misconnects are not uncommon occurrences,
monitoring of breathing system integrity is essential. Circuit low pressure monitors have sometimes been referred to as
disconnect alarms but this may be a misnomer because they monitor pressure and the user may infer circuit integrity
only if the monitor is used appropriately. They annunciate an audible and visual alarm within 15 seconds when a
minimum pressure threshold is not exceeded. The pressure threshold should therefore be set by the user to be just less
than the normal peak inspiratory pressure (PIP) so that any slight decrease will trigger the alarm. If the threshold is not
bracketed close to the PIP, a circuit leak or disconnect may go undetected if the low pressure alarm threshold is
exceeded. Thus, a small diameter tracheal tube (e.g., 3.0 mm I.D.) connected to a circle system might be pulled out of
the patients airway, leaving the lungs unventilated. Because the 3.0 mm tube has high resistance to gas flow, the
pressure increase in the circuit with each positive pressure inspiration may exceed the low pressure alarm threshold. On
modern anesthesia workstations the circuit pressure waveform is displayed, as are the pressure alarm thresholds, so that
the latter can be suitably adjusted by the user. Some workstations offer an auto-limits setting that automatically
brackets the alarm limits for all monitored parameters in relation to the then existing values.
Modern delivery systems incorporate low pressure alarms that are automatically enabled when the ventilator is
turned on, but there may be still in use some older designs of alarm systems that must be enabled by the user. Because
the low pressure alarm is critical during use of IPPV, the user must be aware of the properties of the monitoring system
on the individual machine that he/she is using. If there is any doubt about whether or not a monitor is interfaced with the
ventilator ON/OFF switch, the alarm can be tested by deliberately creating a disconnect. Some low pressure monitoring
alarm systems offer an optional 60 second delay in the event that a slow ventilatory rate, e.g., < 4 breaths/min, is set.
Whereas the breathing system low pressure alarm must be enabled (either automatically or manually) in
association with IPPV, the following pressure monitoring modalities are in continuous operation.
Continuing Pressure Alarm. Annunciated when circuit pressure exceeds 10 cm H
2
O for >15 seconds, it alerts to more
gradual increases in pressure, such as due to a ventilator pressure relief valve malfunction (i.e., valve stuck closed) or a
scavenging system occlusion. In these situations fresh gas continues to enter the breathing system from the machine
flowmeters but is unable to leave. Rate of rise of pressure therefore depends upon the fresh gas flow rate.
10

302
Page 3
High Pressure Alarm. This alarm is annunciated immediately whenever the high pressure threshold is exceeded. On
contemporary workstations this threshold is adjustable by the user. In addition, the ventilator incorporates a high
pressure relief valve, the opening threshold pressure of which is set in conjunction with the high pressure alarm limit.
These are important in preventing positive pressure barotrauma.
Subatmospheric Pressure Alarm. This annunciates an immediate alarm when pressure is < -10 cm H
2
O. It should alert
to potential negative pressure barotrauma situations due to suction being applied to the circuit. Negative pressure in the
circuit may be due to spontaneous respiratory efforts by the patient, a malfunctioning waste gas scavenging system, a
side-stream sampling gas analyzer when fresh gas flow into the circuit is too low, a suction catheter passed into the
airway, or suction via the working channel of a fiberscope passed into the airway via a diaphragm. Workstations that use
fresh gas decoupling and a piston ventilator (e.g., Drager Fabius and Apollo) have a negative pressure relief valve in the
breathing system that opens (at about -2 cm H2O to allow entry of room air if the volume of gas in the circuit is
inadequate. When this valve opens an alarm is annunciated.
Volume Monitoring.
In traditional delivery systems monitoring of expired tidal and minute volumes is achieved using a spirometer placed in
the vicinity of the expiratory unidirectional valve. Spirometry is used to monitor ventilation and circuit integrity. A
breathing system disconnect should result in annunciation of the low volume alarm if an appropriate alarm limit for low
volume has been set. A spirometer located by the expiratory unidirectional valve at the absorber, does not measure the
patients actual exhaled tidal volume, rather the volume measured includes both that exhaled by the patient and the gas
volume compressed in the breathing system.
While the spirometer low volume alarm is generally more useful in alerting to a low volume/possible disconnect
situation, a high volume alarm feature may also be useful. Unanticipated increases in tidal volume have resulted from
increasing the gas flow into the circuit.
11
This may be from the machine flowmeters, by increasing the I:E ratio, or via a
hole in the bellows in a Drger AV-E ventilator (that uses a mixture of oxygen and entrained air to drive the bellows).
Thus any gas entering the patient circuit during inspiration has the potential to be added to the patients inspired tidal
volume. This may be particularly hazardous to the pediatric patient for whom a small tidal volume is intended.
Contemporary workstations measure breathing system compliance during the automated preuse checkout, and
use flow sensors located by the inspiratory and/or expiratory unidirectional valves to accurately monitor inspired (VT
I
)
and expired (VT
E
) tidal volumes. These data can be used to automatically compensate for small leaks in the breathing
system, and changes in the fresh gas flow, respiratory rate and I:E ratio which otherwise might unintentionally change
the intended (set) tidal volume.
12

Gas Composition in the Circuit
Appropriate monitoring of O
2
, CO
2
, N
2
O, N
2
and anesthetic agent in the gas mixture at the patients airway will
alert to most gas delivery, composition, and agent dosing problems.
Oxygen. This is the most important monitor in the gas delivery system because it is both quantitative and qualitative.
Many anesthesia delivery systems incorporate a galvanic fuel cell oxygen sensor at the inspiratory unidirectional valve.
This analyzer actually senses PO
2
(although the display may be in volumes %), is calibrated to 21% using room air and,
unlike other technologies, is not fooled by other gases. Most sidestream sampling multigas monitors use a rapid
responding paramagnetic analyzer that can display the oxygen concentration breath-by-breath. On contemporary
workstations the O
2
analyzer should be automatically enabled whenever the machine is capable of delivering an
anesthetic gas mixture. Causes of inadequate O
2
concentration in the circuit include a hypoxic gas being delivered via
the pipeline or tanks, disconnected fresh gas hose during use of a hanging bellows ventilator, O
2
flow control valve
turned off, fail-safe system failure, proportioning system failure, O
2
leak in the low pressure system of the machine, and
a closed circuit with inadequate O
2
inflow rate.
The O
2
analyzer with low concentration alarm appropriately set is an essential safety feature of all anesthesia
delivery systems. A high O
2
concentration alarm may also be important in certain situations. Thus during an O
2
/helium
anesthetic for laser surgery of the airway, if the helium tank were to become depleted or if the O
2
flush is used, a high O
2

concentration would be delivered that may lead to a fire. Such a situation is now unlikely because a single tank
containing an oxygen-helium mixture is used rather than a tank of pure helium.
One likes to assume that it is O
2
that flows from O
2
wall outlets but this is not always the case. It is important to
recognize that there is no qualitative O
2
analyzer between the wall outlet or tanks and the machine oxygen inlet. Only
the gas in the breathing system is analyzed, but not the presumed-to-be O
2
gas flowing from an auxiliary O
2
flowmeter
on the machine or one connected directly to a wall outlet. In one case two patients died when an auxiliary O
2
flowmeter
was connected to a wall N
2
O outlet.
13

302
Page 4
Capnography. Capnography is discussed elsewhere in more detail.
14
It can provide much information about ventilation
of the patients lungs, as well as about anesthesia delivery system function. Failure to ventilate, which might be due to a
circuit disconnect or misconnect, should result in absence of a capnogram and annunciation of an apnea alarm. An
abnormal capnogram may be caused by CO
2
rebreathing (e.g., exhausted CO
2
absorbent; incompetent inspiratory or
expiratory valves; misconfigured circuit; Bain circuit with inner tube disconnect).
Anesthetic Gases and Nitrogen. Monitoring concentrations of N
2
O and potent inhaled agent with use of appropriate
high and low concentration alarm settings will alert to most agent dosage problems. Low agent concentration may be

due to the vaporizer being off or empty and could result in patient awareness. Excessive agent concentrations may be
due to vaporizer malfunction, tipping, or liquid agent in the circuit. Some analyzers will annunciate an alarm in the
presence of mixed agents (vaporizer contamination; more than one vaporizer on).
15
Agent analysis is also reassuring
whenever a new piece of equipment, e.g., a Tec 6 vaporizer (for desflurane), or the Aladin
vaporizing system (on the

GE ADU and Aisys workstations) is being used. Monitoring of N
2
concentration is rarely performed since it requires
technology now not generally available in the clinical situation (i.e., mass spectrometer, Raman scattering-based
analyzer) but may be useful in alerting to the presence of an air leak into the breathing system. Some multigas analyzers
display the percentage of the total gas mixture that is not analyzed/identified and this value is termed balance gas. By
measuring barometric pressure (PB), and subtracting from this PN2O, PCO2, PAnesthetic agent (measured by infrared
technology) and PO2 (measured by paramagnetic analysis), the result is the PBalance gas. The PBalance gas/PB x 100
gives the balance gas in volumes percent. The unmeasured gas is normally nitrogen. If a helium/O2 mixture were being
administered, then helium would be measured as balance gas.

Flows/Sidestream Spirometry
Contemporary anesthesia workstations use flow sensors in the breathing circuit to monitor gas flows, and from
flow and time they calculate volume. This allows display of plots of volume vs. pressure and volume vs. flow so that
changes in these parameters may easily be detected. The various technologies used are described elsewhere.
12

Most contemporary multigas analyzers use sidestream sampling of gas from the breathing system. The addition
of a Pitot tube flow sensor to the sidestream sampling adapter makes it possible, with only a small increase in size of the
adapter, to monitor and set alarm limits for pressure, flow, volume and gas composition, all of which are sensed at the
airway. Such monitoring of multiple aspects of patient ventilation and delivery system function at the patients airway
offers many potential advantages over the usual pressure and volume monitoring sites, including the ability to monitor
the patients inspired and expired tidal volumes, flow-volume and pressure-volume loops.
16
Continuous measurement of
O
2
and CO
2
concentrations versus inhaled and exhaled volumes makes it possible to monitor CO
2
production, O
2
consumption, and respiratory exchange ratio (respiratory quotient).

Alarms
While delivery system failures, use(r) errors and equipment failures cannot always be prevented, appropriate
monitoring should facilitate detection of most such problems and permit intervention before patient harm occurs.
Monitoring/alarm deficiencies include absence (i.e., no monitor); non-function (i.e., monitor present but broken); and
disabled (i.e., monitor/alarm not turned on or intentionally turned off)
6
and inappropriate alarm thresholds or volume
settings.
In the AIMS study with respect to ventilation it was concluded that critical areas be doubly or even triply
monitored and that monitoring equipment be self-activating.
6
This philosophy might be equally well applied to other
critical variables that are monitored. Alarm setting features are important and easy (user friendly) bracketing of
suitable limits is highly desirable, as is annunciation of adequate volume audible (i.e., loud) as well as visual alerts.

Carbon Dioxide Absorbents, Carbon Monoxide, Compound A, Fires and Explosions
Since 1990 there have been several reports of patients who developed increased levels of carboxyhemoglobin in
response to accumulation of CO in the circle system. The CO is generated when desflurane, enflurane and, to a lesser
extent, isoflurane, interact with dry CO
2
absorbent, particularly Baralyme
.17
While no case of patient harm has been
reported to date, CO represents a potential hazard of which the anesthesia caregiver should be aware.
18
Measures to
decrease this potential hazard include using absorbent that has the standard complement of water, or addition of liquid
water to the top of the absorbent. Fresh gas should be turned off at the end of each case to prevent desiccation of the
absorbent and consideration should be given to replacing the absorbent more frequently, especially if the machine has
been left unused for some time, such as over a weekend.
Another approach is to use a CO
2
absorbent that does not contain strong bases (Ba(OH)
2
and KOH)).
19,20
For
example, Amsorb is a CO
2
absorbent that does not contain strong base and does not form CO (or compound A) in vitro.

302
Page 5
It also turns purple when desiccated, an additional advantage.

While there is currently no analyzer available to monitor
CO in the breathing system, certain multiwavelength pulse oximeters can now measure COHb, MetHb and Hb.
21

Desiccated Baralyme
acting on sevoflurane can produce absorber temperatures that exceed 400C, fires, and
explosions.
22-26
Animal studies and a bench model demonstrate fires and explosions with sevoflurane.
22
and there are
now several reports of fires and explosions in clinical practice with sevoflurane (but none with desflurane or
isoflurane),
23-25
in one case causing patient injury. In late 2004 the manufacturer of Baralyme discontinued its
distribution, which may minimize or even eliminate the problems of fire and explosion. The risk of fire and explosion is

considered to be much less with soda lime, although it has been suggested that the absorber temperature be routinely
monitored using a skin probe.
26

PREVENTION OF FAILURES AND ADVERSE OUTCOMES
Complications due to the anesthesia delivery system are uncommon but when they occur are usually due to
use(r) error rather than actual equipment failure.
27
User education/in-servicing is essential if sophisticated equipment,
such as a new (computerized, electronic) anesthesia workstation, is to be used appropriately.
28
Education of medical and
ancillary (nursing/technical) staff is also important because they may unwittingly contribute to the occurrence of a
complication.
29, 30
Studies have shown that anesthesia providers often fail to properly perform the preuse checkout of their
anesthesia delivery system. This may be due to the complexity of previously published checkouts.
31
An updated
approach to the preuse checkout has recently been published on the ASA website (2008 Pre-anesthesia checkout design
guideline: http://www.asahq.org/clinical/fda.htm). Suggested pre-use checkouts for a number of contemporary
workstations are also presented on this website.
The new electronic workstations have preuse checkouts in which many of the checks have been automated but
some must be completed by the user. It is essential that the user understand how to perform the tasks that are required.
For example, the user must correctly assemble and connect the breathing system to the workstation. The automated
checkout is then able to pressurize the system to measure compliance and check for leaks, but not necessarily for correct
gas flow through the components. It may be possible for a breathing system to be incorrectly assembled, be gas tight, yet
not permit any gas to flow to the patient.
Some anesthesia workstations (e.g., Drager Apollo, Fabius GS; Datascope Anestar) use fresh gas decoupling
(FGD) to ensure that changes in fresh gas flow do not affect the desired (dialed-in) tidal volume delivered to the
patients airway. During the inspiratory phase of IPPV, only gas from the piston chamber (Drager) or bellows (Anestar)
is delivered to the inspiratory limb of the circle system because the decoupling valve closes to divert fresh gas flow into
the reservoir bag. FGD circuits differ from the traditional circle system in design and therefore may be associated with
different problems, including detection of a leak in the breathing system
32
and failure of the FG decoupling valve.
33
All
indicated and required monitors must be available and used correctly with alarm limits and alarm volumes set
appropriately for the individual patients situation. Anesthesia equipment should be regularly serviced by authorized
personnel and the equipment updated as necessary to conform to any existing requirements. A 2004 statement
concerning guidelines to determine anesthesia machine obsolescence is available on the ASA website
(http://www.asahq.org/publicationsAndServices/machineobsolescense.pdf).
A pre-use checkout of the delivery system should be developed by each institution to suit local needs and item
#1 on any pre-use checkout should be that a backup means of ventilation should always be immediately available and
functioning. Testing the function of the self-inflating manual resuscitation device (SIMVD) during the pre-use checkout
is essential. Occasionally, an SIMVD is found to be faulty, either not generating positive pressure when it is squeezed,
or not releasing positive pressure when it is longer being squeezed. Thus in the event of a delivery system failure, the
patients lungs can be ventilated with room air (or oxygen if a tank is available) using an SIMVD. Recent studies suggest
that there is an increased awareness of the importance of the preuse checkout and management of machine-related
critical incidents.
34-37
One national anesthesiology board has even incorporated these into the Objective Structured
Clinical Evaluation (OSCE) component of its Board Examination in Anesthesiology
38

REFERENCES
1. Flanagan JC: The critical incident technique. Psychol Bull 1954; 51-327-358
2. Cooper JB et al.: Preventable anesthesia mishaps. Anesthesiology 1978; 49:399-406
3. Cooper JB et al.: An analysis of major errors and equipment failures in anesthesia management. Anesthesiology
1984; 60:34-42

302
Page 6
4. Webb RK et al.: The Australian Incident Monitoring Study: An analysis of 2000 incident reports. Anaesth Int Care
1993; 21:520-528
5. Webb RK et al.: Equipment failure: An analysis of 2000 incident reports. Anaesth Int Care 1993; 21:673-677
6. Russell WJ et al.: Problems with ventilation: an analysis of 2000 incident reports. Anaesth Int Care 1993; 1: 617-620
7. Caplan RA, Vistica MF, Posner KL, Cheney FW: Adverse anesthetic outcomes arising from gas delivery
equipment: a closed claims analysis. Anesthesiology 1997; 87: 741-8
8. Mehta MP, Posner KL, Domino KB.Patient injuries from anesthesia gas delivery equipment: A closed claims
update. ASA Annual Meeting Abstract #1072, 2012.
9. Eisenkraft JB. Hazards of the Anesthesia Delivery System. In: Anesthesia Equipment: Principles and Applications,
2
nd
edition. Ehrenwerth J, Eisenkraft JB, Berry JM eds. New York, Elsevier, 2013, 591-620.
10. Eisenkraft JB. Potential for barotrauma or hypoventilation with the Drger AV-E ventilator. J Clin Anesth 1989;
1:452-456
11. Scheller MS et al.: Influence of fresh gas flow and I:E ratio on tidal volume and PaCO2 in ventilated patients. J
Cardiothorac Anesth, 1989, 3:564
12. Tham R, Oberle M. How do flow sensors work? APSF Newsletter 2008; 23: 10-14
13. Surgery mix-up causes 2 deaths. New Haven Register. January 20, 2002
14. Giordano CR, Gravenstein N. Capnography. In: Anesthesia Equipment: Principles and Applications, 2
nd
edition.
Ehrenwerth J, Eisenkraft JB, Berry JM eds. New York, Elsevier, 2013, pp 245-255.
15. Eisenkraft JB. Anesthesia Vaporizers. In: Anesthesia Equipment: Principles and Applications, 2
nd
edition.
Ehrenwerth J, Eisenkraft JB, Berry JM eds. New York, Elsevier, 2013, pp. 64-94.
16. Merilinen P et al.: A novel sensor for routine continuous spirometry of intubated patients. J Clin Monit 1993;
9:374-380
!"# Fang ZX et al.: Carbon monoxide production from degradation of desflurane enflurane, isoflurane, halothane and
sevoflurane by soda lime and Baralyme. Anesth Analg 1995; 80:1187-93
18. Berry PD, Sessler DI, Larson MD. Severe carbon monoxide poisoning during desflurane anesthesia. Anesthesiology
1999; 90:613-616.
19. Kharasch ED, Powers KM, Artru AA. Comparison of Amsorb, sodalime, and Baralyme
degradation of volatile anesthetics and formation of carbon monoxide and compound A in swine
in vivo. Anesthesiology 2002; 96:173-182
20. Olympio MA. Carbon dioxide absorbent desiccation conference convened by APSF. APSF Newsletter 2005; 20:
21. Barker SJ. Pulse oximetry. In: Anesthesia Equipment: Principles and Applications, 2
nd
edition. Ehrenwerth J,
Eisenkraft JB, Berry JM eds. New York, Elsevier, 2013, pp 256-272.
22. Laster M, Roth P, Eger EI, II: Fires from the interaction of anesthetics with desiccated absorbent.
Anesth Analg 2004; 99: 769-774
23. Wu J, Previte JP, Adler E, Myers T, Ball J, Gunter JB: Spontaneous ignition, explosion and fire with sevoflurane
and barium hydroxide lime. Anesthesiology 2004; 101: 534-537

302
Page 7
24. Castro BA, Freedman LA, Craig WL, Lynch C, III: Explosion within an anesthesia machine: Baralyme, high
fresh gas flows and sevoflurane concentration. Anesthesiology 2004; 101: 537-539
25. Fatheree RS, Leighton BL: Acute respiratory distress syndrome after an exothermic Baralyme-sevoflurane reaction.
26. Woehlck HJ. Sleeping with uncertainty: anesthetics and desiccated absorbent. Editorial. Anesthesiology 2004;
101:276-8
27. Eisenkraft JB. A commentary on anesthesia gas delivery equipment and adverse outcomes. Editorial.
28. Olympio MA. Formal training and assessment before using advanced medical devices in the OR. APSF
Newsletter 2008; 22: 63.
29. Singh S, Loeb RG: Fatal connection: Death caused by direct connection of
oxygen tubing into tracheal tube connector. Anesth Analg 2004; 99: 1164-5
30. Wax DB, Bhagwan S, Beilin Y. Tension pneumothorax and cardiac arrest from an improvised oxygen delivery
system. J Clin Anesth 2007; 19: 546-8
31. FDA Anesthesia apparatus checkout recommendations, 1993. Available on the FDA website:
www.fda.gov/cdrh/humfac/anesckot.html
32. Sandberg WS, Kaiser S. Novel breathing system architecture: new consequences of old problems. Anesthesiology
2004; 100: 755-6
33. Ortega RA, Zambricki ER. Fresh gas decoupling valve failure precludes ventilation in a Draeger Fabius GS
anesthesia machine. Anesth Analg 2007; 104: 1000
34. Mudumbai SC, Fanning R, Howard SK, et al. . Use of medical simulation to explore equipment failures and
humanmachine interactions in anesthesia machine pipeline supply crossover. Anesth Analg 2010;110:12926
35. Lorraway PG, Savoldelli GL, Joo HS et al. Management of simulated oxygen supply failure: is there a gap in the
curriculum? Anesth Analg 2006;102:8657
36. Weller J, Merry A, Warman G et al. . Anaesthetists' management of oxygen pipeline failure: a room for
improvement. Anaesthesia 2007;62:1226
37. Blasius K, DeMaria S, Neustein SM. Missed steps in the preanesthetic checkout. Anesth Analg 2011; 113: 84-88.
38. BenMenachem E, Ezri T, Ziv A et al. Identifying and managing technical faults in the anesthesia machine: lessons
learned from the Israeli Board of Anesthesiologists. Anesth Analg 2011; 112: 864-6

Disclosure

311
Page 1
Preoperative Identification, Evaluation and Optimization of the Highest Risk Patients
BobbieJean Sweitzer, M.D. Chicago, Illinois
Major surgery is associated with significant physiology stress and frequently with adverse outcomes both acutely
and long-term. Approximately 15% of patients having non-ambulatory non-cardiac surgery are at risk of major
complications including death and disability. Worldwide, 200-250 million patients undergo surgery yearly, many
of them aged with severe comorbidities and advanced disease. Considering a 1% risk of death with a 5% risk of
complications up to 2.5 million patients will die and 12.5 million will have costly adverse events. It is imperative
that we identify those at risk and intervene to lower risk or at least inform patients of their chances for a
meaningful outcome. It has been shown that a little over 12% of patients account for 80% of postoperative
deaths. Mortality varies widely across hospitals and countries. However, evidence suggests that high-risk
patients are often not identified preoperatively, and proven strategies to lower risk are not implemented. Risk
assessment can lead to changes in medical management, planned anesthesia and surgery, postoperative care or
even recommendations to avoid surgery.
In 2010 there was an estimated 40 million individuals over 65 yr of age in the US. Those 85-94 yr old increased
by 30% in the 10 yr since 2000 with a growth rate 3x that of the general population. Advanced age is a strong
predictor of postoperative mortality and morbidity across many domains including cardiovascular (CV),
pulmonary and infectious causes. Elderly patients > 75 yr have up to twice the risk of major morbidity and 3-7
times risk of dying compared to younger patients. The frail elderly and those undergoing major cancer procedures
are at particular risk. Frailty independently predicts postoperative complications, length of stay, and need for
discharge to an assisted- living facility. Determination of a frailty score as shown below enhances other risk
models. Impaired cognition, low albumin, previous falls, low hematocrit, functional dependence and multiple co-
morbidities are associated with 6- month mortality and inability to be discharged home postoperatively.
Up to 6% of patients with risk factors for coronary artery disease (CAD) will experience CV complications after
non-cardiac surgery. CAD varies from mild, stable disease with little impact on perioperative outcome to severe
disease accounting for significant complications during anesthesia. The basis of cardiac assessment is the history,
and the physical examination. Review of records and previous studies especially stress tests and catheterization
results is necessary. The ACC/AHA guidelines for CV evaluation for non-cardiac surgery have decreased
recommendations for testing or revascularization. The guidelines have an algorithm to be followed in stepwise
fashion, stopping at the first point that applies to the patient (Fig 1). For emergency surgery, the focus is
perioperative surveillance (e.g., serial ECGs, enzymes, monitoring) and risk reduction (e.g., beta blockers, statins,
pain management). Active cardiac conditions (acute myocardial infarction [MI], unstable or severe angina,
decompensated heart failure[HF], severe valvular disease, or significant arrhythmias) warrant postponement for all
except life-saving emergency procedures. Step 3 considers the surgical risk and patients without active cardiac
conditions having low-risk surgery need no further cardiac testing. For higher risk surgery, Step 4 assesses
functional capacity, defined by metabolic equivalents. Asymptomatic patients with average functional capacity
can proceed to surgery. Step 5 considers patients with poor or indeterminate functional capacity who need
intermediate- risk or vascular surgery. The number of clinical predictors (CAD, compensated HF, cerebrovascular
disease, diabetes, and renal insufficiency) from the Revised Cardiac Risk Index (RCRI) determines the likely
benefit of further testing. Patients with no RCRI predictors proceed to surgery. Consider further testing for those
with >3 RCRI predictors but only if results will alter management. Traditional risk factors for CAD such as
smoking, hypertension (HTN), age, male gender, hypercholesterolemia, and family history do not predict
perioperative risk. The benefits versus the risk of coronary revascularization before non-cardiac surgery are
controversial. The only randomized prospective study of preoperative revascularization vs. medical management
failed to show an outcome difference. Non-cardiac surgery soon after revascularization has high rates of
morbidity and mortality. Patients who have had a percutaneous coronary intervention (PCI), especially with a
311
Page 2
drug-eluting stent (DES) require months, if
not a lifetime of anti-platelets to prevent restenosis or thromboses. The type of stent, DES or bare metal (BMS),
must be identified. A scientific advisory offers recommendations for managing patients with coronary stents.
Elective procedures that require stopping dual antiplatelet therapy are delayed during the high-risk period (12 m
for DES; 4-6 wk for BMS; 2 wk after angioplasty without stenting). Invasive procedures increase the risk of stent
thrombosis which has a high mortality. Stent thrombosis is best treated with PCI, which can be safely performed
perioperatively if needed. High risk patients may best be managed in facilities with immediate access to
interventional cardiology. There is a low risk of bleeding complications with continued aspirin during most
procedures. Premature discontinuation of dual antiplatelet therapy can cause catastrophic stent thrombosis, MI, or
death. A meta-analysis involving almost 50,000 patients undergoing a variety of non-cardiac surgeries (30% on
perioperative aspirin [ASA]) found that ASA increased bleeding complications by a factor of 1.5, but not the
severity of complications except in patients undergoing intracranial surgery and possibly transurethral resection of
the prostate. When surgeons are blinded to ASA administration they cannot identify patients taking or not taking
ASA based on bleeding. There is an increased risk of vascular events when ASA is stopped in patients who take it
regularly. A rebound hypercoagulable state may result. Acute coronary syndromes occurred 8.5 + 3.6 days and
acute cerebral events 14.3 + 11.3 d after ASA cessation, the typical duration of cessation before surgery. Events
were twice as common in patients who had stopped ASA in the previous 3 wk than in those who had not.
Stopping aspirin for 3-4 days should be sufficient, if ASA is stopped at all, and dosing should be resumed as soon
as possible. New platelets formed after ASA (half-life of ~15 min) is stopped will not be affected. Normally
functioning platelets >50,000/mm
3
are adequate to control surgical bleeding. A review article recommends
discontinuing ASA if taken only for primary prevention (no history of stents, strokes, MI). Continuing ASA, if
taken for secondary prevention (history of stents, vascular disease), is recommended except for procedures with a
risk of bleeding in closed spaces (e.g., intracranial). Statins and beta-blockers when started ahead of the day of
surgery can lower risk. Careful titration of beta-blockers to avoid hypotension is important. Statins have anti-
inflammatory and plaque stabilizing properties. All patients with atherosclerotic vascular disease benefit from
statins, regardless of their cholesterol levels. Continuing statins perioperatively have risk reduction benefits and
withdrawal can result in excessive adverse events.

Heart failure (HF) increases perioperative mortality three- to fivefold and is associated with a substantially higher
risk than CAD. Many studies have shown that HF is the most or among the most significant risk factors for
perioperative complications. Patients with HF are also more likely to require readmission (2-fold) compared to
those with CAD. B-type natriuretic peptide predicts both short and long-term postoperative outcomes.
Determination of ejection fracture with echocardiography can assist with intra- and postoperative care. HF may
be present in up to 20% of elderly surgical patients. Patients with compensated HF have a 5-7% risk of cardiac
complications; those with decompensated HF have a 20-30% incidence. Operative mortality is twice as common
with HF as CAD. HF has also been shown to be a strong predictor of pulmonary complications. HF is at least as
important as a diagnosis of COPD in predicting perioperative respiratory adverse events.

Aortic stenosis (AS) is the most common valvular lesion in the U.S. (2-4% of adults > 65 yr); severe AS is
associated with a high risk of perioperative complications. Aortic sclerosis, present in 25% of people 65-74 yr and
50% of those >84 yr, causes a systolic ejection murmur similar to that of AS, but has no hemodynamic
compromise. Echocardiography is beneficial, especially if more than sedation is planned. Patients with severe AS
should not have anesthesia (unless emergency and life-saving) without a cardiology evaluation. Antibiotic
prophylaxis to prevent infective endocarditis is no longer recommended for patients with valvular abnormalities
except for patients with heart transplants.

Pacemakers and implantable cardioverter-defibrillators (ICDs) can be affected by electromagnetic
interference. Consultation with the manufacturer or cardiologist may be needed. Patients usually have a card
with important designations and phone numbers. Patients with ICDs invariably have HF, ischemic or
valvular disease, cardiomyopathies, or potentially lethal arrhythmias. Special features such as rate adaptive
mechanisms in some
pacemakers are disabled or the device reprogrammed to asynchronous pacing to prevent interference. Some
monitors, ventilators, vibrations, or chest prepping fool the sensors into increasing pacing, leading to ischemia or
inappropriate treatment. Shock functions are disabled before procedures if interference or unexpected movement
is undesirable. During intracranial, spinal, or ocular procedures, an unexpected discharge with movement can be
311
Page 3
catastrophic. Central line placement can trigger cardioversion. ICDs are deactivated only after arrival to a facility
with monitoring and external defibrillation devices. Many devices are complex and reliance on a magnet to
disable them, except in emergencies, is not recommended. Some devices ignore magnet placement. Magnets can
permanently disable cardioversion. A magnet may suspend anti-shock therapies in some ICDs only while it is in
place. Magnets do not affect the pacing function of an ICD. If a pacemaker or ICD is reprogrammed, or if a
magnet is used, the device needs re-interrogated and re-enabled before the patient leaves a monitored setting.

Respiratory failure postoperatively is a significant cause of morbidity and mortality. Patients who develop
perioperative respiratory failure when undergoing general or major vascular surgeries have a mortality as high
as 26.5%. This rate compares to a mortality rate of 1.4% in those who do not have respiratory failure. The
costs associated with postoperative respiratory complications come with a substantial cost, on average almost
$63,000. This is twice the cost associated with the next most costly complication, thromboembolic events. In
contrast cardiovascular complications cost $18,500 on average. Pulmonary complications within 30 days post-
surgery reduce median long-term (5-10yr) survival by 90%.

Established risk factors for pulmonary complications include a history of cigarette use (current or exceeding 40
pack-years), ASA-PS > 2, age > 70 yr, COPD, neck, thoracic, upper abdominal, aortic, or neurologic surgery,
procedures > 2 hr, planned general anesthesia (especially with endotracheal intubation), albumin concentration < 3
g/dL, inability to walk 2 blocks or climb 1 flight of stairs, or a BMI > 30. Surprisingly absent in the above list are
asthma, arterial blood gas or PFT results. The risk of complications is surprisingly low in well-controlled
asthmatics or those treated preoperatively with corticosteroids. Risk is greater in asthmatics with recent
exacerbations, prior postoperative pulmonary complications, recent hospitalizations, or intubations for asthma.
Arterial blood gases are useful in predicting pulmonary function after lung resection surgery but do not predict risk
for complications. The degree of airway obstruction, measured by the FEV1 is not predictive of pulmonary
complications. Similarly, arterial blood gas results and chest radiographs do not predict postoperative pulmonary
complications. The role of PFTs may be for diagnosis (is dyspnea caused by lung disease or heart failure?) or
assess management (can dyspnea or wheezing be improved further?), but not as a risk assessment tool or to
deny a beneficial procedure. Most patients with chronic dyspnea of unclear etiology have one of four diagnoses:
asthma, COPD, interstitial lung disease or cardiac dysfunction. The history and physical examination leads to
accurate diagnoses in two thirds of cases. Initial testing includes an ECG, hematocrit (to exclude anemia), arterial
blood gases, thyroid function tests, chest radiograph, spirometry, and oximetry (resting and after walking several
feet). Pulmonary function tests (PFT) have no perioperative predictive value for asthmatics. Brain natriuretic
peptide (BNP) may also be useful. Most dyspneic patients with heart failure have BNP values exceeding 400
pg/mL, while plasma BNP concentrations between 100 and 400 pg/mL in a dyspneic patient should raise
suspicions for compensated left ventricular dysfunction, pulmonary embolism, and cor pulmonale. Other
specialized testing depends on should be directed by the history, physical examination and initial test results.
Computed tomography scans and cardiopulmonary exercise testing are rarely necessary, but can be useful if the
above tests are not diagnostic.

Some of these factors can be modified to alter risk. The pulmonary status of patients with recent exacerbations
or infections needs to be improved whenever possible. Prescriptions for antibiotics, bronchodilators and
steroids; referral to pulmonologists or internists; or delay of surgery are important in patients at high risk.
Preoperative respiratory muscle training (daily incentive spirometry against an inspiratory load for 2 wk) has
been shown to reduce length of stay and pneumonia in patients undergoing CABG. A change in perioperative
management, including altering the planned surgical procedure, if possible; discussing alternatives to general
anesthesia, especially when regional techniques are an option; and educating the patient about the benefits of
epidural pain management provide effective measures to decrease pulmonary complications.

Sleep-disordered breathing affects up to 9% of middle-aged women and 24% of middle-aged men; less than 15%
of these cases have been diagnosed. Obstructive sleep apnea (OSA), which is the most common serious
manifestation of sleep-disordered breathing, is caused by intermittent airway obstruction. It is characterized by
total collapse of the
airway with complete obstruction for more than 10 seconds. Obstructive hypopnea is partial collapse (30% to
99%) associated with at least a 4% arterial oxygen desaturation. Snoring, daytime sleepiness, hypertension,
obesity, and a family history are risk factors for OSA. The severity of OSA is based on the apnea-hypopnea index
311
Page 4
(AHI), which is the number of apneic and hypopneic episodes per hour of sleep. Patients with severe OSA have
30 or more episodes per hour. Patients with OSA have increased rates of diabetes, hypertension, atrial
fibrillation, bradyarrhythmias, ventricular ectopy, stroke, heart failure, pulmonary hypertension, dilated
cardiomyopathy, and coronary artery disease. Cardiovascular disease is common in patients with OSA. Mask
ventilation, direct laryngoscopy, endotracheal intubation, and fiberoptic visualization of the airway are more
difficult in patients with OSA. Such patients are likely to have perioperative airway obstruction, hypoxemia,
atelectasis, ischemia, pneumonia, and prolonged hospitalizations. Patients with OSA are more sensitive to the
respiratory depressant effects of opioids. The STOP-Bang questionnaire (Fig 2), which was developed and
validated in an anesthesia preoperative clinic, can help screen for OSA. Echocardiography may be indicated if
heart failure or pulmonary hypertension is suspected. Patients should be instructed to bring their continuous
positive airway pressure (CPAP) devices to the hospital on the day of operation. If empiric CPAP is used
postoperatively pressures of 8-12 cm H20 are most effective.

Pulmonary hypertension may occur in isolation or with associated medical conditions. It is defined as a persistent
elevation of mean pulmonary artery pressure of 25 mmHg or greater, with a pulmonary artery occlusion pressure
less than 15 mmHg. Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary
hypertension (PPH) is relatively rare. Other more common forms occur with a variety of diseases including
cardiac, pulmonary, liver, thromboembolic and collagen vascular diseases. Pulmonary hypertension is associated
with human immunodeficiency virus (HIV) infection, sleep apnea, chronic liver disease (especially with portal
hypertension) and collagen vascular diseases (e.g., scleroderma, systemic lupus erythematosus). Patients with
pulmonary arterial hypertension have a high rate of perioperative morbidity and mortality. Hypoxia, hypercarbia,
vasoconstrictors, and increased sympathetic tone (even from anxiety) increase pulmonary vascular resistance, with
the potential for acute decompensation with right heart failure. Mild pulmonary hypertension rarely impacts
anesthetic management, but moderate to severe disease increases the risk of right heart failure.

Exposure to tobacco, directly or through second-hand smoke increases the risk of many perioperative
complications. Smoking is associated with a 40% increased odds of 30 day mortality and a 30%-100% increased
odds of major morbidity including surgical site infection, unplanned intubation, pneumonia and sepsis. Patients
without ischemic heart disease who smoked shortly before operation have significantly more episodes of ST-
segment depression than nonsmokers, former smokers or chronic smokers who do not smoke in the immediate
preoperative period. Smoking decreases macrophage function; negatively impacts coronary flow reserve; and
causes vascular endothelial dysfunction, hypertension and ischemia. Smokers require longer hospital stays and
more often need postoperative intensive care than non-smokers.

The greatest benefit of smoking abstinence is probably only realized after several months of cessation. In addition,
the perioperative clinical benefits of preoperative smoking cessation demonstrated in systematic reviews are only
evident when cessation occurred at least 3 to 4 weeks before surgery. These benefits include reduced respiratory
and wound-healing complications. Despite an early study reporting greater perioperative risk (notably, this
association was not statistically significant) in recent quitters, a recent systematic review found no increased risk
of adverse events with quitting smoking soon before surgery (i.e., within 8 weeks). Thus, motivated patients
should be encouraged to quit smoking at any point before surgery. There are many potential benefits to quitting,
even with a few days before surgery. Soon after a patient quits smoking, carbon monoxide levels decrease, thereby
improving oxygen delivery and utilization. Cyanide levels decrease, which benefits mitochondrial oxidative
metabolism. Lower nicotine levels improve vasodilatation, and many toxic substances that impair wound-healing
decrease.

The United States Public Health Service recommends that all physicians should strongly advise every patient
who smokes to quit because evidence shows that physician advice to quit smoking increases abstinence rates.
Nearly 70% of smokers want to quit. Effective interventions include medical advice and pharmacotherapy, such as
nicotine- replacement therapy, which is safe in the perioperative period. Nicotine patches, gum and lozenges are
available without a prescription; nasal spray, buproprion (i.e., Zyban), and varenicline (i.e., Chantix) require
prescriptions. Clonidine is also effective. Buproprion, varenicline or clonidine is started 1-2 weeks before a quit-
attempt; nicotine replacement therapy is effective immediately. Individual and group counseling may increase
rates of long-term abstinence. Many hospitals, insurance companies and communities offer smoking cessation
programs. Excellent
311
Page 5
resources are available on the Internet and from the U.S. government. Advice and guidelines are available at 1-
800- QUITNOW and http://www.surgeongeneral.gov/tobacco/default.htm.

Renal disease increases perioperative risk, especially cardiovascular complications. Chronic kidney disease
(CKD) is included in several risk scores, including the ACC/AHA cardiac evaluation for non-cardiac surgery
algorithm with a creatinine > 2 a RCRI risk factor equivalent to known stable ischemic heart disease in
predicting cardiac risk. The estimated glomerular filtration rate (eGFR) is a more accurate measure of renal
function, especially for less severe disease. The eGFR predits both short- (< 30 d) and long-term mortality,
especially in vascular and cardiac surgical patients, with even mild disease (eGFR< 60 ml/min/1.73 m
-2
)
associated with a 3-fold risk of death within 30 d and mortality and CV events long-term. Preoperative kidney
disease is the strongest predictor of postoperative renal failure. Risk factors for CKD include advancing age
(>55), smoking, diabetes, hypertension, dyslipidemia, heart failure.

Severe liver disease increases perioperative risk especially when coupled with major surgery. Predictors of
increased risk include Child-Pugh-Turcotte class C, MELD (Model for End-stage Liver Disease) score > 15,
acute liver failure, acute alcoholic hepatitis and a serum bilirubin > 11 mg/dL. Renal insufficiency in association
with hepatic disease carries a particularly poor prognosis. The highest risk surgeries are abdominal (including
cholecystectomy), cardiac, high blood loss and emergency surgeries. Complications in surgical patients with
cirrhosis include pneumonia, infections, and renal and respiratory failure.

Obesity alone has not been shown to significantly increase perioperative risk. However, patients with the
metabolic syndrome are at markedly increased risk of complications with surgery, especially death, cardiac events
and acute kidney injury. It is estimated that 22% of adults in the US have the metabolic syndrome. Obese
individuals are also at risk of pulmonary and wound complications, stroke and sepsis. Super obese patients with
the metabolic syndrome have twice the mortality compared to normal weight individuals.

Patients at particularly high risk of perioperative venous thromboembolism (VTE) such as the elderly, those with
cancer or previous VTE, or bedridden patients benefit from aggressive perioperative VTE prophylaxis. Patients
on oral anticoagulants may need bridging therapy preoperative. Patients who have had an acute venous or arterial
thromboembolism should complete at a minimum 1 month of anticoagulant therapy before undergoing surgery if
at all possible. The risk is further reduced with 3 months of therapy. Patients who have recurrent
thromboembolism or have ongoing risk factors such as cancer or a hypercoagulable state are at persistently
elevated risk. These are the patients who benefit most from bridging. The most common bridge is low-molecular
weight heparin. Patients with atrial fibrillation who have not had a prior embolic event typically do not benefit
from bridging. Those with a history of atrial fibrillation complicated by thromboembolism likely should be
bridged. Patients with mechanical heart valves are bridged on a case-by-case basis depending on the type of valve.
Valves in the mitral position and older types of valves are more thrombotic than aortic valves and bileaflet valves.

Malnourished patients have significantly higher rates of mortality and morbidity, especially poor wound
healing, increased length of stay and infections. Low albumin levels predict both mortality and morbidity.
Adequate perioperative nutritional support decreases postoperative complications. However, parenteral
nutrition may have substantial risks, especially as a preventive intervention.

Hyponatremia, anemia, elevated BNP levels, lower eGFR, large areas of wall motion abnormalities on
dobutamine stress echocardiography and poor exercise capacity on cardiopulmonary exercise testing (CPET) all
predict elevated risk.

Preoperative hyponatremia is associated with higher 30 day mortality (5.2% vs 1.3% and OR 1.44 with 95% CI
1.38-1.50) and complications, including major coronary events, pneumonia and wound infections. Hyponatremia
is
the most common electrolyte abnormality and is a very sensitive marker of severity of underlying disease,
especially heart failure. It remains unknown whether hyponatremia is a marker or a cause of adverse events and
mortality. More importantly it it not known whether correction of hyponatremia will lower risk. Whenever
possible the underlying cause of hyponatremia should be determined and mitigated. However, too rapid of
correction can lead to adverse effects. But, for now preoperative hyponatremia should be considered a sensitive
311
Page 6
indicator of comorbid disease, severity of disease, and perioperative morbidity and mortality.
Preoperative anemia, even when mild, is associated with increased 30 day mortality. A hemoglobin < 8 is
associated with a 16-fold increase in mortality. Morbidity is also increased in patients with mild-moderate
anemia. There is an increased risk of cardiac events, pneumonia and delirium. In patients with risk factors such as
CV disease, diabetes, or CKD who have concomitant anemia the perioperative mortality rate is typically twice
that seen with the underlying disease alone without anemia. . Additionally, perioperative transfusions are
associated with increased morbidity and mortality. A restrictive transfusion strategy (maintaining a hgb between
7 and 9 g/dL) is at least as effective, if not superior, to a more liberal approach (targeting a hgb of 10-12 g/dL) in
critically ill patients, with the possible exception of those with unstable coronary syndromes.

Cardiopulmonary exercise testing (CPET) is a clinical tool that measures cardiopulmonary fitness and functional
capacity. It is the more objective and comprehensive than the 6 minute walk test and other methods of
measurement. CPET can be used to elucidate the cause of unknown dyspnea, determine the severity of diseases
such as heart failure and COPD and as a preoperative risk assessment tool. Many variables are measured during
CPET but 3 in particular are useful in determining preoperative risk, the VO2 peak/max, anerobic threshold (AT)
and ventilatory equivalent for carbon dioxide (VE/VCO2). Studies support that AT can be used to triage patients
to postoperative intensive care. In one study patients deemed at high risk based on an AT < 11 ml/kg/min who
were having major surgery in spite of escalated care the cardiovascular mortality in the high risk group was
4.6% vs 0.5% in the low risk group. An AT < 11 ml/kg/min also predicts in-hospital deaths. Elevated
preoperative levels of C-reactive protein (CRP) and N-terminal pro-brain natriuretic protein (NT-proBNP) are
independent and strong predictors of major postoperative cardiovascular events in patients having non-cardiac
surgery. Elevated troponin levels in the first 3 days after surgery are associated with 30-day mortality. Whether
identifying a population using this marker would allow opportunities to intervene to lower risk has not been
shown. However, there is evidence that patients who have silent ischemia postoperatively have higher mortality
than those with overt myocardial infarctions perhaps due to interventions such as maximal medical risk reduction
suggests that there may be opportunities to decrease adverse events.

High risk patients are best managed in intensive care units (ICUs) immediately postoperatively preferably with
protocolized care with careful attention to pain management, control of hemodynamics, pulmonary toilet and
early interventions. Studies and experience show that post-cardiac and thoracic surgery patients who are typically
routinely cared for in ICUs have better outcomes than patients with similar risk profiles who have abdominal or
orthopedic procedures. High risk patients who go to ICU immediately postoperatively rather than to a general
ward first have improved outcomes.

Optimal preoperative patient preparation is essential if risks are to be lowered. Further research and development
of evidence-based protocols are needed. It is likely that optimal results will require a multidisciplinary approach
with involvement of care providers with various clinical skills. Ideally patients will be managed from several
weeks- months before surgery through a similar timeline postoperatively. Ideally patients would be evaluated
before a date of surgery is even planned and they would be invested in their care. Better data on outcomes of all
surgical procedures is desperately needed to drive development of more effective systems of care need to be
implemented. A starting point would be to use a combination of age, type of procedure, co-morbid conditions and
biomarkers to stratify patients into categories of risk. Low risk patients can proceed to surgery without special
preparation. High risk patients would be evaluated by a specialist in preoperative medicine, undergo more
advanced testing and prehabilitation if needed before proceeding to surgery in specialized, high-volume centers.

References:

1. Banz VM, et al. Improving outcome after major surgery: Pathophysiological considerations. Anesth
Analg 2011;112:1147.
2. Choi JH, et al. Preoperative NT-proBNP and CRP predict perioperative major cardiovascular events.
Heart 2010;96:56.
3. Crossley GH, et al. The Heart Rhythm Society (HRS)/American Society of Anesthesiology (ASA)
expert consensus statement on the perioperative management of patients with implantable defibrillators,
pacemakers and arrhythmia monitors: facilities and patient management: Executive summary. Heart
Rhythm 2011; 8;e1.
311
Page 7
4. Devereaux PJ, et al. Association between postoperative troponin levels and 30-day mortality among
patients undergoing noncardiac surgery. JAMA 2012;307:2295.
5. Dimick JB, et al. Hospital costs associated with surgical complications: A report from the private-sector
National Surgical Quality Improvement Program. J Am Coll Surg 2004;199:531.
6. Hennis PJ, et al. Cardiopulmonary exercise testing for the evaluation of perioperative risk in non-
cardiopulmonary surgery. Postgrad Med J 2011;87:550.
7. Jhani S. Mortality and utilization of critical care resources amongst high-risk surgical patients in a large
NHS trust. Anaesthesia 2008;63:695.
8. Johnson RG, et al. Multivariable predictors of postoperative respiratory failure after general and vascular
surgery: Results from the patient safety in surgery study. J Am Coll Surg 2007;204:1188.
9. Makary MA, et al. Frailty as a predictor of surgical outcomes in elderly patients. J Am Coll Surg
2010;210:901.
10. Mooney JF, et al. Preoperative estimates of glomerular filtration rate as predictors outcome after surgery.
Anesthesiology 2013;118:809.
11. Musallam KM, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: A
retrospective cohort study. Lancet 2011;378:1396.
12. Wallace AW, et al. Association of the pattern of use of perioperative B-blockade and postoperative
mortality. Anesthesiology 2010;113:794.

Table 1. Frailty Score

Shrinking weight: Unintentional weight loss > 10 pounds in last yr
Decreased grip strength (weakness): Measured by patient squeezing a hand-hel dynamometer
Exhaustion: Measured by responses to questions about effort and motivation
Low physical activity: Measured by asking about leisure activities
Slowed walking speed: Measured by the speed patient can walk 15 feet

Makary MA, et al. Frailty as a predictor of surgical outcomes in elderly patients. J Am Coll Surg
2010;210:901.

311
Page 8
Figure 1

Figure 2. STOP-Bang Questionnaire

Please answer the following four questions with a yes or no answer:

1) Do you snore loudly (louder than talking or loud enough to be heard through closed doors)? Yes No
2) Do you often feel tired, fatigued, or sleepy during daytime? Yes No
3) Has anyone observed you stop breathing during your sleep? Yes No
4) Do you have or are you being treated for high blood pressure? Yes No
5) Is the BMI ! 35 kg/m
2
? Yes No
6) Is the patient ! 50 years of age? Yes No
7) Is the neck circumference greater than 15.7 inches (40 cm)? Yes No
8) Is the patient male? Yes No

Total number of questions answered YES: High risk of OSA: Yes to >3 items

Chung F. STOP Questionnaire. A tool to screen patients for obstructive sleep apnea. Anesthesiol 2008;108:812.

316
Page 1
Hospital System Failures and Hazard Management in the Operating Room
P. Allan Klock, Jr, M.D. Chicago, Illinois
Although we gain experience in our daily practice with hazardous situations such as caring for patients with difficult
airways or compromised cardiac function, it is difficult to become experienced with rarely!occurring situations such
as electrical failures or floods in the operating room. Therefore, we need educational activities that show us how
hospital systems work and fail and how we should respond to that failure.
A crisis response template is applied to failures of electrical, oxygen pipeline, and heating, ventilation, and air
conditioning (HVAC) systems and also to hospital floods. A generic crisis response template is presented that can be
applied to a wide range of situations. Anecdotal examples of hospital system failures are given to illustrate the
application of the crisis response template.
The role of the anesthesiologist often involves patient care and managerial or administrative duties. Our function in
both of these roles is integrated into the crisis response template. Improving our understanding of how systems work
and fail should allow us to create a good outcome from a hazardous situation.
GENERIC HAZARDS
Localize Risk
When a hazardous situation arises in a hospital, risks must be localized so resources can be allocated to those areas
most likely to benefit from additional help. This risk localization can be divided into four areas: procedure,
personnel, location, and equipment.
Procedural Risks. A patient on cardiopulmonary bypass or undergoing an endarterectomy with a clamp on the
common carotid artery may be more susceptible to injury from a power failure than a patient undergoing a more
simple procedure, such as a cystoscopy under spinal anesthesia. In the latter case, the surgeon could easily remove
the cystoscope and transport the patient to a safer location.
Personnel Risks. Some staff may be more or less able to perform well under adverse conditions. Resources may
need to be allocated to assist less experienced personnel or those with special needs.
Location Risks. The anesthesiologist delivering anesthesia in the obstetrical suite or remote locations will not have
the support of other operating room personnel when hospital systems fail or hazardous conditions arise. In addition,
they may be isolated if there is a concurrent communications system failure.
Equipment Risks. Certain equipment, especially very new or old equipment, may fail in unexpected ways. For
example, a newly manufactured intensive care unit ventilator ceased to function and was unable to reboot itself after
a transient (less than 1 second) interruption in the power supply to the ventilator was caused by a routine test of a
hospital's backup generator. This ventilator failed without an alarm. An intensive care unit nurse was in the patient's
room at the time and immediately began manual ventilation, protecting the patient from a hypoxic injury.
Preventive Maintenance and Improvements Are Needed but Pose Their Own Risks
Hospital systems require on!the!fly maintenance and improvements, for which patient care cannot be interrupted. As
the infrastructure of many hospitals continues to age, construction and maintenance have become more visible and
potentially problematic.
An example of such a problem occurs when a construction worker accidentally shuts an oxygen supply valve to an
area supporting patients. Testing a backup generator at another hospital caused a relay within part of the hospital to
become stuck, resulting in a 20!minute interruption of electricity to the critical service outlets in the operating suite.

316
Page 2

Hospital Systems Are Complex
Hospitals are complex structures with convoluted and interrelated systems. At many hospitals, construction workers
install new communication cables in the plenum (the space between the ceiling tiles and the structure of the floor
above) over corridors. Adding to the complexity of the system is the fact that old cable is rarely, if ever, removed
when new cable is put in place. This makes troubleshooting difficult when problems arise. In addition, several
systems have elements in the walls or plenum in the operating room suite. When one system fails, causing a water
leak, for example, it may affect other systems that have components nearby.

CRISIS RESPONSE TEMPLATE
The following template may serve as a guide to direct the thoughts and actions of anesthesiologists and other
operating room staff during an operating room crisis. The template has five elements: (1) coping with local
consequences, (2) establishing the scope of the problem, (3) protecting against side effects of the problem, (4)
addressing administrative issues, and (5) preparing for problem resolution or prolonged failure. The template may be
applied to a wide variety of system failures and crises. The elements gain different levels of importance depending
on the specific circumstances.

Cope with the Local Consequences of the Problem
The goal of coping with local consequences is to counteract the immediate effects of the system failure. For
example, if electricity fails in an operating room, a flashlight or laryngoscope should be used for illumination; if the
ventilator fails, manual ventilation should begin immediately. Anesthesiologists are usually proficient at protecting
their patients from immediate injury. For a detailed description of coping with the local consequences of hospital
system or equipment failure, readers should refer to Crisis Management in Anesthesiologv.1

Establish the Scope of the Problem
After the patient has been protected from imminent peril, the scope of the problem should be established. It is
important to determine what backup systems are available and in operation. How many operating rooms are affected
by the problem and what types of resources are at hand must be determined.
Certainly, if only one operating room has lost its pipeline supply of compressed oxygen, surgery can be continued
there ad infinitum, by repeatedly exchanging oxygen E cylinders at the back of the anesthesia machine. However, if
the entire hospital has no piped oxygen, all the E cylinders will be consumed quickly and all but the most urgent
procedures should be finished as quickly as possible.

Protect Against Side Effects of the Problem
The side effects of the problem must be obviated. These may be difficult to predict, delayed in time, distant in
location, or more serious than the primary problem.

Side Effects May Be Difficult to Predict. For example, if medical vacuum (suction) were to fail, it might not be
obvious that control of the hospital's HVAC system may be affected. In many hospitals, a vacuum control system
communicates between the thermostat and the valve that regulates the flow of steam or hot water through a heat
exchanger for the operating room. Normally, this control system vacuum is completely separate from the medical
vacuum system. However, if the medical vacuum fails, the hospital engineers may link the vacuum lines for the
HVAC control system to the main vacuum line. This will improve the suction for the medical vacuum but possibly
weaken the hospital's HVAC system.

Side Effects May Be Delayed. A small amount of water on the floor of an operating room is not inherently
dangerous. However, the aftermath of even a small flood in the operating room may take weeks to resolve. Many
other systems may need to be interrupted to fix a water leak. In addition, it may be several weeks before a room can
be adequately decontaminated to prevent the growth of mold in the ceiling, walls, or ventilation system. Such mold
growth may pose a serious hazard to immunocompromised patients.

Side Effects May Occur at a Distant Site. The University of Chicago Medical Center has its call center in Darien,
Illinois, 20 miles away from the hospital. A communication disruption between the hospital and the call center or a
power disruption in Darien would lead to a loss of the ability to page using beepers, overhead page in the hospital,
and to route calls through the hospital switchboard. In addition, the signals for pages for numeric beepers are
transmitted on subcarrier frequencies from local FM transmission towers. A problem with these transmission
systems, which are remote from the hospital, could lead to total or partial failure of the beeper system that can be
dangerous and difficult to detect.

316
Page 3
Some Side Effects May Be More Severe than the Primary Problem. Consider a problem with a hospital's fresh water
supply. Bottled sterile water can be used for a surgical scrub and to sterilize instniments. However, when the water
supply is reestablished, it may transiently contain bacterial and mineral impurities that may be more hazardous than
the lack of water itself.

Address Administrative issues (Get the Problem Fixed)
After the patient has been protected from immediate injury, the scope of the problem has been established, and side
effects have been obviated, administrative issues should be addressed and work should begin to get the problem
fixed. It is important to understand who can be helpful. Often, the plant department or hospital engineers should be
called first. Sometimes hospital security needs to be contacted to unlock doors or gain access to areas that require
service. Hospital administrators may need to be involved to allocate the resources required to get the problem fixed
in a timely manner.

Prepare for Prolonged Failure or Problem Resolution
Preparation should be made for prolonged failure or secondary problems that arise as the primary problem is
resolved. Sometimes conditions get worse before they get better. A small water leak in an operating room may lead
to interruption of the communication and electrical supply for an unexpectedly large area during the repair process.
A decision will need to be made regarding how to proceed with the operating room schedule if this occurs. Can
elective cases be delayed? Should only emergent cases be performed? Or should the emergency room be closed,
diverting trauma patients to other hospitals? The answer to these questions will depend on the scope of the problem
and the timing of its resolution.

Application of the Template to Specific Examples
Physicians team about anatomy, physiology, and pathophysiology before they learn about disease treatments and
prevention. This organization of learning also applies to hospital systems. We must understand how they work and
fail before we can learn to respond to and prevent system failures and potential injuries. The relevant "anatomy and
physiology" of hospital systems is presented here before the crisis response template is applied to examples of
electrical, oxygen pipeline, and HVAC failure and floods.

Electrical System Failure
Electrical System Design. Most large institutions, including many hospitals, are connected to the external power grid
in more than one location. This protects against a local failure of the power transmission wires where they are linked
to the hospital. In the event of a failure of the external grid, a backup battery in the hospital should provide power
within one half of a cycle (1/120 of a second). If this battery supply works properly, not even a flicker in the lights
will be noticed. This battery provides alternating current to critical service areas of the hospital. The outlets
supplied by the critical service circuits are red. The battery is also used to crank a starter for the diesel engine, which
will then drive the hospital's generator. This backup power generation will fail if any of its components, such as the
battery, starter, diesel engine, generator, relays, or transmission wires, fail. Problems have been reported with
obtaining an agreement for an adequate supply of diesel fuel for some hospitals.
2
In addition, failure of power
transmission relays inside the hospital have resulted in interruption of power to critical service outlets.

Many localized power failures are caused when a circuit breaker trips. If this occurs, the device most recently
plugged in should be unplugged and the circuit breaker reset. A few points are worth remembering about circuit
breakers in hospitals. First, it may be difficult to tell, by looking at an outlet, where the circuit breaker box is located
that supplies that outlet. It may be worthwhile to contact a hospital engineer for help if a overloaded circuit trips.
Second, many hospitals lock the door covering the circuit breaker panel. Hospital security or the plant department
should be contacted for access. Finally, if it is difficult to determine which circuit is tripped, it is not a good idea to
test every circuit, because service to other patient care areas will be interrupted.

Activation of the Line Isolation Monitor Alarm. All operating rooms built before 1984 are equipped with an isolated
electrical power system and a line isolation monitor (LIM). Operating rooms built after that date may have isolaged
power or a ground fault circuit breaker interrupter. Under certain circumstances, the LIM may signal its alarm while
an anesthetic is being delivered. Although this does not constitute a hospital system failure, it is important for
anesthesiologists to understand what the LIM protects against, what causes the LIM to signal its alarm, and what
actions to take when that occurs.

The purpose of isolated power and the line isolation monitor. Many anesthesiologists falsely believe that the LIM is
designed to prevent microshock. On the contrary, an LIM may remain silent if conditions exist that would allow up
to 50 times the amount of current required to produce microshock. Isolated power systems and LIMs were

316
Page 4
developed during the era of explosive anesthetics. They were installed to minimize the chance of faulty equipment
producing sparks that could cause an explosion.

An isolated transformer converts electricity from a "hot" lead and a grounded lead to a configuration in which
neither of the electrical lines that supply power is grounded. In a nonisolated system, current can pass from the hot
lead to the ground. This can result in a spark or forms of macroshock (e.g., an electrical burn or electrocution) if a
low impedance pathway is produced between the hot wire and the ground. Under normal conditions, an isolated
power system will not allow significant amounts of current to pass from either wire of the circuit to the ground, thus
preventing sparks and macroshock. The LIM measures the ability of the isolated circuit to prevent current flow from
the circuit to the ground. If the isolated circuit becomes degraded (see Response to Line Isolation Monitor Alarm),
then the monitor will signal its alarm.

Most early LIM alarms were set to signal when only 1.7 to 2.0 (mA) would be able to flow between the circuit and
ground. Because many operating rooms were plagued with "nuisance alarms," the total hazard current limit was
increased from 2 to 5 mA in 1978.

The line isolation monitor does not protect against microshock. If a patient has an implanted device that allows
electricity to pass directly into the heart, a high current flux (amps per square centimeter) can occur in the
myocardium. Examples of such devices include temporary pacing wires and electrolyte fluid!filled catheters placed
into the heart (such as pulmonary artery or central venous catheters). Microshock results when small amounts of
current pass through these devices, causing ventricular fibrillation. There is no consensus about the minimum
amount of current required to produce ventricular fibrillation, but values of 100 to 200 microamps are usually cited.
Regardless, microshock can occur at a fraction of the current required to make an LIM alarm signal.

The modern advantage of isolated power. Given that flammable anesthetics are no longer used, the one remaining
advantage of an isolated power system is branch circuit protection. If a device with a low impedance connection
between the lead and the ground (a ground!fault) is plugged into an isolated circuit, the LIM will produce audible
and visible signals but the circuit will continue to operate as a nonisolated system with one power line grounded,
similar to a circuit outside the operating room. If the operating room did not have an isolated power system,
plugging in the same device might trip the ground-fault circuit breaker interrupter (GFCI), eliminating power to one
or more operating rooms. Thus, an isolated power system with an LIM will alert the staff that there is a problem but
will allow the system to continue operating in a degraded mode, rather than produce an abrupt and complete circuit
failure.

Recommended response to a line isolation monitor alarm. The LIM alarm will signal when the total possible
leakage current is greater than the threshold value for the monitor; that is, either 2 or 5 mA. This can arise by one of
two circumstances. A faulty device may be plugged in that has a low impedance pathway between the internal
circuitry and the ground (the "faulty device"). Alternatively, several properly functioning devices may each allow a
small amount of leakage current, such that the sum of the leakage current for all the devices on the circuit is greater
than the allowable current limit.

When the LIM alarm signals, the most recently plugged!in or turned!on device should be removed from the circuit.
If the LIM alarm stops, then the offending device should be impounded, labeled "defective, check for ground fault,"
and evaluated by biomedical engineers before it is allowed to be used again. This serves to remove the faulty device
from operation.

If the LIM alarm continues after the most recently plugged!in device has been removed, then small amounts of
leakage current from many devices may be causing the problem and additional equipment should be unplugged until
the alarm ceases. An intermittent alarm can be caused by a device that is turning on and off internally, such as the
heating element of a fluid or blanket warmer. If no single offending device can be identified, then the equipment that
has been unplugged can be plugged into a different circuit in the same operating suite. Hospital engineers may need
to be contacted to determine which circuits supply which outlets. It is common for an operating room to have outlets
supplied by several different circuits and more than one isolated power supply.

Application of the Response Template to Electrical Failure.
Cope with local consequences of the problem. If a patient's ventilator fails, manual ventilation should be started
immediately. Obviously, the function of any other life sustaining equipment (e.g., cardiopulmonary bypass machine)

316
Page 5
should be checked as soon as possible. The cardiopulmonary bypass machine can be hand!cranked to maintain blood
flow. Every anesthesiologist should be familiar with the hand!cranking equipment location and procedure. Many
critical devices have internal batteries that should sustain function for at least a few hours.
Simple monitors may be used at this time. The following may be used to monitor a patient in the setting of an
electrical failure: palpating a pulse, checking the patient's color if there is adequate lighting, auscultation with a
precordial stethoscope, and using a manual blood pressure cuff and sphygmomanometer. A battery!powered
transport monitor may prove valuable, especially if monitoring the electrocardiograph or an invasive pressure is
critical.

Devices that use a cathode ray tube for display require high currents and usually do not have internal battery backup
systems. Many pulse oximeters and transport monitors use light!emitting diodes or liquid crystal displays that
require little current. These devices often have internal batteries that will allow them to function in the event of an
electrical failure.

If the operating room is dark, a decision must be made regarding who holds the flashlight: Should the
anesthesiologist keep it? Should it be given to the surgeon so that surgery can continue? Or should it be given to a
nurse to leave the room to find more flashlights or get help? Pagers have backlighting that provide a small amount
of light. Many smartphones have a screen that is bright enough to provide decent illumination and some phones
have an LED camera flash that can be continuously illuminated to provide a bright light.

Establish the scope of the problem. If only one circuit or one room is without power, the cause must be determined.
Is it possible that a faulty device was plugged in, causing a circuit breaker to trip? If more than one circuit has been
affected, then it is important to establish the scope of the problem. The response to the power failure will be
different if only one operating room or circuit is affected compared with the entire operating room suite or the whole
hospital or city. After investigating the extent of the power failure, it is important to inquire about the expected
duration of the power failure. This may be difficult to determine; however, if the cause can be identified, then it will
be easier to estimate the duration of the failure.

Protect against side effects of the problem. The immediate effects of an electrical failure are obvious. But other
systems that may be affected by the power failure must be considered. Surgery will become more hazardous as a
result of poor lighting and lack of electrocautery. The heating and ventilation systems may fail. Fluid warmers,
heating lamps, and forced hot air warmers will not work, putting patients at risk for hypothermia. Residual heat may
remain in a blanket or bottle warmer for a long time. This heat may be used to carefully warm fluids, but
overheating the fluids must be avoided. Room!temperature blankets and low!flow anesthesia may help prevent
hypothermia during a power failure.

Whether the event that caused the electrical failure has caused other systems to fail must be considered. For
example, a fire or explosion in another part of the hospital may lead to failure of the pipeline oxygen supply in
addition to electrical power. The proper functioning of all systems must be confirmed.
Other systems may be affected by the electrical failure. Will patient transportation to and from the intensive care
unit be possible without elevators? Will the central server for your electronic medical record systems continue to
work; will there be enough comuter workstations powered by critical service outlets powered by your hospitals
generator? Do the pharmacy or nursing stations rely on automated drug!dispensing systems (e.g., Pyxis; Pyxis
Corp., San Diego, CA). Will the blood bank be able to cross!match and dispense blood products without electricity?

Address administrative issues (Get the problem fixed). The hospital plant department and hospital engineers can be
helpful when internal electrical failures occur. They can tell what backup systems are in place and how long they
can be expected to last. Although it is appropriate to call the plant department first, the engineers may not be able to
fix all internal problems. For example, the University of Chicago Medical Center uses six independent electrical
contractors for its electrical work. It may take a long time before internal electrical problems are properly identified
and repaired. Hospital security may need to be contacted to gain access to areas restricted by identification badge
swipe controls. Finally, hospital administrators may need to become involved to authorize the rental of a large
portable generator or to hire contractors to perform their work in a timely manner.

Prepare for prolonged failure or problem resolution. Preparations must be made for problem resolution or
prolonged failure. It is important to determine how many rooms are affected and how long they will be without
power. A decision must be made regarding the performance of surgical cases. This will largely depend on the scope

316
Page 6
and expected duration of the problem. Under the most extreme circumstances, the hospital's emergency room should
be closed and arrangements made for patient transfer. If the backup generator is working properly and only a brief
interruption of the external power supply is expected, then it may make sense to continue with the elective surgical
schedule.

Prevention. Prevention is critical in averting patient injury during a power failure. Every operating room or
anesthetizing location should have a flashlight. Many anesthesiologists may say, "I don't need a flashlight, I have a
laryngoscope." An inexpensive hardware store flashlight will produce significantly more light than a high!quality
laryngoscope.

Many critical devices should have their own emergency power source. Backup batteries need to be checked and
maintained routinely (e.g., yearly for anesthesia machine internal batteries). Some batteries may indicate that they
are fully charged even though their capacity to hold a charge is greatly diminished (i.e., the voltage across the
terminals is maintained while the number of joules stored decreases). Thus, batteries in critical devices should
undergo periodic charge-discharge testing and/or replacement according to the manufacturer's recommendations.

Oxygen Failure
Oxygen System Design. A survey of 200 hospitals in 1976 revealed that 31 % of the hospitals reported problems
with their oxygen pipeline supply.3 Although many anesthesiologists may believe they will never experience an
oxygen pipeline failure, the resulting patient injury can be so severe and rapid that it is important to know what
backup systems are available and how to respond to a system failure.

Oxygen can be supplied to the hospital oxygen pipeline in two ways. The primary method is from a liquid oxygen
tank, which is located outside the building. The second method is through an oxygen tank farm inside the building.
Liquid oxygen flows from the external tanks to evaporator coils, where it is transformed from the liquid phase to the
gas phase and then enters the hospital.

The liquid oxygen supply can be disrupted because the external tanks simply run dry. One hospital had this happen
when the truck dispatcher sent the liquid oxygen truck to the wrong address on three separate occasions. At another
hospital, the delivery truck backed into the liquid oxygen tank, causing the pipes to become disconnected from the
hospital. Liquid nitrogen has been accidentally placed in a liquid oxygen tank leading to episodes of hypoxic injury.
4

To protect against these problems with the external liquid oxygen supply, a backup tank farm is located within the
hospital. The tank farm is a collection of H cylinders attached to a manifold. If the pressure in the pipeline decreases
below a specific level, gas will flow from the H cylinder manifold into the oxygen line. The University of Chicago
has 30 H cylinders in its tank farm, which offer approximately a 6!hour supply under conditions of normal use. Each
H cylinder contains 6,900 l oxygen when full. Obviously, if the tank farm starts to be used, this must be recognized
and efforts made to minimize oxygen demand until the problem is corrected.

Application of the Response Template to Oxygen Pipeline Failure.
Cope with local consequences of the problem. The first action to take when the oxygen pipeline fails is to switch to
an E cylinder immediately. If the wrong gas is thought to be delivered through the oxygen pipes, then the oxygen
pipeline must be disconnected from the anesthesia machine or gas will preferentially flow from the pipeline rather
than the E cylinder, because of the pressure setting of the pressure reducing valve in the cylinder yoke. To conserve
oxygen, fresh gas flows should be minimized and manual ventilation used rather than mechanical ventilation if the
machine uses compressed gas to drive the ventilator.

It is important to remember that in many anesthesia machines compressed oxygen drives the bellows for the
anesthesia machine ventilator. If a 3!1 fresh gas flow is used and the patient has a 7!liter!per minute (lpm)
ventilation, a full E cylinder will be depleted in 62 minutes (625 l @ 10 lpm = 62.5 minutes). If the same patient
receives a 3!l fresh gas flow with manual ventilation, a full E cylinder will last for 3 hours and 28 minutes (625 l @
3 lpm = 208 minutes). If the patient is manually ventilated with a 0.5!l fresh gas flow, a full E cylinder will last for
more than 20 hours (625 1 @ 0.5 lpm = 1,250 minutes = 20 hours, 50 minutes).

Establish the scope of the problem. The physical plant and hospital administrators should be contacted to determine
the cause of the failure: Is there a problem with the liquid oxygen supply outside the building? Has the supply run
out? When will a truck arrive to refill the tank? Perhaps a construction worker adjacent to the operating room
needed to close the oxygen supply in his area and accidentally shut off the supply to the operating room as well. It is

316
Page 7
important to establish the scope of the problem, because the backup resources (E cylinders) will become depleted
more rapidly with a hospital!wide supply interruption than with a localized problem.

Protect against side effects of the problem. There are few side effects of oxygen failure as the direct hazard is
potentially lethal enough. It should be remembered that compressed oxygen may drive the anesthesia ventilator. In
planning the conclusion of the anesthetic, it is desirable to have a patient breathing spontaneously. Intensive care
unit ventilators consume oxygen at rates several times the patient's minute ventilation. If the patient can be
extubated, or receive oxygen via a T!piece attached to the endotracheal tube, the hospital oxygen supply can be
greatly conserved.

Address administrative issues (Get the problem fixed). The plant department should be contacted to determine if
any valves have been closed accidentally, causing the supply interruption. They also may be able to attach new, full
H cylinders in the oxygen tank farm to increase its capacity. Hospital administrators should be contacted to arrange
for an emergency fill of the liquid oxygen tank if it is empty, or to arrange for the emergency delivery of E and H
oxygen cylinders.

Prepare for prolonged failure or problem resolution. A few special considerations are required after work has been
performed on the oxygen pipeline or an inappropriate gas has been inadvertently flowing into the oxygen pipeline
system. The pipes will need to be purged until 100% oxygen is delivered and measured at each wall outlet.
Prevention. Proper daily performance of the anesthesia machine check will protect against many of the perils that
threaten patient oxygen delivery. In addition, it is wise to have at least one full E cylinder attached to the anesthesia
machine and a second E cylinder with a regulator and a manual resuscitation bag available in each anesthetizing
location.

Heating, Ventilation, and Air Conditioning (HVAC) Failure
Heating, Ventilation, and Air Conditioning System Design. The air that is circulated in most hospitals varies from
30% to 70% recycled air, with the balance being fresh air from outside air intakes. This air mixture is triple!filtered
before it is passed over chillers. The chillers are heat exchangers that contain cold water and cool the air to 55 F.
This cold air is blown through the hospital ductwork and passes over a radiator immediately before it enters the area
where it is needed. The radiators are heated by steam or hot water and linked to the thermostat on the wall by the
special "control system" vacuum line. As the setting of the thermostat is adjusted, the amount of vacuum in the
control line is altered, changing the opening of the steam valve. This causes the hissing that can be heard when some
thermostat dials are adjusted.

To have proper HVAC, several elements are necessary: clean fresh and recycled air, fresh water for the chillers,
steam, electricity for the blowers, proper ductwork and plumbing, and a control system vacuum. Any of these
elements may fail, which win produce different failure modes and require appropriate application of the crisis
response template.

Application of the Crisis Response Template to Heating, Ventilation, and Air Conditioning System Failure
Cope with local consequences of the problem. Failure of the HVAC system usually is not immediately
life!threatening. However, it is possible for carbon monoxide poisoning to result from trucks idling near the
hospital's fresh air intake. For this reason, No Idling signs are usually posted by fresh air intakes, and hospital
security should be notified if exhaust fumes are noticed inside the hospital.

Most failures of the HVAC system will challenge patient temperature homeostasis. A forced air blanket (e.g., Bair
Hugger; Augustine Medical, Eden Prairie, MN) blowing warm or ambient air may help to protect patients against
very cold or hot operating room conditions, respectively. In addition, heating lamps, warming blankets, and fluid
warmers should be used if the operating room is unusually cold.

Establish the scope of the problem. Hospital engineers should be informed when a problem with the HVAC system
is possible. It will be helpful to understand the cause of the problem to help guard against side effects of the
problem. Obtaining an estimate of the problem duration will be helpful when plans are made for the rest of the
operating room schedule.

Protect against side effects of the problem. The side effects from HVAC failure will be patient hypo! or
hyperthermia and pollution of the operating room environment. If there is no air circulation in the operating room,
escape of anesthetic gasses into the atmosphere should be minimized (e.g., minimize cuff leak). To limit the amount

316
Page 8
of smoke in the operating room, surgeons may wish to decease the amount of electrocautery used. If cautery is used,
suction should be applied to evacuate the resulting smoke. Often an element of the HVAC system fails as a result of
another system failure (e.g., lack of steam, water, electricity). After determining the cause of the HVAC failure,
preparations must be made for side effects from the primary system failure.
Address administrative issues (Get the problem fixed). Often, when the call is made to establish the scope of the
problem, the necessary parties will begin fixing the problem.

Prepare for prolonged failure or problem resolution. Knowledge of the expected duration of the failure will dictate
what measures should be taken to maintain patient temperature homeostasis and reasonable quality of breathing air.

Floods
Hospital Water Handling Systems. In addition to regular hot and cold running water, hospitals have cooled water
running to and from the chillers and steam or hot water running to and from radiators for the HVAC systems.
Plumbing also includes drainage and sewer lines. Finally, many hospitals have sprinkler systems and dry standpipes
that can be used by firefighters in the event of a fire.

Application of the Crisis Response Template to Floods.
Cope with local consequences of the problem. If a patient is located in a room where water is leaking through the
ceiling, the patient should be relocated as soon as it is safe to do so. If water starts to leak through the ceiling, a large
barrel or garbage can should be brought into the room to catch the overflow when the ceiling tile is pierced or
removed. This will allow the water to drain into a contained space, preventing it from tracking above the ceiling tiles
or over the floor.

Establish the scope of the problem. Water can leak into an operating room from a number of sources. Possible
causes of water entering a basement or a subbasement room include groundwater entry resulting from a sump pump
failure, or sewage backing up because of a clogged pipe or problems with the municipal system. If water is leaking
from the ceiling, possibilities range from something as simple as an overflowing sink on the floor above to a
problem with a pressurized water line, steam pipe, or waste water.

Protect against side effects of the problem. Other critical systems near the leak may be affected. In particular,
electrical and communication lines may fail or need to be interrupted temporarily in the process of repairing the
leak.

Address administrative issues (Get the problem fixed). Simply cleaning up the water is not enough. Hospital
engineers and possibly plumbing contractors need to be involved to fix the problem. Hospital security may need to
be contacted to gain access to the rooms above the leak. Aspergillus and other molds may grow in the ceiling tiles,
wallboard, and ductwork of an area that has been flooded and not properly decontaminated. If immunocompromised
patients are exposed to spores from these molds, they may experience life-threatening infections. Infection control
personnel should oversee the decontamination and disinfection of the area. Although surgeons may be unhappy
about having an operating room unavailable for a prolonged period of time, they will take the threat of a wound
infection seriously.

Prepare for prolonged failure or problem resolution. Other services may need to be interrupted temporarily during
the repair process. Several weeks may be needed before the hospital infection control officers can certify that an
operating room is fit for use. Hospital administrators should be included in the discussion regarding how long the
surgical schedule will need to be altered.

Summary
Hospitals include complex interrelated systems that may fail in unexpected ways.
Application of the five elements of the crisis response template will help guide actions during system failures and
other hazardous circumstances. The patient should be protected from immediate injury, the scope of the problem
should be established, side effects of the problem should be identified and guarded against, administrative action
should be taken to fix the problem, and then preparations should begin for problem resolution or prolonged failure.
Hospital engineers often will be helpful in establishing the scope of the problem, identifying potential side effects,
and fixing the problem. Working as a team, the operating room staff, physicians, engineers, safety officers, and
administrators should aim to minimize the effect of these events on patient care and rectify problems as soon as
possible.

316
Page 9
References
1. Gaba DM, Fish KJ, Howard SK: Crisis Management in Anesthesiology. New York: Churchill Livingstone, 1994,
pp 195!229
2 . Geyelin M: Hospitals Face Complex Task Preparing for Dec. 31. Wall Street Journal, March 29,1999,B1.
3. Feely TW, Hedley!White J: Bulk oxygen and nitrous oxide delivery systems: Designs and dangers.
Anesthesiology 1976; 44:301.
4. Sprague DH, Archer GW: Intraoperative hypoxemia from an erroneously filled liquid oxygen reservoir.
Anesthesiology 1975; 42:360.

Disclosure

321
Page 1
ATLS Update: What Every Anesthesiologist Should Know
Maureen McCunn, MD, MIPP, FCCM Philadelphia, Pennsylvania
The Burden of Injury
Trauma is the 3rd leading cause of death in the U.S. and the leading cause of death in patients under the age of 44
years. The Centers for Disease Control report that falls are now the leading cause of ALL traumatic injury, due to
the aging population, followed by motor vehicle collisions and penetrating trauma. The reported number of people
treated for gunshot wounds from 2001 to 2011 has grown by nearly half, although mortality from firearm injuries is
decreasing: in 2010, 14% of shooting victims died, which is 2% lower than in 2007.
The risk of death following injury is significantly lower when patients are treated at trauma centers compared with
non-trauma hospitals. As of 2010, 90% of the US population was within 60 minutes of a trauma center by helicopter
or ambulance ensuring appropriate care within the Golden Hour. However the work is costly; trauma centers
across the U.S. lose about $230 million/year treating the uninsured, according to estimates by the Trauma Center
Association of America. Emergency care is reimbursed by Medicaid at a rate less than the cost of treatment.
Many patients have multiple trauma-related OR procedures during their initial hospitalization that are treated by the
trauma service (e.g. damage control, with multiple returns to the OR for staged abdominal closure); while other
patients have multiple procedures by different services, all related to their initial surgery (i.e. decompressive
craniotomy or spinal stabilization; ocular repair for globe rupture; fasciotomy; fracture fixation;
tracheostomy/percutaneous gastrostomy tube; skin grafts). Acute and chronic pain management expertise, including
provision of regional anesthesia, has unique and clearly beneficial effects for patients following trauma. Many other
trauma patients are readmitted after their initial injury for further procedures when swelling has decreased in the
surgical field (i.e. pilon fracture repair or facial fracture repair). Anesthesiologists care for these trauma patients at
every stage of their resuscitation and recovery, and occasionally, care for patients who meet criteria for death by
neurological criteria during organ procurement.
Background
In 1976, orthopedic surgeon Dr. James Styner and his family crashed in their plane in rural Nebraska. His wife was
killed instantly, three of their children sustained critical injuries, and he sustained serious injuries. The medical care
that he and his family subsequently received was inadequate by the days standards. Recognizing how inadequate
their the treatment was, Dr. Styner stated : When I can provide better care in the field with limited resources than
what my children and I received at the primary care facility, there is something wrong with the system and the
systems has to be changed. This identified need for training in advanced trauma life support led to the creation of
ATLS: a new approach to the provision of care for individuals who suffer major, life-threatening injury. The first
course was introduced in 1978.
As opposed to traditional teaching of the approach to illness that we were taught in medical school (extensive
history, complete physical exam, differential diagnosis and confirmatory tests), ATLS espouses three underlying
concepts:
Treat the greatest threat to life first
The lack of a definitive diagnosis should never impede the application of an indicated treatment
A detailed history is not essential to begin the evaluation of a patient with acute injuries.
321
Page 2
These concepts were difficult for clinicians to accept with the introduction of the course; the result was the
development of the ABCDE approach to the evaluation and treatment of injured patients. The mnemonic defines the
specific, ordered evaluations ad interventions that should be followed in all injured patients:
Airway with cervical spine protection
Breathing
Circulation with hemorrhage control
Disability or neurologic status
Exposure (undress) and Environment (temperature control)
ATLS incorporates didactic teaching with skills stations in an intensive two-day course. The content includes: initial
assessment and management, airway and ventilatory management, shock, thoracic trauma, abdominal and pelvic
trauma, head trauma, spinal cord trauma, musculoskeletal trauma, thermal injuries, pediatric trauma, geriatric
trauma, trauma in pregnancy and intimate partner violence, and transfer to definitive care.
ATLS Ninth Edition Content Update
New to the most recent edition (2012) of ATLS are:
Concept of balanced resuscitation
Emphasis on the pelvis as a source of blood loss
Use of more advanced airway techniques for the difficult airway
Optional DPL and pericardiocentesis
New FAST skills station
Optional expanded content on heat injury
New initial assessment scenarios
New Skills videos and ATLS App
ATLS 9th Edition Compendium of Changes
Chapter Subject 8th Edition 9th Edition
Initial Assessment Team training New information In many centers, trauma
patients are assessed by a
team, the size and
composition of which
varies from institution to
institution. In order to
perform effectively, one
team member should
assume the role of team
leader. The team leader
supervises the preparation
for the patients arrival,
the assessment, treatment
and transfer of the patient.
Airway Cuffed pediatric tubes Previous concerns about
cuffed endotracheal tubes
causing tracheal necrosis
are no longer relevant due
to improvements in the
design of the cuffs.
Ideally, cuff pressure
should be measured as
soon as it is feasible and,
30mm Hg is considered
safe.

321
Page 3
Use of video laryngoscopy

Alternative intubation
devices have been
developed over the years
with the integration of
video and optic imaging
techniques. Their use in
trauma patients may be
beneficial in specific cases
by experienced providers.
Careful assessment of the
situation, equipment, and
personnel available is
mandatory, and rescue
plans must be available.
Shock

Crystalloid

Warmed isotonic
electrolyte solutions (e.g.
lactate ringers (RL) or
normal saline), are used
for initial resuscitation.
This type of fluid provides
transient intravascular
expansion and further
stabilizes the vascular
volume by replacing
accompanying fluid losses
into the interstitial and
intracellular spaces. An
alternative initial fluid is
hypertonic saline although
current literature does not
demonstrate any survival
advantage.
Hypertonic saline has no
benefit over standard
crystalloid resuscitation.

Fluid Resuscitation

The goal of resuscitation is
to restore organ perfusion.
This is accomplished by
the use of resuscitation
fluids to replace lost
intravascular volume, and
has been guided by the
goal of restoring a normal
blood pressure. It has been
emphasized that if blood
pressure is raised rapidly
before the hemorrhage has
been definitely controlled,
increased bleeding may
occur. This may be seen in
the small subset of patients
in the transient or non-
responder categories.
Persistent infusion of large
volumes of fluids in an
attempt to achieve a
normal blood pressure is
not a substitute for
definitive control of
The concept of balanced
resuscitation is further
emphasized, and the term
aggressive resuscitation
has been eliminated. The
standard use of 2 liters of
crystalloid resuscitation as
the starting point for all
resuscitation has been
modified to initiation of 1
liter of crystalloid.
Early use of blood and
blood products for patients
in shock is also
emphasized, without
mandating or suggesting
any specific ratio of
plasma and platelets.

321
Page 4
bleeding.
Fluid resuscitation and
avoidance of hypotension
are important principles in
the initial management of
blunt trauma patients
particularly with TBI. In
penetrating trauma with
hemorrhage, delaying
aggressive fluid
resuscitation until
definitive control may
prevent additional
bleeding. While
complications associated
with resuscitation injury
are undesirable, the
alternative of
exsanguination is even less
so. A careful balanced
approach with frequent
reevaluation is required.
Balancing the goal of
organ perfusion with the
risks of rebleeding by
accepting a lower than
normal blood pressure has
been called Controlled
resuscitation, Balanced
Resuscitation,
Hypotensive
Resuscitation and
Permissive Hypotension.
The goal is the balance,
not the hypotension. Such
a resuscitation strategy
may be a bridge to but is
also not a substitute for
definitive surgical control
of bleeding.
Abdomen & Pelvis

Reemphasized title
Abdomen and Pelvis to
delineate pelvis as under-
recognized source of
hemorrhagic shock.
Musculoskeletal &
Extremity Trauma

All pelvic content moved
to Abdomen and Pelvis
chapter
Trauma in Women

Retitled Trauma in
Pregnancy and Intimate
Partner Violence
Pediatric Trauma

Cuffed endotracheal tubes

Uncuffed tubes of
appropriate size should be
used to avoid subglottic
edema, ulceration, and
disruption of the infants
Previous concerns about
cuffed endotracheal tubes
causing tracheal necrosis
are no longer relevant due
to improvements in the
321
Page 5
or childs fragile airway. design of the cuffs.
Ideally, cuff pressure
should be measured as
soon as it is feasible and,
30mm Hg is considered
safe.
Skill stations Subject
DPL
FAST
Pelvic binder
Pericardiocentesis
8th edition
Mandatory
Musculoskeletal
Mandatory
9th edition
Optional
New content*
Moved to surgical skills to
emphasize source of
hemorrhagic shock
Optional
ATLS app New to 9th edition.
Contains interactive
algorithms, calculators,
animations, Just in Time
videos demonstrating key
skills, and an interactive
PDF version of the
Student Manual.
*Either DPL or FAST must be taught during the surgical skill station as a method of evaluating
the abdomen as a source of hemorrhagic shock*
The purpose of this ASA Refresher Course Lecture is to:
1. Review the content changes in the most recent edition of ATLS,
2. Highlight the role of the anesthesiologist in treating traumatic injury, and
3. Emphasize the goals of care and appropriate interventions for the most critically injured patients.
The content review will be based upon American College of Surgeons Committee on Trauma official
recommendations and guidelines. However, the speaker will also attempt to focus the presentation from an
anesthesiologists point of view, and to emphasize the truly emergent from the urgent needs for operative
intervention.
322
Page 1
Arterial Blood-Gas Analysis
Interpretation and Use of Arterial Blood-Gas Data
Steven J. Barker, Ph.D., M.D. Tucson, Arizona
Introduction The interpretation and application of arterial blood-gas (ABG) data is a task that anesthesiologists
must often perform under difficult circumstances. The time is 3:00 AM; we are fatigued and distracted by multiple
other simultaneous tasks; we need to take action on these ABG results now. In this setting, which bears similarities
to piloting an aircraft on instruments in bad weather, it is useful to have a simple algorithm or check-list, both to
ensure consistency and obtain a correct answer within a short time. The purpose of this talk is to develop such an
algorithm and apply it to specific clinical examples, wherein we shall interpret both oxygenation and acid-base
status, and then prescribe appropriate treatment.
Case Example At 3:00 AM, you are presented with an 80 year-old, 60 kg man who has been found unconscious on
the floor at home. He is brought to the operating room for emergency laparotomy, with a presumed diagnosis of
ruptured appendix. His vital signs are: BP = 90/60, HR = 120, RR = 26, SpO
2
= 96%. A pre-operative ABG reveals:
pH = 7.20, PaCO2 = 25, PaO2 = 75, HCO3
-
= 8. Give sodium bicarbonate? How much? What else do you change?
Oxygenation The first step in evaluating the arterial oxygen tension (P
a
O
2
) is to calculate the alveolar oxygen
tension, using the alveolar gas equation:
P
A
O
2
= F
I
O
2
(P
B
P
H2O
) (1/RQ)P
a
CO
2
.
[1] For a normothermic (37
o
C) patient,
breathing room air at sea level:
P
A
O
2
= 0.21(760 47) (1.25)40
= 99.73 mmHg .
Thus, the alveolar PO
2
at sea level is roughly 100 mmHg. Next, we calculate the RATIO of arterial to alveolar
oxygen tension: P
a
O
2
/ P
A
O
2
. Do NOT bother with the alveolar-arterial difference, sometimes erroneously referred to
as the gradient. The normal value of this difference is a function of the F
I
O
2
, whereas the normal or healthy value
of the ratio is roughly 0.85 at any F
I
O
2
. Thus a healthy P
a
O
2
during normocarbia at sea level is:
P
a
O
2
~ 0.85 x P
A
O
2
= 85 mmHg.
Now, just for fun, lets go to the top of Mt. Everest, elevation 29,035 ft, barometric pressure P
B
= 247 mmHg. Here
is how some humans have actually made it to the summit without supplemental oxygen:
P
A
O
2
= F
I
O
2
(P
B
P
H2O
) (1/RQ)P
a
CO
2
= 0.21(247 47) (1.25)7.5
= 32.6 mmHg
Yes, your P
a
CO
2
on top of Everest is 7.5 mmHg. Now thats hyperventilation!
Furthermore, your predicted P
a
O
2
, using the arterial/alveolar ratio of 85%, will be
0.85 x 32.6 = 27.7 mmHg. In laboratory simulations of Everest conditions, this is almost exactly the resulting P
a
O
2
value. If you are wondering why the P
a
CO
2
is so low, try repeating this calculation for normocarbia.

322
Page 2
The treatment of hypoxemia is beyond the scope of this lecture, but in general the tools available in the operating
room fall into three categories.
1. Ventilator adjustment: F
I
O
2
, PEEP, vent mode (reverse I/E, pressure, HFV, etc.).
2. Drugs: Diuretics, bronchodilators, PDE-5 inhibitors (Cialis is now used for HAPE).
3. Procedures: Chest tube, bronchoscopy, etc.

Acid-Base Balance At a concentration of 0.00004 mEq/L, hydrogen ion is one of the least plentiful electrolytes in
the extracellular fluid (ECF). Nevertheless, because of its small size and high charge state, H
+
is highly reactive and
must be regulated within narrow limits, or we die. The hydrogen ion concentration, denoted [H
+
], varies between
0.1 Eq/L (gastric) and 0.000000008 Eq/L (duodenal) within the body. We commonly use a logarithmic scale to
measure it: pH = -log[H
+
]. The rather wide concentration range above is thus converted to a pH range between 1.0
and 8.1. An H
+
concentration in the ECF that is either too high (low pH, acidemia) or too low (high pH, alkalemia)
will cause a variety of potentially fatal cardiovascular disturbances. These include decreased myocardial
contractility, vasomotor instability, cardiac dysrythmias, and decreased enzyme function. The body uses several
defenses against pH changes, but to understand these we must first review some basics of acid-base chemistry.
Acids, Bases, Buffers Simply put, and acid is a chemical compound that can give up a free H
+
ion in aqueous
solution; a base is a compound that can accept one. This equilibrium is represented as:
HA ! H
+
+ A
-
, [2]
where HA is and acid, and A
-
is called the conjugate base. A strong acid is one that shifts this equilibrium to the
right, producing large amounts of H
+
. A weak acid shifts the balance to the left, producing less free H
+
. Similar
definitions apply for strong and weak bases. If an acid is strong, then its conjugate base is by definition weak, and
vice versa. Since excess hydrogen ion (acidemia) is bad for our health, we would generally prefer weak acids to
stronger ones. More on this concept later.

The strength of the acid HA can be quantified by the ratio of concentrations of the two sides of equation 2: K =
[H+][A
-
]/[HA] [3]
In this and the following equations, square brackets denote concentrations. K is called the dissociation constant
and equation 3 is referred to as the law of mass action. A large value of K implies a strong acid and weak
conjugate base. Taking the logarithms of both sides of equation 3 and rearranging, we find:
log K = log [H
+
] + log ([A
-
]/[HA])
-log [H
+
] = -log K + log ([A
-
]/[HA])
pH = pK + log ([A
-
]/[HA]) [4]
In this last step we have inserted the definitions pH = -log [H
+
] and pK = -log K, yielding the familiar Henderson-
Hasselbach Equation. This equation is simply a logarithmic form of the law of mass action, or definition of the
dissociation constant.

The most important acid-base equilibrium in the body is that of carbon dioxide and water:
H
2
O + CO
2
! H
2
CO
3
! H
+
+ HCO
3
-
[5]
The pK of this reaction is 6.1, making carbonic acid a rather weak acid. Henderson-Hasselbach (Eq. 4) for this
reaction becomes:
pH = pK + log {[HCO
3
-
]/[H
2
CO
3
]}
pH = 6.1 + log {[HCO
3
-
]/(0.03 P
a
CO
2
)} ` [6]
We dont routinely measure blood carbonic acid concentration, so in the last step we have substituted the empirical
formula: [H
2
CO
3
] = 0.03 P
a
CO
2
. Equation 6 states a simple and important fact about acid-base physiology: the pH is
determined by the RATIO of the bicarbonate concentration to the P
a
CO
2
. We shall see that this is a key feature of the
bodys defenses against pH changes. Inserting normal blood values into Eq. 6:
pH = 6.1 + log {24/(0.03 X 40)} = 7.4 .
It is always reassuring when a new formula gives the correct answer in a known situation.

Body acids, buffers, and defenses Acids are formed in two ways in the human body. Respiratory acid is formed by
the combination of carbon dioxide (product of aerobic metabolism) and water, as shown in Eq. 5. All other acids are
called metabolic acid. The latter include lactic acid produced by anaerobic metabolism, as well as sulphuric,
hydrochloric, and phosphoric acids. We have already noted that carbonic or respiratory acid is a weak acid. In fact,
in the normal ECF equilibrium (Eq. 5) it takes 800,000 molecules of CO
2
to produce 800 molecules of H
2
CO
3
,

322
Page 3
which in turn produce ONE free H
+
ion. This brings us to the bodys first line of defense against acid invasion: a
system of buffers. A buffer is something that effectively exchanges a strong acid for a weaker one, as in the
following.

H
+
+ Cl
-
+ NaHCO
3
! H
2
CO
3
+ NaCl [7]

As this reaction moves to the right, the sodium bicarbonate trades the very strong hydrochloric acid (HCl) for the
very weak carbonic acid (H
2
CO
3
). A buffer solution thus consists of a weak acid (H
2
CO
3
) and a salt of the
conjugate base (NaHCO
3
), and it uses this combination to trade strong acid for weak acid, thereby reducing the
amount of free H
+
released. Bicarbonate, the example we have just considered, is the most important buffer in the
body. Other buffers include proteins, phosphate, and ammonia. Proteins are significant for two reasons: (1) they
are very plentiful in the intracellular milieu (75% of total body buffering power), and (2) they can buffer both
metabolic and respiratory acid, as shown below for the protein hemoglobin (Hb).
[8a
] HCl + KHb ! HHb + KCl

[8b
] H
2
CO
3
+ KHb ! HHb + KHCO
3

There are two other front-line defenses against pH changes: respiratory and renal control. The lungs, driven by
medullary chemoreceptors, regulate the P
a
CO
2
level. The kidneys, by actively excreting H
+
into the urine and
reclaiming Na
+
from the urine, effectively pump bicarbonate from the urine back into the blood. The kidneys
excrete a normal daily metabolic acid load of 50 mM at a urine pH of 6.0, and healthy kidneys can handle as much
as ten times that amount by reducing the urine pH to 4.5. Looking again at equation 6, the lungs control the
denominator and the kidneys the numerator of the ratio that determines pH.

Evaluation of acid-base balance Given the above background on acids, bases, buffers, and the bodys pH controls,
we are now ready to evaluate and treat the acid-base balance. The first step in this process is a plot of the plasma pH
versus bicarbonate, called the Davenport Diagram, shown in Figure 1.

Figure 1. The pH Bicarbonate Diagram.

322
Page 4
Choosing a location on this graph fixes the values of pH and HCO
3
-
, and Eq. 6 (Henderson-Hasselbach) then
determines the corresponding value of P
a
CO
2
. The curves labeled 20, 30, 40, etc. are lines of constant P
a
CO
2
, called
isobars. They are solutions of the Henderson-Hasselbach Equation. The normal acid base status of pH = 7.4, HCO
3
-
= 24, P
a
CO
2
= 40 corresponds to the center of the graph. Note the straight line passing through the center with a slight
negative slope, labeled 10sl. This buffer line is the path followed by a purely respiratory disturbance either
hypercarbia or hypocarbia with no metabolic disturbance at all. The slope of the buffer line represents the bodys
chemical buffering power, and its units are called Slykes, named after the chemist Van Slyke. The normal slope is
actually nearer to 12, but a value of 10 is easier for the calculations that follow and is close enough for our purposes.

The two stippled regions along the buffer line, labeled acute, are the areas in which an acute, uncompensated,
respiratory disturbance will lie. Take for example an acute respiratory acidosis, which is the stippled area to the left
of the center of the graph. Referring again to Eq. 6, we see that the bodys compensation for this acute hypercarbia
will be to increase the HCO
3
-
level (the kidneys job) to bring the ratio back towards normal, thus correcting the pH.
This metabolic compensation may take several days to complete, and it will move us from the acute stippled area
upward along the appropriate isobar into the chronic stippled area in the upper-left quadrant. Thus a quick exam of
the pH-bicarbonate diagram not only tells us that our patient has a respiratory acidosis, but also evaluates thmetabolic
compensation. The same reasoning applies to both acute and compensated respiratory alkalosis, shown in the lower
right quadrant of the diagram.

A pure metabolic acidosis, without compensation, would follow the P
a
CO
2
= 40 isobar down into the lower left
quadrant of Figure 1. (Ignore, for now, the arrow in the lower left quadrant. It will be used later.) Metabolic acidosis
manifests as a decrease in HCO
3
-
, so the bodys compensatory response is to decrease the denominator of the ratio in
Eq. 6, that is, to lower the P
a
CO
2
. This compensatory hyperventilation takes us into the stippled area in the lower left
quadrant of Figure 1. Similarly, the respiratory compensation for metabolic alkalosis is hypoventilation, as indicated
by the stippled area of the upper right quadrant. Since hypoventilation will eventually cause hypoxemia, this
compensation is less effective, as we can see by the slopes of the two stippled areas.

Instead of referring the stippled areas of Figure 1, we can also use empirical rules of thumb to predict
compensation. Remember that the bodys response to pH imbalance is to restore the ratio of HCO
3
-
/P
a
CO
2
toward
its normal value of 24/40 = 0.6, because this ratio controls the pH (Eq. 6). The following rules are based on clinical
data, and are only approximate predictors.
1. Metabolic compensation for a primary respiratory disturbance.
a. Respiratory acidosis: For every 10 mmHg rise in P
a
CO
2
above 40:
i. Acute: HCO
3
-
increases by 1 mEq/L.
ii. Chronic (compensated): HCO
3
-
increases by 4 mEq/L.
b. Respiratory alkalosis: For every 10 mmHg fall in P
a
CO
2
below 40:
i. Acute: HCO
3
-
decreases by 2 mEq/L.
ii. Chronic (compensated): HCO
3
-
decreases by 3 mEq/L.
2. Respiratory compensation for a primary metabolic disturbance.
a. Metabolic acidosis with maximum compensation: P
a
CO
2
=
1.5[HCO
3
-
] + 8.
b. Metabolic alkalosis with maximum compensation: P
a
CO
2
=
0.7[HCO
3
-
] + 20.

One additional tool is required to quantify the metabolic disturbance: base excess or BE. The definition of BE is
as follows. Titrate the pH to 7.40 by varying only P
a
CO
2
. BE is the difference between the resulting HCO
3
-
at the
end of this titration and the normal value of 24 mEq/L. It is easier to understand this definition by using an example
on the pH-bicarbonate diagram, Figure 1. We are given the following arterial blood-gas results: pH = 7.1, P
a
CO
2
=
32, HCO
3
-
= 10, as indicated by the tail of the arrow in the lower left quadrant. To find BE, we titrate back to a pH
of 7.4 by varying only P
a
CO
2
. This titration follows a line parallel to our buffer line, shown by the arrow shaft.
Since the slope of this line is -10 Slyke, and the pH changes by 0.3 units (from 7.1 to 7.4), the bicarbonate will
decrease by 3 mEq/L (0.3 times 10), reaching a new value of 7 (10 minus 3) at the head of the arrow. The BE is thus
7 24, or -14. A negative base excess is also called a base deficit, so our blood-gas analysis shows a base deficit
of 14. You can now calculate BE in your head if you know the pH and the bicarbonate. Should we treat this base

322
Page 5
deficit, and if so, how? This is our next topic.

There are many possible causes of metabolic acidosis, but in the operating room it is most often the result of
inadequate oxygen delivery to various organs and tissues. It is the direct result of anaerobic metabolism, and
therefore manifests as a lactic acidosis. The anion gap, defined as [Na
+
] + [K
+
] [Cl
-
] [HCO
3
-
], is above the
normal range of 8-12. Like most physiological disorders, the ideal prescription is to treat the underlying cause. If
the cause of the lactic acidosis is tissue hypoperfusion resulting from hypovolemic shock, then correcting the patients
volume status may be all that is needed to restore perfusion and rapidly correct the acidemia. On the other hand, a
very low pH (7.1 would fall in that category) will depress cardiac function significantly, and the heart may not be able
to generate sufficient cardiac output to restore organ perfusion while the pH remains so low. This is a judgment call
that we must make on a case-by-case basis. If we decide that the pH must be at least partially corrected before the
heart can do its job, here is how we treat it.

Treatment of acid-base disorders The first step in treating a metabolic acidosis is to determine the bicarbonate
deficit. That is, how much bicarbonate would be required to restore the extracellular fluid to its normal value of 24
mEq/L? This quantity is simply the base deficit times the weight in kg, times the ECF fraction. The ECF comprises
the following fraction of body weight:

ECF fraction = 0.5 (premature neonate)
0.4 (term neonate)
0.3 (2 year-old)
0.25 (older child)
0.2 (adult)

Thus, if the patient above with a BE of -14 is a 70 kg adult, the bicarbonate deficit will be 14 X 70 X 0.2, or 196
mEq.

Treatment of metabolic acidosis with sodium bicarbonate (NaHCO
3
) is not a risk-free therapy. First, bicarb does
not make metabolic acid disappear; it effectively converts it to respiratory acid (see Eq. 7). The additional CO
2
created by this exchange must be removed by increased ventilation. Furthermore, full strength sodium bicarbonate
is a hyperosmolar solution (six times plasma osmolarity) and can thereby cause brain hemorrhage, particularly in
children. Overtreatment can cause alkalemia, which is just as dangerous as acidemia. Therefore, the common
recommendation is to give about half the amount of the total bicarbonate deficit, increase ventilation to compensate
for the additional CO
2
, and reevaluate in roughly 30 minutes. There are two approved alternatives to sodium
bicarbonate: tris-hydroxy amino-methane (THAM) and carbi-carb, which is an equimolar mixture of sodium
bicarbonate and sodium carbonate (Na
2
CO
3
). Both can buffer metabolic acid with little or no increase in CO
2
, but
neither has been shown to have any outcomes advantage over conventional treatment.

Evaluation/Treatment Algorithm We conclude by encapsulating the above approach to acid-base evaluation into a
simple four-step algorithm, which we shall apply to our original case example.

Four Step Evaluation of Acid-Base Status:
1. Evaluate the pH: if pH > 7.45, patient has alkalemia; if pH < 7.35, patient has acidemia.
2. Evaluate the P
a
CO
2
: if P
a
CO
2
> 45, patient has respiratory acidosis; if P
a
CO
2
< 35, patient has respiratory
alkalosis.
3. Find the base excess (BE), using the 10 Slyke approximation: if BE > +2, patient has metabolic alkalosis; if
BE < -2, patient has metabolic acidosis.
4. Evaluate compensation: determine predicted maximum compensation by non-primary variable, using
empirical rules or referring to stippled areas of Figure 1.

322
Page 6
Finally, let us use this algorithm to evaluate and treat our original patient, a 60 kg man with a blood gas analysis
showing 7.20/25/75/8 (pH/ P
a
CO
2
/P
a
O
2
/HCO
3
-
).
1. The patient is acidemic (pH = 7.20).
2. The patient has respiratory alkalosis (PaCO
2
= 25).
3. Calculate BE (see Figure 1): titration to pH = 7.4 requires pH to change by 7.4 7.2 = 0.2; HCO
3
-
therefore
decreases by 0.2 X 10 = 2; new HCO
3
-
= 8 2 = 6; BE = 6 24 = -18.
4. Evaluate compensation: Maximum predicted respiratory compensation for this metabolic acidosis is P
a
CO
2
=
1.5[HCO
3
-
] + 8 = (1.5 X 8) +8 = 20 mmHg. The patients actual P
a
CO
2
is 25 mmHg. Given his physical
status, this patient is nearly at maximum compensation.

Treatment: The amount of bicarbonate required to fully correct the patients BE of -18 is:
NaHCO
3
= 60 kg X 0.2 X 18 mEq/L = 216 mEq.

A reasonable therapy is to give half this amount, or two ampoules (55 mEq per ampoule), increase mechanical
ventilation, and obtain another ABG measurement in 15-30 minutes.

Conclusions Interpretation of arterial blood-gas data is straightforward, if we follow a prescribed algorithm such as
the one presented in this lecture. The simplest interpretation of P
a
O
2
comes from calculating the ratio of arterial to
alveolar oxygen tension (using the alveolar gas equation) and comparing the result with the normal value of 0.85.
To evaluate the acid-base status, simply follow the four step algorithm we have described, which separates
respiratory from metabolic disturbance and evaluates compensation. The pH-bicarbonate diagram (Figure 1) is an
excellent tool for keeping all of these factors in perspective, and understanding the results of treatment. Finally, if
the patient has a severe metabolic acidosis that may require treatment, calculate the bicarbonate deficit as shown
above. I do not recommend an arbitrary BE threshold for treatment with sodium bicarbonate; that decision should
take into account all aspects of the patients clinical status. However, once the decision to treat has been made, it is
usually wise to give about half of the bicarbonate deficit as the initial dose, increase or monitor ventilation, and then
reevaluate the acid-base status a short time later. Of course there are exceptions to every rule that is why you
spent all those years in training. But these guidelines should serve you well as a starting point, and they are simple
enough that even I can follow them at 3:00 AM.

REFERENCES

1. Guyton A, Hall J, Textbook of Medical Physiology, 11
th
Edition, Saunders, New York, 2005.
2. Nunn J, Applied Respiratory Physiology, 6
th
Edition; Butterworth-Heinemann, London, 2005.
3. Severinghaus JW, Astrup PB: History of blood gas analysis II. pH and acid-base balance measurements. J Clin
Mon. 1985; 1(4):259-77.
4. Stewart, PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61:1444-1461.
5. Adrogu HJ, Madias NE: Management of life-threatening acid-base disorders. N Engl J Med, 1998; 338:2634,
107111.
6. Stewart PA: Stewarts Textbook of Acid-Base, AcidBase.org, 2009.
7. Tremper KK, Barker SJ Blood Gas Analysis, in Principles of Critical Care, Hall JB, Schmidt GA, Wood LD
(ed.); McGraw-Hill, New York, 1992.

Disclosure
Masimo, Inc., Equity Position, Stock

328
Page 1
Anesthesia for Urological Surgery
Jerome F. OHara Jr., M.D. Cleveland, Ohio
Objectives:
1) Quantify degree of chronic kidney disease as it correlates with changes in laboratory values
2) Discuss anesthetic management in renal transplantation for donor and recipient
3) Differentiate how new surgical TURP techniques impact anesthetic management and patient outcomes
I. The effect of chronic renal failure on clinical laboratory values
Introduction
The incidence of patients who develop chronic kidney disease (CKD) and develop end stage renal disease (ESRD) is
rising. Upwards of 26 million Americans have CKD [1]. These patients are at a higher risk of associated morbidity
and mortality as their glomerular filtration rate (GFR) declines over time [2,3] What is not so evident is when
clinical laboratory values begin to change as a patient progresses through the different stages of CKD to the point of
ESRD and the need for dialysis therapy to sustain physiologic function to survive. Table 1 lists the stages of CKD as
signalled by alterations in GFR [4]. Identifying when alterations occur in clinical laboratory values for a patient can
provide clinical insight to the degree of CKD a patient may have. This knowledge could influence drug
pharmacokinetics as well as the anesthetic care given; it could also aid in determining the risk of further acute
kidney injury and the nature of postoperative recovery.
In a review of 1,038 patients with CKD in stages 2 through 5, Moranne and associates reported that as measured
GFR decreased from 60 to 90 to <20 ml/min per 1.73 m
2
, the prevalence of hyperparathyroidism increased from
17% to 85%, anemia from 8% to 41%, hyperphosphatemia from 1% to 30%, metabolic acidosis from 2% to 39%,
and hyperkalemia from 2% to 42%. Factors most associated with these metabolic complications included younger
age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and
the use of inhibitors of the renin-angiotensin system for hyperkalemia [2]. Figure 1 displays the incidence of
physiologic derangement by a value as compared to mGFR. Of clinical importance is the finding that at an mGFR
threshold of approximately 40 ml/min per 1.73 m
2
, > 60% of patients would have significant metabolic acidosis and
be hyperkalemic.
! Table 1: Stages of CKD: GFR (ml/min/1.73 m2)
!
! 1 Normal: GFR >90
! 2 Minimal Impairment: GFR 60-89
! 3 Moderate impairment: GFR 30-59
! 4 Severe impairment GFR: 15-29
! 5 Establish ESRD: GFR<15 or need for dialysis

328
Page 2

Figure 1

Prevalence of metabolic complications according to GFR. Hyperparathyroidism was defined as PTH >60
pg/ml or active vitamin D treatment; anemia was defined as Hb <110 g/L according to K/DOQI-based
criteria or erythropoiesis-stimulating agent treatment; acidosis was defined as a tCO
2
<22 mmol/L or
bicarbonate treatment; hyperkalemia was defined as a plasma potassium concentration >5 mmol/L or ion
exchange resin treatment; hyperphosphatemia was defined as a plasma phosphate concentration >4.3 mg/dl
(>1.38 mmol/L) or phosphate binder treatment. mGFR, measured glomerular filtration rate; eGFRcl,
estimated glomerular filtration rate, using the MDRD Study equation with serum creatinine values calibrated
by the Cleveland Clinic Laboratory; eGFRms, eGFR using the MDRD equation with serum creatinine
values standardized to mass spectrometry.

328
Page 3
[This Figure, with its legend, originally appeared in "Timing of onset of CRD-related metabolic
complications" by Olivier Moranne, et al. in the Journal of the American Society of Nephrology, 2009;
20(1), January, pages 164-171. Used by permission of the American Society of Nephrology]

1. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of
chronic kidney disease in the United States. JAMA 2007; 298(17):2038-47.

2. Moranne O, Froissart M, Rossert J, Gauci C, Boffa JJ, Haymann JP, Mrad MB, Jacquot C, Houillier P,
Stengel B, Fouqueray B; Nephro Test Study Group. Timing of onset of CKD-related metabolic
complications. JASN 2009; 20(1): 164-71. doi: 10.1681/ASN.2008020159. Epub 2008 Nov

3. Arulkumaran N, Annear NM, Singer M. Patients with end-stage renal disease admitted to the intensive care
unit: systematic review. BJA 2013; 110(1):13-20. doi: 10.1093/bja/aes401. Epub 2012 Nov 20.

4. 2002 National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI).

II. Anesthetic Management in Renal Transplantation

Introduction

In the U.S. approximately 96,000 ESRD patients are listed for a renal transplant. The mean wait time for a
deceased donor transplant is approximately 3.5 years. The current trend, as reported in 2012, reveals that more
deceased-donor (7,420) than living-donor (5,623) renal transplants are performed in the U.S. [1]. Renal
transplantation remains the preferred treatment for patients with ESRD, and it is more cost-effective than long-term
dialysis [2]. However, there remains a persistent shortage of organs for transplantation.
The outcome in renal transplantation depends upon three perioperative factors: donordeceased or living;
allograft ischemia timewarm or cold; and recipient management.
Anesthesiologists are directly involved in management of the kidney donor patient during allograft
harvesting. In accordance with the standard criteria governing deceased donors, the anesthesiologist manages
physiologic functions to maintain end-organ perfusion for all harvested organs. In living-donor kidney
transplantation the anesthesiologist is responsible for perioperative care of the donor, who is undergoing a surgical
procedure to benefit someone else. Anesthetic care in donation after cardiac death begins after the primary medical
team declares the donor dead, after allograft harvesting has been completed, and when the recipient presents for
transplantation. Paired donation renal transplants involve matching two incompatible living pairs in order to conduct
transplantation involving two living kidney donors. The anesthesia team plays a critical role in coordinating the
initiation of these procedures, especially if each renal transplant is to be performed at separate hospitals.
The surgical team is responsible for monitoring warm ischemia time of the allograft during harvesting and
again at re-implantation. The preservation team is responsible for cold preservation of the allograft.
The anesthesiologist cares for the recipient during allograft re-implantation. The important therapeutic
efforts by anesthesiologists to preserve renal function during allograft harvesting and during reperfusion of the
transplanted kidney are influenced by anesthetic techniques. Factors affecting the outcome for renal preservation
include anesthetic choices, fluid management, and renal preservation therapies.

Donor Management
Deceased donor management centers on the maintenance of adequate intravascular volume and blood
pressure in the operating room prior to organ harvesting. Retrospective data from renal transplant registries show
that the administration of vasopressors (dopamine, dobutamine, isoproterenol) results in a lower incidence of acute
rejection as well as in improved graft survival after transplantation [3]. Although these data do not directly confirm
a benefit in renal preservation, they do nevertheless suggest that these therapies provide adequate cardiac output for
maintaining renal perfusion. Mannitol, dopamine, and diuretics have been characterized as preventing tubular
obstruction by maintaining adequate urine output in the event of acute tubular necrosis. However, clinical evidence
shows that the only diuretic conferring a renal preservation benefit is mannitol [4].

328
Page 4
The management of living donor kidney transplantation usually involves preparation of a general anesthetic
for laparoscopic kidney harvesting. Primary anesthetic goals center upon maintaining adequate renal perfusion,
which is accomplished by inducing a moderate hypervolemic state and administering mannitol before allograft
ischemia as a renal preservation therapy.

Recipient Management
Anesthetic management of the recipient entails optimizing therapy for a patient with comorbidities,
coordinating dialysis, and understanding the pharmacokinetic and pharmacodynamic effects of drugs administered
to patients with ESRD. In deceased donor transplantation, prolonged cold ischemia time becomes urgent for the
allograft; however, urgency should not preclude efficient steps being taken to optimally prepare a recipient for renal
transplant surgery. Although regional anesthesia has been designated for renal transplantation, general anesthesia
remains the predominant choice [5]. Placements of intra-arterial catheters are common and central venous catheters
are routine for intraoperative management.

Renal Preservation Management
Favorable outcomes in postrenal transplantation depend upon optimizing cardiac output while re-
establishing renal allograft perfusion. These steps are more important than the use of any of the multiple renal
preservation therapies previously studied in renal transplantation.
Balanced crystalloid solutions remain the initial volume replacement therapy in renal transplantation.
Potassium-containing solutions should be used cautiously; and saline-based fluids have been associated with acid-
based disturbances because of the high chloride load [4,6]. Both short-term (delayed graft function) and long-term
(graft survival after one year) benefits in renal transplantation have been reported when volume expansion with
human albumin occurred [4]. However, it is debatable whether albumin administration was directly beneficial in
renal preservation or indirectly beneficial by providing adequate intravascular volume. In renal transplantation,
synthetic colloid administration should be used with the understanding that it has the potential to cause renal
dysfunction [4].
Pharmacologic therapies such as diuretics, dopamine agonists, and calcium channel blockers have been
evaluated for renal preservation in allograft function. Mannitol administered (up to 50 gm intravenously) to the
recipient prior to allograft reperfusion demonstrated less immediately delayed graft function, but not a long-term
allograft benefit [7,8,9]. Administration of loop diuretics or dopamine intra-operatively failed to demonstrate an
improvement in allograft outcomes [4]. Perioperative administration of calcium channel blockers to enhance renal
arteriole dilatation decreased the incidence of delayed graft function, but conferred no long-term allograft benefit
[10,11]. The majority of studies undertaken on renal preservation therapy in renal transplantation have been limited
to deceased donors and often studied when other therapies were administered.

1. The Scientific Registry of Transplant Recipients.
http://www.ustransplant.org/

2. Schweitzer EJ, Wiland A, Evans D, Novak M, Connerny I, Norris L, Colonna JO, Philosophe B, Farney AC,
Jarrell BE, Bartlett ST. The shrinking renal replacement therapy "break-even" point. Transplantation
1998;66(12):1702-8.

3. Schnuelle P, Lorenz D, Mueller A, Trede M, Van Der Woude FJ. Donor catecholamine use reduces acute
allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int 1999;56(2):738-
46.

4. Schnuelle P, Johannes van der Woude F. Perioperative fluid management in renal transplantation: a narrative
review of the literature. Transpl Int 2006;19(12):947-59.

5. Akpek E, Kayhan Z, Kaya H, Candan S, Haberal M. Epidural anesthesia for renal transplantation: a preliminary
report. Transplant Proc 1999; 31(8):3149-50.

6. O'Malley CM, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, Bennett-Guerrero E. A
randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation.
Anesth Analg 2005;100(5):1518-24.

328
Page 5
7. Weimar W, Geerlins W, Bijnen AB, Obertop H, van Urk H, Lameijer LD, Wolff ED, Jeekel J. A controlled
study on the effect of mannitol on immediate renal function after cadaver donor kidney transplantation.
Transplantation 1983;35(1):96-100.

8. Tiggeler RG, Berden JH, Hoitsma AJ, Koene RA. Prevention of acute tubular necrosis in cadaveric kidney
transplantation by the combined use of mannitol and moderate hydration. Ann Surg 1985;201(2):246-51.

9. van Valenberg PL, Hoitsma AJ, Tiggeler RG, Berden JH, van Lier HJ, Koene RA. Mannitol as an indispensable
constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric
transplantation. Transplantation 1987;44(6):784-8.

10. Dawidson I, Rooth P, Lu C, Sagalowsky A, Diller K, Palmer B, Peters P, Risser R, Sandor Z, Seney F.
Verapamil improves the outcome after cadaver renal transplantation. JASN 1991;2:983-90.
11. Shilliday IR, Sherif M. Calcium channel blockers for preventing acute tubular necrosis in kidney transplant
recipients. Review. [63 refs] [Update in Cochrane Database Syst Rev. 2007;(4):CD003421; PMID: 17943790].
Update in Cochrane Database Syst Rev. 2004;(1):CD003421; PMID: 14974015]. Cochrane Database of
Systematic Reviews.(2):CD003421, 2005.

III. New Surgical TURP Techniques

Introduction

In males presenting with symptomatic benign prostatic hypertrophy (BPH) the surgeons goal is to resect as much
prostatic tissue as possible while preserving the prostatic capsule. Complications occur when surgical resection of
the rich plexus of prostatic veins is opened. This creates a conduit for bleeding and for absorption of bladder
irrigating fluid when under pressure. As a result, bipolar electrode resection and prostate lasers are replacing
monopolar TURP as alternative surgical techniques for BPH resection.

Monopolar TURP
The conventional gold standard for TURP was the monopolar electrode resectoscope. With the monopolar electrode,
layers of prostatic tissue are resected with a cutting current transmitted through a single-limb electrode which exits
the patient by way of a grounding pad. A non-electrolyte bladder-irrigating solution is required to avoid dispersion
of the electrical current as well as tissue damage at the site of prostatic resection. TURP syndrome is a potentially
serious complication which can occur when a nonelectrolyte, hypo-osmolar bladder-irrigating solution is used. The
severity of the complication depends on the amount of the intravascular bladder-irrigating solution that is absorbed
via prostatic veins opened during resection.

TURP Complications
Complications caused by TURP include dilutional hyponatremia, glycine toxicity, ammonia toxicity, bacteremia,
anemia, hypothermia, bladder perforation, bleeding, and coagulopathy. Factors related to the volume of irrigating
fluid absorption include the duration of resection and the height of the irrigating solution bag above the patient. The
ideal irrigation fluid for monopolar TURP would be isotonic, nonhemolytic, nontoxic, nonelectrolytic,
nonmetabolized, visually non-distorting, rapidly excreted, and inexpensive. However, since there is no ideal
bladder-irrigating fluid for monopolar TURP surgery, 1.5% glycine is used instead, as the standard solution. A
review of the pathophysiology and management of TURP syndrome in monopolar TURP reported that TURP
syndrome may present clinically as early as 15 minutes after resection begins or up to 24 hours postoperatively, with
intravascular rates reaching 200 ml/min of the bladder-irrigating flud [1].

Bipolar TURP
Bipolar TURP electrode technology incorporates a continuous loop electrode to resect prostatic tissue of BPH. This
surgical tool is designed to contain the inflow and outflow of current via the resectoscope for prostatic tissue
resection. By being completely self-contained within the bipolar unit, the current is prevented from passing through
the patient. The advantage of this system is that for the bladder-irrigating solution, an electrolyte-containing

328
Page 6
solution such as normal saline can be used. Although intravascular absorption of normal saline can occur via
resected prostatic veins opened during prostatic resection, hypo-osmolality and hyponatremia associated with TURP
syndrome are prevented. Nevertheless, the risk of volume overload as a consequence of the bladder-irrigating
solution can still occur with the bipolar TURP technique.

In a review of 16 studies conducted over a 10-year period, Issa compared the safety properties of monopolar and
bipolar TURP [2]. He found a statistically significant decrease in overall complication rate, transfusion rate, and
TURP syndrome with bipolar TURP. A randomized outcome study by Chen and colleagues, in which monopolar
and bipolar TURP were compared, found that bipolar TURP was associated with significantly less fluid absorption,
less change in serum sodium and in hemoglobin, and comparable urologic efficacy in prostate symptom scores and
maximum urinary flows [3]. A more recent randomized study also found similar benefits in bipolar TURP with the
exception that irrigating fluid absorption was similar to monopolar when ethanol concentrations were measured [4].
Two meta-analytic studies comparing monopolar and bipolar TURP also reported favorable outcomes in the bipolar
TURP groups [5,6].

Laser TURP
Laser TURP techniques produce a thin coagulation treatment zone (17 mm) during prostatic tissue resection [7].
This prevents excessive bleeding and intravascular absorption of bladder-irrigating fluid. In contrast to monopolar
and bipolar TURP techniques, which open prostatic veins, the thin coagulation treatment zone seals them. As a
result, bleeding and absorption of bladder irrigating fluid are minimized. Laser TURP is accordingly advocated for
use in anti-coagulated patients. Laser TURP can, however, require several hours, depending on the size of the
prostatic gland that is to be resected. Initially, sterile water was used as the bladder-irrigating fluid with laser TURP,
without significant hyponatremia occurring [8].Glycine as the bladder irrigating fluid is also acceptable. Significant
absorption of the bladder-irrigating fluid during laser TURP does not normally occur. At present, normal saline is
generally recommended as the bladder irrigating solution during laser TURP. Of interest is our clinical experience,
which suggests that deactivation of an automatic implantable cardioversion device is not routinely needed during
laser TURP.
In their review of the anesthetic implications of newer laser TURP techniques, Hanson and colleagues [9] found that
there was minimal absorption of bladder-irrigating fluid; that the techniques could be performed on anti-coagulated
patients; and that the techniques carried a lower risk of TURP syndrome. These findings placed less emphasis on
regional as the preferred anesthetic technique. Other studies have suggested that laser TURP is feasible when anti-
coagulation therapy withdrawal was considered a significant patient risk perioperatively [10,11].

Geavlete and colleagues [12] reported in a prospective randomized trial that in contrast to monopolar TURP, laser
TURP demonstrated significantly decreased operative times, a shorter catherization period, shorter hospital stay, and
fewer complications. A meta-analysis comparing laser and monopolar TURP reported less clot retention and
incidence of TURP syndrome, comparable postoperative bleeding and a higher re-operation rate in the first year
postoperatively [6,12]. Overall mortality from TURP has steadily decreased: by 2.5% (in 1962), 1.3% (in 1974),
0.23% (in 1989), and 0.10% (in 2003) [13]. Smith and Patel published a review of the different surgical techniques
for TURP and compared them for safety/complications, advantages/disadvantages, and effectiveness/durability [14].

References

1. Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a review of the pathophysiology and
management. Anesth Analg 1997; 84(2):438-46. Review.

2. Issa MM. Technological advances in transurethral resection of the prostate: bipolar versus monopolar TURP. J
Endourol 2008; 22(8):1587-95.

3. Chen Q, Zhang L, Fan QL, Zhou J, Peng YB, Wang Z. Bipolar transurethral resection in saline vs traditional
monopolar resection of the prostate: results of a randomized trial with a 2-year follow-up. BJU Int 2010;
106(9):1339-43.

4. Fagerstrm T, Nyman CR, Hahn RG. Complications and clinical outcome 18 months after bipolar and
monopolar transurethral resection of the prostate. J Endourol 2011; 25(6):1043-9. Epub 2011 May 13.

328
Page 7
5. Mamoulakis C, Ubbink DT, de la Rosette JJ. Bipolar versus monopolar transurethral resection of the prostate:
a systematic review and meta- analysis of randomized controlled trials. Eur Urol 2009; 56(5):798-809.

6. Burke N. Whelan JP, Goeree L, Hopkins RB, Campbell K, Goeree R, Tarride JE. Systematic review and meta-
analysis of transurethral resection of the prostate versus minimally invasive procedures for the treatment of
benign prostatic obstruction. Urology 2010; 75(5):1015-22. Review.

7. Wosnitzer MS, Rutman MP. KTP/LBO laser vaporization of the prostate. Urol Clin North Am. 2009; 36(4):471-
83.

8. Malek RS, Kuntzman RS, Barrett DM. High power potassium-titanyl-phosphate laser vaporization
prostatectomy. J Urol 2000; 163(6):1730-3.

9. Hanson RA, Zornow MH, Conlin MJ, Brambrink AM. Laser resection of the prostate: implications for
anesthesia. Anesth Analg 2007; 105(2):475-9.

10. Karatas OF, Alkan E, Horasanli K, Luleci H, Sarica K. Photoselective vaporization of the prostate in men with a
history of chronic oral anti-coagulation. Int Braz J Urol 2010; 36(2):190-7.

11. Woo H, Reich O, Bachmann A, Choi B, Collins E, de la Rosete J, et al. Outcome of greenlight HPS 120-W laser
therapy in specific patient populations: those in retention, on anticoagulants and with large prostates (> 80mL).
Eur Urol Suppl 2008; 7: 378-83.

12. Geavlete B, Multescu R, Dragutescu M, Jecu M, Georgescu D, Deavelete P. Transurethral resection (TUR) in
saline plasma vaporization of the prostate vs standard TUR of the prostate: the better choice in benign prostatic
hyperplasia? BJU Int 2010; 106(11):1695-9.

13. Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, Lack N, Stief CG. Morbidity, mortality
and early outcome of transurethral resection of the prostate: a prospective multicenter evaluation of 10,654
patients. Urology Section of the Bavarian Working Group for Quality Assurance. J Urol 2008; 180(1):246-9.

14. Smith RD, Patel A. Transurethral resection of the prostate revisited andupdated. Curr Opin Urol 2011;21(1):36-
41.

IV. Conclusions

Although there is considerable variability in changes in clinical laboratory values in CKD patients, these
values are maintained to near normal levels until GFR is < 40 ml/min per 1.73 m
2
. It is at this point the clinician
would expect 40% of these CKD patients to demonstrate laboratory values consistent with metabolic acidosis and
hyperkalemia. The anesthesiologist plays a critical role in the management of donor and recipient in renal
transplantation. Renal transplant outcomes depend upon the selection of renal preservation strategies, the most
important of which is to maintain adequate cardiac output during allograft reperfusion. The outcome in renal
transplantation depends upon three perioperative factors: donor; allograft ischemia timewarm or cold; and
recipient management. Newer surgical techniques such as bipolar and laser TURP have been developed to minimize
the incidence of TURP syndrome. Laser TURP has been described as a preferred technique in anti-coagulated
patients. These newer techniques are replacing monopolar TURP.

Disclosure

334
Page 1
Physics in Anesthesiology
Jeffrey B. Gross, M.D. Farmington, Connecticut
Why Physics?
a) Understand how our equipment is SUPPOSED to work
b) Understand what might happen if things go WRONG
c) Function as a CONSULTANT in the medical specialty of Anesthesiology
d) Do well on Content Outline Section 1B of the In-Training and Part I American Board of
Anesthesiology Examinations
Pressure
a) Pressure= Force per unit of area
b) Units
Pounds / in
2
(PSI)
- Atmospheric Pressure PATM=14.7 PSI)
Pascals (nt / m
2
) (PATM~100 KPa)
mmHg (7.5 mmHg = 1 KPa)
cmH
2
O (1 mmHg = 1.36 cmH
2
O)
c) Implications
Even a small pressure exerts a large force if area is large
A small force can exert a lot of pressure if the area is small
d) Absolute vs. Gauge Pressures
Gauge pressures: relative to ambient pressure
- Tire pressure, pressure in compressed gas cylinder, blood pressure
Absolute pressures
- Vapor pressure of anesthetics, H
2
O
- Blood gases
- Other cases where you need to use gas laws
e) Pressure Gauges
Bourdon tube (for high pressure gases such as compressed gas cylinders)
- Deformable tube changes shape when filled with pressurized gas causing pointer to move
Diaphragm (for low pressures such as aneroid blood pressure cuffs--the
kind with a pointer)
- Diaphragm at top of a "pancake" shaped cylinder moves outward
causing pointer to move
f) Pressure Regulators
Reduces high pressure in compressed gas cylinder to approximately 50
PSIG
Gas Cylinders
a) E Cylinder (back of machine)
For ideal gases (air, nitrogen, oxygen)
- Full cylinder pressure = 2000 PSI
- Full cylinder volume = 660 liters
- Volume remaining is proportional to pressure
- 1000 PSI --> 330 L 500 PSI-->165 L
334
Page 2

For pressurized liquids (N
2
O, CO
2
, C
3
H
8
[propane--barbecue grill], C
3
H
6
[cyclopropane])
- Pressure depends on vapor pressure of liquid at tank temperature until liquid is gone (740
PSI) for N
2
O at room temperature
- Full cylinder of N
2
O 1590 L
- Remaining quantity of gas best determined by weight
The N
2
O in a full E cylinder weighs about 3 Kg
- Critical temperature (T
c
): gas cannot be liquefied above this temperature regardless of
pressure
For N
2
O TC = 36.5
o
C
b) Some Simple Calculations
What is the weight of N
2
O in an E-cylinder?

What is the internal volume of an E Cylinder?
- Use Boyle's Law: P
1
V
1
=P
2
V
2

c) More Simple Calculations
How many ml of sevoflurane vapor come from 1 ml of sevoflurane liquid?

If the fresh-gas flow is 2 l/min, how many minutes of 2% sevoflurane anesthesia will 5 ml of
liquid provide?

Adiabatic Compression
a) Rapid compression of gas without giving heat a chance to escape
Principle of diesel engine (no spark plugs)
b) If there is oil / grease in valve or regulator and tank opened quickly, explosion can occur :-(

Flows of Liquids and Gases
a) Laminar (streamlined)
Pressure=Flow x Resistance
b) Turbulent
Pressure ! Density x Flow
2

Transition from laminar to turbulent flow when Reynold's number > 2300
1590 L!
mole
24 L
!
44 g
mole
" 2900 g" 2.9kg
2000 V
TANK
! 14.7 660
V
TANK
!
14.7 660
2000
! 4.85 L
1ml liquid!
1.5 g
ml
!
1mole
200 g
!
24 L gas
mole
" 0.18Lgas" 180mL
5ml liquid!
180 ml gas
ml liquid
!
1minute
0.02! 2000 mLgas
" 22.5min
Resistance!
8" L" !
"" R
4
"=viscosity of liquid
R=radius of tube
L=length of tube
R!
!" V " D
"
#=density of liquid
V=velocity of flow
D=diameter of tube
"=viscosity of liquid
334
Page 3

Flowmeters
a) Tapered tube with diameter increasing toward the top
b) Bobbin position determined by equilibrium
Upward force from flowing gas = downward force from gravity
- At low flow rates (laminar flow) upward force depends on
viscosity of gas
- At high flow rates (turbulent flow ) upward force depends on
density of gas
c) Always want O
2
flow tube nearest to the common gas outlet
- Minimizes risk of hypoxia if a flow tube is cracked

Fail Safe Valve
a) Cuts off N
2
O if O
2
supply fails
Does NOT prevent accidental or intentional dialing in of a hypoxic gas mixture
b) Testing
Turn on O
2
and N
2
O flows
Disconnect wall O
2
supply (be sure O
2
tank is "off")
Press O
2
flush valve
Verify that N
2
O flow ceases when O
2
pressure drops to zero

Proportioning Systems
a) Limit N
2
O flow to 3 times O
2
flow
b) Link vs. pressure operated systems
Link system: mechanically turns down N
2
O needle valve if O
2
flow reduced
- N
2
O flow will NOT return to initial value if O
2
flow increased
Pressure system: pneumatically decreases N
2
O flow if O
2
flow reduced
- N
2
O flow will return to initial value if O
2
flow increased

Anesthetic Vaporizers
a) Ye Olde Copper Kettle
Vapor output depends on O
2
inflow and vapor pressure of
anesthetic
For sevoflurane, Pv=190 mmHg = 1/4 ATM
- 1/4 of output molecules will be Sevoflurane; 3/4 of output
molecules will be O
2

- For every 100 ml O
2
input, will get 133 ml of total output
100 ml O
2
(3/4 of total)
33 ml sevoflurane (1/4 of total)
- If you use a total gas flow of 3.3 l/min (magic number :-),
each 100 ml of O
2
through the vaporizer gives you 1% of
sevoflurane concentration
b) Desflurane Vaporizer
Boiling point of desflurane 23.5
o
C (vapor pressure at room temp nearly atmospheric
Variable bypass vaporizer not controllable
- Each 100 ml of O
2
through vaporizing chamber would give about 900 ml of desflurane output
- Large output swings with changes in temperature
Alternative: Use a boiler and deliver as a gas
- Desflurane output determined by a "needle" valve, just like O
2
and N
2
O
- Uses electronics to make desflurane flow proportional to total gas flow, so a constant
percentage is given regardless of fresh gas flow settings
c) Vaporizers at Altitude
Recall that MAC is really a partial pressure
- Sevoflurane MAC = 2% x 760 mmHg =15.2 mmHg
In Tibet P
ATM
= 380 mmHg
15.2 / 380 = 4% (MAC of sevoflurane in Tibet)
334
Page 4

- Vapor pressure of sevoflurane in Tibet (depends on temperature only) = 190 mmHg (same as
at sea level)
Since vapor pressure = 1/2 barometric pressure, for every 100 ml of O
2
flowing into
vaporizer the output will be 100 ml of sevoflurane plus 100 ml of O
2

This is 3 times as much as at sea level--vaporizer output triples
Since MAC is only twice as great as at sea level, actually need to turn vaporizer DOWN
to 1.33% in order to get 1 MAC of anesthetic effect
Desflurane vaporizer
- Percentage output unaffected by altitude
- MAC of desflurane in Tibet is 12%
- Need to dial in 12% desflurane to get 1 MAC of anesthetic effect
Low pressure leak test
a) Checks for leaks in flowmeters, vaporizers, common gas manifold
b) Check valve just before common gas outlet on many machines
Allows patient to be ventilated with O
2
from flush valve even if there is a leak in low pressure
system--therefore, the fact that the breathing circuit "holds pressure" does not guarantee that there
are no low-pressure leaks
To check for leaks
- Turn machine fully off (otherwise minimum mandatory O
2
flow will look like a leak
- Apply suction bulb to common gas outlet and verify that it remains deflated for at least 5 sec
Breathing Circuits
a) Open (non-rebreathing)
Simple face mask or nasal cannula (CO
2
diffuses away from the face)
Bag-Valve-Mask system (Ambu): uses 3 valves to allow either spontaneous or controlled
ventilation while preventing rebreathing
b) Semi-Open (Mapleson / Bain)
Most efficient removal of CO
2
for a given gas flow when
the "pop off" valve is nearest the source of the ventilatory
power
- Spontaneous ventilation: Mapleson A
- Controlled ventilation: Mapleson D
However, the "A" system is very inefficient (requires high
gas flows) to prevent rebreathing during controlled
ventilation, while the "D" system is reasonably efficient for
both controlled and spontaneous ventilation, so the "D" is
preferred for most applications.
- Bain circuit is a coaxial Mapleson D
c) Semi Closed Circle System
Patient gas uptake < fresh gas flow < minute ventilation
Some rebreathing of exhaled gas (following removal of CO
2
by absorber)
d) Closed System
Gas inflow = Patient Uptake
If using sidestream agent / CO
2
analyzer, must route exhaust back into circuit
Starting values
- O
2
: 3-4 ml/kg/min
- Anesthetics: First minute uptake / $time (minutes)
N
2
O (80% concentration, 80 kg patient): First minute uptake 1600 ml
Sevoflurane (2%, 80 kg patient): First minute uptake 50 ml
Desflurane (6%, 80 kg patient): First minute uptake 100 ml
Closed System-Adjustments
- Total flow: Adjust N
2
O and O
2
in proportion to keep volume of bag or bellows constant
- FIO
2
: Adjust ratio of N
2
O and O
2
to maintain desired F
I
O
2
keeping total flow constant
- Depth of anesthesia: Adjust vaporizer setting to maintain desired depth or inspired
concentration
334
Page 5

CO
2
Absorption
a) Granules
Small enough to have large surface area but large enough to avoid channeling
Typically 4-8 mesh
b) Composition
Sodalime: NaOH, Ca(OH)
2

Baralyme: KOH, Ca(OH)
2
, Ba(OH)
2

- More likely to react with anesthetics to form CO (desflurane) or compound A (sevoflurane)
c) Moisture
Necessary for CO
2
absorption
Reduces likelihood of anesthetic breakdown
d) Absorption Chemistry
CO
2
+ H
2
O-->H
2
CO
3

H
2
CO
3
+ 2 NaOH-->Na
2
CO
3
+2H
2
O + heat
Na
2
CO
3
+ Ca(OH)
2
-->CaCO
3
+2NaOH
When the NaOH is gone, acidification causes indicator (ethyl violet) to turn violet
e) Zone of maximum absorption feels warm to touch (may be hot if malignant hyperthermia)

Pressure Transducer Systems
a) Accuracy with which transducer system reproduces actual intravascular pressure depends on
Resonant frequency (higher is better)
Degree of damping (most important if resonant frequency similar to 1/rise-time of waveform)
b) Zeroing Pressure Transducers
Height of patient relative to transducer must remain constant after zeroing
At time of zeroing
- Transducer may be at any height relative to patient (need not be at heart level)
- System should be opened to air by a stopcock at heart level before zeroing is performed
c) Site of Arterial Pressure Measurement
Wave reflection causes systolic pressure to be higher and diastolic pressure to be lower when there
is an acute change in vessel diameter (radial / dorsalis pedis)
This does NOT affect the mean pressure
Resistance to flow causes a (very slight) decrease in mean pressure as
pressure measurement progresses from aorta to more distal vessels
d) Damping
Oscillations within the transducer system may exaggerate or attenuate
certain frequency components of the pressure waveform
Underdamped: Systolic overshoot and diastolic undershoot
Overdamped: Looks like a sine wave with underestimation of
systolic and overestimation of diastolic pressure
Regardless of damping, electronically determined mean pressures
should be accurate
Squeeze and release flush valve to assess damping

Non-Invasive Blood Pressure Measurement
a) Most standard cuff systems use oscillometry
Pulsations in the cuff pressure monitored as cuff deflates
Initial pulsations--just above systolic pressure
Maximal pulsations--mean arterial pressure
Diastolic pressure by mathematical algorithm
b) Continuous non-invasive monitoring
Most systems require intermittent calibration with a cuff
334
Page 6

Cardiac Output Measurement
a) Fick Principle
Conservation of mass
Q=VO
2
/[C
a
O
2
-C
v
O
2
]
Required measurements
- VO
2
(Oxygen uptake--difficult to measure during anesthesia)
- C
v
O
2
(requires PA catheter)
NICO
- Fick formula applied to CO
2
elimination
- Partial rebreathing to estimate mixed venous CO
2

- Requires constant ventilatory pattern (controlled ventilation only)
b) Esophageal Doppler Monitor
Doppler: Change in frequency of sound / ultrasound / light waves when reflected from a moving
object (e.g., RBC)

v! f
d

c
2 f
i
cos !

- v=RBC velocity f
d
= Doppler shift f
i
=frequency of ultrasound
- %=angle between ultrasound beam and direction of blood flow
CO = HR x CSA x VTI
- CO=Cardiac Output CSA=Cross Sectional Area VTI=Velocity-Time Integral
c) Thermodilution

Quantity of indicator = Volume x (T
PATIENT
-
T
INDICATOR
)
Sources of error
- Quantity of indicator is "dialed in" to the C.O.
computer based on the intended volume and
temperature of injectate
- If volume injected is lower than intended, then
!
t " 0
!
!Temp dt
will be too low and the Cardiac
Output reading will be falsely high
- If the temperature of the indicator is colder than
intended (e.g. using iced rather than room
temperature saline) then
!
t " 0
!
!Temp dt
will be too high, and the Cardiac Output reading will
be falsely low

Disclosure

C.O.!
Quantity of Indicator
"
t ! 0
!
!Temp dt
401
Page 1
Coagulation Issues Facing You and Your Patient
Charise Petrovitch, M.D. Washington, D.C.
The intent of this refresher course is to present the basic principles of the hemostatic mechanism, to review some of
the common bleeding disorders, and then with these concepts in mind, to develop an approach to the patient who
may have a bleeding disorder, either in the preoperative or the intraoperative time frames. In addition, current
coagulation issues and newer anticoagulant drugs will be discussed.
The Hemostatic Mechanism
The hemostatic mechanism includes three process, primary hemostasis, coagulation and fibrinolysis.
Primary hemostasis takes place within seconds of vascular injury and involves the action of platelets and blood
vessels. Following vascular injury and disruption of the endothelial layer of a blood vessel, in a process called
platelet activation, platelets spread along the surface of the denuded injured blood vessels and adhere to the
subendothelial collagen layer via glycoprotein receptors and the von Willebrand factor. Following adhesion of the
platelets to the subendothelial layer of the blood vessel, the platelets change shape from a flattened disk to a
spheroid and extend multiple pseudopods. The platelets also undergo a release reaction extruding the contents of
their cytoplasmic granules, and releasing multiple compounds into the blood, including ADP, serotonin, clotting
factors V, VIII, and fibrinogen and many other chemical mediators, important to primary hemostasis and the
subsequent coagulation process that follows. With sufficient stimulus, platelets synthesize thromboxane A
2
, a
prostaglandin, which stimulates further ADP release and also has potent vasoconstrictor actions. ADP increases
platelet activation and leads to the aggregation of platelets to each other. Finally, in the final stage of platelet
activation, the platelets expose a new phospholipid surface called platelet factor 3, which changes the surface charge
of the platelet and creates a procoagulantactivity. In the process of coagulation that follows, clotting factors
interact on the phospholipid surface of the activated platelet and ultimately form fibrin, which reinforces the friable
platelet plug.
Beyond the site of vascular injury, the intact endothelial lining arrests further platelet aggregation. The
intact endothelial cells secrete prostacyclin (PGI2), a prostaglandin, which has actions opposite those of TxA
2
. PGI2
inhibits platelet activation, secretion, and aggregation, and prostacyclin is a potent vasodilator.
Any imbalance in the production of the two prostaglandins, thromboxane or prostacyclin, can lead to a defect in
primary hemostasis or to abnormal coagulation.
Basic Principles of Coagulation
Coagulation involves the interaction of many plasma proteins, called clotting factors, which interact in a
series of reactions to produce fibrin. Most of the clotting factors circulate in an inactive form called a procoagulant
molecule or proenzyme. During the process of coagulation, a portion of this protein molecule is cleaved off and the
remaining protein becomes an active cleavage enzyme, called a serine protease. The activated clotting factor then
cleaves off a portion of the next procoagulant clotting factor, which in turn activates the next factor in turn. In a
chain reaction-like fashion, one factor activates another, until fibrinogen (factor I) is cleaved to form fibrin.
Clotting factors do not simply interact in the bloodstream. Instead, coagulation is a surface based
process. In fact, the proper interaction of many of the clotting factors requires the presence of a phospholipid
surface. This phospholipid surface can be provided by tissue phospholipid, called tissue factor, located extrinsic
to the interior of the blood vessel lumen, or by the surface of platelets, when they become activated and expose
platelet factor 3 phospholipid, inside the blood vessel lumen. The coagulation process that occurs on the surface
of tissue factor is called the extrinsic pathway and the process that occurs on the surface of platelet factor 3 is

401
Page 2
called the intrinsic pathway. Because coagulation requires the presence of a phospholipid surface, the production of
fibrin is localized to the site of vascular injury, where clotting factors are exposed to phospholipid, either platelet
phospholipid or tissue factor.
Some of the reactions of the coagulation cascade involve the formation of a reaction complex in which two
clotting factors are bound in a particular spatial arrangement on a phospholipid surface and together they activate a
third clotting factor. In the reaction complex, one of the clotting factors serves as a cofactor and is not an actual
cleavage enzyme. Factors V and VIII serve as cofactors and are also known as the labile factors because their

coagulant activity does not last long in stored blood. Transfusion of large quantities of stored PRBCs leads to a
deficiency of these labile factors, Va and VIIIa.
Most of the coagulation proteins are synthesized by the hepatocytes of the liver. Their normal structure and
function are dependent upon normal hepatic activity. Four of the clotting factors, (II, VII, IX, and X) are called the
vitamin K dependent factors, because they require the presence of vitamin K for their proper synthesis in the liver.
After these factors have been synthesized, they undergo a final enzymatic reaction, which requires the presence of
vitamin K. In this final step, a carboxyl tail is added to each factor and this carboxyl moiety enables the vitamin K
dependent factors to bind via calcium to phospholipid surfaces. In the absence of vitamin K, these proteins are
produced in normal amounts by the liver, but they are not functional because they cannot bind to phospholipid
surfaces. The warfarin-like drugs work by competing with vitamin K for binding sites on the hepatocyte and in this
way warfarin inhibits carboxylation of the vitamin K dependent factors. Of the four vitamin K dependent factors,
factor VII has the shortest half-life. Factor VII is the first clotting factor to disappear from the circulation when a
patient is placed on warfarin.
Factor VIII is a unique clotting factor. It circulates as a large plasma protein and is really a complex of two
components, each under separate genetic control. The high molecular weight portion (VIIIR:Ag) contains both the
factor VIII antigen and the von Willebrand factor (vWF). The vWF has two major functions it mediates adhesion
of platelets to collagen in the subendothelial layers of blood vessels during the process of primary homeostasis and
the vWF serves as a carrier protein for the smaller moiety of the factor VIII molecule. This smaller moiety contains
the factor VIII coagulant activity (VIIIC). Absence of the smaller portion of the factor VIII molecule (VIIIC), leads
to hemophilia A. Because the vWF mediates platelet adhesion and the vWF serves as a carrier protein for the
coagulant factor VIII portion, deficiencies of vWF make the patient appear to have both a defect in primary
hemostasis and hemophilia A. Restoration of vWF levels returns the level of coagulant factor VIII in the blood to
normal.

Coagulation Initiated by Tissue Factor. The cascade description of coagulation was proposed in 1964.
However, at that time coagulation was thought to proceed via two separate pathways, the intrinsic and the extrinsic
pathways of coagulation, and these were thought to converge with the activation of factor X to Xa. Then fibrin
would be generated through a common pathway of coagulation. This classical understanding has been modified. In
contrast to the previous belief that the intrinsic pathway of coagulation was primarily responsible for coagulation
in vivo, it may be that in vivo coagulation is initiated by the exposure of blood to tissue factor (TF), which is
extrinsic to blood and involves reactions of the classical extrinsic pathway. In this model, when blood is exposed
to TF in the subendothelial layers of the blood vessel, the TF binds factor VII or VIIa, which is circulating in the
blood. The factor VIIa/TF complex then activates two different substrates, factor X and also factor IX producing
some factor Xa and some factor IXa respectively. Factor IXa bound together with cofactor VIIIa can activate X to
Xa on the platelet surface. What this means is that the activation of factor X (by the VIIa/TF complex) can occur by
two different reaction sequences. Once formed, Xa binds together with its cofactor, factor Va, on the platelet
phospholipid surface, (PF3), and together they activate factor II, prothrombin, to thrombin (IIa). Thrombin then
converts fibrinogen to fibrin.
An inhibitor to the tissue factor pathway has been found called tissue factor pathway inhibitor, (TFPI).
TFPI inhibits the VIIa/TF complex after the first flurry of thrombin has been synthesized. Xa must then be
produced by an alternate series of reactions, involving the classical intrinsic pathway of coagulation. It is the
functioning of TFPI that results in the bleeding seen with the hemophilias because TFPI forces coagulation to
proceed via the intrinsic pathway of reactions involving factors XIa, IXa, and VIIIa. It is theoretically possible
that inhibition of TFPI by another inhibitor could allow the TF pathway to function in hemophiliacs and effectively
correct their bleeding problems.
Coagulation is controlled under normal circumstances by several mechanisms. First, the clotting factors
themselves circulate in an inactive form. Once they do become activated, normal blood flow dilutes their

401
Page 3
concentrations and washes them away from sites of injury. In addition, activated clotting factors are preferentially
removed from the circulation by the liver and the reticuloendothelial system. Some of the clotting factors require
the presence of a phospholipid surface for their proper interaction and this requirement localizes clot formation to
phospholipid surfaces. However, when the blood, circulating through the vascular tree, is exposed to large amounts
of phospholipid, (tissue factor), uncontrolled rampant coagulation or disseminated intravascular coagulation (DIC)
may be initiated. Under normal circumstances, coagulation is also limited by the presence of anticoagulants, which
circulate in the blood. Antithrombin III (ATIII) is one such naturally occurring anticoagulant. As its name implies,
ATIII binds to thrombin to inactivate this master coagulation enzyme. ATIII also binds to factors IXa, Xa, XIa, and

XIIa. Under normal circumstances, the binding of AT III to thrombin and the other activated factors of the intrinsic
pathway occurs very slowly. However, in the presence of heparin (the man-made drug), the rate of ATIII binding
is accelerated dramatically. Without ATIII, heparin alone has almost no anticoagulant action.

Fibrinolysis. The process of fibrinolysis involves the conversion of plasminogen to plasmin, the active
fibrinolytic enzyme. However, plasmin does not circulate in the bloodstream freely because it would be rapidly
attacked by antiplasmins present in the bloodstream. Instead the precursor to plasmin, plasminogen, circulates in the
bloodstream. Then, when circulating plasminogen comes into contact with fibrin, plasminogen preferentially binds
to the fibrin clot. When bound to the fibrin clot, plasminogen is converted to plasmin by tissue plasminogen
activator (t-PA). The plasmin formed has a specific binding site for fibrin. This same binding site is also involved
in the interaction of plasmin with the plasmin inhibitor, alpha2-antiplasmin. As long as plasmin remains bound to
fibrin, even though actively involved in degrading the fibrin clot, alph2-antiplasmin cannot neutralize the enzyme.
However, as soon as the binding site is freewhen plasmin is released into the bloodstreamalpha2-antiplasmin
will rapidly neutralize the plasmin. In this way, these antiplasmins, which circulate in blood, prevent widespread
fibrinolysis because only plasmin bound to fibrin is protected from antiplasmin attack. Fibrinolysis is also limited to
the site of fibrin formation because t-PA only activates plasminogen which is bound to fibrin.
The primary action of plasmin is to degrade fibrin clots. The degradation products produced are called
fibrin degradation products (FDPs) or fibrin split products (FSPs). Their structure varies according to whether
plasmin cleaves fibrinogen, fibrin that is cross-linked, or fibrin that is not cross-linked, etc. Under normal
circumstances, FDPs are removed from the blood by the liver, kidney, and reticuloendothelial system and have half-
lives of about nine hours. If the FDPs are produced at a rate that exceeds their normal clearance, they will
accumulate. In high concentrations, FDPs act as anticoagulants. The FDPs impair platelet function, inhibit
thrombin, and prevent the cross-linking of fibrin strands. In such high concentrations, the FDPs lead to bleeding
which is not due to a coagulation defect, but rather due to the accumulation of FDPs which act as inhibitors to
coagulation.

Disorders of the Hemostatic Mechanism.
The disorders of the hemostatic system may be broadly classified according to whether they involve platelets and/or
clotting factors, and/or the presence of inhibitors (such as FDPs). Treatment most often involves transfusion of
hemostatic agentsplatelets and/or clotting factorsor the use of pharmacologic agents, which will affect the
function of platelets (desmopressin, antiplatelet drugs) or clotting factors (vitamin K, warfarin, heparins) or
inhibitors (antifibrinolytics, protamine, fibrinolytic agents).

Hereditary Platelet Disorders
Von Willebrands Disease. Von Willebrands disease is the most common congenital bleeding disorder in
humans. The disease is actually due to a deficiency in plasma of the von Willebrand factor (vWF) and not due to
defective or deficient platelets. The disease is usually discussed in the context of platelet disorders because when the
vWF is deficient, platelet function is impaired. Likewise, treatment of this disease does not involve transfusion with
platelets. Instead, the vWF levels may be increased via transfusion with FFP, cryoprecipitate, or for some types of
Von Willebrands disease, the administration of desmopressin.

Acquired Platelet Disorders
Thrombocytopenia. By definition, when the platelet count falls below 150,000/mm
3,
a patient is said to be
thrombocytopenic. Thrombocytopenia may result from (1) inadequate platelet production by the bone marrow (2)
sequestration in the spleen (3) consumption from tissue injury or platelet activation (4) dilution due to massive
transfusion with colloids or crystalloid or blood and (5) platelet destruction by immune mechanisms.

401
Page 4
Platelet Dysfunction. Myeloproliferative and myelodysplastic syndromes produce intrinsic defects in
platelets. Some systemic conditions, renal failure, liver disease, DIC and cardiopulmonary bypass can produce
platelet dysfunction by altering the milieu in which the platelet circulates. The most common cause of acquired
platelet dysfunction is due to drug administration, such as ASA or NSAIDs. Platelet dysfunction is observed after
platelet storage due to a depletion of energy stores, specifically ATP. Platelet defects can last as long as 8 to 20
hours after they are transfused. Desmopressin is sometimes recommended to treat platelet dysfunction due to
uremia, liver disease, and for patients taking aspirin who present for coronary artery bypass surgery.

Hereditary Factor Deficiencies
Hemophilias A & B. Hemophilia A is caused by a deficiency of factor VIII activity, whereas hemophilia B
(Christmas disease) is due to a deficiency of factor IX, and hemophilia C is due to deficiency of factor XI.
Hemophilia A occurs in approximately 1 in 10,000 males. Clinically, hemophilia A can be classified as mild,
moderate, and severe. The great majority of hemophiliacs have the severe form of the disease. Their factor VIII
levels are less than 1% of normal activity and they frequently experience episodes of spontaneous bleeding.

Acquired Factor Deficiencies
Vitamin K Deficiency. Vitamin K deficiency leads to deficiencies of factors II, VII, IX, and X as well as
deficiencies of the anticoagulatnts, protein C and protein S. In the absence of vitamin K these proteins are
synthesized but are structurally abnormal. When vitamin K deficiency develops, protein C and protein S are
depleted first followed by depletion of Factor VIIthe clotting factor with the shortest half-lifeand then factor IX
and X and finally factor II.
Vitamin K is a fat soluble vitamin, found in leafy green vegetables, that requires bile salts for absorption
from the jejunum. Clinically patients with malabsorption syndromes, pancreatic insufficiency, biliary obstruction,
GI obstruction, or conversely a rapid GI transit time can all develop vitamin K deficiency due to inadequate
absorption of the vitamin. Treatment of vitamin K deficiency is best done by the intramuscular or intravenous
administration of vitamin K (Aquamephyton) in doses of 10 to 20 mg. Within 3- 5 hours, the coagulopathy will
begin to correct.

Acquired Combined Deficiencies of Platelets and Factors
Massive Transfusion. The transfusion of large volumes of stored PRBCs to correct extreme anemia may
result in hemostatic defects similar to the hemostatic defects present in stored bloodthe coagulant activity of
factors V and VIII are significantly reduced and the great majority of platelets are non-functional.

Platelet Dysfunction, Factor Deficiencies and the Presence of Inhibitors
Liver Disease. Liver disease produces a complex coagulopathy that is multifactorial in nature. The liver
synthesizes most of the clotting factors, with the possible exception of factor VIII. The liver also synthesizes the
anticoagulants, antithrombin III, protein C and protein S, and the fibrinolytic precursor, plasminogen. The liver is
responsible for clearing activated clotting factors and for clearing plasminogen activator (t-PA) as well as the
products of fibrinolysis, fibrin degradation products (FDPs). The net effect of the diseased liver on the hemostatic
mechanism may be difficult to predict, difficult to diagnose, and difficult to treat.
Treatment of the hemostatic defects associated with liver disease is difficult. In the alcoholic, platelet
dysfunction is presumed. If thrombocytopenia is also present, platelet transfusions will more than likely be
necessary to prevent bleeding. Vitamin K may be administered even if vitamin K deficiency has not been
diagnosed. Severe factor deficiencies are treated with FFP, but volume overload can be a problem if multiple
transfusions are required. Vitamin K dependent factors can be transfused with Prothrombin Complex Concentrate
(PCC). Cryoprecipitate may be transfused to treat low fibrinogen levels, but cryoprecipitate does not contain the
vitamin K-dependent factors.

Disseminated Intravascular Coagulation (DIC). DIC is characterized by excessive deposition of fibrin
throughout the vascular tree, with simultaneous depression of the normal coagulation inhibitory mechanisms and
impaired fibrin degradation. DIC is triggered by the appearance of procoagulant material (tissue factor or
equivalent) in the circulation in amounts sufficient to overwhelm the mechanisms that normally restrain and localize
clot formation. That appearance may be the result of either extensive endothelial injury, which exposes tissue factor
of fibroblastic origin, or the release of TF into the circulation as occurs with amniotic fluid embolus, extensive soft
tissue damage, severe head injury or any cause of a systemic inflammatory response. For reasons not entirely clear,
the native pathways that inhibit coagulation, antithrombin III and the protein C pathway are simultaneously

401
Page 5
inhibited. The accelerated process of clot formation causes both tissue ischemia and, ultimately, critical depletion of
platelets and factors. Simultaneously, the fibrinolytic system is activated and plasmin is generated to lyse the
extensive fibrin clots. Fibrin degradation products (FDPs) appear in the circulation. FDPs stimulate release of
plasminogen activator inhibitor, type 1 (PAI-1) from the endothelium and thrombolysis becomes impaired. The
FDPs also inhibit platelet aggregation and prevent the normal cross-linking of fibrin monomers. Depleted of
platelets and clotting factors and inhibited by FDPs, the coagulation system fails and the patient who was once

clotting uncontrollably begins to bleed. Simultaneously, the microvascular occlusion by fibrin causes tissue
ischemia contributing to multi-organ failure.
Several clinical entities encountered frequently in anesthetic and critical care practice are associated with
the development of DIC. Sepsis is the most common cause. Endotoxins or lipopolysaccharide breakdown products
from gram negative and positive bacteria respectively incite an inflammatory response that includes the generation
of cytokines (tumor necrosis factor alpha, various inter-leukins). These cytokines in turn stimulate the release or
expression of TF by endothelial cells, macrophages and monocytes and the DIC sequence is initiated.
Several obstetric conditions can cause DIC. Amniotic fluid embolism, placental abruption, and fetal death
in utero result in the direct release of TF-equivalent material into the circulation. Pre-eclampsia is characterized by a
systemic vasculitis. The associated endothelial damage causes an initially low grade DIC that accelerates as
vasculitis-related damage leads to release of TF from ischemic tissues, in particular placenta.
Large burns, extensive traumatic soft tissue injuries, severe brain injury and hemolytic transfusion reactions
can also liberate TF-equivalent material into the circulation and incite DIC. Certain malignancies, most notably
promyelocytic leukemia and adenocarcinomas, are associated with DIC. However, with malignancyassociated
DIC, thrombotic manifestations are more likely to appear first, whereas with the others mentioned above, the
hemorrhagic diathesis is often the first clinical manifestation.
A few general conditions such as acidosis, shock, and hypoxia are associated with DIC. Shock promotes
coagulation because one of the control mechanisms (rapid blood flow) is compromised. Clearance of activated
clotting factors is reduced when blood flow is decreased. Acidosis and hypoxia may contribute to both tissue and
endothelial damage.
The clinical manifestations of DIC are a consequence of both thrombosis and bleeding. Bleeding is a more
common clinical presentation in patients with acute, fulminant DIC. Petechiae, ecchymoses, epistaxis,
gingival/mucosal bleeding, hematuria, and bleeding from wounds and puncture sites may be evident. With the
chronic forms of DIC, thrombotic manifestations are more likely. Organs with the greatest blood flow, e.g., kidney
and brain typically sustain the greatest damage. Pulmonary function may deteriorate as a consequence
microthrombus accumulation.

Diagnosis of DIC. There is no absolutely consistent constellation of laboratory findings among routine
tests. Increased PT and aPTT, thrombocytopenia, a decreased fibrinogen level, and the presence of FDPs and D-
dimer may all be noted. The peripheral smear may reveal schistocytes (fragmented RBCs reflecting the
microangiopathy that occurs as a consequence of widespread fibrin deposition). Thrombocytopenia (<100,00/uL) is
not always evident early in the process, but true DIC without sequential reduction in platelet count is very unlikely.
PT and aPTT may remain normal in spite of decreasing factor levels because of the presence of high levels of
activated factors including thrombin and Xa. Fibrinogen levels may not be decreased, i.e., <100 mg/dL, initially.
Fibrinogen is an acute phase reactant which increases in response to stress and the early consumption of
fibrinogen may simply reduce its levels to normal. FDPs are a sensitive measure of fibrinolytic activity although
they not specific for DIC. D-dimer (which is a breakdown product of the cross-linked fibrin in a mature clot) is
somewhat more specific for DIC, but not entirely so, and should be measured when that diagnosis is suspected.
Various other laboratory assays have been employed to support a diagnosis of DIC, but should probably not be
considered part of the anesthesiologists routine. They include levels of prothrombin fragments F1+F2 (a marker of
prothrombin conversion to thrombin-increased), thrombin-ATIII (TAT) complexes (increased), ATIII (decreased),
alpha2-antiplasmin (decreased by binding to excess plasmin), protein C (decreased), plasminogen (decreased), and
Factor VIII (decreased in DIC but normal with hepatic failure without DIC).

Treatment of DIC. Treatment should focus on management of the underlying condition. Septicemia will
require antibiotic therapy. The obstetric conditions are frequently self-limited, although evacuation of the uterus or
hysterectomy may be warranted. Hypovolemia, acidosis and hypoxemia should be corrected to prevent their
contribution to the DIC process. When bleeding is or may become life threatening, the consumptive coagulopathy
must be treated. Platelets will be required for thrombocytopenia, e.g., < 50,000/mm3. FFP will replace the clotting

401
Page 6
factor deficiencies. Fibrinogen level should be raised to >100 mg/dL. When hypofibrinogenemia is severe (<50
mg/dL) cryoprecipitate may be required. Six units of cryoprecipitate will increase fibrinogen level by
approximately 50 mg/dL in a 70 kg patient. Heparin has been advocated. However, the contemporary practice is to
restrict its use to only those situations where thrombosis is clinically problematic, principally DIC associated with
malignancies. There is no proven benefit in situations in which bleeding is the predominant manifestation.
Antifibrinolytics have been considered. However, their use in the face of widespread thrombosis is potentially

disastrous and they should not be used. Antithrombin III concentrates have been administered. The hope is that its
administration will serve to slow the runaway coagulation process. However, a beneficial effect on outcome from
DIC has not been confirmed and its use should be viewed as experimental. An insufficiency in the protein C
endogenous coagulation inhibition system is thought to contribute to the prothrombotic state in DIC. Activated
protein C has been shown to decrease mortality and organ failure in patients with sepsis and that improvement is
also evident among patients with sepsis with overt DIC. Its use should be considered in any sustained episode of
DIC.

Newer Anticoagulant Medications and Regional Anesthesia

The introduction of low molecular weight heparins into this country brought with it a dramatic increase in the
incidence of spinal epidural hematomas, primarily due to the failure of anesthesiologists to recognize the hazards of
combining regional anesthesia (specifically central neuraxial anesthesia) and anticoagulation. Five years after FDA
approval of the introduction of low molecular heparins into the United States, more than thirty people had suffered
permanent neurologic damage from spinal epidural hematomas thought to be due to combining central neuraxial
anesthetic techniques with the administration of low molecular weight heparins. This led to the creation of practice
guidelines on the use of regional anesthetic techniques in the presence of anticoagulation and these guidelines have
been promulgated by the American Society of Regional Anesthesia.

Guidelines addressing the use of central neuraxial blockade and anticoagulation always include two important time
intervals to be respected. First, there is the time interval between the time of administration of the last dose of an
anticoagulant and the insertion of a needle or catheter into the central neuraxial location or between the last dose of
an anticoagulant and the removal of a catheter from the central neuraxial location. Second, another important time
interval is that time interval between the insertion of a neuraxial needle or catheter (or the removal of that catheter)
and the timing of the next dose of anticoagulant. A final point of concern is the coagulation testing recommended, if
any when performing a central neuraxial technique in a patient receiving an anticoagulant drug.

Newer anticoagulant drugs are being introduced into clinical practice and an approach to the management of these
patients is our next challenge. Rosencher et al have proposed a management scheme in which the first time interval
that time between when a patient has received a dose of a particular anticoagulant and the time when a central
neuraxial needle or catheter is inserted (or a catheter is withdrawn) should be based upon at least two elimination
half-lives for that anticoagulant drug. For the second time interval, which involves the administration of an
anticoagulant drug after the insertion of a neuraxial needle or catheter (or the removal of that catheter) and the
administration of the next dose of anticoagulant --these authors recommend that that time interval be determined by
subtracting the time necessary for that drug to reach maximum plasma levels from 8 hours, which is the time
necessary for a patient to produce a stable blood clot.

The risks of combining regional anesthesia with anticoagulation are dependent on the regional technique used,
patient characteristics, and the pharmacologic properties of the drug used.

Disclosure

407
Page 1
Awake intubation Made Easy!
William H. Rosenblatt, M.D. New Haven, Conneticut
By far the hardest part of performing an awake intubation should be the decision to do it! Once that decision is
made, the mechanics of securing the airway should be routine familiar to you and comfortable for the patient. A
review of the strategy for deciding upon awake intubation can be found in the notes on Decision making in airway
management lecture. Technique of Awake Intubation:
Awake intubation (AI) is one of the most important tools of the airway manager. If you are going to manage
airways, you must be good at AI (one day youll need it)! And if you have not performed an awake intubation in
years, you probably are not doing enough of them (Dont confuse being good with being lucky.) After speaking to
thousands of anesthesiologists, I have come to two conclusions: The typical anesthesia practitioner 1) is insecure
about his or her technique and 2) confuse airway anesthesia with AI technique. The sentinel grounds for these
conclusions are deduced from the single question I have been asked almost every time I speak about airway
management (no matter what the lecture topic): Dr. Rosenblatt, what local anesthetic do you use? This question
betrays the misconception most clinicians have about AI: that AI is about producing a numb airway. In fact the
topical anesthetic(s) chosen matter little. AI involves a systemic approach to patient preparation once appreciated,
and a consistent technique developed, AI can become as easy as routine airway management.
AI has 6 distinct elements in my technique, each element is essential, and rarely do I diverge.
Element Underlying concept/action
Explanation* Patients understand safety
Desiccation Dry the airway
Dilatation Prepare (through) the nose
Topicalization Obtund reflexes
Sedation Maintain patient airway control
Procrastination AI can not be rushed
*substituting the word Account those who like pneumonics can recall ADD a TSP (Benjamin Sherman, MD)
Explanation: All patients presenting to the operating room for surgery harbor some degree of anxiety. Though we
may be comfortable in the OR, it is a foreign environment for most others, and surgery is most often a daunting
prospect. Patients want the safest experience possible. If you have determined (via the AAA or your own method)
that AI is warranted, you have erred on the side of safety and the patient will understand this. A clear explanation
to the patient is usually all that is required to gain cooperation. Explaining that they will feel or remember very little
and that they will have some sedation is all that is needed. My typical explanation is always some variant of the
following:
"#$ %&' () *& +,-. )/0. *1,* $&/ ,0. '0.,*1(23 4/0(23 )/03.0$5 6&/0 ,2,*&+$ 4(77.0) 8, 9&* : , 9(**9.;
70&+ 2&0+,9< ,24 = 1,>. *& +,-. )/0. = ?,2 7(24 $&/0 '0.,*1(23 @,*1A,$5 B1,* = ,+ 3&(23 *& 4& () *&
+,-. $&/0 *10&,* 2/+'< %/)* 9(-. *1. 4.2*()* 4&.) 8.C?.@* = A(99 2&* /). 2..49.) /29.)) ,')&9/*.9$
2.?.)),0$;5 = A(99 *1.2 '. 9&&-(23 (2 $&/0 +&/*1 (2 &04.0 *& 7(24 $&/0 '0.,*1(23 @,*1A,$5 D7*.0 = +,-.
)/0. $&/ ,0. ?&+7&0*,'9. ,24 7..9(23 2&2. &7 *1()< = A(99 @/* *1. '0.,*1(23 */'. (25E

407
Page 2
Desiccation: To desiccate is to dry. Before you begin to manipulate the airway below the nasopharynx it must be
dry: 1) saliva is a protective barrier it will protect the mucosa from your topical agents. 2) saliva dilutes your
topical local anesthetic, and decreases its effectiveness. 3) manipulation of the airway produces more secretions
these secretions are an airway stimulant, causing more cough, laryngospasm, etc. 4) Im likely to use an indirect
optical device which will be neutralized by secretions. I dont exclude patients who have had airway radiation and
are already complaining of dry mouth. My concern is that any remaining functional salivary tissue will counteract
my efforts. My favorite desiccant is glycopyrolate (0.2 to 0.4 mg). Atropine, clonidine and scopolamine are also
effective. Whatever agent you use, it must be given time to be effective -- at least 15 minutes. I will often give the
agent in the nursing intake area as soon as the patient has changed clothes. If there is no IV in place, I do not hesitate
to use an IM injection. This assures that the agent will have time to be effective. If, by the time the patient reaches
the holding area, they are not complaining of cotton mouth I consider giving another 0.2mg.

Dilatation: This is primarily an ellipsis for saying prepare the nose which is done in all cases unless medically
contraindicated, regardless of my intent to intubate via the mouth or nose. A vasoconstrictor is used to decongest the
nasal mucosa. This widens the space and reduces the risk of bleeding during manipulation. Oxymetazoline (e.g.,
Afrin, Gensol) is the most effective and long acting agent. Why prepare the nose in all cases? 1) During preparation
of the nose much of the effect occurs in areas of the oropharynx by both cross innervation, and passive leak of local
anesthetic. Nasal preparation can be started before desiccation has been effective. 2) In the case where an oral
intubation is difficult, the nose is prepared for manipulation too many times I have seen the plan changed from oral
to nasal intubation, and the nose is not prepared. This leads to an ill-fated rush job. This is often started in the
intake area.

Topicalization: Except for cases of retrograde intubation, where a cricothyroid puncture is part of the procedure, I
have not used invasive airway blocks for more than 8 years. Though I have no objection to needle blocks, I have
not found them necessary. Additionally I use the same topical anesthetic technique in all cases: I dont discriminate
based on my intent to intubate by a nasal or oral route, or depending on which instrument I plan to use. There are
also topical blocks that I do not employ. Again, its not because I object to them I just use the techniques which
work best in my routine. I divide the airway into three areas, and use directed blocks for each: Nasal
passage/nasopharynx, base of tongue/posterior oropharyngeal wall, hypopharynx/larynx-trachea. Note, that should
the patient begin coughing during the topical administration, he or she should be assured that the local anesthetic is
getting to the right place. I also do not use atomized local anesthetic: Atomization produces significantly higher
blood concentrations of local anesthetic and completely abolishes the cough reflex, which may be useful in case of
deep lung gastric content aspiration.

Nasal passage/nasopharynx: This area is innervated by the anterior ethmoid nerve (anterior 1/3) and nasopalantine
nerve. I take cotton swabs soaking with local anesthetic (4% lidocaine solution or 5% lidocaine ointment) and
advance them slowly into the nasal passage, first up towards the cribiform plate, and then directly posterior until the
boney feel of the sphenoid bone is encountered. Progress is incremental, and I push to pain that is, I advance the
swab only until the patient winces or otherwise exhibits discomfort. This may take up to 5 minutes to accomplish. I
will often start this procedure in the nursing intake area. It is complete by the time the patient reaches the holding
area.

407
Page 3

Base of tongue/posterior oropharyngeal wall: These are the only two areas in the mouth and pharynx that concern
me. I dont concern myself with the oral cavity my dentist regularly performs an aggressive oral exam which I
readily accept unless he accidentally stimulates my gag reflex. The glossopharyngeal nerve is responsible for the
gag. We can access the glossopharyngeal where it travels in the base of the palatoglossal arch that arch of tissue
which travels from the uvula to the base of the tongue. A new set of lidocaine soaked swabs are inserted along the
tongue until they contact anterior surface of the base of the arch. Some patients will respond to this with a retch.
This is a good indicator that you are in the correct position. A slight backing off will resolve the gag. A few
moments later the swab can generally be readvanced. The patient can close their mouth on the swabs and hold them
in position for 5 minutes. This, and the following technique are generally accomplished in the holding area.

Hypopharynx/larynx-trachea: Many years ago at an ASA annual meeting I learned an old pulmonologist trick from
a young anesthesiologist: a 10 cc syringe fitted with a large plastic angiocatheter is filled with lidocaine (2%). The
patient extends the tongue maximally, and the anesthesiologist takes an unfolded gauze, wraps the tip of the tongue
and does not allow the patient to retract. After the patient is assured that there is no needle, the catheter is inserted
over the tongue until the distal tip is at the oral-pharyngeal juncture. Slowly lidocaine is dripped on to the tongue
base. The procedure may take up to 1-2 minutes, and all 10 cc of lidocaine need not be used: At first the patient will
cough. Once the coughing subsides, yet you can hear the gurgling of the lidocaine deep in the airway, you can let go
of the tongue. Holding the tongue in this manner prevents the patient from swallowing the lidocaine, and encourages
its aspiration. SEE VIDEO 1

If a flexible fiberoptic scope is used for the tracheal intubation, local anesthetic can be injected down the working
channel. I prefer a technique described by Dr. A. Ovassapian in the early 1990s: an epidural catheter is placed via
the working port. Local anesthetic is then administered via the catheter (be sure to cut off a multi-orifice end). This
has several advantages: the image is not obscured by the liquid, the stream can be aimed to an area of need, suction
or oxygen can be administered at the same time.

The hardest airways: I am often called by colleagues to advise on the care of patients who have undergone
extensive upper airway surgery and/or radiation. In these patients, invasive blocks may be difficult or impossible
(altered anatomy). Though these can be frightening airways to manage, they are, paradoxically, often the easiest!
1) The patients are usually aware of anesthetists problem, and are motivated and willing to cooperate 2) There is
reduced saliva production vis-a-vis prior radiation and surgical manipulation 3) there is often post-surgical
analgesia.

Sedation: Any number of sedative agents can be used: bezodiazpines, opiods, droperidol, haldo, benedryl. There are
three general rules I follow: 1) judicious titration do not give significant boluses of the drugs. 2) Avoid
polypharmacy stay with one or two agents. 3) Have reversal agents available. Lastly, dont confuse deep sedation
with awake intubation. During AI the patient should be able to 1) cooperate with procedures and 2) control their
own airway (including coughing). As of October, 2008, Dexmedetomideine is FDA approved for sedation in the
unintubated for or prior to a surgical procedure. Several authors have demonstrated good cooperative patient
conditions with use of this agent during aware intubation.
1

407
Page 4
Procrastination: AI is undertaken when the clinician has decided that it is necessary for the wellbeing of the
patient. As such, the above procedures should be executed in a controlled pace and composed environment.
Procrastination is a tongue-in-cheek way of saying, do not hurry to get into the operating room. The OR is a
highly pressured environment, and it is difficult to allow generous time for antisialogoges and topical anesthetics to
reach their therapeutic effect. Of course, the demands of modern medicine hardly allow such luxury but we can
achieve this goal through starting our procedures early: Oxemetazoline is applied and glycopyrolate is injected in the
intake area (IM if an IV is not yet available). Topical anesthetics are begun in the holding area and continued with
the patients stretcher outside the operating room. The patient does not enter the OR until there is some objective
evidence that a block is being achieved (e.g., the patient tolerates an oral airway.)

1. Abdelmalak B, et al. Dexmedetomidine as sole sedative for awake intubation in management of the critical
airway. J Clin Anesth 2007; 19:370373

Disclosure

413
Page 1
Neuromuscular Management and Patient Outcomes
Glenn Murphy, M.D. Chicago, Illinois
Postoperative residual neuromuscular blockade is a common complication observed in the postanesthesia
care unit (PACU) after general anesthesia. Recent large-scale clinical investigations have demonstrated that up to
24% to 42% of surgical patients arrive in the PACU with evidence of incomplete neuromuscular recovery (1,2).
Although most clinicians are now using intermediate-acting muscle relaxants, the risk of residual neuromuscular
block does not appear to be decreasing over time. Most anesthesiologists now accept that train-of-four (TOF) ratios
must recover to at least 0.9 to exclude clinically significant residual block. Accumulating evidence over the past 20
years has demonstrated that surgical patients arriving in the PACU with TOF ratios < 0.9 are at risk for a variety of
adverse outcomes. Several large database studies have shown an association between neuromuscular blocking agent
(NMBA) use and an increased risk of morbidity and mortality in the early period after surgery (3). Recent clinical
trials have demonstrated that residual neuromuscular block in the PACU results in airway obstruction, hypoxemia,
and pulmonary complications during recovery from general anesthesia (3). In addition, patients with residual block
are at risk for unpleasant symptoms of muscle weakness and prolonged PACU admission times (4,5).
Careful management of neuromuscular blockade in the operating room may reduce the incidence of
postoperative residual paralysis. In addition, the complications associated with residual block can be decreased with
appropriate neuromuscular management. Several principles related to NMBA dosing, monitoring, and reversal have
been shown to reduce the risk of incomplete neuromuscular recovery in postoperative patients. Although use of
these techniques has been recommended in editorials and reviews, at the present time there are no published
standards or guidelines defining optimal neuromuscular management strategies. The aim of this review is to
provide a best-available evidence assessment of methods that can be used by clinicians to reduce the risk of
complications due to residual neuromuscular blockade. Seven important and interrelated questions about
neuromuscular management in the operating room will be reviewed. With each question, evidence supporting (or
refuting) each strategy will be discussed. In order to assess which strategies clinicians are actually using in clinical
practice, the results of a recent survey which sent to anesthesiologists in the United States and Europe will be
reviewed (6).
Question 1: Does qualitative neuromuscular monitoring reduce the risk of residual block?
Qualitative neuromuscular monitors are the standard peripheral nerve stimulators available in many
operating rooms. A subjective (qualitative) visual or tactile assessment of a response to peripheral nerve stimulation
is the most common method of neuromuscular monitoring used in the operating room. Three randomized clinical
studies have examined the usefulness of conventional peripheral nerve stimulators in reducing the occurrence of
postoperative residual neuromuscular blockade. Pedersen et al. randomized 80 subjects to receive either TOF
monitoring or no neuromuscular monitoring (clinical criteria such as breathing or moving)(7). Median TOF ratios
of 0.75 and 0.79 were observed in the PACU in the two groups (no difference). In contrast, a similar study by
Shorten et al. demonstrated that the proportion of patients with postoperative TOF ratios < 0.7 was significantly less
in a monitored group (15%) compared to unmonitored patients (47%, P < 0.05)(8). Another randomized trial
demonstrated that tactile evaluation of the response to double-burst stimulation (DBS) reduced, but did not
eliminate, the occurrence of residual paralysis (9). Significantly fewer patients in the monitored group had TOF
ratios < 0.7 (24%) compared to the unmonitored group (57%, P<0.05). A recent meta-analysis examined the effect
of neuromuscular monitoring (qualitative and quantitative) on the incidence of postoperative residual paralysis (10).
Data were analyzed on 11 observational and 13 randomized trials (total of 3,375 patients) published between 1979
and 2005. The authors were unable to demonstrate that the use of monitoring decreased the incidence of residual
paralysis. However, interpretation of the findings is limited by the poor quality of many of the analyzed trials.
Surveys have consistently demonstrated that most clinicians do not routinely monitor patients with
peripheral nerve stimulators in the operating room. In the survey by Naguib et al., 24.3% of European respondents
indicated that qualitative monitoring was not available in their department, and if such monitoring was available, it
was often shared between 2-3 room (62% of respondents)(6).

413
Page 2
Question 2: Does quantitative neuromuscular monitoring reduce the risk of residual block?
Quantitative neuromuscular monitors are devices which allow clinicians to measure and quantify the degree
of neuromuscular block. These monitors will are typically used to measure TOF ratios and display the results on a
screen. Although five different technologies have been developed, only one is commercially available as a stand-
alone unit (the TOF-Watch, an acceleromyography (AMG) device). Four randomized trials have been performed to
examine the effect of AMG monitoring on the incidence of postoperative residual block. In the initial trial by
Mortensen et al, 40 patients were randomized to AMG monitoring or no monitoring. Fifty percent of the patients in
the no monitoring group had TOF ratios < 0.7 in the PACU, compared to only 5.3% in the AMG group
(P<0.005)(11). In a similar study by Gatke et al, 17% of patients in the no monitoring group had residual block
(defined as a TOF < 0.8) compared to only 3% of patients in the AMG group (P<0.005)(12). In the largest study,
185 patients were randomized to receive either standard qualitative monitoring (peripheral nerve stimulator) or
AMG monitoring (TOF-Watch). Thirty percent of patients in the group monitored with a peripheral nerve
stimulator had a TOF ratio < 0.9 in the PACU, versus only 4.5% in the AMG group (P<0.001)(13). In a another
study using AMG monitoring, these same investigators observed a similar reduction in the incidence of residual
block in patients randomized to monitoring with the TOF-Watch (compared to those monitored with a peripheral
nerve stimulator)(14).
Despite high quality studies demonstrating a beneficial effect of quantitative monitoring on the incidence of
postoperative residual neuromuscular blockade, few clinicians routinely use this type of monitoring. In the survey
by Naguib et al., only 22.7% of respondents from the United States reported that quantitative neuromuscular
monitors were available in their departments (6). The reasons why so few clinicians used objective neuromuscular
monitoring were not determined in the survey.
Question 3: Can neuromuscular monitoring impact postoperative recovery?
Although there is evidence that qualitative monitoring can reduce the risk of postoperative residual block,
at the present time there is no data that this type of monitoring improves clinical outcomes. In contrast, there is
emerging evidence that intraoperative quantitative monitoring can beneficially impact postoperative recovery in
surgical patients. In 1995, Mortensen et al. noted that patients randomized to receive AMG monitoring had fewer
clinical signs of muscle weakness in the PACU (11). Studies in awake volunteers have demonstrated an association
between residual block (TOF ratio < 0.9) and adverse respiratory events (4). Murphy et al. examined the effect of
intraoperative AMG monitoring on the incidence of postoperative airway obstruction and hypoxemic events (13).
Patients were randomized to either AMG monitoring or a standard peripheral nerve stimulator (PNS). During
transport from the operating room to the recovery room, a significantly higher incidence of hypoxemia events
(oxygen saturation <90%) and airway obstruction was observed in the PNS group (21.1% and 11.1%, respectively)
compared to the AMG group (0% and 0%, respectively, P<0.001). In addition, the incidence, severity, and duration
of hypoxemic events was significantly less during the first 30 minutes of PACU admission in the AMG group.
Using a similar study design, the authors also examined the effect of AMG monitoring on the presence or absence of
unpleasant symptom of muscle weakness in the PACU (14). Patients randomized to receive AMG monitoring had
significantly fewer symptoms of muscle weakness in the PACU during the first 60 minutes of admission, and overall
quality of recovery at the time of PACU discharge was significantly improved in these patients.
Question 4: Should an anticholinesterase reversal agent be administered to most patients at the end
of surgery?
A number of studies have examined the risk of residual block in the PACU if anticholinesterase reversal
agents are not administered at the conclusion of surgery. These studies have indicated a high risk of incomplete
neuromuscular recovery if reversal agents are omitted. Caldwell et al. examined the incidence of residual block 1-4
hours after a single intubating dose of vecuronium was given (15). Approximately one-half of patients had not
achieved a TOF ratio of 0.9 four hours after the induction dose of vecuronium. In the largest study looking at this
issue, Debaene et al. quantified TOF ratios on arrival to the PACU in 526 patients who received a single intubating
dose of rocuronium, vecuronium, or atracurium and no reversal agent (16). In the cohort that arrived in the PACU
more than 2 hours after receiving the NMBA, 40% had a TOF ratio < 0.9. These and other similar investigations
have demonstrated that the risk of residual neuromuscular block is high if anticholinesterase reversal agents are not
administered.
Surveys have suggested that anticholinesterase reversal agents are not routinely used by anesthesiologists,
and that the use of reversal agents varies significantly from country to country. In the survey by Naguib et al., only
18% of European respondents and 34% of United States respondents noted that they always used an
anticholinesterase agent at the end of surgery.

413
Page 3
Question 5: At what TOF count will neostigmine produce a rapid and reliable reversal?
Several investigations have examined the time required to achieve a TOF ratio of 0.9 or greater when
neostigmine is administered at various levels of neuromuscular block (TOF count of 1-4 with TOF stimulation).
Neostigmine should not be given until there is some evidence of spontaneous neuromuscular recovery (should not
be administered at a TOF count of 0-the concentration of NMBA at the neuromuscular junction is too high to
competitively antagonize). Kim et al reversed patients receiving a sevoflurane anesthetic with neostigmine at a TOF
count of either 1, 2, 3, or 4 (17). At a TOF count of 1, the median time to achieve a TOF ratio of 0.9 was 28.6
minutes (range 8.8 to 75.8 minutes). Even at a TOF count of 4, the median time to achieve a TOF ratio of 0.9 was
9.5 minutes (range 5.1 to 26.4 minutes). The authors noted that beginning with a TOF count of 4, only 55% of
patients had achieved a TOF ratio of >0.9 within 10 minutes. In a similar investigation by Kirkegaard et al., the
times from reversal until achieving a TOF ratio of 0.9 were 20.2 (6.5 to 70.5) minutes at a TOF count of 2 and 16.5
(6.5-143.3) minutes at a TOF count of 4 (18). These studies demonstrate that reversal of neuromuscular blockade is
not rapid with neostigmine (approximately 15 minutes at a TOF count of 4 at the end of surgery). In addition, there
is large variability in reversal times, even at a TOF count of 4.
In the survey by Naguib et al., more than half of the respondents from the United States stated that rapid
and reliable reversal could be achieved at a TOF count of 2 or less. Furthermore, more than half of the European
respondents stated that they typically allow 5 minutes or less between the time of neostigmine administration and
tracheal extubation. These observations may explain why such a high incidence of residual neuromuscular blockade
is observed following tracheal extubation.
Question 6: Are clinical signs reliable indicators of neuromuscular recovery?
In clinical practice, most anesthesiologists use clinical signs of muscle strength to determine whether
neuromuscular function has recovered and tracheal extubation safely performed. Studies in awake volunteers and
postoperative surgical patients have examined the predictive value of these tests in determining whether full muscle
strength (TOF ratio > 0.9) has occurred. The ability to maintain a 5-second head-lift is a commonly-used test of
muscle recovery in the operating room. In a study in which 12 awake volunteers were given an infusion of
rocuronium, 11 of the 12 volunteers were able to maintain a 5-second head-lift at a TOF ratio of 0.5 (19). In another
investigation, 12 awake volunteers were given an infusion of mivicurium (20). At a TOF ratio of 0.5, all of the
volunteers could speak, open their eyes, and protrude their tongues, and 8 of the 12 could maintain a 5-second head-
lift and swallow. In a study by Cammu et al, the sensitivity, specificity, positive predictive value, and negative
predictive value of eight individual tests for detecting residual block (TOF ratio < 0.9) were examined in a cohort of
640 surgical patients (21). None of the eight tests, or combinations of tests, were able to reliable detect the presence
of residual block. These studies demonstrate that clinical signs of muscle strength are insensitive in determining the
presence or absence of incomplete neuromuscular recovery.
Previous surveys have suggested that clinical signs of muscle strength are the primary method used by
clinicians to determine when neuromuscular function has recovered and tracheal extubation performed. In the
survey by Naguib et al., approximately half of the respondents believed clinical signs such as a 5-second head-lift
were reliable indicators of the adequacy of neuromuscular recovery.
Question 7: Can residual neuromuscular block be reliably excluded with conventional peripheral
nerve stimulators (qualitative neuromuscular monitoring?)
A commonly-used method of determining recovery of neuromuscular function is assessing muscular
responses with a standard peripheral nerve stimulator. At the end of anesthesia and surgery, if no fade is detected
withTOF, DBS, or tetanic stimulation, then neuromuscular function is often assumed to be complete. Several
studies have examined this issue. In 1985, Viby-Mogensen measured the ability of anesthesiologists to detect fade
using TOF stimulation at varying levels of neuromuscular blockade (22). Actual TOF values were quantified with
mechanomyography on one arm, and blinded clinicians asked to assess fade with standard peripheral nerve
stimulators on the other arm. The investigators observed that clinicians inexperienced in use of nerve stimulators
were unable to feel fade unless TOF ratios were < 0.3. However, even clinicians experienced in use of nerve
stimulators were unable to feel fade 80% of time when TOF ratios between 0.5 and 0.7. Brull et al. asked blinded
anesthesia attendings and residents asked to identify fade to TOF nerve stimulation in 25 patients (23). TOF ratios
of 0.4-0.7 were achieved with a vecuronium infusion. Tactile assessments failed to identify fade in 55% of cases
when TOF ratios were between 0.4-0.7. When using DBS stimulation, investigators have demonstrated that
anesthesiologists are able to better detect fade when TOF ratios are in the range of 0.3-0.6 (when compared to TOF
stimulation) (24). However, probability analysis has shown that when no fade was detected with either TOF or
DBS, there was still a 47% risk that the true TOF ratio was < 0.7 (25). Similarly, the probability of detecting fade is
low with 50 Hz tetanic stimulation when TOF ratios are > 0.3.

413
Page 4
In the survey by Naguib et al., 20-25% of the respondents stated that it was possible to exclude the presence
of residual neuromuscular block when a sustained response to a 50-Hz tetanic stimulus was observed.
Conclusions and Recommendations
On the basis of surveys that have been published from around the world, there appears to be a significant
difference between published best-evidence practices and the neuromuscular management strategies used by
clinicians in their daily practices. In order to answer the questions posed above, I would like to summarize the
conclusions reached by Brull et al. in a recent evidence based review on residual neuromuscular blockade (26).
1. Does qualitative neuromuscular monitoring reduce the risk of residual block?
Tactile evaluation of TOF and DBS fade reduces (but does not eliminate) the incidence and degree of
postoperative residual paralysis compared with the use of clinical criteria to assess readiness for tracheal
extubation
2. Does quantitative neuromuscular monitoring reduce the risk of residual block?
-To exclude with certainty the possibility of residual paralysis in patients at risk, clinicians should use
objective (quantitative) neuromuscular monitoring tests.
-Ideally, neuromuscular function should be monitored objectively (quantitatively) in all patients receiving
NMBAs
3. Can neuromuscular monitoring impact postoperative recovery?
Available evidence suggests that use of AMG monitoring intraoperatively reduces residual neuromuscular
blockade, signs of muscle weakness, and adverse respiratory events after tracheal extubation
4. Should an anticholinesterase reversal agent be administered to most patients at the end of
surgery?
If no monitoring used -pharmacologic reversal routine
If TOF count 1 -delay reversal
If TOF count 2-3 -pharmacologic reversal routine
If TOF count 4/fade -pharmacologic reversal routine
If TOF count 4/no fade -pharmacologic reversal/! dose
5. At what TOF count will neostigmine produce reliable and rapid reversal?
Adequate spontaneous recovery (TOF count of 4) should be established before pharmacologic antagonism
of NMBA block with anticholinesterases. This requirement does not apply to reversal with sugammadex
6. Are clinical signs reliable indicators of neuromuscular recovery?
Clinical tests of muscle function (head-lift, jaw clenching, grip strength, tidal volume, ect.) are unreliable
predictors of recovery of neuromuscular function.
7. Can residual block be reliably excluded with conventional qualitative nerve stimulators?
Tactile evaluation of TOF and DBS fade reduces (but does not eliminate) the incidence and degree of
postoperative residual paralysis compared with the use of clinical criteria to assess readiness for tracheal
extubation. To exclude with certainty the possibility of residual paralysis in patients at risk, clinicians
should use objective (quantitative) neuromuscular monitoring tests.

413
Page 5
References:
1. Kim KS, et al. Anesth Analg 2002: 95: 1656-60
2. Baillard C, et al. Br J Anaesth 2000; 84: 394-5
3. Kopman AF. Anesthesiology 1997; 87: 1029-31
4. Murphy GS, et al. Anesth Analg 2010:111:129-40
5. Butterly A, et al. Br J Anaesth 2010;105:304-9
6. Naguib M, et al. Anesth Analg 2010;1111:110-9
7. Pedersen T, et al. Anesthesiology 1990;73:835-9
8. Shorten GD, et al. Can J Anaesth 2006;53:130-5
9. Fruergaard K, et al. Acta Anaesthesiol Scand 1998;42:1168-74
10. Naguaib M, et al. Br J Anaesth 2007;98:302-16
11. Mortensen CR, et al. Acta Anaesthesiol Scand 1995;39:797-801
12. Gatke MR, et al. Acta Anaesthesiol Scand 2002;46:207-13
13. Murphy GS, et al. Anesthesiology 2008;109:389-98
14. Murphy GS, et al. Anesthesiology 2011;115:946-54
15. Caldwell JE, et al. Anesth Analg 1995;80:1168-74
16. Debaene B et al. Anesthesiology 2003;98:1042-8
17. Kim KS, et al. Anesth Analg 2004;99:1080-5
18. Kirkegaard H, et al. Anesthesiology 2002;96:45-50
19. Eikermann M, et al. Anesthesiology 2003;98:1333-7
20. Heier T, et al. Anesthesiology 2010;113:825-33
21. Cammu G, et al. Anesth Analg 2006;102:426-9
22. Viby-Mogensen J, et al. Anesthesiology 1985;63:440-3
23. Brull SJ, et al. Anesth Analg 1993;77:352-5
24. Brull SJ, et al. Anesth Analg 1991;73:627-32
25. Drenck NE, et al. Anesthesiology 1989;70:578-81
26. Brull SJ, et al. Anesth Analg 2010;111129-40
Disclosure
Merck, Consulting Fees, Honoraria
419
Page 1
Trauma Anesthesia
Albert J. Varon, M.D., MHPE Miami, Florida
Introduction
Almost one out of every 10 deaths in the world is the result of injury. In the U.S., trauma is the leading cause of
death among children, adolescents and young adults, and accounts for more years of potential life lost than cancer
and heart disease combined. Although few anesthesiologists care exclusively for trauma patients, most
anesthesiologists care for trauma patients at one time or another in their clinical practice. This presentation will
provide a concise review of the essential elements in the management of the severely injured trauma patient and
identify new trends in trauma and anesthesiology practices that impact the care of these patients.
Initial Evaluation and Management
Active participation of anesthesiologists in the care of the most severely injured patients is essential for improved
outcome and represents an opportunity to highlight the anesthesiologists role as a perioperative physician. The
immediate care required by most severely injured patients is best managed with a multidisciplinary team. As part of
this team, the anesthesiologist can contribute to evaluation and resuscitation while gathering information needed for
anesthetic management.
The Advanced Trauma Life Support (ATLS) course developed by the Committee on Trauma of the American
College of Surgeons helps physicians maximize their resuscitative efforts and avoid missing life-threatening injuries
by using an organized approach in trauma care. Although few anesthesiologists participate in these courses,
familiarity with ATLS guidelines facilitates more effective participation in the trauma resuscitation team and allows
the formulation of airway and perioperative management plans.
The ATLS model consists of four components: a rapid primary survey, simultaneous resuscitation of vital functions,
a more detailed secondary survey, and initiation of definitive care.
Primary Survey. The primary survey involves rapid evaluation and stabilization of the functions that are crucial to
survival: Airway maintenance with cervical spine protection, Breathing and ventilation, and Circulation with
hemorrhage control. This is followed by a brief neurologic exam (Disability) and complete removal of the patients
clothes to search for injuries (Exposure) while preventing hypothermia (Environment). During this phase, life-
threatening conditions are identified and treated simultaneously.
Resuscitation. Simultaneous resuscitation follows the same ABC sequence. A definitive airway (i.e., tracheal
intubation) should be established if there is a need for airway protection or a need for ventilation or oxygenation.
The airway is secured with continuous protection of the cervical spine. This is most frequently achieved by rapid
sequence tracheal intubation (discussed below). Confirmation of tracheal intubation by auscultation and
capnography is followed by assisted ventilation. Bleeding from external wounds is usually controlled by direct
pressure and circulation restored by volume expansion with warm intravenous (IV) fluids. A minimum of two large-
caliber IV catheters should be inserted, preferable in the upper extremities. At the time of IV insertion blood can be
drawn for type and crossmatch and baseline hematologic tests including pregnancy test (when applicable). Monitors
used during the primary survey and resuscitation phases include electrocardiography, blood pressure monitoring,
pulse oximetry, and capnography (or CO
2
colorimetry) in intubated patients. Placement of urinary and gastric

419
Page 2

catheters is also considered part of the resuscitation phase. Essential laboratory and radiologic examinations
(portable AP chest and pelvis) can be performed immediately after the primary survey but should not delay patient
resuscitation.

Ultrasound has become an intrinsic component in the evaluation of trauma patients. Focused assessment sonography
in trauma (FAST) is a useful exam for the quick detection of intraperitoneal or pericardial fluid after blunt or
penetrating injury. More recently, ultrasound scanning has also been used to rapidly identify pneumothorax or the
presence of organized cardiac activity.

Secondary Survey. The secondary survey involves obtaining a history and a more extensive and systematic (head-
to-toe) examination aimed at identifying additional injuries. This information also constitutes the basis for the
preoperative anesthetic evaluation. The mnemonic AMPLE is useful when obtaining the trauma patients history. A
stands for known allergies, M for medications currently taken, P is for past illnesses/surgery or pregnancy, L for
timing and contents of last meal, and E stands for events and environment related to the injury. The complete
topographic examination of the patient at this stage should include a neurologic exam and determination of the
Glasgow Coma Scale (GCS) score, if it was not performed during the primary survey. Specialized diagnostic tests to
identify specific injuries may also be conducted during the secondary survey. Tests may include computed
tomography (CT) imaging of the head, cervical spine, chest, abdomen, and pelvis, followed by x-ray examination of
the injured extremities, as indicated by the patients injuries. Although establishing the type and severity of injuries
is a surgical task, the anesthesiologist must maintain constant communication with the surgeon to anticipate the
course of action and anesthetic implications. The effects of the measures initiated during the primary survey (airway
patency, ventilation, perfusion) should be frequently reassessed during this and all other phases of management.

Definitive Care. After the completion of the secondary survey, a decision must be made as to the type and location
of subsequent management. Patients that require immediate surgical intervention are taken to the operating room.
Some patients may require surgery to control the adverse consequences of injury before the secondary survey is
completed. In such cases the anesthesiologist plays an important role in the identification of additional injuries.
Patients that require support and monitoring are transferred to the intensive care unit. If definitive care cannot be
provided at a local hospital, the patient should be transferred to a facility that has the resources to care for the
patient.

Airway Management

Airway management of trauma patients may take place in a variety of settings. This may occur in a designated
resuscitation area, emergency department (ED), operating room (OR), intensive care unit (ICU), CT imaging suite,
or in the pre-hospital setting.

Before a patients arrival, pre-hospital emergency personnel can convey important information. This includes
mechanism of injury, patients age, GCS score, vital signs, and estimated time of arrival, all of which can aid in
preparation and planning. Upon a patients arrival, immediate assessment of ventilatory status is essential. A simple
question such as What is your name? can provide a wealth of information. A positive, appropriate verbal response
indicates that the airway is open, ventilation is intact, and that circulation is adequate for brain perfusion. On the
other hand, an incoherent or absent response should alert the clinician that one or several issues may be present. If
airway or breathing is of concern, the anesthesiologist should immediately prepare to secure the patients airway.

Indications for tracheal intubation. The latest ATLS guidelines (2012) list the following as indications for
securing an airway in the trauma setting:

Need for ventilation or oxygenation Need for airway protection
Inadequate respiratory efforts
Massive blood loss
Severe head injury (GCS!8)
Apnea
Severe maxillofacial fractures
Risk for obstruction
Risk for aspiration
Unconscious

419
Page 3

In addition to the above, tracheal intubation is sometimes performed for other reasons such as to prevent a patient
from self-harm or to allow proper medical evaluation; the literature has listed these as discretionary indications for
tracheal intubation.

Tracheal tube placement should include adequate preoxygenation, rapid-sequence induction (RSI), cricoid pressure
(CP), and in-line cervical spine stabilization (when indicated). Confirmation of correct tracheal tube placement may
occur by several methods including end-tidal carbon dioxide by capnography (or if unavailable, by semi-quantitative
colorimetry), bilateral breath sounds, absence of gastric sounds, bilateral chest expansion, fogging of the tracheal
tube, maintenance of oxygenation by pulse oximetry, direct confirmation by fiberoptic endoscopy, or direct
visualization of lung expansion during emergency thoracotomy. When perfusion is present, capnography is the most
reliable method for confirmation of tracheal tube placement.

Rapid sequence induction (RSI). RSI is the most commonly used method for securing a definitive airway in
trauma patients. This technique has been associated with high intubation success rates and low complication rates in
emergency and trauma intubations.

Pre-oxygenation before induction should take place whenever possible. This may be difficult in situations where a
patient is uncooperative, combative, or has severe facial deformities that impede proper mask seal. When
preoxygenation is inadequate or not possible, bag-valve-mask (BVM) ventilation (while applying cricoid pressure)
should be used to maintain oxygenation during induction. This is especially important in patients with traumatic
brain injury, where maintenance of oxygenation takes precedence over the potential risk of aspiration if BVM
ventilation results in stomach insufflation. Therefore, it seems prudent to provide small positive pressure breaths
during RSI to patients at risk of prompt oxygen desaturation.

Anesthetic agents and neuromuscular blockings drugs for RSI. All of the commonly used induction drugs have
been used in the trauma setting including propofol, etomidate, midazolam, and ketamine (thiopental is currently not
being manufactured in the U.S.). Use of these agents commonly results in amnesia and intubating conditions within
3060 seconds. Propofol may cause profound hypotension in hypovolemic patients and therefore its dose needs to
be significantly reduced if used for RSI in these patients. Etomidate has the advantage of inducing less
hemodynamic changes in comparison to other induction agents. Although some clinicians have challenged the use
of etomidate for RSI due to the concern that it can induce adrenal suppression, it remains the most frequently used
agent for RSI outside of the OR. Ketamine may cause tachycardia and hypertension from endogenous catecholamine
release, which may be advantageous in the trauma setting. However, concerns of myocardial depression in the
catecholamine-depleted patient, increased intracranial pressure, and increased intraocular pressure may be important
considerations when selecting this drug. It is important to recognize that in the multiple-trauma patient, who is often
in extremis, conventional drug doses of any of these induction agents have the potential for causing hypotension and
cardiovascular collapse. Therefore, when determining which and how much agent is most appropriate, drug dosage
may be more important than the specific medication.

Most neuromuscular blockers (NMB) can be used for rapid sequence intubation if a large enough dose is given. In
clinical practice, the two medications most often used are succinylcholine (depolarizing NMB) and rocuronium
(non-depolarizing NMB). Succinylcholine has withstood the test of time as the most reliable NMB drug for fast and
ideal intubating conditions. Although acute burns and acute paralysis are not contraindications to the use of
succinylcholine, it should not be administered after 24 hours of sustaining such injuries due to the risk of
hyperkalemia. Succinylcholine is also contraindicated if severe hyperkalemia is suspected (e.g., rhabdomyolysis,
renal failure). The recommended dose of succinylcholine for RSI has been cited to be at least 0.6 mg/kg to achieve
ideal intubating conditions within 60 seconds. Common practice includes a range of 1.01.5 mg/kg. Increasing the
dose of succinylcholine above 0.6 mg/kg may not provide better intubating conditions, but will provide faster and a
longer lasting muscle relaxant effect. If a muscle relaxant is needed and there is concern about the capability to
ventilate or intubate, one may prefer to use the smallest possible dose that provides adequate relaxation and avoid
long-lasting blockade. However, patients could still be at risk of hypoxemia if there were failure to intubate and
ventilate, regardless of the dose of succinylcholine administered. The availability of a non-depolarizing NMB drug
for RSI is imperative in the trauma setting, since succinylcholine may be contraindicated in certain patients. A
rocuronium dose of 0.91.2 mg/kg will provide adequate intubating conditions within 60 seconds of administration.

419
Page 4

An alternative plan for securing the airway and ensuring ventilation (including the use of a surgical airway) must be
formulated before proceeding with RSI.

Cricoid pressure. The effectiveness of cricoid pressure (CP) in preventing aspiration continues to be debated.
Recently published guidelines from organizations other than the American Society of Anesthesiologists (ASA) have
recommended eliminating its use or consider it an optional measure. Despite these trends, CP continues to be the
standard for rapid-sequence induction in the U.S. due to its low risk/benefit ratio. In a recent national survey of
teaching hospitals, 91 percent of participants indicated the use of CP as part of their modified RSI technique.
Furthermore, the most recent ATLS guidelines include cricoid pressure as a component of RSI. It is the authors
opinion that CP should be applied throughout induction and attempts at intubation in trauma patients. However, if
necessary, CP should be altered or removed to ease intubation or insertion of a laryngeal mask airway because
securing the airway and providing ventilation should take precedence over the potential risk of aspiration.

Cervical spine immobilization. The incidence of cervical spine injury associated with major trauma is 25%, but it
is 10% in comatose patients. Given the fact that the largest forces are applied to the cervical spine at the time of
injury, it is unlikely that airway intervention will result in subsequent neurological deterioration. However, because
of the potential devastating consequences of spinal cord injury, measures need to be taken to avoid further damage.
The use of cervical spine manual in-line stabilization (MILS) is recommended by ATLS guidelines and is
commonly applied in patients with suspected cervical injury. Cervical collars do not reliably immobilize the neck
during intubation and may significantly limit mouth opening. Therefore, after induction the anterior portion of the
collar is temporarily removed to improve mouth opening and facilitate airway management. The safety and
effectiveness of MILS has been demonstrated in observations on uninjured patients, cadaver studies, and large
retrospective case series. Although the use of MILS has recently come into question, there are no outcome data
suggesting that direct laryngoscopy with MILS is inferior to any other intubation method, including fiberoptic
intubation. However, the benefits of MILS must be balanced against the potential for hypoxic damage if intubation
and ventilation cannot be accomplished. Therefore, as was noted for CP, MILS may be reduced if its use impedes
tracheal intubation.

ASA difficult airway algorithm modified for trauma. The American Society of Anesthesiologists (ASA)
difficult airway algorithm offers an excellent guideline for the approach to the difficult airway and can easily be
modified for trauma patients (http://www.asahq.org/For-Members/About-ASA/ASA-Committees/Committee-on-
Trauma-and-Emergency-Preparedness.aspx). These modifications are necessary because the urgency and
circumstances of the trauma setting may require deviations from the original algorithm. Trauma patients may be
uncooperative or unstable for awake intubation and therefore may be automatically allocated into the intubation after
induction category. If noninvasive methods to secure the airway are unsuccessful, invasive airway access may be the
only other alternative since awakening the patient or canceling the case is rarely an option. Establishing an
institutional trauma airway protocol that takes into consideration available personnel and resources may enhance the
safety and effectiveness of airway management in trauma patients.

Role of video laryngoscopy. A variety of video laryngoscopes are currently available. Their popularity is due to
their increased ability to improve the laryngoscopic view (when compared to the direct approach) and increased
portability. Although video laryngoscopes have shown to provide better glottic view than other devices, this does
not always translate into an easier intubation. Intubation may still be difficult despite a good view because the tube
or stylette insertion path may not line up with the view obtained by the video laryngoscope. In addition, the presence
of blood, emesis, or airway injury may disrupt the video laryngoscopic view. Another potential difficulty is the oral
insertion of fixed-angle video laryngoscopy devices (e.g., Glidescope) in patients receiving MILS. Although the
advent of video laryngoscopes continues to expand the armamentarium of the airway specialist, these devices have
not yet replaced direct laryngoscopy in the trauma setting.

Tracheal tube introducers. The Eschmann tracheal tube introducer (often incorrectly referred to as a "gum elastic
bougie) has a coude tip that allows the anesthesiologist to advance the introducer into the trachea despite a limited
glottic view, which may be common in the trauma setting due to MILS or CP. The incorporation of this device into
ATLS is the result of its success in aiding to secure a difficult airway in other settings. Many institutions have
incorporated algorithms that include a bougie if a tracheal tube cannot be inserted on the first attempt.

419
Page 5

The Aintree intubation catheter (Cook Medical Inc, Bloomington, USA) may be used as a bridge to convert a
supraglottic airway into a secure airway with a tracheal tube. One of the main characteristics of an Aintree catheter
is its hollow center, which can accommodate a flexible fiberoptic scope or allow oxygen insufflation. This
introducer is shorter than conventional hollow catheters that serve as airway exchange catheters. Due to its shorter
length, it allows a fiberoptic scope to protrude through it and offer visibility beyond the catheter.

Supraglottic airways. The use of supraglottic devices has greatly increased in the last 25 years and their use has
now been incorporated into ATLS. In the trauma setting, supraglottic airways are most frequently encountered when
patients arrive in the ED. The laryngeal mask airway (LMA), esophageal-tracheal combitube, and the laryngeal tube
airway (LTA) are examples of airway devices commonly used by pre-hospital personnel. Anesthesiologists must
recognize these airways, know their function and capabilities, determine if they provide adequate ventilation, and
have the skill set to safely exchange them for a definitive airway. This may entail removal of the supraglottic airway
followed by tracheal intubation, use of an LMA as a conduit for fiberoptic tracheal intubation, use of an Aintree
catheter to remove the supraglottic airway followed by tracheal intubation over the catheter, or leaving the
supraglottic airway in place to provide ventilation until a surgical airway can be emergently obtained. Although a
detailed discussion of supraglottic airways is beyond the scope of this presentation, an excellent review of this topic
can be found in the references provided.

Fiberoptic endoscopy. The fiberoptic bronchoscope (FOB) is the most versatile of the intubating tools currently
available. With patient cooperation and adequate anesthetic topicalization the airway can be secured in a safe
manner in most cases. This is especially important in patients with suspected cervical spine or airway injury.
Unfortunately, awake intubation can only be performed in a small number of trauma patients. Many times the reason
a patient requires tracheal intubation is the same reason an awake intubation is impractical (e.g., combative,
hemodynamically unstable, soiled oropharynx). Asleep fiberoptic intubations are infrequently performed in the
trauma setting due to the risk of aspiration, except when used as a rescue technique (e.g., through an LMA) or as
part of a rapid tracheal inspection and intubation in patients with penetrating neck injury.

Management Priorities in Multiple Trauma

Setting priorities in the management of patients with multiple injuries is difficult and will depend on the likelihood
that these injuries will impact survival or functional outcome.

Head CT imaging versus emergent laparotomy. In hypotensive patients with a diminished level of consciousness
after blunt trauma it may be challenging to decide whether to proceed with immediate head CT imaging or urgent
laparotomy. Although head CT imaging may precede surgery in injured patients who respond to initial resuscitation,
demonstration of a large intraperitoneal fluid accumulation during initial sonography assessment in combination
with unstable vital signs should lead to immediate laparotomy. Anesthesiologists play a significant role expediting
the care and transfer of these patients to the OR.

Cervical spine clearance. Patients that sustain blunt trauma should be evaluated for cervical spine injury and if
cleared, their cervical collars removed. Radiologic imaging is not necessary in alert trauma patients without
distracting injury, neurologic deficit, or neck pain or tenderness on full range of motion of the cervical spine. All
other patients in whom cervical spine injury is suspected must have imaging studies. Computed tomography (CT)
has replaced plain radiography as the primary technique for screening suspected cervical spine injury. Controversy
persists regarding cervical spine clearance in the obtunded patient. Options include leaving the cervical collar in
place until a clinical exam can be performed, removing the collar on the basis of CT alone, or obtaining a magnetic
resonance imaging (MRI) study. In the trauma setting, it is often not possible to obtain cervical spine clearance
before airway intervention due to the need for urgent life or limb saving surgical procedures, or due to the inability
to clear the spine when a patients altered sensorium or distracting pain interferes with clinical evaluation. In these
patients RSI with MILS followed by direct laryngoscopy and oral intubation appears to be safe.

Timing of bone fracture fixation. The optimal timing of surgical stabilization of fractures in the patient with
multiple injuries is controversial. Early (<24 h) fixation of long-bone fractures may reduce pulmonary
complications, length of mechanical ventilation, and duration of ICU and hospital stay. However, unstable patients
with multiple injuries or traumatic brain injury (TBI) should be resuscitated and adequately stabilized before

419
Page 6

receiving definitive orthopedic care. In such patients debridement and temporary fixation of fractures using external
fixators, followed by definitive fixation (when physiological parameters have stabilized), may increase their chance
for survival. Factors that should be considered when assessing the appropriateness of early fracture fixation include
severity of brain injury, degree of pulmonary dysfunction, presence of hypotension, hypothermia or coagulopathy,
and the patients response to initial resuscitation interventions.

Damage control. In the U.S. Navy, the term damage control (DC) is used for the emergency control of situations
that may hazard the sinking of a ship. In the context of trauma the term refers to providing only interventions
necessary to control hemorrhage and contamination and focusing on reestablishing a survivable physiologic status.
This approach consists of a rapid abbreviated laparotomy to stop hemorrhage and peritoneal contamination, and
staged sequential repair. Patients would then undergo continued resuscitation and aggressive correction of the lethal
triad of coagulopathy, hypothermia and acidosis in the ICU before returning to the OR for definitive repair.
Retrospective studies have reported that this strategy is associated with better than expected survival rates for major
abdominal trauma. However, there are no randomized control studies comparing the efficacy of damage control
laparotomy with traditional laparotomy.

Based on the DC strategy for abdominal injuries, similar principles have been applied to the management of
multiply injured patients with associated long bone and pelvic fractures (i.e., damage control orthopedics) or with
traumatic brain injury (i.e., damage control neurosurgery). Damage control orthopedics (see section above)
represents a safer initial approach in unstable patients by significantly decreasing the initial operative exposure and
blood loss. Damage control neurosurgery involves stopping intracranial bleeding, evacuation of intracranial
hematomas, and early surgical debridement to limit wound contamination. Although damage control neurosurgery
may also include decompressive craniectomy, surgical reduction of intracranial pressure has not resulted in better
outcomes in patients with severe TBI.

Damage Control Resuscitation

Damage control resuscitation (DCR) is a concept that has been made popular by the military and is now being used
in the civilian trauma setting. DCR attempts to couple the surgical control of life-threatening injury with earlier and
more aggressive correction of the conditions that exacerbate hemorrhage in trauma patients. DCR includes the use of
blood products over isotonic fluid for volume replacement, permissive hypotension (hypotensive resuscitation),
and rapid and early correction of coagulopathy with component therapy. This resuscitation strategy begins in the
prehospital and ED settings and continues through the OR and ICU until the resuscitation is complete.

Volume replacement. Control of bleeding and fluid resuscitation with crystalloid and blood products are the
mainstays of therapy for trauma patients with hemorrhagic shock. However, aggressive fluid resuscitation before the
bleeding is controlled can be detrimental, as the increased blood pressure and circulating volume may result in clot
disruption and reversal of compensatory vasoconstriction. In addition, the dilution of clotting factors from excessive
crystalloid administration may worsen the coagulopathy often present in severely injured patients. Overly aggressive
crystalloid resuscitation in patients requiring massive transfusion has been associated with a higher risk of acute
respiratory distress syndrome, abdominal compartment syndrome, and multiple organ failure. Therefore one of the
strategies in DCR is the use of blood products over isotonic fluid for volume replacement in the trauma patient with
massive hemorrhage. Artificial colloids have not been associated with an improvement in survival in trauma patients
and because they are more expensive than crystalloids some have suggested that their continued use in civilian
trauma patients cannot be justified.

Hypotensive resuscitation. Over the past few years, an alternative to high-volume fluid resuscitation termed
hypotensive resuscitation has been actively investigated in the trauma setting. In contrast to standard fluid
resuscitation, this strategy uses less fluids and blood products during the early treatment of hemorrhagic shock.
Animal studies indicate that hypotensive resuscitation reduces blood loss and transfusion requirements in both blunt
and penetrating trauma. However, in human studies, decreased blood loss and transfusion requirements have only
been confirmed in penetrating injury. The evidence supporting hypotensive resuscitation in patients with blunt
trauma or traumatic brain injury is limited and the overall long-term outcome of this fluid resuscitation strategy has
not been determined. Concerns about the use of hypotensive resuscitation include the possibility of cardiac arrest (if
small volumes of fluid are insufficient to prevent exsanguination) and late complications from organ damage

419
Page 7

sustained during hypotension. Recommendations based on expert opinion and the results of the above studies
suggest titrating fluid to restore consciousness, radial pulse, and a systolic blood pressure of 8090 mmHg until
major bleeding has been stopped. Fluid treatment is aimed to a mean arterial pressure of at least 80 mmHg in
patients with combined hemorrhagic shock and severe head trauma.

Blood component therapy. Hemorrhage is the most common cause of shock and preventable early death in trauma
patients. Traditional therapy for hemorrhagic shock consists of crystalloid and packed red blood cell (PRBC)
resuscitation with the subsequent use of fresh frozen plasma (FFP) and platelets as indicated by the patients
evolving condition and laboratory data. Over the past few years this therapy has being replaced by earlier and more
liberal use of FFP during massive blood transfusion. In many trauma centers the use of a 1:1 ratio of FFP to PRBC
has been implemented based on observational studies that reported a survival advantage associated with the
administration of relatively higher FFP:PRBC ratios. However, the apparent survival advantage associated with high
FFP:PRBC transfusion ratios could be explained by a survival bias. Because component blood products are not
administered evenly and simultaneously in clinical practice, and many deaths occur early, it is possible that the
survival benefit observed among patients receiving higher FFP:PRBC ratios may merely reflect the fact that they
live long enough to receive the higher ratio of products. Without randomized controlled trials controlling for
survivor bias, the available evidence supporting higher FFP:PRBC ratios is inconclusive. Currently, American and
European evidence-based guidelines recommend early intervention with FFP but without a preset FFP:PRBC ratio.
The Pragmatic Randomized Optimum Platelet and Plasma Ratio (PROPPR) trial is an ongoing large multicenter trial
that will evaluate different blood product ratios to be administered to trauma patients in need of massive transfusion
and offer an opportunity to determine the ideal ratio (http://cetir-tmc.org/research/proppr).

Massive-transfusion protocols. In addition to providing continued resuscitation and anesthesia care,
anesthesiologists are closely involved with ordering blood products for patients receiving massive transfusion (>10
units PRBC in 24-hour period). Efforts to obtain a continuous and sufficient supply of blood products require
valuable time; communication breakdowns may result in inappropriate or insufficient products for patient
requirements. Several institutions have shown that predefined massive transfusion protocols (MTP) can be
successfully implemented and have a positive impact on patient outcome. The purpose of such protocols is to
provide blood products in an immediate and sustainable manner to patients with hemorrhagic shock. The MTP is
usually initiated by a single phone call to the blood blank by an attending surgeon or anesthesiologist. The blood
bank will provide a continuous supply of blood products (PRBC, FFP, platelets and cryoprecipitate) in a
predetermined sequence, quantity, and ratio until the attending physician calls again to stop. The requirement for
uncross-matched blood during acute resuscitation or the presence of at least 2 out of 4 specific bedside parameters
(penetrating mechanism, ED systolic blood pressure <90 mm Hg, ED heart rate >120 bpm, positive FAST) can help
predict the need for massive transfusion. Although no prospective trial outcome data is available, anesthesiologists
and trauma surgeons have found MTPs to be more efficient than traditional blood bank delivery methods and that
they relieve anesthesia and OR personnel from worrying about the availability of blood supplies while caring for a
severely injured patient. Sample MTPs can be found on ASAs website (http://www.asahq.org/For-Members/About-
ASA/ASA-Committees/Committee-on-Blood-Management/MTP-for-Hemorrhagic-Shock.aspx).

Hemostatic Agents

Although the etiology of the coagulopathy associated with trauma is multifactorial, the primary factors appear to be
tissue injury and shock with systemic hypoperfusion. Endothelial activation of protein C is a central mechanism of
the acute traumatic coagulopathy, which is characterized by global anticoagulation and hyperfibrinolysis. As shock
progresses and fluid therapy is initiated, hemodilution exacerbates these hemostatic derangements. Further blood
loss, consumption of clotting factors, acidemia, and hypothermia also exacerbate the deranged coagulation response.
Although FFP, platelets, and cryoprecipitate are considered mainstay hemostatic therapies, there has been an
increased interest in the use of other hemostatic agents for the treatment of acute traumatic coagulopathy. These
include the use of recombinant activated factor VII, prothrombin complex concentrates, fibrinogen concentrate, and
the antifibrinolytic lysine analogue tranexamic acid.

Recombinant activated factor VII (rFVIIa) is thought to act locally at the site of tissue injury by binding to exposed
tissue factor and generating a tight fibrin hemostatic plug through increased thrombin generation. Although initial

419
Page 8

observational reports on the use of rFVIIa in traumatic hemorrhage were quite positive, prospective randomized
trials showed no survival benefit.

Prothrombin complex concentrates (PCCs) contain the vitamin K-dependent coagulation factors II, VII, IX, and X.
PCCs are used for the urgent reversal of vitamin K antagonist anticoagulation (e.g., warfarin) in adults with acute
major bleeding. When compared to FFP, PCCs provide quicker INR correction, have smaller infusion volume, and
do not require cross-matching. Nevertheless, no prospective controlled studies have investigated the effectiveness
and safety (i.e., thrombotic complications) of PCCs as a first-line therapy for acute traumatic coagulopathy.

Encouraging reports have been published on the use of fibrinogen concentrate as a hemostatic agent in bleeding
trauma patients. However, the clinical utility of fibrinogen concentrate in the trauma setting remains unclear.

Tranexamic acid (TXA) is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity. As a
lysine analogue, TXA occupies the lysine-binding sites on plasminogen inhibiting its binding to fibrin and impairing
fibrinolysis. The cost of TXA is drastically lower than that of rFVIIa and the PCCs. More importantly, this is the
only drug with prospective clinical evidence to support its use in bleeding trauma patients. A prospective
randomized placebo-controlled trial (CRASH-2) investigated the effectiveness of TXA (1 g loading followed by 1 g
over 8 h) in 20,211 trauma patients. This multicenter study demonstrated significant reductions in all-cause mortality
and in deaths due to bleeding in the TXA group, compared to the placebo group. Further analysis by the
investigators revealed that the benefit was only seen when TXA was administered within 3 h of injury and that
increase mortality occurred when the drug was given after this period. More recently, the Military Application of
Tranexamic Acid in Trauma and Emergency Resuscitation study (MATTERs) evaluated the use of TXA in
hemorrhagic shock after combat injury. This retrospective analysis of U.S. and U.K. military trauma registries
reported that the unadjusted mortality was lower in the TXA group, despite being more severely injured. Patients
who received massive transfusion benefited the most from the administration of TXA, with improved survival and
reduced coagulopathy. This inexpensive drug is now being incorporated into trauma clinical practice guidelines and
treatment protocols.

Coagulation Monitoring

Evidence is accumulating for the use of coagulation testing to identify trauma-induced coagulopathy and guide
management. Conventional coagulation tests such as PT, PTT, fibrinogen and platelet count involve substantial time
delays, provide limited details on clot formation, and are unable to identify or quantify the degree of platelet
dysfunction. In contrast, viscoelastic hemostatic assays such as rapid thromboelastography (TEG) or rotation
thromboelastometry (ROTEM) can rapidly identify and functionally characterize trauma-induced coagulopathy.
These assays measure clot formation and dissolution and identify coagulopathies secondary to dilution,
consumption, deficiencies, and hyperfibrinolysis. Recent studies in trauma patients have reported on the benefit of
using viscoelastic coagulation tests to rapidly identify coagulopathy, predict increased transfusion requirements and
mortality, and guide blood component and antifibrinolytic therapy. However, further studies are needed to validate
the use of viscoelastic hemostatic assays in the trauma setting.

References

1. American College of Surgeons Committee on Trauma. Advanced Trauma Life Support. 9th Edition. Chicago:
American College of Surgeons, 2012.
2. ATLS Subcommittee, American College of Surgeons Committee on Trauma, and the International ATLS
working group. Advanced trauma life support (ATLS): The ninth edition. J Trauma Acute Care Surg
2013;74:13631366.
3. Berkow LC, Schwartz JM, Kan K, et al. Use of the laryngeal mask airway-Aintree intubating catheter-fiberoptic
bronchoscope technique for difficult intubation. J Clin Anesth 2011;23:534539.
4. Bickell W, Wall M, Pepe P, et al, Immediate versus delayed fluid resuscitation for hypotensive patients with
penetrating torso injuries. N Engl J Med 1994;331:11051109.
5. Bolliger D, Gorlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage
and hemodilution. Anesthesiology 2010;113:10161018.

419
Page 9

6. Brenner M, Stein DM, Hu PF, eta al. Traditional systolic blood pressure targets underestimate hypotension-
induced secondary brain injury. J Trauma Acute Care Surg 2012;72:11359.
7. Brohi K, Cohen MJ, Davenport RA, et al. Acute coagulopathy of trauma: mechanism, identification and effect.
Curr Opin Crit Care 2007;13:680685.
8. Center for Disease Control and Prevention. Ten leading causes of death and injury.
http://www.cdc.gov/injury/wisqars/LeadingCauses.html [Accessed 22 May 2013].
9. Cirocchi R, Montedori A, Farinella E, et al. Damage control surgery for abdominal trauma. Cochrane Database
Syst Rev 2013 Mar 28;3:CD007438.
10. Cohen MJ, Call M, Nelson M, et al. Critical role of activated protein C in early coagulopathy and later organ
failure, infection and death in trauma patients. Ann Surg 2012;255:37985.
11. Cook TM, Hagberg CA. Non-laryngeal mask airway supraglottic airway devices. In: CA Hagberg (ed)
Benumof and Hagbergs Airway Management, 3rd edition. Elsevier, St. Louis, pp. 466-507, 2012.
12. Cotton BA, Dossett LA, Haut ER, et al. Multicenter validation of a simplified score to predict massive
transfusion in trauma. J Trauma 2010;69:S33S39.
13. Cotton BA, Faz G, Hatch QM, et al. Rapid thrombelastography delivers real-time results that predict transfusion
within 1 hour of admission. J Trauma 2011;71:407414.
14. CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood
transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.
Lancet 2010;376:2332.
15. CRASH-2 trial collaborators. The importance of early treatment with tranexamic acid in bleeding trauma
patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377:1096101.
16. Crosby ET. Airway management in adults after cervical spine trauma. Anesthesiology 2006; 104:1293318.
17. Cureton EL, Yeung LY, Kwan RO, et al. The heart of the matter: utility of ultrasound of cardiac activity during
traumatic arrest. J Trauma Acute Care Surg 2012;73:102110.
18. Curry N, Davis PW. Whats new in resuscitation strategies for the patient with multiple trauma? Injury
2012;43:10211028.
19. Davenport R, Manson J, De'Ath H, et al. Functional definition and characterization of acute traumatic
coagulopathy. Crit Care Med 2011;39:26522658.
20. Davenport R. Pathogenesis of acute traumatic coagulopathy. Transfusion 2013;53:23S27S.
21. Dente CJ, Shaz BH, Nicholas JM, et al. Improvements in early mortality and coagulopathy are sustained better
in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma
center. J Trauma 2009;66:16161624.
22. Diez C, Varon AJ. Airway management and initial resuscitation of the trauma patient. Curr Opin Crit Care
2009;15:542547. 25.
23. Duchesne JC, Kimonis K, Marr AB. et al. Damage control resuscitation in combination with damage control
laparotomy: A survival advantage. J Trauma 2010;69:4652.
24. Duchesne JC, McSwain NE, Cotton BA, et al. Damage control resuscitation: The new face of damage control. J
Trauma 2010;69:976990.
25. Ehrenfeld JM, Cassedy EA, Forbes VE, et al. Modified rapid sequence induction and intubation: a survey of
United States current practice. Anesth Analg 2012;115:95101.
26. El-Orbany M, Connolly LA. Rapid sequence induction and intubation: Current controversy. Anesth Analg
2010;110:13181325.
27. Goodnough LT, Shander A. Current status of pharmacologic therapies in patient blood management. Anesth
Analg 2013;116:1534.
28. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope video-laryngoscopy versus direct laryngoscopy for
endotracheal intubation: a systematic review and meta-analysis. Can J Anaesth 2012;59:4152.
29. Grissom TE, Varon AJ. Airway management controversies in trauma care. ASA Newsl 2013;77(4):1214.
30. Hauser CJ, Boffard K, Dutton R, et al. Results of the CONTROL Trial: Efficacy and safety of recombinant
activated factor VII in the management of refractory traumatic hemorrhage. J Trauma 2010;69:489500.
31. Ho AM, Dion PW, Yeung JH, Holcomb JB, et al. Prevalence of survivor bias in observational studies on fresh
frozen plasma:erythrocyte ratios in trauma requiring massive transfusion. Anesthesiology 2012;116:716728.
32. Holcomb JB, Del Junco DJ, Fox EE, et al. The prospective, observational, multicenter, major trauma
transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks.
JAMA Surg 2013;148:127136.

419
Page 10

33. Holcomb JB, Gumbert S. Potential value of protocols in substantially bleeding trauma patients. Curr Opin
Anaesthesiol 2013;26:215220.
34. Holcomb JB, Minei KM, Scerbo ML, et al. Admission rapid thrombelastography can replace conventional
coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg
2012;256:476486.
35. Inaba K, Teixeira PGR, Shulman I, et al. The impact of uncross-matched blood transfusion on the need for
massive transfusion and mortality: Analysis of 5166 uncross-matched units. J Trauma 2008;65:12221226.
36. Johansson PI. Coagulation monitoring of the bleeding traumatized patient. Curr Opin Anaesthesiol
2012;25:235241.
37. Kasotakis G, Sideris A, Yang Y. Aggressive early crystalloid resuscitation adversely affects outcomes in adult
blunt trauma patients: An analysis of the Glue Grant database. J Trauma Acute Care Surg 2013;74:12151222.
38. Krumrei NJ, Park MS, Cotton BA, Zielinski MD. Comparison of massive blood transfusion predictive models
in the rural setting. J Trauma Acute Care Surg 2012;72:211215.
39. Maegele M, Spinella PC, Schchl H. The acute coagulopathy of trauma: mechanisms and tools for risk
stratification. Shock 2012;38:450458.
40. Magnotti LJ, Zarzaur BL, Fischer PE, et al. Improved survival after hemostatic resuscitation: Does the emperor
have no clothes? J Trauma 2011;70:97102.
41. Manoach S, Paladino L. Laryngoscopy force, visualization, and intubation failure in acute trauma: Should we
modify the practice of manual in-line stabilization? Anesthesiology 2009;110:67.
42. Mayglothling J, Duane TM, Gibbs M, et al. Emergency tracheal intubation immediately following traumatic
injury: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care
Surg 2012;73:S333340.
43. McSwain N Jr, Barbeau J. Potential use of prothrombin complex concentrate in trauma resuscitation. J Trauma
2011;70:S5356.
44. Meyer MA, Ostrowski SR, Windelv NA, et al. Fibrinogen concentrates for bleeding trauma patients: what is
the evidence? Vox Sang 2011;101:18590.
45. Morrison CA, Carrick MM, Norman MA, et al. Hypotensive resuscitation strategy reduces transfusion
requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: Preliminary
results of a randomized controlled trial. J Trauma 2011;70:652663.
46. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma
emergency resuscitation (MATTERs) Study. Arch Surg 2012;147:113119.
47. Nahm NJ, Vallier HA. Timing of definitive treatment of femoral shaft fractures in patients with multiple
injuries: a systematic review of randomized and nonrandomized trials. J Trauma Acute Care Surg
2012;73:104663
48. Neal MD, Hoffman MK, Cuschieri J, et al. Crystalloid to packed red blood cell transfusion ratio in the
massively transfused patient: when a little goes a long way. J Trauma Acute Care Surg 2012;72:892898.
49. Norton R, Kobusingye O. Injuries. N Engl J Med 2013;368:17231730.
50. Nunez TC, Voskresensky IV, Dossett LA, et al. Early prediction of massive transfusion in trauma: Simple as
ABC (Assessment of blood consumption)? J Trauma 2009;66:346352.
51. Nunez TC, Young PP, Holcomb JB, Cotton BA. Creation, implementation, and maturation of a massive
transfusion protocol for the exsanguinating trauma patient. J Trauma 2010;68:14981505.
52. Pape HC, Tornetta P, Tarkin I, et al. Timing of fracture fixation in multitrauma patients: The role of early total
care and damage control surgery. Am Acad Orthop Surg 2009;17:541549.
53. Pezold M, Moore EE, Wohlauer M, et al. Viscoelastic clot strength predicts coagulation-related mortality within
15 minutes. Surgery 2012;151:4854.
54. Rajasekhar A, Gowing R, Zarychanski R, et al. Survival of trauma patients after massive red blood cell
transfusion using a high or low red blood cell to plasma transfusion ratio. Crit Care Med 2011;39:15071513.
55. Rice MJ, Mancuso AA, Gibbs C, et al. Cricoid pressure results in compression of the postcricoid hypopharynx:
The esophageal position is irrelevant. Anesth Analg 2009;109:15461552.
56. Santoni BG, Hindman BJ, Puttlitz CM, et al. Manual in-line stabilization increases pressures applied by the
laryngoscope blade during direct laryngoscopy and orotracheal intubation. Anesthesiology 2009;110:2431.
57. Sise MJ, Shackford SR, Sise CB, et al. Early intubation in the management of trauma patients: Indications and
outcomes in 1,000 consecutive patients. J Trauma 2009;66:3240.
58. Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an
updated European guideline. Crit Care 2013;17:R76 [doi:10.1186/cc12685]

419
Page 11

59. Stephens, CT, Kahntroff, S, Dutton, RP. The success of emergency endotracheal intubation in trauma patients: a
10-year experience at a major adult trauma referral center. Anesth Analg 2009;109:866872.
60. Theusinger OM, Levy JH. Point of care devices for assessing bleeding and coagulation in the trauma patient.
Anesthesiol Clin 2013;31:5565.
61. Tobin JM, Varon AJ. Update in trauma anesthesiology: Perioperative resuscitation management. Anesth Analg
2012;115:132633.
62. Varon AJ, Smith CE (editors). Essentials of Trauma Anesthesia. Cambridge University Press, Cambridge, 2012.
63. Zentai C, Grottke O, Spahn DR, et al. Nonsurgical techniques to control massive bleeding. Anesthesiol Clin
2013;31:4153.

Disclosure

425
Page 1
Massive Transfusion Protocol in Trauma
Charles E. Smith, M.D. Cleveland, Ohio
Principle:
A massive transfusion protocol (MTP) is activated in response to a trauma patient experiencing severe
bleeding. Once a patient is in the protocol, the blood bank is able to insure rapid and timely availability of blood
components to facilitate resuscitation. When the protocol is activated, a team approach is required and appropriate
support staff are necessary. Surgical control of hemorrhage and timely volume resuscitation with warmed fluids and
blood components remains the cornerstone of treatment. Once definitive control of bleeding has been achieved, a
restrictive approach to blood product transfusion is preferred because of the well-known risks of transfusion such as
multiple organ failure, systemic inflammatory response syndrome, TRALI (transfusion related acute lung injury),
increased infection and mortality. The protocol at MetroHealth Medical Center has been in use since 2008 (Table 1).
Rationale:
Transfusion of packed red cells (RBCs), plasma, and platelets in a similar proportion as whole blood (e.g.,
1:1:1) may minimize the effects of dilutional coagulopathy and hypovolemia. Retrospective studies in trauma patients
demonstrate a survival advantage of increased plasma: red cell ratio on mortality in massive transfusion after trauma.
Some studies have demonstrated a survival advantage with increased platelet: red cell transfusion ratio. Because these
studies were retrospective, survivor bias may have occurred, in which surviving patients had more opportunity to receive
increased volumes of plasma and/or platelet transfusions, thus potentially leading to higher calculated ratios. Ho et al
examined 26 such studies and found that only 10 of the studies did not have a survival bias for or against 1:1 transfusion
ratios. The American Association of Blood Banks (AABB) and the European Task Force recommend early intervention
with plasma but do not endorse a specific plasma to RBC ratio. The level of evidence supporting use of a MTP is weak
since outcome studies in trauma are difficult to perform because current evidence-based trauma care reduces
mortality (e.g., Hauser et al, CONTROL trial).
Definitions:
The traditional definition of massive transfusion in trauma is 1 blood volume transfusion in a 24 hr period. A
commonly used definition in the trauma literature is > 10 units RBCs in 24 hours. Both of these definitions are
reasonable for publications, but are not practical in an ongoing resuscitation. Other definitions include: loss of 0.5 blood
volume within 3 hours; use of 50 units of blood components in 24 hours; and use of 6 units RBCs in 12 hours. From a
practical standpoint, requirement for > 4 RBC units in 1 hour with ongoing need for transfusion, or blood loss > 150
ml/min with hemodynamic instability and need for transfusion are reasonable definitions in the setting of a MTP
situation. The variability in defining massive bleeding may result in variability initiating a MTP.
Predicting Need for MTP in Trauma
3-5% of civilian adult trauma patients receive massive transfusion. Early identification of patients requiring
MTP has been evaluated by assigning a value of 0 or 1 to the following four parameters: penetrating mechanism,
positive FAST for fluid (focused assessment sonography in trauma), arrival blood pressure <90 mm Hg, and arrival
pulse >120 bpm. A score of 2 or more is considered positive. The score is 75% sensitive and 85% specific. Patients
receiving uncross-matched RBCs in the emergency department are three times more likely to receive massive
transfusion. In military trauma, casualties presenting with any two of four possible variables (heart rate >110 bpm,
systolic blood pressure <110 mm Hg, base deficit < -6, and hemoglobin <11 g/dl) had a 54% incidence of massive
transfusion.

425
Page 2
Pathophysiology of Hemorrhagic Shock in Trauma:
Major trauma causes tissue injury and hemorrhage. Shock occurs due to decreased circulating volume, cardiac
output and oxygen delivery which is compounded by inflammation, acidosis, and tissue hypoperfusion. Hypothermia is
aggravated by altered thermoregulation, environmental exposure, and initial resuscitation with unwarmed fluids.
Aggressive crystalloid fluid resuscitation leads to hemodilution with decreased oxygen carrying capacity and dilution of
coagulation factors. Progressive coagulopathy leads to further hemorrhage and shock. Refractory coagulopathy,
progressive hypothermia and persistent metabolic acidosis lead to end stage shock and death.

Mechanism(s) of Trauma-Induced Coagulopathy:
The coagulation disturbance in trauma is more than just the result of consumption of clotting factors at sites
of injury and dilution from the infusion of fluids and RBCs. In 2003, Brohi et al analyzed a cohort of 1088 trauma
patients and found that 24% had a coagulopathy on arrival. Patients presenting abnormal laboratory test results had a
higher rate of death (46% vs 11%). The incidence of coagulopathy was strongly associated with the injury severity
score, suggesting that the degree of tissue injury and/or hypoperfusion was a causative factor. Acute coagulopathy
appears to be due to activation of anticoagulant and fibrinolytic pathways, although the exact mechanism has yet to
be elucidated. The thrombomodulinprotein C pathway has been implicated. Shock and hypoperfusion are key
drivers of the trauma-induced coagulopathy of trauma. According to Frith and Brohi, hypoperfusion increases the
expression of thrombomodulin on endothelium which then complexes with thrombin. This reduces the amount of
thrombin available to produce fibrin and increases circulating concentrations of anticoagulant activated protein C.
In trauma, hypothermia and acidosis play a key role by reducing thrombin generation due to altered enzyme
kinetics. Both coagulation factors and platelets are reduced by hemodilution. Platelet count is higher than predicted
due to release of platelets sequestered in the spleen and lungs. Antithrombin activity decreases to less than 30% of
normal with extensive hemodilution. A threshold level of fibrinogen 1g/L (100 mg/dL) is reached after losing 150%
of circulating blood volume as opposed to 200% for clotting enzymes. Systemic hyperfibrinolytic states may be seen
in up to 20% of trauma patients. Fibrinolysis is significantly increased due to dilution of FXIII and !
2
antiplasmin
which reduces fibrin cross-linking, decreases resistance to fibrinolysis and prolongs plasmin half-life. Plasminogen
activator inhibitor is decreased, prolonging tissue plasminogen activator (tPA) activity. Stress, thrombin,
epinephrine, vasopressin, desmopressin, and bradykinin trigger tPA release. Excessive fibrinolysis contributes to
coagulopathy and is associated with increased mortality.

Recommendations for Resuscitation during MTP:
In addition to a MTP, all efforts must be directed towards damage control resuscitation including control of
surgical bleeding and correction of hypothermia, acidosis, shock, and coagulopathy. Limiting the use of isotonic
crystalloid will help prevent dilutional coagulopathy. Permissive hypotension (systolic blood pressure 80-100
mmHg) until bleeding is controlled is generally recommended, unless there is concern for brain or spinal cord
injury. Early use of plasma, platelets as well as RBCs is necessary. Fibrinogen levels above 1.5 g/L (150 mg/dL) are
targeted, using cryoprecipitate 50 mg/kg or fibrinogen concentrate doses of 3-4 g. Base deficit and lactate are
monitored to assess adequacy of resuscitation. Electrolyte abnormalities are corrected (e.g., hypocalcemia from
citrated anticoagulants). Early administration of tranexamic acid to adult trauma patients results in reduced all-cause
mortality, reduced mortality from bleeding and a safe side effect profile in bleeding trauma patients. The use of
coagulation factors (4 factor prothrombin complex concentrates- PCCs and fibrinogen concentrates) has been
adopted in some centers, especially Europe. Use of rFVIIa merits consideration in trauma patients undergoing
massive transfusion who continue to exsanguinate, with an understanding of the limitations of its effect (see section
below).

Coagulation Testing in Trauma:
Standard coagulation tests such as PT, PTT, INR, platelet count, and fibrinogen usually require 3060
minutes for results to be available. For patients requiring acute interventions, results may not be an accurate
reflection of coagulation function. Evidence is growing for use of thromboelastography (TEG) and
thromboelastomety (ROTEM) to guide hemostatic therapy. These point of care hemostatic assays provide a graph of
the displacement caused by viscoelastic changes in whole blood as clotting progresses and fibrin strands form
between the cup and pin. Clot strength is decreased by hypofibrinogenemia, thrombocytopenia, low FXIII level, or
reduced thrombin generation. Rapid TEG (coagulation is initiated by the addition of tissue factor) gives faster results
compared to kaolin TEG. ROTEM, EXTEM (uses recombinant tissue factor to activate coagulation) and FIBTEM
(measures contribution of fibrinogen to clot strength) allow differential diagnosis of thrombocytopenia and

425
Page 3
hypofibrinogenemia. Higher hemoglobin levels reduce TEG/ROTEM signals. Conversely, low hemoglobin makes
signals larger.

Factor VIIa and MTP in Trauma:
FVIIa can reverse coagulation abnormalities and decrease blood loss. However, a well-defined outcome
benefit is less clear. Two randomized, double blinded, placebo controlled trials with 143 blunt and 134 penetrating

trauma patients have been carried out. The initial dose of rFVIIa was given after the 8
th
RBC unit and then 1 and 3
hours after (200, 100, 100 mcg/kg). RBC transfusion was significantly reduced in blunt trauma patients, as was the
need for massive transfusion (14% vs 33%). There was a trend towards similar results in penetrating trauma which
did not reach statistical significance. Subgroup analysis of coagulopathic patients from both trials showed reduced
blood component per patient, fewer massive transfusions (6% vs 29%) and less multi-organ failure and ARDS (3%
vs 20%) in the rFVIIa group. Thromboembolic complications were similar to the placebo group. In a study of early
vs late administration of rFVIIa (before vs after 8 RBC units) in combat casualties, the early group required less
blood (20.6 vs 25.7 units). Mortality, ARDS, infection and thrombotic events were similar between groups. In the
CONTROL trial, rFVIIa decreased RBC, FFP, and total allogeneic blood product use but did not affect mortality.
The study was terminated early because of low mortality and there was no difference in arterial and venous
thrombotic events in the rFVIIa vs the placebo group.
In a review of 35 randomized clinical trials involving 4468 subjects, the rate of venous thromboembolic
events was similar between rFVIIa and placebo treated subjects (approximately 5.3-5.7%). However, arterial
thromboembolic events were higher in patients who received rFVIIa vs placebo (2.9% vs 1.1%). The rate of arterial
events was highest in patients > 65 yrs receiving rFVIIa (9.0%). Because of the risk of serious adverse effects,
treatment with rFVIIa must be individualized based on a risk-benefit analysis.

Complications of MTP in Trauma:
Blood transfusion is an independent predictor of multi-organ failure in a retrospective and prospective
study of trauma patients with injury severity score > 15 and survival greater than 24 hours. There is a 2-6 fold
increase in SIRS, 4 fold increase in ICU admission and mortality in transfused patients. One study showed that
transfusion was an independent predictor of death in non-operative blunt trauma and the risk of death increased with
each additional RBC unit. In a retrospective review of 1312 patients, the mean transfusion volume for elderly
survivors vs young was 4.6 units vs 6.7 units; No patient over age 75 who was transfused > 12 units RBCs survived.
In a meta-analysis of 20 studies, the odds ratio for bacterial infection in transfused vs non-transfused patients was
3.45. The odds ratio increased to 5.26 in the subgroup analysis for trauma patients. TRALI is likely under-diagnosed
after trauma since it is difficult to differentiate from other causes of lung injury in trauma. In transfusion associated
micro-chimerism, a small population of donor hematopoetic stem cells may engraft into the recipient, persisting
sometimes for years.

MTP after the Bleeding has Stopped:
A restrictive approach to blood product utilization is advocated once hemorrhage is stopped and the patient
is stable. The MTP is discontinued (requires a phone call to Blood Bank). Signs and symptoms of impaired oxygen
delivery and decreased tissue perfusion are closely monitored. RBC transfusion is generally required for persistent
base deficit, lactic acidosis, and signs of end organ ischemia.

Summary:
The use of a MTP facilitates rapid availability of components in an increased ratio of plasma and platelets to
RBCs. Based on retrospective data, increased ratios of plasma and platelets to RBCs and their early administration
are associated with improved outcome in trauma, decrease coagulopathy and transfusion requirements. A restrictive
transfusion strategy should be adopted once hemorrhage is controlled to minimize unnecessary exposure to blood.
There are many unresolved issues with MTP including use of fibrinogen concentrates, PCCs, rFVIIa, optimal timing
and ratios of product and point-of care testing. Prospective randomized trials are required to determine optimal ratios
and timing of blood component administration (e.g., PROPPR study- Pragmatic Randomized Optimal Platelet and
Plasma Ratios, http://cetir-tmc.org/research/proppr; and PAMPer study- Prehospital Air Medical Plasma,
http://acutecareresearch.org/studies/current/prehospital-air-medical-plasma-pamper-trial). Better understanding of
trauma-induced coagulopathy is clearly needed (e.g., TACTIC- Trans-Agency Research Consortium for Trauma-
Induced Coagulopathy. http://www.grants.gov/search/search.do?mode=VIEW&oppId=207954).

425
Page 4
The author is grateful to members of the ASA Committee on Blood Management for their input. Individuals
interested in trauma anesthesia can join the discussion group of the Trauma Anesthesiology Society
([email protected]).

Table 1. Massive Transfusion Protocol @ MetroHealth Medical Center, Cleveland, Ohio

The clinician contacts the Blood Bank and activates the MTP. Once a particular patient is identified as being
entered into the Massive Transfusion Protocol, the following is followed. This situation is encountered in surgical
or medical emergencies as well as in trauma.

SPECIMEN:
Pre- or post-transfusion blood sample (signed, 7mL pink top tube) from massively transfused patient .

QUALITY CONTROL:

See procedure: DAILY REAGENT QUALITY CONTROL

MATERIALS/REAGENTS:

See procedure ABO GROUPING, D ANTIGEN TESTING, ANITBODY SCREENING TEST, COMPATIBILITY
TESTING

PROCEDURE:

1. When clinician contacts Blood Bank on the distinct-ring, MTP Hot-line phone (X89000) and gives a verbal
order to begin the MTP on a patient, complete a pink verbal PHONE ORDER form. Record two patient
identifiers, the date, location, the physicians name/PIN #, and the person calling and initiating the MTP.

2. A runner will come to the Blood Bank to obtain the products. Do NOT tube the blood.

3. FIRST MTP PACK - Collect the 4 O Negative RBCs and 2 AB plasma units already set-up for Emergency
Release. Pack in a Blood Bank Insulated Cooler. Complete the pink ALERT label for the insulated
cooler, the INSULATED COOLER BLOOD STORAGE TRACKING SHEET and the INSULATED
COOLER SIGN-OUT SHEET. See procedure BB1 65.0 Transportation of Blood in an Insulated Cooler.

4. As soon as the 1
st
MTP pack is issued, begin preparing the 2
nd
MTP pack.

5. If a sample has not yet been submitted contact the Blood Bank Medical Director and inquire as to whether
the patient should be switched to O Rh Positive.

6. SECOND MTP PACK 6 units of RBCs (O Neg/Pos or type specific if sample has been submitted)
4 units of Plasma (AB or type specific if sample has been submitted)
Second Insulated Cooler
Necessary Emergency Release/Insulated Cooler paperwork

7. As soon as the 2
nd
MTP pack is issued, begin preparing the 3
rd
MTP pack.

8. Third and subsequent packs should be have the RBCs crossmatched using the BB1 43.0 -Massive
Transfusion Abbreviated Crossmatch Procedure since 10 RBCS will at that point be issued in less than a
24 hour period. (See procedure.)

425
Page 5
9. THIRD AND ALL SUBSEQUENT MTP PACKS CONSIST OF THE FOLLOWING

6 units of RBCs (O Neg or type specific if sample has been submitted)
4 units of Plasma (AB or type specific if sample has been submitted)
6 random A/AB platelets (or one 5-day pool or 1 apheresis platelet product)
Insulated Cooler (Do NOT place platelets in cooler, for RBCs/Plasma only)
Necessary Emergency Release/Insulated Cooler paperwork

10. Continue with preparing an MTP PACK after an MTP pack has been issued until the Blood Bank has been
notified by a clinician to discontinue the MTP. Record on a verbal Phone Order the two patient identifiers,
the date, location, the physicians name/PIN #, and the person calling to inactivate the MTP order.

Procedural Notes:

1. Once the second MTP PACK has been issued, the BB1 43.0 - Massive Transfusion Abbreviated Crossmatch
Procedure may be initiated since 10 units of RBCs will have been issued.

2. Clinician should send a blood sample to the Blood Bank as soon as possible (signed, 7mL pink top tube) via
pneumatic tube station 122 or via a runner.

3. Since there are only 2 Insulated Coolers, remind runners to bring back the empty Insulated Cooler each time
they come back for another MTP pack of blood so that Blood Bank tech can pack the next MTP pack in it.
Remind runner to also bring any completed Emergency Release forms and INSULATED COOLER BLOOD
STORAGE TRACKING SHEETs.

4. As long as RBCs and Plasma remain in properly packed insulated cooler, their storage is good for up to 8 hours
and may be returned to inventory if not used and otherwise acceptable.

5. Keep ahead as much as possible with the platelet orders. Order two 6-packs of platelets from the blood supplier
each time a courier run of platelets is needed during an MTP.

6. If it is discovered that the patient has a history of clinically significant alloantibodies, all RBC units prepared for
the patient MUST be screened antigen negative for the patient's antibody(ies) if possible. It is important to
remember that the patient's antibody(ies) may not be demonstrating due to dilution with large volumes of donor
blood and components, but if antigen positive units were infused they would have shortened survival.

7. In the above situation, antigen positive blood may be issued upon written or verbal approval of the Blood Bank
Medical Director. Document approval on the Emergency Blood Product Release Request Form. If the request
is at a time when the Blood Bank Medical Director is unavailable, the ER physician may sign for the antigen
positive blood and the Blood Bank Medical Director and/or Blood Bank Supervisor should be notified that day.
Record this event in the deviation book for Blood Bank Medical Director to review and sign. Notify clinician
or nurse of the situation. Document who you spoke to in Patient Comments in LIS. As soon as possible, units
should be tested for the antigen and the test results conveyed to the Supervisor/Medical Director for guidance.

8. Patients involved in a Massive Transfusion Protocol (see procedure) will only receive RBCs crossmatched via
the abbreviated method once the Blood Bank has issued 10 units of RBCs and not before.

9. Paperclip the start and stop verbal PHONE ORDERs to the Emergency Release forms for the Medical Director
review.

REFERENCES:
AABB Technical Manual, Current Edition.
AABB Standards, Current Edition
MHMC Policy, 2008

425
Page 6

References:

1. Boffard KD et. al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured
trauma patients. J Trauma 2005;59:8-16
2. Bolliger D et al. Finding the optimal concentration range for fibrinogen replacement after severe
haemodilution: an in vitro model. Br J Anaesth 2009;102: 793-9
3. Bolliger D et al. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution.
Anesthesiology. 2010 Nov;113(5):1205-19
4. Brohi K et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and
hyperfibrinolysis. J Trauma. 2008 May;64(5):1211-7
5. Brohi K et al. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C
pathway? Ann Surg. 2007 May;245(5):812-8.
6. Brohi K, et al. Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care
2007; 13:680685.
7. Callum JL, Rizoli S. Assessment and management of massive bleeding. Hematology 2012;522-528
8. Carroll RC et. al. Early evaluation of acute traumatic coagulopathy by thromboelastography.
Trans Res 2009; 154:34-39
9. Cotton BA et al. Multicenter validation of a simplified score to predict massive transfusion in trauma. J
Trauma 2010;69 Suppl 1:S33-9
10. Cotton BA et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and
improvement in survival in 390 damage control laparotomy patients. Annals Surgery 2011; 254(4):598-605
11. Curry N et al. Trauma-Induced Coagulopathy A Review of the systematic reviews. Transfusion Medicine
Reviews, Vol 25, No 3 (July), 2011:pp 217-231
12. Frith D, Brohi K. The acute coagulopathy of trauma shock: Clinical relevance. Surgeon 2010;8: 159-163
13. Hauser CJ et al. Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in
the management of refractory traumatic hemorrhage J Trauma. 2010 Sep;69(3):489-500
14. Hayter MA et al. Massive transfusion in the trauma patient. Can J Anesth 2012;59:1130-45
15. Hess JR et al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008 65:748-54.
16. Hiipala et al. Hemostatic factors and replacement of major blood loss with plasma-poor red cell
concentrates. Anesth Analg 1995;81:360-5
17. Hill GE et. al. Allogenic blood transfusion increases the risk of post-operative bacterial infections: a meta-
analysis. J Trauma, 2003; 54(5)
18. Ho AM et al. Prevalence of survivor bias in observational studies on fresh frozen plasma:erythrocyte ratios
in trauma requiring massive transfusion. Anesthesiology. 2012;116(3):716-28
19. Inaba K et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J
Am Coll Surg. 2010;210:957-65
20. Johansson PI et al. Thrombelastography and thromboelastometry in assessing coagulopathy in trauma.
Scand J Trauma Resusc Emerg Med. 2009 Sep 23;17:45
21. Johansson PI, Stensballe J. Hemostatic resuscitation for massive bleeding: the paradigm of plasma and
platelets--a review of the current literature. Transfusion. 2010 Mar;50(3):701-10
22. Johansson PI. Management of major blood loss: an update. Acta Anaesthesiol Scand. 2010;54:1039-49
23. Kashuk JL et al. Postinjury coagulopathy management: Goal directed resuscitation via POC
thrombelastography. Ann Surg. 2010;251(4):604-14
24. Kashuk JL et al. Primary fibrinolysis is integral to the pathogenesis of the acute coagulopathy of trauma.
Ann Surg. 2010;252(3):434-42
25. Kaufman CR et. al. Usefulness of thromboelastography in assessment of trauma patient coagulation. J
Trauma 1997; 42:716-720
26. Larson CR et al. Association of shock, coagulopathy, and initial vital signs with massive transfusion in
combat casualties. J Trauma. 2010 Jul;69 Suppl 1:S26-32
27. Levi M et al. Safety of Recombinant Activated Factor VII in randomized clinical trials. NEJM 2010: 363
28. Robinson WP et. al. Blood transfusion is an independent predictor of increased mortality in non-operatively
managed blunt hepatic and splenic injuries. J Trauma 2005; 58(3)
29. Levrat et al. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma
patients. Br J Anaesth 2008; 100: 7927
30. Nunez TC et al. Creation, implementation, and maturation of a massive transfusion protocol for the
exsanguinating trauma patient. J Trauma. 2010;68:1498-505.

425
Page 7
31. Nunez TC et al. Emergency department blood transfusion predicts early massive transfusion and early
blood component requirement. Transfusion. 2010;50:1914-20.
32. Perkins et. al. Early versus late recombinant factor VIIa in combat trauma patients requiring massive
transfusion. J Trauma 2007;62:1095-1099
33. Phan HH, Wisner DH. Should we increase the ratio of plasma/platelets to red blood cells in massive
transfusion: what is the evidence? Vox Sang 2010;98(3 Pt 2):395-402
34. Repine TB et al. The use of fresh whole blood in massive transfusion. J Trauma. 2006;60(6 Suppl):S59-69.
35. Rizoli SB et. al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severe trauma
patients with coagulopathy: subgroup analysis from two randomized trials. Crit Care 2006:10:R178
36. Roback JD et al. Evidence-based practice guidelines for plasma transfusion. Transfusion 2010;50:1227-
1239.
37. Rossaint R et al. Management of bleeding following major trauma: an updated European guideline. Crit
Care 2010;14:R52
38. Schochl H. et al. Goal-directed coagulation management of major trauma patients using
thromboelastometry (ROTEM). Critical Care 2010, 14:R55
39. Schreiber MA et. al. Hyercoagulability is most prevalent early after injury and in female patients. J
Trauma; 2005; 58:475-480
40. Schuster KM. The status of massive transfusion protocols in United States trauma centers: massive
transfusion or massive confusion? Transfusion. 2010;50(7):1545-51
41. Shakur H et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in
trauma patients with significant haemorrhage (CRASH-2). Lancet. 2010;376(9734):23-32
42. Sihler KC, Napolitano LM. Complications of massive transfusion. Chest, 2010; 137:209-220
43. Sihler KC, Napolitano LM. Massive transfusion: new insights. Chest 2009;136(6):1654-67
44. Simmons JW et al. Impact of policy change on US Army combat transfusion practices. J Trauma. 2010
Jul;69 Suppl 1:S75-80
45. Smith CE, Bauer AM, Pivalizza EG, Tanaka K, Boral L, Shander A, Waters JH. . Massive transfusion
protocol (MTP) for hemorrhagic shock. ASA Committee on Blood Management. http://www.asahq.org/for-
members/about-asa/asa-committees/committee-on-blood-management.aspx
46. Tien H et al. An approach to transfusion and hemorrhage in trauma: current perspectives on restrictive
transfusion strategies. Can J Surg. 2007;50(3):202-9
47. Tobin J. Massive transfusion in trauma care. In Smith CE. Trauma Anesthesia, 2
nd
edition. Cambridge
University, 2013. In Press
48. Yank V, et al. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-
label indications. Ann Intern Med. 2011;154:529-540

Disclosure

"#$
%&'( $
WMDs: High Energy Explosives - What We Have Learned from the Military in
Afghanistan
Michael J Murray M.D. Ph.D* COL MC USAR
Introduction: Weapons of mass destruction traditionally referred to the use of chemical, biologic and radiologic
agents during combat to cause mass destruction. There are probably multiple reasons for this-chemical agents were
used in World War I, biologic agents were used in World War II and there have been enough accidents at nuclear
power plants that the public is aware of these agents, and is justifiably concerned about the sequelae associated with
their use. Terrorists have used these agents in the last several years, and recently Syria has been accused of using
chemical agents against rebels in its Civil War and Shannon Guess Richardson of New Boston, Texas, was arrested
for her role in sending Ricin containing letters to the White House, CIA and other government agencies. Anthrax
was sent in letters in 2001 and 2002, and sarin was used in Tokyo subway stations in 1995.
However, the "weapon of mass distraction" most frequently used by terrorists over the last 3 decades has been
improvised explosive devices (IEDs). Increasingly we are finding that the United States is not as insulated as it once
was and terrorists are using IEDs against us. Faisal Shahzad was sentenced to life in prison on charges of terrorism
and planning to use a weapon of mass destruction for trying to detonate a car bomb in Time Square in May 2010. In
July 2011, Naser Jason Abdo, a U.S. Army private at Fort Hood, Texas, who learned about making a pressure-
cooker bomb from an Al-Qaeda magazine article, was arrested for planning to blow up a restaurant frequented by
U.S. soldiers. Two pressure cookers and bomb-making materials were found in his hotel room. He also was
sentenced to life in prison. Obviously the most significant use of IEDs in the US was on April 15, 2013 at the finish
line of the Boston Marathon when two pressure cookers loaded with gunpowder, nails, and ball bearings were
detonated. Three people were killed, and 264 were injured and treated at 29 local hospitals. As has occurred in other
mass disasters victims do not preferentially go to level I trauma centers! There were at least 16 patients with
traumatic amputation, limbs were severed either during the explosion or they sustained such damage that they
required amputation in the hospital. Three of the 16 lost more than one limb. On April 22, 2013 Dzhokhar Tsarnaev
was charged with use of a weapon of mass destruction, and with malicious destruction of property resulting in death.
The charges carry potential sentences of life imprisonment or the death penalty.

"#$
%&'( )

* The views expressed are the personal views of COL M J Murray. The information does not represent the views of
the Department of Defense, nor of the US Army.
During the conflicts in Iraq (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF])
US forces have been confronted with the extensive use of IED's. In 2012 alone in Afghanistan there were more than
16,000 incidents involving IED's. Of note the injuries caused by IED's in OIF and OEF have been quite different but
in both situations the military responded appropriately. In Iraq, troops traveled in Humvees; they were easily
penetrated by explosive devices resulting in many patients with thermal injury and with amputation. Well-designed
and heavily protected vehicles eg MRAPs (Mine-Resistant Ambush Protected) provide the mounted soldier superior
protection against roadside explosive devices. Extensive thermal injuries among mounted soldiers, more common
early in the wars, have nearly disappeared. Current personal protective equipment (PPE) has mitigated head, eye and
torso injuries drastically. Extremities, therefore, are at greatest risk for injuries, especially among dismounted
soldiers. In Afghanistan, because of the difference in terrain, troops frequently patrol on foot; the force of the blast
of an IED is enough to cause significant injury. As in Boston many soldiers have traumatic amputations. Unlike
Boston, because of larger, more sophisticated IEDs in 2011 2012 there were more soldiers with multiple traumatic
amputations than there were single amputations (Figure 1) and for every major amputation (i.e., from the wrist or
ankle and higher), there were ~ four additional casualties with severe extremity injuries.

Etiology of Injury
Mechanism of Injury:
An explosion produces a blast wave an instantaneous (just a few milliseconds) expansion of over-
pressurized air that travels outward at very high speed (3000 m/sec to 8000 m/sec) in all directions. The explosive
material used to produce the IED influences the duration of the blast wave, the strength of which dissipates the
further one is from the blast. The degree of injury (and damage) an IED causes is dependent on the blast wave it
creates. Factors that influence the degree of damage are related to: 1) the peak of the initial pressure wave 2) the
duration of the overpressure associated with the wave; 3) the medium in which the IED explodes; 4) the distance one
is from blast; and 5) the degree of focusing of the blast by structures eg an alleyway.
Classification of Injuries:
Primary Injuries: Primary injuries are caused by the shock waves caused by the blast. The eardrums are
frequently ruptured by the pressure wave, followed by the lungs and the hollow organs of the gastrointestinal tract.
If a patient has normal eardrums and normal oxygenation as assessed by pulse oximetry it is unlikely that they have
an injury caused by the primary effects of the blast. Gastrointestinal injuries may present after a delay of hours.
When triaging patients if eardrums and O
2
saturation are normal and no other injuries can be found they can be sent
home from the emergency department and told to return if they develop abdominal pain. Injury from blast is
pressure and time dependent function. As terrorists typically detonate IEDs when soldiers are in close proximity to

"#$
%&'( #
the IED they are exposed to a blast wave of enormous proportions, one that creates enough force to traumatically
amputate one or more extremities 192 soldiers lost their genitalia from primary blast injury. In years past
casualties with this degree of injury had a 30% to 50% mortality rate. Currently the mortality rate of such injuries is
< 10%.
The size of the IEDs in Afghanistan has also resulted in many patients having moderate to severe traumatic
brain injury. Normally the skull is thought of as an inflexible structure, and the brain a solid organ. However,
researchers have demonstrated that the helmet in current use may focus or concentrate the pressure-wave, and
depending on the force transmitted to the brain may result in injury (Figure 2). The blast wave creates two types of
stress waves and shear waves in internal organs. Stress waves are longitudinal forces that move at supersonic speeds.
Shear waves are transverse waves that cause asynchronous movement of tissue. The net effect can rupture blood
vessels with intra-cerebral hemorrhage a sequelae. Even if no hemorrhage on computerized tomographic exam 60%
to 80% of mild traumatic brain injury in OEF has been caused by exposure to blast injury.
Secondary blast injury is the result of fragments (shrapnel the bomb casing, screws, nails, nuts ball
bearings, bolts) flying through the air. Material external to the bomb can be propelled by the force of the blast wave
contributing to the amount of shrapnel spread by the explosion. Patients will typically have penetrating injury to
multiple body areas. Blunt trauma can be caused by secondary injury though that is more common with tertiary
injury.
Tertiary blast injury occurs when the individual is thrown by the force of the blast into a solid object such
as a wall, a window, a steering wheel or is injured from a structure such as a building collapsing on them. The
former cause the types of injuries similar to those observed following high-speed motor vehicle crashes where as the
latter create crush injuries seen in earthquakes.
Quaternary blast injury occurs from the fire ball created from the exposure, from inhalation of toxic gases,
from radioisotopes as might be found in a dirty bomb or from significant blood loss from wounds.

12

Figure 2 Pressure and skull motion for impact and blast simulations
(pressure contour limits are the same for a, b, and c):
(a) Angled impact at maximum deceleration. A helmet consisting of steel and crushable foam
reduces the acceleration to produce a HIC of ~1000.
(b) Blast wave propagating past the simulated victim.
(c) Expanded view of the head as the blast wave passes over it. Inward and outward rippling of the
skull cause maximum and minimum pressures in the brain.

"#$
%&'( "
Treatment
Examining figure 1 one is struck by how dramatically the number of casualties with amputations has increased since
2008. Not only has the number of casualties increased, but there has been a concomitant increase in the severity of
injuries. The military has coined a new term to describe the injury from IEDs in OIF: dismounted complex blast
injury (DCBI). A review of the records of 437 patients with DCBI and who were alive on admission to a Level III
NATO Hospital over 38 months (1 Jan 2009 to 29 Feb 2012).
Demonstrated that 99.5% of casualties were male with a median age of 23. The majority, 394, had been transported
directly from the point of injury. The median injury severity score (ISS) was 10 (25-75% IQR 4, 21). Trauma to the
skeletal system was most commonly observed with traumatic amputation the most frequent injury; 175 (40%)
patients had at least a single amputation, and 23 had amputations of 3 or more limbs.
Traumatic amputation per se did not correlate with mortality though the ISS, massive transfusion and
pelvic fracture did. Surprisingly the mortality rate was only 1.8 %, which speaks to the quality of care provided. The
lessons learned by the military in dealing with DCBIs should provide civilian healthcare providers with insight to
how they might best manage patients with traumatic injury, especially those from blasts.
Management in the Field/Damage Control Resuscitation: All soldiers carry tourniquets in the field, and are quick to
apply them at the point of injury when helping a buddy with a DCBI. Evidence from the US Army Institute of
Surgical Research (ISR) suggests that severely injured casualties survive due to the immediate application of
extremity tourniquets by first responders. Soldiers are transported by "Dustoff" helicopters to the nearest combat
support hospital; medics on board also have training in maintaining temperature (see below) and in the principles of
damage control resuscitation. The administration of crystalloid on the helicopter is very limited with the medics
focusing their attention on controlling the bleeding. When at the combat support hospital the staff replace what was
lost i.e. packed red blood cells, fresh frozen plasma, and platelets, or if necessary whole blood. While controversial,
and open to clinical judgment, on average, the majority of patients receive a ratio of pRBCs:FFP:platelets of 1:1:1.
Managing Hypothermia
The association of hypothermia, acidosis and coagulopathy (the triad of death) with increased mortality has been
well described. A review of records demonstrated that patients were arriving at combat support hospitals with core
temps < 35, even during combat operations in summertime. The mortality in combat casualties with hypothermia
was double that of normothermic casualties with similar injuries. The military therefore has expended a great deal of
effort in educating providers about the importance of preventing hypothermia in combat operations and casualty
management, at all levels of care. Preventive measures are taken during transport, and for soldiers with DCBI the
guidelines are to maintain the OR temp at
>85-90 F during casualty resuscitation and operative procedures. Fluids that are administered are warmed and
when possible forced air warming devices (Bair Hugger) are used.
Debridement
Wound debridement and irrigation (D&I) are the most frequently performed surgical procedure in the combat
theater. Recommendations are for the wounds to be debrided at least every 2 days (or more often depending on the
nature of the wound) to remove nonviable tissue, debris, blood and bacteria, which is important to prevent local and
systemic complications associated with such a wound. While the goal is to remove all nonviable tissue, one tries to
preserve as much soft tissue as possible for later reconstructive surgery. Following debridement the wounds are
irrigated, typically with sterile isotonic solution (the fluid of choice for irrigation) using large volumes of fluid;
bacterial loads drop logarithmically with increasing volumes of 1, 3, 6, and 9 liters of irrigation. Negative Pressure
Wound Therapy with Reticulated Open Cell Foam (NPWT/ROCF) dressing, commonly referred to as the VAC
dressing, is used to cover the wounds before transporting the patient from the OR.
Treating Infection:
Early during OIF and OEF bacterial infections were major concerns. Although definitive data do not exist, DCBI
wounds are particularly susceptible to infection, and that the risk of infection (especially fungal infection) is greater
when multiple limbs are involved. With every trip to the OR debrided tissue is sent to the pathology department for
microscopic examination for vascular invasion by fungi. Soldiers with evidence of invasion are treated aggressively
with antifungal agents and with more frequent and aggressive debridement.

Conclusion: As many have been concerned, terrorists have struck the United States with improvised explosive
devices that killed three, injured many, and presented challenges for the 29 hospitals in the Boston area. We as
anesthesiologists need to be prepared- we should know our departments emergency preparedness plan, we should
anticipate the day when we may be called into assist during a disaster, and to continue to educate ourselves on the
latest information on how to manage patients injured by improvised explosive devices.

"#$
%&'( *
1) Dismounted Complex Blast Injury
Report Of The Army Dismounted Complex Blast Injury Task Force
2) Joint Theater Trauma System Clinical Practice Guideline
Initial Management Of War Wounds: Wound Debridement and Irrigation
3) Joint Theater Trauma System Clinical Practice Guideline
Hypothermia Prevention, Monitoring, And Management
4.) Joint Theater Trauma System Clinical Practice Guideline
Damage Control Resuscitation At Level Iib/Iii Treatment Facilities
5) Ritenour, A E; Baskin T W; Primary blast injury: Update on diagnosis and treatment; Crit Care Med 2008;
36:[Suppl.]:S311S317
6) William C. Moss, Michael J. King, and Eric G. Blackman
Skull Flexure from Blast Waves: A New Mechanism for Brain Injury with Implications for Helmet Design
Lawrence Livermore National Laboratory, Livermore, CA 94551

Disclosure

501
Page 1
Anesthetic Implications of Pharmacogenetics
Itay Bentov, M.D. Seattle, Washington
In a recent editorial in Anesthesiology the authors stated that education in genomics will be essential for
practitioners to translate genomic discoveries into clinical practice
1
. This RCL is designed to be part of this effort.
First, basic concepts and nomenclature of genetics will be reviewed. We will then discuss examples of the influence
of genetic information and genetic research strategies, on patient care in anesthesia.
In the very near future, looking up the lab work for your next patient you find that the CBC, chemistry and imaging,
are all within normal limits. HOWEVER you notice that your patient is carrying the allele G681A for the gene
CYP2C19 and homozygote for butyryl-cholinesterase Asp70Gly polymorphism. Furthermore you are alarmed by
the SNPs analysis of her NPR3 and NPPA/NPPB genes. As she comes into your office you notice that she has
flaming red hair. During the interview she claims that she needs large dosed of local anesthetics when she visits the
dentist. Should this information change your anesthetic plan?
What are: transcription, Promoter, mRNA, intron, exon, translation?
DNA is the nucleic acid that is the genetic material determining the makeup of all living cells and many viruses. It
consists of two long strands of nucleotides linked together in a structure resembling a ladder twisted into a spiral.
DNA can replicate itself. DNA also serves as a template for the synthesis of RNA.
Transcription is the process of transcribing or making a copy of genetic information stored in a DNA strand into a
complementary strand of RNA (messenger RNA or mRNA) with the aid of RNA polymerases.
Promoter is a site on DNA to which the enzyme RNA polymerase can bind and initiate the transcription of DNA
into RNA.
Messenger RNA (mRNA) is synthesized from a DNA template during transcription; it mediates the transfer of
genetic information from the cell nucleus to ribosomes in the cytoplasm, where it serves as a template for protein
synthesis.
Intron is a segment of a gene situated between exons that is removed before translation of messenger RNA and does
not function in coding for protein synthesis
Exon is a segment of a gene that contains information used in coding for protein synthesis.
Translation is the process by which the genetic code carried by mRNA directs the production of proteins from amino
acids.
What are: gene, locus, allele, mutation, SNP?
Gene is the basic physical unit of heredity; a linear sequence of nucleotides along a segment of DNA that provides
the coded instructions for synthesis of RNA, which, when translated into protein, leads to the expression of
hereditary character.
Locus is the chromosomal position of a gene as determined by its linear order relative to the other genes on that
chromosome.
Allele is an alternative form of a gene (one of a pair) that is located at a specific position on a specific chromosome.
An allele determines distinct traits that can be passed on from parents to offspring. The process by which alleles are
transmitted was reported by Mendel.
Mutation is a permanent, heritable change in the nucleotide sequence in a gene or a chromosome.

501
Page 2
Single nucleotide polymorphism (SNP) is DNA sequence variations that occur when a single nucleotide (A,T,C or
G) in the genome sequence is altered. Each individual has many single nucleotide polymorphisms that together
create a unique DNA pattern.

What are: phenotype, genotype, homozygous, heterozygous?
Phenotype is the outward, physical manifestation of the organism. These are the physical parts, structures,
metabolism, energy utilization, organs and so on (for example tall or short stature).
Genotype is the internally coded, inheritable information carried by all living organisms.
Homozygous refers to having identical alleles for a single trait
Heterozygous refers to having two different alleles for a single trait.

What is gene polymorphism and what is the nomenclature used to label it?
Genetic polymorphism occurs when many forms of DNA sequences at a locus within the population, exist together.
It also implies a discontinuous genetic variation that results in different forms or types of individuals among the
members of a single species.
Gene polymorphisms are labeled using three different nomenclature systems:
1. A118G SNP of the !-opioid receptor gene codes for the replacement of the nucleotide adenine (A) at base
pair 118 with guanine (G). A number to signify the gene locus (118). The letter before the number signifies
the nucleotide most commonly found at the gene locus (i.e., the wild-type or major allele), whereas the
letter after the number represents the nucleotide found in the mutant or minor allele.
2. Asp70Gly polymorphism of the butyrylcholinesterase gene describes a glycine substitution for aspartate at
the 70
th
amino acid of the protein. (same as the first but this system describes protein and the first describes
DNA)
3. Numbering the different alleles (e.g., *1). For example, the CYP2D6*5 allele is the fourth identified
variant in the cytochrome P-450 (CYP) enzyme 2D6. This system is the least descriptive but most flexible.

What are the potential anesthetic implications for medicating a patient carrying the allele A290G (*1b) for
the gene CYP3A4 and homozygote for butyryl-cholinesterase Asp70Gly polymorphism.
Pharmacogenetics is the study of how the actions of and reactions to drugs vary with the patient's genes. In a study
performed in young healthy men (our patient is a female), Hepatic CYP3A activity and the systemic clearance of
midazolam were about 30% lower in G/G homozygotes than in A/A homozygotes
2
. In addition there is considerable
inter-individual variability, and body size appears to be an important determinant
3
. Furthermore, it is not known
whether the patient carries a single allele with the substitution (heterozygote) or two alleles (homozygote). For these
reasons the information concerning CYP3A4 is not very helpful in managing this patient.
However being homozygote for butyrylcholinesterase Asp70Gly polymorphism is very informative: After a single
dose of succinylcholine the normal population usually recovers within ten minutes. Heterozygous (single allele)
expression of the butyrylcholinesterase Asp70Gly polymorphism results in production of a less effective form of
plasma butyrylcholinesterase. These patients typically take three to eight times longer to recover neuromuscular
function after succinylcholine administration. Homozygous expression (both alleles) of the butyrylcholinesterase
Asp70Gly polymorphism prolongs the recovery of neuromuscular function even further, resulting in a recovery
period up to 60 times longer than that associated with the normal allele

What are genetic linkage and gene association studies?
Genetic linkage is the tendency of certain loci or alleles to be inherited together. Assume we observe individuals of
an experimental population by looking at the relationships among phenotypes. Some phenotypes or traits can occur
randomly with respect to one another (independent assortment), or with some correlation with respect to one
another. Independent assortment occurs when the genes affecting the phenotypes are found on different
chromosomes or separated by a great enough distance on the same chromosome. The exception to independent
assortment occurs when genes appear near one another on the same chromosome. This phenomenon causes the

501
Page 3
genes to usually be inherited as a single unit. Genes inherited in this way are said to be linked. A haplotype is a
combination of alleles at closely linked loci on a single chromosome that tend to be inherited together.

Classical Linkage studies typically examine families with a high prevalence of an anomalous phenotype
comparing thousands of genes between family members with and without the anomaly. Gene association studies are
used to determine the influence of human genetic variation on the pathogenesis of disease, variability in disease
expression, and response to treatment. SNPs have been shown to be a powerful tool for identifying disease genes by
association analysis of patients and controls. However association analyses must be statistically powered, they must
also include an adequate genetic variation within each of the groups (cases or controls). Lastly, the assumption that
trait-influencing genes are inherited by descent may not identify influential genes, because the association will be
divided between multiple loci in the sample of affected individuals.
An example of these studies is the association between Ventricular dysfunction and specific gene variants as will be
discussed below.

Can an SNPs profile predict postoperative complications?
After cardiac surgery 10 -20% of the patients suffer from ventricular dysfunction. In a study blood sample were
collected from over one thousand patients undergoing coronary artery bypass graft operation and genotyped them
for 139 different SNPs within seven genes (genes that belong to the natriuretic peptide system)
4
. Results showed
that seven genetic variants (within the genes NPPA/NPPB and NPR3) predicted postoperative ventricular
dysfunction (defined by the need for two or more inotropes, IABP or ventricular assist device and dyspnea score).
Similar association between genotypes within the natriuretic peptide system and cardiovascular outcomes were
found when patients with known coronary heart disease were followed for a median of 2.8 years
5
.
The SNPs do not have to be part of a known gene, they can be just a marker, for example, noncoding SNPs within
the chromosome 4q25 region are independently associated with postoperative atrial fibrillation after coronary artery
bypass graft surgery
6

What is the genetic basis for the difference in pain sensitivity in redheads?
Red hair is a classical phenotype, the genetic basis for red hear is a dysfunctional melanocrotin-1 receptor on the
surface of melanocytes. Women with red hair require almost 20% more anesthetic (desflurane) than women with
dark hair
7
and are more resistant to the effect of subcutaneous lidocaine
8
. The melanocrotin-1 receptor gene
mediates not only mechanisms of analgesia in a mouse model in which the gene is mutated and rendered
dysfunctional (interestingly, for females only) but had the same effect in healthy redhead women as well
9
. The
explanations for this phenomenon are not thoroughly understood; although melanocrotin-1 receptor is expressed in
glial cells and the pituitary, the CNS is not a major site expression.

References
1. Eisenach JH, Schroeder DR. Genomic discoveries in perioperative medicine: educating the audience.
Anesthesiology. 2009 Apr;110(4):693-5.
2. Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR. CYP3A activity in African American and
European American men: population differences and functional effect of the CYP3A4*1B5'-promoter region
polymorphism. Clin Pharmacol Ther. 2000 Jul;68(1):82-91.
3. Tateishi T, Watanabe M, Nakura H, Asoh M, Shirai H, Mizorogi Y, Kobayashi S, Thummel KE, Wilkinson GR.
CYP3A activity in European American and Japanese men using midazolam as an in vivo probe. Clin Pharmacol
Ther. 2001 May;69(5):333-9.

501
Page 4
4. Fox AA, Collard CD, Shernan SK, Seidman CE, Seidman JG, Liu KY, Muehlschlegel JD, Perry TE, Aranki SF,
Lange C, Herman DS, Meitinger T, Lichtner P, Body SC. Natriuretic peptide system gene variants are associated
with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology. 2009 Apr;110(4):738-47.
5. Ellis KL, Newton-Cheh C, Wang TJ, Frampton CM, Doughty RN, Whalley GA, Ellis CJ, Skelton L, Davis N,
Yandle TG, Troughton RW, Richards AM, Cameron VA. Association of genetic variation in the natriuretic peptide
system with cardiovascular outcomes. J Mol Cell Cardiol. 2011 Apr;50(4):695-701
6. Body SC, Collard CD, Shernan SK, Fox AA, Liu KY, Ritchie MD, Perry TE, Muehlschlegel JD, Aranki S,
Donahue BS, Pretorius M, Estrada JC, Ellinor PT, Newton-Cheh C, Seidman CE, Seidman JG, Herman DS,
Lichtner P, Meitinger T, Pfeufer A, Kb S, Brown NJ, Roden DM, Darbar D. Variation in the 4q25 chromosomal
locus predicts atrial fibrillation after coronary artery bypass graft surgery. Circ Cardiovasc Genet. 2009
Oct;2(5):499-506.
7. Liem EB, Lin CM, Suleman MI, Doufas AG, Gregg RG, Veauthier JM, Loyd G, Sessler DI. Anesthetic
requirement is increased in redheads. Anesthesiology. 2004 Aug;101(2):279-83.
8. Liem EB, Joiner TV, Tsueda K, Sessler DI. Increased sensitivity to thermal pain and reduced subcutaneous
lidocaine efficacy in redheads. Anesthesiology. 2005 Mar;102(3):509-14.
9. Mogil JS, Wilson SG, Chesler EJ, Rankin AL, Nemmani KV, Lariviere WR, Groce MK, Wallace MR, Kaplan L,
Staud R, Ness TJ, Glover TL, Stankova M, Mayorov A, Hruby VJ, Grisel JE, Fillingim RB. The melanocortin-1
receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad Sci U S A.
2003 Apr 15;100(8):4867-72.

Disclosure

505
Page 1
Depth of Anesthesia and Outcome
Pedro Amorim, M.D. Porto, Portgual
509
Page 1
Perioperative Management of Pulmonary Hypertension
Ronald G. Pearl, M.D., Ph.D. Stanford, California
When the World Health Organization organized the first international conference on pulmonary
hypertension (PH) in 1973, there were no effective therapies, and median survival for patients with primary
pulmonary hypertension (now termed idiopathic pulmonary arterial hypertension) was less than three years. Today,
there are multiple therapies, and survival has more than doubled. As a result, more patients with PH undergo
anesthesia and surgery. Successful management of the perioperative patient with PH requires seven steps:
recognizing the disorder, diagnosing the etiology, assessing the severity of the disease, assessing the risks and
benefits of anesthesia and surgery, developing an anesthetic plan, and managing the anticipated complications of
systemic hypotension and right heart failure (Pritts).
The pulmonary circulation is normally a low pressure, low resistance circulation. PH is defined as a mean
pulmonary artery pressure (PAP) ! 25 mmHg at rest (Humbert). The stroke volume of the thin-walled right ventricle
decreases in response to increased PAP. In patients with PH, altered vascular endothelial and smooth muscle
function lead to vasoconstriction, localized thrombosis, and vascular growth and remodeling (Chan). These
processes increase pulmonary vascular resistance (PVR), resulting in RV failure, inadequate oxygenation and death.
PH markedly increases morbidity and mortality among patients undergoing surgery (Carmosino, Kaw, Price,
Ramsay, Ramakrishna). Understanding the pathophysiology of PH allows accurate risk assessment, optimization
prior to surgery, and rational intraoperative and postoperative treatment.
An approach to understanding the pathophysiology of PH is derived from the equation for PVR:
PVR = (PAP - LAP) x 80 / CO
where PVR is in dynes
.
sec
.
cm
-5
, PAP is mean pulmonary artery pressure (in mm Hg), LAP is left atrial pressure (in
mm Hg), and CO is cardiac output (in L
.
min
-1
). Rearranging this equation for PAP demonstrates that:
PAP = LAP + (CO x PVR) / 80.
Thus, the three factors which account for increased PAP are increased LAP, increased cardiac output, and increased
PVR. Therapy of the perioperative patient with PH requires an assessment of the quantitative contribution of each of
these components. For example, patients with mitral stenosis who have increased PAP due solely to increased LAP
have uncomplicated perioperative courses, but patients with mitral stenosis who have increased PAP due to
increased PVR commonly have severe RV failure after surgery and may not wean from cardiopulmonary bypass.
Pulmonary vasodilator therapy would be inappropriate in one patient but life-saving in the other. In patients with
PH, analyzing whether cardiac output remains normal or is markedly decreased has prognostic value in assessing
perioperative risk (see section on risk assessment).
The current classification of PH involves five major categories (pulmonary arterial hypertension,
pulmonary venous hypertension, PH associated with disorders of the respiratory system and/or hypoxemia, chronic
thrombotic and/or embolic disease, and PH due to disorders directly affecting the pulmonary vasculature)
(Simonneau). The above equation for PAP can be used to characterize the common etiologies. Increased LAP
includes LV failure and valvular heart disease (particularly mitral stenosis and/or regurgitation). Increased cardiac
output includes patients with congenital heart disease with cardiac shunts. The major categories of chronically
increased PVR are pulmonary disease (parenchymal or airway), hypoxia without pulmonary disease
(hypoventilation syndromes, high altitude), pulmonary arterial obstruction (thromboembolism), and idiopathic
(primary) pulmonary hypertension. In addition to these etiologies of chronic PH, acute increases in PVR may result
from hypoxia, hypercarbia, acidosis, increased sympathetic tone, and endogenous or exogenous pulmonary
vasoconstrictors such as catecholamines, serotonin, thromboxane, and endothelin. Most perioperative patients with

509
Page 2
decompensated PH have an acute increase in PVR superimposed on chronic PH; in general, therapy is directed at
reversing this acute increase in PVR.

Evaluation: The diagnosis of PH is usually suspected either from symptoms or from associated diseases which
increase risk. Evaluation of the patient with pulmonary hypertension should determine the underlying diagnosis and
the severity of the disease (Badesch). History and physical examination should focus on issues such as underlying
lung disease, congenital heart disease, myocardial or valvular heart disease, thromboembolic disease, connective
tissue disease, liver disease, HIV infection, prior intravenous drug use, prior use of appetite-suppressant drugs, and
family history of pulmonary hypertension. Patients should be considered for evaluation for sleep-disordered
breathing, either as the primary etiology or as a complicating factor. Laboratory tests should include routine
chemistries, hematology, thyroid function tests, HIV serology, and autoimmune screen (antinuclear antibodies
including anti-centromere antibody, anti-SCL70, and ribonucleoproteins). Ventilation-perfusion lung scan should be
performed to exclude chronic thromboembolic pulmonary hypertension; patients with this disorder should be
considered for pulmonary angiography and surgical thromboendarterectomy (Piazza). Echocardiography with
Doppler measurements can determine right ventricular function and right ventricular systolic pressure (Cacciapuoti,
Janda, Pedoto). Pulmonary artery catheterization will quantify pulmonary hemodynamics and demonstrate whether
the pulmonary circulation is reactive to vasodilators (Badesch, Barst, McLaughlin, Tonelli). Measurement of
vasodilator responsiveness should be performed with a short-acting vasodilator such as inhaled nitric oxide, inhaled
prostacyclin, intravenous prostacyclin, or intravenous adenosine; vasodilator-responsive patients should be
considered for chronic therapy with calcium channel blockers. Measurement of pulmonary artery pressure, cardiac
index, and right atrial pressure can be used to predict survival. Other major prognostic factors include the etiology of
PH, functional status, mixed venous oxygen saturation, and evidence of right heart failure. The six minute walk test
can be used to evaluate functional impairment, prognosis, and response to therapy.

Perioperative risk assessment: In the face of increased impedance to RV ejection, the compensatory reserves of
the RV are limited (Greyson). Reductions in RV stroke volume and cardiac output occur, eventually resulting in
ventricular interdependence with decreased LV filling (Afifi, Bogaard, Gan). In the patient with PH, anesthesia and
surgery may produce hemodynamic deterioration and death due to additional increases in PVR and decreases in RV
function.

Patients with PH have markedly increased morbidity and mortality with anesthesia and surgery (Hill, Kaw,
Madden, Memtsoudis, Price, Ramakrishna, Ramsay). For patients with Eisenmenger's syndrome undergoing
cesarean section, mortality is as high as 70% (Lane). However, recent data suggest much lower mortality rates in
both non-cardiac surgery and in obstetrics, particularly in experienced centers with multidisciplinary PH teams (Jais,
Maxwell, Meyer). Patients undergoing liver transplantation have increased mortality related to the severity of the
PH, with mortality rates as high as 100% when the mean PAP exceeds 50 mm Hg (Ayoub). The risks associated
with idiopathic (primary) PH appear to be even higher than those related to secondary PH. Reports of successful
outcomes of surgery in patients with severe PH include curative procedures such as lung or heart-lung
transplantation, cesarean section, and minor procedures such as lung biopsy, cholecystectomy, femoral artery repair,
and laparoscopic tubal ligation.

Survival in patients with PH correlates with the ability of the RV to compensate for the increased PVR as
assessed by cardiac output, right atrial pressure, and functional status. These factors also are major predictors of
perioperative risk in the surgical patient. Perioperative risk is also related to the surgical procedure (Ramakrishna).
Procedures with rapid blood loss may result in fatal hypotension since venous return is required to compensate for
increased RV afterload. Major procedures which result in a systemic inflammatory response syndrome (SIRS) may
exacerbate PH. Finally, some procedures may pose special risks for the patient with PH, such as pulmonary
embolization of air, bone marrow, and cement during joint replacement surgery. Risk assessment requires balancing
the functional reserves of the patient against the anticipated increased demands of the surgical procedure.

Progressive or acute increases in PAP leading to acute RV failure are the major complications of anesthesia
and surgery in patients with PH. For the patient at high risk, a preoperative pulmonary vasodilator trial may provide
additional prognostic information and be used for perioperative therapy. An inhaled vasodilator such as nitric oxide
or prostacyclin is an ideal agent since it produces rapid pulmonary vasodilation without systemic vasodilation.

509
Page 3
In patients who pose an unacceptably high risk following optimization of therapy, consideration should be
given to lung or heart-lung transplantation or to chronic treatment to decrease PH to acceptable levels before
surgery. Several authors and societies have created guidelines for the management of pulmonary hypertension
(Barst, McLaughlin). In general, oral calcium channel blockers are used for patients with a positive acute
vasoreactivity test, and prostanoids (epoprostenol or treprostinil), endothelin antagonists (bosentan), and PDE5
inhibitors (sildenafil) are used in patients who either do not have acute vasoreactivity or fail calcium channel blocker
therapy. The choice of specific agents is primarily based upon the patients functional status, and combination
therapy is increasingly used.

Preparation of the Patient for Anesthesia and Surgery: Prior to anesthesia and surgery, patients with PH should
have an electrocardiogram, chest X-ray, arterial blood gas, and echocardiogram. Evidence of significant RV
dysfunction should prompt re-evaluation of the need for surgery. All attempts to reduce PH prior to surgery should
be performed, such as the administration of oxygen, bronchodilators, antibiotics, and steroids to the patient with
obstructive lung disease, and vasodilators and inotropes to the patient with cardiac disease.

Patients receiving chronic therapy for PH should continue on such therapy throughout the perioperative
period (Vachiry). Patients on chronic prostacyclin (epoprostenol) or treprostinil infusions should have the infusion
continued throughout the perioperative period, and management of hypotension should be with vasopressor therapy
rather than with downward titration of the infusion. Our approach at Stanford has been that a nurse specializing in
PH converts the infusion to the hospital pump system prior to surgery. Although prostacyclin inhibits platelet
aggregation, surgical bleeding is rarely a problem. Patients on chronic inhaled iloprost should receive a treatment
prior to surgery. If they are unable to continue inhaled iloprost after surgery, consideration should be given to
inhaled nitric oxide, nebulized iloprost, or intravenous or nebulized prostacyclin.

Anesthetic management: The anesthetic management of patients with PH undergoing noncardiac surgery remains
controversial (Galante, Gille, Gordon, MacKnight, Pritts, Ross, Salehi, Strumpher, Teo). Most reports have involved
obstetrical anesthesia in adults and repair of congenital heart defects in pediatrics. Most authors agree that the way a
specific anesthetic technique is managed is as important as the choice of the technique. In the absence of evidence-
based recommendations, anesthesiologists need to focus on basic hemodynamic principles.

Physiologic Considerations and Goals: The anesthetic plan for the patient with PH is designed to account for the
underlying pathophysiology. The major abnormality is the elevated PVR, which increases RV afterload, thereby
increasing RV work and decreasing RV (and thus LV) output (Afifi). Based on the underlying pathophysiology, the
major anesthetic considerations include:
1) Preload: Maintenance of preload (intravascular volume) at normal or increased levels is essential to
maintain cardiac output in the face of increased RV afterload.
2) Systemic vascular resistance (SVR): In normal hemodynamic states, SVR is a major determinant of LV
afterload (and, therefore, cardiac output). In PH, cardiac output is limited by RV function and is therefore
independent of SVR. In order to avoid systemic hypotension, SVR must be maintained in the normal-to-high range.
3) Contractility: Maintenance of normal-to-high contractility is essential to maintain cardiac output in the
face of increased RV afterload.
4) Heart rate and rhythm: Sinus rhythm is important for adequate filling of a hypertrophied right ventricle.
Stroke volume is limited by ventricular afterload, so bradycardia should be avoided. Patients with PH commonly
have excess vagal activity.
5) Avoidance of myocardial ischemia: Right ventricular subendocardial ischemia due to myocardial oxygen
supply-demand imbalance is common in PH. Systemic hypotension and excessive increases in preload, contractility,
and heart rate must be avoided.
6) Pulmonary vascular resistance: In PH, PVR is the major factor governing RV afterload and cardiac
output. Therefore, increases in PVR must be avoided and therapy to decrease PVR may be required.
7) Avoidance of hypotension: Systemic hypotension precipitates RV failure by decreasing coronary
perfusion of the RV and by decreasing the contribution of the interventricular septum to RV ejection.

Perioperative Monitoring: Monitoring during anesthesia must be adequate to detect the causes and complications
of increased PVR. Arterial catheterization allows continuous blood pressure monitoring and arterial blood gas
measurements. Monitoring of preload requires understanding the altered physiology of PH. In the absence of PH,
cardiac output is determined by LV function, and preload is estimated by pulmonary artery occlusion (wedge)

509
Page 4
pressure (PAOP). However, in severe PH, cardiac output is limited by RV function, so the relevant measurement is
right atrial pressure or CVP. Therefore, in severe PH, volume administration should be governed by CVP rather than
PAOP. In fact, excess volume administration may exacerbate RV failure and produce further hemodynamic
deterioration. In moderate PH, cardiac output varies with both left and right ventricular performance. In this case,
monitoring both CVP and PAOP and observing the response to volume administration is the best method for
assessing preload. Intraoperative transesophageal echocardiography (TEE) allows continuous assessment of the
filling and function of both ventricles (Pedoto).

Pulmonary artery catheterization allows measurement of CVP, PAOP, PAP, cardiac output, PVR, and
SVR. These values can guide therapy of systemic hypotension (see below). Monitoring mixed venous oxygen
saturation by pulmonary artery oximetry (or central venous saturation by oximetry) allows continuous assessment of
the adequacy of cardiac output. However, the risk of pulmonary artery catheterization in patients with PH is
increased, due to the high mortality of associated arrhythmias, pulmonary artery rupture, and venous air embolism or
thromboembolism. Thermodilution cardiac output determinations may be misleading if PH is associated with
anatomic shunting or tricuspid regurgitation. The risks and benefits of pulmonary artery catheterization must be
individually assessed. Pulmonary artery catheterization is usually not indicated in patients with intracardiac shunting
due to the high risk of catheter misdirection and the limited additional information over measurement of CVP alone.

Choice of Anesthetic Technique: Many anesthetic techniques have been successfully used in patients with PH.
Since general anesthesia in patients with PH has significant risks, peripheral nerve blocks should be considered
when appropriate. The use of neuraxial regional techniques (spinal or epidural block) may decrease SVR, and
thereby produce systemic hypotension when cardiac output is fixed due to PH. Thus, spinal anesthesia is
contraindicated in many patients. Epidural anesthesia has been successful in selected patients (Martin), particularly
when the magnitude of the block is limited, e.g., management of labor. Epidural anesthesia allows a slow onset of
block and titration of the extent of block so that adverse hemodynamic effects may be recognized in early stages and
corrected. Thoracic epidural blockade by itself has only minor hemodynamic effects but must be titrated slowly to
avoid bradycardia and decreased RV contractility. Excess sedation which may decrease SVR and produce
respiratory depression should be avoided when regional anesthesia is used. Intrathecal and epidural narcotics
provide excellent pain relief postoperatively or during labor without producing sympathetic blockade.

General anesthesia remains the method of choice for major surgery in many patients with PH. Isoflurane,
sevoflurane, and desflurane may produce beneficial pulmonary vasodilation, but decreased contractility and
decreased SVR can result in systemic hypotension. In general, patients with PH with adequate functional reserve
will tolerate volatile agents. Narcotic-nitrous oxide techniques maintain SVR, but may produce hypoxia and
decreased contractility; in addition, nitrous oxide increases PVR in patients with PH. In patients undergoing short
procedures with intense stimulation such as bronchoscopy, a remifentanil infusion can provide short-acting
analgesia. In poorly compensated patients, a high-dose narcotic-oxygen technique maintains preload, SVR, and
contractility without increasing PVR; in fact, the use of 100% oxygen may produce pulmonary vasodilation.
Dexmedetomidine has no direct effect on PVR and can be useful as an adjunct for general or regional anesthesia.

Anesthetic induction is an unstable period during which patients with PH are prone to develop systemic
hypotension and cardiovascular collapse; continuous monitoring of blood pressure by an arterial catheter is therefore
usually indicated prior to induction. Etomidate (supplemented by fentanyl) maintains systemic hemodynamics
during induction without affecting PVR and is usually the agent of choice. In contrast, pentothal and propofol may
decrease SVR, venous return, and/or contractility. Ketamine maintains systemic hemodynamics, but questions have
been raised about possible increases in PVR. Studies suggest that there is little or no increase in PVR when adequate
ventilation is maintained (Williams), and that any increase in PVR will be less than the increase in SVR.

Ventilatory management may affect PVR. Alveolar hypoxia produces pulmonary vasoconstriction, and
high inspired oxygen concentrations may produce pulmonary vasodilation. Hypercarbia with acidosis is a potent
pulmonary vasoconstrictor, and hypocarbia is a pulmonary vasodilator. Hyperventilation decreases the pulmonary
hypertensive response to various stimuli. PVR is dependent upon functional residual capacity (FRC), such that PVR
is increased whenever FRC is increased or decreased from its normal value. Ventilatory parameters may affect both
FRC and peak lung volume. FRC is decreased during general anesthesia. This decrease in FRC can be reversed with
PEEP, resulting in a decrease in PVR. However, excessive PEEP will increase FRC above optimal values and
increase PVR. The effect of tidal volume on PVR may similarly be bimodal. At low tidal volumes, alveolar hypoxia

509
Page 5
and hypercarbia may occur and thereby increase PVR. At high tidal volumes, lung volume intermittently exceeds
normal FRC, resulting in compression of intra-alveolar vessels and increased PVR. Therefore, ventilation of the
patient with PH should use high concentrations of oxygen, moderate tidal volumes, rates sufficient to prevent
hypercarbia, and low levels of PEEP (5-10 cm H
2
O).

Management of emergence from anesthesia requires maintaining hemodynamic stability and adequate
alveolar ventilation. The major factor responsible for hemodynamic stability is the ratio of pulmonary to systemic
vascular tone. Extubation in a deep plane of anesthesia to avoid pulmonary vasoconstriction may be complicated by
decreased SVR, decreased contractility, and inadequate ventilation (producing hypoxemia or hypercarbia and
increasing PVR). Extubation in a light plane of anesthesia can result in severe pulmonary vasoconstriction. The
addition of narcotics to a primarily inhalational technique may allow extubation in a light plane of anesthesia
without increasing sympathetic tone. A narcotic-oxygen anesthetic technique followed by postoperative mechanical
ventilation is sometimes required for patients with severe PH undergoing major surgery.

Patients with PH have limited ability to tolerate any further increase in PVR. It is therefore important to
avoid introduction of air or particulate matter into the venous system. In patients with anatomic shunting (such as a
PFO), venous embolization may also result in systemic embolization.

Treatment of Perioperative Hypotension: Hemodynamic management in PH should maintain blood pressure and
cardiac output and minimize PVR. When cardiac output is inadequate, inovasodilator agents such as dobutamine and
milrinone can increase cardiac output and decrease PVR. Systemic hypotension should be aggressively treated since
it decreases right ventricular myocardial perfusion (producing ischemia) and decreases the contribution of the
interventricular septum to right ventricular cardiac output (Bronicki). The management of systemic hypotension in
the patient with PH can be challenging. As shown below, systemic hypotension may result from four etiologies,
each of which has a specific hemodynamic pattern:

Etiology CVP PAP PAOP CO
Decreased preload !! ! ! !
Decreased contractility " ! " !
Decreased SVR # # # or ! " or #
Increased PVR " " ! !

Pulmonary artery catheterization allows differentiation among these etiologies. Decreased preload is the only
etiology which decreases CVP; titrated volume therapy is indicated since excess volume administration with a
failing RV may result in further distention and dysfunction. Decreased contractility is the only condition that results
in an increase in CVP with a decrease in PAP; inotropic therapy is indicated. When decreased systemic blood
pressure occurs without a decrease in PAP, the ratio of PVR to SVR has increased. The initial approach should be to
reverse correctable causes of increased PVR such as hypoxia, hypercarbia, acidosis, increased sympathetic tone, and
endogenous or exogenous vasoconstrictors. In patients without correctable factors, cardiac output measurement will
differentiate between decreased SVR (cardiac output increased or unchanged) and increased PVR (cardiac output
decreased with unchanged or increased PAP). Decreased SVR may be treated by using relatively selective systemic
vasoconstrictors such as phenylephrine or vasopressin (Price). A combined inotropic-vasopressor agent such as
epinephrine or norepinephrine may also be useful.

When an increase in PVR decreases cardiac output and produces systemic hypotension, pulmonary
vasodilator therapy is required to interrupt the cycle of PH producing hypotension which decreases RV coronary
perfusion with a further decrease in cardiac output; similarly, low cardiac output produces desaturation of mixed
venous blood, resulting in increased pulmonary vasoconstriction. The goals of pulmonary vasodilator therapy are
two-fold: first, to reduce PVR and thereby decrease PAP and/or increase cardiac output, and, second, to reduce the
PVR/SVR ratio (Granton). All systemic vasodilators can produce pulmonary vasodilation, but use of these agents
frequently results in systemic hypotension. In PH, cardiac output varies with RV function. For the majority of drugs,
systemic vasodilator effects occur at doses which do not produce pulmonary vasodilation. Thus, with a decrease in
SVR and no change in PVR, cardiac output cannot increase and systemic blood pressure must decrease (BP = CO X
SVR).

509
Page 6
Pulmonary vasodilators include direct-acting nitrovasodilators such as nitroglycerin and nitroprusside;
alpha-adrenergic blockers; beta-adrenergic agonists; calcium channel blockers; and prostaglandins. In the
perioperative setting, short-acting titratable agents should be used, and the effects should be assessed at each dose
before increasing to a higher dose.

For severe perioperative PH resulting in RV failure, inhaled vasodilator therapy is the treatment of choice
(Zamanian). This approach was first developed with inhaled nitric oxide (NO) (Creagh-Brown). Inhaled NO diffuses
from the alveoli to the adjacent pulmonary vascular smooth muscle cells to produce pulmonary vasodilation. Inhaled
NO does not produce systemic vasodilation because any NO which diffuses into the blood is inactivated by binding
to hemoglobin. Inhaled NO may improve ventilation-perfusion matching by increasing blood flow to ventilated
alveoli. Inhaled NO decreases perioperative PH in multiple settings, particularly following cardiopulmonary bypass.
Inhaled NO may be useful in patients with allograft dysfunction following lung transplantation since NO may
decrease PH, improve ventilation-perfusion mismatch, and decrease ischemia-reperfusion lung injury. Inhaled NO
improves outcome in neonatal PH with hypoxic respiratory failure as judged by a decreased frequency of death or
ECMO. Although inhaled NO improves oxygenation and decreases PH in the acute respiratory distress syndrome,
randomized studies have not demonstrated sustained improvement or improved outcome (Adhikari).

In general, inhaled NO in patients with PH demonstrates maximal responses at doses of 10 ppm or less. A
trial of 20 ppm inhaled NO is sufficient to determine if the patient will have a beneficial response. Discontinuation
of inhaled NO after several hours of administration may produce rebound PH. Rebound PH may represent
progression of underlying PH, decreased endogenous NO synthesis, downregulation of guanylyl cyclase, or
activation of endogenous vasoconstrictor pathways such as endothelin. Approximately one-third of patients with PH
have little or no response to inhaled NO. Inhibition of cyclic GMP phosphodiesterase with sildenafil can increase the
frequency, the magnitude, and the duration of response to inhaled NO and decrease rebound effects. Sildenafil alone
is commonly used to prevent perioperative exacerbation of PH or to allow weaning of inhaled NO in the
postoperative period.

Other inhaled vasodilators may also produce selective pulmonary vasodilation (Buckley, De Wet, Ewert,
Fattouch, Lowson, Winterhalter, Wang). These include prostaglandin derivatives (prostacyclin, prostaglandin E1,
and iloprost), nitrovasodilators (nitroglycerin, nitroprusside), and milrinone. Multiple studies indicate that inhaled
prostacyclin is as effective as inhaled nitric oxide, and many centers routinely use inhaled prostacyclin due to cost
considerations. Combinations of agents which affect different mechanisms of vasodilation (e.g., NO which
increases cGMP and prostacyclin which increases cAMP) may produce additive pulmonary vasodilation
(OCallaghan).

Finally, patients undergoing cardiac surgery who develop intractable RV failure due to PH may be
candidates for a percutaneous or surgically implanted right ventricular assist device, either on a temporary basis until
RV function recovers or as a bridge to transplantation. Drugs with combined intropic and pulmonary vasodilator
effects such as dobutamine, the phosphodiesterase 3 inhibitor milrinone, or the calcium sensitizer levosimendan can
increase cardiac output in patients with PH (Gillies) and are commonly used in the ICU or in the setting of cardiac
surgery. However, their systemic vasodilator effects frequently contraindicate their use in patients with PH-induced
systemic hypotension until after correction of the hypotension.

Postoperative Management: Although the focus in the literature has been on intraoperative management of PH,
most patients who die in the perioperative period do so several days after surgery. Causes of death include
progressive increases in PVR, progressive decreases in cardiac function, and sudden death. Patients should be
monitored in an appropriate setting. The use of epidural narcotics and local anesthetics, continuous regional
anesthesia, and non-narcotic analgesic adjuvants should be considered. Dexmedetomidine has been used for sedation
and analgesia without producing respiratory depression (Toyama). PDE-5 inhibitors such as sildenafil may be useful
postoperatively in allowing weaning from inhaled pulmonary vasodilators (Boffini).

Summary: Patients with PH have markedly increased morbidity and mortality during anesthesia and surgery.
However, management based on physiologic principles using the seven steps outlined above can allow the majority
of patients with PH to safely undergo anesthesia and surgery.

509
Page 7
REFERENCES

Afifi S, Shayan S, Al-Qamari A. Pulmonary hypertension and right ventricular function: interdependence in
pathophysiology and management. Int Anesthesiol Clin 2009; 47:97-120.
Afshari A, Brok J, Mller AM, et al. Inhaled nitric oxide for acute respiratory distress syndrome and acute lung
injury in adults and children: a systematic review with meta-analysis and trial sequential analysis. Anesth
Analg 2011; 112:1411-21.
Ayoub T. Pulmonary hypertension in liver transplant. Curr Opin Organ Transplant 2011; 16:331-7.
Badesch DB, Champion HC, Sanchez MAG, et al. Diagnosis and assessment of pulmonary arterial hypertension. J
Am Coll Cardiol 2009; 54:S55-S66.
Barst RJ, Gibbs SR, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial
hypertension. J Am Coll Cardiol 2009; 54:S78-S84.
Boffini M, Sansone F, Ceresa F, et al. Role of oral sildenafil in the treatment of right ventricular dysfunction after
heart transplantation. Transplant Proc 2009; 41:1353-1356.
Bogaard HJ, Abe K, Noordegraaf AV, Voelkel NF. The right ventricle under pressure cellular and molecular
mechanisms of right-heart failure in pulmonary hypertension. Chest 2009; 135:794-804.
Bronicki RA, Baden HP. Pathophysiology of right ventricular failure in pulmonary hypertension. Pediatr Crit Care
Med 2010; 11(2 Suppl):S15-22.
Buckley MS, Feldman JP. Inhaled epoprostenol for the treatment of pulmonary arterial hypertension in critically ill
adults. Pharmacotherapy 2010; 30:728-40.
Cacciapuoti F. Echocardiographic evaluation of right heart function and pulmonary vascular bed. Int J Cardiovasc
Imaging 2009; 25:689-697.
Carmosino MJ, Friesen RH, Doran A, et al. Perioperative complications in children with pulmonary hypertension
undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007; 104:521-7.
Creagh-Brown BC, Griffiths MJ, Evans TW. Bench-to-bedside review: Inhaled nitric oxide therapy in adults. Crit
Care 2009; 13:221.
De Wet CJ, Affleck DG, Jacobsohn E, et al. Inhaled prostacyclin is safe, effective, and affordable in patients with
pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J
Thorac Cardiovasc Surg 2004; 127:1058-67.
Ewert R, Schper C, Halank M, et al. Inhalative iloprost - pharmacology and clinical application. Expert Opin
Pharmacother 2009; 10:2195-2207.
Fattouch K, Sbraga F, Bianco G, et al. Inhaled prostacyclin, nitric oxide, and nitroprusside in pulmonary
hypertension after mitral valve replacement. J Card Surg 2005; 20:171-6.
Galante D. Intraoperative management of pulmonary arterial hypertension in infants and children. Curr Opin
Anaesthesiol 2009; 22:378-82.
Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J
Med 2005; 353:2148-57.
Gan CT, Lankhaar JW, Marcus JT, et al. Impaired left ventricular filling due to right-to-left ventricular interaction in
patients with pulmonary arterial hypertension. Am J Physiol 2006; 290:H1528-33.
Gille J, Seyfarth HJ, Gerlach S, et al. Perioperative anesthesiological management of patients with pulmonary
hypertension. Anesthesiol Res Pract 2012:356982.
Gillies M, Bellomo R, Doolan L, et al. Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery--
a systematic literature review. Crit Care 2005; 9:266-79.
Gordon C, Collard CD, Pan W. Intraoperative management of pulmonary hypertension and associated right heart
failure. Curr Opin Anaesthesiol 2009; 23:49-56.
Granton J, Moric J. Pulmonary vasodilators--treating the right ventricle. Anesthesiol Clin 2008; 26:337-53.
Greyson CR. Pathophysiology of right ventricular failure. Crit Care Med 2008; 36(1 Suppl):S57-65
Hill NS, Roberts KR, Preston IR. Postoperative pulmonary hypertension: etiology and treatment of a dangerous
complication. Respir Care 2009; 54:958-968.
Humbert M, McLaughlin VV. The 4th World Symposium on Pulmonary Hypertension. J Am Coll Cardiol 2009;
54:S1-S2.
Jas X, Olsson KM, Barbera JA, et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern
management era. Eur Respir J 2012; 40:881-5.
Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: a
systematic review and meta-analysis. Heart 2011; 97:612-22.

509
Page 8
Kaw R, Pasupuleti V, Deshpande A, et al. Pulmonary hypertension: an important predictor of outcomes in patients
undergoing non-cardiac surgery. Respir Med 2011; 105:619-24.
Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy
subjects: a systematic review. Eur Respir J 2009; 34:888-894.
Lane CR, Trow TK. Pregnancy and pulmonary hypertension. Clin Chest Med 2011; 32:165-74.
Lowson SM. Inhaled alternatives to nitric oxide. Crit Care Med 2005; 33:S188-95.
MacKnight B, Martinez EA, Simon BA. Anesthetic management of patients with pulmonary hypertension. Semin
Cardiothorac Vasc Anesth 2008; 12:91-6.
Madden BP. Pulmonary hypertension and pregnancy. Int J Obstet Anesth 2009; 18:156-64.
Martin JT, Tautz TJ, Antognini JF. Safety of regional anesthesia in Eisenmenger's syndrome. Reg Anesth Pain Med
2002; 27:509-13.
Maxwell BG, El-Sayed YY, Riley ET, et al. Peripartum outcomes and anaesthetic management of parturients with
moderate to complex congenital heart disease or pulmonary hypertension. Anaesthesia 2013; 68:52-9.
McLaughlin VV, Archer SL, Badesch DB, et al. ACC/AHA 2009 expert consensus document on pulmonary
hypertension: a report of the American College of Cardiology Foundation Task Force on expert consensus
documents and the American Heart Association. Circulation 2009; 119:2250-2294.
Memtsoudis SG, Gonzlez Della Valle A, et al. In-hospital complications and mortality of unilateral, bilateral, and
revision TKA: based on an estimate of 4,159,661 discharges. Clin Orthop Relat Res 2008; 466:2617-27.
Meyer S, McLaughlin VV, Seyfarth HJ, et al. Outcome of non-cardiac, non-obstetric surgery in patients with
pulmonary arterial hypertension: results from an international prospective survey. Eur Respir J 2012; Epub
ahead of print
O'Callaghan D, Gaine SP. Combination therapy and new types of agents for pulmonary arterial hypertension. Clin
Chest Med 2007; 28:169-85.
Pedoto A, Amar D. Right heart function in thoracic surgery: role of echocardiography. Curr Opin Anaesthesiol
2009; 22:44-9.
Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2011; 364:351-60
Price LC, Forrest P, Sodhi V, et al. Use of vasopressin after Caesarean section in idiopathic pulmonary arterial
hypertension. Br J Anaesth 2007; 99:552-5
Price LC, Montani D, Jas X, et al. Non-cardiothoracic non-obstetric surgery in mild-moderate pulmonary
hypertension: perioperative management of 28 consecutive individual cases, Eur Respir J 2010; 35:1294-
302..
Pritts CD, Pearl RG. Anesthesia for patients with pulmonary hypertension. Curr Opin Anaesthesiol 2010: 23:411-6.
Raja SG, Danton MD, MacArthur KJ, Pollock JC. Treatment of pulmonary arterial hypertension with sildenafil:
from pathophysiology to clinical evidence. J Cardiothorac Vasc Anesth 2006; 20:722-35.
Ramakrishna G, Sprung J, Ravi BS, et al. Impact of pulmonary hypertension on the outcomes of noncardiac surgery:
predictors of perioperative morbidity and mortality. J Am Coll Cardiol 2005; 45:1691-9.
Ramsay MA. Portopulmonary hypertension and hepatopulmonary syndrome, and liver transplantation. Int
Anesthesiol Clin 2006; 44:69-82.
Ross AF, Ueda K. Pulmonary hypertension in thoracic surgical patients. Curr Opin Anaesthesiol 2010; 23:25-33.
Salehi A. Pulmonary hypertension: a review of pathophysiology and anesthetic management. Am J Ther 2012;
19:377-83.
Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll
Cardiol 2009; 54:43-54.
Strumpher J, Jacobsohn E. Pulmonary hypertension and right ventricular dysfunction: physiology and perioperative
management. J Cardiothorac Vasc Anesth 2011; 25:687-704.
Subramaniam K, Yared JP: Management of pulmonary hypertension in the operating room. Semin Cardiothorac
Vasc Anesth 2007; 11:119-36.
Teo YW, Greenhalgh DL. Update on anaesthetic approach to pulmonary hypertension. Eur J Anaesthesiol 2010;
27:317-23.
Tonelli AR, Alnuaimat H, Mubarak K. Pulmonary vasodilator testing and use of calcium channel blockers in
pulmonary arterial hypertension. Respir Med 2010; 104:481-96.
Toyama H, Wagatsuma T, Ejima Y, et al. Cesarean section and primary pulmonary hypertension: the role of
intravenous dexmedetomidine. Int J Obstet Anesth 2009; 18:262-7.
Vachiry JL, Simonneau G. Management of severe pulmonary arterial hypertension. Eur Respir Rev 2010; 19:279-
87.

509
Page 9
Wang H, Gong M, Zhou B, Dai A. Comparison of inhaled and intravenous milrinone in patients with pulmonary
hypertension undergoing mitral valve surgery. Adv Ther 2009; 26:462-468.
Williams GD, Philip BM, Chu LF, et al. Ketamine does not increase pulmonary vascular resistance in children with
pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation. Anesth Analg
2007; 105:1578-84.
Winterhalter M, Simon A, Fischer S, et al. Comparison of inhaled iloprost and nitric oxide in patients with
pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective
randomized trial. J Cardiothorac Vasc Anesth 2008; 22:406-13.
Zamanian RT, Haddad F, Doyle RL, et al. Management strategies for patients with pulmonary hypertension in the
intensive care unit. Crit Care Med 2007; 35:2037-50.

Disclosure

512
Page 1
Frail, Feeble or Fit? The oldest old what should we do differently for the geriatric patient
undergoing anesthesia- if anything?
Sheila Ryan Barnett, M.D. Boston, Massachusetts
Introduction
It is well known that the population is aging. It is estimated that by 2030 the percent of the population over the age
of 65 years will rise to 20%. The oldest old those over 85 years - actually represent one of the fastest growing
segments of the population and this population is expected to increase to over 20 million in the next 20 years. The
demographic shift in the population in the United States and developed countries in general has significant
ramifications- for health care and socioeconomically. For anesthesiologists, healthcare costs are often estimated
using estimates from surgical volume, however true estimates of cost need to take into account the patients medical
services associated with an operation, the hospitalization and the cost to the caretakers and society in general. As
leaders in perioperative care, there are few populations where the impact of our anesthetic care beyond the operating
room is more important than to the elderly individual and our aging population in general.
General Guidelines for treating Geriatric Patients
1. Advanced chronological age is not a contraindication to surgery
2. Clinical presentation of disease may have been atypical, leading to delays and errors in diagnosis
3. Assume inter-individual variability and titrate medications to physiological effect when possible
4. Expect complexity: multiple medications and illnesses: individuals > 65 y have on average 3.5 medical
diseases
5. Diminished organ reserve can be unpredictable and difficulty to measure preoperatively - limitations
may only become apparent during stress
6. A disproportionate increase in perioperative risk may occur without adequate preoperative
optimization for example following emergent procedures
7. Meticulous attention to detail can help avoid minor complications - which in elderly patients can
rapidly escalate into major adverse events
8. Impact of extrinsic factors - smoking, environment, socioeconomic - is difficult to quantify
Surgical Volume
Surgery is common in the older patient; this is not surprising given the steady increase in comorbid conditions
associated with advanced age. Sixty five percent of all visits to general surgeons occur in patients over 65 years, so
it not surprising that many of these patients are subsequently seen in the operating room. It is estimated that almost
50% of adult surgeries are performed in patient over the age of 65 years. In addition, specialty surgery also
continues to expand in orthopedics there has been marked increase in volume, and similar trends have been
observed in urological and other specialty surgeries.
Morbidity and Mortality
Older patients have higher complication rates and increased morbidity and mortality compared to younger patients,
especially in the oldest age range over 85 years. The highest mortality occurs following emergency surgery;
additional general risk factors for mortality include a low albumin, high ASA classification, limited preoperative
functional status and renal impairment. The development of a complication is one of the most significant predictors
of decreased survival. Hamel et al compared outcomes following non cardiac surgery in patients over 80 years with
a younger population, and found that in patients over 80 years who developed one or more complications the 30 day
mortality was 26 percent vs. 4 percent in patients without a complication. The type of complication mattered and
mortality rate was highest following a cardiac arrest (88 percent), acute renal failure (52 percent) and MI (48

holders.
512
Page 2
percent). In this analysis they found that each year over age of 80 was associated with a 5 percent increase in
mortality, thus a 90 year old had a 50 percent higher risk of mortality compared to an 80 years old. In general
studies looking at outcomes in patients over 90 years, mortality following non-cardiac emergency surgery ranges
from 19% to 35%. Of note in a study looking at non hip fracture emergency surgery they found a perioperative
morbidity rate of 62%, and the most common causes were confusion, renal failure and abdominal problems.
In summary, surgery in the very old patient carries a high mortality especially when complications occur. The lack
of tolerance for complications following surgery in older patients reflects an overall lack of physiological reserve in
the aged patient from both age related physiological changes and the impact of comorbid conditions.

Frailty definitions and impact
Historically preoperative risk has been largely determined through the identification of individual diseases that carry
inherent risk during anesthesia. Congestive heart failure is a good example of a preoperative condition that is
associated with increased morbidity following anesthesia, similarly patients with poor pulmonary function may be at
increased risk of complications following anesthesia and surgery. Most preoperative screening is focused on
specific diseases and there are limited ways to estimate the physiological reserve function in the elderly patient.
Frailty describes a distinct syndrome that is becoming increasingly recognized as an important predictor of survival
and prognosis. Frailty is associated with functional decline, loss of independence and increased mortality. Although
the risk of frailty increases with multiple comorbidities, frailty may also develop in the absence of a major disease.
It is not defined as one single disease entity, instead features of frailty include slow walking speed, sarcopenia,
osteoporosis, malnutrition, immune deficiency and anemia. Frailty is associated with an increased vulnerability
from adverse events such as disability, hospitalization and death.
Makary et al examined the utility of frailty as a preoperative risk marker for adverse events following surgery.
Using a validated 5 point scale they classified patients scheduled for elective surgery into 3 groups: Frail,
intermediately frail, and non frail. The determination of Frailty was based on established criteria: 1. unintentional
weigh loss >10 lbs 2. Weakness measure using a had grip strength 3. Exhaustion with activity 4. Low physical
activity 5. Slowed walking speed measured in 15 secs. Using NSQIP data they looked at rates of surgical
complications, length of stay and discharge to a place other than home within 30 days. They then compared the
utility of the Frailty index with more standard risk indices such as the ASA classification; Lees revised cardiac
index and the Eagle score. They found that frail patients had a higher incidence of adverse events, length of
discharge and discharge to institution. The frailty index improved the predictive value of the more standard risk
indices.
Similarly Robinson et al found that frailty in patient undergoing colorectal surgery was associated with significantly
higher costs from discharge to 6 months, and higher degrees of frailty were associated with increased
institutionalization post surgery and 30 day readmission.
In summary, frailty appears to provide a marker of physiological reserve and as such may become an important
preoperative risk factor for older patients. Simple methods to rapidly assess frailty are likely to become increasingly
important as the population ages.

Age related changes predisposing the elderly to poor outcomes
Excess mortality observed in older patients is mostly due to comorbid conditions as opposed to chronologic age per
se, however, some age related deterioration in organ function is observed in all body systems, leading to a reduction
in reserve function. By the age of 80 years an older healthy patient can only increase organ function by about 50%
compared to a healthy 30 year old patient, and in the presence of chronic disease this is further reduced. When
taking care of elderly patients, it is important to consider the underlying age related changes that occur, below is a
brief summary of the key age related changes.

Cardiovascular system
Age related cardiac changes are amongst the most predictable and important physiological changes that impact
anesthesia administration. Aging is associated with progressive stiffening and decreased compliance in the vessels
and the myocardium. These changes occur secondary to the combined effects of glycosylation and deposition of
free radicals in collagen and connective tissue leading to a gradual loss of elasticity. Ventricular compliance is
further reduced as systolic blood pressure and pulse wave velocity increase, leading to greater impedance to
ventricular outflow and subsequent myocardial hypertrophy. At the same time left ventricular relaxation during
diastole is impaired, leading to a decrease in early diastolic filling. This is known as diastolic dysfunction; it is

holders.
512
Page 3
estimated that one third of patients with normal preoperative left ventricular function have diastolic dysfunction.
These patients are very susceptible to fluid overload in the perioperative period.
During aging , vagal or parasympathetic tone is decreased and there is an increase in sympathetic nerve activity and
plasma levels of noradrenaline. Alpha receptor activity appears largely preserved, and beta receptors are less
responsive to stimulation with a lesser increase in heart rate and less arterial and venous relaxation with direct
stimulation. The accompanying reduction in baroreflex function and overall vascular stiffening leads to more labile
blood pressure and predisposes elderly patients to orthostatic hypotension. This may be exaggerated during
anesthesia especially in volume depleted patients. The impaired beta receptor responsiveness reduces an older
patients ability to respond to an increase in demand through increased heart rate alone and the elderly patient
becomes very reliant on vascular tone and preload.
The incidence of ischemic heart disease increases exponentially with aging and in contrast to younger counterparts,
older patients often present with shortness of breath instead of classic chest pain. This may cause it to be overlooked
preoperatively. Hypertension in the in older individuals and is a leading cause of congestive heart failure.
Congestive heart failure remains one of the most significant risk factors for mortality following anesthesia and
surgery.

Pulmonary System
Risk factors for postoperative pulmonary complications include severe chronic obstructive pulmonary disease,
advanced age and high risk procedures, such as upper abdominal or intrathoracic surgery. Unlike cardiac risk, age
alone remains a significant risk factor for postoperative pulmonary complications. The risk of a postoperative
pulmonary complication is twice as high in patients age 60 to 69 years compared to those aged 60 or less, and there
is a 3 fold increase in patients aged 70-79 years.

There are several predictable changes that occur during aging predisposing the older patient to complications; these
include a reduction in respiratory muscle strength, a decrease in chest wall compliance and a decrease in the elastic
recoil.
With aging, chest wall and muscular changes lead to an increase in the work of breathing. The diaphragm becomes
flattened and the chest becomes more barrel shaped; negatively impacting chest wall dynamics. These changes can
lead to diaphragmatic fatigue and a predisposition to respiratory failure in the postoperative period; this may
manifest as difficulty weaning from a ventilator, especially in frail older patients. Pulmonary changes with aging are
similar to those that occur with emphysema and central airways increase in size leading to increased anatomic and
physiologic deadspace. The lack of elastic recoil in smaller airways can result in air trapping with positive pressure
ventilation. Closing capacity is increased, and by mid 60s it exceeds FRC leading to closure of small airways and
increase in shunt fraction, predisposing older patients to hypoxemia.
Central nervous system changes lead to a decrease in hypoxemic and hypercapnic ventilatory drive this can be as
much as by 50%. This can result in a significant increase in susceptibility to narcotic induced apnea potentially
leading to unexpected hypoxemia and hypercapnia. The susceptibility to hypoxemia is enhanced by the gradual age
related decrease in resting arterial oxygen tension.

Metabolism and renal function
Changes in body composition, renal function and drug metabolism render the older patient vulnerable from drug
overdoses at usual adult doses. There is a decrease in the total body water and an increase in percentage of body
fat, accompanied by a reduction of protein and muscle mass. This can change the distribution of water and fat
soluble medications. For example declines in plasma volume and intracellular water can result in a significant
increase in the initial volume of distribution of a drug like propofol, resulting in an increase in plasma concentration
if the initial dose is not reduced. The change central volume, in addition to a potential delay in redistribution of the
propofol from the central compartment, may explain some of the exaggerated effects seen with propofol boluses in
older patients. In contrast, fat soluble medications, such as some of the opioids, may be deposited in larger fat
stores leading to prolonged and unpredictable recovery.
Glomerular filtration rate and creatinine clearance decline steadily and the degree of baseline impairment may be
underestimated by the serum blood urea nitrogen and creatinine alone. Postoperative renal failure is rare but is
associated with a high mortality rate, accounting for one fifth of postoperative deaths in elderly patients. Although
albumin levels are usually preserved in health, they may be diminished in older patients with chronic disease, and
reduced albumin levels remain a predictor of poor outcome in older patients.

holders.
512
Page 4
Central Nervous System
In addition to predictable anatomical changes in the central nervous system, there is an increase in dementia,
memory loss and degenerative diseases such as Parkinsons disease. Anatomical changes include gradual atrophy of
the brain, reduction in gray cells, and widening of the ventricles. The number of neuroreceptors and
neurotransmitters appear to decrease even in the absence of dementia or recognized neurodegenerative diseases.
The most significant declines observed are in acetylcholine and serotonin receptors in the cortex, dopamine
receptors in the neostriata, and dopamine levels in substantia nigra and neostrata. These alterations in
neurotransmitter levels and neuronal circuits leads to pharmacodynamic changes and changes in sensitivity to
certain medications such as midazolam and some of the opioids. Decrease in cholinergic receptor activity may
explain some of the sensitivity elderly patients have when exposed to medication such as scopolamine with high
anticholinergic potency.
Thermoregulation
Older patients are particularly vulnerable from developing hypothermia. Aged patients demonstrate diminished
effectiveness of peripheral vasoconstriction and shivering and have more difficulty maintain body temperature
during surgery and anesthesia. It is known that perioperative hypothermia can lead to significant negative effects
including reduced metabolism of medications, an increased oxygen demand associated with shivering leading to
potential myocardial ischemia, and coagulopathy. These may be poorly tolerated in the older patient with reduced
physiological reserve and comorbid conditions.

Adverse consequences in elderly patients and potential prevention strategies

Postoperative cognitive disorders
Delirium is the one of the most common and dreaded complications occurring postoperatively in the elderly
surgical patient. Delirium is an acute confusional state, usually appearing 1-3 days after surgery; it may persist for
weeks to months in afflicted patients. The etiology is multifactorial including acute medical conditions such as
sepsis, hypoxemia, urinary tract infections, and alcohol withdrawal. Certain medications including meperidine and
medications with anticholinergic effects such as diphenhydramine and scopolamine are associated with delirium.
Pain in the postoperative period may be an important and overlooked cause of delirium. Patients with preexisting
dementia, baseline cognitive difficulties and depression carry a higher risk of developing delirium postoperatively.
Delirium is associated with an increase in morbidity and mortality as well as an increase in the length of stay and
dependent living situations.
There is no magic bullet to treat or prevent delirium in elderly surgical patients. Some of the initiatives that have
been the most successful include the use of structured clinical protocols an specialized geriatric care units focusing
on risk factor modification. Other approaches include avoiding drugs known to precipitate delirium such as the
anticholinergic medication and avoiding meperidine in particular. Other strategies are largely practical including
appropriate treatment of postoperative pain, and careful selection and titration of drugs when sedation is required.
Low dose haloperidol (1.5 mg / per day) has been shown to reduce the length and severity or delirium and may have
some utility in high risk patients.
The initial assessment and treatment of delirium should be directed towards any reversible condition such as pain,
abnormal electrolytes, hypoxia, alcohol withdrawal and infection. Midazolam has been associated with a
paradoxical excitation in elderly patients with delirium and in general is not recommended, similarly long acting
benzodiazepines can accumulate in the older patient and should be avoided. For hip fracture patients, who are at
very high risk from developing delirium, there is some evidence that suggests lighter sedation levels combined with
spinal anesthesia may reduce the incidence of delirium.
In contrast to delirium, post operative cognitive dysfunction (POCD) refers to a specific cognitive disorder
generally recognized in the post operative period and is ultimately diagnosed through neuropsychological testing.
Studies have demonstrated that almost 10% of elderly patients receiving a general anesthesia had some cognitive
dysfunction 3 months after surgery. The etiology of PCOD is unclear at this point in time.

Avoiding Pulmonary complications
As discussed advanced age is associated with a gradual decrease in chest wall compliance and decreased respiratory
muscle strength, so any diminution in strength for example from residual effects of neuromuscular blockade, may
lead to hypoventilation and postoperative pulmonary complications. Long acting neuromuscular blockers such as
pancuronium should be avoided in elderly patients.

holders.
512
Page 5
Poor pain control may be a factor the contributing to the development of post operative pulmonary complications.
Although the data is limited, it does appear good pain control including epidural analgesia for can be beneficial for
aortic, vascular and thoracic surgery. Finally elderly patients are predisposed to aspiration, and precautions should
be taken to avoid this complication. Patients with swallowing disorders, Parkinsons and other neurological
syndromes are particularly high risk.

Cardiac risk in the elderly patient
Age is not a consistent independent predictor of perioperative cardiac risk, the role of disease is probably more
relevant as well as functional capacity. However in the event of an acute myocardial infarction, the intraoperative or
perioperative mortality is higher in geriatric vs. younger patients. Thus cardiac care is a very important aspect of
geriatric care. When considering reducing risk in the elderly patient a few important factors are: the use of beta
blockade and statins, the importance of blood pressure control perioperatively and the utility of a preoperative ECG.
In general beta blockers should be continued around surgery and administered perioperatively to high risk
individuals undergoing intermediate or high risk surgery as outlined by the American College of Cardiology
Foundation/American Heart Association guidelines. Indiscriminate and wide spread use of beta blockers is not
recommended.
Perioperative statin use should not be abruptly discontinued in the perioperative period. Statins in the perioperative
period are indicated in patients with high risk indices undergoing intermediate and high risk surgery.
The role of hypertension in attributing risk in the perioperative period is difficult to ascertain. However
observational data suggests that perioperative hypertension and intraoperative hypotension may be associated with
increased risk of myocardial infarction and mortality following surgery.

Age based criteria for patients undergoing low risk surgery is not recommended to guide ordering of preoperative
ECGs. However preoperative ECGs are indicated in patients with cardiac risk factors and active disease under
going at least intermediate surgery.
Anesthetic administration
Due to age related changes in physiology and comorbidities outlined above, anesthetic administration should be
tapered for the elderly. Older patients represent a heterogeneous group and each anesthetic should be tailored for the
individuals. In general start low, go slow remains a valid axiom when taking care of elderly patients and most
older patients require less anesthesia compared to younger counterparts. For example the MAC of inhalational
agents decreases predictably by 6% every decade after age 20 years. Thus the MAC at age 90 year is reduced by
30% compared to a 40 year old. Similarly, pharmacodynamic changes in elderly patients increase the sensitivity of
the brain to opioids, and as a general rule, opioid doses can be reduced by 50% in older patients. A carefully titrated
anesthetic may have advantages in the older patients especially if medication with known side effects such as
anticholinergic drugs can be avoided.

Dosing in the Elderly
1. Reduce initial dose of opioids by 50%
2. Increase intervals between boluses
3. Minimize medications
4. Monitor vitals signs
5. Consider supplemental oxygen
6. Consider significant comorbidities / complexity
7. Expect a potential longer recovery

Quality measures
In contrast to the standard quality assessment performance measures for surgery (myocardial infarction, surgical site
infection and deep venous thrombosis), process measures looking at multiple aspects of care such as interpersonal
communication, diagnostic and treatment strategies may be more relevant for elderly patients. Examples of areas
that may be included in a geriatric quality index are: frailty scores, comorbidity assessment, medication usage and
polypharmacy, documentation of a discussion regarding a patients decision making ability and advanced directives,
postoperative management including functional expectations, and discharge planning including a plan for at home
care or post discharge institutionalization. These are some examples, unfortunately there are significant difficulties
in implementing follow up on a large number of both objective and subjective indicators. Despite the difficulties,

holders.
512
Page 6
measuring quality of care will be especially important given the excess morbidity and mortality observed in this
growing population.

Summary of Challenges of the Geriatric Patient

1. Population is heterogeneous
2. Wide disparity between physiologic and chronological age
3. Advancing age is associated with a steady decline in organ function
4. Preoperative reserve organ function unknown
5. Multiple acute and chronic co-morbidities may co-exist
6. Common conditions may present atypically
7. Emergency procedures are associated with increased mortality and morbidity
8. Patients can have complex medication regimes
9. Potential diminished mental capacity makes history taking difficult

Conclusion
The elderly represent an heterogeneous and significant portion of the population. As anesthesiologists it will be
important to avoid complications, streamline perioperative care and ensure the highest quality of care for this
vulnerable population. There is no magic bullet for the elderly, instead vigilance , careful titration of medication and
a thorough understanding of the basic physiologic changes and commonly encountered comorbidities is needed.

Recommended Reading
General
Story D.A. Postoperative mortality and complications. Best Pract & Research Clinical Anesthesiology
2011: 25: 319-327
Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of anesthesia-related mortality in the United
States, 1999-2005 Anesthesiology. 2009 Apr;110(4):759-65
Liu, LL; Leung, JM. Predicting Adverse Postoperative Outcomes in Patients Aged 80 Years or Older.
Journal of the American Geriatrics Society 48 (2002): 405-412.
Kheterpal, S; OReilly, M; Englesbe, MJ; Rosenberg, AL; Shamks, AM; Zhang,L;Rothman,ED;
Campbell,DA; Tremper, KK. Preoperative and intraoperative predictors of cardiac adverse events after
general, vascular and urological surgery. Anesthesiology 2009; 110-58-66
Turrentine FE, Wang H, Simpson VB, Jones, RS. Surgical Risk factors, morbidity, and mortality in elderly
patients. J Am Coll Surg 2006: 203: 865-877
Leung, JM; Dzankic, S. Relative Importance of Preoperative Health Status Versus Intraoperative Factors in
Predicting Postoperative Adverse Outcomes in Surgical Patients. Journal of the American Geriatrics
Society 49 (2001): 1080-1085.
Hamel, MB; et al. Surgical Outcomes for Patients Aged 80 and Older: Morbidity and Mortality from Major
Noncardiac Surgery. Journal of the American Geriatrics Society 53.3 (2005): 424-429.
Liu SS, Della Valle AG, Besculides MC, Gaber LK, Memtsoudis SG. Trends in mortality, complications,
and demographics for primary hip arthroplasty in the united states. Int Orthop. 2009;33(3):643-651.
Frailty
Robinson TN, Wu DS, Stiegman GV, Moss M. Frailty predicts increased hospital and six month healthcare
cost following colorectal surgery in older adults. Am J Surgery 2011; 201: 511-514
Kanapuru B, Erschler WB. Inflammation, Coagulation and the Pathway to Frailty. Am J Medicine 2009;
122: 605- 613
Makary MA, Segev DL, Pronovost PJ, et al Frailty as a predictor of surgical outcomes in older patients. J
AM Coll Surg 2010; 210:901-908
Cook, DJ, Rooke GA. Priorities in Perioperative Geriatrics. Anesth Analg; 2003: 96:1823-1836

holders.
512
Page 7
General Age Related Changes
Rooke, GA. Cardiovascular Aging and Anesthetic Implications. Journal of Cardiothoracic and Vascular
Anesthesia 17.4 (2003): 512-523.
Silvey G, Castillo JG, Chikwe J, Flynn B, Filsoufi F. Cardiac Anesthesia and Surgery in Geriatric Patients.
Semin Cardiothorac Vasc Anesth 2008;12:18-28
Groban, L. Diastolic Dysfunction in the Older Heart. Journal of Cardiothoracic and Vascular Anesthesia
19.2 (2005): 228-236.
Phillip B, Pastor D, Bellows W, Leung JM: The prevalence of preoperative diastolic filling abnormalities in
geriatric surgical patients. Anesth Analg 2003; 97:1214-21
Sprung J, Gajic O, Warner DO. Review article: Age related alterations in respiratory function - anesthetic
considerations: Can J Anaesth 2006;53:1244-57.
Schucker DL; Age related changes in liver structure and function: implications for disease? Exper
Gerontol; 2005: 40:650-659
Kenney WL, Munce TA. Invited review: aging and human temperature regulation. J Appl Physiol
2003;95:2598-603.
Medications
Jacobs, JR; et al. Aging Increases Pharmacodynamic Sensitivity to the Hypnotic Effects of Midazolam.
Anesthesia and Analgesia 80.1 (1995): 143-148.
Nickalls, RW; Mapleson, WW. Age-related Iso-MAC Charts for Isoflurane, Sevoflurane and Desflurane
in Man. British Journal of Anaesthesia 91.2 (2003): 170-174.
Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, Cadoret C, Fish LS, Garber L,
Kelleher M, Bates DW. Incidence and preventability of adverse drug events among older persons in the
ambulatory setting. JAMA. 2003 Mar 5;289(9):1107-16.
Delirium
Silverstein, JH; Timberger, M; Reich, DL; Uysal, S. Central Nervous System Dysfunction after
Noncardiac Surgery and Anesthesia in the Elderly. Anesthesiology 106.3 (2007): 622-628.
Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM, Postoperative Delirium: The Importance of Pain
and Pain Management Anesth Analg 2006;102:1267-1273
Moller, JT; et al. Long-term Postoperative Cognitive Dysfunction in the Elderly: ISPOCD1 Study.
Lancet 351 (1998): 857-861.
Marcantonio, ER; Flacker, JM; Michaels, M; Resnick, NM. Delirium is Independently Associated with
Poor Functional Recovery after Hip Fracture. Journal of the American Geriatrics Society 48.6 (2000):
618-624.
Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-65.
Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac
surgery. Anesthesiology. 2008;108(1):18-30.
Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic
adverse effects in older persons. Arch Intern Med. 2008;168(5):508-513.
Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in
hospitalized older patients. N Engl J Med. 1999;340(9):669-676.
Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and the development of
postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010;85(1):18-
26.
Cardiac and Pulmonary risk
Lee A. Fleisher, et al: ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care
for Noncardiac SurgeryA Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines:Circulation. 2007;116:e418-e500.)
Poldermans D, Hoeks SE, Feringa HH. Pre-operative risk assessment and risk reduction before surgery. J
Am Coll Cardiol. 2008;51(20):1913-1924.
Liu L, Dzankic S, Leung JM. Preoperative Electrocardiogram Abnormalities Do Not Predict Postoperative
Cardiac Complications in Geriatric Surgical Patients. J Am Geriatr Soc 2002;50:1186-1191
Fleisher LA, Beckman JA, Brown KA, et al. 2009 ACCF/AHA focused update on perioperative beta
blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and
care for noncardiac surgery: A report of the american college of cardiology foundation/American heart

holders.
512
Page 8
association task force on practice guidelines. Circulation. 2009;120(21):e169-276.
Noordzij PG, Bersma E, Bax JJ, Feringa HH, Schreiner F,Schouten, OKertai MD, Klein J, van Urk H,
Elhendy A, Poldermans D Prognostic value of routine preoperative electrocardiography in patients
undergoing noncardiac surgery. Am J Cardiol (2006 Apr 1) 97(7):1103-6
Lawrence VA, Cornell JE,Smetana GW, Strategies to reduce postoperative pulmonary complications
after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern
Med (2006 Apr 18) 144(8):596-608
Quality
Bentrem DJ, Cohen ME, Hynes DM, Ko CY, Bilimoria KY. Identification of specific quality improvement
opportunities for the elderly undergoing gastrointestinal surgery. Arch Surg. 2009;144(11):1013-1020.
McGory ML, Kao KK, Shekelle PG, et al. Developing quality indicators for elderly surgical patients. Ann
Surg. 2009;250(2):338-347

DISCLOSURE

104
Page 1
Physiological Monitoring of the Brain: Whats New AND Useful?
Optimizing Cerebral Perfusion during Surgery
Charles W. Hogue, M.D. Baltimore, Maryland
Autoregulation Monitoring
Autoregulation of cerebral blood flow (CBF) normally ensures a constant supply of oxygenated blood to the brain
over a range of blood pressures. Impaired autoregulation may result in cerebral hypoperfusion when blood pressure
is low and cerebral hyperperfusion when blood pressure high. Disturbed autoregulation occurs in a variety of
intracranial conditions, including traumatic brain injury (TBI), where it has been found to predict poor functional
outcome and mortality.
1
We have found that impaired autoregulation that occurs during cardiopulmonary bypass
(CPB) in patients undergoing cardiac surgery identifies high risk for stroke.
2
Optimizing cerebral perfusion pressure
(CPP) to remain within the optimal autoregulatory range might provide a means for improving patient outcome.
3

Monitoring of CBF autoregulation at the bedside is possible using a variety of approaches.
Autoregulation Testing vs. Monitoring
Autoregulation testing involves introducing a hemodynamic stimulus and measuring the CBF response.
Hemodynamic changes can be induced by administering vasodilating or vasoconstricting drugs, releasing a thigh
cuff, manipulating PaCO
2
, tilt-table testing, or even placing the patient in a negative pressure chamber.
1

Autoregulation testing can verify the presence of functional autoregulation with high precision, but its use is
restricted to infrequent measurements. Thus, dynamic changes in autoregulation that may occur with changing
patient condition might be missed. Further, imparting hemodynamic stress in critically ill patients, or in those with
cerebrovascular disease, might not be tolerated and could potentially lead to patient harm.
Autoregulation monitoring relies on comparing spontaneous fluctuations in CBF in relation to spontaneous changes
in CPP or mean arterial pressure (MAP) over the low frequencies (20 s to 3 min) associated with autoregulatory
vasoreactivity (and outside the cardiac and respiratory frequencies).
1
Although it allows for continuous monitoring,
this approach is less precise than autoregulation testing. This deficiency, or low signal-to-noise ratio, is compensated
for by averaging data, typically over a 30-min period. Changes in CBF (or its surrogates) can be evaluated in the
frequency or time domains. The former involves evaluation of the transfer function variables gain, phase shift, and
coherence generated from cross-spectral analysis. When autoregulation is functional, the phase shift between CBF
and CPP/MAP approaches 180
o
, whereas a 0
o
phase relationship (CBF and MAP waves occur at the same time) is
consistent with impaired autoregulation.
1,4
High gain is suggested to indicate impaired autoregulation. Coherence
provides information on the association between CBF and CPP (or MAP when ICP is not measured or CVP is low
such as during CPB) at the component frequencies. Coherence < 0.5 may indicate that the relation between CBF and
CPP/MAP is nonlinear, negating the predicating assumptions of this approach to autoregulation monitoring.
Time domain analysis can be performed by calculating the Pearson correlation coefficient between CBF surrogates
and CPP/MAP. Low signal-to-noise ratio considerations apply for this method as well, but assumptions that changes
in CBF are due to fluctuations in CPP/MAP are strengthened by averaging the data. Time averaging the data over a
5-min period with a sliding window with updates every 60 s provides a continuous assessment of autoregulation in a
format that is clinically intuitive. The correlation between CBF velocity measured with transcranial Doppler (TCD)
monitoring of the middle cerebral artery and CPP/MAP has been termed the mean velocity index, or Mx (Fig 1).
Unlike frequency domain methods, time domain methods of monitoring autoregulation do not require assumptions
of a linear relation between CBF and CPP/MAP. The exact Mx at which CPP/MAP is below or above the
autoregulation limits is not known. A value of Mx ! 0.4 is often chosen, and this value has been associated with

104
Page 2
delirium in patients with sepsis.
5
Clinically it is more
precise to consider the optimal CPP/MAP rather than
that pressure below or above the autoregulatory limits.

A novel approach for improving the precision of
continuous autoregulation monitoring results is to
introduce oscillations into the systemic circulation and
then measure the phase shift of the resultant CBF
surrogate response. In a laboratory experiment,
oscillation in PEEP in mechanically ventilated animals
between 5 and 10 cm H
2
O was introduced at a
frequency of 1/min.
6
Oscillations of arterial blood
pressure at these frequencies resulted in similar
oscillations in CBF velocity. The lower limit of
autoregulation (LLA) was determined with 91%
sensitivity and 97% specificity.

Clinical Surrogates of CBF for Autoregulation
Monitoring

There is no gold standard for measuring CBF for
autoregulation monitoring or testing, and each method
has its limitations. For example, TCD monitoring
provides a measure of CBF velocity but not CBF per
se. Nonetheless, changes in the diameter of the middle
cerebral artery that might influence the relationship
between flow and flow velocity are small and within a
clinically acceptable error range. Monitoring CBF
autoregulation with TCD, though, is challenging
because of motion artifact, insufficient transcranial
insonating window in some patients, and interference from electric cautery during surgery. The difficulties in
monitoring CBF autoregulation continuously with TCD have led to evaluations of clinically useful means for
continuous monitoring.

Pressure reactivity index (PRx) monitoring is based on the continuous calculation of the correlation between low-
frequency changes in intracranial pressure (ICP) and CPP similar to, but not synonymous with, Mx. Physiologically,
arteriolar vasodilation occurs when blood pressure is low, and vasoconstriction occurs when blood pressure is high.
The collective changes in the diameter of the small arteries that mediate vasoreactivity produce changes in cerebral
blood volume (CBV). Functional autoregulation results in slow wave changes in CBV that are not correlated with
changes in CPP, resulting in a PRx that approaches zero or is negative. When autoregulation is impaired, PRx
approaches 1 because ICP changes are pressure passive. PRx has been validated against PET and Mx.
1,7,8
The value
of PRx monitoring is that it provides a seamless, continuous output that is not associated with motion artifact or
other limitations of TCD. These features enhance the ease of clinical use. This method requires invasive ICP
monitoring and therefore is limited to select patients with subarachnoid hemorrhage (SAH), TBI, or major
hemorrhagic or ischemic stroke, and in some instances of hepatic coma.
1

Monitors of brain oxygenation, such as direct tissue O
2
tension measurement and jugular bulb O
2
saturation
measurement, have been proposed as methods for autoregulation monitoring.
9
Near-infrared spectroscopy (NIRS) is
increasingly used clinically, particularly for patients undergoing cardiac surgery. Measurement of regional cerebral
oxygen saturation (rScO
2
) with NIRS provides an index of the ratio of oxyhemoglobin to total hemoglobin. Since
most intracranial blood is venous blood, rScO
2
is a measure of cerebral O
2
supply vs. demand. Over short time
periods, factors that influence rScO
2
, such as cerebral metabolic rate for O
2
, hemoglobin level, PaO
2
, and tissue
diffusivity, are relatively constant such that rScO
2
might serve as a surrogate for CBF for autoregulation monitoring.

The variable cerebral oximetry index (COx) is generated as the linear correlation coefficient between rScO
2
and
CPP/MAP. Similar to Mx and PRx, COx approaches zero when CBF is autoregulated, but it approaches 1 when
Fig. 1. Mx and COx recording during cardiac surgery.
The top graph is the MAP time series. The bottom
graphs show the percent time at each MAP. Mx and
COx data are placed in 5 mmHg bins. Each increase
when MAP is outside autoregulation limits (ie,
increasing correlation between CBF and MAP).
Optimal MAP in this patient is 85-90 mmHg.

104
Page 3
autoregulation is impaired. COx has been validated in laboratory experiments against laser Doppler flux and against
TCD-derived Mx in patients with sepsis and in those undergoing cardiac surgery.
10-12
Unlike TCD, the use of
COx does not require a trained technician and, thus, can be widely applied in a broad range of clinical
settings and locations. Monitoring COx has many obvious clinical advantages, including the fact that it is
noninvasive, continuous, and requires little caregiver intervention. These features will allow for
widespread autoregulation monitoring in a variety of clinical locations.

The absorption spectrum for oxyhemoglobin and deoxyhemoglobin are distinct (~wavelengths of 600 and 1000 nm),
but they have an isobestic wavelength near 800 nm. Total relative hemoglobin (rTHb) measured at the isobestic
wavelength is the basis for the calculation of the ratio of oxyhemoglobin to rTHb in reporting rScO
2
. Assessing low
frequency fluctuations in rTHb in relation to CPP/MAP may provide an indicator of vessel reactivity analogous to
PRx. That is, the collective changes in the diameter of arteriolar resistance vessels that mediate autoregulation lead
to changes in rTHb: increases in rTHb indicate vasodilation whereas decreases indicate vasoconstriction. The
variable hemoglobin volume index (HVx) is generated as the correlation coefficient between rTHb and CPP/MAP.
Laboratory and clinical investigations have shown that HVx compares favorably with PRx, providing a
supplemental assessment of clinical autoregulation.
13,14
Since it does not require invasive ICP monitoring, HVx
provides many advantages over PRx for monitoring vasoreactivity.

Autoregulation and Neurocritically Ill Patient Outcome

Continuous monitoring of autoregulation provides an assessment of intracranial dynamics in patients with a variety
of conditions, including TBI, SAH, ischemic or hemorrhagic stroke, carotid artery endarterectomy, hepatic
encephalopathy, and sepsis. Monitoring of autoregulation might provide important risk stratification information as
well as a therapeutic target for optimizing CPP to reduce the risk of primary or secondary brain injury. In patients
with TBI, impaired autoregulation determined with Mx or PRx can distinguish patients at risk for poor functional
outcome and mortality independent of other factors.
1,15,16
When PRx increases to >0.3, mortality abruptly increases
from 20% to 70%.
1
An Mx >0.3 identified disturbed autoregulation in patients with TBI, whereas a value <0.05
indicated good autoregulation.
17
In those studies, the relation between autoregulation indices and outcome were
retrospectively determined. In a study of 327 patients with TBI, the investigators recorded MAP, ICP, and CPP
continuously and calculated PRx.
18
An automated, real-time algorithm was used at the bedside to determine the
CPP associated with the best cerebral vasoreactivity (CPPoptimal) averaged over a 4-h window updated every
minute. Patient outcome and mortality 6 months after the event were correlated with the median difference between
actual CPP and CPPoptimal. Of note, mortality was associated with a hypoperfusion pattern signified by CPP <
CPPoptimal. In contrast, disability was associated with a hyperperfusion pattern, or CPP > CPPoptimal.

These data confirm and extend prior findings and provide a method for prospectively testing the clinical value of
PRx monitoring in the management of TBI. Another condition for which autoregulation monitoring might be used
is detecting delayed cerebral ischemia in patients with SAH. Impaired autoregulation may contribute to this
condition by jeopardizing perfusion to brain areas distal to vasospastic vessels. In a study of 98 patients with SAH,
impaired autoregulation during the first 5 days after the event, but not TCD monitoring, independently predicted
delayed cerebral ischemia.
19
Other studies have found that impaired autoregulation identifies risk for subsequent
cerebral ischemic events in patients with severe carotid artery stenosis.
20
This observation suggests that monitoring
of autoregulation may provide a means for risk stratification of patients with carotid artery atherosclerosis.

Autoregulation Monitoring During Cardiac Surgery

Brain injuries that manifest as stroke, silent cerebral infarcts determined with MRI, or cognitive decline are an
important source of patient morbidity and mortality after cardiac surgery. Cerebral hypoperfusion might be a
primary or secondary cause of brain injury in this population of patients.
21
During CPB, MAP targets are chosen
empirically based on older data showing that CBF autoregulation is functional when "-stat pH management is used.
The fundamentals of patient blood pressure management during CPB are mostly derived from data obtained with
autoregulation testing. In these studies, investigators raised or lowered blood pressure in patients with vasoactive
drugs and gathered intermittent measurements of CBF response with xenon-washout or the Kety-Schmidt method
using arterial N
2
O injection. These methods provided discrete data from individual patients.
22,23
However, the

104
Page 4
validity of these methods that summarized CBF-blood pressure data from several patients (often 1 to 2
measurements per patient) to determine characteristics of autoregulation has been questioned.
24

Variability in the LLA is likely wide given the growing prevalence of hypertension and cerebrovascular disease that
may affect the LLA. We have monitored autoregulation in patients undergoing cardiac surgery and found that the
LLA varies widely from 40 to 90 mmHg.
25,26
Further, as many as 20% of patients have impaired autoregulation
during CPB, a condition associated with high risk for stroke.
27
Since MAP targets during CPB are chosen
empirically (often between 50 and 60 mmHg), many patients are likely to be at risk for cerebral and systemic
hypoperfusion. We recently reported that the product of magnitude and duration that MAP is below the LLA during
CPB based on COx monitoring is independently associated with risk for acute kidney injury.
2
An ongoing
prospective, randomized trial is underway to compare neurological outcomes between patients who have MAP
targets during CPB determined empirically and those whose targets are based on real-time CBF autoregulation
monitoring.

References

1. Neurocrit Care 10:373-86, 2009.
2. Crit Care Med 41:464-71, 2013.
3. J Neurotrauma. 2007 24(Suppl 1):S5964, 2007.
4. Stroke 26:1801-4, 1995.
5. Crit Care Med 12:R63Epub 2008 May 52008.
6. J Appl Physiol 113:1362-8, 2012.
7. Neurosurgery 41:11-7, 1997.
8. Stroke 34:2404-9, 2003.
9. Physiol Meas 19:305-38, 1998.
10. Neurocrit Care 10:122-8, 2009.
11. Stroke 38:2818-25, 2007.
12. Stroke 41:1951-6, 2010.
13. Stroke 40:1820-6, 2009.
14. Anesth Analg 113:849-57, 2011.
15. Neurocrit Care 4:8-13, 2006.
16. Crit Care Med 30:733-8, 2002.
17. Neurocrit Care 14:188-93, 2011.
18. Crit Care Med 40:2456-63, 2012.
19. Stroke 43:3230-7, 2012.
20. J Neurol 255:1182-9, 2008.
21. Anesth Analg 103:21-37, 2006.
22. Anesth Analg 76:849-65, 1993.
23. Anesth Analg 66 825-32, 1987.
24. Anesthesiology 86:1431-3, 1997.
25. Anesth Analg 110:321-8, 2010.
26. Anesth Analg in press, 2011.
27. Br J Anaesth 109:391-8, 2012.

Disclosure
Codman, Honoraria, Johnson and Johnson, Honoraria

104
Page 1
Physiological Monitoring of the Brain: Whats New AND Useful?
Multimodal Monitoring of the Brain
Martin Smith, M.D. London, United Kingdom
Several techniques are now available for global and regional brain monitoring which provide an assessment of
cerebral perfusion, oxygenation and metabolic status, and early warning of impending brain hypoxia/ischemia.
Some monitoring modalities are well established whereas others are relatively new to the clinical arena and their
indications are still being evaluated. Monitoring of several physiological variables simultaneously (multimodal
monitoring) has enabled a move away from rigid physiological target setting to an individually tailored, patient-
specific approach to management after acute brain injury.
The pathophysiology of acute brain injury is complex and involves the inter-relation between changes in cerebral
blood flow (CBF), cerebral oxygen and glucose delivery and utilization, and electrophysiological derangements.
1

There is also substantial regional and temporal heterogeneity in these pathophysiological changes, particularly in the
acute phase after injury.
2
Whilst intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are crucially
important and routinely monitored variables, they do not provide an assessment of the adequacy of cerebral
perfusion. Therapeutic targets and choice of therapy are therefore best determined by multimodal monitoring.
3;4

Intracranial pressure
ICP monitoring is a standard of care in many acute brain injury scenarios despite the absence of high-quality
evidence demonstrating outcome benefits of ICP-guided management. Until recently, the majority of studies have
examined ICP monitoring in the context of severe traumatic brain injury (TBI), where it is widely accepted to be a
low-risk, high-yield and cost-effective intervention.
5
Some studies have suggested that ICP monitoring and
aggressive treatment of intracranial hypertension might in fact be detrimental,
6;7
but a 2010 meta-analysis
demonstrated that such interventions are associated with improved outcome after severe TBI.
8
However, a recent
randomized controlled trial conducted in Bolivia and Ecuador found no difference in three- or six-month outcomes
after severe TBI in patients whose treatment was guided by ICP monitoring and management compared to those
whose care was based on imaging and clinical examination in the absence of ICP monitoring.
9
Whether the findings
of this study are applicable to wealthier nations with superior pre-hospital care and rehabilitation services remains to
be seen. This study, and indeed others, do not conclude that ICP monitoring should be abandoned, but rather that
treatment should not be guided by ICP monitoring in isolation because it does not provide a comprehensive picture
of cerebral physiology and pathophysiology.
10

Cerebral oxygenation
Continuous measurement of brain tissue oxygen tension (PtiO
2
) allows real-time monitoring of the adequacy of
cerebral oxygenation, and provides important therapeutic information at the bedside about the balance between
cerebral oxygen supply and demand. Although PtiO
2
is strongly influenced by CPP, studies utilizing PtiO
2

monitoring, cerebral microdialysis (MD) and perfusion CT imaging have demonstrated that secondary brain hypoxic
insults may go unnoticed when therapy is guided by ICP/CPP monitoring alone, and that brain hypoxia can occur
despite ICP and CPP being within accepted thresholds for normality.
11-13
Normal brain PtiO
2
values are in the region
of 35 to 50 mmHg, and PET studies suggest that the ischemic threshold lies below 14 mmHg.
14
However, PtiO
2

values should be considered within a range rather than as a precise threshold, and ischemia is best defined by both
duration and depth of hypoxia.
15

Since arterial blood pressure (ABP) and CPP augmentation can significantly increase cerebral oxygenation, it has
been suggested that PtiO
2
may be a reasonable surrogate of CBF and cerebral ischemia, and used to guide optimal

104
Page 2
ABP and CPP thresholds to prevent brain hypoxia.
14
Several other systemic physiological variables, such as FiO
2

and haemoglobin concentration, also affect PtiO
2
, but which intervention or combination of interventions are most
effective in terms of outcome remains unclear. In fact it appears that it is the responsiveness of the hypoxic brain to
a given intervention that is the prognostic factor, with reversal of hypoxia being associated with reduced mortality.
16

A recent systematic review confirmed that PtiO
2
-directed therapy is associated with improved outcome compared to
ICP/CPP-guided therapy alone.
17

Cerebral microdialysis
Cerebral MD has contributed to our understanding of the pathophysiology of acute brain injury and, as a clinical
tool, it is used to assess cerebral bioenergetics and detect impending hypoxia/ischemia.
18
By analyzing changes in
brain extracellular fluid, MD can monitor the evolution of neurochemical changes in the injured brain, and the
response to treatment. Each sampled substance is a marker of a particular cellular process associated with glucose
metabolism, hypoxia/ischemia or cellular energy failure. In clinical practice, glucose, lactate, pyruvate, glycerol and
glutamate are the most commonly measured biochemical variables.
18-20
Because lactate can be an energy substrate
for the brain as well as an indicator of anaerobic metabolism,
21
it is usual to monitor the lactate:pyruvate (LP) ratio
rather than lactate alone.
19
Any molecule that can pass through the semi-permeable MD membrane can in theory be
sampled using the MD technique, and the availability of high molecular weight cut-off membrane catheters has
allowed macromolecules, such as cytokines, to be sampled for research purposes.
22

One of the main advantages of cerebral MD monitoring is its ability to assess glucose metabolism. Whilst reduced
oxygen and glucose supply because of inadequate cerebral perfusion is a major contributor to secondary brain
injury, several other factors are also implicated. Glucose utilization may increase dramatically even in the presence
of adequate supply (cerebral hyperglycolysis), leading to critical reductions in cerebral glucose levels.
23
Cerebral
oxidative metabolism of glucose may also be impaired because of mitochondrial dysfunction and cellular energy
failure, and MD monitoring offers unique insights into the ensuing metabolic crisis.
24
Thresholds for abnormality
applied in the clinical setting are glucose < 0.7 mmol/L and LP ratio > 40,
25
although there is no established value
above which the LPR is considered indicative of tissue hypoxia,
26
and a lower threshold of abnormality (> 25) is
used by some investigators.
18
An elevated LP ratio in combination with low brain glucose is a sign of severe
hypoxia/ischemia and associated with poor outcome.
27
It has been suggested that LP ratio can be used to guide CPP
management,
28
but some studies have found that elevation of LP ratio may occur at CPP values that are customarily
considered to be adequate.
29
This reinforces the importance of using physiological data from multiple sources to
guide individualized patient management. Because MD measures changes at the cellular level, it has the potential to
identify abnormalities before changes can be detected by other monitoring techniques or clinical status.
30

Whilst the pathophysiological importance of biochemical changes in the injured brain is undisputed, what it less
clear is whether monitoring and managing them affects outcome. Whilst well-designed outcome studies are
required, the future success of cerebral MD depends on the choice of biomarkers, their sensitivity, specificity, and
predictive value for secondary events, as well as the availability of practical methods for analysis in real-time at the
bedside.

Near infrared spectroscopy
First described in 1977 by Franz Jbsis, near infrared (NIR) spectroscopy (NIRS) is based on two key principles;
light in the NIR spectrum (700-950nm) can traverse biological tissue because of the relative transparency of tissue to
light in this wavelength range, and several biological molecules, termed chromophores, have distinct absorption
spectra in the NIR.
31
From a clinical perspective, oxyhemoglobin (O
2
Hb) and deoxyhemoglobin (HHb) are the most
commonly measured chromophores, although cytochrome c oxidase (CCO) may prove clinically more important
32;33

and was in fact the target of Jbsiss original investigations.
31
NIRS has potential advantages over other
neuromonitoring techniques; it is non-invasive, has high temporal and spatial resolution and offers simultaneous
measurement over multiple regions of interest. Although there has been interest in the use of NIRS to detect cerebral
hypoxia/ischemia since its first description, the extensive use of the technology in the research setting has not been
matched by widespread translation into the clinic.
34

Early NIRS monitors were limited to measuring only changes in the concentrations of O
2
Hb and HHb, but modern
cerebral oximeters incorporating spatially resolved spectroscopy (SRS) provide an absolute measure of regional
cerebral oxygen saturation (rScO
2
) as a continuous measure of the balance between cerebral oxygen delivery and
utilization.
34
There is a plethora of commercial NIRS-based cerebral oximeters but a lack of standardization.

104
Page 3
Different manufacturers use different nomenclature, although most do provide an absolute measure of rScO
2

displaying this as a simple percentage value; the algorithms and even the variables measured also vary, making
comparisons between devices and studies difficult.

There has been a rapid expansion in the clinical experience of cerebral oximetry during cardiac surgery in the last
decade following evidence from early retrospective studies that NIRS-guided brain protection protocols might lead
to a reduction in peri-operative stroke and postoperative cognitive dysfunction.
35
Although subsequent prospective,
randomized controlled trials have failed to replicate these outcome benefits, multiple studies have confirmed an
association between intraoperative cerebral desaturation and an increased risk of perioperative cognitive decline.
36

Consequently, cerebral oximetry is increasingly being used to monitor and manage cerebral oxygenation during
cardiac surgery.
37
NIRS is also widely used to monitor the adequacy of cerebral oxygenation during carotid surgery,
during which it has similar accuracy and reproducibility in the detection of cerebral ischemia compared to other
monitoring modalities, and some advantages in terms of simplicity and temporal resolution.
38
However, it is
currently impossible to specify an rScO
2
threshold that can be widely applied to guide shunt placement and other
neuroprotective interventions; reductions in rScO
2
between 5% and 25% from baseline have been reported as
potential ischemic thresholds.
39
It has been suggested that NIRS might have utility for monitoring the healthy but at
risk brain during routine surgical procedures under general anesthesia. Whilst the potential to monitor cerebral
well-being continuously is an attractive proposition, and early detection of cerebral desaturation might lead to
targeted intervention that could improve perioperative outcome, the evidence for such benefit has thus far proved
elusive.
39

There has been limited investigation of the utility NIRS after acute brain injury, where it might be expected to be of
benefit. Only small observational studies have been performed,
40;41
and these serve to highlight two key difficulties
in investigating NIRS in this context - the definition of ischemic thresholds in an injured brain with acutely
disordered hemodynamic and metabolic function, and the lack of a gold standard against which to compare NIRS-
derived variables.
33
Factors such as the presence of intracranial hematoma, cerebral edema and subarachnoid blood
present further challenges since they may invalidate some of the assumptions upon which NIRS algorithms are
based. In fact this has been utilized to advantage in studies using NIRS to identify intracranial hematomas
42
and
cerebral edema.
43
Modern technology will play an important role in overcoming these confounding issues as
demonstrated by a recent study that used time-resolved spectroscopy to predict cerebral vasospasm with high
sensitivity in patients with poor-grade SAH.
44
NIRS-monitored changes in the oxidation status of CCO, which is the
final electron acceptor in the mitochondrial electron transport chain and responsible for over 95% of oxygen
metabolism, provides additional information about cellular energy status that, in association with hemoglobin-based
variables, may aid in the determination of ischemic thresholds.
33
Changes in the oxidation status of CCO have
recently been measured in the healthy and injured adult brain using an optimized, multi-wavelength (broadband)
NIRS device.
45;46

There are several concerns over the clinical application of NIRS and the one most often highlighted is the potential
for contamination of the signals by extracranial tissue. Some commercial cerebral oximeters use two detectors and
a subtraction based algorithm to deal with this issue, assuming that the detecting optode closest to the emitter
receives light that has passed mainly through the scalp whereas that arriving at the farthest detector has mainly
passed through brain tissue. Although the proprietary algorithms on which this assumption is based are not
published, there is weighting in favor of intracerebral tissue with an inter-optode spacing greater than 4cm. SRS has
high sensitivity and specificity for intracranial changes when appropriate rScO
2
thresholds are chosen,
47
but it is still
prone to some degree of extracerebral contamination.
48
The NIRS-derived CCO signal is highly specific for
intracerebral changes, potentially making it a superior biomarker to other, hemoglobin-based, NIRS variables.
49

Cerebral blood flow
Transcranial Doppler ultrasonography (TCD) is an established, non-invasive technique for assessing cerebral
hemodynamics in real-time; it measures relative changes rather than actual CBF. The TCD flow velocity (FV)
waveform resembles an arterial pulse wave and may be quantified into peak systolic, end diastolic and mean FVs,
and pulsatility index; the latter provides an assessment of distal cerebrovascular resistance. TCD is widely used in
the perioperative period and during intensive care, most commonly in the diagnosis and management of cerebral
vasospasm and to assess cerebral autoregulatory reserve.
50
It is operator dependent and long-term recordings are
limited by the need for accurate and immovable probe fixation, realistically restricting it to an intermittent
monitoring technique. Quantitative measurement of absolute regional CBF is possible using thermal diffusion

104
Page 4
flowmetry (TDF). TDF catheters are available for clinical use but clinical data are limited and there has been some
concern about the accuracy and reliability of the technique.
51

Cerebrovascular autoregulation
Cerebrovascular autoregulation (CA) is frequently impaired after brain injury, but established methods of testing
static and dynamic CA are interventional or intermittent and may be not be possible in critically ill patients.
Cerebrovascular pressure reactivity is a key component of CA, and monitoring and correlation of spontaneous slow
waves in ABP and ICP allows calculation of a pressure reactivity index (PRx) as a novel method of measuring CA.
52

PRx can be monitored continuously and may be used to define individual CPP targets after TBI.
53
PtiO
2
-derived
oxygen reactivity provides additional information about CA,
54
and, because PtiO
2
is a focal measure, ORx may
better represent regional autoregulation than PRx.
55
There has also been interest in the non-invasive and continuous
measurement of cerebrovascular reactivity using NIRS-derived hemoglobin and oxygenation variables.
56

Continuous electroencephalography
Nonconvulsive seizures and nonconvulsive status epilepticus occur in up to one third of patients after acute brain
injury, and are best detected by continuous electroencephalography (cEEG) monitoring
57
Integrating cEEG into
multimodal neuromonitoring strategies has identified associations between seizures, intracranial hypertension and
metabolic derangements.
58
cEEG is limited by its attenuation by anesthetic and sedative agents, and is a resource
intense technology requiring skilled personnel for interpretation. Telemedicine allows interpretation away from the
bedside and may increase the adoption of cEEG, as might the development of automated seizure detection software.

Cortical spreading depolarizations (SD) are pathological events characterized by near-complete sustained
depolarization of neurons and astrocytes, resulting in secondary injury related to mitochondrial damage,
accumulation of intracellular calcium and excitotoxicity. Episodes of SD have been reported in more than half of
TBI patients and are independently associated with unfavorable outcome.
59
They may represent a potential target for
therapy, although a definite cause-effect relationship has not been proven. Detection of SDs currently requires
placement of an electrode strip directly onto the brain surface, limiting its routine use, but developments in scalp
EEG and NIRS technology are likely to lead to non-invasive monitoring methods.

The future
Multiparameter probes incorporating ICP, PtiO
2
, and temperature measurements are already available, and
quantification of CBF is likely to be added to such devices. Stereotactic placement of invasive probes may help
target regions of interest with improved accuracy in selected patients.

Technological developments will lead to the availability for clinical use of non-invasive brain monitoring systems
with multiple capabilities. Diffuse correlation spectroscopy provides non-invasive measures of CBF in addition to
cerebral tissue oxygen saturation.
60
A combined NIRS/EEG system using a co-located opto-electrode that allows
the acquisition of regional cerebral electrophysiological and hemodynamic data simultaneously and non-invasively
has been described for research use.
61
The use of supercontinuum light sources will allow the combination of time-
resolved and broadband spectroscopy to yield absolute measurements of optical absorption and scattering across a
range of wavelengths, and thus measurement of absolute concentrations of multiple chromophores, leading to the
development of a single NIRS-based device able to monitor absolute cerebral oxygenation, hemodynamics and
metabolic status over multiple regions of interest.
62

References
1. Greve MW, Zink BJ. Pathophysiology of traumatic brain injury. Mt Sinai J Med 2009; 76: 97-104
2. Vespa P, McArthur DL, Alger J, et al. Regional heterogeneity of post-traumatic brain metabolism as studied by
microdialysis, magnetic resonance spectroscopy and positron emission tomography. Brain Pathol 2004; 14:
210-4
3. Kirkman MA, Smith M. Multimodal intracranial monitoring: implications for clinical practice. Anesthesiol Clin
2012; 30: 269-87
4. Oddo M, Villa F, Citerio G. Brain multimodality monitoring: an update. Curr Opin Crit Care 2012; 18: 111-8
5. Smith M. Monitoring intracranial pressure in traumatic brain injury. Anesth.Analg. 2008; 106: 240-8
6. Cremer OL, van Dijk GW, van Wenson E, et al. Effect of intracranial pressure monitoring and targeted
intensive care on functional outcome after severe head injury. Crit Care Med 2005; 33: 2207-13

104
Page 5
7. Shafi S, Diaz-Arrastia R, Madden C, Gentilello L. Intracranial pressure monitoring in brain-injured patients is
associated with worsening of survival. J Trauma 2008; 64: 335-40
8. Stein SC, Georgoff P, Meghan S, et al. Relationship of aggressive monitoring and treatment to improved
outcomes in severe traumatic brain injury. J Neurosurg 2010; 112: 1105-12
9. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N
Engl J Med 2012; 367: 2471-81
10. Hutchinson PJ, Kolias AG, Czosnyka M, et al. Intracranial pressure monitoring in severe traumatic brain injury.
BMJ 2013; 346: doi: 10.1136
11. Chang JJ, Youn TS, Benson D, et al. Physiologic and functional outcome correlates of brain tissue hypoxia in
traumatic brain injury. Crit Care Med 2009; 37: 283-90
12. Oddo M, Levine JM, Mackenzie L, et al. Brain hypoxia is associated with short-term outcome after severe
traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure.
Neurosurgery 2011; 69: 1037-45
13. Wintermark M, Chiolero R, Van MG, et al. Relationship between brain perfusion computed tomography
variables and cerebral perfusion pressure in severe head trauma patients. Crit Care Med 2004; 32: 1579-87
14. Johnston AJ, Steiner LA, Coles JP, et al. Effect of cerebral perfusion pressure augmentation on regional
oxygenation and metabolism after head injury. Crit Care Med 2005; 33: 189-95
15. van den Brink WA, van Santbrink H, Steyerberg EW, et al. Brain oxygen tension in severe head injury.
Neurosurgery 2000; 46: 868-76
16. Bohman LE, Heuer GG, Macyszyn L, et al. Medical management of compromised brain oxygen in patients with
severe traumatic brain injury. Neurocrit Care 2011; 14: 361-9
17. Nangunoori R, Maloney-Wilensky E, Stiefel M. Brain tissue oxygen-based therapy and outcome after severe
traumatic brain injury: a systematic literature review. Neurocrit Care 2012; 17: 131-8
18. Tisdall MM, Smith M. Cerebral microdialysis: research technique or clinical tool. Br J Anaesth 2006; 97: 18-25
19. Bellander BM, Cantais E, Enblad P, et al. Consensus meeting on microdialysis in neurointensive care. Intensive
Care Med 2004; 30: 2166-9
20. Goodman JC, Robertson CS. Microdialysis: is it ready for prime time? Curr Opin Crit Care 2009; 15: 110-7
21. Gallagher CN, Carpenter KL, Grice P, et al. The human brain utilizes lactate via the tricarboxylic acid cycle: a
13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain 2009; 132: 2839-49
22. Helmy A, Carpenter KL, Menon DK, et al. The cytokine response to human traumatic brain injury: temporal
profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab 2011; 31: 658-70
23. Bergsneider M, Hovda DA, Shalmon E, et al. Cerebral hyperglycolysis following severe traumatic brain injury
in humans: a positron emission tomography study. J Neurosurg 1997; 86: 241-51
24. Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic
brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab
2005; 25: 763-74
25. Timofeev I, Carpenter KL, Nortje J, et al. Cerebral extracellular chemistry and outcome following traumatic
brain injury: a microdialysis study of 223 patients. Brain 2011; 134: 484-94
26. Hutchinson PJ, Gupta AK, Fryer TF, et al. Correlation between cerebral blood flow, substrate delivery, and
metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study. J
Cereb Blood Flow Metab 2002; 22: 735-45
27. Vespa PM, McArthur D, O'Phelan K, et al. Persistently low extracellular glucose correlates with poor outcome
6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb
Blood Flow Metab 2003; 23: 865-77
28. Nordstrom CH, Reinstrup P, Xu W, et al. Assessment of the lower limit for cerebral perfusion pressure in
severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 2003; 98: 809-14
29. Vespa PM, O'Phelan K, McArthur D, et al. Pericontusional brain tissue exhibits persistent elevation of
lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med 2007; 35: 1153-60
30. Belli A, Sen J, Petzold A, et al. Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a
microdialysis study. Acta Neurochir (Wien) 2008; 150: 461-9
31. Jbsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory
parameters. Science (New York, NY) 1977; 198: 1264-7
32. Kakihana Y, Matsunaga A, Tobo K, et al. Redox behavior of cytochrome oxidase and neurological prognosis in
66 patients who underwent thoracic aortic surgery. Eur J Cardiothorac Surg 2002; 21: 434-9
33. Smith M, Elwell C. Near-infrared spectroscopy: shedding light on the injured brain. Anesth Analg 2009; 108:
1055-7

104
Page 6
34. Ghosh A, Elwell C, Smith M. Cerebral near-infrared spectroscopy in adults: a work in progress. Anesth Analg
2012; 115: 1373-83
35. Goldman S, Sutter F, Ferdinand F, Trace C. Optimizing intraoperative cerebral oxygen delivery using
noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart SurgForum
2004; 7: E376-E381
36. Slater JP, Guarino T, Stack J, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital
stay after cardiac surgery. Ann Thorac Surg 2009; 87: 36-44
37. Vohra HA, Modi A, Ohri SK. Does use of intra-operative cerebral regional oxygen saturation monitoring during
cardiac surgery lead to improved clinical outcomes? Interact Cardiovasc Thorac Surg 2009; 9: 318-22
38. Moritz S, Kasprzak P, Arlt M, et al. Accuracy of cerebral monitoring in detecting cerebral ischemia during
carotid endarterectomy: a comparison of transcranial Doppler sonography, near-infrared spectroscopy, stump
pressure, and somatosensory evoked potentials. Anesthesiology 2007; 107: 563-9
39. Smith M. Shedding light on the adult brain: a review of the clinical applications of near-infrared spectroscopy.
Phil Trans R Soc 2011; 369: 4452-69
40. Dunham CM, Ransom KJ, Flowers LL, et al. Cerebral hypoxia in severely brain-injured patients is associated
with admission Glasgow Coma Scale score, computed tomographic severity, cerebral perfusion pressure, and
survival. J Trauma 2004; 56: 482-9
41. Leal-Noval SR, Cayuela A, Rellano-Orden V, et al. Invasive and noninvasive assessment of cerebral
oxygenation in patients with severe traumatic brain injury. Intensive Care Med 2010; 36: 1309-17
42. Robertson CS, Gopinath SP, Chance B. A new application for near-infrared spectroscopy: detection of delayed
intracranial hematomas after head injury. J Neurotrauma 1995; 12: 591-600
43. Gill AS, Rajneesh KF, Owen CM, et al. Early optical detection of cerebral edema in vivo. J Neurosurg 2011;
114: 470-7
44. Yokose N, Sakatani K, Murata Y, et al. Bedside monitoring of cerebral blood oxygenation and hemodynamics
after aneurysmal subarachnoid hemorrhage by quantitative time-resolved near-infrared spectroscopy. World
Neurosurg 2010; 73: 508-13
45. Tisdall MM, Tachtsidis I, Leung TS, et al. Near-infrared spectroscopic quantification of changes in the
concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia. J Biomed Opt
2007; 12: 024002
46. Tisdall MM, Tachtsidis I, Leung TS, et al. Increase in cerebral aerobic metabolism by normobaric hyperoxia
after traumatic brain injury. J Neurosurg 2008; 109: 424-32
47. Al-Rawi PG, Smielewski P, Kirkpatrick PJ. Evaluation of a near-infrared spectrometer (NIRO 300) for the
detection of intracranial oxygenation changes in the adult head. Stroke 2001; 32: 2492-500
48. Davie SN, Grocott HP. Impact of extracranial contamination on regional cerebral oxygen saturation: a
comparison of three cerebral oximetry technologies. Anesthesiology 2012; 116: 834-40
49. Kolyva C, Ghosh A, Tachtsidis I, et al Cytochrome c Oxidase Response to Changes i/n Cerebral Oxygen
Delivery in the Adult Brain Shows Higher Brain-Specificity than Haemoglobin. Neuroimage. 2013; in press
50. Kincaid MS. Transcranial Doppler ultrasonography: a diagnostic tool of increasing utility. Curr Opin
Anaesthesiol 2008; 21: 552-9
51. Vajkoczy P, Horn P, Thome C, et al. Regional cerebral blood flow monitoring in the diagnosis of delayed
ischemia following aneurysmal subarachnoid hemorrhage. J Neurosurg 2003; 98: 1227-34
52. Czosnyka M, Pickard JD. Monitoring and interpretation of intracranial pressure. J Neurol Neurosurg Psychiatry
2004; 75: 813-21
53. Steiner LA, Czosnyka M, Piechnik SK, et al. Continuous monitoring of cerebrovascular pressure reactivity
allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care
Med 2002; 30: 733-8
54. Jaeger M, Schuhmann MU, Soehle M, Meixensberger J. Continuous assessment of cerebrovascular
autoregulation after traumatic brain injury using brain tissue oxygen pressure reactivity. Crit Care Med 2006;
34: 1783-8
55. Diedler J, Karpel-Massler G, Sykora M, et al. Autoregulation and brain metabolism in the perihematomal
region of spontaneous intracerebral hemorrhage: an observational pilot study. J Neurol Sci 2010; 295: 16-22
56. Zweifel C, Castellani G, Czosnyka M, et al. Noninvasive monitoring of cerebrovascular reactivity with near
infrared spectroscopy in head-injured patients. J Neurotrauma 2010; 27: 1951-8
57. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG
monitoring in critically ill patients. Neurology 2004; 62: 1743-8

104
Page 7
58. Friedman D, Claassen J, Hirsch LJ. Continuous electroencephalogram monitoring in the intensive care unit.
Anesth Analg 2009; 109: 506-23
59. Hartings JA, Bullock MR, Okonkwo DO, et al Spreading depolarisations and outcome after traumatic brain
injury: a prospective observational study. Lancet Neurol 2011; 10: 1058-64
60. Kim MN, Durduran T, Frangos S, et al. Noninvasive measurement of cerebral blood flow and blood
oxygenation using near-infrared and diffuse correlation spectroscopies in critically brain-injured adults.
Neurocrit Care 2010; 12: 173-80
61. Cooper RJ, Hebden JC, O'Reilly H, et al. Transient haemodynamic events in neurologically compromised
infants: a simultaneous EEG and diffuse optical imaging study. Neuroimage 2011; 55: 1610-6
62. Elwell CE, Cooper CE. Making light work: illuminating the future of biomedical optics. Phil Trans R Soc 2011;
369: 4358-79

Disclosure
Codman, Honoraria, Johnson and Johnson, Honoraria
107
Page 1
Preventing CNS Complications During Anesthesia and Surgery
James E. Cottrell, M.D. Brooklyn, New York
The assumption that anesthesia has no serious, long-term, adverse CNS consequences is probably true for most patients.
However, for patients younger than 6 months, or older than 60 years, that assumption is under challenge from a substantial body
of evidence. Fetuses and newborns appear to be at risk because systems that would enable them to fully recover from the effects
of more than 2 hours of anesthesia are still in development. In distinction, seniors may be at risk because systems that once
enabled full recovery have ever-diminishing capacity. Even for some patients between the age of 6 months and 60 years, full
recovery may require replacing apoptosed neurons and pruning dendritic spines perhaps leaving them not quite the same
person that they were before they were anesthetized.
THE YOUNG BRAIN
After 28 weeks of gestation, fetal neurons develop an acute ability to die from boredom.
1
Given estimates of 40-50 billion
neurons at birth,
2
and evidence that at least one fetal proto-neuron, and more likely two, undergo apoptosis for each neuron that
survives,
3
a midpoint estimate is that the human brain averages about 8,000 proto-neuronal+neuronal apoptotic deaths per second
during the last 11 weeks in utero. Those cellular suicides are selective, leaving the core material and sculpting the primary
architecture for subsequent CNS development.
4

The trigger for that avalanche of apoptosis is a lack of synaptic feedback. Apoptosis appears to be the default program of
many excitable cell types, with cell-typical activity promoting proteins like anti-apoptotic Bcl-2s that prevent the default
program from running its course. Put differently, the old saying Use it or lose it is not only for the old synaptic activity may
be as crucial to the survival of late-term fetal neurons as are O
2
, ATP and CBF. So what happens to fetal neurons that would be
receiving and sending signals were it not for the presence of anesthesia?
In laboratory animals
One of the first animal models to test the effect of anesthesia on fetuses was developed by Chalon in 1981. He exposed pregnant
mice to halothane and found that their offspring, and the offspring of those offspring, learned significantly more slowly than first
and second generation controls.
5
Analogous findings for offspring exposed in utero have been extended to isoflurane
6,7
and
sevoflurane
8
in rats, to ketamine in fetal rhesus macaques,
9
and Hogan has found first generation epigenetic effects of fetal
exposure to nitrous oxide that may extend to those offsprings offspring.
10
Recent studies notwithstanding, early laboratory
reports indicating a potential problem did not receive the attention they deserved until 2003 when Jevtovic-Todorovic and
colleagues published Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat
brain and persistent learning deficits a title that says it all.
11
Many subsequent studies have confirmed and augmented those
findings for neonatal exposure to desflurane, isoflurane, sevoflurane, propofol, nitrous oxide and ketamine in rodents, and some
of those effects have been extended down the taxonomic tree to nematode worms, suggesting that relevant gene/anesthetic
interactions are highly conserved and occur throughout the animal kingdom.
12

Postnatal apoptosis subsequent to a clinically relevant depth and duration of general anesthesia also occurs in mammals with
periods of rapid synaptogenesis more analogous to humans, including pigs
13,14
and a non-human primate.
15-17

Potentially
relevant for burn victims, twenty-four hours of a light surgical plane of ketamine anesthesia also causes long term cognitive
deficits in Rhesus macaque neonates.
18
Apoptosis notwithstanding, Stratmann and colleagues found that exposing 7-day-old rats
to four hours of isoflurane induced a decrease in neurogenesis that contributed to a permanent deficit in hippocampal-dependent
learning and memory.
19
Neurogenesis, of course, requires neural stem cells, and Culley et al have presented evidence that 1
MAC of isoflurane reduces the production of neural stem cells by 20% in vitro twenty four hours after exposure.
20
Decreased
neurogenesis and decreased neural stem cell proliferation notwithstanding, using 16-day-old rats, Briner and coauthors found that
sevoflurane, desflurane, isoflurane
21,22
and propofol
23
rapidly increase dendritic spine density, which could interfere with
physiologic patterns of synaptogenesis and thus might impair appropriate circuit assembly in the developing cerebral cortex
while Mintz et al found that general anesthetics interfere with axon polarization
24
and guidance
25
in vitro.

107
Page 2
In humans
Since 1945, investigators have observed an association between impaired neuro-cognitive-behavioral development and post-natal
exposure to surgery and anesthesia prior to 3 or 4 years of age,
26-45
with Levy
26
having found a statistically significant association
between near-term emotional sequelae and younger age at anesthetic exposure (p<0.0004, data not statistically analyzed in
original 1945 article). However, Bartels and colleagues investigation of monozygous twins addressed the hypothesis that
children who need to undergo surgery and anesthesia at an early age are inherently predisposed to impaired neuro-cognitive-
behavioral development. They studied 110 pairs of identical twins, one of whom had been anesthetized prior to age 3 with the
other having not been anesthetized prior to age three. They found, in pair-by-pair analyses, that the anesthesia-exposed twins had
virtually the same score as their non-exposed twin on a national measure of educational achievement administered near age
twelve.
46
Unfortunately, the Bartels study is not known to have included children who were anesthetized prior to six months of
age. That shortcoming, together with Kalkman and colleagues finding of a trend toward a greater detrimental effect of anesthesia
on neuro-cognitive development with decreasing age at administration,
40, see also 26,43
suggests that if there is a period of
extraordinary vulnerability in humans, it is similar to that found at analogous developmental stages in non-humans in utero to
six months post partum.

Bartels et als methodology was also not able to provide an estimate of duration of anesthetic exposure.
If duration of anesthesia is as important in human fetuses and neonates as it is in nonhumans,
13
then a 30-60 minute exposure
may not be sufficient to affect long term learning capacity, even in the high-vulnerability age group. Accordingly, Hansen and
colleagues finding of no substantive impairment in children exposed to a single, brief anesthetic procedure in infancy suggests
that deleterious effects start taking affect near 2 or more hours of exposure.
47

A recent examination of children under 1 year of age (average age 101 days) exposed to anesthesia for procedures that lasted
up to about 3.75 hours found an association with decreased academic performance after correcting for related CNS
complications. Block and colleagues analyzed achievement test scores of 7-17 year old children who received general anesthesia
during infancy for procedures that are not independently associated with cognitive impairments: inguinal hernia
repair/orchiopexy, pyloromyotomy and circumcision. After excluding children with any of 14 pre-specified CNS problems or
medical conditions associated with learning disabilities, they found that a substantial proportion of children without such risk
factors scored below the 5
th
percentile of the normative population (p<0.01), with increased duration of anesthesia associating
with reduced performance.
43

To date, perhaps the most intriguing evidence for anesthesia-induced neurodevelopmental deficits comes from a
retrospective dose-response study of 96 infants who underwent staged reconstructive surgery for hypoplastic left heart syndrome.
Initial surgery with cardio-pulmonary bypass was performed at less than two months of age. All subsequent surgical
interventions as well as ICU stays, up to neurodevelopment assessment at age 4 years, were included in a cumulative anesthetic
exposure analysis. Total exposure to VAA [volatile anesthetic agents] and fentanyl from birth to testing was calculated from an
anesthetic database and intensive ICU flowsheets. Exposure to halothane, isoflurane, sevoflurane and/or desflurane was
calculated, converted to age-adjusted minimum alveolar concentration-hours (MAC-hrs) and summed to yield total VAA
exposure Of 537 total anesthetic exposures, 478 had VAA, with total VAA exposure ranging from 0.9-35.3 MAC-hrs (median
7.54). There were 337 intraoperative fentanyl exposures. Cumulative intraoperative and ICU fentanyl dosage ranged from 118.59
to 3998.28 g/kg (median 309.87). After adjustment for patient and operative confounders (including stage 1 length of stay and
number of cardiac operations), increasing VAA exposure was associated with worse full-scale IQ, total language, executive
function, memory, reading and math skills (all p< 0.05). Increasing fentanyl exposure predicted worse full scale IQ, total
language, processing speed, memory, fine motor skills and math skills (all p< 0.05)."
44

Findings for fetuses may be stronger than those for post-natal humans. In 1986 Hollenbeck and coauthors reported
decreased cognitive capacity in four-year-olds whose mothers had been anesthetized while they were in utero.
48
Several
subsequent studies found analogous associations between pre-natal exposure to anesthetics and developmental problems
including autism,
49
hydrocephalus,
50
diminished general intelligence,
51
impaired spatial ability,
52
small head size and mental
retardation.
53

Ongoing Trials
With an anticipated completion date of December, 2016 and a projected sample size of 660 children, the GAS study will test for
a difference in preschool IQ between children who received sevoflurane or neuraxial bupivacaine for inguinal hernia repair when
they were 26-60 weeks old.
54
A recent laboratory experiment does not support nor challenge the GAS study because although it
found substantially reduced neuronal apoptosis in post-natal rats that received spinal injection of bupivacaine compared to rats
anesthetized with isoflurane, the spinal analgesia did not last long enough (40 to 60 minutes) to be expected to trigger apoptosis,
while the apoptosis-inducing sevoflurane exposure lasted for 6 hours.
55
Also disconcerting, the duration of anesthesia during
hernia repair in the GAS study may be too brief to test the anesthesia-development question (as per Hansen et al
47
). It may also
be the case that the sample size of the GAS study will be effectively diminished because too high a proportion of participants will
be too old at their age of exposure (per Bartels et al
46
).
The other major prospective study scheduled for completion in 2016, the Infant Anesthesia Exposure and Neuro-Outcome
study (formerly PANDA) is shooting for 1000 participants to compare Global and Domain-specific Neurocognitive Function
between children exposed to general anesthesia prior to 3 years of age during hernia repair versus siblings of nearly the same age
(within 3 years) who were not exposed to general anesthesia prior to age three. Unfortunately, like the GAS study
54
and the
study,
47
this investigation will test for an effect of exposures that are probably too brief to have an effect in a study population
that may be substantially comprised of children who are also too old to be sufficiently susceptible.
56

107
Page 3
So where do we stand?
The data in laboratory rodents are conclusive: clinically relevant doses and durations of anesthesia during the period of rapid
synaptogenesis cause neuronal apoptosis, other neuronal and glial derangements, and long term learning deficits. The same has
been established in pigs and a non-human primate with regard to apoptosis and glia. In distinction, the effect of anesthesia in
human neonates remains a concern that is confounded by genetics, by age at anesthetic exposure, by the duration of anesthesia
exposure, and by the effects of surgery independent of anesthesia. Data from human fetuses may be telling because they are
probably less confounded by genetics (the mothers genetic predispositions would be the primary association with a need for
surgery, but half of her fetus genes are not derived from her), by age at exposure (second and third trimester have now been
implicated as high risk periods in rodents, perhaps translating back to late-first-trimester in humans), and by the effects of surgery
independent of anesthesia (although the fetus and mother are equally anesthetized, the effects of surgery on the mother are likely
to be diminished in the fetus).

What might be done?
Olney and his group have proposed that anesthetic drug effects on fetal and neonatal gamma-aminobutyric acid and N-methyl-D-
aspartic acid receptors cause translocation of the Bcl-2-associated protein to mitochondrial membranes, leading to an apoptotic
cascade.
57
Perhaps this problem can be alleviated by anesthetic choice in pregnant females. Maze and his group have presented
evidence that xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain,
58
as does
dexmedetomidine.
59
Xenon is currently in clinical trials for perinatal hypoxic-ischemic brain injury
60
and for delirium in older
patients undergoing hip fracture surgery.
61

Several adjunct pharmaceuticals have also shown promise. L-carnitine, an l-lysine derivative that transports long-chain fatty
acids into mitochondria, appears to have a beneficial effect in N2O/isoflurane-damaged neonatal rats,
62
lithium reduces damage
from ketamine and propofol in neonatal mice
63
and clonidine reduces the apoptotic and behavioral effects of ketamine in neonatal
mice.
64
Patels lab has shown that inhibition of p75 neurotrophin receptors attenuates both isoflurane
65,66
and propofol
67

neurotoxicity in mice. Using the early post-natal rat model, Yon and coauthors found that melatonin reduced anesthetic-induced
damage in the most vulnerable brain regions: Melatonin-induced neuroprotection was mediated, at least in part, via inhibition of
the mitochondria-dependent apoptotic pathway since melatonin caused an up-regulation of the anti-apoptotic protein, bcl-X
L
,
reduction in anesthesia-induced cytochrome C release into the cytoplasm and a decrease in anesthesia-induced activation of
caspase-3 [precursor of apoptosis].
68
More recently, Jevtovic-Todorovics lab found that both EUK-134, a synthetic reactive
oxygen species scavenger, and R(+) pramepexole, a synthetic aminobenzothiazol derivative that restores mitochondrial integrity,
completely prevented general anesthesia-induced cognitive impairment in rats that had been exposed to 6 hours of
midazolam/isoflurane/N2O anesthesia on post-natal day 7.
69 see also 70-72
It would be a perfect circle if the investigator who did so
much to bring this problem to the worlds attention also heads the team that finds its solution. What about hypothermia and
neonatal brain damage? Creeley and Olney have reported laboratory evidence that hypothermia (30 C) attenuates anesthesia-
induced apoptosis in neonatal mice,
73
and human trials looking at whole-body
74,75
and head
76
hypothermia in neonates with
hypoxic-ischemic encephalopathy have found a decrease in death and/or moderate-to-severe disability.

Prevention of perinatal anesthesia-induced neurotoxicity notwithstanding, Stratmanns lab has produced evidence that
delayed environmental enrichment can mitigate sevoflurane-induced memory impairment in rats.
77
Unfortunately, as put by
Davidson, it is difficult to see how we could practically further enrich the environment for the average [human] infant in the 21
st

century
78
because, as put by Stratmann, we already live in a vastly enriched environment, compared with lab rats.

Have the data already changed clinical practice?
How would you answer the following question?
---------------------------------------------------------
A 27-year-old woman presents with an operable, slow-growing, benign, mildly symptomatic brain tumor. Her neurosurgeon has
scheduled the case and estimates an operation time of 4.5 hours. She is 25 weeks pregnant. Would you:

A. Use state-of-the-art equipment, procedures and drugs to proceed with the case?

B. Discuss evidence that has emerged or gained renewed recognition since 2003 that 4.5 hours of anesthesia may cause
neurodegeneration and persistent learning deficits in the developing brain with the neurosurgeon and leave the decision in his/her
hands?

C. Discuss the above evidence with the neurosurgeon and the parents and leave the decision in their hands?

D. Discuss the above evidence with the neurosurgeon and the parents and, barring development of substantive symptoms, advise
postponing surgery until after the patient has given birth or undergone a caesarian section?
---------------------------------------------------------
Our guess is that prior to Jevtovic-Todorovic and coauthors 2003 shot-heard-round-the-anesthesia-world,
11
most of us were
on the A train. In the absence of survey data, our best guess is that most of us would now follow a suggestion from the FDA
79

and opt for B, C or D because, as put by Drasner, If you arent concerned, you havent been paying attention.
80 cf.

81

107
Page 4
THE OLDER BRAIN

The older brain has less cognitive reserve less resilience to neurological challenges. Oxidative phosphorylation does not work
as well. We have acquired genetic mutations that can alter outcomes. Genetic alleles that were silent when we were young
manifest themselves (have phenotypic effects) as we age. And then there is free radical build-up with reduced levels of
scavengers like vitamin C, melatonin and vitamin E. All of these dreary realities probably contribute to Kline and coauthors
finding that Elderly subjects after surgery experienced an increased rate of brain atrophy a time associated with enhanced risk
for postoperative cognitive dysfunction [and] subjects with mild cognitive impairment suffered greater subsequent cognitive
effects.
82

POCD After Non-Cardiac Surgery
In 1955 P.D. Bedford published "Adverse cerebral effects of anaesthesia on old people."
83
He reviewed 1,193 (presumably non-
cardiac) patients over 50 years old who had received general anesthesia. Mental deterioration in 10% of patients appeared to be
long-term or permanent a figure that concurs with subsequent findings. Bedford concluded that cognitive decline is related to
anesthetic agents and hypotension. He recommended that Operations on elderly people should be confined to unequivocally
necessary cases and that postoperative medication should not be a routine matter. The next major study to report POCD skips
ahead 43 years to 1998 the first International Study of Postoperative Cognitive Dysfunction (ISPOCD).
84
In non-cardiac
patients more than 59 years old, the incidence of cognitive dysfunction 1 week after surgery was 22% higher than in age-matched
controls and 7% higher 3 months after surgery (p<0.004 for both) with 10% of patients (91/910) evidencing POCD (identical to
Bedfords finding at a longer postoperative interval). Increasing age, duration of anesthesia, lesser education, a second operation,
postoperative infection, and respiratory complications were risk factors for early postoperative cognitive dysfunction. However,
under a circumstance of significantly reduced statistical power due to a 22% loss of follow-up at 3 months, among the risk factors
that were significant in the early postoperative period, only age remained statistically significant.
Monk and colleagues found that 12.7% of elderly (>59 y o) non-cardiac patients had POCD three months after surgery
85

again, within a narrow confidence interval around Bedfords 1955 report. Corroborating earlier work,
86
this study also found a
substantial relationship between POCD and death within one year of surgery.
see also 87,88
Independent risk factors for sustained
POCD included greater age, less education, POCD at hospital discharge and a history of stroke without residual damage.
Consistent with many investigations, more education may indicate greater pre-surgical cognitive reserve, just as prior stroke may
indicate pre-surgical reduction of cognitive reserve.
88,89
Notably, Monks 08 study did not find duration of anesthesia to be a
risk factor. However, the risk of a false negative conclusion is high in that regard, because the sample size of elderly patients at
the 3-month measurement was even smaller (308 with 39 POCD patients
85
) than in the International Study of POCD (901 with
91 POCD patients
84
). The longest follow-up study of POCD patients (median = 8.5 years) was published by the ISPOCD group
in 2009: "Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor
market prematurely, and dependency on social transfer.
90

POCD After Cardiac Surgery
Most of us have heard friends or relatives say something like since he had open-heart surgery, hes not the same he cant
think as well, hes not as happy. The New York Times brought attention to this problem with an article entitled Saving the
Heart Can Sometimes Mean Losing Your Memory.
91
In that article, Juhar explained the basics of extracorporeal circulation and
discussed reasons for memory loss, focusing on a patient who had gone back to work and found that he had difficulty with his job
a patient who could not perform functions that he had performed for many years. That article raised a great deal of concern,
setting the stage for a paper published a year later in the New England Journal of Medicine by Newman and colleagues.
92 see also 93

They found POCD in 53% of Coronary Artery Bypass Graft (CABG) patients at discharge and in 36% of patients six weeks later.
That proportion went down to 24% six months after surgery, but came back up to 42% five years after surgery a pattern of
early improvement followed by subsequent decline that was predicted by POCD at discharge.
see also 94

The factors that cause decline in cognitive capacity among non-CABG patients also affect CABG patients. However, some
of those risk factors, like duration of exposure to anesthetics, may be masked by damage done to CABG patients from increased
liability to cerebral emboli, cerebral ischemia during re-perfusion, and over-warming after bypass.
95

Aggravating Factors

- On-pump vs. Off-pump
Does on-pump versus off-pump make a neurocognitive difference? Two major studies have failed to detect a neurocognitive
advantage for off-pump patients.
96,97
Although Shroyer et al failed to find a statistically significant difference across their
composite test battery, they did find a significant difference on one important test in favor of off-pump, suggesting the possibility
of a false negative conclusion.
96 cf. 98
More recently, Puskas and colleagues found that After a mean of 7.5 years of follow-up,
patients undergoing off-pump coronary artery bypass performed better than those undergoing [on-pump] cardiopulmonary bypass
in several neuropsychological domains,
99
and in a sort of positive-control study, Li et al found that preconditioning with
hyperbaric oxygen reduced markers of cerebral injury in patients undergoing on-pump bypass but not in patients having off-
pump bypass, reasoning that the protective effects of HBO preconditioning may only manifest when there is a relatively severe
injury, such as an on-pump procedure and not in off-pump CABG surgery patients.
100
Less direct evidence came from a study of
over 16,000 patients in whom a greater incidence of delirium occurred after on-pump cardiopulmonary bypass, with duration of

107
Page 5
surgery (and so anesthesia) as a significant risk factor.
101
Although these patients were not followed up for POCD, Girard and
coauthors found that in mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially
modifiable) was independently associated with long-term [12 month] cognitive impairment
102
and Morandi et al found that
delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months later.
Similarly, white matter disruption was associated with worse cognitive scores up to 12 months after discharge.
103
Most recently,
in a prospective study of 225 CABG patients, Saczynski and and coauthors found that Delirium is associated with a significant
decline in cognitive ability during the first year after cardiac surgery
104
and in 263 Alzheimers disease patients, Gross and
colleagues concluded that Delirium is highly prevalent among persons with Alzheimers disease who are hospitalized and is
associated with an increased rate of cognitive deterioration that is maintained for up to 5 years.
105
Clearly, a relationship
between depression, sedation, delirium, poor neurological outcome and POCD should not be discounted,
101-111

such that off-
pump patients may be at lesser risk for POCD. Most recently, both the 1-year follow-up from the CORONARY investigators
97

and the GOPCABE study group
112
failed to find a statistically significant advantage of off-pump bypass. Statistical significance
aside, both investigations did find a lower incidence of stroke in off-pump patients. If those results were added to Afilalo and
colleagues recent meta-analysis, they would increase the statistical significance of an already significant finding of a 30%
reduction in relative risk of stroke for off-pump patients.
113
So we are left wondering how patients who experience far more
strokes (on-pump patients) did not evidence statistically significantly worse neurocognitive outcome. One reason is that in the
CORONARY study some surgeons took the liberty of performing off-pump surgery on 102 patients who had been randomly
assigned to on-pump surgery because those patients had calcification of their aortas. In the intention-to-treat analysis, those
patients results were analyzed as if they had on-pump surgery.
114
These very non-random protocol violations were accompanied
by patient-selected, as distinct from randomly selected, inclusion in neurocognitive testing.
97
Dr. Hartung and I have argued that
intention-to-treat analysis should always be accompanied by on-treatment analysis,
115
and calculating a p value for non-random
samples makes no sense. In this case absence of evidence is not evidence of absence,
116
and unless strokes do not have neuro-
cognitive consequences, my best-guess appraisal of the evidence is that on-pump bypass increases neuro-cognitive impairment.

- Inflammation
Inflammation caused by surgical trauma may also aggravate POCD and is associated with the pathogenesis of Alzheimers
Disease (AD) in a mouse models.
117
Evidence that the association is causal comes from vom Berg and coauthors finding that
intracerebroventricular delivery of anit-p40, and inhibitor of inflammatory signaling, significantly reduces the concentration of
amyloid ! (A!) and reverses cognitive deficits in aged Alzheimers mice.
118
We know about the up-regulation of IL-1, and this
in turn can affect anesthetic receptors.
119
The ensuing cascade of events ultimately affects the anesthetic gamma-aminobutyric
acid and N-methyl-D-aspartic acid receptors and increases production of A! and we know that soluble oligomers of A!, even
in non-demented patients, associate with cognitive problems. Genetic predispositions are another aggravating factor. For
example, Matthew and coauthors have shown the contribution of P-selectin and C-reactive protein alleles in modulating
susceptibility to cognitive decline caused by inflammation after cardiac surgery,
120
and Cai et al found an association between
APOE4 and early POCD in elderly patients undergoing inhalation anesthesia.
121

- Anesthetics
Are anesthetics aggravating factors? If so, are some more toxic than others? Le Freche and coauthors were able to link an
increase in phosphorylated tau to diminished memory in sevoflurane-exposed adult mice
122
and Liu et al found that sevoflurane
accelerates the progression of mild cognitive impairment (MCI) in MCI patients undergoing spinal surgery.
123
Dong and
colleagues found that just 2 hours of clinical anesthesia with isoflurane generates caspase-3
124
and increases phosphorylated tau
in adult mice,
125
and Eckenhoffs group has found that a presenilin-1 mutation associated with familial AD renders

PC12 cells
more vulnerable to isoflurane cytotoxicity, but not to sevoflurane

or desflurane cytotoxicity,
126
while Xies group found that
isoflurane induces more caspase-3 activation and A-beta oligomerization in AD transgenic neonatal mice than does propofol.
127

Xies group also found increased levels of A! and caspase-3 in adult mice exposed to 1.4% isoflurane for 2 hours,
128
but greater
cognitive decline in patients 1 week after surgery who received spinal anesthesia with desflurane versus spinal anesthesia with
isoflurane or spinal anesthesia alone.
129, cf. 130

Jevtovic-Todorovic and Carter reported that old rat brains are equally (nitrous oxide) or more sensitive (ketamine w/ and
w/o nitrous) to anesthetic neurotoxicity than infant rat brains,
131
and Culley and coauthors found that spatial memory is impaired
for 2 weeks after 2 hours of 1.2% isoflurane with 70% nitrous oxide in aged rats.
132
What about nitrous oxide alone? Culley et al
found that aged rats exposed to 70% nitrous oxide for 4 hours took more time to complete a maze and made fewer correct choices
before making their first error compared to control rats for two weeks after exposure.
133

In a separate group of rats, they found
that the same nitrous oxide exposure profoundly, but transiently, reduced the activity of cortical methionine synthase an
enzyme that is implicated in dementia and may be

related to accumulation of homocysteine (a cytotoxic amino acid

normally
remethylated to methionine, an essential amino acid,

by methionine synthase).
133
Examining autopsy brain tissue, Crary and
coauthors found that PKMzeta, an atypical protein kinase C isoform, accumulates in the neurofibrillary tangles of Alzheimers
patients, but not in control patients.
134
One wonders whether anesthetics might increase this tangling in both AD and non-AD
patients. My lab is currently investigating the effect of anesthetics on PKMzeta in the adult mouse hippocampus.
134,135

- Deeper vs. Lighter & Regional vs. General Anesthesia
Although a study by Farag and colleagues found that deeper anesthesia (bispectral index 39) associated with better cognitive
function than lighter anesthesia (bispectral index 50) in 74 patients 4-6 weeks after surgery,
136
in a study of 921 elderly patients

107
Page 6
undergoing major non-cardiac surgery, the CODA Trial Group found that patients with a median BIS of 53 experienced less
delirium and had less POCD 3 months after surgery than a control group maintained at a median BIS of 36.
137
This discrepancy
in results parallels the frequently observed lack of difference in POCD, or the weakness of the difference in POCD, between
patients who receive general anesthesia and patients who receive regional anesthesia with substantial sedation.
138-140
Ancelin
found that Adding sedation to peridural anaesthesia led to a decline in

verbal secondary memory
141
and Sieber et al found that
lighter sedation during spine surgery led to less delirium.
142, cf. 143
Again, there are empirical and neuropathological reasons to
suspect a link between delirium, deep sedation, poor neurological outcome, and POCD.
101-111
Examining results from 980
patients who underwent intra-arterial therapy for acute ischemic stroke under conscious (light) sedation versus (light) general
anesthesia, Abou-Chebl and colleagues found poorer neurological outcome and higher mortality in the general anesthesia
patients.
144
Neuman et al also found higher mortality and more pulmonary complications in general anesthesia patients,
compared to regional anesthesia patients, undergoing hip fracture surgery.
145
If the association between POCD and deep sedation
had been discovered before the association between POCD and general anesthesia, perhaps we would have come more readily to
the hypothesis that regional anesthesia with deep sedation

is equivalent to general anesthesia when it comes to increasing the risk
of POCD.
146

- Anesthesia and Neurodegenerative Diseases
Do anesthetics affect neurodegenerative diseases? Hydrophobic cavities keep sticky proteins from becoming irreversibly glued
together. Unfortunately, molecules of inhalational anesthetics can fill those cavities and reduce the amount of energy required to
maintain protein assembly.
147
This anesthesia-facilitated disinhibition of protein binding helps monomers aggregate into
oligomers, and if those monomers are A!, the resulting oligomerization can lead to protofibrils that are small enough to diffuse
into neurons and large enough to be neurotoxic. Inhalational anesthetics notwithstanding, Yamamoto and colleagues recently
found that ketamine reduces A! degradation in primary astrocyte cultures, leading to the conclusion that ketamine might have
adverse effects on patients at high risk of AD [Alzheimers Disease].
148
Soluble A! oligomers
149
and alpha-Synuclein
150
appear
to contribute to the neurodegeneration characterized by Alzheimer in the early 20
th
Century. Thirteen million Americans are
projected to have AD by the middle of the 21
st
Century.

Many of them will need to be anesthetized, and many of them will have
been anesthetized before they became demented.
The role of inhalational anesthetics in the above scenario has been verified in vitro by a decade of work from Eckenhoff and
coauthors,
151
and is also supported by in vivo by mouse models.
124,152
In addition to the A!-anesthesia connection, Xie's group
has utilized human neuroglioma cell cultures to add anesthesia-induced apoptosis as a factor contributing to AD
124, 153-154
and
they have found that isoflurane, but not desflurane, degrades mitochondrial function and impairs learning and memory in mice.
155

Do the rodent and cell culture findings apply to humans? Eckenhoffs group reported that the total-tau/A!(1-42) ratio in CSF,
the only biomarker validated for use in the diagnosis of AD by the Alzheimers Disease Neuroimaging Initiative (ADNI),
elevates during surgery and anesthesia in healthy patients and rises above ADNIs threshold for mild cognitive impairment within
48 hours.
156
In an article entitled Coronary artery bypass surgery provokes Alzheimers disease-like changes in the
cerebrospinal fluid, Palotas and colleagues found an increased tau/A! ratio in patients 6 months after surgery.
157

Results from retrospective studies remain inconclusive, but are unsettling. Examining records of 9,170 veterans, Lee et al
compared the risk of developing AD within 5-6 years of cardiac surgery (CABG) under inhalational anesthesia versus the risk of
developing AD within 5-6 years of percutaneous transluminal coronary angioplasty, the latter seldom requiring general
anesthesia.
158
After adjustment for age, length of hospital stay, co-morbidity and number of procedures, the CABG patients
developed AD at nearly twice the rate of percutaneous transluminal coronary angioplasty patients (hazard ratio 1.71, p<0.04).
Yes, CABG patients faced more predisposing factors than percutaneous transluminal coronary angioplasty patients, including
embolic ischemia, but given in vitro evidence supporting mechanisms for a causal link between anesthesia and AD, it would be
reckless to dismiss prolonged inhalational anesthesia as an independent contributing factor to Lee and coauthors finding.
Bohnen and coauthors performed a case-controlled retrospective study of 252 AD patients.
159
Unfortunately, 199 of the 252
controls (non-AD patients) had prior exposure to general anesthesia, which greatly dilutes their statistical power to evidence an
effect of anesthesia relative to AD patients. Nevertheless, Bohnen et al found non-statistically significant effects in the direction
of a link between AD and general anesthesia on each of three independent variables: cumulative exposure to anesthesia,
exposure to six or more episodes of general anesthesia (OR = 1.44) and cumulative exposure to 600 minutes or more of general
anesthesia (OR = 1.63). Gasparini and coauthors also performed a retrospective case-controlled study of AD patients. In their
study the controls were Parkinsons disease patients and patients with other neurological diseases
160
but a link between general
anesthesia and other neurological diseases has been hypothesized,
147
such that lack of

a difference in anesthetic exposure between
AD patients and patients with Parkinsons or other neurological diseases does not imply a lack of a deleterious effect of
anesthetic exposure.
Although a connection between anesthetics and AD has received more attention than a possible relationship between
anesthesia and Parkinsons or Huntingtons disease, two investigations suggest that further research is warranted. Peretz and
coauthors have found evidence that supports an elevated risk of Parkinsons disease among anesthesiologists as compared to
internists
161
and Wang et al have found in vitro laboratory evidence that isoflurane may exacerbate Huntingtons disease.
162

So there is evidence that anesthetics are a particular problem for older patients, but before we make recommendations more
firm than Bedfords admonition from 1953 that Operations on elderly people should be confined to unequivocally necessary
cases
83
we need to know more about genetic profiles in order to know which older patients are most at risk.

107
Page 7
Potential Alleviating Factors

- Anesthetics
How might we reduce the risk of POCD in older patients? Are some anesthetics less deleterious than others? Crosbys group has
presented data indicating that In aged rats, propofol anesthesia is devoid of the persistent memory effects observed with other
general anesthetic agents in this model. Thus, it appears that general anesthesia-induced memory impairment may be a function
of the agent rather than the anesthetic state itself.
163
Complementary in vitro work by Wei and Xie also suggests that
sevoflurane and desflurane are less potent triggers of apoptosis than isoflurane.
164
In a hippocampal slice model, desflurane was
more protective than propofol
165
and in a rat cardiopulmonary bypass model, isoflurane with 60% Xenon has been shown to
prevent the decrement in neurocognitive function caused by bypass under isoflurane alone.
166
Xenons potential to reduce the
incidence of postoperative delirium in elderly patients after hip fracture surgery is currently being evaluated by Coburn and
colleagues.
167

One of my departments laboratories has investigated the effects of lidocaine during global ischemia in rats, finding that
neuron death in the hippocampus is substantially reduced in animals that have received clinically relevant doses of lidocaine.
Function was also better retained after global ischemia in animals that received lidocaine.
168,169
Looking at CABG patients,
Wang and coauthors found that lidocaine (1.5 mg/kg bolus

followed by a 4 mg/min infusion during operation and 4 mg/kg

in the
priming solution of cardiopulmonary bypass) reduced POCD measured 9 days after surgery.
170
Looking at a larger number of
CABG patients, Mitchell and colleagues also found reduced POCD in patients that received lidocaine from 75% to 40% at 10
days (p<0.025), from 75% to 46% at 10 weeks (p<0.05) and then from 48% to 28% at 6 months (ns).
171 cf. 172
More recently,
Newman's group at Duke reported a significant reduction in POCD at 6 weeks and 1 year among non-diabetic cardiac patients.
This effect was most pronounced in non-diabetic patients who received less than 43 mg/kg lidocaine (total dose), while lidocaine
appears to have had a deleterious effect in diabetic patients and in patients who received higher total doses.
173

- A Grab Bag of Adjuvants
What about erythropoietin, prophylactic anti-psychotics, melatonin, cholinesterase inhibitors, memantine, insulin, statins,
dantrolene, bexarotene, an N-terminal fragment of a prion protein, crenezumab, and exercise? Lauretani and colleagues found
that EPO levels are lower in 60-to-98-year-olds with impaired peripheral nerve function and/or clinical diagnosis of
polyneuropathy.
174
Haljan et al found a trend toward improved neurocognitive recovery with erythropoietin use in CABG
patients,
175
and in post-hoc analyses Tseng et all found EPO to be protective in SAH patients who are younger, non-septic, and on
statin therapy.
176
Most recently, a double-blind trial by Abrishamkar and colleagues found improved Glasgow Outcome Scores
in patients with diffuse axonal injury who received subcutaneous injections of EPO every other day for two weeks.
177
Hakim and
coauthors found that the anti-psychotic risperidone reduces delirium after on-pump cardiac surgery in elderly patients
178
and
Teslyar and coauthors meta-analysis found that prophylactic anti-psychotics reduce post-operative delirium more generally,
179

which may auger well for reduction of subsequent POCD. Cheng and colleagues review of the beneficial effects of melatonin in
experimental models of AD is encouraging,
180
as is Ni and coauthors finding that melatonin premedication attenuates isoflurane-
induced A! in the hippocampus of aged rats.
181
A clinical study by Furio et al found that melatonin improved cognitive function
in elderly outpatients who suffered from mild cognitive impairment.
182
More recent studies indicate that cholinesterase
inhibitors,
183
memantine,
184-185
and insulin therapy,
186
improve cognitive function, or delay clinical worsening, in AD patients and
dantrolene has been shown to reduce memory deficits and amyloid plaque in AD mice.
187
Bexarotene, an FDA-approved anti-
cancer drug that dramatically reduces A! in mice and improves behavior
188
is now in a clinical trial.
189
The jury has looked hard
for evidence that statin therapy prevents or ameliorates AD, but a definitive verdict is still pending.
190
In distinction, Blanco et al
found that statin withdrawal increased the incidence of poor outcome in ischemic stroke patients
191
and a retrospective review of
12,689 patients by Flint and colleagues found that Statin use during ischemic stroke hospitalization is strongly associated with
improved poststroke survival
192
and discharge disposition,
193
even for patients without prior statin use. On the far edge of
pharmacological approaches, an N-terminal fragment of the cellular prion protein that binds A! oligomers is showing promise in
the laboratory.
194,195 cf. 196
Pharmacological approaches notwithstanding, unless crenezumab
197
and or bexarotene
188,189
fulfill their
promise, perhaps age-appropriate exercise remains the best all-round regimen for both prevention and cure of POCD.
198-201

- Preconditioning
Although fetuses and the elderly are particularly sensitive to ischemia, hypo-perfusion and hypoxia, Nietzsches Toxicology:
whatever doesnt kill you might make you stronger
202
could lead to improved clinical management of patients with fragile
brains.
In 1964 Dahl and Balfour published evidence of prolonged anoxic survival due to anoxia pre-exposure.
203
This
phenomenon was eventually replicated in a model of cerebral ischemia,
204
and induction of endogenous proteins of repair and the
genes that code for them are now well documented. Our laboratory has added sevoflurane as a potential preconditioner,
205,206
and
Maze's group reported that in comparison to sevoflurane,
207
nitrous oxide and hypoxia,
208
xenon preconditions in a manner that
"might mimic the intrinsic mechanism of ischemic preconditioning most closely." But if a limited dose of anesthesia triggers the
same protective mechanisms as a limited bout of hypoxia, how much anesthesia can we give before what would have been a
protective effect becomes a deleterious effect on balance?
146

Clinically acceptable means of accomplishing cerebral preconditioning are being sought. Volatile anesthetics
notwithstanding, pharmacological cerebral preconditioning may be eclipsed by mechanical Remote Ischemic Preconditioning
(RIPC). Clinical studies have established that three 5-minute inflations of a blood pressure cuff to 200 mmHg around a patient's

107
Page 8
upper arm, followed by 5-minute intervals of reperfusion, improves outcome after some cardiovascular procedures

and evidence
from laboratory investigations indicates that the same technique initiated prior to neurosurgery may improve outcome.
208-211

Clinical studies of RIPC in neurosurgical patients are underway or have recently been completed,
212
and a published study by Hu
and colleagues has reported reduced biochemical markers of neuronal ischemia and improved rate of recovery after cervical
decompression in patients who received RIPC.
213

- Neurogenesis
The old adage that neurogenesis is only for the young was shown to be wrong for rodents in 1965,
214
is known to be wrong for
non-human primates,
215
and is almost certainly wrong for humans.
216
This raises the possibility that negative effects of surgery
and anesthesia on the elderly, as well as the very young, can be compensated by therapies that strengthen the neurogenic
response. Results in rats encourage the conclusion that "neural precursors resident in the brain initiate a compensatory response
that results in the production of new neurons. Moreover, administration of growth factors can enhance this compensatory
response [and] we may eventually be able to manipulate these precursors to improve recovery of function."
217-218
In addition
to ischemic preconditioning,
219
granulocyte-colony stimulating factor
220
and erythropoietin
221,222
appear to be such manipulators,
and neurogenesis may be the therapeutic mechanism of electroconvulsive therapy in patients with depression.
223,224

Unfortunately, however, as noted above, Culley and colleagues have presented evidence that 1 MAC isoflurane reduces the
production of neural stem cells by 20% in vitro 24 hours after exposure.
20
Noting that a 15-20% decrease in neurogenesis in vivo
is sufficient to impair hippocampal-dependent memory in rodents,
225
and even more striking, recall of remote spatial memory in
adult animals depends on recruiting as few as 1-4% newly-born neurons into hippocampal circuits
226
even a transient adverse
effect of isoflurane on self-renewal of NSCs [neural stem cells] might have far-reaching consequences for brain development and
function across the life-span. If so, this raises concern about the effect of all anesthetics on NSC proliferation at critical periods
of brain development as well as in adulthood.
20

CONCLUSION

Reports of possible adverse cognitive effects of anesthetics on young patients appeared in our literature during the 1940s, on
elderly patients in the 1950s, and on fetuses in the 1980s ... so these problems and some of their potential solutions are not new,
but our awareness of them has experienced a renaissance over the past decade. Fortunately, the vast majority of anesthetics
delivered to infants last less than 1.5 hours or are administered to children that are more than 6 months old. For that majority, I
agree that the evidence is most consistent with the premise that anesthesia per se, given to an otherwise healthy child who
needs only a routine surgical procedure, is not neurotoxic
227
or is not toxic enough to cause a currently measurable adverse
effect. However, for children less than 6 months old, fetuses of any age and patients over 60, until and unless we are able to
classify substantive anesthetic neurotoxicity as a rare complication, the conservative first-do-no-harm approach should: 1) add
anesthesia to surgery on the cost side of the cost/benefit equation when making decisions about whether and when to proceed
with surgery; 2) avoid nitrous oxide,

isoflurane

and ketamine

because multiple laboratory studies indicate that they are
particularly toxic; 3) limit the duration of continuous anesthesia to less than 2 hours whenever possible; and 4) consider the
possibility that regional anesthesia with deep sedation may trigger as much neuronal apoptosis as general anesthesia.
At the very least, newfound concerns generated by available data should inspire a great deal of translational research. If that
research is funded, my guess is that we will soon have anesthetic, sedative and adjuvant drugs ranked according to their
deleterious effects and cerebral preconditioning with augmentation of endogenous processes of regeneration will deliver brain
protection and recovery to the very young, the old, and everyone in between before the younger among us are too far gone to
benefit!

References: (Most references are given as PubMed ID number put just the number in the PubMed search box.)
1
8786390
2
9215725
3
12773370
4
6474175
5
7197490
6
21307768
7
22705347
8
23314109
9
22222480
10
Hogan K. ASA 2011
Abstract BOS01
11
12574416
12
23223110
13
20633108
14
22576279
15
20234312
16
Brambrink AM. ASA 2012 Abstract A103
17
23109147
18
21241795
19
19293705
20
21666433
21
20124985
22
20124984
23
21701379
24
23085784
25
23364597
26
Levy,
1945, Am J Dis Child 69:7-25
27
14838345
28
13103772
29
7545411
30
9156529
31
8839088
32
9370839
33
15385017
34
15741374
35
16184065
36
16394717
37
17307535
38
19293700
39
19955889
40
19293699
41
21969289
42
22305025
43
22801049
44
Diaz et al,
2012, IARS Abstract S-400 (ms submitted)
45
22908104
46
19456216
47
21368654
48
3792096
49
1709436
50
7977913
51
7474220
52
9803015
53
10852187
54
(google) NCT00756600
55
21555934
56
57
15277906
58
17413912
59
19352168
60
61
23016882
62
18201836
63
19293695
64
22694670
65
19293698
66
21169791
67
22198221
68
16289675
69
22198380
70
21909020
71
23411726
72
23626588
73
19955510
74
16221780
75
23450604
76
20488453
77
22354242
78
22258021
79
22258021
80
20508495
81
19955510
82
22293721
83
13243706
84
9525362
85
18156878
86
15616043
87
20418692
88
19910621
89
16894104
90
19225398
91
Jauhar, New York Times, September 19, 2000 (Science, p.1)
92
11172175
93
22256807
94
16645936
95
11823666
96
19890125
97
23477676
98
16387994
99
21334013
100
21868252
101
14752413
102
20473145
103
22584766
104
22762316
105
23403619
106
17234824
107
19414723
108
21474660
109
21372278
110
21386669
111
20838332
112
23477657

113
21987177
114
22449296
115
15840989
116
6829975
117
20711073
118
23178247
119
16402109
120
17498578
121
22108393
122
22343471
123
23044653
124
19433662
125
22745746
126
18227305
127
22069482
128
19006075
129
22075020
130
23438677
131
15718054
132
15502036
133
17578961
134
Tsokas, P. Abstract BOSO4, ASA, Oct. 2012
135
22674720
136
16931673

137
23027226
138
15138912
139
16803914
140
20858956
141
11282816
142
20042557
143
20042555
144
20395617
145
22713634
146
22238041
147
19820235
148
23624023
149
22121920
150
22836259
151
17346857
152
16564662
153
17287498
154
18326038
107
Page 9
155
22368036
156
21857497
157
21504113
158
16131734
159
8126336
160
12111615
161
16078210
162
21059370
163
18806029
164
19199872
165
19236906
166
12606913
167
23016882
168
15099683
169
21777661
170
12401580
171
10320260
172
19231397
173
19164788
174
18439654
175
19556536
176
19929191
177
23248657
178
22436797
179
23380670
180
16412260
181
23256744
182
17910609
183
22541366
184
22513699
185
23635410
186
21911655
187
22516463
188
22323763
189
www.alzheimersweekly.com
/2013/04/fda-approved-bexarotene-rushes-to.html
190
22473869
191
17724294
192
22020026
193
22614435
194
23362282
195
23335053
196
23627220
197
22935790
198
16177036
199
22267788
200
Reynolds, New York Times, Exercising to fire up the
bodys trash furnaces. February 7, 2012
201
21971406
202
12951822
203
14205366
204
2797463
205
17291693
206
19352153
207
20613483
208
16781056
209
17577439
210
18201834
211
20216397
212
http://clinicaltrials.gov /ct2/results?term=remote
+preconditioning
213
19996767
214
5861717
215
17405451
216
21519376
217
15271491
218
19860727
219
17434685
220
17346168
221
18089462
222
20142991
223
20190603
224
21570438
225
18758458
226
19321751
227
22021792
Disclosure
120
Page 1
Supratentorial Tumors: Evolving Management and Techniques
Alex Bekker, M.D., Ph.D Newark, New Jersey
Awake Craniotomy
Awake craniotomy represents an important option for resection of tumors which are located in close proximity to
functionally important (termed eloquent) areas of the cortex (e.g. speech, motor). The main reason for performing
surgery on awake patient is a need for intraoperative testing of neurological function.
1,2
During an awake
craniotomy, a patient is conscious as the surgical team stimulates different areas of the brain while asking the patient
to perform certain tasks. With the patient awake, the eloquent areas of the brain can be mapped before lesion
resection.
Potential Advantages of Awake Craniotomy:
- Opportunity for brain mapping allows maximal tumor resection, minimizing postoperative neurologic deficits due
to retraction, edema, and/or resection of eloquent tissue.
3,4

- Cortical mapping results, the extent of the resection, and intraoperative neurological changes are better predictors
of neurological outcomes than tumor histologic features, tumor location, or preoperative deficits
5

- Avoidance of general anesthesia and need for more intensive monitoring intraoperatively and postoperatively
1, 6

- Low complication rate and reduction in resource utilization (shorter intensive care time and total hospital
stay).
1,6,7
Awake Craniotomy: Challenges
- Requirement for providing analgesia and sedation during periods of intense surgical stimulation and having the
patient awake and cooperative during functional testing.
- Uncontrolled pain during head-holder placement, skin incision, craniotomy, and dura opening may lead to
hemodynamic instability, emotional distress, and loss of patients cooperation.
- Excessive sedation may result in hypoventilation and hypoxemia, both hazardous to the patient with intracranial
lesion. Uncooperative, oversedated or agitated patient may require urgent induction of general anesthesia. Either
controlled ventilation or endotracheal intubation is exceedingly difficult in a patient positioned laterally under
surgical drapes while the head holder fixes the head.
- Relatively high incidence of seizures that may be caused by the cortical stimulation.
Preoperative Evaluation and Preparation:
The preoperative visit to the patient scheduled for awake craniotomy is of paramount importance irrespective of the
chosen technique, especially in pediatric patients.
The objectives of the preoperative visit are to:
- identify a motivated patient with good psychological profile and establish a relationship of confidence and trust;
- inform the patient about the procedure and what to expect (e.g., detailed verbal description, video tape);
(It should be emphasized that a patient would be deeply sedated for the most painful episodes which,
usually, occur during the initial and final parts of the operation.)
- inform and reassure the patient that the anesthesiologist will be at bedside throughout the procedure and will
administer analgesics and sedative, if required.
- Benzodiazepine premedication is generally avoided because of its residual and amnestic effects during
intraoperative functional testing
- It is common to administer gastrointestinal premedications such as ondansetron, metoclopramide, or famotidine.
O.R. equipment and staff must be prepared in advance.

104
Page 2
Intraoperative Management.
Various intraoperative management strategies have been proposed. Adequate analgesia and sedation are needed for
head frame application, skin incision, craniotomy, and opening of the dura. During brain mapping and tumor
resection, the patient should be fully awake and cooperative to enable continuous neurologic assessment. Several
different anesthetic protocols have been recommended for awake craniotomy.
8
The current trend is to use controlled
ventilation with LMA airway protection for the initial part of the procedure and awaken the patient for functional
testing. This approach became popular with the introduction of short acting, titratable drugs, and, more recently,
monitors of depth of sedation (i.e. BIS).

Many sedation techniques have been described for awake craniotomy. Several reports have endorsed the use of
propofol for sedation during awake craniotomy
9
. The rapid onset and a fast redistribution offer flexibility and ease
of titration. In addition, the use of propofol reduced the incidence seizures and nausea/vomiting. Oversedation and
respiratory depression are ever-present concern. Skucas and Artru have reported SpO2 of 91% -95% in16.9 percent
and SpO2 < 90% in 1.5% of 332 patients who were sedated with propofol without other sedatives
10
. Obesity was a
consistent risk factor requiring a secure airway. Other complications included hypotension (56.3%), tachycardia
(14.2%), seizures (3%), and patient movement (1.5%). Asleep-awake-asleep technique without airway devices was
used in that series of cases.

A combination of propofol and remifentanil has been successfully used for the awake brain lesion resection
11,12
.
Remifentanils context-sensitive half-life is less than 5 minutes and independent of infusion duration. These
characteristics allow a rapid modulation of analgesia and sedation that is required during the course of the surgery.
The adverse effects of remifentanil, however, are similar to those of all fentanyl congeners and include respiratory
depression, oversedation, and nausea. A retrospective chart review of 98 procedures revealed high incidence of
respiratory depression
13
. The authors report PaCO
2
of 50 (36-69) mm Hg and at least one 30-s epoch of apnea in 69
patients. In addition, 8 patients experienced nausea, 3 had intraoperative seizures, and 7 were unable to tolerate
awake state (include disoriented patients).

Dexmedetomidine (DEX), a highly specific alpha-2 adrenoreceptor agonist, has been recommended for use during
awake craniotomy.
14,15,16
It does not suppress ventilation. The sedation produced by alpha-2 adrenoreceptor
agonists, unlike that by traditional sedatives such as benzodiazepines and propofol, does not depend primarily on
activation of the gamma-amino butyric acid (GABA) system. Furthermore, the primary site of alpha-2 agonist
sedative action does not appear to be the cerebral cortex, as would be the case with GABA-mimetic drugs. Perhaps
because of a non-cortical site of action, alpha-2 agonists appear to engender a different type of sedation when
compared to GABA-mimetic drugs. DEX produces an unusually cooperative form of sedation, where patients easily
transition from sleep to wakefulness and task performance when aroused, and then back to sleep when not
stimulated.

Furthermore, disinhibition, cited as a common problem for propofol and the benzodiazepines, has not
been described for DEX. It is possible that given DEX appears to exert its sedative action at the LC, a brain
wakefulness and anxiety center, cognitive compromise and accompanying disinihibition is less prominent. This
theory is consistent with healthy volunteer data indicating that cognitive integrity is well preserved in patients
receiving DEX.

Regional scalp blockade supplemented with field blocks are commonly used to reduce pain associated with the bone
flap removal and dura opening. Techniques for regional analgesia is well described and include blockade of the
greater and lesser occipital, auriculotemporal nerve, supraorbital, and zygomaticotemporal nerves
17
. Bupivacaine
0.5% with epinephrine 1:200,000, 2.5 cc is usually injected at each site. In addition, approximately 40 cc of
bupivacaine 0.33% with epinephrine 1:200,000 is injected along the incision line prior to commencing surgery.
Ropuvacaine, 0.5%, which is less cardiotoxic, but has a pharmacological profile similar to that of bupivacaine, is a
good alternative. The regional block is done at least 1 hr prior to skin incision to allow maximal diffusion of
anesthetic agent and reduces local anesthetic toxicity.

All awake procedures with sedation run the risk of respiratory depression and poor patient cooperation.
Complications such as seizures, increased ICP, hypertension, nausea and vomiting can occur.
10,13,14
Nossek et al
have retrospectively analyses the medical records of 424 patients who undergone awake craniotomy to identify the
reasons behind conversion to general anesthesia and/or inadequate mapping
18
. The main causes of failure were
inadequate communication with the patient (4.2%) and/or intraoperative seizures. Failure of awake craniotomy were

104
Page 3
associated with a compromised resection of the lesion and increased postoperative morbidity. Therefore, most
anesthetic protocols include prophylaxis with antihypertensives, anticonvulsants and antiemetics.

Patient acceptance of awake craniotomy.
Most studies suggest that patients tolerate awake craniotomy well and that they would undergo this procedure again
if needed
19
. Moreover, patients who underwent tumor removal under general anesthesia stated that they would be
willing to undergo awake craniotomy if their surgeon recommended it.
20
In one recent study, 87% of patients felt at
ease during surgery
21
. Twenty four percent experienced some discomfort during surgery. Fifty six percent of patients
reported no postoperative pain. Eighty four percent of patients were happy with timing of their discharge. The
suggested areas for improvement include provision of written information, enhancing post-discharge support and
allowing more time for discussion with the anesthesiologist.

Summary

A number of studies suggest that aggressive resection of certain brain lesions (e.g. tumors, epilepsy foci, etc.) can
prolong survival
22
. When these lesions are located near eloquent areas, awake craniotomy is a preferable way to
confirm sparing of these highly functional regions of the brain. Modern awake craniotomy with functional brain
mapping is safe and well tolerated approach for removal of lesions located in close proximity to the eloquent areas
of the brain. Currently, propofol with opioid (usually remifentanil) or, alternatively dexmedetomidine, is the most
commonly used regimen for the awake craniotomy. Careful patient selection and extensive preoperative
evaluation/preparation are the foundation for s seamless intraoperative functional mapping of the brain.

References and Suggested Reading

1. Bilotta F, Rosa G. Anesthesia for awake neurosurgery. Curr Opin Anaesthesiol 2009; 22:560-5.
2. Bulsara KR, Johnson J, Villavicencio AT. Improvements in brain tumor surgery: the modern history of
awake craniotomies. Neurosurg Focus 2005; 18:1-3.
3. Meyer FB, Bates LM, Goerss SJ, et al. Awake craniotomy for aggressive resection of primary gliomas
located in eloquent brain. Mayo Clin Proc 2001; 76:677-87.
4. Vitaz TW, Marx W, Victor JD, et al. Comparison of conscious sedation and general anesthesia for motor
mapping and resection of tumors located near motor cortex. Neurosurg Focus 2003; 15:1-5.
5. Kim S, McCutcheon I, Suki D, et al. Awake craniotomy for brain tumor near eloquent cortex: correlation of
intraoperative cortical mapping with neurological outcome in 309 consecutive patients !""#! !"! !"# ! !"
6. Manninen PH, Tan TK. Postoperative nausea and vomiting after craniotomy for tumor surgery: A
comparison between awake craniotomy and general anesthesia. J Clin Anesth 2002; 14:279-83
7. Blanshard HJ, Chung F, Manninen PH, et al. Awake craniotomy for removal of intracranial tumor:
Considerations for early discharge. Anesth Analg 92:89-94, 2001.
8. Dinsmore J. Anesthesia for elective neurosurgery. Br J Aneaesth 2007; 99:68-74.
9. Herrick I, Craen R, Gelb A, et al. Propofol sedation during awake craniotomy for seizures. Anesth Analg
1997; 84, 1280-4.
10. Skucas A, Artru A. Anesthetic complications of awake craniotomy for epilepsy surgery. Anesth Analg
2006; 102:882-7.
11. Berkestadt H, Perel A, Hadami M, et al. Monitored anesthesia care using remifentanil and propofol for
awake craniotomy. J Neurosurg Anesth 2001; 13:246-9.
12. Sarang A, Dinsmore J: Anaesthesia for awake craniotomy evolution of a technique that facilitates awake
neurological testing. Br J Anaesth 2003; 90:161-5.
13. Keifer J, Dentchev D, Little K et al. Retrospective analysis of a remifentanil/propofol general anesthetic for
craniotomy before awake functional brain mapping. Anesth Analg 2005; 101:502-8.
14. Bekker A, Kaufman B, Samir S, et al. The use of dexmedetomidine foe awake craniotomy. Anesth Analg
2001; 92:1251-3.
15. Ard J, Bekker A, Doyle W. Dexmedetomidine in awake craniotomy: a technical note. Surg Neurol 2005;
63:114-7..
16. Mack PF, Perrine K, Kobylarz E, et al. Dexmedetomidine and neurocognitive testing in awake craniotomy.
J Neurosurg Anesth 2004; 16(1):20-5.
17. Pinosky M, Fishman R, Reeves S, et al. The effect of bupivacaine skull block on the hemodynamic
response to craniotomy. Anesth Analg 1996; 83:1256-61.

104
Page 4
18. Nossek E, Matot I, Shahar T, at al. Failed awake craniotomy: a retrospective analysis in 424 patients
undergoing craniotomy for brain tumor. J Neurosurg 2013; 118:243-9
19. Khu KJ, Doglietto F, Radavanovic I, et al. Patients perceptions of awake and outpatient craniotomy for
brain tumor: a qualitative study. J Neurosurg 2010;112:1056-60
20. Wrede K, Stieglitz L, Fiferna A, et al. Patient acceptance of awake craniotomy. Clin Neuorol Neurosurg
2011; 113:880-4
21. Wahab S, Grundy P, Weidman C. Patient experience and satisfaction with awake craniotomy for brain
tumor. Br J Neurosurg 2011; 24:606-13
22. Berger M, Deligans A, Dobbins, et al. The effect of extent of resection on recurrence in patients with low
grade cerebral hemisphere gliomas. Cancer 1994; 74:1784-91

Disclosure

120
Page 1
Supratentorial Tumors: Evolving Management and Techniques
Cerebrovascular Physiology and Pharmacology Craniotomy Under General Anesthesia
Audre A. Bendo, M.D. Brooklyn, New York
Introduction
Anesthetic management of supratentorial tumors is evolving as we develop a greater understanding of
neurophysiology and new techniques to guide tumor resection. Traditionally, neuroanesthetic care focused on
intracranial hypertension and therapeutic modalities to reduce intracranial volume. Through more sophisticated
preoperative work-up and diagnosis of the disease, tumor location and size, we have learned to individualize therapy
and anesthetic management of these patients.
This lecture will discuss cerebrovascular physiology and pharmacology, traditional craniotomy under general
anesthesia and neuronavigation/computer-assisted surgery. A rational approach to anesthetic management and
control of intracranial hypertension will be described, and the impact that new techniques have on patient care and
outcome will be reviewed.
Pathophysiology
Supratentorial tumors (meningiomas, gliomas and metastatic lesions) change intracranial dynamics predictably.
Initially, when the lesion is small and slowly expanding, volume-spatial compensation occurs by compression of the
CSF compartment and nearby cerebral veins, which prevents increases in intracranial pressure (ICP). As the lesion
grows, compensatory mechanisms become exhausted, and any further increase in tumor mass will cause
progressively greater increases in ICP. The intracranial compartment can compensate, up to a point, and patients
may exhibit minimal neurologic dysfunction despite the presence of a large mass, elevated ICP, and shifts in the
position of brain structures. Significant changes in ICP can occur if the tumor enlarges and develops a central area
of hemorrhagic necrotic tissue and/or a wide border of brain edema (non-autoregulating). With such compromised
intracranial compliance, small increases in arterial pressure can produce large increases in cerebral blood flow
(CBF), which can markedly increase intracranial volume and ICP with its attendant complications.
Significant increases in ICP result in two major deleterious effects on the brain cerebral ischemia and herniation.
Cerebral perfusion pressure (CPP) is determined by mean arterial pressure (MAP) minus ICP. If ICP increases to a
greater extent than MAP, CPP is reduced. If ICP rises sufficiently, the brain becomes ischemic. The second
important effect of increased ICP is its ability to induce brain herniation. The herniation could be across the
meninges, down the spinal canal, or through a craniotomy. Herniation can rapidly lead to neurologic deterioration
and death. Those elements that can increase cerebral blood volume, such as hypertension, hypercarbia and hypoxia
are treatable and should be avoided perioperatively.
The goal of neuroanesthetic care for patients with intracranial hypertension is to maximize therapeutic modalities
that reduce intracranial volume.
1,2
Various maneuvers and pharmacologic agents can be used to reduce brain bulk
(Table 1). The application of these methods selectively, or together when necessary, is often accompanied by
marked clinical improvement.

120
Page 2
Table 1. Methods to Control Intracranial Hypertension

Corticosteroids: Dexamethasone
3
: effective for localized cerebral edema surrounding tumors;
requires 12-36 hours.
Diuretics: Osmotic: Mannitol (0.25-1 g/kg iv); hypertonic saline 3%
4,5,6

Furosemide: (0.5-1 mg/kg iv alone or 0.15-0.3 mg/kg iv) in combination with mannitol.
Adequate ventilation: Pa0
2
> 100 mm Hg, PaC0
2
33-35 mm Hg; hyperventilation on demand
7
.
Maintain hemodynamics (MAP, CVP, PCWP, HR)
8,9
: Target normotension and maintain cerebral
perfusion pressure (CPP = MAP ICP) to avoid cerebral ischemia.
Fluid therapy: Target normovolemia before anesthetic induction to prevent hypotension. Use glucose
free isoosmolar crystalloid solutions to prevent increases in brain water content (from
hypoosmolality) and ischemic damage (from hyperglycemia).

Position to improve cerebral venous return: neutral, head-up position
10
.
Drug-induced cerebral vasoconstriction: e.g., thiopental, propofol.
Temperature control: Avoid hyperthermia perioperatively.
Cerebral spinal fluid damage to acutely reduce brain tension.

Preoperative Evaluation
The initial approach to the neurosurgical patient is similar to that of all other patients. However, there is additional
information that must be obtained prior to craniotomy. This includes:
1. a complete baseline neurologic evaluation with special attention paid to the patients level of
consciousness, magnitude of intracranial hypertension, extent of neurologic deficits, and seizure history;
2. review of all neurodiagnostic studies with the neurosurgeon;
3. discussion preoperatively, with the neurosurgeon, of the planned operative intervention [patient position,
surgical approach (tumor size, proximal structures, vascular involvement, radical excision), tumor type
(working diagnosis)].

Anesthetic Management: Special Considerations
Whether the patient is anesthetized, awake or sedated, anesthesia for craniotomy must be conducted with
emphasis on:
- hemodynamic stability and maintenance of CPP;
- avoidance of agents and techniques that increase ICP;
- producing a slack brain that facilities surgical dissection; and
- planning for smooth emergence and rapid awakening for early neurologic assessment and follow-up.

I. Craniotomy Under General Anesthesia
Induction. Before laryngoscopy and intubation of the trachea, the patient is smoothly and deeply anesthetized with
agents that reduce ICP. In the presence of elevated ICP, propofol is commonly used to induce anesthesia; however,
alternative agents such as thiopental or midazolam may be administered depending on the patients medical
condition.

A typical induction sequence might include the following:
Preoxygenation, then the intravenous administration of propofol (1.25 2.5 mg/kg) is followed by an opioid
(fentanyl 3-5 mcg/kg) and muscle relaxant. If no airway difficulties are anticipated, a nondepolarizing muscle
relaxant is administered while controlled hyperventilation with 100% oxygen is instituted. In patients who have
been vomiting because of elevated ICP, cricoid pressure is applied during mask ventilation. To deepen the
anesthetic, fentanyl is administered in 50-mcg increments to a total dose of 10 mcg/kg, depending on the blood
pressure response. Lidocaine (1.5 mg/kg) is also administered intravenously 90 seconds before intubation to
suppress laryngeal reflexes. When the peripheral muscle twitch response disappears, an additional 2-3 mg/kg bolus
of thiopental is administered, and endotracheal intubation is performed as rapidly and smoothly as possible. An
esmolol infusion or bolus may also be used to reduce the heart rate and blood pressure response to laryngoscopy and
intubation. After induction of anesthesia, ventilation of the lung is controlled mechanically. Arterial blood gases
are measured after intubation to establish the arterial end-tidal C0
2
gradient.

120
Page 3
Routine institution of hyperventilation is no longer recommended in neurosurgical patients because of the risk of
cerebral ischemia in some conditions. Although not evidence-based in brain tumor patients, current
recommendations are to adjust PaC0
2
between 33-35 mm Hg when using volatile agents or when significant
intracranial hypertension exists. In other words, surgical conditions should define the PaC0
2
for each patient.

Maintenance. Since anesthetics affect the intracranial environment, there continues to be controversy over the best
choice of anesthetics for neurosurgical patients, i.e., intravenous or volatile-based anesthetics. In practice, the
anesthetics most frequently administered to neurosurgical patients are either propofol-fentanyl or isoflurane-
fentanyl.
9
There have been no large clinical outcome studies conducted comparing anesthetic techniques in patients
undergoing craniotomy. Our choice of anesthetics has been based primarily on information derived from
experimental and clinical studies of cerebral hemodynamics (CBF, CMR0
2
) and ICP.

Volatile anesthetics (isoflurane, sevoflurane and desflurane) have been shown to increase CBF (direct
vasodilation), reduce CMR0
2
, increase ICP and impair autoregulation.
1,11,12,13,14,15,16,17,18,19
Nitrous oxide (N
2
0)
alone is known cerebrostimulant (! CBF, ! CMR0
2
and ! ICP).
1
For the normal brain, these effects can be
controlled by hypocapnia or intravenous anesthetics. Volatile anesthetics add to the increases in CBF obtained with
N
2
0
12
Recommendations: Volatile anesthetics should be used only for cases without elevated ICP or brain bulk
problems; use with early moderate hyperventilation; use less than 1 MAC and avoid combination with N
2
0.

Intravenous anesthetics (thiopental, propofol and midazolam) show a dose-related decrease in CBF, CMR0
2
and
ICP and intact autoregulation.
1,17,20,21
Opioids (fentanyl and remifentanil) cause either a minor reduction or no
effect on CBF and CMR0
2
. Remifentanil, a rapidly metabolized opioid, allows a more rapid postoperative
neurologic assessment of the patient.
22,23
Dexmedetomidine, a highly specific alpha-2 adrenoreceptor agonist, has
been recommended as a maintenance adjuvant anesthetic during craniotomy.
24,25,26,27
It has the advantage of
providing analgesia without respiratory depression.
Recommendations: Intravenous anesthetics should be used for patients at risk for elevated ICP/brain bulk
problems. Consider using a continuous infusion of propofol (50-150 mcg/kg/min) or thiopental (2-3 mg/kg/h),
fentanyl (0.016-0.03 mcg/kg/min) or remifentanil (0.125-0.2 mcg/kg/min) with midazolam and a nondepolarizing
muscle relaxant.

Emergence. In the usual craniotomy for excision of a supratentorial tumor, the conduct of the anesthetic is aimed at
awakening and extubating the patient at the end of the procedure to permit early assessment of surgical results and
postoperative neurologic follow-up.
13
The risks and benefits of an early versus delayed recovery in neurosurgical
patients have been reviewed.
28
Factors other than anesthetics that may delay awakening include: large intracranial
tumor,
29
preoperative decreased level of consciousness, surgical complications (seizures, cerebral edema, hematoma,
pneumocephalus, vessel occlusion/ischemia), metabolic or electrolyte disturbances, and residual hypothermia.

Emergence from anesthesia should be as smooth as possible, avoiding straining or bucking on the endotracheal tube,
arterial hypertension and elevated ICP.
30,31
To avoid bucking during emergence, muscle relaxants are not reversed
until the head dressing is applied. Intravenous lidocaine (1.5 mg/kg) can be administered 90 seconds before
suctioning and extubation to minimize cough, straining, and hypertension. Antihypertensive agents such as labetalol
and esmolol are also administered during emergence to control systemic hypertension. It has been shown that many
patients who develop postoperative hematomas have had episodes of hypertension during emergence or early
recovery.
30

II. Neuronavigation / Computer Assisted Surgery
Neuronavigation allows precise anatomic mapping and orientation of tumors before the operation and throughout
the procedure.
32,33,34,35
Image-guided surgery can be performed with an MRI in the operating room or in a twin
operating theater close by the conventional operating room. Studies comparing the impact of neuronavigation on
patients undergoing glioblastoma surgery have found that absolute and relative residual tumor volumes were
significantly lower with neuronavigation.
36.37
Furthermore, the use of the intraoperative MRI to guide radical tumor
resection was associated with a highly significant prolongation in survival.
37
In another study, image-guided
resection of meningiomas was associated with less complications and shorter hospital stays when compared to
conventional surgery.
38
Anesthetic management concerns regarding intraoperative MRI have been discussed in
recent articles.
39,40,41
Along with concerns of administering anesthesia in a remote location and using MRI

120
Page 4
compatible anesthesia equipment, neuroanesthetic principles must also be applied when caring for these
patients.
32,42,43

Summary
There are several challenges to anesthetizing patients with intracranial mass lesions. Patients with large tumors and
mass effect will continue to require intensive monitoring and aggressive methods to lower ICP. Other patients with
small tumors may require standard monitoring and minimal techniques to lower ICP. As we develop facility with
intraoperative MRI and other technological advances, we must continue to balance the needs of the patient (e.g.,
maintaining cerebral homeostasis and cardiorespiratory status) with those of the surgeon (e.g., unusual position,
brain exposure without retraction, intraoperative neurologic assessment, and early emergence for neurologic
examination). Appropriate selection of anesthetics and monitoring with meticulous general management of the
patients respiration, circulation, fluid replacement and positioning are necessary to avoid morbidity and improve
outcome.


1. Bendo AA, Kass IS, Hartung J, Cottrell JE. Anesthesia for Neurosurgery. In Barash PG, et al (eds).
Clinical Anesthesia, 5th ed., Lippincott Williams & Wilkins, Philadelphia, 2006, pp 746-789.
2. Bruder N, Ravussin PA. Supratentorial Masses: Anesthetic Considerations. In Cottrell JE and Young
WL (eds): Cottrell and Youngs NA, 5
th
al., Phil. 2010, Mosby Elsevier, pp. 184-202.
3. Lukins, MB and Manninen PH. Hyperglycemia in patients administered dexamethasone for
craniotomy. Anesth Analg (2005) 100: 1129-33.
4. Sorani MD, Manley GT. Dose-response relationship of mannitol and intracranial pressure: A
metaanalysis. J Neurosurg (2008)108: 8087.
5. Wu CT, Chen LC, Kuo CP, Ju DT et al. A comparison of 3% hypertonic saline and mannitol for brain
relaxation during elective superatentorial brain tumor surgery. Anesth Analg (2010) 110 (3): 903-7.
6. Lazaridis, C, Neyens R, Bodle J, DeSantis S. High-osmolarity saline in neurocritical care: Systematic
review and meta-analysis. Crit Care Med (2013) 41(5): 1353-60.
7. Gelb AW, Craen RA, Rao GS, et al. Does hyperventilation improve operating condition during
supratentorial craniotomy? A multicenter randomized crossover trial. Anesth Analg (2008) 106(2):
585-94.
8. Moore LE, Sharifpour M. Shanks A, et al. CPP below 60 mm Hg is common in the Intraoperative
Setting. J. Neurosurgl Anesthesiol (2012) 24: 58-62.
9. Rasmussen M, Bundgaard H, Cold GE. Craniotomy for supra-tentorial brain tumors: risk factors for
brain swelling after opening the dura mater. J Neurosurg (2004) 101:6216.
10. Tankisi A, Cold GE. Optimal reverse trendelenburg position in patients undergoing craniotomy for
cerebral tumors. J Neurosurg (2007) 106: 239:44.
11. Kaye A, Kucera IJ, Heavner J, et al. The comparative effects of desflurane and isoflurane on lumbar
cerebrospinal fluid pressure in patients undergoing craniotomy for supratentorial tumors. Anesth Analg
(2004) 98:1127-32.
12. Kaisti KK, Lngsj JW, Aalto S, et al. Effects of sevoflurane, propofol and adjunct nitrous oxide in
regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology
(2003) 99:603-13.
13. Magni G, Baisi F, La Rosa I, et al. No difference in emergence time and early cognitive function
between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for
supratentorial intracranial surgery. J Neurosurg Anesthesiol (2005) 17:1348.
14. Sneyd JR, Andrews CJH, Tsubokawa T. Comparison of propofol/remifentanil and sevoflurane /
remifentanil for maintenance of anaesthesia for elective intracranial surgery. Br. J. Anaesth. (2005)
94(6): 778-783.
15. Myles PS, Leslie K, Chan MT, et al. Avoidance of nitrous oxide for patients undergoing major
surgery: a randomized controlled trial. Anesthesiology. (2007) 107(2):221-31.
16. Turan A, Mascha EJ, You J, et al. The association between Nitrous Oxide and postoperative mortality
and morbidity after noncardiac surgery. Anesth Analg (2013) 116: 1026-33. Editorials: Hogan K,
Myles PS. (2013) 116: 955-7; Vetter TR, McGwin G. (2013) 116: 959-61.
17. Petersen KD, Landsfeldt U, Emil Cold, G, et al. Intracranial pressure and cerebral hemodynamic in
patients with cerebral tumors: A randomized prospective study of patients subjected to craniotomy in

120
Page 5
propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia. Anesthesiology (2003)
98(2): 329-36.
18. Holstrm A, keson J. Desflurane increases intracranial pressure more and sevoflurane less than
isoflurane in pigs subjected to intracranial hypertension. J Neurosurg Anesthesiol 16(2):136-43, 2004.
19. Strebel S, Lam AM, Matta B, et al. Dynamic and static cerebral autoregulation during isoflurane,
desflurane and propofol anesthesia. Anesthesiology (1995) 83:66-76.
20. Larsen B, Seitz A, Larsen R. Recovery of cognitive function after remifentanil-propofol anesthesia: A
comparison with desflurane and sevoflurane anesthesia. Anesth Analg (2000) 90: 168-74.
21. Cenic A, Craen RA, Lee T-Y, et al. Cerebral blood volume and blood flow responses t hyperventilation
in brain tumors during isoflurane or propofol anesthesia. Anesth Analg (2002) 94:661-6.
22. Guy J, Hindman BJ, Baker KZ, et al. Comparison of remifentanil and fentanyl in patients undergoing
craniotomy for supratentorial space-occupying lesions. Anesth Analg (1997) 86(3):514-24.
23. Balakrishnan G, Raudzens P, Samra SK, et al. A comparison of remifentanil and fentanyl patients
undergoing surgery for intracranial mass lesions. Anesth Analg (2000) 91:163-9.
24. Drummond JC, Dao AV, Roth DM, et al. Effect of dexmedetomidine on cerebral blood flow velocity,
cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. (2008)
108(2):225-32.
25. Gnes Y, Gndz M, zcengiz D, et al. Dexmedetomidine-Remifentanil or Propofol-Remifentanil
anesthesia in patients undergoing intracranial surgery. Anesthesiology. (2008) 108(2):225-32.
26. Tanskanen PE, Kytt JV, Randell TT, Aantaa RE: Dexmedetomidine as an anaesthetic adjuvant in
patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled
study. Br J Anaesth (2006) 97:658-65.
27. Ilhan O, Koruk S, Serin G, et al. Dexmedetomidine in the Supratentorial Craniotomy. Eurasian J
Medicine. (2010) 42: 61-65.
28. Bruder N, Ravussin P. Recovery from anesthesia and postoperative extubation of neurosurgical
patients: A review. J Neurosurg Anesth (1999) 11(4):282-93.
29. Schubert A, Mascha EJ, Bloomfield EL, et al. Effect of cranial surgery and brain tumor size on
emergence from anesthesia. Anesthesiology. (1996) 85(3):513-21.
30. Basali A, Mascha EJ, Kalfas I, et al: Relation between perioperative hypertension and intracranial
hemorrhage after craniotomy. Anesthesiology (2000) 93:48-54.
31. Bhagat H, Dash HH, Bithal PK, Chouhan RS, Pandia MP. Planning for early emergence in
neurosurgical patients: a randomized prospective trial of low-dose anesthetics. Anesth Analg. (2008)
107(4):1348-55.
32. Leuthardt EC, Lim CC, Shah MN, Evans JA, Rich KM, Dacey RG, et al. Use of movable high-field
strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas:
Preliminary experience. Neurosurgery. (2011)69:194206.
33. Keles GE. Intracranial neuronavigation with intraoperative magnetic resonance imaging. Curr Opin
Neurol (2004) 17:497-500.
34. Tuominen J, Yrjana SK, Katisko JP, et al: Intraoperative imaging in a comprehensive neuronavigation
environment for minimally invasive brain tumor. Acta Neurochir Suppl (2003) 85:S115-20.
35. Bernstein M, Al-Anazi AR, Kucharczyk W, et al: Brain tumor surgery with the Toronto-open magnetic
resonance imaging system: Preliminary results for 36 patients and analysis of advantages,
disadvantages, and future prospects. Neurosurgery (2000) 46:900-9.
36. Wirtz CR, Knauth M, Staubert A, et al: Clinical evaluation and follow-up results for intraoperative
magnetic resonance imaging in neurosurgery. Neurosurgery (2000) 46:1112-20.
37. Schneider JP, Trantakis C, Rubach M, Schulz T, Dietrich J, et al. Intraoperative MRI to guide the
resection of primary supratentorial glioblastoma multiformea quantitative radiological analysis.
Neuroradiology (2005) 47:489500.
38. Paleologos TS, Wadley JP, Kitchen ND, et al: Clinical utility and cost-effectiveness of interactive
image-guided craniotomy: Clinical comparison between conventional and image-guided meningioma
surgery. Neurosurgery (2000) 47:40-7.
39. Manninen PH, Kucharczyk W: A new frontier: Magnetic resonance imaging-operating room. J
Neurosurg Anesth (2000) 12(2):141-8.
40. Archer DP, McTaggart Cowan RA, Falkenstein RJ, Sutherland GR: Intraoperative mobile magnetic
resonance imaging for craniotomy lengthens the procedures but does not increase morbidity. Can J
Anesth (2002) 49:420-6.
120
Page 6
41. Schmitz B, Nimsky C, Wendel G, et al: Anesthesia during high-field intraoperative magnetic
resonance imaging experience with 80 consecutive cases. J Neurosurg Anesth (2003) 15:255-62.
42. Vitaz TW, Marx W, Victor JD, et al. Comparison of conscious sedation and general anesthesia for
motor mapping and resection of tumors located near motor cortex. Neurosurg Focus (2003) 15:1-5.
43. Peruzzi P, Bergese SD, Viloria A, et al. A retrospective cohort-matched comparison of conscious
sedation versus general anesthesia for supratentorial glioma resection. J Neurosurg (2011) 114: 633-9.
Disclosure
120
Page 1
""#$% &
Supratentorial Tumors: Postoperative management after brain tumor resection
Federico Bilotta, M.D., Ph.D. Rome, Italy
Tight clinical monitoring with aggressive prevention and treatment of risk factors for secondary brain damage is
strictly recommended for post operative management of brain tumor patients [1]. Post operative intracranial
bleeding, even after elective uncomplicated procedures, when undiagnosed can lead to significant morbidity
with permanent neurological or cognitive permanent deficits and death [1, 2]. Several physiological variables
affect brain perfusion and influence early and long term clinical outcome [1].
In this presentation, clinical variables affecting the early postoperative phase after brain surgery that require our
close surveillance will be reviewed. These include: neurological and cognitive status, hemodynamics,
ventilation, fluids and electrolytes, metabolism, pain, temperature and shivering.
Neurological and cognitive status
Clinical monitoring of neurological and cognitive status should be systematically evaluated and recorded in the
postoperative period. Extubation should be delayed when new post operative neurological or cognitive deficits
develop that affect respiratory drive or airway protection [3] . New neurological or cognitive deficit developing
in the post operative period usually represent presenting signs of intracranial surgical complication [2, 4-8].
Clinical monitoring should be performed on a pre defined time schedule and according to a systematic approach.
Subjective evaluation, when not supported by objective criteria (i.e. delay/inability to obey commands, lack of
ability to move a limb, differences in pupils diameter, etc), can delay diagnosis and necessary treatment.
Hemodynamics
Hemodynamic variables should be continuously monitored and maintained within normal values. The
postoperative course of patients undergoning brain surgery is often complicated by arterial hypertension due to
sympathetic overdrive [5]. When cerebral auto-regulation is disturbed, arterial hypertension can result in direct
increase of cerebral blood flow (CBF) that can lead to high intracranial pressure, cerebral edema and intracranial
hemorrhage with an increase in the risk of postoperative hemorrhage [1,5,6]. In patients who have undergone
elective craniotomy, thigh monitoring of arterial pressure and thoughtful titration of anti hypertensive drugs can
effectively blunt the postoperative sympathetic overdrive [5,6]. Infusion of nitrates-based drugs, including
nitroglycerin and nitroprusside, is strongly discouraged because these drugs have a direct cerebral vasodilatory
action and can induce intracranial hypertension [6].
Ventilation
Should the patients need ventilator support or breath spontaneously, normooxic (with PaO2 100-200mmHg) and
normocapnic (with PaCO2 values >38 mmHg) blood gas analysis (BGA) should be ensured. Reduced
ventilation can result as residual effect of anesthetics and induce systemic acidosis with cerebral hyperperfusion
as hyperventilation is associated with a 3% CBF decrease for each PaCO2mmHg reduction [7]. Tight
surveillance of ventilatory function and BGA (every 6-12 hours in patients with normal BGA values) is
necessary to prevent secondary brain damage.
Metabolism
Adequate nutrition and blood glucose concentration (BGC) management is a high priority after intracranial
surgery. The BGC should kept within strict limits (not higher than 180 mg/dl not below 80 mg/dl). Tight BGC
monitoring with repeated measures (every 4-8 hours in patients with normal BGC values) using whole blood
BGC should be scheduled [10-12]. In patients with acute brain damage there might be a reduction of the
peripheral BGC/cerebrospinal fluid glucose concentration ratio, owing to blood brain barrier dysfunction, and
BGC should not be actively targeted to values <110 mg/dl.
Fluids and electrolytes
Fluid therapy should be based on iso-osmolar solutions (0.9% saline) and adequate nutrition with enteral or
parenteral solutions should be instituted using high protein. The use of glucose-enriched solution (5-10%
glucose solutions) should be avoided, because these solutions when the glucose is metabolized or transferred

120
Page 2
""#$% '
into the cells induce a reduction in plasma osmolarity that can contribute to brain edema formation[13-14].
After brain surgery, glucose-enriched solutions are indicated only when hypernatermia develops, for example, in
patients with diabetes insipidus. Electrolyte abnormalities can also be induced by diuretic therapies, and
although not frequent, are potentially related to secondary brain damage and poor outcome.
Pain
After brain surgery, pain should be agrresively prevented and treated. Prevention should start right from the
intraoperative period with the use of local anesthestics and selective block of the scalp sensory branches. The
use of NSAIDs after brain surgery is controversial because of the potential risks related to reduce platelet
aggregation and the potential to facilitate or worsen intracranial hemorrhage [6,15-17-18-19]. Opioids are
effective, but should be used cautiously because of the possible effects on ventilator drive, consciousness and
because can facilitate the occurrence of PONV.
Temperature and shivering
Unless active intraoperative warming is ensured, postoperative shivering, with systemic increase in oxygen
extraction and increase in intracranial pressure, can complicate the postoperative course after brain surgery
[6,9]. On the other hand, the presence of hyperthermia and the associated increase in cerebral metabolic rate of
oxygen is potentially harmful and associated with secondary brain damage. Continuous temperature monitoring
with special attention to intra and postoperative normothermia is recommended.
Summary
Several clinical and physiological variables must be tightly monitored and aggressively treated to minimize
secondary brain damage after craniotomy for brain tumor resection. This requires qualified surveillance of these
variables and communication among health care professionals to avoid iatrogenic complications and morbidity
and improve outcome [20].
1. Basali A, Mascha EJ, Kalfas I, Schubert A Relation between perioperative hypertension and intracranial
hemorrhage after craniotomy. Anesthesiology 2000;93:48-54
2. Aldrete JA, Kroulik D A postanesthetic recovery score. Anesth Analg 1970;94:924-934
3. Namen AM, Ely EW, Tatter SB, Case LD, Lucia MA, Smith A, et al. Predictors of successful extubation in
neurosurgical patients. Am J Respir Crit Care Med 2001;51:658-664
4. Bruder N, Pellissier D, Grillot P, Gouin F (2002) Cerebral hyperemia during recovery from general anesthesia
in neurosurgical patients. Anesth Analg 2002;94:650-654
5. Bilotta F, Lam AM, Doronzio A, Cuzzone V, Delfini R, et al. Esmolol blunts postoperative hemodynamic
changes after propofol-remifentanil total intravenous fast-track neuroanesthesia for intracranial surgery. J Clin
Anesth 2008;20:426-430
6. Bruder N Awakening management after neurosurgery for intracranial tumours. Curr Opin Anaesthesiol
2002;54:477-482
7. Bilotta F, Doronzio A, Cuzzone V, Caramia R, Rosa G, et al. Early postoperative cognitive recovery and gas
exchange patterns after balanced anesthesia with sevoflurane or desflurane in overweight and obese patients
undergoing craniotomy: a prospective randomized trial. J Neurosurg Anesthesiol 2009;21:207-213
8. Bilotta F, Caramia R, Paoloni FP, Favaro R, Araimo F, et al Early postoperative cognitive recovery after
remifentanil-propofol or sufentanil propofol anaesthesia for supratentorial craniotomy: a randomized trial. Eur J
Anesthesiol 2007;24:122-127
9. Bilotta F, Pietropaoli P, La Rosa I, Spinelli F, Rosa G Effects of shivering prevention on haemodynamic and
metabolic demands in hypothermic postoperative neurosurgical patients. Anesthesia 2001;56:514-519

120
Page 3
""#$% (
10. Bilotta F, Giovannini F, Caramia R, Rosa G, Glycemia management in neurocritical care patients. J
Neurosurg Anesthesiol 2000;21:2-9
11. Bilotta F, Rosa G Glucose management in the neurosurgical patient: are we yet any closer? Curr Opin
Anaesthesiol 2010;23:539-543
12. Bilotta F, Rosa Glycemia management in critical care patients. World J Diabetes, 2012in press.
13. Bilotta F, Giovannini F, Aghilone F, Stazi E, Titi L, Orlando Zeppa I, Rosa G, et al. Potasssium sparing
diuretics as adjunct to mannitol therapy in neurocritical care patients with cerebral edema: effects on potassium
homeostasis and cardiac arrhythmias. Neurocritical care 2012;16:280-285
14. Tommasino C, Picozzi U, Bilotta F. Fluids and electrolyte management (2013) In : Newfield P and Cottrell
J. Handbook of Neuroanesthesia, Leaderbook, USA
15. Manninen PH, Tan TK Postoperative nausea and vomiting after craniotomy for tumor surgery: a comparison
between awake craniotomy and general anesthesia. J Clin Anesth 2002;14:279-283
16. Mordhorst C, Latz B, Kerz T, Wisser G, Schmidt A, et al. Prospective Assessment of postoperative pain
after craniotomy. J Neurosurg Anesthesiol 2010;22:202-206
17. Hansen MS, Brennum J, Moltke FB, Dahl JB Pain treatment after craniotomy: where is the (procedure
specific) evidence? A qualitative systematic review. Eur J Anaesthesiol 2011;28:821-829
18. Lai LT., Ortiz-Cardona JR, Bendo AA . Perioperative Pain Management in the Neurosurgical Patient.
Anesthesiology Clinics 2012 30: 347-67
19. Flexman AM, Ng JL, Gelb AW Acute and chronic pain following craniotomy. Curr Opin Anaesthesiol
2010;23:551-557
20. Theofilou P Communication among healthcare professionals: a central factor in patients outcome. J Nurs
Care 2011;1:1
Disclosure
225
Page 1
Neuroanesthesia: Physiology and Pharmacology That Really Matters
John C. Drummond, M.D. FRCPC San Diego, California
Perspective. I have committed considerable professional time to anesthesia for neurologic surgery. That
commitment has caused me to hear a great deal related to neuroanesthesia. I have been asked by faculty colleagues
in anesthesia, What do you suppose might have gone wrong during that case yesterday? I have listened to ABA
oral exam candidates misapplying or frankly misunderstanding fundamental principles. I have been involved in
third party scrutiny of procedures that were perceived to have gone astray. I acknowledge that it is those
interactions that inform the selection of topics that follows (rather than any evidence based material from the peer
reviewed literature). Not all of the topics will be addressed during the course of the presentation.
The Lower Limit of CBF Autoregulation. Diagrams in standard texts have frequently depicted the lower limit of
human cerebral blood flow autoregulation (LLA) as being a mean arterial pressure (MAP) of 50 mmHg. While this
number may in fact be a reasonable representation of the LLA in several animal species, it is unlikely to be an
accurate value in adult humans. The first rendering of a CBF autoregulation curve was probably that drawn by
Lassen.
1
His diagram depicted an LLA that might be easily interpreted to be 50 mmHg. On close inspection,
however, the inflection point is probably at 60 mmHg. However, the inflection point on that hand-drawn curve
(where ever it is) is anchored by only two CBF values, both of which were obtained in pregnant females at term in
whom blood pressure was lowered using cerebral vasodilating drugs and in whom base line pressures were probably
well below the population average for normal adult humans. Furthermore, numerous subsequent investigations
2
(see
Drummond
3
for additional references) suggest that the LLA in non-anesthetized adult humans is nothing less than
70 mmHg. However, it should be acknowledged that the rules might be different during general anesthesia for at
least two reasons. The first is the frequent inclusion of vasodilating substances in anesthetic recipes. Vasodilators
might serve to shift the autoregulation curve in a leftward direction. The second resides in the observation that
sympathectomy in both experimental animals and humans during hypotension increases CBF.
4
This suggests that
the normal autonomic response to hypotension includes some vasoconstriction of large extracranial and perhaps
intracranial vessels thereby producing effective right shifting of the autoregulation curve. If a general anesthetic
were to effectively prevent that autonomic response, it is possible that some resultant left shifting of the curve might
occur. The reality, however, is that there has been exceptionally little systematic study of normal (non injured) adult
human cerebral autoregulation during anesthesia. The only context in which extensive study has occurred is during
cardiopulmonary bypass (typically involving, hypothermia, non-pulsatile flow, relative anemia and high-dose
narcotic anesthesia). In those circumstances, which are very poorly representative of the physiology that prevails
during the majority of general anesthetic states, the LLA is in fact about 65 mmHg (with a very large confidence
interval indicating considerable inter-individual heterogeneity.
5
However, it seems inappropriate to extrapolate that
average value (obtained in the context of non-pulsatile flow, low hematocrit and well maintained cardiac output) to
all other anesthetic circumstances. In fact, it further seems likely that what pertains to any one anesthetic
circumstance, e.g., spontaneous ventilation during anesthesia with a volatile agent, might not be relevant in another,
e.g. a TIVA anesthetic with remifentanil and propofol. We know very little about the LLA during general
anesthesia in humans and conservative assumptions should be made in the absence of more detailed knowledge.
The Physiologic Central Nervous System Blood Flow Reserve. Many clinicians may well respond to the
preceding discussion of the LLA with their own observation that numerous patients in the span of their experience
have tolerated MAPs in the 40s, 50s and 60s, i.e., well below the proposed LLA of 70 mmHg. That is inevitably
true. Patients tolerate blood pressures below the LLA because there is a substantial CNS blood flow reserve. CNS
flow can fall by approximately 40% of baseline values before symptoms of ischemia begin to occur.
6-8
That reserve
is, in essence, a physiologic buffer that protects patients in the event of hypotension. However, it is important that

225
Page 2
clinicians recognize the situations in which that buffer may not be present, often because it has been encroached
upon by some preexisting pathologic process. The most common situations in which the buffer is likely to have been
attenuated occur in circumstances in which CNS tissue is under increased pressure. This may occur in the
circumstances of increased ICP, increased ocular pressure or when CNS tissue is under extrinsic pressure, e.g.,
compressed under retractors or by a bulging disc. The significance of these situations is that the principal
determinant of flow to the tissue is transmural pressure rather than blood pressure. Transmural pressure (which
is commonly but probably erroneously referred to as perfusion pressure equals MAP minus local tissue pressure.
Among the most commonly overlooked situations in which tissue pressure is increased (and the effective perfusing
pressure is therefore less for a given value of MAP) is in the circumstances of spinal stenosis, in particular cervical
spinal stenosis. In that group of patients, the normally wide latitudes for intraoperative blood pressure that
anesthesiologists commonly allow should be tightly restricted. It is our approach at UCSD to maintain MAPs during
anesthesia in these patients (at least until the decompression is complete) very close to normal waking levels. The
agent we use most commonly to achieve this is phenylephrine. This introduces another common misconception,
which is addressed in the second paragraph below.

The Effect of Hydrostatic Gradients on CPP. In patients who undergo anesthesia in horizontal positions (supine,
prone, lateral), it is standard to measure blood pressure with cuffs or transducers at the level of the heart. When
positions are used that result in a vertical height difference between the height of the heart and the head, a pressure
differential between the two that is equivalent to the weight of a column of blood of that height can be expected to
occur. That gradient will be equal to approximately 2 mmHg for each one inch of height difference. The standard
teaching in neuroanesthesia has long been that blood pressure should be transduced at (or an arithmetic correction
imposed to correct to) the level of the external auditory meatus (EAM). Clinicians who are unfamiliar with the use
of the sitting position have occasionally failed to make this correction in transducer height, or have raised it only to
the level of the heart with sometimes severe adverse consequences for the perfusion of the brain and/or the cervical
spinal cord. This issue has been popularized recently in the context of injuries occurring in the so called beach-
chair position. A minority have disputed this notion, arguing that siphon-like mechanism maintains CBF in spite of
reductions in CPP calculated in the manner above.
9
Unless and until there is wider proof of that concept,
conventional hydrostatic gradient concepts should apply, and arterial transducers should be raised to the level of the
EAM or arithmetic corrects should be applied to cuff pressures in order to think in terms of BP at the EAM.
10

Alpha 1 Agonists and Cerebral Vasoconstriction. It is often asserted that the various alpha1 agonists are
significant CNS vasoconstrictors. While that may be so in canines, it is not true in humans. See "Miller's
Anesthesia", 6
th
Ed., Ch. 21, p 818 for references. (The references were regrettably omitted in the corresponding
section in the 7
th
edition Ch. 13, p 311.) In human investigations done many years ago, alpha one agonists were
infused directly into the cerebral circulation in concentrations sufficient to produce substantial increases in systemic
arterial pressures; and no changes in CBF were observed. The concern that phenylephrine is a CNS vasoconstrictor
has too often restricted its use in situations where there was a pressing need to augment CCP. Clinicians should get
it out of their heads. Phenylephrine is NOT a significant CNS vasoconstrictor in the doses that we commonly
employ. When blood pressure support is warranted in patients who have sustained SAH or TBI or when CNS
structures are under compression (spinal stenosis, retractor pressure), after assuring appropriate volume status and
depth of anesthesia, phenylephrine is a reasonable choice!

The Effect of Volatile Agents on CBF. Figures that appear widely in standard texts indicate that the common
volatile agents (isoflurane, sevoflurane and desflurane) cause little or no increase in CBF at sub-MAC
concentrations. In the majority of elective neurosurgical patients that is almost certainly true. In fact, in subjects with
generally normal cerebral physiology, CBF actually decreases from the awake state to reach a nadir in the vicinity of
0.75-1.0 MAC. Thereafter, CBF increases in parallel with increasing end-tidal concentrations of volatile agents.
11

This superficially unusual bi-phasic pattern is almost certainly the product of the very substantial suppression of
cerebral metabolic rate that occurs with the initial exposure to volatile agents. The reduction in CBF is probably
largely a coupled reduction in the CBF recurring as a consequence of the reduction of CMR. The important issue
for clinicians is that in patients in whom CMR has already been depressed by either pathologic processes or CMR
suppressing drugs (benzodiazepines, narcotics, propofol) or who have sufficiently disordered physiology that the
coupling mechanism may not be functional, volatile agents may act as potent vasodilators even at the sub-MAC
concentrations that are normally associated with a reduction in CBF. The consequence for the clinician is that in
patients with badly impaired intracranial compliance (or, as some would say, elastance) especially in whom those
in whom CMR is already depressed, volatile agents should be introduced very cautiously. In the ideal, in those

225
Page 3
extreme circumstances, they should probably not be introduced unless ICP is being monitored or until the cranium is
open and the brain can be observed directly.

Obstruction of venous drainage. The venous side of the cerebral circulation is a passive, but relatively large
intracerebral compartment. It is quite commonly the cause of raised intracranial pressure or tightness in the
surgical field and is relatively under-recognized. The cerebral venous drainage is easily obstructed by anything that
puts pressure on the underlying jugular veins including circumferential ties and cervical collars. Extremes of head
position can also obstruct venous drainage. Any rotation of the head that is sufficient to put tension on the sterno-
cleido-mastoid muscles is sufficient to compress the underlying jugular vein. In addition, the jugular veins drain
downstream into the chest. Accordingly, anything that raises intrathoracic pressure can impair cerebral venous
drainage. This includes a medley of common entities including coughing against an endotracheal tube, kinking of
the endo-tracheal tube, bronchospasm, and pneumothorax. Confirmation of the patency of the jugular venous system
and verification of normal airway pressures are accomplished easily and should be the first things that the clinician
does when evaluating increased intracranial pressure or a tight surgical field.

Hyperventilation. It has become a well-established concept that the vasoconstriction associated with
hyperventilation has the potential to cause sufficient cerebral vasoconstriction to result in ischemia when imposed on
the low flow circumstances that can prevail after acute cerebral injuries, in particular head injury
12
and sub-
arachnoid hemorrhage (SAH). Routine hyperventilation in neuroanesthesia and neurosurgical critical care has
ceased. While prophylactic hyperventilation is never appropriate, hyperventilation is by no means totally "verboten".
Hyperventilation remains an adjunct in the management of patients with critically increased ICP at risk of herniation
in whom other measures, short of barbiturate coma, have proven inadequate. Its use should be as brief as allowed for
by patient circumstances.

Tension Pneumocephalus. Tension pneumocephalus is a phenomenon that can occur when gas is trapped within
the intracranial space with no communication to the outside atmosphere. The phenomenon is widely associated with
the sitting position and many clinicians associate its occurrence with the use of N2O. It most certainly is a
phenomenon that can be both caused or exaggerated by N2O and many clinicians will have decided to omit N2O
from the anesthetics used for posterior fossa procedures done in the sitting position as a result. However, the
assumption that one no longer needs to be concerned about tension pneumocephalus if one has made the decision to
omit N2O is an erroneous one. Clinically significant, and even life threatening, tension pneumocephalus can occur
in the absence of the use of N2O. Imagine a situation in which a craniotomy has been performed in a head up
posture with the craniotomy located such that a significant portion of the cranium is above the surgical site. With
optimal venous drainage, mannitol administration, hyperventilation, the use of anesthetic agents that reduce brain
bulk and opening of the arachnoid membrane resulting in drainage of CSF, a substantial potential space can occur
between the surface of brain parenchyma and the highest point of the skull. That space will fill with air. When the
procedure is concluded and the patient is restored to a near supine position, venous blood, arterial blood, CSF and
extra cellular fluid all begin to return. Albeit that the oxygen is absorbed quickly from the air within the cranium, the
remaining nitrogen can represent a substantial and unyielding "mass" that will diffuse away only very slowly (over a
period of days).
13
Frontal craniotomies performed in a brow up position in which the frontal bone is removed and
replaced, are particularly prone to the development of tension pneumocephalus in the immediate postoperative
period. Tension pneumocephalus is an underappreciated and under-recognized cause of postoperative delayed
awakening, delirium and non-awakening. When it is suspected, the diagnosis can be made by a cross table lateral X-
ray or, more commonly, in these days of readily available CT scans, by computed tomography. The treatment entails
a twist drill hole and dural perforation, ideally performed by the surgeon.

The brain parenchyma is insensate but the cranial nerves are not. When Wilder Penfield performed the brain
surface stimulation surveys that lead to the development of the now familiar homunculus diagrams, the craniotomies
were performed under local anesthesia. While the meninges have some innervation and required gentle handling
and some local anesthesia at the skull base, brain stimulation and/or resection of brain parenchyma required no
anesthesia whatsoever. The brain parenchyma is insensate. Accordingly, when a general anesthetic is used for
intracranial neurosurgery, the intracranial portion requires only light anesthesia. An error occasionally made by
clinicians is the failure to anticipate stimulation of the extra-axial but intracranial portion of cranial nerves. The issue
arises most often in the context of procedures formed in the vicinity of the fifth cranial nerve. The fifth cranial nerve
subserves the sensation from the entire face and mouth. Stimulation of the extra axial portion of the fifth cranial
nerve can result in very sudden arousal. In circumstances in which this has occurred in non-paralyzed patients, the

225
Page 4
arousal has resulted in sudden straining against the endotracheal tube with herniation of brain around retractors and
around the edges of the bony craniotomy. Substantial injury to brain parenchyma and adverse neurologic events
have occurred. Where feasible, patients should be maintained paralyzed during surgery in this vicinity of CN V.
When patients are not paralyzed, clinicians should be very attentive to the possibility of arousal and should be ready
to deepen anesthesia at a second's notice, e.g., a syringe of induction agent should be maintained in line at all times.

Stridor/Narrow airway. Swelling and expanding hematomas occurring after carotid endarterectomy or anterior
cervical discectomy/fusion procedures have the potential to encroach upon the extra-thoracic airway. The clinician
should keep several principles in mind. 1) The airway will always look much worse on the inside than it does on the
outside. Swelling of peri-glottic structures is a larger component of airway compromise than is mechanical
encroachment. I suspect that the enlarging mass impairs lymphatic and venous drainage. When one visualizes in
the airway, there is often remarkable swelling of peri-glottic structures. 2) Stridor is a late (and ominous sign).
Delaying in the face of progressive enlargement of the neck until stridor occurs raises the likelihood of extreme
difficulty in securing the airway. 3) Racemic epinephrine (or Heliox) may buy you time in the event of respiratory
compromise, but they should not be viewed as cures. When an airway has become sufficiently narrow to produce
stridor and labored respiration (and concomitant turbulent flow), very small increases in airway diameter will reduce
airway resistance enough to mitigate symptoms. But the clinician should assume that progressive swelling will
occur if the mass lesion is not relieved and distress will recur.

John C. Drummond, M.D., FRCPC
Professor of Anesthesiology
The University of California, San Diego;
Staff Anesthesiologist
The Veterans Affairs Medical Center, San Diego

1. Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiological Reviews; 39: 183-238, 1959
2. Morris GC, Moyer JH, Snyder HB, et al.: Cerebral hemodynamics in controlled hypotension. Surg Forum; 4:
140-3, 1953
3. Drummond JC: The lower limit of autoregulation: Time to revise our thinking? Anesthesiology 86:1431-3,
1997
4. Fitch W, MacKenzie ET, Harper AM: Effects of decreasing arterial blood pressure on cerebral blood flow in the
baboon. Influence of the sympathetic nervous system. Circ Res; 37: 550-7, 1975
5. Joshi B, Ono M, Brown C, et al.: Predicting the limits of cerebral autoregulation during cardiopulmonary
bypass. Anesth Analg; 114: 503-10, 2012
6. Astrup J, Symon L, Branston NM, et al.: Cortical evoked potential and extracellular K
+
and H
+
at critical levels
of brain ischemia. Stroke; 8: 52-57, 1977
7. Branston NM, Symon L, Crockard HA, et al.: Relationship between the cortical evoked potential and local
cortical blood flow following acute middle cerebral artery occlusion in the baboon. Exptl Neurol; 45: 195-208,
1974
8. Jones TH, Morawetz RB, Crowell RM, et al.: Thresholds of focal cerebral ischemia in awake monkeys. J
Neurosurg; 54: 773-782, 1981
9. Hicks JW, Munis JR: The siphon controversy counterpoint: the brain need not be "baffling". Am J Physiol
Regul Integr Comp Physiol; 289: R629-32, 2005
10. Drummond JC, Hargens AR, Patel PM: Hydrostatic gradient is important - Blood pressure should be corrected.
Anesthesia Patient Safety Foundation Newsletter 24: 6, 2009
11. Maekawa T, Tommasino C, Shapiro HM, et al.: Local cerebral blood flow and glucose utilization during
isoflurane anesthesia in the rat. Anesthesiology; 65: 144-151, 1986
12. Muizelaar JP, Marmarou A, Ward JD, et al.: Adverse effects of prolonged hyperventilation in patients with
severe head injury: A randomized clinical trial. J Neurosurg; 75: 731-739, 1991
13. Reasoner DK, Todd MM, Scamman FL, et al.: The incidence of pneumocephalus after supratentorial
craniotomy. Anesthesiology; 80: 1008-12, 1994

Disclosure
Hospira, Honoraria

Neuroanesthesia and Interventional Neuroradiology
Phoenix, Arizona Daniel J. Cole, M.D.
Adrian Gelb, FRCPC M.B. B.Ch. San Francisco, California
Introduction
There are about 800,000 strokes and 300,000 transient ischemic attacks each year in the United States; and, with an
estimated 130,000 deaths each year, stroke is the third leading cause of death.
1
With six million stroke survivors
and an age-dependent prevalence of asymptomatic carotid artery disease as high as 7.5%,
2
carotid artery disease is a
significant anesthetic issue for patients over 50 years of age.
Risk factors for stroke include hypertension, diabetes, atrial fibrillation, hyperlipidemia, smoking, inactivity,
genetics, chronic kidney disease, and sleep apnea.
1
Medical therapy for stroke is directed at prevention by
correcting modifiable risk factors, and by utilizing antiplatelet/anticoagulant/fibrinolytic agents for patients whom
have suffered cerebral ischemia of atherothrombotic origin. A stroke occurs due to occlusive or hemorrhagic
conditions. Occlusive cerebrovascular disease can be thrombotic, embolic, or stenotic in origin. Performing an
accurate history and physical examination should identify nearly all significant neurological symptoms.
Patients with a history of prior stroke or transient ischemic attack have an increased risk of recurrent perioperative
stroke. Major symptoms of carotid artery disease include changes in vision, headache, changes in speech, or
facial/extremity weakness. Signs suggestive of carotid artery disease include a high-pitched bruit at the origin of the
internal carotid artery, increase in size and pulsation of the ipsilateral superficial temporal artery, and changes in the
retinal examination. Confirmation of carotid artery disease is achieved by vascular imaging which may include
ultrasound, MR angiography, or catheter angiography.
Carotid Artery Revascularization
Carotid endarterectomy (CEA) was introduced in 1954 as treatment for occlusive carotid artery disease. Efficacy
data on CEA was limited until the 1990s. Analysis of three trials
3-5
has demonstrated that CEA has a marginal
benefit in symptomatic patients with 50%-69% stenosis of the carotid artery, and was of greatest benefit in patients
with >70% stenosis.
6
The ACAS trial demonstrated a marginal benefit for CEA in asymptomatic patients with
>60% stenosis.
7
It should be noted that medical therapy for asymptomatic carotid artery disease has improved
significantly since the above trials; which would indicate a need to refresh the data comparing any interventional
therapy to medical therapy.
Stenting and angioplasty of the carotid artery (CAS) has been performed for almost two decades. Potential
advantages of this technique include avoiding cranial nerve damage, wound hematoma, and general anesthesia. In
addition, stenting and angioplasty is utilized for patients who present a technical surgical challenge (e.g., post
radiation, restenosis after previous CEA, and surgically inaccessible lesions) or have severe cardiovascular disease.
The anesthetic technique for this procedure involves minimal or no sedation. This procedure can cause severe
bradycardia and hypotension, and can result in cerebral hyperperfusion. Although the frequency of CAS has been
increasing while CEA has been decreasing, it is unclear whether CAS offers an advantage over CEA (see Table 1).
The salient trial, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) compared CEA and
CAS for both symptomatic and asymptomatic carotid artery stenosis.
8
There was no significant overall difference in
230
Page 1

230
Page 2
the primary end-point of stroke, MI or death. There was, however, a lower rate of stroke following CEA and a
lower rate of MI following CAS. Of note, age had a meaningful difference with CEA being superior for patients
older than 70 and CAS demonstrating superiority for patients 69 years and younger.

Although the estimates vary dependent upon the database, there are approximately 140,000 carotid artery
interventions performed each year with CAS constituting !13% of the procedures in 2008.
1
The current indication
for CAS by the Center for Medicare and Medicaid Services is restricted to high surgical risk symptomatic patients.

Table 1-stroke and death rate following comparative trials of CEA versus CAS.

Stroke/Death (%)
CAVATAS-2001 CEA-9.9 CAS-10.0

SAPPHIRE-2004 CEA-8.4 CAS-5.5

CARESS-2005 CEA-13.6 CAS-10.0

SPACE-2006 CEA-6.3 CAS-6.8

EVA-3S-2006 CEA-6.1 CAS-11.7

ICSS-2010 CEA-4.7 CAS-8.5

CREST-2010

CEA-2.3 CAS-4.4

Anatomic/Physiologic Considerations

Carotid artery disease is typically the result of atherosclerosis at the bifurcation of the common carotid artery or the
origin of the internal carotid artery. Ischemia is most often embolic in origin but may also have a hemodynamic
component. There are three phases of the response of various cerebral variables to progressive carotid artery disease
(see Figure 1). During ischemia, collateral flow is a cornerstone of cerebral blood flow (CBF) compensation. The
principal pathways of collateral flow are the Circle of Willis, extracranial anastomotic channels, and leptomeningeal
communications that bridge "watershed" areas between major arteries. The risk of ischemia with carotid artery
disease is related to the dependency of the circulation on the ipsilateral internal carotid artery, and the
cerebrovascular reserve of the contralateral hemisphere.

230
Page 3

Preoperative Concerns

CAS has an inherent risk of perioperative stroke and cardiovascular events. The literature suggests that risk is
associated with age, hypertension, and coronary artery disease.
9
In general, carotid artery disease should be
considered a manifestation of systemic vascular disease, and an appropriate evaluation of other organ systems is
indicated..

Anesthetic Management

Basic Monitoring-this should include standard ASA monitoring. Most often no invasive intra-arterial blood pressure
monitoring is done other than that performed as part of the procedure.

Anesthetic Technique-most often no or very minimal sedation is all that is required, thus allowing for clinical
neurologic monitoring. Neurologic complications have been substantially reduced with the implementation of
neurologic protection devices which most often include a basket distal to the area of plaque that prevent plaque
migration beyond the basket (see Figure 2). There are three periods during which the patient is at risk for cerebral
emboli (see Figure 2):

a. Advancing the device past the area of plaque
b. Inflating the balloon
c. Deployment of the stent

Figure 1. Relative changes in CBV (cerebral blood volume), CBF, OEF (oxygen extraction fraction), and
CMR (cerebral metabolic rate) in relation to progressive hemodynamic changes in cerebral perfusion.

!
" ! !
# ! !
$ ! !
CBV
!
" ! !
!
" ! !
# ! !
CBF
OEF
I III II
Figure 1. Relative changes in CBV
(cerebral blood volume), CBF, and OEF
(oxygen extraction fraction) in relation to
progressive hemodynamic changes in
cerebral perfusion (phase I!phase
II!phase III.
Figure 2. Stages of carotid artery stenting
and angioplasty. Arrow indicates
placement of the neuroprotection device
(basket) distal to the culprit lesion.

230
Page 4
During inflation of the balloon or deployment of the stent there is also the risk of profound bradycardia which is
often attenuated with prophylactic anticholinergic treatment and/or treatment at the time of bradycardia with
anticholinergic or transthoracic pacing. Hypotension may also occur.

The Postoperative Period

The objectives are optimal systemic and cerebral hemodynamics. Concerns in the immediate postoperative period
include:
1. Hemodynamic instability.
2. Hyperperfusion-is most likely to occur in patients with high grade carotid artery stenosis who develop
>100% increase in CBF after CAS.
3. Myocardial Infarction.
4. Stroke.

Conclusions

Although controversial, randomized, trials have validated the efficacy of CAS showing similar results to CEA
although the risk of stroke seems to be higher and the risk of MI lower in comparison to CEA.

Careful patient selection with attention to comorbidities, with skilled operators in experienced centers may lead to
better outcomes. In addition to purported advantages of CAS, including avoiding cranial nerve damage, wound

hematoma, and general anesthesia, CAS may overcome anatomical surgical challenges and minimize risk of
myocardial infarction.

References
1. Go AS, et al. Circulation. 2013;127:e6
2. de Weerd M, et al. Stroke. 2010;41:1294
3. NASCET. N Engl J Med 1991;325:445
4. ECST Collaborative Group. Lancet 1998;351:1379
5. Mayberg MR, et al. JAMA 1991;266:3289
6. Rothwell PM, et al. Lancet. 2003;361:107
7. Executive Committee for the ACAS. JAMA 1995;273:1421
8. Brott TG, et al. N Engl J Med 2010;363:11
9. Touze E, et al. Stroke 2009;40:e683

Disclosure
The speakers have indicated that he or she has no significant financial relationship with the manufacturer of a

304
Page 1
Postoperative Cognitive Dysfunction
Gregory Crosby, M.D.
Deborah Cully, M.D.
Adrian Gelb, FRCPC, M.B., B.Ch.
Boston, Massachusetts
Boston, Massachusetts
San Francisco, California
Certain surgical procedures (notably cardiac surgery) have long been known to be associated with postoperative
cognitive morbidity. Over the past 15 years, however, it has become increasingly clear that disruption or decline in
cognitive function is fairly widespread among elderly non-cardiac surgical patients as well. The reasons are a matter
of considerable controversy and this brief overview will recap current perspectives on the problem.
Postoperative Cognitive Dysfunction (POCD)
Many elderly patients experience cognitive dysfunction weeks to months after surgery.
1,2
This POCD is manifest
mainly as subtle deficits in memory and/or executive function that, unlike delirium, are diagnosed by performance
on a battery of neuropsychological tests rather than by clinical criteria. POCD is present after non-cardiac surgery in
30-40% of patients in the 1
st
postoperative week regardless of age but 3 months later it is 2-3 times more common in
aged patients (10-13%) than younger adult surgical controls or age-matched non-hospitalized controls (4-6%).
3-5

Persons with POCD leave the workforce prematurely and, if they have POCD at both hospital discharge and 3
months postoperatively, are nearly 5-times more likely to be dead 1 year later.
3,6
Thus, prolonged postoperative
cognitive impairment is real, common, and associated with poor functional outcomes and higher 1-year mortality.
The key question, of course, is what causes it? The short answer is that no one is certain but the problem is almost
certainly multifactorial. Advanced age clearly plays a role but it is not known whether this reflects loss of brain
reserve, prevalence of comorbid diseases (especially cerebrovascular disease), lack of neurotrophic factors, poor
reparative ability, etc. Although it is reasonable to speculate that poor baseline cognitive performance might identify
patients at greatest risk for POCD, most trials have excluded such people in part because poor baseline performance
makes decline difficult to detect.
7
Genetic susceptibility may be a factor; a recent study found a strong association
between the Apo E4 alle, a major susceptibility gene for Alzheimers disease and other types of cognitive decline,
and POCD following inhalation but not intravenous anesthesia but previous work does not confirm greater
vulnerability.
8-10
Similarly, physiologic changes seem to contribute minimally or not at all to POCD. Investigation of
perioperative hypotension (defined as MAP 45-55 mmHg or < 60% of baseline for ! 30 min) and/or hypoxia (SpO2
" 80 for > 2 min) during non-cardiac surgery, for example, has found little evidence of an association with
POCD.
5,11
Even the abnormal physiology of CPB does not explain late POCD, as comparison of on-pump and off-
pump CABG reveal similar cognitive (and neurologic) outcomes.
12-14

This means we need to look elsewhere. Surgery is a good place to start, as surgery induces inflammation and
inflammation can impair cognition. Consistent with this hypothesis, the incidence of POCD is higher after major
inpatient than minor outpatient procedures, suggesting the magnitude of the surgical insult and inflammatory
response play a role.
7
Recent work in young animals shows that a surgical procedure disrupts the blood brain barrier,
increases migration of macrophages into the brain, and produces transient neuroinflammation and learning
impairment that is reversed by a cytokine antagonist, a nicotinic acetylcholine receptor agonist, or an aspirin-
triggered resolving.
15-18
Unexpectedly, however, isoflurane anesthesia alone also produces an inflammatory response
in the brain.
19
So, the neuroinflammation hypothesis is viable and may be as relevant for explaining anesthetic-
induced cognitive impairment as it is for understanding surgically-induced cognitive deficits. Moreover, if
perioperative cognitive impairment is caused by neuroinflammation, it might be possible to do something about it.

304
Page 2
Could general anesthesia be the problem? Surely, among all the things that happen in the perioperative period,
general anesthesia has the most obvious effect on the brain (i.e. coma). The data, however, are inconsistent. Several
studies have found general anesthesia without surgery in old rodents induces prolonged changes in gene and protein
expression and learning impairment that lasts days to weeks, implying either that the neurobiological machinery of
memory is altered in an enduring way or that damage occurs.
20-23
In addition, there is evidence that some volatile
anesthetics promote processes implicated in the neuropathogenesis of Alzheimers disease
24
including promoting
formation and/or reducing clearance of A#, increasing A# aggregation and oligomer formation, augmenting its
neurotoxic qualities, and hyper-phosphorylating the microtubule protein tau (which also occurs with
hypothermia).
23,25,26-31
What this means clinically is unclear. Thus far, clinical studies reveal no difference in the risk
of prolonged POCD between regional and general anesthesia
32
and retrospective epidemiological studies report no

link between general anesthesia (plus surgery) and the development or progression of Alzheimers disease.
33-35

However, the studies are either underpowered or challenged on methodological grounds and should be interpreted
cautiously.
36
The fact that hospitalization for non-critical illness increases the risk of incident dementia
37
makes it
reasonable to worry that the same might be true for surgical illness, although it could also point to the importance of
patient factors.

Indeed, what about the patient? Could it be they come to the OR with a cognitive deficit and we dont know it?
Absolutely! About 20% of patients coming for elective total hip surgery meet criteria for MCI (mild cognitive
impairment) and the incidence of cognitive impairment is probably twice that in patients having CABG surgery.
38-40

These patients go undetected, however, because we dont ordinarily perform a preoperative cognitive
assessment.
40,41
In addition, some studies indicate the type of surgery or anesthesia does not matter as far as POCD
is concerned.
42
Furthermore, when one examines the cognitive trajectory of patients with coronary artery disease
who do or do not have CABG surgery, it turns out that over 5 years both groups decline but do so at the same
rate.
43,44
Therefore, the likelihood of experiencing cognitive impairment postoperatively may be determined as much
or more by preoperative cognitive status and comorbid conditions such as cerebrovascular disease than the details of
the surgery or anesthesia.

So, while we know a little about what it isnt (e.g. cardiolpulmonary bypass), we have no definitive answer for what
causes perioperative cognitive morbidity. Patient, medication, and surgical factors are likely to interact in a way still
poorly understood. What is clear is that like a weak heart, having a bad brain puts seniors at high risk for serious
cognitive morbidity perioperativelywhich is at least as debilitating and ominous as problems we worry about in
other organ systems (e.g. low cardiac ejection fraction). Whatever the cause, the brain appears to take a hit that
manifests as volume loss in cortical gray matter and the hippocampus that lasts for several months.
45
With this in
mind, there is good reason for anesthesiologists and surgeons to be informed about the issue, as many of our elderly
patients and their families are justifiably interested.

REFERENCES

1. Silverstein JH, Timberger M, Reich DL, Uysal S: Central nervous system dysfunction after noncardiac
surgery and anesthesia in the elderly. Anesthesiology 2007; 106: 622-628
2. Newman S, Stygall J, Hirani S, Shaefi S, Maze M: Postoperative cognitive dysfunction after noncardiac
surgery: a systematic review. Anesthesiology 2007; 106: 572-590
3. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS: Predictors
of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008; 108: 18-30
4. Price CC, Garvan CW, Monk TG: Type and severity of cognitive decline in older adults after noncardiac
surgery. Anesthesiology 2008; 108: 8-17
5. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K,
Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein
JH, Beneken JE, Gravenstein JS: Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study.
ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998; 351: 857-861
6. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen L, Group tI: Long-term Consequences of
Postoperative Cognitive Dysfunction. Anesthesiology 2009

304
Page 3
7. Silverstein JH, Steinmetz J, Reichenberg A, Harvey PD, Rasmussen LS: Postoperative cognitive
dysfunction in patients with preoperative cognitive impairment: which domains are most vulnerable?
8. Yingmin C, Hu H, Liu P, Feng G, Dong W, Yu B, Zhu Y, Song J, Zhao M: Association between the
Apolipoprotein E4 and Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Intravenous Anesthesia
and Inhalation Anesthesia. Anesthesiology 2011
9. Abildstrom H, Christiansen M, Siersma VD, Rasmussen LS: Apolipoprotein E genotype and cognitive
dysfunction after noncardiac surgery. Anesthesiology 2004; 101: 855-861
10. McDonagh DL, Mathew JP, White WD, Phillips-Bute B, Laskowitz DT, Podgoreanu MV, Newman MF,
Group NOR: Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of
brain injury. Anesthesiology 2010; 112: 852-9
11. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME: Cognitive effects after epidural vs
general anesthesia in older adults. A randomized trial [see comments]. JAMA 1995; 274: 44-50
12. Mller CH, Perko MJ, Lund JT, Andersen LW, Kelbaek H, Madsen JK, Winkel P, Gluud C, Steinbrchel
DA: No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump
coronary bypass surgery: the best bypass surgery trial. Circulation 2010; 121: 498-504
13. Hueb W, Lopes NH, Pereira AC, Hueb AC, Soares PR, Favarato D, Vieira RDO, Lima EG, Garzillo CL,
Paulitch FdS, Csar LAM, Gersh BJ, Ramires JAF: Five-year follow-up of a randomized comparison between off-
pump and on-pump stable multivessel coronary artery bypass grafting. The MASS III Trial. Circulation 2010; 122:
S48-52
14. Rodriguez RA, Rubens FD, Wozny D, Nathan HJ: Cerebral Emboli Detected by Transcranial Doppler
During Cardiopulmonary Bypass Are Not Correlated With Postoperative Cognitive Deficits. Stroke; a journal of
cerebral circulation 2010
15. Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M: Postoperative impairment of cognitive function in rats: a
possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007; 106: 436-443
16. Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J,
Fanselow MS, Maze M: Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 2010; 68:
360-8
17. Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF,
Akassoglou K, Maze M: Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 2011; 70:
986-95
18. Terrando N, Gomez-Galan M, Yang T, Carlstrom M, Gustavsson D, Harding RE, Lindskog M, Eriksson
LI: Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. The FASEB Journal 2013
19. Wu X, Lu Y, Dong Y, Zhang G, Zhang Y, Xu Z, Culley DJ, Crosby G, Marcantonio ER, Tanzi RE, Xie Z:
The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-$, IL-6, and IL-1#. Neurobiol Aging
2012; 33: 1364-78
20. Culley DJ, Xie Z, Crosby G: General anesthetic-induced neurotoxicity: an emerging problem for the young
and old? Current Opinion in Anaesthesiology 2007; 20: 408-13
21. Culley DJ, Yukhananov RY, Xie Z, Gali RR, Tanzi RE, Crosby G: Altered hippocampal gene expression 2
days after general anesthesia in rats. Eur.J.Pharmacol. 2006
22. Culley DJ, Baxter MG, Crosby CA, Yukhananov R, Crosby G: Impaired acquisition of spatial memory 2
weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth.Analg. 2004; 99: 1393-1397
23. Bianchi SL, Tran T, Liu C, Lin S, Li Y, Keller JM, Eckenhoff RG, Eckenhoff MF: Brain and behavior
changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 2008; 29: 1002-
10
24. Tang J, Eckenhoff M, Eckenhoff R: Anesthesia and the Old Brain. Anesth Analg 2009
25. Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF:
Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004; 101: 703-
709
26. Xie Z, Dong Y, Maeda U, Alfille P, Culley DJ, Crosby G, Tanzi RE: The common inhalation anesthetic
isoflurane induces apoptosis and increases amyloid beta protein levels. Anesthesiology. 2006; 104: 988-994
27. Zhang G, Dong Y, Zhang B, Ichinose F, Wu X, Culley DJ, Crosby G, Tanzi RE, Xie Z: Isoflurane-induced
caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine, J Neurosci, 2008, pp
4551-60

304
Page 4
28. Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE: The common
inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann
Neurol 2008; 64: 618-27
29. Dong Y, Zhang G, Zhang B, Moir RD, Xia W, Marcantonio ER, Culley DJ, Crosby G, Tanzi RE, Xie Z:
The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Arch
Neurol 2009; 66: 620-31
30. Planel E, Richter KE, Nolan CE, Finley JE, Liu L, Wen Y, Krishnamurthy P, Herman M, Wang L,
Schachter JB, Nelson RB, Lau LF, Duff KE: Anesthesia leads to tau hyperphosphorylation through inhibition of
phosphatase activity by hypothermia. J.Neurosci. 2007; 27: 3090-3097
31. Whittington RA, Virg L, Marcouiller F, Papon M-A, Khoury NBE, Julien C, Morin F, Emala CW, Planel
E: Propofol directly increases tau phosphorylation. PLoS ONE 2011; 6: e16648
32. Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A,
Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller
JT: Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general
anaesthesia in 438 elderly patients. Acta Anaesthesiol.Scand. 2003; 47: 260-266
33. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT: Alzheimer's disease and cumulative
exposure to anesthesia: a case-control study. J Am Geriatr Soc 1994; 42: 198-201
34. Avidan M, Searleman A, Storandt M, Barnett K, Vannucci A, Saager L, Xiong C, Grant E, Kaiser D,
Morris J, Evers A: Long-term Cognitive Decline in Older Subjects Was Not Attributable to Noncardiac Surgery or
Major Illness. Anesthesiology 2009
35. Sprung J, Jankowski CJ, Roberts RO, Weingarten TN, Aguilar AL, Runkle KJ, Tucker AK, McLaren KC,
Schroeder DR, Hanson AC, Knopman DS, Gurrieri C, Warner DO: Anesthesia and incident dementia: a population-
based, nested, case-control study. Mayo Clinic proceedings Mayo Clinic 2013; 88: 552-561
36. Silverstein JH, Allore HG, Deiner S, Sano M, Rasmussen L: Is postoperative cognitive decline clinically
relevant? Anesthesiology 2010; 112: 1280-1; author reply 1283-5
37. Ehlenbach WJ, Hough CL, Crane PK, Haneuse SJPA, Carson SS, Curtis JR, Larson EB: Association
between acute care and critical illness hospitalization and cognitive function in older adults. JAMA 2010; 303:763-
70
38. Millar K, Asbury AJ, Murray GD: Pre-existing cognitive impairment as a factor influencing outcome after
cardiac surgery. British Journal of Anaesthesia 2001; 86: 63-7
39. Silbert BS, Scott DA, Evered LA, Lewis MS, Maruff PT: Preexisting cognitive impairment in patients
scheduled for elective coronary artery bypass graft surgery. Anesth Analg 2007; 104: 1023-8, tables of contents
40. Evered LA, Silbert BS, Scott DA, Maruff P, Ames D, Choong PF: Preexisting Cognitive Impairment and
Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement. Anesthesiology 2011; 114:
1297-1304
41. Crosby G, Culley DJ, Hyman BT: Preoperative cognitive assessment of the elderly surgical patient: a call
for action. Anesthesiology 2011; 114: 1265-8
42. Evered L, Scott DA, Silbert B, Maruff P: Postoperative cognitive dysfunction is independent of type of
surgery and anesthetic. Anesth Analg 2011; 112: 1179-85
43. Selnes OA, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Mckhann GM: Cognition 6
years after surgical or medical therapy for coronary artery disease. Ann Neurol 2008; 63: 581-90
44. Selnes OA, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Mckhann GM: Do
management strategies for coronary artery disease influence 6-year cognitive outcomes? Ann Thorac Surg 2009; 88:
445-454
45. Kline RP, Pirraglia E, Cheng H, De Santi S, Li Y, Haile M, de Leon MJ, Bekker A, Initiative ftADN:
Surgery and Brain Atrophy in Cognitively Normal Elderly Subjects and Subjects Diagnosed with Mild Cognitive
Impairment. Anesthesiology 2012; 116: 603-612

304
Page 5
Disclosure-Dr. Crosby and Dr. Gelb
These speakers have indicated that he or she has no significant financial relationship with the manufacturer of a

Disclosure-Dr. Culley
American Board of Anesthesiology, Self, Honoraria

Disclosure-Dr. Lubenow
Medtronic, Self, ConsultingFees ; Boston Scientific, Self, Funded Research, Consulting Fees, Honoraria

423
Page 1
Perioperative Management of Patients Undergoing Spine Surgery
Susan Black, M.D. Birmingham, Alabama
Management of patients undergoing spine surgery varies with location and type of the planned surgical procedure.
Understanding of the patients spine disease, planned procedure, and other co morbidities are crucial to providing
optimal perioperative care.
Airway Management
Patients with cervical spine pathology require special consideration for airway management. Patients with cervical
spine disease have a higher incidence of difficult intubation, in particular those with rheumatoid disease, cervical
fractures or tumors, disease involving the upper cervical spine, and with internal or external fixation.1
Endotracheal intubation in the presence of cervical spine disease may be associated with risk of neurologic injury.
In patients with an unstable cervical spine, intubation is not associated with an increased risk of neurologic
deterioration compared to those not requiring intubation (1-2%) if the instability is recognized.2 In patients with
unrecognized cervical spine instability, risk of neurologic deterioration with intubation is approximately 10%.3
Studies have attempted to identify optimal techniques for intubation in patients at risk for cervical spine injury.2,4-7
During airway maneuvers, the greatest motion of the cervical spine has been shown to occur at the atlanto-occipital
junction followed by the junction of the first two cervical vertebrae.8 In evaluation of stabilization maneuvers,
manual in line stabilization has been shown to effectively decrease motion of the cervical spine during direct and
indirect laryngoscopy in severe cervical spine injury, while axial traction may increase motion and hard collars have
no impact on motion and increase intubation difficulty.6,8 In the presence of a recognized unstable cervical spine a
variety of intubation techniques in experienced hands have consistently been shown to be safe with no single best
technique identified.2 Results of studies of cervical motion and intubation characteristics of different intubation
tools suggest potential advantages with fiberoptic bronchoscopy, indirect laryngoscopes, video laryngoscopes and
use of intubation guides for decreasing cervical spine motion during intubation.2-9 Use of the laryngeal mask
airway (LMA) and intubating LMA have generated considerable interest. Potential benefits of the LMA include less
motion of the cervical spine and higher success rate when used emergently by physicians with limited airway
experience. Potential disadvantages include increased risk of aspiration and the impact of flexion of the cervical
spine.7,10 Both awake intubation and intubation after induction of general anesthesia have been used safely.2
Advantages of awake intubation include maintenance of normal muscle tone and the ability to perform a neurologic
examination following intubation. Intubation after induction of general anesthesia also has advantages including the
ability to secure the airway with limited neck movement in the patient who is unable to cooperate. In planning
airway management of patients undergoing cervical spine surgery awareness of the risk of spinal cord injury with
intubation, recognition of the increased risk of encountering a difficult airway, and attention to minimizing motion
of the cervical spine are more important to success than choice of a particular technique.
Certain patient groups may also have risk of postoperative airway problems the difficult extubation patient.
Patients undergoing multiple level anterior cervical spine procedures may be at risk for postoperative neck and
airway edema causing airway compromise with airway complications occurring in up to 6%, requiring reintubation
in approximately 2%, and leading to mortality in 0.3%. Identified risk factors are operative time > 10 hours,
requirement for > 4 units transfusion, obesity, reoperations, and operations of 4 or more cervical spine levels or
involving the second cervical vertebrae.11
Hemodynamic Management
In some circumstances induced hypertension or induced hypotension are utilized in spine procedures. It is a
common practice to maintain very strict control of blood pressure intraoperatively utilizing direct arterial pressure
monitoring and attempting to maintain systemic perfusion pressure at or very near awake levels. While this has not
been studied in a prospective fashion, it is believed by many neurosurgeons and neuroanesthesiologists to be
important in minimizing risk for new neurologic injury in this patient population. 12 On the other hand, induced
hypotension continues to be utilized in some centers for patients undergoing procedures associated with high
423
Page 2
perioperative blood loss, in particular multilevel thoracic and lumbar reconstructive procedures. There is little
evidence to indicate that mild degrees of induced hypotension as is most commonly utilized in these procedures is
effective to significantly decrease perioperative estimated blood loss or perioperative transfusion requirement.
However, less bleeding in the operative field, may improve surgical exposure. This may be an appropriate and
effective strategy in patients that are not placed at increased risk of perioperative morbidity by the use of mild
degrees of induced hypotension.13
Regional Anesthesia
There has been a recent resurgence in use of regional anesthesia for some lumbar spine procedures, primarily
discectomy. Studies suggest that spinal anesthesia may be associated with decreased blood loss, early postoperative
pain, incidence of nausea and vomiting, and incidence of deep venous thrombosis.14 Additional use of epidural
clonidine may further decrease postoperative pain.15 Of note, most authors who utilize this technique avoid patients
with severe spinal stenosis. Use of spinal anesthesia in patients with severe spinal stenosis not undergoing spine
surgery has been reported to be associated with increased risk for new neurologic deficits.16
Minimally Invasive Procedures
Endoscopy is utilized in lumbar spine disease in posterior approaches for discectomy as well as anterior approaches
for instrumentation. In addition thoracoscopic approaches are utilized for thoracic procedures. Benefits
demonstrated in some clinical scenarios include shortened hospital stay, decreased postoperative pain, and shortened
disability duration with similar long term results.17 Vertebroplasty and kyphoplasty, done percutaneously with
fluoroscopic guidance are being used increasing to treat painful osteoporotic fractures of the thoracic and lumbar
spine. It has a high success rate, but may be associated with pulmonary embolism (in up to 4% of patients) or
pericarditis caused by intravenous administration of the cement material. These complications may manifest during
or several hours after the procedure.18,19
Spine Surgery in the Elderly
Lumbar decompressive surgery for spinal stenosis is being performed increasingly in the very elderly (over 75 to 80
years of age). Recent long term studies suggest that these patients who present with on average 3 to 4 comorbid
conditions have significant improvement in symptoms and quality of life, with low perioperative morbidity and
hospital stays of 2 to 4 days on average.20,21 Interestingly, obesity was related to increased incidence of major
complications, while increasing age was related to incidence of minor complications.22
Transfusion Management
While many surgical procedures of the spine are not associated with large blood loss, procedures involving
significant bone work at multiple levels, particularly in the thoracic and lumbar regions, may be associated with
large intraoperative blood loss and a high incidence of transfusion. During lumbar spine surgery a number of factors
have been found to predict requirement for transfusion including age greater than 50, female sex, ASA classification
of 3 or greater, preoperative hemoglobin level (less than 12 gm/dl) fusion of more than 2 levels, and transpedicular
osteotomy.23, 24 Strategies to reduce transfusion of homologous blood products include attempts at reduction of
intraoperative blood loss (induced hypotension, alteration of operative position, changes in surgical techniques, and
administration of antifibrinolytic agents) and reduction of transfusion of homologous products (preoperative
recombinant human erythropoietin, intraoperative and/or postoperative blood salvage, preoperative autologous
donation, and perioperative hemodilution and apheresis). Each of these techniques have demonstrated efficacy in
some clinical scenarios. Of note a recent large retrospective review (>1000 patients) of transfusion practice during
spine surgery comparing early practice (1980-1985) to more recent practice (1995-2000) revealed older patients
with more co-morbidities undergoing longer procedures in the recent practice group. Over time allogeneic
transfusion decreased, preoperative donation and intraoperative salvage increased. Of particular interest was the
observation that in the late practice group postoperative hemoglobin values were significantly lower in an admittedly
higher risk group of patients with no increased risk of complications.25
Several techniques to decrease intraoperative blood loss have been investigated. Induced hypotension is applied
most commonly to multiple level thoracic or lumbar spine procedures in healthy patients without neurologic deficits.
Efficacy in decreasing blood loss and transfusion has not been consistently demonstrated.26 Operative positions
which prevent abdominal compression (such as the Jackson table) have been reported to result in less blood loss and
lower incidence of transfusion as compared to positions in which some degree of abdominal compression may occur
(prone on bolsters or Wilson frame).27 Antifibrinolytic agents, tranexamic acid and aminocaproic acid, have been
shown in many studies to decrease intraoperative and total perioperative blood loss with some studies demonstrating
a decrease in transfusion of blood products and others revealing no difference in transfusion requirements. Use of
these agents has not been associated with complications related to hypercoagulation.23,26,28 In a small series,
recombinant activated factor VII was shown to be effective at decreasing intraoperative blood loss and transfusion in
patients undergoing multiple level spinal fusion procedures when given after loss of 10% of estimated blood
volume.29 However this practice has not been studied in a large population.
423
Page 3
Numerous approaches to decrease requirement for homologous blood transfusion have also been investigated.
Epoetin alfa administration preoperatively has been shown to decrease requirement for homologous transfusion in
combination with preoperative autologous donation by increasing the number of units that could be collected, and
without preoperative autologous donation in procedures associated with lower intraoperative blood loss.30 In
patients undergoing procedures with likely high intraoperative blood loss such as correction of neuromuscular
scoliosis, erythropoietin was not effective at decreasing transfusion requirements when used alone.31 In one
prospective study, use of erythropoietin was associated with a higher incidence of deep venous thrombosis when
pharmacologic antithrombotic prophylaxis was not used, but no increase in symptomatic thromboembolic
complications. This lead the authors to recommend consideration of pharmacologic antithrombotic prophylaxis
when erythropoietin was to be used.32 Preoperative donation of autologous blood, immediate preoperative
hemodilution and collection of autologous blood, and perioperative blood salvage have all been utilized in spine
surgery to decrease requirement for intraoperative homologous transfusion. Each has been shown to be similarly
effective used alone to decrease requirement for transfusion of homologous blood products during major spine
procedures. However, in most circumstances combination of more than one of these techniques does not further
decrease requirement for homologous blood products compared to use of a single technique.27,30,33-35 In
addition, numerous recent studies have pointed out the high rate of wasting of autologous units collected prior to
spine surgery with wasting of at least one unit in up to 50% of patients undergoing scoliosis correction.36
1able 1: Lfflcacy of Maneuvers for uecreaslng 8lood Loss and 1ransfuslon
uecrease LsLlmaLed 8lood
Loss
uecrease 1ransfuslon
AnLlflbrlnolyLlcs 9-38 31-80
oslLlonlng wlLh abdomen free 60-63
8ecomblnanL lacLor vll 36-84 41-82
reoperaLlve auLologous
donaLlon
32-71 homologous
Lransfuslon
PemodlluLlon 39-62 homologous
Lransfuslon)
Cell Salvage 0-43 homologous
Lransfuslon)
LryLhropoleLln 20-83
A recent meta analysis reviewing available maneuvers to decrease transfusion found that there was good evidence to
support the use of antifibrinolytic agents, while there was little of no evidence to support recombinant factor VII,
induced hypotension, staging of long procedures, normovolemic hemodilution, or intraoperative cell salvage.
Erythropoietin use and preoperative autologous donation were not evaluated by these authors.13
Neurologic Monitoring and Injury Prevention
Neurologic monitoring may be utilized in a number of spine procedures. To monitor integrity of the spinal cord
somatosensory evoked potentials (SSEP) are the modality with the longest history of intraoperative use with more
recent introduction of transcranial motor evoked potentials (TcMEP). The wake up test is an adjunct technique.
Electromyography (EMG) may be utilized to monitor nerve root function. SSEP monitoring during scoliosis repair
is considered an indicated technique by the Scoliosis Research Society and is felt to result in a lower risk of
intraoperative neurologic injury.37 Neurologic monitoring of other spine procedures in patients felt to be at high
risk for neurologic injury is felt by some to decrease risk of neurologic injury, but is not utilized consistently in all
centers. SSEP and TcMEP monitoring are utilized in patients felt to be at risk for spinal cord injury either from
surgical trauma, operative position, or impairment of blood supply. EMG is utilized when it is felt that nerve roots
may be at risk during the procedure, most commonly with lumbar stabilization procedures. Conclusions from a
recent literature review were that there is good evidence that neurologic monitoring effectively detects intraoperative
neurologic injury, but little evidence that use of monitoring decreases the risk of developing a new neurologic
deficit. The authors recommend consideration of intraoperative neurologic monitoring during spine surgery.38
SSEP monitoring places some limitation on anesthetic management, most notably limiting the dose of volatile
agents and benzodiazepines. Likewise TcMEP monitoring impacts anesthetic management. Most commonly
intravenous techniques are utilized (propofol and/or narcotic infusion with nitrous, benzodiazepines, ketamine, or
423
Page 4
lose dose volatile agents). With use of multi-pulse stimulators and determination of optimal stimulating parameters
for each patient, reliability and success of TcMEP monitoring has greatly increased so that monitoring is gaining
more widespread acceptance.39,40 Patients disease states influence ability to successfully monitor their neurologic
function intraoperatively. Patients with preexisting neurologic deficits, diabetes mellitus, and hypertension have an
increased rate of inability to monitor MEPs intraoperatively. Having more than one disease or use of volatile
anesthetic agents increased the risk of failure to monitor further.41 EMG requires avoidance of muscle relaxants.
1able 2: 8aLe of neurologlc ln[ury, SenslLlvlLy, SpeclflclLy, and oslLlve and negaLlve
redlcLlve value
CuLcome SSL 1cML LMC MulLlmodal
8aLe new
neurologlc
deflclL
0.09-28.3 0.8-3.2 3.2 4.9-28.3
SenslLlvlLy 0-100 81-100 46 70-100
SpeclflclLy 27-100 81-100 73 33-100
oslLlve
predlcLlve value
13-100 17-96 3 3.2-100
negaLlve
predlcLlve value
93-100 97-100 97 96-100
Postoperative Pain Management
Thoracic and lumbar spine procedures may be associated with significant postoperative pain. Postoperative epidural
analgesia has been shown to be more effective compared to intravenous patient controlled analgesia (PCA) for
anterior as well as posterior approaches in both children and adults. The catheter is usually placed by the surgeon in
the operative field. It is not associated with increased incidence or delayed diagnosis of neurologic injury if the
dosing regimen is planned to allow early neurologic assessment. Benefits include earlier return of bowel function,
earlier mobilization, shorter hospital stay, improved pain control at rest and with movement, less nausea and
vomiting, and less puritis.42,43 Wound catheters with infiltration of local anesthetic have also been effective in
pain relief and to decrease the incidence of chronic dysesthesias.44 Epidural infusions of clonidine alone have been
shown to have significant benefits in terms of pain control, lower required doses of systemic narcotics.45 Other
techniques including pre and post operative oral controlled release narcotics, preoperative methadone (0.2 mg/kg),
perioperative oral pregabalin (150 mg preop and 12 hours post op), and local anesthetic wound infiltration have been
shown to improve pain management and decrease systemic narcotic side effects.46-50 In patients requiring chronic
narcotics preoperatively, intraoperative ketamine (0.5 g/kg on induction, 10 g/kg/min infusion) has been shown
to effectively decrease pain scores and narcotic use in both the early and late postoperative period.50 Add review
article info
Outpatient Spine Surgery
Increasingly, spine procedures are being performed as outpatient procedures. Not only are lumbar procedures
commonly outpatient procedures, but in addition cervical spine procedures are being considered as outpatient
procedures. Available literature suggests this can be done successfully provided careful patient and procedure
selection is carried out. Patients undergoing outpatient spine surgery tend to be relatively healthy, without
myelopathic symptoms, younger than the inpatient spine surgery population, undergoing shorter procedures, and
live nearby with a caregiver available. Unplanned admission or readmission is uncommon (2-5%), with no reported
complications specifically related to the outpatient status. The most common causes of admission are dural tear,
anesthetic complications, poor pain control, new neurologic symptoms, and urinary retention. In centers with
successful outpatient spine surgery practices, common exclusion criteria for outpatient procedures include
significant co-morbidities, difficult airway, living a long distance away or living alone, and procedures finishing late
in the day. In general postoperative stay is at least 4 to 6 hours. The majority of complications after spine surgery
will have occurred by this time. With careful perioperative planning, outpatient spine surgery can be performed
safely offering our patients the benefits associated with outpatient procedures including lower cost and lower risk for
hospital associated complications.51-54
423
Page 5
Postoperative Vision Loss
Postoperative vision loss is a rare complication of spine surgery occurring in 0 0.1% of cases.55-59 While
awareness of this complication has increased over the last decade, the incidence nationally appears to be
decreasing.59 Postoperative vision loss is most often due to posterior ischemic optic neuropathy (PION), less
commonly anterior ischemic optic neuropathy (AION), and rarely due to other reported causes of postoperative
vision loss; central retinal artery or vein occlusion and occipital lobe infracts. Reported risk factors for
postoperative ION include patient factors such as risk factors for atherosclerotic disease and intraoperative factors.
While occasional cases of vision loss due to positioning errors with pressure on the eye are reported, this rarely
appears to be a factor. Intraoperative hypotension and anemia are the most consistent observations in patients
developing postoperative ION. However, in the majority of spine cases the level and duration of hypotension and
anemia are not different from values reported in patients who undergo similar procedures without developing vision
loss.56-57 Cases of ION after procedures without any perioperative hypotension or anemia have occurred. The
prone position is associated with significant increases in intraocular pressure and potentially, retrobulbar pressure.
Some have postulated that acute venous congestion and a compartment-like syndrome develops in the retrobulbar
space predisposing these patients to ischemic of the optic nerve. Both head dependent positioning and vigorous
fluid resuscitation could contribute to this phenomenon.60 In procedures with high blood loss, avoidance of
administration of large volumes of fluid requires either earlier transfusion or reliance on vasopressors. Use of
vasopressors while supporting blood pressure at a higher level might also cause vasoconstriction of the optic nerve
blood supply. Whether fluid therapy or vasopressors is the ideal approach has not been determined. Long operative
duration, high intraoperative blood loss, fluid resuscitation, and periorbital edema have been reported to be
associated with increased risk for ION.56 Because most patients undergoing even long prone spine surgery with
large intraoperative blood loss do not develop ION, other as yet unidentified risk factors are felt to exist such are
variations in optic nerve blood flow and autoregulation. It has also been suggested that changes in transfusion
practice over the last decade to lower hematocrit values as triggers for transfusion may have led to an increased
incidence in postoperative ION. In a recent case control study the Postoperative Visual Loss Study Group
investigated factors reported to be with PION.61 Results are shown in Table 3.
1able 3: roposed 8lsk lacLors osLoperaLlve lCn
8lsk facLors assoclaLed lCn 8lsk facLors noL assoclaLed wlLh lCn
Male sex Age
CbeslLy Comorbld condlLlons (dlabeLes,
hyperLenslon, smoklng)
use of Wllson frame number levels
AnesLheLlc duraLlon Pead poslLlonlng devlce
LsLlmaLed blood loss PypoLenslon
Lower collold use (as of nonblood
lnfuslons)
LowesL PC1
vasopressor use
1oLal volume, LoLal nonblood volume
replacemenL
Because neither the mechanisms nor definitive risk factors have been identified, methods to prevent this
complication are unknown. In fact, the patient profile for those suffering this complication after spine surgery is
males aged 45 to 55 with risk factors for vascular disease present in only about 50%. The recommendations from
the ASA Practice Advisory are:
There is a subset of patients who undergo prone spine procedures and receiving general anesthesia that has an
increased risk for development of perioperative visual loss, including patients who are anticipated to undergo
procedures that are prolonged, have substantial blood loss, or both.
Consider informing high-risk patients that there is a small, unpredictable risk of perioperative visual loss.
The use of deliberate hypotensive techniques during spine surgery has not been shown to be associated with the
development of perioperative visual loss.
Colloids should be used along with crystalloids to maintain intravascular volume in patients who have
substantial blood loss.
423
Page 6
At this time, there is no apparent transfusion threshold that would eliminate the risk of perioperative visual loss
related to anemia.
High-risk patients should be positioned so that their heads are level with or higher than the heart when possible.
In addition, their heads should be maintained in a neutral forward position when possible.
Consideration should be given to the use of staged spine procedures in high-risk patients.
Postoperative surgical site infections (SSI) after spine surgery cause significant increases in morbidity, hospital
length of stay and health care cost. SSIs occur at rate of 0.7 to 4.0 per 100 cases. A number of risk factors have
been identified, many of which are not amenable to perioperative intervention and are reflections of the patients
disease or co-morbid conditions. These include ASA physical classification, prior spine surgery, operative duration,
obesity, and age. However a number of factors can be modified and are under the purview of the anesthesiologist.
These include perioperative glucose management, temperature control, and administered FiO2. A recent case
control study revealed elevated postoperative glucose and administration of FiO2 below 50% as predictors of
increased risk of postoperative infection after spine surgery, with a low FiO2 carrying an adjusted odds ratio of
12.63
Patients undergoing spine surgery present diverse challenges to the anesthesiologist. Optimal management depends
on the anesthesiologist understanding the pathologic process and the risk and needs of the operative procedure.
References
1. Calder I, Calder J, Crockard HA: Difficult direct laryngoscopy in patients with cervical spine disease.
Anaesthesia 50:756-763, 1995
2. Suderman VS, Crosby ET: Elective oral tracheal intubation in cervical spine-injured adults. Can J Anaesth
38:785-789, 1991
3. Hastings RH, Kelley SD: Neurologic deterioration associated with airway management in a cervical spine-
injured patient. Anesthesiology 78:580-583, 1993
4. Saha AK, Higgins M, Walker G, Badr A, Berman L: Comparison of awake endotracheal intubation in
patients with cervical spine disease: the lighted intubating stylet versus the fiberoptic bronchoscope. Anesth Analg
87:477-479, 1998
5. Hastings RH, Vigil AC, Hana R, Yang BY, Sartoris DJ: Cervical spine movement during laryngoscopy
with the Bullard, Macintosh, and Miller laryngoscopes. Anesthesiology 82:859-869, 1995
6. Hastings RH, Wood PR: Head extension and laryngeal view during laryngoscopy with cervical spine
stabilization maneuvers. Anesthesiology 80:825-831, 1994
7. Waltl B, Melischek M, Kabon W, Erlacker W, Nasel C, Fuchs M, Kapral S: Tracheal intubation and
cervical spine excursion: direct laryngoscopy vs. intubating laryngeal mask. Anaesthesia 56:221-226, 2001
8. Lennarson PJ, Smith DW, Sawin PD: Cervical spinal motion during intubation: efficacy of stabilization
maneuvers in the setting of complete segmental instability. J Neurosurg (Spine 2) 94:265-270, 2001
9. Robitaille A, Williams SR, Tremblay MH, Guilbert F, Theriault M, Drolet P: Cervical spine motion during
tracheal intubation with manual in-line stabilization: direct laryngoscopy versus GlideScope videolaryngoscopy.
Anesth Analg 106:935-941, 2008
10. Reeves MD, Skinner MW, Ginifer CJ: Evaluation of the intubating laryngeal mask airwayTM used by
occasional intubators in simulated trauma. Anaesth Intensive Care 32:73-76, 2004
11. Epstein NE, Hollingsworth R, Nardi D, Singer J: Can airway complications following multilevel anterior
cervical spine surgery be avoided: J Neurosurg 94(2 Suppl):185-188, 2001
12. Kim KA, Wang MY: Anesthetic considerations in the treatment of cervical myelopathy. Spine J6:207S-
211S, 2006
13. Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D: Blood loss in major spine surgery: are there
effective measures to decrease massive hemorrhage in major spine fusion surgery? Spine 20;35(9 Suppl):S47-56,
2010.
13. Rosenthal D, Dickman CA: Thoracoscopic microsurgical excision of herniated thoracic discs. J Neurosurg
89:224-235, 2000.
14. Jellish WS, Thalji Z, Stevenson K, Shea J: A prospective randomized study comparing short- and
intermediate-term perioperative outcome variables after spinal or general anesthesia for lumbar disk and
laminectomy surgery. Anesth Analg 83:559-564, 1996
15. Jellish WS, Abodeely A, Fluder EM, Shea J: The effect of spinal bupivacaine in combination with either
epidural clonidine and/or 0.5% bupivacaine administered at the incision site on postoperative outcome in patients
undergoing lumbar laminectomy. Anesth Analg96:874-880, 2003
16. Yuen EC, Layzer RB, Weitz SR, Olney RK: Neurologic complications of lumbar epidural anesthesia and
analgesia. Neurology 45:1795-1801, 1995
423
Page 7
17. Hermantin FU, Peters T, Quartararo L, Kambin P: A prospective, randomized study comparing the results
Surgery 81-A:958-965, 199 29.
18. Barbero S, Casorzo I, Durando M, Mattone G, Tappero C, Venturi C, Gandini G: Percutaneous
vertebroplasty: the follow-up. Radiol Med 113:101-113, 20089
19. Stricker K, Orler R, Yen K, et al. Severe hypercapnia due to pulmonary embolism of
polymethylmethacrylate during vertebroplasty. Anesth Analg 98;1184-1186, 2004.
20. Shabat S, Arinzon Z, Folman Y, Leitner J, David R, Pevzner E, Gepstein R, Ilya P, Shuval I: Long-term
outcome of decompressive surgery for lumbar spinal stenosis in octogenarians. Eur Spine J 17;193-198, 2008
21. Rosen DE, OToole JE, Eichholz KM, Hrubes M, Huo D, Sandhu FA, Fessler RG: Minimally invasive
lumbar spinal decompression in the elderly: Outcomes of 50 patients aged 75 years and older. Neurosurg 60:503-
509, 2007
22. Patel N, Bagan B, Vadera S, Maltenfort MG, Deutsch H, Vaccaro AR, Harrop J, Sharan A, Ratliff JK:
Obesity and spine surgery: relation to perioperative complications. J Neurosurg Spine 6;291-297, 2007
23. Lenoir B, Merckx P, Paugam-Burtz C, Dauzac C, Agostini M, Guigui P, Mantz J: Individual probability of
allogeneic erythrocyte transfusion in elective spine surgery. The predictive model of transfusion in spine surgery.
24. Torres-Claramunt R, Ramrez, M, Lopez-Soques M, Salo G, Molina-Ros A, LladoA, Caceres E: Arch
Orthop Predictors of blood transfusion in patients undergoing elective surgery for degenerative conditions of the
spine. Arch of Orthop Trauma Surg E Pub June 2012.
25. Wass CT, Long TR, Faust RJ, Yaszemkie MJ, Joyner MJ: Changes in red blood cell transfusion practice
during the past two decades: a retrospective analysis with the Mayo database, of adult patients undergoing major
spine surgery. Transfusion 47;1022-1027, 2007
26. Bess RS, Lenke LG: Blood loss minimization and blood salvage techniques for complex spine surgery.
Neursurg Clin N Am 17:227-234, 2006
27. Nuttall GA, Horlocker TT, Santrach PJ, Oliver WC, Dekutoski MB, Bryant S: Predictors of blood
transfusions in spinal instrumentation and fusion surgery. Spine 25(5):596-601, 2000
28. Shapiro F, Zurakowski D, Sethna NF: Tranexamic acid diminishes intraoperative blood loss and
transfusion in spinal fusions for Duchene muscular dystrophy scoliosis. Spine 32:2278-2283, 2007
29. Sachs B, Delacy D, Green J, Graham S, Ramsay J, Kreisler N, Kruse P, Khutoryansky N, Hu SS:
Recombinant activated factor VII in spinal surgery. Spine 32:2285-2293, 2007
30. Shapiro GS, Boachie-Adjei O, Dhawlikar SH: The use of epoetin alfa in complex spine surgery. Spine
27:2067-2071, 2002
31. Vitlae MG, Privitera DM, Matsumoto H, Gomez JA, Waters LM, Hyman JE, Roye DP: Efficacy of
preoperative erythropoietin administration in pediatric neuromuscular scoliosis. Spine 32:2662-2667, 2007
32. Stowell CP, Jones SC, Enny C, Langhooff W, Leitz G: An Open-label, randomized, parallel-group study
of perioperative epoetin alfa versus standard of care for blood conservation in major elective spine surgery. Spine
34:2479-2485, 2009.
33. Blais RE, Hadjipavlou AG, Shulman G: Efficacy of autotransfusion in spine surgery: comparison of
autotransfusion alone and with hemodilution and apheresis. Spine 21(23):2795-2800, 1996
34. Cavallieri S, Riou B, Roche S, Ducart A, Roy-Camille R, Viars P: Intraoperative autologous transfusion in
emergency surgery for spine trauma. J of Trauma 36(5):639-643,1994
35. Cha CW, Deible C, Muzzonigro T, Lopez-Plaza I, Vogt M, Kang JD: Allogeneic transfusion requirements
after autologous donations in posterior lumbar surgeries. Spine 27:99-104, 2002
36. Bess RS, Lenke LG, Bridwell KH, Steger-May K, Hensley M: Wasting of preoperatively donated
autologous blood in surgical treatment of adolescent idiopathic scoliosis. Soine 31:2375-2380
37. Nuwer MR, Dawson EG, Carlson LG, Kanim LE, Sherman JE: Somatosensory evoked potential spinal
cord monitoring reduces neurologic deficits after scoliosis surgery: results of a large multicenter survey.
Electroencephalography Clin Neurophysiology 96:6-11, 1995
38. Fehlings MG, Brodke DS, Norvell DC, Dettori JR: The evidence for intraoperative neurophysiological
monitoring in spine surgery. Does it make a difference: Spine 37:S37-S46, 2010
39. Lyon R, Feiner J, Lieberman JA. Progressive suppression of motor evoked potentials during general
anesthesia. J Neurosurg Anesthesiol 17:13-19, 2005.
40. Scheufler KA, Reinacher PC, Blumrich W, et al. The modifying effects of stimulation pattern and propofol
plasma concentration on motor-evoked potentials. Anesth Analg 100:440-447, 2005.
41. Stacie G. Deiner, MD,* Shawn G. Kwatra, BS, Lin H, Weisz DJ: Patient characteristics and anesthetic
technique are additive but not synergistic predictors of successful
motor evoked potential monitoring. Anesth Analg 111:421, 2010.
423
Page 8
42. Tobias JD. A review of intrathecal and epidural analgesia after spine surgery in children. Anesth Analg
98;956-965, 2004.
43. Van Boerum DH, Smith JT, Curtin MJ: A comparison of the effects of patient controlled analgesia with
intravenous opioids versus epidural analgesia on recover after surgery for idiopathic scoliosis. Spine 25:2355-2357,
2000
44. Bianconi M, Ferraro L, Ricci R, et al. The pharmacokinetics and efficacy of ropivacaine continuous wound
instillation after spine fusion surgery. Anesth Analg 98:166-172, 2004
45. Farmery AD, Wlison-MacDonald J: The analgesic effect of epidural clonidine after spinal surgery: a
randomized placebo-controlled trial. Anesth Analg 108: 631-4, 2009.
46. Blumenthal S, Min K, Marquardt M, Borgeat A: Postoperative intravenous morphine consumption, pain
scores, and side effects with perioperative oral controlled-release oxycodone after lumbar discectomy. Anesth
Analg 105:233-237, 2007
47. Ersayli DT, Gurbert A, Bekar A, Uckunkaya N, Bilgin H: Effects of perioperatively administered
bupivacaine and bupivacaine-methylprednisolone on pain after lumbar discectomy. Spine 31:2221-2226, 2006
48. Gottschalk A, Durieux ME, Nermergut EC: Intraoperative methadone improves postoperative pain
control in patients undergoing complex spine surgery. Anesth Analg 112:218-223, 2011
49. Kim JC, Choi YS, Kim KN, Shim JK, Lee JY, Kwak YL: Effective dose of peri-operative oral pregablin
as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery. Spine 36:428-433, 2011
50. Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML: Intraoperative
ketamine reduces periperative opiate consumption in opiate-dependent patients with chronic pain undergoing back
surgery. Anesthesiology 113:639-646, 2010
51. Trahan J, Abramova MV, Richter EO, Steck JC: Feasibility of anterior cervical discectomy and fusion as
an outpatient procedure. World Neurosurg 75(1):145-8, 2011.
52. Wohns R: Safety and cost-effectiveness of outpatient cervical disc arthroplasty: Surg Neurol Int13;1:77,
2010.
53. Walid MS, Robinson JS 3rd, Robinson ER, Brannick BB, Ajjan M, Robinson JS Jr: Comparison of
outpatient and inpatient spine surgery patients with regards to obesity, comorbidities and readmission for infection.
J Clin Neurosci17(12):1497-8, 2010.
54. Purzner T, Purzner J, Massicotte EM, Bernstein M: Outpatient brain tumor surgery and spinal
decompression: a prospective study of 1003 patients. Neurosurgery. 69(1):119-26, 2011.
55. Stevens WR, Glazer PA, Kelley SD, Lietman TM, Bradford DS: Ophthalmic complications after spine
surgery. Spine 22:1319-1324, 1997
56. Myers MA, Hamilton SR, Bogosian AJ, Smith CH, Wagner TA: Visual loss as a complication of spine
surgery. A review of 37 cases. Spine 22:1329, 1997
57. Cheng MA, Sigurdson W, Tempelhoff R, Lauryssen C: Visual loss after spine surgery: a survey.
Neurosurgery 46(3):625-631, 2000.
58. Lee LL, Newman NJ, Wagner TA, Dettoir JR, Dettori NJ: Perioperatie Ischemic Optic Neuropathy. Spine
35:S105-S116, 2010
59. Shen Y, Drumm M, Roth S: The prevalence of perioperative visual loss in the United States: A 10-year
study from 1996-2005 of spinal, orthopedic, cardiac, and general surgery. Anesth Analg 109:1534-1545, 2009
60. Cheng MA, o A, Tempelhoff R,et al: The effect of prone positioning on intraocular pressure in
anesthetized patients. Anesthesiology 95:1351-1355, 2001.
61. The Postoperative Visual Loss Study Group: Risk factors associated with ischemic optic neuropathy after
spinal fusion surgery. Anesthesiology 116:15-24, 2012.
62. Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery. Anesthesiology 104:1319
28, 2006
63. Maragakis LL, Cosgrove SE, Martinez EA, Tucker MG, Cohen DB, Perl TM: Intraoperative fraction of
inspired oxygen is a modi!able risk factor for surgical site infection after spinal surgery. Anesthesiology 110:556
62, 2009.
Disclosure
430
Page 1
Sleep Anesthesia Coma
Emery Brown, M.D., Ph.D Boston, Massachusettes
433
Page 1
Perioperative Management of Traumatic Brain Injury
Arthur M. Lam M.D. Seattle, Washington
Introduction
Traumatic brain injury (TBI) imposes a significant burden on society, the presence of which is the primary
determinant in quality of outcome following trauma.
1
Although the Brain Trauma Foundation has provided
guidelines for the management of severe traumatic brain injury (www.braintrauma.org),
2
there are still many
institutional differences in the care these patients receive, potentially affecting outcome.
3
Patients with TBI often
experience multiple trauma, contributing to secondary injury and poor outcome.
4

Pathophysiology
The primary injury may be focal or diffuse; it may include skull fractures, vascular injuries, subdural and
epidural hemorrhage, subarachnoid hemorrhage, and injury to the brain parenchyma, such as contusions and diffuse
axonal injury. Secondary injury includes systemic hypotension, hypoxemia, hypercapnia, and hyperthermia.
Presence of other injuries can potentially aggravate these complications.
Initial Resuscitation
The approach to patients with traumatic brain injury should be the similar to any victim of trauma, and
focus on ABC of resuscitation.
Airway and Breathing
Controversy exists concerning the appropriateness for rapid sequence intubation in the field by
paramedics.
5
Indications for intubation include: decreased level of consciousness, increased risk of aspiration, as
well as concern for hypoxemia and hypercapnia. Sometimes these patients must be intubated and sedated simply to
allow further diagnostic studies. Patients with TBI have a 5-6% incidence of an unstable cervical spine injury.
6
Risk
factors include a motor vehicle accident and GCS < 8. Therefore, all attempts at intubation should include in-line
neck stabilization to decrease the chance of worsening a neurological injury. In patients with known cervical spine
injury the use of videolaryngoscopy may reduce movement and improve safety. The initial ventilation parameters
should include 100% oxygen; arterial carbon dioxide should be maintained in the low normal range (35 mmHg).
Circulation
The goal of resuscitation in any trauma patient is to establish adequate circulation so that organ perfusion
may be maintained. In the setting of TBI, a common misconception is that the patient should be run dry in order to
minimize cerebral edema. Isotonic intravenous fluid should be administered as necessary to restore intravascular
volume and avoid hypotension. The goal is to maintain cerebral perfusion pressure (CPP) in the range of 60 to 70
mmHg, as recommended by the updated guidelines from the Brain Trauma Foundation in 2007. Hypertonic fluids,
such as 3% saline, may be useful in this setting, although there is insufficient evidence to justify its routine use.
7

Vasopressors and inotropes may be needed. In the absence of ICP monitoring, MAP should be maintained in the 70
to 80 mmHg range. Other systems must be surveyed to rule out potential causes of systemic hypotension.
Diagnosis and Monitoring
These should include neurologic exam, CT of head, trauma survey, hematocrit, electrolytes, toxicology,
and coagulation studies. Advanced monitoring might include monitoring of ICP (e.g. GCS<8), jugular venous
oxygen saturation,, tissue PO
2
(LiCox), and microdialysis catheter. Although ICP monitoring is considered standard
monitoring for patients with severe TBI, a recent randomized controlled trial conducted in South American
comparing ICP monitoring Vs imaging and clinical exam failed to demonstrate a difference in outcome.
8
However,

433
Page 2
other non-randomized studies are supportive of ICP monitoring
9
and enough doubts have been expressed
10
about the
generalizability of the study that the practice will likely continue, at least in North America. Monitoring of brain
tissue PO
2
has been shown to be superior to ICP monitoring in the detection of cerebral ischemia, but its impact on
outcome remains controversial.
11,12
A multi-centered randomized controlled trial examining the impact of brain
tissue oxygen monitoring on outcome in patients with TBI is currently underway.( Brain Tissue Oxygen Monitoring
in Traumatic Brain Injury (BOOST 2) ClinicalTrials.gov:NCT00974259)

Management Principles
The principles are to optimize cerebral perfusion, avoid ischemia, and prevent secondary insults including
seizure. CPP can be optimized by controlling ICP using osmotic therapy (mannitol or hypertonic saline), and
maintaining mild hyperventilation or normoventilation. 2% hypertonic saline can be administered via a peripheral
line, but higher concentrations (3%, 7.5%, 14.6% and 23.5%) must be infused via a central line. No randomized
studies have demonstrated a difference between mannitol and hypertonic saline. Both are efficacious in decreasing
ICP, but increasingly concentrated hypertonic saline is given as a bolus therapy. The presence of coagulopathy in
TBI is an indicator of poor prognosis, and must be treated vigorously. Systemic hypothermia can ameliorate an
elevated ICP, but may aggravate coagulopathy, the presence of which should prompt an aggressive warming of the
patient.
Glycemic Control
The development of hyperglycemia in patients with severe TBI is associated with poor prognosis.
However, there is evidence that patients with severe brain trauma may develop hyperglycolysis in the injured areas,
with increased glucose consumption. Thus while it is prudent to treat hyperglycemia in patients with TBI, caution
must be exercised to avoid hypoglycemia, and a reasonable goal would be 140 mg%, consistent with recent
guidelines issued by American College of Physicians.
13
Crystalloid vs. Colloid
Despite the theoretical advantage of colloid in trauma, there is no clinical evidence to support its use in
TBI. In a subgroup analysis of patients with brain trauma enrolled in the SAFE trial, the mortality rate was
significantly higher in the 4% albumin group compared to the saline group
14
Thus normotonic or isotonic crystalloid
is the preferred fluid in patients with TBI, and the most appropriate colloid to be used is blood when indicated.
Regarding blood transfusion, no current guideline exists on the threshold in patients with TBI. Although a
restrictive strategy (Hct of 21) is associated with better outcome in critically ill patients, patients with TBI have not
been specifically studied.

Hypothermia
Hypothermia can be used to treat refractory elevation of ICP, but thus far clinical trials to improve outcome
have been negative, both in adult and the pediatric population.
15,16

Barbiturates and Propofol
Barbiturates may be used as an adjunct to other therapy for controlling ICP. In addition, barbiturates may
have an antioxidant effect, although the use of barbiturate coma is associated with immunologic suppression, with
increased risk of pneumonia and sepsis. Propofol may function in a similar manner to barbiturates by decreasing
cerebral metabolic rate and cerebral blood volume. Because of its relatively quick off-set time, it has largely
superseded barbiturates for the purpose of ICP control. One should be aware of the potential of propofol infusion
syndrome, which carries significant morbidity and mortality, and particularly in children.
17

Use of Steroids
Steroids have profound anti-inflammatory actions, and can reduce cytotoxic edema. However, results
from CRASH trial indicated that, not only does steroid show no benefit in brain trauma, it quite possibly increases
mortality, because of increased incidence of infection, particularly pneumonia.
18

Decompressive Craniectomy
Decompressive craniectomy is increasingly employed early to treat elevated ICP refractory to medical
treatment, although its efficacy in improvement of outcome is being debated. A recent multi-centered randomized
trial using an ICP of 20 mmHg as a threshold showed that, although ICP is decreased, there is no difference in
mortality and an increase in the proportion of patients with poor outcome.
19
However, the sample size is small, and

433
Page 3
many suggest that 25 mmHg is a more appropriate threshold for decompressive craniectomy.
20
A European trial
(RESCUEicp) has been underway since 2006 and should achieve the target of 400 patients this year.
21

ANESTHETIC MANAGEMENT
Patients with TBI may require emergent intracranial or extracranial surgery, or non-emergent extra-cranial
surgery.

Emergent Surgery
Trauma patients will probably have other systemic injuries which need to be assessed and addressed.
Patients may demonstrate Cushings response of hypertension and bradycardia which signifies brainstem
compression form raised intracranial pressure. Severe hypovolemia may be masked by this hypertensive response.
In adults, isolated brain injury generally does not result in systemic hypotension, although in small children scalp
blood loss alone can cause hypotension. Appropriate monitoring must be established and must also take into account
the immediate need for surgical decompression. In addition to standard monitors, an arterial catheter is highly
desirable. Intravenous anesthetics are appropriate when there is a concern for cerebral edema and an elevated ICP.
Volatile anesthetic agents may be used if a tight brain is not a concern. Nitrous oxide should probably be avoided .
However, choice of anesthetic agents has not been shown to have an effect on neurologic outcome.
22

Non-emergent
Patients who have sustained traumatic brain injuries frequently have other injuries, especially fractures
requiring operative fixation. The timing of surgery in these patients remains a controversial issue.
23
One must
balance the need for operative fixation of these fractures to decrease the incidence of complications related to
immobility such as atelectasis, pneumonia, and venous thromboembolism against the risks of performing surgery in
patients with unstable head injuries.
In the absence of good evidence, the following recommendations provide a conservative approach to
management of these patients: 1) Uncontrolled intracranial hypertension should preclude all but emergent surgery;
2) Patients with an abnormal head CT scan should have intracranial pressure monitoring in the OR, particularly for
long-duration surgeries in the first 48 hours after injury; 3) Consideration should be given to advanced
neuromonitoring including: transcranial Doppler, jugular bulb oximetry and brain tissue oxygenation; 4) Surgery
should be terminated and a head CT should be obtained should ICP become unstable.

OUTCOME
Overall, the outcome of patients with severe traumatic brain injury has continued to improve over the last
30 years. Most authorities contribute this to improvements in overall trauma care and critical care as opposed to
specific interventions. The practical approach has recently been reviewed.
24

References:
1. Lefering R, Paffrath T, Linker R, et al. Head injury and outcome- what influence do concomitant injuries
have? J Trauma 65: 1036-44, 2008.
2. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on
Neurotrauma and Critical Care. Guidelines for the management of severe traumatic brain injury.24:
Supplement S1-S106, 2007.
3. Bulger, E.M., et al., Management of severe head injury: institutional variations in care and effect on
outcome. Crit Care Med,30(8): p. 1870-6, 2002.
4. Chesnut RM. Care of central nervous system injuries. Surg Clin North Am. 87(1):119-56, 2007..
5. Davis, D.P., et al., The effect of paramedic rapid sequence intubation on outcome in patients with severe
traumatic brain injury. J Trauma 54(3): p. 444-53, 2003.
6. Holly, L.T., et al., Cervical spine trauma associated with moderate and severe head injury: incidence, risk
factors, and injury characteristics. J Neurosurg, 96(3 Suppl): p. 285-91, 2002.
7. Bulger EM, Jurkovich GJ, Nathens AB, et al. Hypertonic resuscitation of hypovolemic shock after blunt
trauma. Arch Surg 143: 139-148, 2008.
8. Chesnut RM, Temkin N, Carney N , et al. A trial of intracranial-pressure monitoring in traumatic brain
injury. N Engl J Med 367: 2471-81, 2012.

433
Page 4
9. Farahvar A, Gerber L, Chiu Y, et al. Increased mortality in patients with severe traumatic brain injury
treated without intracranial pressure monitoring. J Neurosurg 117: 729-734, 2012.
10. Hutchinson PJ, Koliass AG, Czosnyka M, et al. Intracranial pressure monitoring in severe traumatic brain
injury should not be abandoned on the basis of recent evidence..Editorial. BMJ 346: f1000, 2013.
11. Maloney-Wilensky E, Gracias V, et al. Brain tissue oxygen and outcome after severe traumatic brain
injury: a systematic review. Crit Care med 37: 2057-2063, 2009
12. Martini RP, Deem S, Treggiari MM. Targeting brain tissue oxygenation in traumatic brain injury. Respir
Care 58: 162-169, 2013.
13. Qaseem A, Chou R, Humphrey LL, et al. Inpatient glycemic control: best practice advice from the Clinical
Guidelines Committee of the American College of Physicians. Am J Med Qual. Published online May 23,
2013.
14. SAFE Study investigators. Saline or albumin for fluid resuscitation in patients with traumatic brain injury.
N Engl J Med 357: 874-884, 2007.
15. Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury.
N Engl J Med 344:556-563, 2001.
16. Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia after traumatic brain injury in children. N Engl J
Med 358: 2447-56, 2008.
17. Otterspoor LC, Kalkman CJ, Cremer OL. Update o n the propofol infusion syndrome in ICU management
of patients with head injury. Curr Opin Anaesthesiol 21:544-551.
18. CRASH trial collaborators. Final results of MRC CRASH, a randomized placebo-controlled trial of
intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 365: 1957-1959, 2005.
19. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N
Engl J Med 364: 1493-1502, 2011.
20. Sahuquillo J, Martinez-Ricarte F, Poca M-A. Decompressive craniectomy in traumatic brain injury after the
DECRA trial. Where do we stand? Curr Opin Crit Care 19: 101-106, 2013.
21. Hutcinson PJ, Kirkpatrick PJ. Craniectomy in diffuse traumatic brain injury. N Engl J Med 365: 375, 2011
22. Grathwohl KW, Black IH, Spinella PC, et al. Total intravenous anesthesia including ketamine versus
volatile gas anesthesia for combat-related operative traumatic brain injury. Anesthesiology 109: 44-53,
2008.
23. Morshed S, Miclau III T, Bembom O, et al. Delayed internal fixation of femoral shaft fracture reduces
mortality among patients with multisystem trauma. J Bone Joint Surg Am. 91: 3-13, 2009.
24. Kolias AG, Guilfoyle MR, Helmy A, et al. Traumatic brain injury in adults Pract Neurol 0: 1-8, 2013.

Disclosure

115
Page 1
Neurologic Complications of Neuraxial Anesthesia in Obstetrics
David Wlody, M.D. Brooklyn, New York
The increasing use of neuraxial anesthesia in obstetrics has unquestionably led to decreases in maternal morbidity
and mortality associated with general anesthesia. However, this has been accompanied by subsequent increase in
the number of complications of regional anesthesia. While some of these complications may be mild and self-
limited, others may lead to permanent neurologic injury or even death. In this presentation, the risk factors and
underlying pathophysiology of the neurologic complications of regional anesthesia will be described, with the dual
goals of permitting the quantitation of the risk of neurologic injury in patients receiving neuraxial anesthesia, as well
as describing techniques designed to decrease the risk of those complications. The obstetric nerve palsies will be
described, with the goal of enabling the practitioner to distinguish those deficits from those due to regional
anesthesia. Finally, a review of diagnostic studies for evaluating neurologic deficits will enable the anesthesiologist
to choose a tool that can identify lesions requiring urgent intervention, those in which intervention is not indicated,
and to utilize these tools to determine the prognosis of a neurologic deficit.
Incidence-Studies in the obstetric population have demonstrated a consistently low risk of significant neurologic
injury after neuraxial anesthesia. In a prospective study, 8150 French anesthesiologists reported two peripheral
neuropathies and no serious sequelae in 5640 obstetric spinal anesthetics. In almost 30,000 epidurals, there were no
neurologic sequelae. (1) A retrospective postal survey and national registry search of complications of obstetric
neuraxial block in Sweden from 1990-1999 demonstrated that the risk of serious complications was 1:25,000 for
both spinal and epidural anesthesia. (2) The third National Audit of the Royal College of Anaesthetists estimated
that the incidence of permanent neurologic injury caused by obstetric neuraxial anesthesia ranged from 0.3 to 1.2 per
100,000 anesthetics. (3)
Infectious complications-overview-Infection after neuraxial anesthesia is much more common in elderly,
immunocompromised patients than in the obstetric population. Nevertheless, the ASA Closed Claims Project
revealed that 46% of all obstetric anesthesia claims filed from 1980-1999 involved infectious complications. (4) It
is clear that common anesthetic practices and lapses in operator technique can have a significant impact on the
development of these complications.
Infectious complications-Risk factors and prevention-In a 2008 review of neurological infection after neuraxial
anesthesia, Reynolds illustrated the difficulty of identifying risk factors for infection in the obstetric population. The
incidence of meningitis after spinal anesthesia was 1:39,000, and that of epidural abscess after epidural anesthesia
was 1:303,000. It was impossible to identify risk factors for infection due to the small number of cases. (5) In the
surgical literature, patient age, immunocompromise, and prolonged epidural catheterization have been identified as
risk factors for epidural abscess. (6) Spontaneous epidural abscess unrelated to epidural anesthesia has also been
reported and should be considered, as should coincidental community-acquired meningitis.
Hand hygiene is an integral part of infection control in the health care setting. Appropriate hand washing with an
antimicrobial soap containing alcohol will decrease the bacterial inoculum should a glove be punctured during the
procedure. Rings and wristwatches should be removed prior to hand washing.
Appropriate skin preparation is essential to the prevention of neuraxial infection. Numerous studies have shown the
superiority of chlorhexidine-alcohol to povidone-iodine in reducing growth of staphylococcus aureus, and in the
prevention of central line associated infections. (7-9)

Chlorhexidine is not inactivated in the presence of blood, and
its penetration of the skin gives it a prolonged duration of action, and effectively kills bacteria within hair follicles
and sebaceous glands. While the package insert for chlorhexidine-alcohol states that it is not to be used prior to
lumbar puncture (10), both the ASA (11) and ASRA (12) have recommended the routine use of chlorhexidine-
115
Page 2
alcohol solutions. Following the manufacturers instructions to allow the solution to dry for two to three minutes after
application can further minimize any risk of toxicity of chlorhexidine.
Wearing a facemask results in a marked reduction in the bacterial contamination of a surface in close proximity to
the upper airway. ASA and ASRA recommend the routine use of a face mask during neuraxial anesthesia, and this
is also a requirement of the CDC. (13) Two separate outbreaks of meningitis in five obstetric patients receiving
neuraxial anesthesia have been described by the CDC. (14) Three women in New York who received CSEA from
the same anesthesiologist were found to have the identical strain of streptococcus salivarius, a common
nasopharyngeal organism. While the anesthesiologist reported wearing a mask during the procedures, the hospital
allowed unmasked visitors to freely enter labor rooms during epidural placement. In Ohio, two women received
spinal anesthesia from the same anesthesiologist, who routinely performed neuraxial procedures without a mask; one
of these women died. The causative organism in both cases was a strain of s. salivarius that was genetically
identical to an organism cultured from the anesthesiologists nasopharynx. The need for the operator to wear a
mask during neuraxial procedures cannot be overemphasized. Requiring any other personnel in the labor room
during the neuraxial procedure to wear a mask, including family members, should be considered as well.
The integrity of the epidural infusion system must be maintained at all times; this is of particular importance in
patients receiving postoperative analgesia on the postpartum ward, where the level of surveillance for breaks in
sterility may not be as great as in a labor and delivery unit. Disconnections and reconnections should be minimized,
and catheter removal should be seriously considered in the setting of an unwitnessed disconnection.
ASA suggests consideration of the use of in-line bacterial filters in the setting of long-term epidural catheterization,
although the ability of these filter to prevent catheter tip colonization and neuraxial infection is unproven. (15-18)
Clinical aspects of infectious complications-The two major infectious complications of neuraxial anesthesia are
meningitis and epidural abscess. While there may be some overlap in their clinical presentations, they differ
significantly in their incidence, risk factors, microbial etiology, pathophysiology, and treatment.
Meningitis-The frequent clustering of cases of meningitis after neuraxial anesthesia, which suggests a unique
causation, (e.g. a practitioner using poor sterile technique), makes the task of estimating the incidence of infection a
difficult one. Older surveys and case reports may reflect obsolete practices; multi-institutional surveys may reflect a
wide range of clinical practices that influence the risk for infection. A review of large-scale nationwide surveys may
be useful in determining the risk of meningitis. In a Swedish survey of complications after neuraxial anesthesia, the
incidence of meningitis after spinal block was 1;53,000; a cluster of four cases in a single institution clearly skewed
the results. (2). The Third National Audit Project of the Royal College of Anesthetists identified three cases of
meningitis in over 700,000 neuraxial anesthetics, performed for obstetric, surgical, and chronic pain indications. (3)
Much of our knowledge of the clinical presentation of anesthesia-related meningitis is based on case reports.
Reynolds identified 38 cases of meningitis in obstetric patients that received neuraxial anesthesia; in all but two
cases the anesthetic was determined to be the causative factor. (5) The clinical presentation is not unlike that of
meningitis seen in other settings, with headache, nausea, fever, meningeal signs, and alterations in consciousness
appearing hours to several days after anesthesia. Notably, meningitis has been confused with PDPH, one of these
patients having received two epidural blood patches.
A practitioner confronted by a patient developing meningitis after neuraxial anesthesia would understandably
consider the possibility that this was unrelated to the anesthetic procedure, and that the development of meningitis
was coincidental. However, the organisms responsible for community-acquired meningitis are only rarely found in
obstetric patients. Most often, meningitis seen in the setting of neuraxial anesthesia is caused by alpha-hemolytic
streptococcus, typically streptococcus salivarius, an organism found in both the nasopharynx and the vagina.
Epidural abscess-The great majority of epidural abscesses are unrelated to neuraxial anesthesia, usually a result of
hematogenous seeding of the epidural space from a distant infection. The most common risk factors are diabetes,
trauma, intravenous drug abuse, and alcoholism, i.e. conditions that predispose to immune suppression. (19)
Bacterial colonization of epidural catheters is surprisingly common; in one study, 5.8% of patients receiving
postoperative epidural analgesia for an average of five days had positive catheter tip cultures, 75% of which were
staphylococcus epidermidis. None of these patients developed an epidural abscess. (20) It is difficult to describe a

115
Page 3
true incidence of epidural abscess in the obstetric population, but it appears to be extremely low; in Moens study,
one case of epidural abscess was identified in 200,000 obstetric epidurals (2), and in the Royal College survey, one
case of epidural abscess was identified in 161,000 obstetric patients receiving epidurals. (3)
Kindler described the clinical presentation of 42 cases of epidural abscess after epidural anesthesia in both surgical
and obstetric patients. (21)

Back pain and fever were seen in over 90% of patients. Leukocytosis was common, and
the erythrocyte sedimentation rate and C-reactive protein levels were elevated in all patients in whom those studies
were obtained. 36% of patients had a risk factor, including diabetes, corticosteroid therapy, and alcoholism.
Staphylococcus species were the causative organism in 70% of cases. Only 45% of patients had a full recovery;
early surgical decompression after symptom onset was a key factor in improved outcome. A consistent pattern in
case reports of epidural abscess is the poor outcome seen when definitive therapy is delayed. In the setting of
fever, back pain, and leukocytosis, prompt imaging of the spine is essential, especially when lower extremity
neurologic changes are present. MRI is the imaging technique of choice. (22)

Epidural hematoma-The presentation of epidural hematoma is similar to that of epidural abscess, that is, back pain,
sometimes severe, eventually followed by weakness and sensory alterations in the lower extremities. Unlike
epidural abscess, however, which may take days to manifest itself, the signs and symptoms of epidural hematoma
may develop within 12 hours of the initial neuraxial procedure. Thus, epidural hematoma may develop during the
time period in which motor and sensory blockade might be expected to persist after an uncomplicated neuraxial
anesthetic. Recurrence of motor block after partial recovery, or prolonged block in patients at risk for an
epidural hematoma, should serve as a red flag to initiate diagnostic studies to rule out possible spinal cord
compression. As with epidural abscess, optimal results of surgical intervention are seen when decompression
occurs soon after the development of neurologic changes.
Epidural hematoma is exceedingly rare in the obstetric population. In the Royal College survey, there was not a
single incidence of epidural hematoma in 295,000 neuraxial anesthetics. (3) A retrospective study of 505,000
obstetric epidurals administered over a five year period revealed one epidural hematoma. (23) In Moens study, two
patients with HELLP syndrome developed an epidural hematoma, one after subarachnoid block and one after
epidural block, yielding an incidence of epidural hematoma after spinal and epidural anesthesia of 1:50,000 and
1:200,000, respectively. (2) In contrast, the incidence of epidural hematoma in female patients undergoing knee
arthroplasty was 1:3,600. This difference is likely due to combination of the greater use of anticoagulants in this
population, as well as a less compliant epidural space secondary to anatomic changes in the osteoporotic spine. (24)

A common antecedent to most cases of epidural hematoma after neuraxial anesthesia is a disturbance of coagulation.
These disturbances can be divided into two groups: coagulopathy due to underlying disease, and iatrogenic
disturbances due to therapeutic anticoagulation.
Coagulopathy due to underlying disease-The most common disturbance of coagulation seen in pregnancy is
thrombocytopenia, which can be due to gestational thrombocytopenia, pre-eclampsia, or immune disorders. (25)
For many years a platelet count of 100x10
9
/l was considered the minimum acceptable level for performing neuraxial
anesthesia. There is a large and growing experience in the administration of neuraxial anesthesia to obstetric
patients with platelet counts lower than the traditional threshold. Rasmus described 14 parturients who received
epidural anesthesia with platelet counts between 15-99 x10
9
/l with no complications. (26) In a retrospective review
of 119 deliveries in patients with idiopathic thrombocytopenic purpura (ITP), 19 epidurals were placed with platelet
counts of 76-100 x10
9
/l, 6 with platelet counts of 50-75 x10
9
/l, and one with a platelet count of less than 50 x10
9
/l;
no complications were noted. (27)

Nevertheless, patients with thrombocytopenia should be approached with. Pre-eclampsia is a dynamic process; the
pre-eclamptic parturient with a rapidly dropping platelet count is likely at higher risk than a patient with chronic,
stable ITP and an identical platelet count. Clinical markers of coagulopathy such as widespread petechiae suggest
that regional anesthesia is contraindicated. Identification of additional risk factors, such as an abnormality of
platelet function, another disorder affecting coagulation (e.g. hepatic dysfunction), or concomitant antiplatelet
therapy should influence the decision to perform a regional anesthetic. Corticosteroid therapy, should be considered
in patients with ITP as there is usually a significant response to such treatment. (28) There may also be a benefit to
corticosteroid therapy in the patient with HELLP syndrome. (29, 30)

Ultimately, the decision to perform a regional

115
Page 4
anesthetic in a patient with significant thrombocytopenia will be based on a assessment of the risks and benefits in
that patient; a morbidly obese patient with an anticipated difficult airway and a platelet count of 60 x10
9
/l about to
undergo an urgent cesarean section may be a better candidate for regional anesthesia than a fully-dilated grand
multipara with a platelet count of 80 x10
9
/l requesting epidural labor analgesia.
Coagulopathy due to drug therapy-Pregnant patients can receive a variety of medications that affect coagulation.
ASRA has published guidelines for the use of regional anesthesia in patients receiving antithrombotic or
thrombolytic therapy. (31)
Non-steroidal anti-inflammatory agents (NSAIDs) are widely used during pregnancy, for example in the form of
low-dose aspirin administered for the prevention of severe pre-eclampsia in patients thought to be at high risk of
developing the disease. ASRA has concluded that the use of NSAIDs added no significant risk for the development
of spinal hematoma. It was recommended, however, that regional anesthesia be avoided if the patient was receiving
any additional medications affecting coagulation.
Subcutaneous unfractionated heparin is commonly administered to pregnant patients at high risk of developing
DVT. ASRA has concluded that a q12 hour 5000 unit dosing regimen is not a contraindication to regional
anesthesia. The guidelines, however, noted the increasingly widespread utilization of q8 hour 5000 unit dosing, and
indicated that the risk of hematoma in this setting could not be estimated; they recommended enhanced monitoring
for the development of neurologic deficits in patients on this treatment regimen.
Low molecular weight heparin (LMWH) is increasingly used for thromboprophylaxis during. Unfortunately, the
anticoagulant effect of LMWH is not easily quantitated, making it difficult to determine when its effect has waned to
a level at which neuraxial anesthesia is safe; further, reversal of anticoagulant effect with protamine is unpredictable.
ASRA recommends that in patients receiving preoperative, once daily thromboprophylaxis with LMWH, needle
placement should be delayed at least 10-12 hours after a dose; that regional anesthesia be delayed at least 24 hours
after LMWH administration in patients receiving twice daily, therapeutic dosing; that epidural catheters be removed
at least two hours prior to the first postoperative dose when twice daily dosing is planned; and that an epidural
catheter can be maintained during once-daily postoperative dosing, but that catheter removal should not occur any
sooner than 12 hours after a dose.
ASRA recommends that patients chronically anticoagulated with warfarin should not undergo neuraxial anesthesia
until the INR is within normal range; this can be expected to take 4-5 days after warfarin therapy is discontinued. If
warfarin therapy is restarted after delivery, epidural catheters should be removed when the INR is still less than 1.5,
and enhanced surveillance of neurologic function should occur for at least 24 hours after catheter removal.
Chemical injury-A wide variety of drugs have been accidentally injected into the epidural space, including
neuromuscular blockers, thiopental, and potassium chloride. Permanent neurologic injury is rare, but has been
reported, as in the case of a parturient who received an accidental injection of chlorhexidine through an epidural
catheter and was rendered paraplegic. (32). The causes for such errors are numerous, including look-alike drug
ampoules, incorrect labeling of syringes, and the accidental attachment of intravenous lines to epidural catheters.
Drug administration errors can never be eliminated, but appropriate vigilance should minimize their occurrence.
Ampoules should be identified by their labeling, and not by color; syringes should be carefully labeled, preferably
with pre-printed labels; hospital pharmacies should be notified if a potentially neurotoxic agent has labeling similar
to commonly used local anesthetics.
In vitro and animal studies demonstrate that commonly used local anesthetics, when administered in sufficiently
high doses, can be neurotoxic. Toxicity may be enhanced in the setting of pre-existing neurologic injury, such as
diabetic neuropathy. (33) Of the agents that are currently in common use in obstetric anesthesia, hyperbaric
lidocaine for subarachnoid block and 2-chloroprocaine are most commonly associated with such injury.
Hyperbaric lidocaine: Cauda equina syndrome and transient neurologic symptoms-In 1991 six cases of
persistent neurologic injury consistent with the cauda equina syndrome were reported in patients that received
continuous spinal anesthesia. (34, 35) In 5 of these cases hyperbaric lidocaine was administered via a 28 gauge
spinal microcatheter. An initial failure to achieve adequate levels of surgical anesthesia led to the administration of
additional doses of local anesthetic, one patient receiving 285 mg over 30 minutes. Both publications suggested that

115
Page 5
the limited extent of sensory blockade reflected a limited spread of local anesthetic within the subarachnoid space.
It was hypothesized that the limited spread of lidocaine within the subarachnoid space produced localized drug
concentrations that exceeded the level necessary to produce neurotoxicity. In 1992, spinal catheters were withdrawn
from the United States market by the FDA. However, cauda equina syndrome has been reported after a single-
injection spinal anesthetic; should limited spread of sensory block occur after attempted subarachnoid anesthesia, the
risk of producing toxic drug levels in the CSF should be considered before repeating the block.
In 1993 Schneider et al. described 4 patients who reported transient neurologic dysfunction after spinal anesthesia
with 5% lidocaine. (36) The patients received 50-75 mg of lidocaine, and all underwent procedures performed in
the lithotomy position. They all developed postoperative pain in the buttocks radiating to the thighs and calves.
There were no motor or sensory disturbances, and symptoms resolved within several days. Transient neurologic
symptoms (TNS), as this phenomenon has been named, is significantly more common with lidocaine than
bupivacaine. (37) In patients receiving lidocaine, procedures performed in the lithotomy position were more likely
to be complicated by TNS than procedures performed in other positions, and outpatients receiving lidocaine were
more likely to develop TNS than inpatients. Age, gender, and lidocaine dose and concentration did not influence
risk. (37) Pregnancy, however, appears to have a protective effect; the incidence of TNS after postpartum tubal
ligation performed under lidocaine spinal anesthesia was 3% (38), and the incidence after Cesarean section with
lidocaine spinal anesthesia was 0%. (39)
The range of neurologic complications that can follow the use of intrathecal lidocaine has called the continuing
usefulness of that agent into question. Unfortunately, there are few alternative agents that have a similar clinical
profile and less toxicity. Procaine and mepivacaine have a similarly short duration, and are less toxic, but are not
readily available. Removal of glucose from the commercial preparation of lidocaine does not appear to offer any
advantages with respect to neurotoxicity. (40) Drasner made several recommendations regarding the use of
lidocaine, including limiting the total dose of drug to 60 mg and avoiding the use of epinephrine to prolong the
duration of the block. (41)
Local anesthetic neurotoxicity: 2-chloroprocaine- 2-chloroprocaine (2-CP) is unique due to its rapid onset, short
duration, and minimal systemic toxicity due to rapid hydrolysis by plasma cholinesterase. However, 2-CP can
produce significant, prolonged neurotoxicity when large volumes are accidentally injected into the subarachnoid
space. An in vitro study by Gissen et al. suggested that the cause of neural injury was a combination of low pH and
the antioxidant sodium metabisulfite, and not 2-CP itself.

(42) Subsequent to this study, 2-CP was reformulated in a
less acidic solution without sodium metabisulfite. Since that reformulation occurred, there have been no case reports
of 2-CP neurotoxicity, although other factors, such as the more widespread use of fractionated dosing, may be the
reason for this. However, more recent work suggests that the role of bisulfite in producing neuronal injury has been
overstated, and that 2-CP in fact does have intrinsic neurotoxicity (43), although this conclusion has been
challenged. (44) To further complicate the issue, there is a growing experience in the use of preservative-free 2-CP
as a spinal anesthetic without any evidence of neurotoxicity. (45) Nevertheless, we cannot assume that the
accidental intrathecal injection of large volumes and large doses of drugs meant for epidural anesthesia will
be as benign as small doses of 2-CP intended for subarachnoid use. It thus remains critically important that
confirmation of appropriate placement of the catheter within the epidural space be demonstrated before large doses
of local anesthetics are injected, and that fractionated dosing be utilized unless there is an extremely compelling
argument to do otherwise.
Direct injury to the spinal cord- The ASA Closed Claims Project reported two cases in which spinal cord injury
was felt to be related to direct injury to the spinal cord. (4) Reynolds reported 6 patients who underwent spinal or
combined-spinal epidural anesthesia for cesarean section or vaginal delivery and were found to have deficits
consistent with injury to the conus medullaris. (46)

In all cases, injection was reported to be no higher than the L
2-3

interspace. Pain during needle insertion occurred in all cases, but free flow of CSF was noted, and spinal anesthesia
was adequate in most cases. All patients were found to have residual unilateral sensory loss involving several
dermatomes, most had residual foot drop, and three had urinary symptoms. MRI usually revealed a syrinx on the
side corresponding to both the initial paresthesia, as well as the residual deficit. It was concluded that these injuries
were in large part due to puncture at a level higher than the actual termination of the spinal cord.
Reynolds noted a number of possible predisposing factors that may have led to these injuries. (46) An MRI study
has shown that the conus medullaris extends below the L1-2 interspace in over 21% of subjects (47), rendering

115
Page 6
lumbar puncture at that interspace potentially hazardous. Tuffiers line, connecting the posterior superior iliac
spines, and which is widely thought to indicate the L4-5 interspace, may indicate a level ranging up to one
interspace higher. (48) Finally, anesthesiologists are remarkably unsuccessful at identifying lumbar interspaces by
external landmarks alone. One radiologic study demonstrated that the level of lumbar puncture was misidentified in
59% of cases. (49)

Given the uncertainties in determining the site of injection, the L
3-4
interspace should remain the
level of choice for spinal and combined spinal-epidural anesthesia. Pain upon injection of medication into the
subarachnoid space should prompt cessation of injection and repositioning of the needle.

Obstetric nerve palsies-Any postpartum neurologic deficit in a patient that received a neuraxial anesthetic is likely
to be attributed to that anesthetic.. In reality, neurologic deficit after childbirth is most often secondary to
compression or stretching of a peripheral nerve as a consequence of pregnancy or delivery itself. Wong et al. asked
over 6200 women on the first postpartum day if they had leg weakness or numbness. Positive responses led to
formal evaluation by a physiatrist. 0.92% of women were diagnosed with a peripheral nerve injury consistent with
obstetric nerve palsy. (50) Familiarity with and the ability to diagnose the common obstetric nerve palsies is
important, both for medicolegal reasons, as well as to be able to provide the patient with a more accurate prognosis
for recovery. A summary of the most common obstetric nerve palsies follows.
Lumbosacral trunk injury is caused by compression of this structure, consisting of fibers derived from the L4 and
L5 roots, by the fetal head at the sacral ala. Patients present with weakness of ankle dorsiflexion and eversion (foot
drop), and decreased sensation along the lateral aspect of the lower leg and the dorsal surface of the foot. Risk
factors include prolonged labor, a large fetus, and a flattened, wide posterior pelvis with pronounced sacroiliac
joints. (51) In Wongs study the incidence was less than 0.05%.

Common peroneal nerve palsy results secondary to compression of the nerve against the fibular head, usually due
to poorly positioned stirrups when patients are placed in the lithotomy position. It may be difficult to distinguish this
lesion from lumbosacral trunk injury, but normal ankle inversion and normal ankle jerk suggest the more peripheral
lesion. (52)
Meralgia paresthetica is the most common of the obstetric nerve palsies, seen in 0.4% of patients studied by Wong.
This injury is secondary to compression of the lateral femoral cutaneous nerve under the inguinal ligament. There is
a unique pattern of decreased sensation in the superior portion of the anterolateral thigh; motor impairment is absent.
The major risk factor is prolonged hyperflexion of the hips, as in the lithotomy position or when a McRoberts
maneuver is performed.
Femoral nerve palsy was the second most common injury seen in Wongs study. It can result from compression of
the nerve within the pelvis by the fetal head, or by retraction during pelvic surgery. It can also be compressed more
peripherally under the inguinal ligament due to exaggerated hip flexion, but this mechanism is less common. This
lesion presents with quadriceps weakness, perhaps most noticeably during stair climbing. There is commonly a loss
of sensation on the medial calf and foot.
Pre-existing disease and the risk of neurologic injury-Pregnant patients may have any of a variety of pre-existing
disorders that may increase the risk of neurologic complications after neuraxial anesthesia. Hebl et al. reviewed the
experience with 937 patients at the Mayo Clinic who carried a diagnosis of spinal stenosis or lumbar disk disease
and received neuraxial anesthesia over a 15 year period. (53) New neurologic deficits or worsening of pre-existing
deficits were seen in 1.1% of patients, higher than the rate reported in previous studies of the general population.
The presence of preoperative compressive radiculopathy or multiple neurologic diagnoses were risk factors for
postoperative injury; previous spinal surgery, however, did not increase risk. It is not clear that this study is directly
applicable to the obstetric population, however, as 8 of 10 patients with new or worsened deficits were greater than
70 years of age.
Parturients with multiple sclerosis clearly have an increased rate of relapse in the first three postpartum months (54,
55), and there are some who would argue that a neuraxial anesthetic will be implicated should such a relapse occur,
and should therefore be avoided. However, Bader et al. demonstrated that the rate of relapse was no higher in
women who received epidural analgesia than in those who received local anesthetic infiltration alone. (56) Hebl et
al. showed a similar lack of effect of neuraxial anesthesia in patients with multiple sclerosis, as well as a wide
variety of other chronic neurologic diseases. (57)

115
Page 7
Reynolds

points out that patients with diabetes may be vulnerable to neurologic complications of neuraxial
anesthesia on several grounds: they are susceptible to infection, they may have vascular disease, and they may have
a peripheral neuropathy. (58) Hebl et al. retrospectively investigated 567 patients with pre-existing peripheral
sensorimotor neuropathy or diabetic polyneuropathy who underwent neuraxial anesthesia. Two patients suffered a
new or worsening deficit in the postoperative period. (59) While low, this still represented a higher level of
postoperative neurologic deficit than that reported in the general population.
Vascular abnormalities may predispose the parturient to neurologic injury in the postpartum period. An
arteriovenous malformation of the spinal cord can decrease cord perfusion through a steal effect, rupture and
produce an epidural hematoma, or compress the cord via mass effect. In patients with a so-called high take-off of
the artery of Adamkiewicz, perfusion of the lower spinal cord will be dependent upon lumbar branches arising from
the iliac arteries. These vessels can be compressed by the fetal head, resulting in spinal cord ischemia. (58)
Evaluation of neurologic deficit after regional anesthesia-The most important step in evaluating a post-anesthetic
neurologic deficit is to rule out a rapidly expanding mass lesion, such as an epidural hematoma or epidural abscess.
As cannot be overemphasized, the prognosis for recovery decreases dramatically if compression is delayed for more
than eight hours; urgent radiologic investigation should not be delayed if there is any suggestion of spinal cord
compression.
With a non-progressive deficit, investigation can occur at a more leisurely pace. History and physical examination
alone may be sufficient to make the diagnosis of an obstetric nerve palsy. The use of both routine lumbosacral films
and more advanced imaging techniques can be helpful in delineating the anatomic location of an injury.
Electromyography (EMG) can be helpful in defining both the anatomic and temporal location of a lesion, as
denervation potentials do not develop until two weeks after a nerve injury; the presence of such potentials soon after
a regional anesthetic suggests that the injury preceded the anesthetic.
References
!" Auroy Y et al. Anesthesiology 2002; 97:1274-1280.
#" Moen V et al. Anesthesiology 2004; 101:950-959.
$" Cook TM et al. Br J Anaesth 2009; 102:179-90.
%" Davies JM et al. Anesthesiology 2009;110:131-139.
&" Reynolds F. Anesthesiol Clin 2008; 26:23-52.
'" Wang LP et al. Anesthesiology 1999; 91:19281936.
(" Sakuragi T et al. Anesth Analg 1995; 81:555558.
)" Mimoz O et al. Crit Care Med 1996; 24:18181823.
*" Maki DG et al. Lancet 1991; 338:339343.
!+" http://www.carefusion.com/medical-products/infection-prevention/skin-preparation/labeled-warnings.aspx.
!!" ASA task force on infectious complications associated with neuraxial techniques. Anesthesiology 2010;
112:530-545.
!#" Hebl JR. Reg Anesth Pain Med 2006; 31:311-323.
!$" CDC Clinical reminder: Spinal injection procedures performed without a facemask pose risk for bacterial
meningitis. http://www.cdc.gov/injectionsafety/PDF/Clinical_Reminder_Spinal-Infection_Meningitis.pdf.
!%" MMWR Morb Mortal Wkly Rep 2010; 59:65-69.
!&" Abouleish E et al. Anesthesiology 1977 46:351-354.
!'" Bevacqua BK et al. Anesthesiology 1994; 80:1234-1240.
!(" Seth N et al. Paediatr Anaesth 2004; 14:996-1000
!)" James FM et al. Anesth Analg 1976; 55:187190
!*" Reihsaus E et al. Neurosurg Rev 2000; 232:175-204.
#+" Steffen P et al. Journal Clin Anesth 2004; 16:92-97.
#!" Kindler Chet al. Acta Anaesthesiol Scand 1998; 42:614-620.
##" Diehn FE. Radiol Clin N Am 2012; 50: 777-798.
#$" Scott DB et al. Br J Anaesth 1990; 64:537-541.
#%" Usubiaga JE et al. Anesth Analg 1967; 46:440-446.
#&" Kadir RA et al. Semin Thromb Hemost 2011; 37:640-652.

115
Page 8
#'" Rasmus KT et al. Obstet Gynecol 1989; 73:943-946.
#(" Webert KE et al. Blood 2003; 102:4306-4311.
#)" Fujita A et al. Int J Hematol 2010; 92:463-467.
#*" Basaran A et al. J Matern Fetal Neonatal Med; Epub ahead of print 30 July 2012.
http://informahealthcare.com/doi/abs/10.3109/14767058.2012.712571
$+" Woudstra DM et al. Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No.: CD008148. DOI:
10.1002/14651858.CD008148.pub2.
$!" Horlocker TT et al. Reg Anesth Pain Med 2010; 35:64-101.
$#" O'Connor M. Law Med 2012; 19:436-443.
$$" Kalichman MW et al. Anesthesiology 1992; 77:941947.
$%" Rigler ML et al. Anesth Analg 1991; 72:275-281.
$&" Schell RM et al. Can J Anaesth 1991; 38:908-911.
$'" Schneider M et al. Anesth Analg 1993; 76:1154-1157.
$(" Freedman JM et al. Anesthesiology 1998; 89:633-641.
$)" Philip J et al. Anesth Analg 2001; 92:405-409.
$*" Aouad MT et al. Anesth Analg 2001; 92:401-404.
%+" Hashimoto K et al. Reg Anesth Pain Med 1998; 23:444-450.
%!" Drasner K. Anesthesiology 1997; 87:469-472.
%#" Gissen A et al. Reg Anesth 1984; 9:135-44.
%$" Taniguchi M et al. Anesthesiology 2004; 100:85-91.
%%" Lambert DH et al. Anesthesiology 2004; 101:1246-1247
%&" Gonter AF et al. Anesth Analg 2005; 100:573-579.
%'" Reynolds F. Anaesthesia 2001; 56:238-247.
%(" Saifuddin A et al. Spine 1998; 23: 1452-1456.
%)" Hogan QH. Anesthesia and Analgesia 1994; 78: 194-195.
%*" Van Gessel EF et al. Anesthesia and Analgesia 1993; 76: 1004-1007.
&+" Wong CA et al. Obstet Gynecol 2003; 101:279-288.
&!" Donaldson JO. Neuropathy. In Neurology of Pregnancy. 2
nd
ed. London: W.B. Saunders, 1989, pp. 23-59.
&#" Wong CA. Reg Anesth Pain Med 2004; 29:341-351.
&$" Hebl JR et al. Anesth Analg 2010; 111:1511-1519.
&%" Confavreux C et al. N Engl J Med 1998; 339:285-291.
&&" Vukusic S, et al. Brain. 2004;127:1353-1360.
&'" Bader AM et al. J Clin Anesth 1988; 1:21-24.
&(" Hebl JR et al. Anesth Analg 2006; 103:223-228.
&)" Reynolds F. Neurologic complications of pregnancy and regional anesthesia. In Chestnut DH, Polley LS, Tsen
LC & Wong CA (eds.). Obstetric anesthesia: principles and practice. 4th ed. Philadelphia: Elsevier Mosby,
2009, pp. 701726.
&*" Hebl JR, Kopp SL, Schroeder DR, Horlocker TT. Neurologic complications after neuraxial anesthesia or
analgesia in patients with preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy. Anesth
Analg 2006; 103:1294-1299.

Disclosure

119
Page 1
Hail Caesar: Anesthesia for Cesarean Delivery
Lawrence C. Tsen, M.D. Boston, Massachusetts
Cesarean delivery predates the Roman Emperor Julius Cesar (100 BC), who was most likely not born in this
manner. Associated with high maternal mortality until the turn of the 20
th
century, cesarean delivery now accounts
for approximately one third of all births in developed countries;
1
this increase has resulted from improvements in
surgical and anesthetic techniques, diminished use of forceps for extractions, fewer breech and multiple gestation
vaginal deliveries, and greater use of repeat cesarean deliveries. The provision of anesthesia for this method of
delivery is multifaceted, which in turn represents a number of opportunities to influence maternal and fetal care and
outcomes.
PREVENTION OF CESAREAN DELIVERY
The relationship between neuraxial analgesia and the progress and outcome of labor deserves a separate discussion,
however, recent evidence confirms that neuraxial (particularly CSE) analgesia techniques result in shorter, more
comfortable labor compared to systemic techniques without increasing the cesarean delivery rate.
2
Anesthetic
participation can also reduce the incidence of cesarean deliveries [e.g. improving forcep/vacuum analgesia,
increasing the success of multiple gestation vaginal births, reducing fetal head entrapment with intravenous
nitroglycerin, and improving external cephalic version (ECV) success].
The use of ECV for term breech pregnancies (3-5% prevalence) can decrease maternal and fetal morbidity and costs
associated with a breech or operative delivery. Neuraxial techniques improve ECV success by relaxing the
abdominal wall muscles, improving patient comfort, and allowing a more concerted attempt. Even in the setting of a
previously failed ECV attempt without analgesia, spinal anesthesia (lidocaine 45 mg with fentanyl 10 !g) combined
with uterine tocolysis (nitroglycerin 50 !g iv, wait 50 sec) has been associated with a high success rate (83%).
3
Whether utilized for primary or failed ECV attempts, a CSE technique with a short duration spinal anesthetic may be
optimal: the short spinal allows for a timely discharge in the event of a successful version, and if success merits a
trial of labor, or failure results in an operative delivery, the epidural catheter allows for the extension of either
analgesia or anesthesia.
3

ANESTHESIA FOR CESAREAN DELIVERY
The updated Practice Guidelines for Obstetrical Anesthesia from the ASA Task Force on Obstetrical Anesthesia
observe that neuraxial techniques (spinal, epidural, CSE) are associated with improved maternal and fetal outcomes
when compared to general anesthesia (GA), particularly in the presence of high body mass index and airway issues.
4

However, specific anesthetic management should be chosen on a case-by-case assessment of patient, medical,
anesthetic, and obstetric issues.
5

Is there a Preferred Anesthetic Technique?
Complications related to anesthesia still represent the sixth leading cause of peripartum maternal mortality in the
United States.
6
Not surprisingly, these deaths most commonly result from failures in oxygenation and ventilation,
however, these episodes are currently being witnessed more frequently during extubation and postoperative
recovery, rather than with intubation.
6, 7

The estimated case-fatality risk ratio for GA versus neuraxial anesthesia has undergone a significant reduction from
16.7 in 1985-1990 to a non-significant risk ratio of 1.7 in 1991-2002.
8
This change most likely represents two
trends: 1) a reduction in GA use, coupled with improved attention
9
and more successful manipulation (e.g. alternate
airway devices) of the maternal airway, and 2) a growing acceptance of neuraxial technique use in parturients with

119
Page 2
significant comorbidities (e.g. obesity, severe preeclampsia, hematologic and cardiac disease). A review of
anesthetics used for cesarean deliveries performed at the Brigham & Womens Hospital from 1990-1995 indicated a
GA rate of 3.5-7.2%;
10
further rate reductions to less than 1% annually occurred between 2000-2005.
5
This low GA
rate reflected advanced planning and communication with patients, obstetricians and nursing colleagues about
patient characteristics and co-morbid conditions including those associated with a potentially difficult airway or
prolonged neuraxial technique attempts; early patient assessment and prophylactic epidural catheter placements,
even if not utilized for labor analgesia, have been associated with improved outcomes.
4

The combined spinal epidural (CSE) technique may offer the most flexibility in terms of reducing the initial drug
dose (allowing for potentially less hypotension and faster recovery), as well as prolonging the blockade should
operative complications or postoperative pain management issues occur.

Should Newer Local Anesthetics be used?
Potentially reduced recovery times and toxicity profiles have fostered an interest in the newer local anesthetics,
ropivacaine and levobupivacaine. Although established to be safe and acceptable for elective cesarean deliveries,
11,
12
these two local anesthetics may not be significantly less cardiotoxic than bupivacaine when adjusted for potency.
Moreover, because the toxicity of ropivacaine and bupivacaine does not appear to be enhanced in pregnancy,
13

cardiac toxicity should only occur with unintentional large intravascular doses. With the common and more
forgiving use of chloroprocaine 3% and lidocaine 2% for conversion of epidural labor analgesia to cesarean
anesthesia, coupled with proper drug administration practices (e.g. attention to incremental dosing practices, total
dose guidelines, and toxicity symptoms), toxic intravascular levels should be a rare.
Should Lower Doses of Bupivacaine be used?
The dose of local anesthetics has been reduced as a method to potentially obtain less hypotension, faster motor
recovery and discharge times, and improved maternal satisfaction. Such dose reductions may be achieved by using
spinal versus epidural anesthesia, as well as less total local anesthetic; with these changes, reductions in time, costs,
charges, and complications have been realized.
14
When spinal bupivacaine in intermediate to low doses (3-9 mg) are
used, the need for supplemental medications can be significant (up to 40%), and thus a catheter based technique
(CSE) should be used.

Intrathecal Bupivacaine Dose (hyperbaric) Motor Recovery to T10 (min) Notes
15 mg
15
162.1 33.8 7/12 cervical level
12 mg
22
140 16.5 3/16 cervical level
7.5-8.0 mg + 25 mg epidurally
16
146 43.9 CSE
6.6 mg + 3.3!g sufenta
17
110 27 plain; 92 24 hyperbaric CSE

Epidural catheters placed for labor and used subsequently for surgery have a low failure rate following a traditional
epidural versus CSE technique (6% (n = 133) vs. 4% (n = 183), respectively).
18

Can Hypotension be prevented?
Neuraxial-induced hypotension, when severe and sustained, can impair uterine and intervillous blood flow and result
in fetal hypoxia, acidosis, and neonatal depression.
20
Left uterine displacement and treatment or prophylaxis with
vasopressors have reduced the incidence of hypotension with variable success.
21
Preloading with crystalloid has
limited effects on mitigating hypotension, even with large doses (30 mL/kg); more effective is preloading with
colloids, or simultaneously giving rapid crystalloid or colloids coincident (co-loading) with the spinal technique.
Hypotension may also be reduced with the use of smaller spinal local anesthetic doses.
22
Prophylaxis and treatment
of maternal hypotension with phenylephrine, versus in combination with ephedrine or ephedrine alone,
23
is more
effective in improving maternal hemodynamics and fetal acid-base values; this is particularly true when an infusion
target of 100% baseline value is used.
24

What Adjuvant Medications should be used?
Adjuvant medications express a number of benefits, including the ability to reduce the dose and side effects of local
anesthetics. Neostigmine and clonidine are two novel agents undergoing clinical investigation. In women
undergoing elective cesarean delivery, neostigmine in spinal doses up to 100 !g significantly reduced post-operative

119
Page 3
pain with no effect on fetal heart rate or Apgar scores.
27
However, in spinal doses as little as 6.25 !g, a high
incidence of side effects including prolonged motor blockade, nausea, and vomiting have been observed.
28
As a
consequence, the spinal route will most likely be abandoned; however, some promise has been noted with the
epidural route.
29

Clonidine, in spinal and epidural doses varying from 15-50 !g and 50-120 !g, respectively, can prolong analgesia
and decrease shivering; however, mild hypotension and sedation are not infrequent side effects.
30
Currently

clonidine has only one specific neuraxial indication (intractable cancer pain), and a black box FDA warning that
epidural clonidine is not recommended for obstetrical, postpartum, and perioperative pain management. Further
research will most likely advance the clinical use of this drug in the postcesarean delivery setting.

Preservative free morphine sulfate can provide 17-27 h of post-cesarean analgesia. Palmer et al. evaluated the dose
responses to intrathecal
31
and epidural
32
morphine following cesarean delivery. Intrathecally, a comparison of 0.0,
0.025, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg doses observed that 0.1mg produced analgesia comparable to doses as high
as 0.5mg. The incidence of pruritus, but not nausea and vomiting, appeared dose related. In the epidural space, a
comparison of 1.25, 2.5, 3.75, and 5 mg doses observed that the quality of post-cesarean analgesia did not improve
beyond 3.75 mg. Pruritus, nausea and vomiting did not appear dose related. Extended-release epidural morphine
(Depodur) can provide analgesia for 48 hrs with 10 and 15 mg doses; however, caution should be applied to dosing
the epidural catheter with local anesthetic immediately after the Depodur dose, and even up to 1 hour before, as the
maximum plasma concentrations of morphine will be higher.
33

Does a Perfect Cocktail Exist?

The most recent evidence would suggest the following combinations are optimal:

Medication Spinal Epidural
Local Anesthetic Bupivacaine 9-12 mg Lidocaine 2% + Bicarb 8.4% (10 mL/1 mL ratio)
Fentanyl 15-35 !g
34
50-100 !g
Morphine 0.1 mg 3.75 mg

ASSOCIATED ANESTHETIC CONCERNS DURING CESAREAN DELIVERY

Antibiotic Use and Timing

Postpartum infection is 5 to 20-fold greater in those patients delivering by cesarean versus vaginal routes and
remains within the top five causes of pregnancy-related mortality.
35
The traditional practice of administering
antibiotics after infant delivery and umbilical cord clamping originated to prevent fetal exposure to antibiotics.
However, recent studies of antibiotic use prior to cesarean skin incision have observed significantly fewer maternal
infections with no differences in the frequency of neonatal sepsis work-ups or proven sepsis cases.
35
The recent joint
publication from the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics
acknowledges these findings, however, does not explicitly recommend pre-incision antibiotic prophylaxis or
extended spectrum antibiotic coverage.
36
Regardless, the implementation of pre-incisional antibiotic coverage
appears to be increasing, unifying the obstetric practice with other operative settings.

Oxytocin and Uterotonic Agent Use

The administration of oxytocin is associated with significant maternal, fetal, and neonatal adverse events, including
maternal death. The current guidelines for the administration of oxytocin during cesarean delivery are diverse,
empiric, and vague, with nonevidence-based doses of 20-40 IU being advocated. However, adequate uterine
contractions during elective cesarean deliveries in non-laboring women require only small loading doses of oxytocin
(ED 90 = 0.35 IU);
37
a similarly low loading dose (ED 90 = 2.99 IU) is required in laboring women.
38

119
Page 4
Consequently, a lower oxytocin, evidence-based protocol has been advocated:
Oxytocin Protocol for Cesarean Delivery: Rule of Threes
39
3 IU Oxytocin IV Loading Dose (administered by rapid infusion, rather than a bolus, no faster than 15 seconds
40
)
3 Minute Assessment Intervals. If inadequate uterine tone, give 3 IU Oxytocin IV rescue dose.
3 Total Doses of Oxytocin (Initial Load + 2 Rescue Doses)
3 IU Oxytocin IV Maintenance Dose (3 IU/L at 100 mL/h) up to 8 hrs.
3 Pharmacologic Options (e.g. ergonovine, carboprost and misoprostol) if inadequate uterine tone persists

Intra- and Post- partum Hemorrhage

Hemorrhage occurring during or following cesarean delivery is an increasing complication that is associated with
significant maternal morbidity and mortality. The identification of risk factors associated with uterine atony
requiring blood transfusion is of value,
41
to allow preventative and therapeutic measures to be considered, including
the use of intrauterine balloons, pro-coagulation and antifibrinolytic agents, and interventional radiology and blood
bank/hematology consultations.
42

Predictors of PPH Odds Ratio P
Retained Placenta 4.1 (3.1-5.5) < 0.001
Antepartum Hemorrhage 3.8 (3.0-4.8) < 0.001
Multiple Gestation 2.8 (2.2-3.6) < 0.001
Chorioamnionitis 2.5 (1.9-3.3) < 0.001
Hypertensive Diseases of Pregnancy 2.5 (2.1-2.8) < 0.001
Polyhydramnios 2.5 (1.9-3.1) 0.01
Age < 20 1.8 (1.5-2.2) < 0.001
Age > 40 1.7 (1.3-2.2) < 0.001
Cesarean with Labor 1.7 (1.5-2.0) < 0.001
Cesarean without Labor 1.3 (1.1-1.5) 0.002
Vaginal Delivery, Age 20-34 Reference
Post-operative Bliss
Pain, pruritis, nausea/vomiting, and postoperative shivering are the postoperative elements that concern patients.
Pain is optimally handled with neuraxial morphine administered intra-operatively, which provides good analgesia of
long duration. With breakthrough pain, analgesia can be augmented with a non-steroidal agent; Wilder-Smith et
al.
43
observed that the combination of an opioid and NSAID was more effective for post-cesarean analgesia and
preventing sensitization, than the two drugs given individually. Torodol has been listed as being compatible with
breast-feeding by the American Academy of Pediatrics, and has been demonstrated to be effective for post-cesarean
analgesia.
44

Although pruritus following neuraxial blockade has a number of postulated mechanisms and treatments,
45
a direct
antagonist or partial antagonist, such as nalbuphine 4 mg IV, appears to have a greater effect than some other
modalities. Nausea and emesis following cesarean delivery can be difficult to treat; recently cyclizine 50 mg IV has
been observed to be superior to dexamethasone 8mg IV following intrathecal morphine for cesarean delivery.
46

Finally, postoperative shivering can have a number of causes and treatments. Intravenous meperidine 25 mg,
clonidine 150 !g, doxapram 100 mg, ketanserin 10 mg, or alfentanil 250 !g have all been demonstrated to be
effective, although meperidine appears to be the most consistently effective.
47

CONCLUSION

The rapidly changing field of obstetrical anesthesia has placed more emphasis on certain techniques and dosing
regimens. By reflecting on and adopting many of these advances, more parturients (and anesthesiologists) will have
a favorable experience before, during, and after a cesarean delivery.

119
Page 5
REFERENCES

1. Gibbons L, Belizan JM, Lauer JA, et al. Inequities in the use of cesarean section deliveries in the world.
Amer J Obstet Gynecol 2012; 206:331.e1-19.
2. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia given
early versus late in labor. The New England journal of medicine 2005;352:655-65.
3. Cherayil G, Feinberg B, Robinson J, Tsen LC. Central neuraxial blockade promotes external cephalic
version success after a failed attempt. Anesthesia and analgesia 2002;94:1589-92, table of contents.
4. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists
Task Force on Obstetric Anesthesia. Anesthesiology 2007;106:843-63.
5. Palanisamy A, Mitani A, Tsen LC. General anesthesia for cesarean delivery at a tertiary care hospital from
2000-2005: A retrospective analysis and 10-year update. . International journal of obstetric anesthesia 2010;20/1.
6. Cooper GM, McClure JH. Anaesthesia chapter from Saving mothers' lives; reviewing maternal deaths to
make pregnancy safer. British journal of anaesthesia 2008;100:17-22.
7. Mhyre JM, Riesner MN, Polley LS, Naughton NN. A series of anesthesia-related maternal deaths in
Michigan, 1985-2003. Anesthesiology 2007;106:1096-104.
8. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States, 1997-
2002. Obstet Gynecol 2011;117:69-74.
9. Kodali BS, Chandrasekhar S, Bulich LN, Topulos GP, Datta S. Airway changes during labor and delivery.
10. Tsen LC, Pitner R, Camann WR. General anesthesia for cesarean section at a tertiary care hospital 1990-
1995: indications and implications. International journal of obstetric anesthesia 1998;7:147-52.
11. Morton CP, Bloomfield S, Magnusson A, Jozwiak H, McClure JH. Ropivacaine 0.75% for extradural
anaesthesia in elective caesarean section: an open clinical and pharmacokinetic study in mother and neonate. British
journal of anaesthesia 1997;79:3-8.
12. Bader AM, Tsen LC, Camann WR, Nephew E, Datta S. Clinical effects and maternal and fetal plasma
concentrations of 0.5% epidural levobupivacaine versus bupivacaine for cesarean delivery. Anesthesiology
1999;90:1596-601.
13. Santos AC, DeArmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during
continuous intravenous infusion to nonpregnant and pregnant ewes. Anesthesiology 2001;95:1256-64.
14. Riley ET, Cohen SE, Macario A, Desai JB, Ratner EF. Spinal versus epidural anesthesia for cesarean
section: a comparison of time efficiency, costs, charges, and complications. Anesthesia and analgesia 1995;80:709-
12.
15. De Simone CA, Leighton BL, Norris MC. Spinal anesthesia for cesarean delivery. A comparison of two
doses of hyperbaric bupivacaine. Regional anesthesia 1995;20:90-4.
16. Choi DH, Kim JA, Chung IS. Comparison of combined spinal epidural anesthesia and epidural anesthesia
for cesarean section. Acta anaesthesiologica Scandinavica 2000;44:214-9.
17. Vercauteren MP, Coppejans HC, Hoffmann VL, Saldien V, Adriaensen HA. Small-dose hyperbaric versus
plain bupivacaine during spinal anesthesia for cesarean section. Anesthesia and analgesia 1998;86:989-93.
18. Norris MC. Are combined spinal-epidural catheters reliable? International journal of obstetric anesthesia
2000;9:3-6.
19. Davies SJ, Paech MJ, Welch H, Evans SF, Pavy TJ. Maternal experience during epidural or combined
spinal-epidural anesthesia for cesarean section: a prospective, randomized trial. Anesthesia and analgesia
1997;85:607-13.
20. Corke BC, Datta S, Ostheimer GW, Weiss JB, Alper MH. Spinal anaesthesia for Caesarean section. The
influence of hypotension on neonatal outcome. Anaesthesia 1982;37:658-62.
21. Ngan Kee WD. Prevention of maternal hypotension after regional anaesthesia for caesarean section.
Current opinion in anaesthesiology 2010;23:304-9.
22. Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output
monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal
anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856-63.
23. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized double-blinded comparison
of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for
cesarean delivery: the effects on fetal acid-base status and hemodynamic control. Anesthesia and analgesia
2008;107:1295-302.

119
Page 6
24. Ngan Kee WD, Khaw KS. Low-dose spinal anesthesia with low-dose phenylephrine infusions for cesarean
delivery: better but not necessarily best. Anesthesiology 2009;111:210-1; author reply 3-6.
25. Tsen LC, Boosalis P, Segal S, Datta S, Bader AM. Hemodynamic effects of simultaneous administration of
intravenous ephedrine and spinal anesthesia for cesarean delivery. Journal of clinical anesthesia 2000;12:378-82.
26. Sarvela PJ, Halonen PM, Korttila KT. Comparison of 9 mg of intrathecal plain and hyperbaric bupivacaine
both with fentanyl for cesarean delivery. Anesthesia and analgesia 1999;89:1257-62.
27. Krukowski JA, Hood DD, Eisenach JC, Mallak KA, Parker RL. Intrathecal neostigmine for post-cesarean
section analgesia: dose response. Anesthesia and analgesia 1997;84:1269-75.
28. Liu SS, Hodgson PS, Moore JM, Trautman WJ, Burkhead DL. Dose-response effects of spinal neostigmine
added to bupivacaine spinal anesthesia in volunteers. Anesthesiology 1999;90:710-7.
29. Eisenach JC. Epidural neostigmine: will it replace lipid soluble opioids for postoperative and labor
analgesia? Anesthesia and analgesia 2009;109:293-5.
30. D'Angelo R. Should we administer epidural or spinal clonidine during labor? Regional anesthesia and pain
medicine 2000;25:3-4.
31. Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for
postcesarean analgesia. Anesthesiology 1999;90:437-44.
32. Palmer CM, Nogami WM, Van Maren G, Alves DM. Postcesarean epidural morphine: a dose-response
study. Anesthesia and analgesia 2000;90:887-91.
33. Atkinson RL, Drover DR, Clavijo CF, Carvalho B. Prior epidural lidocaine alters the pharmacokinetics of
extended-release epidural morphine (DepoDur) after cesarean delivery. Anesthesia and analgesia 2011;113:251-8.
34. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic
efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a
qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999;91:1919-27.
35. Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging concepts in antibiotic
prophylaxis for cesarean delivery: a systematic review. Obstetrics and gynecology 2009;113:675-82.
36. Gynecologists AAoPaACoOa. Guidelines for Perinatal Care. 2007;6.
37. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a
dose-finding study. Obstet Gynecol 2004;104:1005-10.
38. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for
labor arrest. Obstet Gynecol 2006;107:45-50.
39. Tsen LC, Balki M. Oxytocin Protocols during Cesarean Delivery: Time to Acknowledge the Risk/Benefit
Ratio? International journal of obstetric anesthesia 2011;20 In Press.
40. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin
during elective Caesarean delivery. Br J Anaesth 2010;104:338-43.
41. Bateman BT, Berman MF, Riley LE, Leffert LR. The epidemiology of postpartum hemorrhage in a large,
nationwide sample of deliveries. Anesthesia and analgesia 2010;110:1368-73.
42. Kodali BS. Bloodless trilogy? Anesthesia, obstetrics and interventional radiology for cesarean delivery.
International journal of obstetric anesthesia 2010;19:131-2.
43. Wilder-Smith CH, Hill L, Dyer RA, Torr G, Coetzee E. Postoperative sensitization and pain after cesarean
delivery and the effects of single im doses of tramadol and diclofenac alone and in combination. Anesthesia and
analgesia 2003;97:526-33, table of contents.
44. Lowder JL, Shackelford DP, Holbert D, Beste TM. A randomized, controlled trial to compare ketorolac
tromethamine versus placebo after cesarean section to reduce pain and narcotic usage. American journal of
obstetrics and gynecology 2003;189:1559-62; discussion 62.
45. Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. Journal of clinical
anesthesia 2003;15:234-9.
46. Nortcliffe SA, Shah J, Buggy DJ. Prevention of postoperative nausea and vomiting after spinal morphine
for Caesarean section: comparison of cyclizine, dexamethasone and placebo. British journal of anaesthesia
2003;90:665-70.
47. Sessler DI. Treatment: meperidine, clonidine, doxapram, ketanserin, or alfentanil abolishes short-term
postoperative shivering. Canadian journal of anaesthesia 2003;50:635-7.

Disclosure

125
Page 1
State of the Art Labor Analgesia
Kenneth E Nelson, M.D. Winston-Salem, North Carolina
Introduction
The options for providing labor analgesia have undergone continuous change over the past few decades,
culminating in the current state of the art. Although the available number of topics, issues, and controversies in
labor analgesia are nearly unlimited, the current discussion will be limited to the following three topics:
Maintenance of Labor Analgesia, Controversies, and Techniques.
Maintenance of Labor Analgesia
PCEA/PIEB
Once a catheter has been placed into the epidural space, several options exist to maintain analgesia. The
first methods to be employed was intermittent bolusing on patient request. Once the effect of the initial dose of local
anesthetic began to subside, contraction pain would return and the patient would request more medication, at which
time the anesthesiologist would provide analgesia using another bolus dose of local anesthetic. The obvious
disadvantage to this technique is the relatively large amount of manpower required, and other disadvantages include
non-continuous pain relief, and an intermittent increase in side effects such as hypotension and motor block. The
natural progression in management was to employ infusions to maintain analgesia, but early infusion pumps were
relatively primitive and sometimes unreliable, and data were lacking to guide infusion rates
1
. A large volume of
research was eventually published to help rectify this problem, and it was during this time that the next step in the
evolution of maintenance of labor analgesia occurred: patient controlled epidural analgesia (PCEA)
2
. By this time, a
large amount of experience had accumulated with the use of intravenous PCA, and the same principles were then
applied to PCEA. However, it was soon discovered that there are some important differences between opioid-based
IVPCA for acute postoperative pain and local anesthetic-based PCEA for labor analgesia. Perhaps most
importantly, a basal infusion was found to be very effective with PCEA
3
. Studies continued, however, and further
information has emerged over the past 2 decades suggesting that even more effective methods can be employed,
such as intermittent bolusing at programmed intervals
4
. Pumps are currently being developed in order to exploit this
advantage. The next step might be computerized pumps with a feedback loop that can continuously adjust basal
infusion rates based on average patient requirements, allowing for automatic changes in infusion rates to match the
changing analgesic needs during the course of labor.
Intravenous Opioids
There are several acceptable opioids that can be used to provide labor analgesia. Partial agonists such as
butorphanol have a ceiling effect for respiratory depression, thus making them an attractive choice in laboring
women due to a theoretically lower risk of maternal side effects and neonatal depression
5
. However, the analgesic
effect is likewise limited, and analgesic efficacy has been reported to range from moderate to non-existent. A
commonly used dose of butorphanol is 1mg IV every hour as needed, held when delivery is imminent.
Other opioids without ceiling effect have also been used, and one of the most commonly studied is
meperidine. However, as with all intravenous opioids for labor analgesia, the reported efficacy is variable and often
disappointing. One report even concluded that intravenous opioids for labor analgesia are unethical and medically
incorrect
6
, but the vast majority of studies report at least a moderate effect
7
. Potential drug interactions with
meperidine have contributed to its decline in popularity, including serotonin syndrome in patients taking MAOIs or
SSRIs. Another potential problem with meperidine is accumulation of the metabolite norrmeperidine, which has
been reported to cause convulsions, yet should only be an issue with chronic administration.

125
Page 2
Fentanyl is another commonly used intravenous opioid for labor analgesia, and it has been extensively
studied for this use. It rarely causes allergic reaction, and is relatively free of drug interactions, but has no ceiling
effect for respiratory depression, so must be used with caution on the labor ward. It can have a cumulative effect,
and therefore neonatal respiratory depression is an important concern
8
. Dosage recommendations will be discussed
during the lecture.
Remifentanil is a newer opioid analgesic with a rapid onset and short duration of action. Its unique
pharmacodynamic profile created early enthusiasm for its use in labor analgesia. However, even with the rapid
onset, it is nearly impossible to deliver remifentanil in such a way that the analgesic effect mirrors the time course of
the contraction. In spite of this shortcoming, there are several reports of its successful use in labor analgesia,
including a comparison with fentanyl, which concluded that either one provides moderate analgesia, with
remifentanil causing more maternal oxygen desaturation, and fentanyl causing more neonatal depression
8
. Dosage
recommendations will be discussed during the lecture.

Neuraxial Adjuvants
Although epidural labor analgesia relies primarily on local anesthetic agents (and likely will continue to do
so in the foreseeable future), there are a variety of adjuncts that have proven to be effective in reducing the amount
of local anesthetic required. The common goal of using adjunctive agents is to reduce the amount of local anesthetic
required, thereby reducing side effects such as motor block, hypotension, and toxicity. The list of spinal adjuvants
which have been studied is extremely long, and this discussion will be limited to four: morphine, fentanyl, clonidine,
and neostigmine.
Morphine is a very commonly used adjuvant for postoperative analgesia, and less so for labor analgesia. It
is one of the few spinal adjuvants that has FDA approval. Although several reports of its use for labor analgesia
have shown promising results, its long duration of action means that a longer period of monitoring for respiratory
depression is required
9
. Morphine is also likely to increase the incidence of side effects such as nausea and
pruritus
10
.
Fentanyl is a very commonly used adjuvant for labor analgesia, because it reduces the amount of local
anesthetic required to produce labor analgesia, thereby reducing side effects such as motor block. The most
common side effect is pruritus, and clinically significant respiratory depression is very rare when 20mcg or less is
used.
Clonidine is an alpha-2 agonist which has been shown to be effective in a variety of pain states when used
neuraxially. Early studies showed promise as an adjunct in labor analgesia
11
, but side effects such as maternal
sedation, hypotension, and bradycardia resulted in a black box warning against its use in this setting
12
.
Neostigmine is an inhibitor of the enzyme acetylcholinesterase, and therefore causes acetylcholine to
remain for a longer period of time in the synapse, thus prolonging its action. Acetylcholine is known to be an
important neurotransmitter in the descending inhibitory pathway initiated by opioid receptor activity in the midbrain,
and it is this pathway by which it is believed that neostigmine exerts its analgesic effect. Although intrathecal
neostigmine is effective as an analgesic adjunct to local anesthetics, the nausea that it causes is prohibitive to routine
use
13
. However, when used in the epidural space, it is equally effective as fentanyl, yet does not increase the
incidence of nausea
14
. It is currently being used only as an investigational drug, but shows promise in replacing
lipid soluble opioids as an epidural adjunct to local anesthetic, which would eliminate opioid side effects, and the
need to account for a controlled substance on the labor and delivery ward.

Controversies

Air vs Saline for Loss of Resistance
Either air or saline can be safely used to test for loss of resistance when accessing the epidural space.
Recent debates on the subject have brought to light the list of reasons to avoid air, whereas no such list exists for the
argument against saline. The proponents of air correctly argue that the efficacy and overall incidence of clinically
significant morbidities have not been shown to differ between the two techniques, yet case reports and clinical
experience have amassed a list of reasons to avoid air. Incomplete analgesia due to air pockets in the epidural space
has been reported in pediatric patients
15
. For the same to occur in obstetrics, it would presumably require large
volumes of air, but this is still a potential risk that is avoided by using saline. Venous air embolism
16
and
pneumocephalus
17
are more likely to occur with the use of air, and although a small amount of intravenous air is
rarely a problem, pneumocephalus is the presumed reason that using air for loss of resistance is more likely to cause
headache than when using saline. Finally, nerve root compression
18
and subcutaneous emphysema
19
have been
suggested as additional potential complications. One argument against saline that is now antiquated, but deserves

125
Page 3
mention, is the theoretical possibility of confusing saline for CSF when performing a CSE. In a recent study
comparing air to saline for LOR during the CSE technique, no difference was seen in failure rates, and there were no
cases of saline being confused for CSF
20
. This scientific report concurs with what should be expected under these
circumstances, where saline injected into the epidural space distributes amongst the tissues such as fat and blood
vessels, and is then not available to subsequently aspirate through a spinal needle.

Accidental Dural Puncture: What Next?
The risk of accidental dural puncture (ADP) can be minimized, but not completely eliminated, with an
overall risk of approximately 1 in 200. Once an ADP occurs, there are two basic management choices that can be
made: 1) resite the epidural, or 2) thread a spinal catheter. When choosing a spinal catheter, potential complications
to keep in mind include infectious risk
21
, spinal cord trauma
22
, neurotoxicity
23
, and inappropriate injection through
the catheter
24
. When choosing to resite an epidural, potential complications to consider include inferior analgesia
25

(compared to a spinal catheter), increased headache risk
26
(also compared to the spinal catheter), and the risk of
unexpected high block
27
. The data are mixed on whether the use of a spinal catheter after wet tap can reduce the
incidence of PDPH, but no study has demonstrated an increase in headache risk. The SCORE (Serious
Complications Obstetrics REpository) Project has demonstrated that one of the highest risk scenarios for developing
high spinal is when an epidural that is resited after a wet tap is being dosed for surgery.

Techniques

Combined Spinal Epidural (CSE)
A discussion on state of the art labor analgesia would not be complete without a look at the techniques
involved. Combined spinal epidural analgesia was developed as a way of combining the attributes of both
techniques, i.e. the reliability and fast onset of the spinal combined with the duration and versatility of the epidural.
Although the CSE technique is well established, its role in labor analgesia is still in the process of being defined.
For instance, the use of CSE for patients at high risk for Cesarean delivery remains controversial to some, due to the
untested nature of the catheter immediately after placement. This theoretical concern has not been borne out in
studies, but the thought of a STAT Cesarean delivery in an obese parturient with an untested catheter is enough to
dissuade the most conservative anesthesiologist.

Dural puncture epidural
A recent addition to the obstetric anesthesiologists toolbox is the dural puncture epidural
28
. This
technique seeks to improve the quality and reliability of epidural analgesia by making a small dural puncture during
epidural placement, but without the introduction of spinal medication. Then, the catheter can be fully tested for
efficacy, while small amounts of the epidural drug passes through the dural puncture to improve efficacy. While
still not in widespread use, this technique has been thoroughly investigated and appears to improve analgesia
without increasing side effects.

Ultrasound guided neuraxial block
Advancing technology has made its way onto the labor ward in the form of ultrasound guided epidural
placement
29
. Popular for many years in the arena of peripheral nerve blocks, the use of ultrasound has recently seen
a flurry of activity in the obstetric anesthesia literature.
Beyond the use of hand held ultrasonography, the use of ultrasonic waves emanating from the tip of the
needle has proven successful in animal models, and is expected to reach clinical trials in the future. The hope is that
some day, our current blind approach to the epidural space through loss of resistance will be replaced with
technologically advanced techniques that will allow identification of the tissue planes and epidural space with real-
time visualization.

References
1. Glover DJ. Continuous epidural analgesia in the obstetric patient: a feasibility study using a mechanical
infusion pump. Anaesthesia. 1977 May;32(5):499-503.
2. Gambling DR, Yu P, Cole C, McMorland GH, Palmer L. A comparative study of patient controlled
epidural analgesia (PCEA) and continuous infusion epidural analgesia (CIEA) during labour. Can J
Anaesth. 1988 May;35(3 ( Pt 1)):249-54.
3. Halpern S. Recent advances in patient-controlled epidural analgesia for labour. Curr Opin Anaesthesiol.
2005 Jun;18(3):247-51.

125
Page 4
4. Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of
programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth
Analg. 2006 Mar;102(3):904-9.
5. Atkinson BD, Truitt LJ, Rayburn WF, Turnbull GL, Christensen HD, Wlodaver A. Double-blind
comparison of intravenous butorphanol (Stadol) and fentanyl (Sublimaze) for analgesia during labor. Am J
Obstet Gynecol. 1994 Oct;171(4):993-8.
6. Olofsson C, Ekblom A, Ekman-Ordeberg G, Hjelm A, Irestedt L. Lack of analgesic effect of systemically
administered morphine or pethidine on labour pain. Br J Obstet Gynaecol. 1996 Oct;103(10):968-72.
7. Nelson KE, Eisenach JC. Intravenous butorphanol, meperidine, and their combination relieve pain and
distress in women in labor. Anesthesiology. 2005 May;102(5):1008-13.
8. Marwah R, Hassan S, Carvalho JC, Balki M. Remifentanil versus fentanyl for intravenous patient-
controlled labour analgesia: an observational study Can J Anaesth. 2012 Mar;59(3):246-54.
9. Carvalho B. Respiratory depression after neuraxial opioids in the obstetric setting Anesth Analg. 2008
Sep;107(3):956-61.
10. Vasudevan A, Snowman CE, Sundar S, Sarge TW, Hess PE. Intrathecal morphine reduces breakthrough
pain during labour epidural analgesia. Br J Anaesth. 2007 Feb;98(2):241-5.
11. Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, Kainz C, Germann P, Klimscha W.
Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of
labor: a dose-response study. Anesthesiology. 1999 Aug;91(2):388-96.
12. Missant C, Teunkens A, Vandermeersch E, Van de Velde M. Intrathecal clonidine prolongs labour
analgesia but worsens fetal outcome: a pilot study. Can J Anaesth. 2004 Aug-Sep;51(7):696-701.
13. Nelson KE, D'Angelo R, Foss ML, Meister GC, Hood DD, Eisenach JC. Intrathecal neostigmine and
sufentanil for early labor analgesia. Anesthesiology. 1999 Nov;91(5):1293-8.
14. Ross VH, Pan PH, Owen MD, Seid MH, Harris L, Clyne B, Voltaire M, Eisenach JC. Neostigmine
decreases bupivacaine use by patient-controlled epidural analgesia during labor: a randomized controlled
study. Anesth Analg. 2009 Aug;109(2):524-31.
15. Dalens B, Bazin JE, Haberer JP. Epidural bubbles as a cause of incomplete analgesia during epidural
anesthesia. Anesth Analg. 1987 Jul;66(7):679-83.
16. Naulty JS, Ostheimer GW, Datta S, Knapp R, Weiss JB. Incidence of venous air embolism during epidural
catheter insertion Anesthesiology. 1982 Nov;57(5):410-2.
17. Nafiu OO, Urquhart JC. Pneumocephalus with headache complicating labour epidural analgesia: should we
still be using air? Int J Obstet Anesth. 2006 Jul;15(3):237-9.
18. Overdiek N, Grisales DA, Gravenstein D, Bosek V, Nishman R, Modell JH. Subdural air collection: a
likely source of radicular pain after lumbar epidural. J Clin Anesth. 2001 Aug;13(5):392-7.
19. Viel EJ, de La Coussaye JE, Bruelle P, Sassi G, Bassoul BP, Eledjam JJ. Epidural anesthesia: a pitfall due
to the technique of the loss of resistance to air. Reg Anesth. 1991 Mar-Apr;16(2):117-9.
20. Grondin LS, Nelson K, Ross V, Aponte O, Lee S, Pan PH. Success of spinal and epidural labor analgesia:
comparison of loss of resistance technique using air versus saline in combined spinal-epidural labor
analgesia technique. Anesthesiology. 2009 Jul;111(1):165-72.
21. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric
practice. Br J Anaesth. 1990 May;64(5):537-41.
22. Broadbent CR, Maxwell WB, Ferrie R, Wilson DJ, Gawne-Cain M, Russell R. Ability of anaesthetists to
identify a marked lumbar interspace. Anaesthesia. 2000 Nov;55(11):1122-6.
23. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, Bohner D. Cauda equina
syndrome after continuous spinal anesthesia. Anesth Analg. 1991 Mar;72(3):275-81.
24. Mappes A, Schaer HM. Accidental injection of ether into the epidural space Anaesthesia. 1991
Feb;46(2):124-5.
25. Arkoosh VA, Palmer CM, Yun EM, Sharma SK, Bates JN, Wissler RN, Buxbaum JL, Nogami WM,
Gracely EJ. A randomized, double-masked, multicenter comparison of the safety of continuous intrathecal
labor analgesia using a 28-gauge catheter versus continuous epidural labor analgesia Anesthesiology. 2008
Feb;108(2):286-98.
26. Ayad S, Demian Y, Narouze SN, Tetzlaff JE. Subarachnoid catheter placement after wet tap for analgesia
in labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003 Nov-
Dec;28(6):512-5.
27. Leach A, Smith GB. Subarachnoid spread of epidural local anaesthetic following dural puncture.
Anaesthesia. 1988 Aug;43(8):671-4.

125
Page 5
28. Cappiello E, O'Rourke N, Segal S, Tsen LC. A randomized trial of dural puncture epidural technique
compared with the standard epidural technique for labor analgesia. Anesth Analg. 2008 Nov;107(5):1646-
51.
29. Fanning N, Arzola C, Balki M, Carvalho JC. Lumbar dural sac dimensions determined by ultrasound helps
predict sensory block extent during combined spinal-epidural analgesia for labor. Reg Anesth Pain Med.
2012 May-Jun;37(3):283-8

Disclosure
.
211
Page 1
Strategies to Optimize Post-Cesarean Delivery Analgesia
Brendan Carvalho MBBCh, FRCA. Stanford California
Lecture Synopsis:
This lecture summarizes various multi-modal analgesic options to optimize pain management post-cesarean
delivery. The role of neuraxial opioids, non-steroidal anti-inflammatories, acetaminophen, gabapentin, wound
infiltration, transversus abdominis plane block, and future analgesic options will be reviewed. Analgesic drug
exposure in breastfeeding neonates, and techniques to minimize the transfer of analgesics into breast milk will also
be discussed.
Introduction:
As a result of changing obstetric practices, the cesarean delivery rate in the United States has steadily increased, and
cesarean deliveries now account for over 30% of births annually.
1
Pain after cesarean delivery is moderate to severe
and equivalent to that reported after abdominal hysterectomy.
2
Management of postoperative pain is often
incompletely relieved by current pain management protocols. Pain associated with cesarean delivery is the most
important concern for expectant mothers (Table 1).
3
In an effort to improve pain management in the United States,
the Joint Commission has proposed postoperative pain as the fifth vital sign with a goal of consistently attaining
postoperative pain scores of less than 3 out of 10. However studies suggest that these goals for analgesia are
infrequently attained after cesarean delivery.
4
Good post-cesarean analgesia improves maternal functional ability
and interaction with newborn infants,
5
and effective pain management is an essential element of good postoperative
care.
Table 1: Patient preferences for anesthesia
outcomes prior to cesarean delivery
3

Data are mean standard deviation;
Rank = 1 to
10 from most (1) to least desirable (10) outcome;

Relative value = dollar value patients would pay to
avoid an outcome (e.g., pay $18 of a theoretical
$100 to avoid postoperative pain).
Neuraxial Opioids:
In the United States, most cesarean deliveries are performed with neuraxial anesthesia (spinal, epidural, or combined
spinal-epidural techniques),
6
with the vast majority (85% of elective cesareans) performed with spinal anesthesia.
7

Neuraxial opioids provide superior postoperative pain relief compared to intravenous opioids.
8,9

Neuraxial morphine is currently the gold-standard single-dose neuraxial post-cesarean opioid and provides
prolonged effective analgesia. A meta-analysis found the median time to first post-cesarean analgesic request
following intrathecal morphine was 27 hours (range, 11 to 29 hours).
10
Another meta-analysis of intrathecal
morphine (50-200 mcg) for non-cesarean surgery reported a mean postoperative analgesic duration of 503 min (95%
CI 315 to 641).
11
The duration of analgesia provided by neuraxial morphine is likely dose dependent.
10

Intrathecal vs. epidural morphine: The route of neuraxial morphine administration does not influence the post-
cesarean analgesic efficacy, and both intrathecal and epidural administration provide similar efficacy and duration of
analgesia.
12,13
However, intrathecal morphine administration may result in a faster onset of analgesia, requires a
smaller dose with potentially less neonatal effects, and therefore is considered the preferred route.
Optimal neuraxial morphine dosing: Optimal dosing is difficult to determine because of variability in patient
response to neuraxial opioids. Neuraxial morphine appears to have an analgesic ceiling (50-200 mcg intrathecally
14

Outcome Rank
Relative Value

Pain during cesarean 8.4 2.2 27 18
Pain after cesarean 8.3 1.8 18 10
Vomiting 7.8 1.5 12 7
Nausea 6.8 1.7 11 7
Cramping 6.0 1.9 10 8
Itching 5.6 2.1 9 8
Shivering 4.6 1.7 6 6
Anxiety 4.1 1.9 5 4
Somnolence 2.9 1.4 3 3
211
Page 2
and 2-4 mg epidurally
15
). Larger doses may increase side effects without conferring significant additional analgesic
benefit.
Lipophilic opioids (e.g., intrathecal fentanyl and sufentanil) improve intraoperative analgesia (especially during
uterine exteriorization). Lipophilic opioids have a very quick onset, whereas neuraxial morphine requires 45 to 60
minutes to achieve a peak effect. Intrathecal fentanyl or sufentanil also reduce intraoperative nausea and vomiting,
decrease local anesthetic requirements (less hypotension), and provide a better postoperative transition to other pain
medications during recovery from neuraxial anesthesia for cesarean delivery.
16-18
However intrathecal fentanyl 10-
50 mcg provides a limited duration of post-cesarean delivery analgesia, with a median analgesic duration of 2-4
hours.
10,11
Although greater postoperative pain and opioid requirements have been reported in patients receiving
intrathecal fentanyl and morphine compared to morphine alone,
19
this phenomenon (hypothesized to be due to spinal
opioid receptors being preferentially occupied by fentanyl or because of acute spinal opioid tolerance) is clinically
very subtle and of uncertain significance especially in light of the intraoperative benefit of using intrathecal
fentanyl.
20
A combination of a quick-acting lipophilic intrathecal opioid (e.g., fentanyl 10-20 mcg) with a long-
acting hydrophilic opioid (e.g., morphine 100-200 mcg) is commonly used in the United States,
7
with the aim of
optimizing both intraoperative and postoperative analgesia.
Hydromorphone has an intermediate lipid solubility between that of morphine and meperidine, and a potency ratio
of 3:1 to 5:1 compared to neuraxial morphine.
21
The quality of neuraxial analgesia with hydromorphone after
cesarean delivery appears to be similar to that observed with epidural morphine;
22
although its onset is faster, and
duration is slightly shorter.
23,24

Continuous or patient-controlled epidural analgesia (PCEA) with neuraxial opioids such as fentanyl, sufentanil,
meperidine, hydromorphone or morphine local analgesics has been used with some success post-cesarean
delivery.
25,26
However, these analgesic techniques decrease maternal mobility, increase nursing workload, incur
additional costs, and may increase the risk of catheter-related complications (e.g., hematoma, infection) in
comparison with single-dose neuraxial morphine.
27
PCEA may be worthwhile for patients with high postoperative
analgesic requirements (e.g., chronic pain patients). No consensus currently exists regarding optimal continuous or
PCEA regimens.
Extended-release epidural morphine (EREM): The effective postoperative analgesia provided by neuraxial
morphine shifts the post-cesarean pain experienced from the first day to the second post-operative day, with peak
levels around 36 hours post-delivery.
28
These peak pain levels coincide with maternal mobilization and
breastfeeding activity, and may delay functional recovery. EREM (standard morphine in a multi-vesicular lipid
drug-delivery system, DepoFoam) provides prolonged (up to 48 hours) pain relief and reduces the need for
supplemental analgesics in comparison with standard epidural morphine after cesarean delivery.
29,30
This analgesic
advantage must be weighed against potential disadvantages (e.g., increased side-effects, longer duration of
monitoring for respiratory depression, greater cost). The role of EREM for cesarean delivery analgesia is unclear;
31

selective use in a subset of patients with significant analgesic needs may be beneficial. A single dose of EREM 6-8
mg is recommended after the umbilical cord is clamped. Early pharmacokinetic studies suggest a physicochemical
interaction between epidural local anesthetics and EREM that could negate the sustained-release effect. Epidural
lidocaine top-up (20-35 mL) for cesarean delivery administered 1 hour before epidural EREM administration
increased peak venous morphine levels and increased vomiting, oxygen use and hypotension.
32
No differences in the
pharmacokinetic and pharmacodynamic profiles of EREM were observed when EREM was administered 15, 30,
and 60 minutes after epidural bupivacaine 0.25%.
33

Maternal and neonatal side effects: All opioids have the potential for placental transfer and neonatal effects.
Therefore it is preferable to utilize small intrathecal doses or to administer epidural opioids after cord clamping to
avoid placental transfer. Although neuraxial opioids provide superior post-cesarean analgesia compared to systemic
opioids, certain maternal opioid-related side effects such as pruritus occur more frequently after neuraxial
administration.
34,35
However, patients receiving spinal anesthesia for cesarean delivery rank pain relief above side
effects such as nausea, vomiting or pruritus.
3
The analgesic benefits derived from neuraxial opioids outweigh the
risks of respiratory depression that these agents pose. Prophylactic metoclopramide and 5-HT
3
receptor antagonists
reduce the incidence of postoperative nausea and vomiting and the need for rescue antiemetic treatment in women
receiving intrathecal opioids for cesarean delivery.
36,37
Combination regimens may be more effective than individual
antiemetic agents in treating nausea and vomiting. Opioid antagonists (e.g., nalbuphine 2.5 to 5 mg, naloxone 0.1-
0.2 mg) are considered first choice measure for managing opioid-related pruritus.
38
Antihistamines have been a
popular treatment, however, these agents are less effective than the opioid antagonists.
39
5-HT
3
receptor antagonists
may be useful prophylaxis for neuraxial opioid-induced pruritus after cesarean delivery.
40

211
Page 3
Multimodal Analgesics and Adjuvants:
There is over-reliance on opioids for the management of post-operative pain. Although neuraxial analgesia offers
excellent postoperative analgesia, the majority of women will require additional analgesics post-cesarean.
Multimodal analgesic approaches should be used to augment the analgesic effects of neuraxial opioids.
41

Non-steroidal anti-inflammatories (NSAIDs): A number of studies have shown NSAIDs are very effective for post-
cesarean pain, especially in relieving the visceral cramping pain.
42
The pain relief numbers needed to treat (NNT)
for NSAIDs range from 1.8-2.7. NSAIDs reduce the need for opioid analgesics by 30-50%,
43,44
and decrease
opioid-related side-effects (such as nausea, pruritus, sedation).
45
There are no comparative studies between various
NSAIDs in the post-cesarean patients and selection should be based on availability and breast-feeding compatibility.
COX-2 inhibitors (e.g., celecoxib) have been shown to be effective perioperative analgesics with pain relief NNT of
4.2 (200 mg) and 2.5 (400 mg).
46,47
Although there are potential advantages in using COX-2 inhibitors in this setting
(no effect on platelet function, less risk of bleeding), the routine use of these drugs is not currently recommended
because the two studies evaluating COX2 inhibitors in the post-cesarean population showed limited analgesic
benefit.
48,49
In select patients that are intolerant of NSAIDs, celecoxib should be considered.
Acetaminophen is an effective analgesic with a 10-20% opioid-sparing effect.
50
Recent evidence suggests it has an
additive effect when combined with NSAIDs,
51
therefore the scheduled use of acetaminophen and NSAIDs for 2-3
days after cesarean delivery is recommended. Intravenous preparations are useful in women unable to take oral
medications, and in one study provided analgesia comparable to NSAIDs post-cesarean delivery.
52

Gabapentin and pregabalin have been shown to be useful perioperative analgesics and to have an opioid-sparing
effect in the acute postoperative period.
53,54
In the cesarean delivery setting, a single-dose of gabapentin 600 mg
after delivery decreased acute not persistent pain.
55
However in a follow-up study, no significant analgesic
differences were found with gabapentin 300 and 600 mg compared to placebo.
56
The high umbilical vein to maternal
vein ratio (0.86) of gabapentin limits its use as a pre-emptive drug in this setting, and the relative infant dose of
2.34% and sedation side effects may limit routine use of this agent.
55,57
In selected patients with pain that is difficult
to manage, gabapentin may be a suitable drug.
Ketamine: Sub-anesthetic doses of intravenous ketamine have been shown to reduce opioid use for 24 hours after
non-cesarean surgery.
58
Intravenous doses of 0.5-0.15 mg/kg may have some analgesic benefit after cesarean
delivery under general anesthesia, but is of limited efficacy after cesarean delivery with neuraxial opioids and
multimodal postoperative analgesia.
59
Ketamine may be better suited in selected patients with specific pain
management needs.
Intrathecal and epidural adjuncts (e.g., clonidine, neostigmine) do not appear to offer substantial improvement in
acute postoperative pain over that of neuraxial opioids. Many of these neuraxial adjuvants are also associated with
side-effects that has limited the routine use of these drugs.
60
However, these drugs may decrease pain sensitization
and wind-up and therefore may have a role in reducing persistent post-operative pain.
61

Local anesthetic infiltration: Studies investigating the analgesic benefit of local anesthetic wound infiltration in the
obstetric populations have shown mixed results, and the analgesic effect is generally limited to the early post-
operative period following general anesthesia.
62
Single-dose wound infiltration at the time of surgery is not usually
effective following spinal anesthesia since the local anesthetic effect does not last beyond the duration of the
neuraxial anesthesia (especially if an intrathecal opioid is added). Extended-release bupivacaine has not been
evaluated following cesarean delivery. A continuous irrigation of local anesthetic into the wound can prolong
analgesia and decrease opioid consumption for 48 hour post-cesarean delivery.
62,63
However, limitations of this
catheter-based technique include patient preference, higher cost, potential for wound infection, and a modest
analgesic effect compared to NSAIDs.
64
If continuous irrigation of local anesthetic is utilized, sub-fascial insertion
of the wound catheter appears more effective than subcutaneous placement.
65
Continuous irrigation of local
analgesia into the wound has been proposed as an alternative to an epidural technique for cesarean delivery
analgesia,
66,67
however analgesic efficacy is limited (only provides incisional analgesia) and reliability of this
technique is variable.
62,63,68
Neuraxial opioids provide coverage of incisional and visceral analgesia, and are
particularly effective after abdominal surgery.
69
Local anesthetic infiltration or instillation techniques should be
considered as adjuvants for and not as replacements for neuraxial opioids.
Incisional wound administration of drugs may be more effective than systemic administration. Wound
instillation of diclofenac (300 mg over 48 hours) into a cesarean wound demonstrated a greater opioid-sparing effect
and less postoperative pain than the same dose administered intravenously.
70
Low-dose ketorolac (30 mg over 48
hours) administered into surgical wounds exerted a significant analgesic and anti-inflammatory (decreased
interleukin-6 and interleukin-10) effect after cesarean delivery.
71
Once the biological implications of wound
211
Page 4
administration are better understood, wound administration of drugs (NSAIDs, opioids, ketamine) may become a
valuable analgesic alternative to systemic administration but with less potential side effects.
Transversus abdominis plane (TAP) block at the time of surgery decreases pain and analgesic consumption in
women who undergo cesarean delivery under general anesthesia,
72
and spinal anesthesia without intrathecal
morphine.
73
However minimal additional analgesic benefit is found with TAP blocks in women already receiving
intrathecal morphine with multimodal analgesia.
73,74
Additionally, studies show that intrathecal morphine provides
better post-cesarean delivery analgesia compared to TAP blocks.
73
A proposed indication for TAP blocks is for
rescue analgesia to manage breakthrough pain after offset of spinal anesthesia and to reduce the need for escalating
opioid doses and associated opioid-related side effects following cesarean delivery.
75
Differentiation between
somatic incisional and visceral cramping pain is important before offering TAP blocks since this technique is only
effective for incisional pain. The duration of analgesia after TAB blocks with a single dose of ropivacaine or
bupivacaine is limited to approximately 12 hours. A case series suggests a role for continuous TAP blocks following
cesarean delivery.
76

Future Developments:
Identifying patients at risk for severe postoperative pain: There is significant inter-individual variability in pain
reporting and analgesic use postoperatively. Standardized pain management protocols may lead to under-treatment
of some patients and over-treatment (with increased side effects) of other patients. The ability to identify women at
risk for experiencing greater post-cesarean pain prior to surgery will allow individualized or stratified treatment
plans that are tailored around specific patient needs. (e.g., using larger neuraxial drug doses; adding adjunct
medications (e.g., ketamine, clonidine) with narrow therapeutic indexes and adverse side-effect profiles; allocating
additional resources for patients at risk of severe, postoperative pain).
Demographic (younger patients), psychological (anxiety, depression, pain catastrophizing and coping
styles) and surgical factors (type of surgery: abdominal, thoracic, emergency surgery; indication e.g., cancer
diagnosis; and duration of surgery) are associated with increased postoperative pain.
77
Quantitative sensory tests
(heat, cold, pressure and electrical) of patients basal pain perception prior to surgery have been applied to predict
the magnitude of pain and analgesic requirements after surgery.
78-80
The ideal sensory modality and technique has
not been established. The patients preoperative responses to static quantitative sensory tests are variable with 4-
54% of acute postoperative pain variance predicted.
80
Chronic pain (persistent incisional pain beyond 3 months) is
reported to occur in approximately 10% of patients undergoing cesarean delivery surgery.
81-83
A consistent
association between severe, acute postoperative pain and the likelihood of ongoing persistent incisional pain has
been reported.
82,84,85
Dynamic quantitative sensory tests demonstrate the intensity of an individuals endogenous
nociceptive inhibitory pathway (diffuse noxious inhibitory controls), and the propensity for nociceptive excitation or
sensitization (temporal summation).
79,86
These dynamic tests may better predict an individuals likelihood to
develop persistent postoperative pain than static experimental pain tests which are better suited for acute pain
prediction. Genetics studies of human pain sensitivity have revealed potential to predict post-operative pain;
however since phenotypes (pain perception and analgesic requirements) are multifactorial and subjective, and
genotypic susceptibility is polygenic and complex, it has
proven difficult to evaluate the association between
genotype and phenotype.
86

Measures to attenuate or prevent pain
sensitization may reduce the development of chronic
postoperative pain. Neuraxial blockade and
antihyperalgesic effects of certain analgesics (e.g.,
ketamine, gabapentin and clonidine) may help reduce the
incidence of persistent pain.
87,88
Persistent postoperative
pain is more frequent after cesarean delivery and
hysterectomy performed with general anesthesia compared
to neuraxial anesthesia.
85,89
Additional studies are needed
to provide a better understanding of the mechanisms
involved in the development of persistent pain after
cesarean delivery and refine treatments that can reduce
the occurrence of chronic pain after cesarean delivery.
41

Neonatal drug exposure depends on a number of
maternal, drug and neonatal factors (Figure 1).

211
Page 5
Breastfeeding Considerations:
The majority (>65%) of women in the United States attempt breastfeeding in the early postpartum period.
90

Breastfeeding is promoted as the ideal method of infant nutrition due to both maternal (diminished plasma cortisol,
decreased blood pressure, increased uterine tone, enhanced uterine involution and improved lactation) and neonatal
benefits (better nutrition, greater maternal-neonatal bonding, increased immunity and higher levels of cognitive
development).
91

Neonatal drug exposure is expressed either as absolute infant dose (AID) or relative infant dose (RID):
AID is the drug concentration in milk (derived from maternal drug plasma concentration multiplied by the milk-to-
plasma ratio) multiplied by the volume ingested per day (~150 ml/kg/day). RID is the AID divided by the maternal
dose (mg/kg/day), and is a standardized method relating infant to maternal drug doses. A RID >10% is a level of
concern.
92,93
Most post-operative analgesics are fortunately well below this level. Neonates are sensitive to drugs
due to decreased protein binding, reduced oxidative and conjugative capacity of the liver, decreased renal function
and drug clearance capacity. Medication clearance is highly variable and is significantly decreased with prematurity.
Neonatal drug exposure can be minimized by: utilizing the lowest effective drug dose and most effective route of
administration (spinal vs. intravenous/oral opioids); understanding breastfeeding physiology and drug transfer
(avoiding breastfeeding at peak drug concentrations, breastfeeding before drug administration or withholding
breastfeeding for brief periods); selecting drugs with low breast milk transfer; and utilizing drugs with a long safety
record in this setting.
All opioids enter the breast milk, transfer to the feeding infant and may cause neonatal sedation and opioid-
related side-effects. Morphine has a high milk to plasma ratios (1-4 %) however its low bioavailability (~25%)
limits neonatal exposure.
94
Meperidine is metabolized to active normeperidine with a very long half-life (t !70 h)
and associated with neurobehavioral effects. Meperidine is best limited to small doses (e.g., 12.5-25 mg for
shivering) or avoided in this setting.
95
Fentanyl exhibits low breast milk transfer (RID of 0.9-1.7%), has a short
half-life and is rapidly redistributed. Fentanyl is considered compatible with breastfeeding, and is a preferred
intravenous opioid in the breastfeeding setting.
95,96
Oxycodone and hydrocodone have been used extensively in
nursing women with no reports of significant adverse effects to breastfed neonates, and may be a better oral opioid
than codeine.
95,97

Due to their large molecular size and high degree of protein binding, there is minimal transfer of NSAIDs
to breastfed neonates compared to opioids. The American Academy of Pediatrics and Academy of Breastfeeding
Medicine considers most NSAIDs compatible with nursing mothers.
95,96
NSAIDs with short half-lives, long history
of safe use, and minimal breast milk transfer (ibuprofen RID of 0.6, half-life of 2 hours); ketorolac (RID of 0.2-0.4)
are most suited for breastfeeding women.
93,94
Celecoxib has minimal transfer to breast milk (RID of 0.3) and is
considered safe if breastfeeding.
98
Acetaminophen is a drug with an excellent side-effect profile, a RID of 1-2%, and
no reported cases of neonatal harm. Acetaminophen is considered compatible with breastfeeding, although caution
should be exercised in preterm neonates or neonates with liver dysfunction.
95,96
Gabapentin has a RID of 2.3% and
may result in sedation.
55,57
Caution to be exercised with the routine use of gabapentin especially with high dose
administration. Local anesthetics result in very limited breast milk transfer. Ropivacaine is probably the best suited
long-acting local anesthetic with high protein binding and very low breast milk transfer.
99

In conclusion, there is currently no analgesic wonder drug and post-cesarean delivery pain must be
managed using a multi-modal analgesic approach to optimize early postoperative analgesia and reduce opioid-
related side effects.
100
A combination of intrathecal fentanyl (10-20 mcg), morphine (100-200 mcg), around the
clock NSAIDs (e.g., ibuprofen 600 mg every 6 hours) and acetaminophen (650 mg every 6 hours) should be
administered in all appropriate women undergoing cesarean delivery. The majority of women will require additional
analgesics, and breakthrough pain is best managed with oral opioids (e.g., oxycodone, hydrocodone) while reserving
intravenous opioids for severe or refractory pain. Local anesthetic wound instillation, TAP blocks, EREM and
gabapentin are additional analgesic options in select patients or as rescue analgesia following cesarean delivery. In
the future, standardized treatment plans may be replaced with individual plans that utilize treatments tailored around
specific patient needs.
References:
1. Hamilton BE, Martin JA, Ventura SJ: Births: National Center for Vital Statistics, 2011
2. Fassoulaki A, Gatzou V, Petropoulos G, Siafaka I: Br J Anaesth 2004; 93: 678-82
3. Carvalho B, Cohen SE, Lipman SS, Fuller A, Mathusamy AD, Macario A:
Anesth Analg 2005; 101: 1182-7
211
Page 6
4. Wrench IJ, Sanghera S, Pinder A, Power L, Adams MG: Int J Obstet Anesth 2007; 16: 17-21
5. Hirose M, Hara Y, Hosokawa T, Tanaka Y: Anesth Analg 1996; 82: 1166-9
6. Bucklin BA, Hawkins JL, Anderson JR, Ullrich FA: Anesthesiology 2005; 103: 645-53
7. Aiono-Le Tagaloa L, Butwick AJ, Carvalho B: Anesthesiol Res Pract 2009; 2009: 510642
8. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, Lin EE, Liu SS:
9. Bonnet MP, Mignon A, Mazoit JX, Ozier Y, Marret E: Eur J Pain 2010; 14: 894 e1-9
10. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S: Anesthesiology 1999; 91: 1919-27
11. Popping DM, Elia N, Marret E, Wenk M, Tramer MR: Pain 2012; 153: 784-93
12. Sarvela J, Halonen P, Soikkeli A, Korttila K: Anesth Analg 2002; 95: 436-40
13. Duale C, Frey C, Bolandard F, Barriere A, Schoeffler P: Br J Anaesth 2003; 91: 690-4
14. Palmer CM, Emerson S, Volgoropolous D, Alves D: Anesthesiology 1999; 90: 437-44
15. Palmer CM, Nogami WM, Van Maren G, Alves DM: Anesth Analg 2000; 90: 887-91
16. Dahlgren G, Hultstrand C, Jakobsson J, Norman M, Eriksson EW, Martin H:
Anesth Analg 1997; 85: 1288-93
17. Siddik-Sayyid SM, Aouad MT, Jalbout MI, Zalaket MI, Berzina CE, Baraka AS:
Anesth Analg 2002; 95: 209-13
18. Meyer RA, Macarthur AJ, Downey K: Int J Obstet Anesth 2012; 21: 17-23
19. Cooper DW, Lindsay SL, Ryall DM, Kokri MS, Eldabe SS, Lear GA: Br J Anaesth 1997; 78: 311-3
20. Carvalho B, Drover DR, Ginosar Y, Cohen SE, Riley ET: Int J Obstet Anesth 2012; 21: 29-34
21. de Leon-Casasola OA, Lema MJ: Anesth Analg 1996; 83: 867-75
22. Quigley C: Cochrane Database Syst Rev 2002: CD003447
23. Dougherty TB, Baysinger CL, Henenberger JC, Gooding DJ: Anesth Analg 1989; 68: 318-22
24. Chestnut DH, Choi WW, Isbell TJ: Obstet Gynecol 1986; 68: 65-9
25. Parker RK, White PF: Anesth Analg 1992; 75: 245-51
26. Cooper DW, Garcia E, Mowbray P, Millar MA: Anaesthesia 2002; 57: 266-70
27. Vercauteren M, Vereecken K, La Malfa M, Coppejans H, Adriaensen H:
Acta Anaesthesiol Scand 2002; 46: 85-9
28. Angle PJ, Halpern SH, Leighton BL, Szalai JP, Gnanendran K, Kronberg JE:
Anesth Analg 2002; 95: 741-5
29. Carvalho B, Riley E, Cohen SE, Gambling D, Palmer C, Huffnagle HJ, Polley L, Muir H, Segal S, Lihou
C, Manvelian G: Anesth Analg 2005; 100: 1150-8
30. Carvalho B, Roland LM, Chu LF, Campitelli VA, 3rd, Riley ET: Anesth Analg 2007; 105: 176-83
31. Nagle PC, Gerancher JC: Techniques in Reg Anesth and Pain Management 2007; 11: 9-18
32. Atkinson Ralls L, Drover DR, Clavijo CF, Carvalho B: Anesthesia & Analgesia 2011; 113: 251-258
33. Gambling D, Hughes T, Gould E, Manvelian G: Reg Anesth Pain Med 2009; 34: 316-25
34. Cohen SE, Subak LL, Brose WG, Halpern J: Reg Anesth 1991; 16: 141-9.
35. Terajima K, Onodera H, Kobayashi M, Yamanaka H, Ohno T, Konuma S, Ogawa R:
J Nippon Med Sch 2003; 70: 327-33
36. Mishriky BM, Habib AS: Br J Anaesth 2012; 108: 374-83
37. George RB, Allen TK, Habib AS: Anesth Analg 2009; 109: 174-82
38. Cohen SE, Ratner EF, Kreitzman TR, Archer JH, Mignano LR: Anesth Analg 1992; 75: 747-52
39. Alhashemi JA, Crosby ET, Grodecki W, Duffy PJ, Hull KA, Gallant C: Can J Anaesth 1997; 44: 1060-5
40. Bonnet MP, Marret E, Josserand J, Mercier FJ: Br J Anaesth 2008; 101: 311-9
41. Lavand'homme P: Curr Opin Anaesthesiol 2006; 19: 244-8
42. Huang YC, Tsai SK, Huang CH, Wang MH, Lin PL, Chen LK, Lin CJ, Sun WZ:
Can J Anaesth 2002; 49: 384-7.
43. Pavy TJ, Paech MJ, Evans SF: Anesth Analg 2001; 92: 1010-4.
44. Elia N, Lysakowski C, Tramer MR: Anesthesiology 2005; 103: 1296-304
45. Marret E, Kurdi O, Zufferey P, Bonnet F: Anesthesiology 2005; 102: 1249-60
46. Derry S, Moore RA: Cochrane Database Syst Rev 2012; 3: CD004233
47. Chen LC, Elliott RA, Ashcroft DM: J Clin Pharm Ther 2004; 29: 215-29
48. Carvalho B, Chu L, Fuller A, Cohen SE, Riley ET: Anesth Analg 2006; 103: 664-70
49. Lee L, Irwin, MG, Lim, J, Wong, CK: Anaesthesia 2004; 59: 876-80
50. Remy C, Marret E, Bonnet F: Br J Anaesth 2005; 94: 505-13
51. Ong CK, Seymour RA, Lirk P, Merry AF: Anesth Analg 2010; 110: 1170-9
52. Alhashemi JA, Alotaibi QA, Mashaat MS, Kaid TM, Mujallid RH, Kaki AM:
211
Page 7
Can J Anaesth 2006; 53: 1200-6
53. Ho KY, Gan TJ, Habib AS: Pain 2006; 126: 91-101
54. Zhang J, Ho KY, Wang Y: Br J Anaesth 2011; 106: 454-62
55. Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho JC: Anesth Analg 2011; 112: 167-73
56. Short J, Downey K, Bernstein P, Shah V, Carvalho JC: Anesth Analg 2012; 115: 1336-42
57. Kristensen JH, Ilett KF, Hackett LP, Kohan R: J Hum Lact 2006; 22: 426-8
58. Bell RF, Dahl JB, Moore RA, Kalso E: Cochrane Database Syst Rev 2006: CD004603
59. Bauchat JR, Higgins N, Wojciechowski KG, McCarthy RJ, Toledo P, Wong CA:
Int J Obstet Anesth 2011; 20: 3-9
60. Roelants F: Curr Opin Anaesthesiol 2006; 19: 233-7
61. Lavand'homme P: Int J Obstet Anesth 2010; 19: 1-2
62. Bamigboye AA, Hofmeyr GJ: Cochrane Database Syst Rev 2009: CD006954
63. Liu SS, Richman JM, Thirlby RC, Wu CL: J Am Coll Surg 2006; 203: 914-32
64. Zohar E, Shapiro A, Eidinov A, Fishman A, Fredman B: J Clin Anesth 2006; 18: 415-21
65. Rackelboom T, Le Strat S, Silvera S, Schmitz T, Bassot A, Goffinet F, Ozier Y, Beaussier M, Mignon A:
Obstet Gynecol 2010; 116: 893-900
66. Ranta PO, Ala-Kokko TI, Kukkonen JE, Ohtonen PP, Raudaskoski TH, Reponen PK, Rawal N:
Int J Obstet Anesth 2006; 15: 189-94
67. O'Neill P, Duarte F, Ribeiro I, Centeno MJ, Moreira J: Anesth Analg 2012; 114: 179-185
68. Carvalho B, Clark DJ, Yeomans DC, Angst MS: Anesth Analg 2010; 111: 1452-9
69. Meylan N, Elia N, Lysakowski C, Tramer MR: Br J Anaesth 2009; 102: 156-67
70. Lavand'homme PM, Roelants F, Waterloos H, De Kock MF: Anesthesiology 2007; 106: 1220-5
71. Carvalho B, Lemmens HJ, Ting V, Angst MS: J Pain 2013; 14: 48-56
72. Eslamian L, Jalili Z, Jamal A, Marsoosi V, Movafegh A: J Anesth 2012; 26: 334-8
73. Mishriky BM, George RB, Habib AS: Can J Anaesth 2012; 59: 766-78
74. Costello JF, Moore AR, Wieczorek PM, Macarthur AJ, Balki M, Carvalho JC:
Reg Anesth Pain Med 2009; 34: 586-9
75. Mirza F, Carvalho B: Can J Anaesth 2013; 60: 299-303
76. Bollag L, Richebe P, Ortner C, Landau R: Int J Obstet Anesth 2012; 21: 176-80
77. Ip HY, Abrishami A, Peng PW, Wong J, Chung F: Anesthesiology 2009; 111: 657-77
78. Edwards RR, Sarlani E, Wesselmann U, Fillingim RB: Pain 2005; 114: 315-9
79. Granot M: Curr Opin Anaesthesiol 2009; 22: 425-30
80. Werner MU, Mjobo HN, Nielsen PR, Rudin A: Anesthesiology 2010; 112: 1494-502
81. Kehlet H, Jensen TS, Woolf CJ: Lancet 2006; 367: 1618-25
82. Eisenach JC, Pan PH, Smiley R, Lavand'homme P, Landau R, Houle TT: Pain 2008; 140: 87-94
83. Sng BL, Sia AT, Lim Y, Woo D, Ocampo C: Anaesth Intensive Care 2009; 37: 46-53
84. Vermelis JM, Wassen MM, Fiddelers AA, Nijhuis JG, Marcus MA:
Curr Opin Anaesthesiol 2010; 23: 295-9
85. Nikolajsen L, Sorensen HC, Jensen TS, Kehlet H: Acta Anaesthesiol Scand 2004; 48: 111-6
86. Landau R, Kraft JC: Curr Opin Anaesthesiol 2010; 23: 323-9
87. De Kock M, Lavand'homme P, Waterloos H: Anesth Analg 2005; 101: 566-72
88. Lavand'homme P, De Kock M, Waterloos H: Anesthesiology 2005; 103: 813-20
89. Brandsborg B, Nikolajsen L, Hansen CT, Kehlet H, Jensen TS: Anesthesiology 2007; 106: 1003-12
90. Li R, Zhao Z, Mokdad A, Barker L, Grummer-Strawn L: Pediatrics 2003; 111: 1198-201
91. Pediatrics 1997; 100: 1035-9
92. Ilett KF, Kristensen JH: Expert Opin Drug Saf 2005; 4: 745-68
93. Hale TW: J Hum Lact 1999; 15: 185-94
94. Spigset O, Hagg S: Paediatr Drugs 2000; 2: 223-38
95. Montgomery A, Hale TW: Breastfeed Med 2006; 1: 271-7
96. Pediatrics 2001; 108: 776-89
97. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ: Lancet 2006; 368: 704
98. Hale TW, McDonald R, Boger J: J Hum Lact 2004; 20: 397-403
99. Matsota PK, Markantonis SL, Fousteri MZ, Pandazi AK, Manikis DE, Christodoulopoulou TC, Loizou
MM, Kostopanagiotou GG: Reg Anesth Pain Med 2009; 34: 126-9
100. Rosaeg OP, Lui AC, Cicutti NJ, Bragg PR, Crossan ML, Krepski B: Can J Anaesth 1997; 44: 803-9
Disclosure
Pacira Pharmaceuticals, Funded Research; vTITAN, Stock Options
211
Page 8
217
Page 1
Post Dural Puncture Headache: How to Keep It the Patient's Headache
Robert R. Gaiser, M.D. Mount Laurel, New Jersey
The Problem
Headache remains a major problem to both the obstetrician and the obstetric anesthesiologist. Headache is
one of the most common symptoms encountered in the postpartum period. In a study of 95 postpartum parturients
with a headache lasting greater than 24 hours, 47% were due to tension/migraines, 24% to preeclampsia, and 16%
were PDPHA.(1) When examining obstetric anesthesia claims from the Closed Claims Study, the proportion of
claims filed for PDPHA has not changed from the period before 1990 to the period 1990-2003(2) The third most
common reason for a claim was headache (14% of obstetric claims). The number of claims for headache was more
common than maternal death, back pain, and maternal brain damage. Headache remains a problem even after the
patient is discharged. Hayes, et al, reviewed the records of those parturients who contacted the department after
discharge. Of the 98 parturients who contacted after discharge, 43 complained of headache (44%). Of these, only 4
were felt to be due to PDPHA (all received CSE). Seven of the 43 patients received radiologic investigations; all
were normal.(3) Academic anesthesiologists disclose to patients that headache is the greatest risk of neuraxial
anesthesia with an incidence of 1:100.(4)
Symptoms
The International Headache Society has defined a PDPHA as a bilateral headache that develops within 7
days after lumbar puncture and disappears within 14 days after the lumbar puncture. The headache worsens within
15 minutes of assuming the upright position and disappears or improves within 30 minutes of resuming the
recumbent position.(5). These symptoms are helpful in distinguishing from migraine headaches. PDPHA usually
occurs in the frontal, occipital, or both areas, but also may involve the neck and upper shoulders. Although it
generally occurs within 48 hours of the dural puncture, it can occur later than 3 days in 25% of the cases.(6) In
regard to duration, the largest study is by Vandam and Dripps.(7) They followed 8,460 patients who received
10,098 spinal anesthetics. The needles used were Quincke gauges 16 to 24. They reported that 72% of the
headaches resolved within 7 days and 87% by six months. The persistence of headache beyond 6 months has been
documented and has been successfully treated by epidural blood patch.(8) Duration of the headache is directly
related to the gauge of the needle causing the dural puncture. Accidental dural puncture with a 17-g Tuohy needle
increases the risk (OR = 7) of the patient developing chronic headache, as evaluated 18 months later. An epidural
blood patch reduces the risk of this prolonged complication but does not get rid of it.(9)
Other symptoms include nausea, vomiting, neck stiffness, visual disturbances, and hearing alteration.
Visual disturbances (blurred vision or double vision) are due to dysfunction of the extraoccular muscles from
transient paralysis of the cranial nerves (CN) of the eyes (CN III, IV, and VI) due to traction from downward
displacement of the cranial contents.(10) CN VI is the most frequently affected because of its long intracranial
course. Hearing (CN VIII) is also affected. Alterations in hearing are variable and depend upon the patency of the
adult cochlear aqueduct. If the aqueduct is open, loss of CSF leads to an endolymphatic hydrops which affects the
hair cells of the inner ear.(11)
Incidence
The incidence of accidental dural puncture (ADP) with an epidural needle is 1.5% but the incidence of
headache in the parturient depends upon the type of delivery.(12) The incidence of ADP in patients with prior
history of spine surgery is 2.7%.(13) The incidence of headache with a 16-gauge epidural needle is 88% and is 64%
with an 18-gauge Tuohy needle.(14) See Table
217
Page 2
Etiology
In the central nervous system, there is approximately 150 cc CSF. Of this CSF, 75 cc is located
supraspinally and 75 cc spinally. The production rate of CSF is approximately 0.35 ml/min.(15) It is believed that
PDPHA is due to leakage of CSF though the dural tear. Kunkle showed that in volunteers, removal of 10% of CSF
through a lumbar needle reliably produced a headache that was relieved by replacement with an equal volume
saline.(16) An extradural collection of CSF has been seen on MRI in a patient with a PDPHA.(17)
If the rate of leakage exceeds production, low CSF pressure results in a loss of the cushion effect provided
within the cranium. The decrease in CSF volume results in sagging of the brain in the cranial vault, pulling on the
falx cerebri, cerebral blood vessels and tentorium. In seven patients with positional headache, downward descent of
the brain was seen in five patients.(18) Another hypothesis is cerebral venous dilation. Loss of CSF causes a
decrease in CSF pressure without a decrease in intravenous pressure. The pressure difference causes these veins to
dilate.(19) There is another component to PDPHA. A total of 3730 epidural blocks were performed in 2955
patients.(20) The identification of the epidural space was by loss-of-resistance to either saline or air using a total of
1-5 ml of either substance. In all patients with evident or suspected ADP, a CT scan was immediately obtained.
Although ADP occurred to a similar extent in both groups (2.6% for air and 2.7% for saline), the incidence of
headache was different, 66.7% for air and 9.8% for saline. In the air group, supraspinal intrathecal air bubbles were
found on CT examination in 78% of those with a PDPHA. Air can enter the subarachnoid space with nicking the
dura. The headache from intrathecal air was more rapid in onset and has a shorter duration than a PDPHA. The
entry of air into the intrathecal space when using LORA after a previous dural puncture has been reported.(21) A
meta-analysis comparing loss-of-resistance with air to saline demonstrated no difference in adverse outcome when
used for the obstetric patient.(22) If the provider chooses the preferred medium (air vs saline), there is less attempts,
fewer paresthesias, and fewer ADPs.(23)
Risk Factors
Not all patients who have dural puncture develop a PDPHA. The frequency of PDPHA is inversely
associated with age.(24) A meta-analysis comparing men vs women (excluding obstetric patients) demonstrated that
the odds of developing a PDPHA were significantly lower for men than women (odds ratio 0.55).(25) In a model of
human cadaveric dura, the outflow of fluid was higher when the dura was obtained from a woman.(26)
The greatest influence on the incidence of PDPHA is technique and choice of needle. Technique is
important for the Quincke needle, ensuring the direction of the bevel is parallel to the longitudinal axis of the dural
cylinder. The dura mater is a laminated structure built up from well-defined layers oriented concentrically with no
predominant direction to the fibers.(27) The cells of the arachnoid mater are oriented parallel to the long axis of the
spinal cord and parallel insertion my result in less disruption.(28) For epidural needles, bevel orientation is not as
important. Leakage from puncture with a 18-gauge Tuohy needle is similar whether the puncture is parallel or
transverse.(29) The thickness of the lumbar dura mater varies. The hole created when the needle penetrated a
thinner part of the dura mater resulted in a larger hole and greater leakage than when punctured in a thicker part.
For needle type, size of needle and needle design are important. Smaller needles have a lower incidence of
PDPHA, especially with the Quincke needle. Kang showed the incidence of PDPHA was 9.6% with the 26-gauge
needle and 1.5% with the 27-gauge.(30) Gauge is not as important for the pencil point needle. I feel that some of
the headaches from the pencil point needle are due to advancing the local infiltration needle too far. Absalom
described a case of cord injury when the local infiltration needle was inserted to the hub.(31) Another example
would be the occurrence of a PDPHA following acupuncture for the treatment of back pain.(32) For needle design,
the pencil point needles have a low incidence of PDPHA. Comparing 676 ASA I or II patients undergoing spinal
anesthesia with either a 27-gauge Quincke or 27-gauge Whitacre needle, the incidences of PDPH in the Quincke and
Whitacre groups were 2.7% and 0.37%, respectively.(33) The Practice Guidelines for Obstetric Anesthesia
recommend the use of the pencil-point needles to reduce the frequency of PDPHA.(34) The incidence of PDPHA
may be reduced even further by inserting the stylet prior to removal of the needle.(35)
Another factor affecting the incidence of PDPHA after accidental dural puncture is management of the
second stage. In 33 patients with accidental dural puncture, 23 engaged in active pushing and 10 went to cesarean
section before pushing. 17/23 patients developed a headache in the pushing group and 1/10 in the nonpushing
group.(36) Active bearing down causes a marked increase in cerebrospinal fluid pressure and possibly leads to
greater CSF loss, accounting for the higher incidence in parturients.
A patient with a previous PDPHA is at risk for subsequent PDPHA. In 258 patients who received a repeat
spinal anesthetic, 42 had a previous PDPHA. Of these, 19% developed PDPHA again as compared to an incidence
of 6.9% in those who did not have a previous PDPHA.(37)

217
Page 3
Prevention
Various maneuvers are used to prevent PDPHA and the majority are poorly supported by the literature. A
survey of practicing anesthesiologists in the United States revealed that the majority of hospitals do NOT have
written protocols for the management of unintended dural puncture.(38) Many recommend bed rest to prevent a
PDPHA. A systematic examination of recumbence showed no benefit.(39)
Following dural puncture during attempted epidural analgesia, a subarachnoid (SA) catheter may be passed.
Norris and Leighton failed to note any difference in the incidence or severity of PDPHA with a SA catheter.(40) In
this study, the catheter was pulled at the end of delivery. Ayad studied 115 parturients who had accidental dural
puncture.(41) The patients were randomized into one of three groups: resite the epidural catheter, SA catheter with
removal after delivery, and SA catheter with removal 24 hours after delivery. The incidence of PDPHA was 91.1%
in the resite group, 51.4% in the immediate group, and 6.2% in the delayed group. This data suggest the placement
of a SA catheter after the occurrence of a wet tap and leaving it in for 24 hours may be helpful. Extreme care should
be used when a SA catheter is left in place for 24 hours. A case report discussed a patient who had the catheter
adapter dislodge, resulting in a CSF leak while another presented a patient who developed meningitis.(42) The use
of SA catheters is increasing. An audit of a ten year experience failed to demonstrate a benefit to the intrathecal
catheter.(43) A randomized study of 115 women with ADP who were randomized to intrathecal catheter placement
with leaving it in place for 24 hours or to resiting the epidural was conducted.(44). This important study did NOT
demonstrate an advantage to intrathecal catheters in preventing headache. The only benefit was that approximately
one-third of the patients in the resiting group had a second dural puncture.
A randomized study compared 3 mg of preservative free morphine injected epidurally at delivery and 24
hours later in 50 parturients who had dural puncture. As compared to saline, there was a lower incidence of
headache (12% vs 48%) and a lower need for EBP (0 vs 6). There was also a higher incidence of pruritus in the
epidural morphine group.(45) Consyntropin 1.0 mg has been shown to decrease the incidence of PDPHA following
accidental dural puncture and to decrease the need for EBP.(46) The concerns with the study were the lack of
postulated reason for effectiveness as well as the lack of definition for PDPHA and for need for EBP.

Treatment
The treatment of PDPHA ranges from conservative to invasive. Conservative measures include bed rest,
analgesics, intravenous hydration, and other medications. Caffeine is commonly recommended for PDPHA because
of its ability to increase cerebral vascular resistance, decrease cerebral blood flow, and decrease cerebral blood
volume. The original study examining intravenous caffeine was published in 1978. The authors studied 1932
patients undergoing spinal anesthesia with a 22-gauge Quincke needle.(47) 41 patients developed PDPHA and were
randomized to either intravenous saline or intravenous caffeine benzoate 500 mg. Caffeine had an overall
effectiveness of 85%. To achieve this effectiveness, 2 patients required a repeat dose. There has been no study
examining its effectiveness for accidental dural puncture with an epidural needle. A review concluded that there is
no valid pharmacological rationale for caffeine as a treatment for PDPHA.(48)
It is thought that epidural saline increases pressure in the area and decreases the outflow of CSF. In 15
patients who had a PDPHA following dural puncture with a 25-gauge needle, 30 ml of saline administered
epidurally provided relief in 9/15 patients. No patient who had a PDPHA following dural puncture with a 17-gauge
needle had relief.(49) Epidural saline provides temporary relief that disappears once the saline is absorbed.
In 1960, Gormley reasoned that blood could serve as the sealing material. In his report of 7 cases (one of
which was himself), 2-3 ml of blood injected into the lumbar epidural space at the same level as the dural puncture
was effective.(50) Crawford recommended up to 20 ml of blood, stopping if the patient complains of back or leg
pain. Using this method, he reported 97/98 had complete success.(51) Some practitioners recommend injecting
blood until the patient develops symptoms but a case report of hematoma in one patient and arachnoiditis in another
patient raises a concern with this practice.(52) A recent study upheld Crawfords recommendation of 20 cc for an
EBP.(53) The postulated mechanism for its effectiveness is compression of the thecal space and elevating the
subarachnoid pressure. An EBP was performed in a patient with ICP monitoring failed to detect any change in ICP
after the EBP.(54) Maintenance of the therapeutic effect is attributed to clot preventing further CSF leak.(55)
Blood in the epidural space will spread between 7 and 14 spinal segments. The mean spread of blood is six
segments upward and three segments downward.(56) MRIs performed in two patients after 20 ml of blood being
injected into the lumbar epidural space revealed blood in the upper cervical region.(57) MRI shows the blood patch
as a large extradural collection mainly in the posterior space, with spread to the anterior epidural space as well as out
the intervertebral foramina and into the paravertebral space.(58) Complications of the EBP include back pain
(occurs during the first 48 hours in 35% of patients and persists in 16% of patients with a mean duration of 27
days)(59) and bradycardia(60). A previous EBP is not a contraindication to epidural anesthesia although EBP may

217
Page 4
cause scarring in the space and ineffective anesthesia.(,61) An EBP is contraindicated if the patient is febrile.
During an epidural blood patch, it is possible to inject the blood subarachnoid.(62) The literature concerning this
complication is scant. Subarachnoid injection may result in meningitis, arachnoiditis, or paresthesias. In the first
randomized trial of EBP, 42 patients with PDPHA following lumbar puncture with a 22-gauge Quincke needle were
randomized to conservative treatment or EBP. (63) EBP reduced the severity of PDPHA and resulted in quicker
resolution. In the literature, there are 5 patients who developed cerebral venous thrombosis after EBP. Pregnancy is
associated with a hypercoagulable state and it is unclear if this association of cerebral venous thrombosis with EBP
is valid.(64)
The timing of the EBP is debated. Loeser noted a 71% failure rate if the epidural blood patch was done
within 24 hours of dural puncture as compared to a 4% failure rate if done greater than 24 hours. Subsequent studies
have also noted this finding.(65) The largest series consists of 504 patients. 75% achieved complete relief, 18%
incomplete relief, and 7% no relief.(66) Performing the EBP within 3 days was a risk factor for failure (odds ratio
2.63). Vilming et al questioned when should an EBP be done.(67) According to these authors, an EBP should be
performed after an initial observation period of 24 hours if the patient is symptomatic. This delay increases the
success rate while reducing the suffering of the patients. The optimal time to place an epidural blood patch is >24
hours after development of the PDPHA. This 24 hour delay is supported by a survey of Nordic countries.(68)
Given the improved outcome if the EBP is delayed, one would have to question the prophylactic EBP. A
prophylactic blood patch involves the injection of blood through the epidural catheter before the development of a
headache. 64 parturients with accidental dural puncture with a 17-gauge epidural needle were randomized either to
blood patch through a catheter or to sham blood patch (blood drawn but not injected).(69) There was no difference
between groups in the incidence of PDPHA or in the need for therapeutic blood patch. A Cochrane review did not
recommend prophylactic epidural blood patch and determined that therapeutic EBP to be beneficial.(70)

Conclusion
PDPHA continues to be a problem following neuraxial anesthesia. It is due to a decrease in CSF volume
and is not easily prevented. It is easily treated with an EBP. An EBP performed within the first 24 hours of PDPHA
may decrease its effectiveness.

References
1. Stella CL, et al. Postpartum HA: Is your work-up complete? Am J Obstet Gynecol 2007;196:318e1-e7.
2. Davies JM, et al. Liability associated with obstetric anesthesia. Anesthesiology 2009;110:131-9.
3. Hayes NE, Wheelahan JM, Ross A. Self-reported post-discharge symptoms following obstetric neuraxial
blockade. Int J Obstet Anesth 2010;19:405-9.
4. Brull R, et al. Disclosure of risks associated with regional anesthesia: a survey of academic regional
anesthesiologists. Reg Anesth Pain Med 2007;32:7-11
5. Evans RW, et al. Assessment/prevention of post-lumbar puncture headaches. Report of the Therapeutics
and Technology Assessment Subcommittee of the Academy of Neurology. Neurology 2000;55:909-14.
6. Wang LP Schmidt JF. Central nervous side effects after lumbar puncture. Dan Med Bull 1997;44:79-81.
7. Vandam LD, Dripps RD. Long-term follow-up of patients who received 10,098 spinal anesthetics. Failure
to discover major neurological sequelae. JAMA 1954;156:1486-91.
8. Klepstad P. Relief of postural post dural puncture headache by an epidural blood patch 12 months after
dural puncture. 1999;43:964-6.
9. Webb CAJ. Unintentional dural puncture with a Tuohy needle increases risk of chronic headache. Anesth
Analg 2012;115:124-32.
10. Yaman ME, Ayberk G, Eylen A, Ozveren MF. Isolated abducens nerve palsy following lumbar puncture:
case report and review of the mechanism of action. J Neurosurg Sciences 2010;54:119-23.
11. Pogodzinski MS, et al. Hearing loss and cerebrospinal fluid pressure: Case report and review of the
literature. ENT J 2008;87:144-7.
12. Choi P, et al. PDPH is a common complication of neuraxial blockade in parturients: A meta-analysis of
obstetrical studies. Can J Anesth 2003;50:460-9.
13. Hebl JR, et al. Neuraxial blockade in patients with preexisting spinal stenosis, lumbar disk disease, or piror
spine surgery: Efficacy and neurologic complications. Anesth Analg 2010;111:1511-19.
14. Sadashivaiah J, McLure H. 18-G Tuohy needle can reduce the incidence of severe post dural puncture
headache. Anaesthesia 2009;64:1371-82
15. Levine DN, et al. The pathophysiology of lumbar puncture headache. J Neurol Science 2001;192:1-8.

217
Page 5
16. Kunkle EC, Ray BS, Wolff HG. Experimental studies on headache: Analysis of the headache associated
with changes in intracranial pressure. Arch Neurol Psychiatry 1943;49:323-58.
17. Vakharia SB, et al. Magnetic resonance imaging of cerebrospinal fluid leak and tamponade effect of blood
patch in postdural puncture headache. Anesth Analg 1997;84:585-90.
18. Pannullo SC, et al. MRI changes in intracranial hypotension. Neurology 1993;43:919-926.
19. Nowaczewska M. Cerebral blood flow characteristics in patients with post-lumbar puncture headache. J
Neurol 2012;259:665-669.
20. Aida S, et al. Headache after attempted epidural block. The role of intrathecal air. Anesthesiology
1998;88:76-81.
21. Hurtado TR, et al. Pneumocephalus secondary to an EBP. Am J Emerg Med 2007;25:244-6.
22. Schier R, Guerra D, Aguilar J, et al. Epidural space identification: A meta-analysis of complications after
air versus liquid as the medium for loss of resistance. Anesth Analg 2009;109:2012-21.
23. Segal S, Arendt KW. A retrospective effectiveness study of loss of resistance to air or saline for
identification of the epidural space. Anesth Analg 2010;110:558-63.
24. Lybecker H, et al. Incidence and prediction of postdural puncture headache. A prospective study of 1021
spinal anesthesias. Anesth Analg 1990;70:389-94
25. Wu CL, et al. Gender and post-dural puncture headache. Anesthesiology 2006;105:613-8.
26. Amorim JA. Post-dural (post-lumbar) puncture headache: Risk factors and clinical features. Cephalalgia
2012;32:916-23.
27. Runza M, et al. Lumbar dura mater biomechanics: Experimental characterization and scanning electron
microscopy observations. Anesth Analg 1999;88:1317-21.
28. Richman JM, et al. Bevel direction and PPHA: a meta-analysis. The Neurologist 2006;12:224-228.
29. Angle PJ, et al. Dural tissue trauma and cerebrospinal fluid leak after epidural needle puncture: Effect of
needle design, angle, and bevel orientation. Anesthesiology 2003;99:1376-82.
30. Kang SB, et al. Comparison of 26- and 27-G needles for spinal anesthesia for ambulatory surgery patients.
31. Absalom AR, et al. Spinal cord injury caused by direct damage by local anaesthetic infiltration needle. Br J
Anaesth 2001;87:512-5.
32. Horng HC, et al. Postdural puncture headache following acupuncture. J Anesthesia 2011;25:788-9.
33. Santanen U, et al. Comparison of 27-gauge (0.41 mm) Whitacre and Quincke spinal needles with respect
to PDPHA and non-dural puncture headache. Acta Anaesthesiol Scand 2004;48:474-479.
34. Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of
Anesthesiologists Task Force on Obstetric Anesthesia, 2006.
35. Strupp M. Incidence of post-lumbar puncture syndrome reduced by reinserting the stylet: a randomized
prospective study of 600 patients. J Neurol 1998;245:589-592.
36. Angle P, et al. Second stage pushing correlates with headache after unintentional dural puncture in
parturients. Can J Anesth 1999;46:861-6.
37. Amorim JA, Valenca MM. Postdural puncture headache is a risk factor for new postdural puncture
headache. Cephalalgia 2007;28:5-8.
38. Harrington BE, et al. Meningeal (Postdural) puncture headache, unintentional dural puncture, and the
epidural blood patch. A national survey of United States practice. Reg Anesth Pain Med 2009;34:430-7.
39. Jacobus CH. Does bed restprevent post-lumbar puncture headache? Annals Emerg Med 2012;59:139-40.
40. Norris MC, Leighton BL. Continuous spinal anesthesia after unintentional dural puncture in parturients.
Reg Anesth 1990;15:285-7.
41. Ayad S, et al. Subarachnoid catheter placement after wet tap for analgesia in labor: Influence on the risk of
headache in obstetric patients. Reg Anesth Pain Med 2003;28:512-5.
42. Cohen S, Hunter CW, Sakr A, Hijazi RH. Meningitis following intrathecal catheter placement after
accidental dural puncture. Int J Obstet Anesthe 2006;15:172.
43. Van de Velde M, , et al. Ten years of experience with accidental dural puncture and post-dural puncture
headache in a tertiary obstetric anaesthesia department. Int Obstet Anesh 2009;17:329-35.
44. Russell IF. A prospective controlled study of continuous spinal analgesia versus repeat epidural analgesia
after accidental dural puncture in labour. Int J Obstet Anesth 2012;21:7-16.
45. Al-metwalli RR. Epidural morphine injections for prevention of post dural puncture headache.
Anaesthesia 2008;63:847-50.
46. Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural
puncture. Anesthesiology 2010;113:413-20.

217
Page 6
47. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine. Evaluation with demand
method. Part 1. Current Therapeutic Research 1978;24:307-12.
48. Halker RB, Demaerschalk BM, et al. Caffeine for the prevention and treatment of postdural puncture
headache: Debunking the myth. The Neurologist 2007; 13: 323-7.
49. Bart AJ, Wheeler AS. Comparison of epidural saline placement and epidural blood placement in the
treatment of post-lumbar puncture headache. Anesthesiology 1978;48:221-3.
50. Gormley JB. Treatment of postspinal headache. Anesthesiology 1960;21:565-6.
51. Taivainen T, et al. Efficacy of epidural blood patch for postdural puncture headache. Acta Anaesthiol
Scand 1993;37:702-5.
52. Riley CA, et al. Complications following large-volume epidural blood patches for postdural puncture
headache. Lumbar subdural hematoma and arachnoiditis: initial cause or final effect? J Clin Anesth
2009;21:355-9.
53. Paech MJ. The volume of blood for epidural blood patch in obstetrics: a randomized, blinded clinical trial.
Anesth Analg 2011;113:126-33.
54. Fichtner J. Lack of increase in intracranial pressure after epidural blood patch in spinal cerebrospinal fluid
leak. Neurocrit Care 2012;16:444-449.
55. Rosenberg PH, Heavner JE. In vitro study of the effect of epidural blood patch on leakage through a dural
puncture. Anesth Analg 1985;64:501-4.
56. Szeinfeld M, et al. Epidural blood patch: Evaluation of the volume and spread of blood injected into the
epidural space. Anesthesiology 1986;64:820-2.
57. Beards SC, et al. Magnetic resonance imaging of extradural blood patches: appearances from 30 min to 18
h. Br J Anaesth 1993;71:182-8.
58. Su CS, et al. Clinical features, neuroimaging and treatment of spontaneous intracranial hypotension and
magnetic resonance imaging evidence of blind epidural blood patch. European Neurology 2009;61:301-7
59. Abouleish E, et al. Long-term follow-up of epidural blood patch. Anesth Analg 1975;54:459-63.
60. Andrews PJD, et al. Transient bradycardia associated with extradural blood patch after inadvertent dural
puncture in parturients. Br J Anaesth 1992;69:401-3.
61. Collier CB. Blood patches may cause scarring in the epidural space: two case reports. Int J Obstet Anesth
2011;20:347-51.
62. Kalina P, et al. Intrathecal injection of epidural blood patch: a case report and review of the literature.
Emergency Radiology 2004;11:56-59.
63. van Kooten F, et al. Epidural blood patch in post dural puncture headache: A randomized, observe-blind,
controlled clinical trial. J Neurol Neurosurg Psychiatry 2008;79:553-8.
64. Kueper M, Goericke SL, Kastrup O. Cerebral venous thrombosis after epidural blood patch: Coincidence
or causal relation? A case report and review of the literature. Cephalalgia 2008;28:769-773.
65. Loeser EA, et al. Time vs. success rate for epidural blood patch. Anesthesiology 1978;49:147-8.
66. Safa-Tisseront V, et al. Effectiveness of epidural blood patch in the management of post-dural puncture
headache. Anesthesiology 2001;95:334-9.
67. Vilming ST, et al. When should an epidural blood patch be performed in postlumbar puncture headache?
A theoretical approach based on a cohort of 79 patients. Cephalalgia 2005;25:523-7.
68. Darvish B, et al. Management of accidental dural puncture and post-dural puncture headache after labour:
a Nordic survey. Acta Anaesthesiol Scand 2011;55:46-53.
69. Scavone BM, et al. Efficacy of a prophylactic EBP in preventing post dural puncture headache in
parturients after inadvertent dural puncture. Anesthesiology 2004;101:1422-7.
70. Boonmak P, Boonmak S. Epidural blood patching for preventing and treating post-dural puncture
headache. Cochrane Database of Systematic Reviews 2010;1:CD001791

217
Page 7
Incidence of PDPHA
Needle Type Gauge Incidence of PDPHA
Quincke 16 18%
Quincke 19 10%
Quincke 20 16%
Quincke 22 10%
Quincke 24 6%
Quincke 25 6%
Quincke 26 6%
Quincke 27 1.5%
Pencil Point 22 1.6%
Pencil Point 24 2%
Pencil Point 25 1.1%
Tuohy 16 88%
Tuohy 18 64%
Data is extrapolated from several various studies

Disclosure

231
Page 1
Neuraxial Labor Analgesia and Pregnancy Outcome: Fact and Fiction
Cynthia A. Wong, M.D. Chicago, Illinois
Objectives: To describe the effects, if any, of neuraxial labor analgesia on the progress of labor, rate of cesarean
delivery, and need for instrumental delivery.
Labor is a complex physiologic process. The mechanisms responsible for the progress of labor are not well
understood.
1
The effects of analgesia on the progress and outcome of labor are of concern to anesthesiologists,
obstetricians, and parturients. This lecture will review the available data on the effects of neuraxial analgesia on the
progress of labor and mode of delivery.
Cesarean Delivery
Factors associated with risk of cesarean delivery: Multiple studies have attempted to identify factors associated
with cesarean delivery. These factors include maternal age and body habitus, maternal obstetric complications (e.g.,
diabetes, preeclampsia), fetal weight, obstetric practitioner and type of maternal insurance, parity, induction of labor,
and premature rupture of membranes. Additionally, observational studies suggest that epidural analgesia,
particularly epidural analgesia in early labor,
2,3
is associated with an increased risk of cesarean delivery.
Association, however, does not necessarily mean cause and effect.
Randomized controlled trials: Our understanding of the nature of the association between neuraxial labor analgesia
and mode of delivery is limited by the difficulty in performing controlled trials in which parturients are randomized
to receive neuraxial analgesia vs. placebo. It is not ethical to assign women to placebo (no analgesia). Therefore,
randomized controlled trials have compared labor outcomes in parturients assigned to receive neuraxial vs. systemic
opioid analgesia. Because neuraxial analgesia is markedly superior to all other forms of analgesia, it is not possible
to blind these studies. The cross-over rate may be high.
4
Other factors which influence the outcome of labor are
difficult to control. Nonetheless, in the twopast decades there have been a number of randomized controlled trials
comparing neuraxial (mostly epidural) to systemic labor analgesia (mostly IM or IV meperidine).
Systematic reviews (meta-analyses) have all reached similar conclusions: epidural analgesia compared to systemic
opioid analgesia does not cause an increased incidence of cesarean delivery (Fig. 1).
5,6
The most recent systematic
review included data from over 8417 parturients from 27 randomized controlled trials.
6
The incidence of cesarean
delivery did not differ between patients who received epidural compared to systemic opioid analgesia (relative risk
1.10, 95% CI 0.97 to 1.25). Investigators from Parkland Hospital in Texas, USA published a meta-analysis of 5
randomized trials comparing neuraxial to systemic meperidine analgesia conducted at their institution between 1993
and 2000 in over 2,700 nulliparas.
5
The incidence of cesarean delivery was not different between groups (OR 1.04,
95% CI 0.81 to 1.34).
Impact studies: A number of studies have compared the cesarean delivery rate immediately before, and shortly after,
the introduction of epidural analgesia in a single institution. For example, epidural analgesia was introduced into a
tertiary military hospital in 1993.
7
The rate of epidural labor analgesia increased from 1% to 84% in a one-year
period. The rates of cesarean delivery immediately before and after the introduction of epidural analgesia were the
same (adjusted relative risk 0.8, 95% CI 0.6 to 1.2), as was the rate of instrumental vaginal delivery. Segal
performed a meta-analysis using data from 9 impact studies (n = 37,753).
8
The rate of cesarean delivery and
operative vaginal delivery did not differ between periods of low and high epidural analgesia rate.

231
Page 2
Dose-response effect: If neuraxial analgesia adversely affects the outcome of labor, one would expect to observe a
dose-response effect, i.e., more dense analgesia should be associated with a higher cesarean delivery rate. Several
large randomized controlled trials compared traditional epidural analgesia with 0.25% bupivacaine to epidural or
combined spinal-epidural (CSE) techniques resulting in less dense analgesia (low-dose bupivacaine/fentanyl).
9,10

These studies found no difference in the rate of cesarean delivery between the traditional epidural and low-dose
techniques.

Given that the totality of these studies suggests that neuraxial labor analgesia does not increase the risk of cesarean
delivery, why do women who choose neuraxial analgesia more often have cesarean deliveries compared to those
who do not? Studies have shown that women who have more pain during labor are at increased risk for cesarean
delivery. Women who required ! 3 manual epidural boluses during continuous low-dose epidural bupivacaine-
fentanyl labor analgesia were at increased risk for cesarean delivery compared to women who received " 2 boluses
(odd ratio 2.6, 95% CI 2.0 to 3.4).
11
The minimum local anesthetic concentration (MLAC, concentration required to
produce satisfactory epidural labor analgesia for 50% of parturients) of bupivacaine required to initiate epidural
analgesia was lower for women who went on to deliver vaginally compared to the MLAC for those who delivered
by cesarean (0.085% vs. 0.106%).
12
A secondary analysis of data obtained from women who were randomized to
receive patient controlled intravenous analgesia (PCIA) with meperidine found that women who gave themselves
meperidine ! 50 mg/h had a 20% cesarean delivery rate compared to 2% for women who gave themselves
meperidine < 50 mg/h (P < 0.001).
13
These data suggest that pain, and the subsequent request for epidural analgesia,
is a marker for risk of cesarean delivery. Dysfunctional labor, large fetuses, and malpositioned fetuses may increase
labor pain and are associated with risk for cesarean delivery.

231
Page 3
Figure 1. Meta-analysis: Neuraxial vs. systematic opioid analgesia, effect on rate of cesarean delivery.
6

Timing of neuraxial analgesia in labor
Multiple observational studies have found that early labor initiation of epidural analgesia is associated with a higher risk
of cesarean delivery.
2,14
In randomized controlled trials, however, early initiation of neuraxial compared to systemic
opioid analgesia, followed by later labor initiation of epidural analgesia, has not been shown to result in a increased risk
of cesarean delivery. Chestnut found no difference in cesarean delivery rate between nulliparas randomized to early
epidural analgesia (cervical dilation between 3 and 5 cm) compared to late epidural analgesia (cervical dilation ! 5 cm,
nalbuphine in early labor).
15,16
Wong et al. randomized 750 nulliparas in spontaneous labor who requested labor
analgesia at cervical dilation < 4 cm to receive early initiation of neuraxial analgesia (combined spinal-epidural [CSE]
analgesia) or early systemic hydromorphone analgesia followed by epidural analgesia at 4 cm dilation.
17
The median
cervical dilation at the time of initiation of neuraxial analgesia was 2 cm in the early group and 4 cm in the late group.
There was no difference in the cesarean delivery rate between groups (early 17.8%, late 20.7%; 95% CI of the difference
-9.0 to 3.0%; P=0.31). A study of both induced and spontaneously laboring nulliparas (N=449) randomized to early
epidural analgesia (mean cervical dilation 2.4 cm), compared to early meperidine followed by late epidural analgesia
(mean cervical dilation 4.6 cm) found no difference in the rate of cesarean delivery (13% vs. 11%, P=0.77).
18
A
randomized controlled trial of 806 nulliparas with induced labor randomized to receive early CSE vs. systemic

231
Page 4
hydromorphone analgesia found there was no difference in the cesarean delivery rate (early 32.7%, late 31.5%; 95% CI
of difference, -3% to 6%: P=0.65).
19
Finally, a randomized controlled trial of over 12,000 nulliparas in China found no
difference in the rate of cesarean delivery in women randomized to early labor (cervical dilation ! 1 cm, < 4 cm)
epidural vs. systemic opioid analgesia.
20
A 2011 meta-analysis which included 6 studies (15,399 nulliparous women)
found no difference in the rate of cesarean delivery between the early and late groups (pooled risk ratio 1.02; 95% CI
0.96 to 1.08) (Fig. 2).
21

Figure 2. Meta-analysis early vs. later labor initiation of neuraxial labor analgesia, effect on rate of cesarean delivery.
21

Taken together, these studies suggest that the request for analgesia early in labor is a marker for some other risk
factor for cesarean delivery (see discussion of labor pain above) and that early labor initiation of neuraxial analgesia
does not increase the risk of cesarean delivery. In a Committee Opinion from June 2006, the American College of
Obstetricians and Gynecologists (ACOG) stated that that they previously recommended that practitioners delay
initiation of epidural analgesia in nulliparous women until cervical dilation reached 4-5 cm. However, more recent
studies have shown that epidural analgesia does not increase the risks of cesarean delivery The fear of
unnecessary cesarean delivery should not influence the method of pain relief that women can choose during labor.
22

Instrumental vaginal deliveries
Multiple randomized controlled trials comparing epidural to systemic opioid analgesia have also assessed the rate of
instrumental vaginal delivery (forceps or vacuum) as a secondary outcome variable. Most systematic reviews have
concluded that epidural analgesia is associated with an increased risk of instrumental vaginal delivery compared to
systemic opioid analgesia (Table 1).
5,6
In contrast, the systematic review of impact studies by Segal found no
increase in instrumental vaginal delivery rate after the institutional initiation of neuraxial labor analgesia.
8

Table 1. Meta-analyses: Rate of instrumental vaginal delivery, epidural compared to systemic opioid analgesia
Study N Included Study
Designs
Outcome 95% CI
Sharma
5
2,703 RCT Odds ratio: 1.86 1.43 2.40
Anin-Somuah
6
7935 RCT Risk ratio: 1.42 1.28 1.57
Segal
8
28,443 Impact Percent change: 0.76 -1.2 2.8

Although study results are inconsistent, the weight of evidence suggests there may be a dose-response effect in
terms of risk of instrumental vaginal delivery. A multi-center study in over 1000 nulliparas found that the rate of
instrumental vaginal delivery was higher in women who received traditional epidural analgesia with bupivacaine
0.25% compared to women who received low-concentration bupivacaine techniques (bupivacaine 0.1% and
fentanyl) (37% vs. 29%).
9
Similarly, in another study, women randomized to receive CSE analgesia (maintained
with bupivacaine 0.0625% plus fentanyl) had a lower rate of instrumental vaginal delivery (31%) compared to
women who received epidural analgesia initiated with bupivacaine 0.25% and maintained with bupivacaine 0.125%
with fentanyl (40%).
10
Olofsson et al. demonstrated a lower risk of instrumental vaginal delivery in women
randomized to low-dose epidural bupivacaine 0.125% with sufentanil compared to high-dose epidural
bupivacaine 0.25% with epinephrine.
23
In contrast, Collis et al. found no difference in mode of delivery in women
randomized to receive low-dose vs. high-dose neuraxial analgesia.
24
It is possible that these inconsistent results can

231
Page 5
be explained by the absolute differences in bupivacaine dose and motor blockade. For example, there may be a
clinically significant difference in outcome between bupivacaine 0.25% and 0.125%, but not between 0.125% and
0.0625%.

Several investigators have randomized women with first stage epidural analgesia to continue to receive epidural
analgesia vs. epidural saline during the second stage of labor.
25-28
A meta-analysis concluded that 1) there is
insufficient evidence to support the hypothesis that discontinuing epidural analgesia during the second stage of labor
reduces the rate of instrumental vaginal delivery, but that a larger study was needed, and 2) there is evidence that
this practice increases the rate of inadequate pain relief in the 2
nd
stage of labor.
29

The current evidence suggests that effective second stage neuraxial analgesia may cause an increased risk of
instrumental vaginal delivery.
30
The effect of neuraxial analgesia on the outcome of the second stage of labor may
be influenced by the density of neuraxial analgesia. High concentrations of epidural local anesthesia may cause
maternal motor blockade, causing relaxation of pelvic and pelvic floor musculature, which in turn may interfere with
fetal rotation during descent. Abdominal muscle relaxation may decrease the effectiveness of maternal expulsive
efforts. The risk of motor blockade and instrumental vaginal delivery may be minimized by using low-dose
neuraxial techniques, but this may be associated with less effective analgesia and requires that anesthesiologists
tailor the density of analgesia to the needs of individual parturients. The specific techniques used to maintain
epidural analgesia (e.g., manual bolus, continuous infusion, patient-controlled epidural analgesia), as well as the
concentration of local anesthetic, may influence the density of neuraxial blockade.

Duration of the first stage of labor
The data as to whether neuraxial analgesia adversely effects the duration of the first stage of labor are conflicting.
The results of meta-analyses of randomized studies comparing epidural to systemic analgesia differ, depending in
which studies are included in the analysis. The most recent meta-analysis included duration of labor data from 11
studies and 2981 patients.
6
The mean difference in the duration of the first stage of labor was not significantly
different between epidural and systemic opioid analgesia (mean difference 19 min, 95% CI -13 to 50 min. However,
the heterogeneity among trials was significant (I
2
86%, P < 0.0001) and the 95% CI of the mean difference is quite
wide. In contrast, in the meta-analysis of the five Parkland Hospital studies (N=2703), the first stage of labor
duration was significantly longer in the epidural group (8.1 5 h vs. 7.5 5 h (P=0.01).
5
Finally, most study
protocols did not dictate regular cervical examinations, therefore, the diagnosis of complete cervical dilation may
have been made later in women with effective neuraxial analgesia compared to women with systemic opioid
analgesia, thus artificially prolonging the calculation of the duration of the first stage of labor.

It is unclear whether specific neuraxial techniques differ in their effects on the progress of labor. Tsen found a faster
rate of cervical dilation in nulliparas randomized to CSE compared to epidural analgesia.
31
In contrast, Norris found
no difference in the duration of the first stage of labor between these two types of neuraxial analgesia.
32
This area
requires further study. The early compared to late initiation of neuraxial analgesia was associated was a significantly
faster first stage of labor in two large studies (one CSE
17
and one epidural analgesia
18
).

In summary, it is unclear whether neuraxial analgesia prolongs the first stage of labor. Differences may be due to
management of labor (e.g., active management of labor) and fluid management protocols or the timing of the
diagnosis of the end of the 1
st
stage. If neuraxial analgesia does prolong labor, it appears to do so to a minor degree.
There is no evidence that this has an adverse effect on the mother or fetus/neonate.

Duration of the second stage of labor
The bulk of evidence suggests that neuraxial analgesia causes a longer second stage of labor (Table 2).
5,6

Table 2. Meta-analyses of RCTs: Duration of second stage
Study N Duration 2
nd
stage (min) P
Epidural Systemic
Anim-Somuah
6
4233 Mean difference: 14 min (95% CI 7 21) < 0.001
Sharma
5
2,703 60 56 47 57 < 0.001

231
Page 6
Several studies have sought to determine whether immediate or delayed pushing for women with epidural analgesia
during the second stage of labor effects labor duration and outcome. Data are conflicting. A meta-analysis that
included 9 randomized controlled trials and approximately 3000 women concluded that delayed pushing did not
change the rate of instrumental vaginal delivery (RR 0.92, 95% CI 0.84 to 1.01) or second stage cesarean delivery,
but did result in a decreased incidence of rotational or mid-pelvic instrumental deliveries (RR 0.69, 95% CI 0.55 to
0.87).
33
The total duration of the second stage was longer with delayed pushing, but there were no differences in
neonatal outcomes.

Conclusions
Neuraxial analgesia does not increase the risk of cesarean delivery.
Effective neuraxial analgesia may increase the risk of instrumental vaginal delivery, but this may be
dependent on the density of neuroblockade. More dense neuroblockade is associated with a higher rate of
instrumental vaginal delivery than less dense neuroblockade.
It is unclear whether neuraxial analgesia prolongs the duration of the first stage of labor, but if it does it is
only by a small amount.
Neuraxial analgesia prolongs the duration of the second stage of labor.

References

1. Liao JB, Buhimschi CS, Norwitz ER. Normal labor: mechanism and duration. Obstet Gynecol Clin North
Am 2005;32:145-64, vii.
2. Seyb ST, Berka RJ, Socol ML, Dooley SL. Risk of cesarean delivery with elective induction of labor at
term in nulliparous women. Obstet Gynecol 1999;94:600-7.
3. Sheiner E, Levy A, Feinstein U, Hallak M, Mazor M. Risk factors and outcome of failure to progress
during the first stage of labor: a population-based study. Acta Obstet Gynecol Scand 2002;81:222-6.
4. Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural
versus intravenous analgesia during labor. Obstet Gynecol 1995;86:783-9.
5. Sharma SK, McIntire DD, Wiley J, Leveno KJ. Labor analgesia and cesarean delivery: an individual
patient meta-analysis of nulliparous women. Anesthesiology 2004;100:142-8.
6. Anim-Somuah M, Smyth RM, Jones L. Epidural versus non-epidural or no analgesia in labour. Cochrane
Database Syst Rev 2011;12:CD000331.
7. Zhang J, Yancey MK, Klebanoff MA, Schwarz J, Schweitzer D. Does epidural analgesia prolong labor and
increase risk of cesarean delivery? A natural experiment. Am J Obstet Gynecol 2001;185:128-34.
8. Segal S, Su M, Gilbert P. The effect of a rapid change in availability of epidural analgesia on the cesarean
delivery rate: a meta-analysis. Am J Obstet Gynecol 2000;183:974-8.
9. Comparative Obstetric Mobile Epidural Trial Study Group UK. Effect of low-dose mobile versus
traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet 2001;358:19-23.
10. Nageotte MP, Larson D, Rumney PJ, Sidhu M, Hollenbach K. Epidural analgesia compared with combined
spinal-epidural analgesia during labor in nulliparous women. N Eng J Med 1997;337:1715-9.
11. Hess PE, Pratt SD, Soni AK, Sarna MC, Oriol NE. An association between severe labor pain and cesarean
delivery. Anesth Analg 2000;90:881-6.
12. Panni MK, Segal S. Local anesthetic requirements are greater in dystocia than in normal labor.
13. Alexander JM, Sharma SK, McIntire DD, Wiley J, Leveno KJ. Intensity of labor pain and cesarean
delivery. Anesthesia & Analgesia 2001;92:1524-8.
14. Thorp JA, Hu DH, Albin RM, McNitt J, Meyer BA, Cohen GR, Yeast JD. The effect of intrapartum
epidural analgesia on nulliparous labor: A randomized, controlled, prospective trial. Am J Obstet Gynecol
1993;169:851-8.
15. Chestnut DH, McGrath JM, Vincent RD, Penning DH, Choi WW, Bates JN, McFarlane C. Does early
administration of epidural analgesia affect obstetric outcome in nulliparous women who are in spontaneous
labor? Anesthesiology 1994;80:1201-8.
16. Chestnut DH, Vincent RD, McGrath JM, Choi WW, Bates JN. Does early administration of epidural
analgesia affect obstetric outcome in nulliparous women who are receiving intravenous oxytocin?

231
Page 7
17. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, Yaghmour E, Marcus RJ,
Sherwani SS, Sproviero MT, Yilmaz M, Patel R, Robles C, Grouper S. The risk of cesarean delivery with
neuraxial analgesia given early versus late in labor. N Engl J Med 2005;352:655-65.
18. Ohel G, Gonen R, Vaida S, Barak S, Gaitini L. Early versus late initiation of epidural analgesia in labor:
does it increase the risk of cesarean section? A randomized trial. Am J Obstet Gynecol 2006;194:600-5.
19. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE, Yaghmour EA. Early compared with late
neuraxial analgesia in nulliparous labor induction: a randomized controlled trial. Obstet Gynecol
2009;113:1066-74.
20. Wang F, Shen X, Guo X, Peng Y, Gu X. Epidural analgesia in the latent phase of labor and the risk of
cesarean delivery: a five-year randomized controlled trial. Anesthesiology 2009;111:871-80.
21. Wassen MM, Zuijlen J, Roumen FJ, Smits LJ, Marcus MA, Nijhuis JG. Early versus late epidural analgesia
and risk of instrumental delivery in nulliparous women: a systematic review. BJOG 2011;118:655-61.
22. American College of Obstetricians and Gynecologists Committee Opinion No. 339, June 2006. Analgesia
and cesarean delivery rates. Obstet Gynecol 2006;107:1487.
23. Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L. Obstetric outcome following epidural analgesia
with bupivacaine-adrenaline 0.25% or bupivacaine 0.125% with sufentanil--a prospective randomized
controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998;42:284-92.
24. Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard
epidural analgesia in labour. Lancet 1995;345:1413-6.
25. Johnsrud ML, Dale PO, Lovland B. Benefits of continuous infusion epidural analgesia throughout vaginal
delivery. Acta Obstet Gynecol Scand 1988;67:355-8.
26. Chestnut DH, Bates JN, Choi WW. Continuous infusion epidural analgesia with lidocaine: efficacy and
influence during the second stage of labor. Obstet Gynecol 1987;69:323-7.
27. Chestnut DH, Laszewski LJ, Pollack KL, Bates JN, Manago NK, Choi WW. Continuous epidural infusion
of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor. Anesthesiology 1990;72:613-
8.
28. Luxman D, Wolman I, Niv D, Cohen JR, Lottan M, Pauzner D, Groutz A, David MP. Effect of second-
stage 0.25% epidural bupivacaine on the outcome of labor. Gynecol Obstet Invest 1996;42:167-70.
29. Torvaldsen S, Roberts CL, Bell JC, Raynes-Greenow CH. Discontinuation of epidural analgesia late in
labour for reducing the adverse delivery outcomes associated with epidural analgesia. Cochrane Database
Syst Rev 2004:CD004457.
30. Chestnut DH. Epidural anesthesia and instrumental vaginal delivery. Anesthesiology 1991;74:805-8.
31. Tsen LC, Thue B, Datta S, Segal S. Is combined spinal-epidural analgesia associated with more rapid
cervical dilation in nulliparous patients when compared with conventional epidural analgesia?
32. Norris MC, Fogel ST, Conway-Long C. Combined spinal-epidural versus epidural labor analgesia.
33. Roberts CL, Torvaldsen S, Cameron CA, Olive E. Delayed versus early pushing in women with epidural
analgesia: a systematic review and meta-analysis. BJOG 2004;111:1333-40.

Disclosure

406
Page 1
Anesthetic Management of the Morbidly Obese Parturient
Brenda A. Bucklin, M.D. Aurora, Colorado
In the past two decades, rates of obesity have increased by 82% worldwide.
1
Although reports from the National
Health and Nutrition Examination Survey suggest that rates of obesity in the U.S. have plateaued, more than one
third of all U.S. women are obese, more than 50% of pregnant women are overweight or obese, and nearly 10% of
women of reproductive age are extremely obese.
2
In 2009, the Institute of Medicine released a new range for weight
gain during pregnancy that limits the gain to 11 to 25 pounds when the BMI is greater than 30 kg/m
2
and 15 to 25
pounds when the BMI is between 25 and 29.9 kg/m
2
.
3
The costs associated with the care of an obese parturient have
been shown to increase in direct proportion with the body mass index (BMI).
4

MORBID OBESITY AND PREGNANCY
Maternal complications Several studies have documented higher rates of preeclampsia, gestational diabetes
mellitus, and cesarean delivery in obese women.
5-7
Results from a prospective multicenter study of more than 16,000
patients suggest that the incidence of gestational diabetes mellitus (OR 2.6, 4.0), gestational hypertension (OR 2.5,
3.2), preeclampsia (OR 1.6, 3.3), and fetal macrosomia (OR 1.7, 1.9) were all increased in patients with a BMI of
30-39.9 compared with women of a BMI < 30 kg/m
2
.
8
In the study, rates of cesarean delivery (CS) were 20.7%
when the BMI was < 29.9, 33.8% when the BMI was between 30 and 34.9, and 47.7% when the BMI was between
35 and 39.9.
Maternal morbidity and mortality Obesity and CS have been identified as independent risk factors for maternal
mortality.
8
Obesity is also an important risk factor for anesthetic-related maternal mortality.
9
Although there has
been longstanding concern about risk of general anesthesia and anesthetic-related maternal mortality, there are
emerging concerns about complications occurring during the administration of neuraxial anesthesia as well as during
the postoperative period in the obese. A review by the Doctors Company of 22 anesthesiology claims that were filed
after maternal arrests on labor and delivery wards between 1998 and 2006 revealed morbid obesity as a significant
risk factor for maternal arrest.
10
Morbid obesity was documented in 3 out of the 8 labor epidural cases and in 1 out of
5 CS. Resuscitation of the mother was delayed in 7 of the epidural cases because of a lack of airway equipment in
the labor room or a delay in transfer of the patient to the operating room (OR).
A state review of 855 maternal deaths in Michigan between 1985 and 2003 revealed 8 of these deaths were
anesthesia-related and 7 were anesthesia-contributing.
11
Of the anesthesia-related deaths, 6 of the patients were
obese. None of the deaths occurred during induction of anesthesia, however hypoventilation and airway
obstruction occurred during emergence or recovery. More than half of the deaths resulted from lapses in
postoperative monitoring and inadequate supervision by an anesthesiologist.
In the most recent triennial report of maternal deaths in the United Kingdom (UK) between 2006-2008, 49% (n =
227) of the women who died from either Direct (e.g., thromboembolic disease, preeclampsia, Hemorrhage) or
Indirect (e.g., cardiac disease) causes and for whom the BMI was known were either overweight or obese.
12
Of
these deaths, perioperative anesthetic management was contributory in 18 of the cases. The authors caution that
many of the avoidable factors identified remain the same as in previous reports and more research is needed to
identify methods, tools and training to reduce substandard care by health professionals.
12

Near miss morbidity and mortality There has been increasing interest in near miss maternal morbidity and
mortality. A near-miss occurs when a pregnant or recently postpartum woman survives a life-threatening event,
either by chance or because of high-quality medical care.
13
Although obesity was not independently associated with
near-miss morbidity/mortality, Mhyre et. al
14
identified the most common comorbidities in the 2003-06 Nationwide
Inpatient Sample that were associated with near-miss morbidity/mortality: hypertensive disorders of pregnancy
(34.7%); previous cesarean delivery (15.7%); diabetes mellitus (10.5%); preexisting hypertension (10.2%); and
multiple gestation (9.8%). Because women with preexisting conditions or antenatal obstetric complications suffered
the majority of near-miss morbidities as well as mortalities, antepartum multidisciplinary coordination, careful
delivery planning and implementation can improve outcomes for these high-risk patients.
406
Page 2
Patient safety A recent report by the Centers for Disease Control and Prevention determined that ~50% of
maternal deaths were preventable.
15
In addition, there are recent calls for national standards and levels of maternity
care to improve maternal care and neonatal outcome.
16
Hankins et al.
16
suggest a network that would function
similar to stroke and emergency care models. Higher functioning facilities would be integrated to accept transfers,
educate, use evidence-based best practices, develop policies, institute quality reviews and improvement within the
network. Recently Clark and Hankins identified 10 specific recurrent errors that account for the majority of maternal
deaths including: pulmonary embolism, severe preeclampsia, cardiac disease, and postpartum hemorrhage.
17
The
authors suggest development and adoption of local or regional clinical protocols that could be used to help reduce
the risk of error and of maternal mortality. In addition, the American College of Obstetricians and Gynecologists
(ACOG) recommends anesthesiology consultation for obese women ante-partum or early in labor to allow
adequate time for development of an anesthetic plan.
18

Fetal complications Babies of obese women have increased risk of congenital anomalies, prematurity, stillbirth,
macrosomia, as well as childhood and adolescent obesity.
19

PREOPERATIVE ASSESSMENT
Airway The airway undergoes important changes during pregnancy due to mucosal edema of the nasopharynx,
oropharynx, and larynx. Preeclampsia, upper respiratory tract infections, stridor, and voice changes are all indicators
of airway edema. The effects of obesity are additive. Obesity and pregnancy each increase the risk of difficult
intubation. The incidence of failed tracheal intubation is estimated to be ~1 in 250 in the obstetric population
20,21

compared to 1 in 2230 in the general surgical population.
22
A recent report also identified predictive factors.
21

Multivariate analyses showed that age, BMI, and a recorded Mallampati score were significant independent
predictors of failed tracheal intubation. A careful airway examination should be completed immediately prior to any
anesthetic procedure because this exam is known to change during labor. In a recent evaluation of airway changes
during labor, there was a significant increase in airway class from prelabor to postlabor.
23
Thirty-eight of 61
parturients developed a class 3 or 4 airway that was independent of duration of labor or fluid administration.
Anatomic changes associated with obesity that contribute to a potentially difficult airway include limited
movement of the atlantoaxial joint and cervical spine by upper thoracic and low cervical fat pads; excessive tissue
folds in the mouth and pharynx; a short thick neck; a thick submental fat pad; suprasternal, presternal, and posterior
cervical fat; and large breasts. Difficult laryngoscopy and failed intubation in obstetric patients have been associated
with large breasts, increased anteroposterior diameter of the chest, airway edema and reduced chin-to-chest
distance.
24

Cardiopulmonary Hypertensive disorders (e.g., preeclampsia, chronic hypertension),
8
cerebrovascular disease,
ischemic heart disease,
25
and respiratory disorders (e.g., asthma, sleep apnea) are all increased in parturients with
obesity. Obesity and pregnancy are associated with increases in circulating blood volume, pulmonary blood volume,
stroke volume, and cardiac output.
Obese parturients often have limited exercise tolerance and may appear asymptomatic even though they have
significant cardiovascular disease. These patients should be evaluated for systemic hypertension, pulmonary
hypertension, signs of right and/or left heart failure, and ischemic heart disease. Signs of cardiac failure such as
elevated jugular venous pressure, pathologic heart sounds, pulmonary crackles, hepatomegaly, and peripheral edema
may all be difficult to detect because of excess adiposity as well as the pregnant state. Chronic pulmonary
impairment may lead to pulmonary hypertension. The common features of pulmonary hypertension are exertional
dyspnea, fatigue, and syncope (which reflects an inability to increase cardiac output during activity). An ECG may
demonstrate signs of right ventricular hypertrophy such as tall precordial R waves, right axis deviation, and right
ventricular strain. The higher the pulmonary artery pressure the more sensitive the ECG. Chest radiographs may
show evidence if they demonstrate signs and symptoms of cardiovascular compromise prior to labor and delivery.
The prevalence of obstructive sleep apnea (OSA) in pregnancy is unknown. Evidence of sleep apnea and
obstructive hypoventilation syndrome (increased cardiac output, pulmonary hypertension, cardiomegaly,
polycythemia, and right heart failure) should be obtained preoperatively not only because patients with these
syndromes may present with difficult airway management issues, but also because the conditions are associated with
increased perioperative complications. Diagnosis of OSA during pregnancy may be difficult because sleep
disturbance and daytime fatigue are common during pregnancy, especially near term. Obstructive sleep apnea
should be suspected in women with BMI > 35, neck circumference > 16 inches, frequent/loud snoring, periods of
apnea during sleep, frequent arousals during sleep, or profound daytime somnolence. When CPAP is used at home,
patients should be instructed to bring it with them to the hospital.
26
Although arterial blood gases measurements help
to evaluate ventilation and the need for supplemental oxygen administration, routine pulmonary function tests are
406
Page 3
not cost effective. Pulse oximetry measurements in the sitting and supine positions can be helpful to determine the
degree of pulmonary reserve.
Metabolic Diabetes mellitus and gestational diabetes are frequent endocrine disorders in morbidly obese parturients
and increase risk of obstetric complications. More obese reproductive-aged women are undergoing bariatric surgery
and these pregnancies are less likely to be complicated by diabetes, hypertensive disorders, and fetal macrosomia,
but nutritional deficiencies can increase the risk for neuropathies and coagulation abnormalities.
Coagulation Morbid obesity is a known risk factor for perioperative thromboembolic events including sudden
death from acute pulmonary embolism. Recently, TEG
was used to assess the effect of both pregnancy and BMI on

blood coagulation.
27
The study confirmed that obesity is a significant factor in determining hypercoagulability but
pregnancy has no additional coagulation effect in obese women.
ANALGESIA FOR ANTICIPATED VAGINAL DELIVERY
If anesthesiology consultation was not obtained ante-partum, it should be occur early in labor because of the risk of
emergent cesarean delivery and anesthetic complications. Neuraxial analgesia may precede the onset of labor or a
patients request for labor analgesia
28
in order to reduce oxygen consumption and attenuate increases in cardiac
output but it may be technically difficulty or impossible because of obscure landmarks, difficult positioning, and/or
excessive layers of adipose tissue. In such cases, parenteral opioid and inhalation techniques can be used but often at
the expense of maternal drowsiness, airway obstruction, and hypoxemia. If epidural placement is successful, the
catheter can be easily converted to a surgical catheter in the event of urgent CS in order to avoid the risks of general
anesthesia. Multiple studies have demonstrated that obese patients require more attempts, catheter replacements,
have a higher risk of failures, and more inadvertent subarachnoid catheter placements compared to nonobese
parturients.
29-31
The block should be bilateral and almost perfect. Any epidural catheter that is questionable should
be promptly replaced. Hood and Dewan
29
demonstrated a high rate of success when catheters were carefully
evaluated and replaced early. In their series, only 1 of 55 patients required conversion to general anesthesia because
of inadequate epidural anesthesia.
Preparation Preparation should include placement of adequate intravenous access early in labor. Central venous
access may be necessary if peripheral access is unobtainable or inadequate. Blood pressure (BP) monitoring may be
particularly problematic in these patients. If the BP cuff is too small, the BP reading will be overestimated. The
forearm can be used if the upper arm is too large or cylindrical in shape. In some cases, an arterial line will be
necessary to accurately determine the BP as well as obtain arterial blood gases in patients with respiratory
compromise.
Positioning An important step in successful catheter placement is positioning. The sitting position is recommended
to assist with identification of the midline. The patients back should be parallel to the edge of the bed to prevent
lateral needle deviation away from the midline. If spinal processes cannot be appreciated with deep palpation, a line
can be drawn from the cervical vertebral spinal process to the uppermost portion of the gluteal cleft. This line marks
the midline of the patient over the vertebral column. When iliac crests are difficult to appreciate, the skin indentation
from the fetal heart rate monitor belt can be used as a guide. This belt usually rests on the iliac crests over the
Tuffier line. By drawing a perpendicular line from the cervical spinal processes down to this line, the intersection
point is a reasonable spinal or epidural needle insertion guide.
Identification of the epidural space Identification of the epidural space is often problematic, especially when bony
landmarks are nonpalpable, there is limited back flexion,
32
and there are false loses of resistance due to fat
deposition. It is also difficult to predict the depth to the epidural space but, the depth often positively correlates with
BMI.
33
A long 25-gauge needle can be used for infiltration of local anesthetic as well as to identify spinal processes.
To determine whether needle placement is midline or lateral, the patient is often helpful in directing the needle to the
midline. Failure of midline placement increases the depth to the epidural space and chance of catheter malposition.
34

In most cases, standard neuraxial needles (9-10 cm) are usually of sufficient length.
35
However, longer needles (16
cm) are sometimes needed in extremely obese parturients.
Use of ultrasonography Prepuncture ultrasonography may be useful to facilitate epidural placement in obese
parturients.
36
In obese parturients the distance to the epidural space is often underestimated because of compression
of the subcutaneous tissue that is often required to compensate for poor visibility. A recent study evaluated scanning
in the paramedian sagittal oblique (PSO) plane compared with the transverse median plane to determine whether
scanning in the PSO plane resulted in a more precise estimate of the skin to epidural space measurement.
37
The
authors concluded that the estimates were comparable with PSO vs. TM and that the ability to use both estimates
interchangeably may prove useful in patients with poor visibility in the TM plane.
Combined spinal-epidural (CSE) Combined spinal-epidural labor analgesia is one alternative to conventional
epidural analgesia, however there is concern that the technique is more complicated than either spinal or epidural
406
Page 4
alone and the epidural catheter is unproven during the duration of spinal analgesia. Although CSE catheters fail at
similar rates compared with conventional epidural catheters,
38
delayed recognition of a non-functional epidural
catheter is a disadvantage of this technique. However, even if the patient does not receive a spinal dose during
CSE placement, the return of CSF in the spinal needle is confirmation of midline needle placement. This increases
the likelihood of a bilateral block.
Dosing and infusions Dilute local anesthetic and opioid solutions will provide pain relief with minimal motor
blockade.
28
Practitioners will often initiate the block with only local anesthetic to document a bilateral block before
adding opioid to the epidural solution to ensure a functional catheter.
Catheter dislodgement Before an epidural catheter is secured, the patient should assume an upright sitting position
then a lateral position.
39
Because the ligamentum flavum has a mild grip on the epidural catheter, repositioning
allows the epidural catheter to be pulled into the subcutaneous fat, sometimes by several centimeters. My practice is
to insert the catheter 5 cm into the epidural space while the patient is in the sitting position. Before taping, the
patient moves to a lateral position. The catheter is subsequently taped in place without adjusting the catheter.
Inadvertent dural puncture In cases of inadvertent dural puncture, catheters may be threaded into the
subarachnoid space for continuous spinal analgesia to reduce the risk of postdural puncture headache.
40
However,
routine use of spinal catheters is not recommended because accidental administration of an epidural dose of local
anesthetic through the spinal catheter increases the risk of a high spinal, respiratory compromise, and loss of the
airway in a labor room. When inadvertent dural puncture has occurred, these catheters can be used during labor and
used for CS when more concentrated local anesthetics are administered.
ANESTHESIA FOR CESAREAN DELIVERY
General considerations Failure to progress, abnormal labor, nonreassuring fetal status, abnormal presentation,
shoulder dystocia, and birth trauma are more common in this patient population. A meta-analysis of studies suggests
an odds ratio of 2.05 for CS in obese women compared to those with normal BMI.
41
Although the use of general
anesthesia for CS has decreased in the last two decades and deaths attributed to anesthesia have decreased,
42
obesity
and CS remain independent risk factors for maternal morbidity and mortality.
8
Morbidly obese women undergoing
scheduled CS have greater overall anesthesia complications, more complicated placement of neuraxial anesthesia,
and more frequent requirements for general anesthesia than lower-weight women.
43
Obese women who require CS
have also an increased incidence of wound breakdown and infections. A higher dose of preoperative antibiotics
should be considered for surgical prophylaxis.
44

Goals of anesthetic management include:
Aspiration prophylaxis
Avoid aortocaval compression
Neuraxial anesthesia unless contraindicated
Preparation (personnel, equipment, monitoring, positioning)
Careful evaluation and management of the airway and ventilation
Reduction of cardiovascular stress
Management of hypotension
Judicious use of neuraxial, oral, or intravenous opioids
Careful postoperative monitoring
Operating room considerations Weight limits of standard operating room tables range from 130 to 160 kg.
Although some newer tables will support up to 454 kg, recent concerns were raised when an operating room tables
floor locks were released and the fulcrum of the table shifted ~3 inches to the patients feet.
45
This changed the OR
tables weight capacity and made the table prone to tipping. The authors recommend that it is necessary to comply
with manufacturer (Amsco 3085 SP surgical table) recommendations and DO NOT RELASE FLOOR LOCKS
WHILE PATIENT IS ON TABLE. In some cases the width of the table can be extended with side extensions. If
extensions are unavailable, it may be possible to improvise with arm boards placed along the sides of the OR table.
Adequate padding should be used to prevent pressure-related injuries. If the maternal weight exceeds the capacity of
the OR table, the surgery should be performed on a hospital bed. Transport gurneys should be of similar size limits.
Patients must be properly secured so that left uterine displacement can be achieved. If patient-moving assistance
devices are unavailable, additional personnel are required to prevent lifting injuries.
Surgical considerations A panniculus in a morbidly obese patient may weigh more than 70 kg. Therefore it is an
important surgical consideration with respect to the surgical approach. The panniculus can either be retracted caudad
to permit a vertical incision above, retracted cephalad to permit a transverse incision, or retracted vertically to
increase surgical exposure. Many techniques (retention sutures or towel clamps attached to IV poles, an assistant to

406
Page 5
retract the panniculus during the surgery, suspender-type taping to the shoulders, securing the panniculus to the
anesthesia screen, suspending the panniculus from hooks in the ceiling) are used to achieve exposure. However,
cephalad retraction of the panniculus can cause hypotension, respiratory distress, nonreassuring fetal heart tones, and
even fetal death.
46
During retraction, the force exerted on the upper abdomen and chest can causes compression of
the inferior vena cava as well as decreased respiratory compliance. The increased pressure can decrease venous
return resulting in a profound decrease in cardiac output and arterial BP and/or may exacerbate an already
compromised respiratory state. Regardless of the surgical approach, the uterus must be displaced adequately, but
carefully, to avoid aortocaval compression.
Positioning for airway management Careful positioning is vital regardless of the primary anesthetic technique. A
study investigating the effects of position on laryngoscopic view in 60 morbidly obese non-pregnant patients
determined that the ramped position or head elevated laryngoscopy position (HELP) clearly improved the
laryngeal view when compared with the standard sniff position"
#$
Blankets, or one of the commercially available
pillow devices can be placed underneath the patients upper body and head until horizontal alignment is achieved
between the external auditory meatus and the sternal notch. This allows easy access to the airway and facilitates
placement of a laryngoscope (short-handled), if general anesthesia becomes necessary. However, some operating
room tables are equipped with a head section capable of angulation. By tilting this section downwards and then
flexing the table forwards, the ramped position can be created with the use of only one pillow to produce the exact
degree of angulation desired.
48
Since neuraxial anesthesia has been associated with a significant decrease in
spirometric parameters
49
a 30-degree head-up position may improve respiratory mechanics and oxygenation. Uterine
displacement is also necessary to avoid aortocaval compression by either the uterus and/or the panniculus.
Anesthetic plan Spinal (single-injection or continuous), epidural, CSE, and general anesthesia are all acceptable
techniques for CS but the choice of technique is dependent upon the clinical situation. Skills of the surgical and
anesthesia team, anticipated operative time, and communication
28
are imperative for making a decision about
anesthetic choice.
Although the 30 min decision to delivery interval (DDI) for CS is an optimal goal as defined by the ASA Optimal
Goals For Anesthesia Care in Obstetrics,
50
a DDI of 30 min is difficult to achieve consistently even when caring for
non-obese patients.
51,52
In morbidly obese parturients, the ability to achieve a DDI of 30 min is often unrealistic.
53

Most agree that these women should be delivered safely and not by the clock.
Spinal anesthesia Spinal anesthesia is the most common type of anesthesia utilized for CS because of its quick
onset, reliability, and dense surgical anesthesia. However, there are concerns about technical difficulties,
exaggerated spread of local anesthetic, hemodynamic compromise, and an inability to prolong the block. Spinal
anesthesia is reasonable if the airway exam is normal, there is no cardiorespiratory disease, and the surgery is
expected to be less than 90 minutes. It is often easier to identify the epidural space with a large gauge stiff epidural
needle compared to a smaller flexible spinal needle so that the epidural needle acts as an introducer.
In a large series of obese patients undergoing non-obstetric surgery who had received spinal anesthesia, more than
one-third developed hypotension.
54
Three of the patients also experienced cardiac arrest. Although decreased
cerebral spinal fluid volume has been confirmed in obese patients by magnetic resonance imaging.
55
Although,
higher levels of spinal anesthesia may result from reduced CSF volume,
55
the median dose of bupivacaine for
successful anesthesia in morbidly obese parturients undergoing CS was 9.8 mg using a randomized dose response of
spinal bupivacaine with fentanyl and morphine.
56
These study findings were similar to a previous study in nonobese
parturients. In order to avoid a high block when hyperbaric bupivacaine is used, a ramp can be placed under the
patients chest to elevate the cervical and thoracic spines to avoid the Trendelenburg position induced by large
buttocks since large buttocks may also increase cephalad spread. Regardless, spinal anesthesia should be performed
with caution because of the consequences of extensive blockade, prolonged surgery and the hazards of
intraoperative induction of general anesthesia. Continuous spinal anesthesia may offer the benefits of a single-
injection spinal (i.e., reliability, density).
57

Epidural anesthesia Epidural anesthesia offers several advantages over single-injection spinal anesthesia including
titratable dosing of local anesthetics, ability to prolong the block, decreased risk of excessive motor block, more
controllable hemodynamic changes, and utilization for postoperative analgesia. However, a multicenter prospective
observational study found that epidural anesthesia failed more often than spinal or CSE techniques.
58
Increased
maternal BMI was significantly related to failure of neuraxial techniques. Hodgkinson and Hussain
59
demonstrated
that the height of an epidural block for a given volume of local anesthetic is proportional to BMI and maternal
weight but not height. Incremental dosing of local anesthetics reduces risk of hypotension and high block.
Combined spinal-epidural anesthesia CSE offers advantages in cases where the surgical duration is unclear by
providing rapid onset and dense blockade with the flexibility of prolonging the anesthetic. However, one potential
disadvantage is an untested epidural catheter.

406
Page 6
General anesthesia should be avoided unless necessary. Hood and Dewan
29
found that one-third of morbidly obese
parturients were difficult to intubate versus none in the nonobese control group. The anatomic changes produced by
both pregnancy and obesity increase risk for difficult intubation, rapid desaturation, and hypoxia during periods of
apnea. The physiologic demands of pregnancy and obesity as well as reduced FRC reduce the period of time
available for direct laryngoscopy and intubation before hypoxemia ensues. The urgency of the obstetric situation
must be weighed against the risk of general anesthesia. If general anesthesia is necessary, additional experienced
personnel and difficult airway equipment must be available. In all cases, proper positioning of the neck,
shoulders, and chest is imperative and the key to successful intubation. In some cases, an awake fiberoptic
intubation may be the safest option but it poses its own problems. Nasal intubation should be avoided due to
mucosal engorgement and risk of hemorrhage. Hypertension and catecholamine release can adversely affect uterine
blood flow.
60
Fiberoptic intubation can be difficult and time-consuming. However, a recent study of patients with
anticipated difficult randomized to either awake fiberoptic (BMI 31 [14-57]) vs. awake video laryngoscopic (BMI
29 [18-47]) tracheal intubation determined that there was no difference of performance between the two
techniques,
61
suggesting that videolaryngoscopy may be useful as the primary device or first alternative for securing
the trachea, even when awake intubation is being considered.
62
If the patients airway appears normal, a rapid
sequence intubation in a ramped position can be performed following denitrogenation. Denitrogenation can be
accomplished with 3 minutes of tidal breathing or 4 maximal breaths with 100% oxygen.
63

Lean body weight is optimal for dosing most drugs used in anesthesia including opioids and induction agents.
64

Lean body weight is defined as 20-30% more than ideal body weight. Succinylcholine is the muscle relaxant of
choice. The dose of succinylcholine (1.0-1.5 mg/kg up to a maximum of 200 mg) is based on total body weight.
65

Verification of proper endotracheal intubation can only be accomplished by capnography. If intubation is
unsuccessful, a failed intubation drill should be instituted immediately.
66
The goal of failed intubation management
is to ensure maternal oxygenation despite concerns of fetal well-being or aspiration. Mask ventilation may require
several people, one to continue cricoid pressure, a second to institute jaw-thrust, and the third to squeeze the bag and
monitor the patient. Repeated attempts and additional succinylcholine are detrimental but a laryngeal mask airway
can be lifesaving.
67
In a recent report of 57 cases of failed intubation, the classical laryngeal mask airway was the
most commonly used rescue airway (39/57 cases).
21
There was one emergency surgical airway but no deaths or
cases of hypoxic brain injury. Gastric aspiration occurred in four (8%) cases.
In morbidly obese parturients, there are further reductions in FRC due to supine positioning, use of volatile
anesthetics, muscle relaxants, and retraction of the panniculus.
68
This leads to early closure of small airways and
hypoxemia. Increased tidal volumes, high-inspired oxygen concentrations, reverse Trendelenburg positioning, and
positive end-expiratory pressure
69
have been used to maintain oxygenation and ventilation. However, use of positive
end-expiratory pressure can worsen cardiac output and oxygen delivery to the fetus. Although isoflurane,
sevoflurane, and desflurane can be used in standard concentrations, desflurane provides a faster recovery.
70
Titration
of additional muscle relaxant may be needed besides an intubating dose of succinylcholine. Although the induction
of anesthesia was previously reported to be the most critical time during anesthetic administration in parturients,
more recent reports suggest that emergence, extubation, and recovery are the most critical periods of
anesthetic care in the obese parturient.
11
The morbidly obese parturient should only be extubated when she is
awake with adequate reversal of muscle relaxant. A head-up position should also be used instead of supine
positioning.

POST-OPERATIVE CARE
Morbid obesity increases the risk for postoperative complications, including: hypoxemia, atelectasis, deep venous
thrombosis, pulmonary embolus, pneumonia, pulmonary edema, postoperative endometritis, wound infection, and
dehiscence. Goals of effective postoperative care should be aimed at enhancing pulmonary function and preventing
venous thrombosis. Early ambulation, thromoboprophylaxis, chest physiotherapy, and effective postoperative pain
control are essential in preventing complications in these patients.
Postoperative respiratory depression Effective postcesarean analgesia is important to hasten recovery. Opioids
can be administered either neuraxially or parenterally but epidural morphine administration in the morbidly obese
has been shown to result in earlier ambulation, fewer pulmonary complications, and shorter hospital stay compared
to parenteral morphine administration.
71
Multimodal analgesic techniques (e.g., nonsteroidal anti-inflammatory
agents) should be used to decrease total opioid requirements.
26

Obesity and postoperative respiratory complications have been identified as significant risk factors for anesthesia-
related mortality in non-pregnant patients.
11
Postoperative respiratory depression from opioids continues to be a
significant cause of high-severity injuries often resulting in death or brain damage. After review of the Joint
Commissions Sentinel Event Database from 2004-11, the Joint Commission issued Sentinel Event Alert Issue 49 in

406
Page 7
2012 regarding the safe use of opioids.
72
The events included: wrong-dose medication (47%); improper monitoring
(29%); and excessive dosing, medication interactions, adverse drug effects (11%). To further evaluate the associated
factors for postoperative respiratory depression, The American Society of Anesthesiologists (ASA) Closed Claims
Database was examined and identified 341 acute pain claims occurring between 1990 and 2009.
73
In the study, there
was a higher proportion of claims for respiratory depression in obese patients compared to other acute pain claims.
There was also a higher proportion of these claims with death or severe brain damage. The authors concluded that
postoperative respiratory depression is a significant cause of death and brain damage associated with neuraxial
and/or patient controlled analgesia use and multimodal therapy. The authors suggested, poor communication
between prescribing physicians and nursing personnel is a common theme in opioid-induced respiratory depression
claims. Moreover, many physicians and nurses do not appreciate the synergistic effects that opioids,
benzodiazepines, some antietmtics and sleep aids have on respiratory drive.
The ASA has published recommendations for the postoperative care of patients with sleep apnea although they are
not pregnancy-specific.
26
Included in the guidelines are recommendations for postoperative monitoring:
Regional anesthetic techniques should be considered to reduce or eliminate the requirements for systemic
opioids in patients with OSA.
If neuraxial anesthesia is planned, the benefits and risks of using an opioid or opioid-local anesthetic
mixture as compared to local anesthetic alone must be considered.
If patient-controlled systemic opioids are used, continuous background infusions should be avoided or used
with extreme caution.
Nonsteroidal anti-inflammatory agents and other modalities should be considered to reduce opioid
requirements.
Supplemental oxygen should be administered continuously to all patients who are at increased
perioperative risk from OSA until they are able to maintain their baseline oxygen saturation while breathing
room air.
Hospitalized patients at increased risk of respiratory compromise from OSA should be monitored with
continuous pulse oximetry after discharge from the recovery room.

CRITICAL CARE AND RESUSCITATION
Caring for the critically ill obese parturient poses many of the same challenges that are seen on labor and delivery, in
terms of equipment, monitoring, and comorbidities. In addition, the nutritional status of these patients may be
difficult to address. Obese patients are also more likely to become ventilator-dependent and at increased risk for
developing acute lung injury (ALI) or acute respiratory distress syndrome (ARDS),
74
but the effect on outcomes in
these patients is still being explored.
Cardiopulmonary resuscitation in the morbidly obese parturient can also be challenging because of equipment and
technical concerns. Mechanical compression devices may be required. The maximum 400 J of energy delivered by
regular defibrillators is sufficient for the morbidly obese patient.
75
Several attempts at defibrillation may be required
because of there is a higher transthoracic impedance from the fat. Airway management may be challenging and may
require percutaneous cricothyrotomy, transtracheal jet ventilation, or retrograde wire intubation.

CONCLUSION
A complete understanding of the physiology, pathophysiology, comorbidies and their implications for analgesia and
anesthesia in morbidly obese parturients should lead to improved safety and anesthetic care. Communication
between the anesthesiologist, obstetrician, nursing staff, and patient is imperative in caring for these patients.

1. Popul Health Metr. 2012;10(1):22.
2. JAMA. 2012;307(5):491-497.
3. Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. 2009. Washington, DC:
The National Academies Press
4. J Obstet Gynaecol. 2006;26(6):527-530.
5. J Public Health. 2001;91(3):436-440.
6. Obstet Gynecol. 2004;103(2):219-224.
7. Int J Obes Relat Metab Disord. 2001;25(8):1175-1182.
8. Am J Obstet Gynecol. 2004;190(4):1091-1097.
9. Am J Obstet Gynecol.1988;159(1):187-193.
10. APSF Newsletter Summer 2007.
11. Anesthesiology. 2007;106(6):1096-1104.

406
Page 8
12. BJOG. 2011;118 Suppl 1:1-203.
13. Am J Obstet Gynecol. 2004;191(3):939-944.
14. Anesthesiology. 2011;115(5):963-972.
15. Obstet Gynecol. 2005;106(6):1228-1234.
16. Obstet Gynecol. 2012;120(4):929-934.
17. Obstet Gynecol. 2012;119:360-364.
18. Obstet Gynecol. 2013;121(1):213-217.
19. Int J Gynaecol Obstet.1990;31(3):227-230.
20. Anaesthesia. 2000;55(7):690-694.
21. Br J Anaesth. 2013;110(1):74-80.
22. Anaesthesia. 1987;42(5):487-490.
23. Anesthesiology. 2008;108(3):357-362.
24. Eur J Anaesthesiol. 2008;25(9):714-720.
25. Obstet Gynecol. 2012;119(2 Pt 1):345-359.
26. Anesthesiology 2006;104(5):1081-1093.
27. Int J Obstet Anesth. 2013;22(2):113-118.
28. Anesthesiology. 2007;106(4):843-863.
29. Anesthesiology. 1993;79(6):1210-1218.
30. BJOG. 2006;113(10):1178-1181.
32. Anesth Analg. 2009;109(4):1225-1231.
34. Anaesthesia. 1983;38(9):840-851.
35. Anaesth Intensive Care. 1993;21(3):309-310.
36. Anesth Analg. 2009;108(6):1876-1881.
37. Anesth Analg. 2013;116(4):829-835.
39. Anesthesiology. 1997;86(4):778-784.
40. Reg Anesth Pain Med. 2003;28(6):512-515.
41. Obes Rev. 2007;8(5):385-394.
42. Obstet Gynecol. 2011;117(1):69-74.
43. Am J Obstet Gynecol. 2010;203(3):276 e271-275.
44. Obstet Gynecol. 2011;117(6):1472-1483.
45. APSF Newsletter. 2013;Spring-Summer 2013:23-24.
46. BJA. 1980;52(9):919-923.
47. Obes Surg. 2004;14(9):1171-1175.
48. Anaesthesia. 2012;67(2):184.
49. Anaesthesia. 2006;61(3):215-221.
50. http://www.asahq.org/ForMembers/~/media/
For%20Members/documents/Standards%20Guidelines%20Stmts/Opitmal%20Goals%20Anesthesia%20Ca
re%20Obstetrics.ashx. date accessed: 6/4/13.
51. Obstet Gynecol. 2006;108(1):6-11.
52. BJOG. 2002;109(5):498-504.
54. JAMA. 1961;175:657-665.
55. Anesthesiology. 1996;84(6):1341-1349.
56. Anesthesiology. 2011;114(3):529-535.
58. Obstet Gynecol. 2005;106(2):281-287.
59. Anesth Analgesia. 1981;60(6):421-424.
60. Anesthesiology. 1979;50(6):524-527.
61. Anesthesiology. 2012;116(6):1210-1216.
62. Anaesthesia. 2012;67(3):232-235.
63. Anesthesiology. 1985;62(6):827-829.
64. BJA. 2010;105 Suppl 1:i16-23.
65. Anesth Analg. 2006;102(2):438-442.

406
Page 9
66. Anesthesiology. 2003;98(5):1269-1277.
67. Anaesthesia. 2005;60(2):168-171.
68. Ann Surg. 1976;184(1):35-42.
69. Anesthesiology. 1999;91(5):1221-1231.
70. Anesth Analg. 2004;99(6):1848-1853, table of contents.
71. Anesth Analg. 1984;63(6):583-592.
72. Commission J. Safe use of opioids in hospitals. Sentinel Event Alert. August 8, 2012 2012;49:1-5.
73. American Society of Anesthesiologists Newsletter. 2013;77:34-36.
74. Thorax. 2010;65(1):44-50.
75. Circulation. 1978;57(4):827-830.

Disclosure
412
Page 1
Anesthetic Management of the Preeclamptic Patient
Joy L. Hawkins, M.D. Aurora, Colorado
Introduction
Hypertensive disorders of pregnancy are responsible for 15% of maternal deaths after a live birth in the U.S, with
death usually resulting from a cerebrovascular accident. (1) Preeclampsia occurs in 6-8% of pregnancies; 75% of
cases are mild and 25% are classified as severe. Anesthesiologists will be involved when these high risk parturients
deliver, and we should consider ourselves an important part of the team caring for these and all critically ill obstetric
patients. The most recent triennial report on maternal mortality in the United Kingdom found that the anesthetic
management (or its lack) contributed in 8 of 19 deaths due to preeclampsia or eclampsia.(2)
Definitions
The American College of Obstetricians and Gynecologists (ACOG) has a classification system for hypertensive
diseases of pregnancy.(3) The system clarifies terminology and provides an estimate of risk for the mother and fetus.
Preeclampsia / Eclampsia presents after 20 weeks gestation with hypertension > 140/90, proteinuria, and a
spectrum of multi-organ system dysfunction such as thrombocytopenia. HELLP syndrome is a subset of
severe preeclampsia defined by hemolysis (H), elevated liver enzymes (EL) and low platelets (LP).
Chronic hypertension is unrelated to pregnancy and presents before 20 weeks gestation (or before
conception).
Preeclampsia superimposed on chronic hypertension presents with new onset thrombocytopenia or
proteinuria. This diagnosis carries substantial risk for the mother and fetus.
Transient or gestational hypertension is hypertension in late pregnancy without other evidence of
preeclampsia that completely resolves postpartum. There is minimal risk to the mother or her fetus.
The terms PIH or pregnancy-induced hypertension are no longer used.
Etiology and Pathogenesis
Despite decades of research, the etiology of preeclampsia remains unknown. Theories include placental ischemia,
immunologic origin, and genetic predisposition. No theory has withstood the test of time, and no preventive
measure has proven useful. Preventive measures that have been tested include supplementation with magnesium,
zinc, fish oil, anti-oxidant vitamins (C and E) and calcium, protein or salt restriction, antihypertensive medications
in women with chronic hypertension, heparin or LMWH treatment, and exercise.(4) None have reduced the
incidence of preeclampsia. Low-dose aspirin therapy has led to a small decrease in preeclampsia and fetal/neonatal
deaths in some studies, and may be used in high-risk pregnancies. In contrast, the risk factors for developing
preeclampsia are well known: nulliparity, extremes of age (< 18 and > 35), a family or personal history of
preeclampsia, barrier contraception, donor egg or sperm, African-American race, obesity, multiple gestation (twins,
triplets), thrombophilias, and vascular diseases such as diabetes, collagen vascular disorders, and chronic
hypertension.
The pathophysiology of preeclampsia develops in early and late stages. The early stage involves abnormal
placentation. The spiral arteries fail to become the dilated, flaccid vessels seen in normal pregnancies, and may even
show signs of atherosis. The placenta becomes ischemic and releases vasoactive substances. Later in gestation, the
disease manifests as a maternal systemic disorder with increased vascular sensitivity to any pressor agent, activation
of the coagulation cascade, microthrombi and intravascular fluid loss. Vasospasm, hemoconcentration, and
ischemic changes in the placenta, kidney, liver and brain are seen.
Prediction and Diagnostic Tools
A gene encoding a protein (sFlt1) is overactive in preeclamptic placentas. sFlt1 is known to thwart blood vessel
growth; i.e., it is anti-angiogenic. There is growing evidence that measuring elevated antiangiogenic proteins such

412
Page 2
as soluble Flt1 and soluble endoglin can predict preeclampsia months before its clinical onset.(5) These proteins are
secreted by the placenta and increase in the maternal circulation weeks before the onset of preeclampsia, producing
systemic endothelial dysfunction such as hypertension, proteinuria and other manifestations of preeclampsia. A
systematic review of the literature on use of elevated sFlt-1 and reduced placental growth factor (PlGF a pro-
angiogenic protein) to predict preeclampsia concluded that third-trimester increases in sFlt-1 combined with
decreases in placental growth factor levels are associated with severe preeclampsia. Measuring soluble sFlt-1 and
soluble endoglin levels in gestational hypertension, chronic hypertension, preeclampsia and normal pregnancies
demonstrated a high sensitivity and specificity in differentiating women with preeclampsia from those with other
hypertensive diseases during pregnancy.(5) In the future, alterations of these proteins might be used as a screening
test for early diagnosis of preeclampsia. A pilot study of 5 very preterm pre-eclamptic women used apheresis
treatments to remove elevated circulating sFlt-1, in an attempt to prolong the pregnancy.(6) In addition to lowering
circulating sFlt-1 levels, the treatment reduced proteinuria and stabilized blood pressure without adverse effects on
mother and with evidence of interim fetal growth.

Controversial Areas in the Clinical Management of the Patient with Preeclampsia
When and by what route should delivery occur, especially when preeclampsia develops early in the 3
rd

trimester?
When is invasive monitoring needed to optimize care of the mother?
What are the benefits and risks of various anti-hypertensive medications?
How should we manage an eclamptic seizure?
Why administer magnesium sulfate rather than other anti-seizure medications?
How should we optimize fluid intake?
Platelet counts how low can we go and still safely administer neuraxial anesthesia?
Is spinal anesthesia for cesarean delivery safe and appropriate in severe preeclampsia?
Should !-agonists (e.g. phenylephrine) replace ephedrine as our first-line pressor to treat hypotension?

Current Obstetric Management Strategies
The only cure for preeclampsia is delivery, but the benefit to the mother must be weighed against the risks of
prematurity to the fetus. Women with gestational hypertension or mild preeclampsia may be managed expectantly
at home with frequent maternal monitoring and fetal surveillance. Patients with severe preeclampsia must be
admitted to L&D for maternal and fetal assessment and development of a delivery plan. Those with a favorable
cervical exam may undergo induction, but elective cesarean delivery may be preferable in very preterm pregnancies
if the cervical exam is unfavorable. Neonates delivered vaginally have a lower incidence of RDS.
Maternal assessment must define the extent of end-organ involvement. Systems evaluated should include:
hematologic (" platelets, hemolysis), hepatic (epigastric pain, # LFT), neurologic (headache, visual changes), renal
(oliguria, proteinuria, # creatinine), pulmonary (pulmonary edema), and placental (growth restricted fetus,
oligohydramnios, abnormal umbilical artery Doppler studies). Fetal evaluation will include a non-stress test,
ultrasound for amniotic fluid volume, fetal growth percentile and estimate of gestational age, and a biophysical
profile. Based on these results, a decision for immediate delivery or in-hospital expectant management will be
made. If the pregnancy is < 34 weeks, the obstetrician may delay delivery for 48 hours to administer steroids for
fetal lung maturity, but this requires daily maternal and fetal monitoring, magnesium sulfate infusion, and anti-
hypertensive drugs as needed for systolic BP > 160 or diastolic BP > 110 mmHg.(7) Delivery is required for
worsening maternal or fetal condition. Patients who are not candidates for expectant management include women
with eclampsia, pulmonary edema, DIC, renal insufficiency, abruption, abnormal fetal testing, HELLP syndrome, or
persistent symptoms of severe preeclampsia.
HELLP syndrome is a variant of severe preeclampsia. Administration of high-dose glucocorticoids
(dexamethasone 10 mg BID for example) has been reported to improve maternal and fetal outcome, but without
large multicenter trials to define the limits of benefit and any maternal or fetal risk. A review of the literature on
glucocorticoids for HELLP syndrome (including a management algorithm) concludes that the bulk of evidence to
date is positive - improved platelet count, reduced stroke and death, and less hepatorenal morbidity. The authors
conclude that glucocorticoids should be considered during treatment of HELLP syndrome.(8)

Management of Hypertension and Use of Invasive Monitoring
The goal of anti-hypertensive therapy is prevention of maternal morbidity from pulmonary edema or cerebral
hemorrhage by decreasing systolic blood pressure < 160 mmHg and diastolic < 110 mmHg. At the same time,

412
Page 3
treatment should not impair uteroplacental perfusion or cause fetal compromise. Systolic hypertension may be more
important than diastolic for preventing stroke related to severe preeclampsia.(9) A review found that 93% of the
strokes in their series were hemorrhagic, 54% of women died, and almost all who lived had severe permanent
disability. All had systolic pressure >155 mmHg while only 12% had diastolic pressure >110.
Use of invasive monitoring is rarely necessary in obstetric patients. To quote, Critically ill obstetric
patients differ from those usually encountered in medical-surgical intensive care units. They are likely to be
younger, to have fewer major organ systems involved, to have fewer chronic illnesses, and to recover fully with
supportive care.(Chest 1992) However, arterial lines are low risk and can be useful when blood pressures are
consistently > 160/110 mmHg and when vasodilator infusions are used. They may also be helpful for patients with
coagulopathy who need frequent blood draws, and when the patient is obese or has marked edema making
venipuncture difficult. If pulmonary edema develops, the arterial line can be used to monitor arterial blood gases.
Pulse waveform analysis (e.g., LiDCOplus) can be used with an arterial line for hemodynamic monitoring as it
correlates well with thermodilution measurements from a pulmonary catheter.(10) In contrast, central venous
monitoring is higher risk and has not been shown to affect outcome. A CVP or PA catheter may be useful if there is
cardiac failure or pulmonary edema, a large A-a oxygen gradient, or oliguria despite fluid administration and
afterload reduction. Consider your nursing resources on L&D before initiating invasive monitoring however. Can
the L&D nursing staff manage a CVP or pulmonary artery catheter on L&D, or will ICU admission be necessary?
The ACOG Committee Opinion entitled Emergent Therapy for Acute-Onset, Severe Hypertension with
Preeclampsia or Eclampsia defines a hypertensive emergency as lasting 15 minutes or longer with systolic pressure
> 160 mmHg or diastolic pressure > 110 mmHg.(11) Previous work has shown hypertension is the most important
predictor of cerebral hemorrhage or infarction and can result in maternal death. Intravenous labetalol or hydralazine
are considered first-line treatments, and the document includes order sets for both. Importantly for
anesthesiologists, the document states that if these two medications fail to control her blood pressure, emergent
consultation with an anesthesiologist, maternal-fetal medicine subspecialist, or critical-care specialist to discuss
second-line intervention is recommended.
Many agents are effective and safe to use as anti-hypertensives:
1. Magnesium sulfate has no substantial long-term effect on blood pressure, but has other benefits. It
attenuates the vascular response to pressor substances (either endogenous or exogenous) and dilates
vascular beds by increasing prostacyclin release from endothelial cells, decreasing plasma renin activity,
and decreasing ACE levels.
2. Hydralazine 5-20 mg is a popular choice in obstetrics because it is an arteriolar vasodilator that increases
uterine and renal blood flow. However it has an unpredictable onset and duration, causes reflex
tachycardia and occasional ventricular arrhythmias. It has also been reported to cause neonatal hypotension
by crossing the placenta.
3. Labetalol decreases systemic vascular resistance without maternal tachycardia and while preserving
placental blood flow. It does not cause sympathetic blockade in the neonate. It can be transitioned to an
oral form after delivery. However its dosing and duration may be quite variable.
4. Nitroprusside has a fast onset, short duration, and preserves uterine blood flow. However there is reflex
tachycardia and the potential for cyanide toxicity. It causes cerebral vasodilation and potential hypoxia
from decreased hypoxic pulmonary vasoconstriction. Finally, it is inconvenient to use and requires an
arterial line, as does nitroglycerin.
5. Calcium channel blockers such as nifedipine and nimodipine cause a rapid smooth fall in blood pressure
while increasing renal perfusion and urine output. Although there has been concern about combining
magnesium with nifedipine therapies, a study found that in women receiving magnesium sulfate therapy,
there was no increase in muscle weakness over magnesium alone and there was less hypotension with
nifedipine than with other anti-hypertensives. Nimodipine reverses cerebral vasospasm as measured by
trans-cranial Doppler, and is well-tolerated by mother and fetus. However, calcium channel blockers cause
uterine relaxation, making induction of labor more difficult and potentially causing atony and hemorrhage
after delivery.
6. ACE inhibitors and angiotensin receptor blockers are contraindicated in all trimesters of pregnancy due to
teratogenicity. Also avoid atenolol (IUGR concerns) and diuretics for chronic management. (12)

Prevention and Management of Seizures / Eclampsia
Eclampsia has a maternal mortality rate of ~ 4% and a perinatal mortality rate of up to 30%. Seizures occur
antepartum in 50% of patients, intrapartum in 25% and postpartum in 25%. Why do we use magnesium to prevent
eclampsia versus other anti-seizure medications? In large randomized clinical trials, magnesium has been proven

412
Page 4
superior to placebo (58% lower risk of seizures), phenytoin (no seizures in the magnesium group versus ~1% in the
phenytoin group), diazepam (52% lower risk of recurrent convulsions), and nimodipine (risk of eclampsia was 3.2
times higher in the nimodipine group). No drug is superior to magnesium at preventing eclampsia.(13,14)
Magnesium therapy can cause maternal morbidity and unpleasant side effects however. It has tocolytic
properties that prolong labor and increase bleeding at delivery. It decreases fetal heart rate variability, depresses
maternal and neonatal neuromuscular function, and can cause maternal respiratory depression and cardiac toxicity at
toxic blood levels. Clearance is reduced with renal insufficiency, and signs of toxicity are only partially reversed
with calcium.
Since major complications of preeclampsia primarily occur in the 25% of patients with the severe form of
the disease, should mild preeclampsia even be treated with magnesium? What is the risk/benefit ratio for the
mother? A decision analytic model of magnesium therapy or no magnesium therapy found that 400 women with
mild preeclampsia need to be treated to prevent one seizure. The number needed to treat to prevent a seizure (NNT)
fell to 129 in severe preeclampsia, and the NNT fell to only 36 in severely preeclamptic women who had symptoms
such as headache, visual disturbances or epigastric pain.(15) Not all women with mild preeclampsia will need to
receive magnesium sulfate therapy.
When an eclamptic seizure occurs, the following steps should be taken:
Administer high flow supplemental oxygen by mask and place a pulse oximeter.
Turn her full left or right lateral decubitus and have suction immediately available.
Give a small dose of propofol or benzodiazepine to terminate the seizure if available. Avoid poly-
pharmacy and long-lasting medications so that a neurologic exam can be done as soon as possible.
Administer an additional 2 gram magnesium sulfate bolus.
Monitor the fetus if possible, but realize that heart rate abnormalities are common during a seizure and
usually resolve soon after the seizure is terminated. Do not intervene to deliver immediately unless
abruption or cord prolapse has occurred.
Consider CT or MRI imaging to rule out a cerebral hemorrhage if seizures are recurrent or focal, if
seizures occur despite therapeutic and repeated magnesium dosing, or if there is decreasing level of
consciousness when not post-ictal.
Although eclampsia is an indication for delivery, it is not an indication for cesarean delivery. When
eclamptic patients were randomized to vaginal delivery or cesarean, there was no difference in maternal or
newborn adverse events. (34) Consider whether induction of labor is feasible.

Anesthetic Management During Labor and Delivery
When the decision has been made to proceed to delivery, the anesthesiologist must have plans for three potential
scenarios in mind: 1) labor followed by a spontaneous or instrumented vaginal delivery, 2) trial of labor followed
by an urgent or emergent cesarean for fetal or maternal reasons, and 3) planned cesarean for the patient who is not a
candidate to labor. All plans must take into account whether neuraxial techniques are appropriate based on platelet
count or other measures of coagulopathy.
Labor Analgesia
The advantages of neuraxial analgesia for labor are numerous. It provides the best quality of pain relief,
attenuates hypertensive responses to pain, reduces circulating catecholamines, and does not require fluid preload
when dilute local anesthetic + opioid solutions are used. Two studies have compared the use of intravenous patient-
controlled opioids (IV PCA) to epidural analgesia for women with severe preeclampsia. In the first, 738 women
were randomized to IV PCA or epidural, and cesarean delivery rates were similar.(16) Neonates in the IV PCA
group required more naloxone (12% versus 1%), but women in the epidural group had a longer second stage of
labor, more forceps deliveries and required ephedrine more often (11% versus 0%). Not surprisingly, epidural pain
relief was superior.(16) Results were similar in the second study.(17) They found no difference in cesarean
delivery rates, but neonates were more likely to receive naloxone in the opioid group (54% versus 9%), and epidural
patients had significantly better pain relief but required more ephedrine (9% versus 0%). Perhaps most importantly,
there were no differences in preeclampsia-related complications.(17) ACOG makes a strong statement in their
Practice Bulletin Diagnosis and Management of Preeclampsia and Eclampsia: With improved techniques over the
past two decades, regional anesthesia has become the preferred technique for women with severe preeclampsia and
eclampsia both for labor and delivery. A secondary analysis of women with severe preeclampsia in the NICHD
trial of low-dose aspirin reported that epidural anesthesia was not associated with an increased rate of cesarean
delivery, pulmonary edema or renal failure.(18)

412
Page 5
Fluid Management
Fluid management has been a controversial subject, with obstetricians wanting to restrict fluids and
anesthesiologists wanting to administer fluids, however the obstetric view is probably correct. The vasculature in
preeclamptic patients has been described as contracted and porous due to endothelial damage but not underfilled. In
addition to endothelial damage, the colloid oncotic pressure is low in pregnancy, and even lower in preeclamptic
patients with proteinuria. Crystalloids and colloids readily leak out, increasing the risk of postpartum pulmonary
edema. Typical obstetric management is to run dry at 80-100 ml per hour total fluid intake including magnesium
and oxytocin infusions. Anesthetic fluid management should complement theirs, using conservative preload for
surgical regional anesthesia and no preload for labor analgesia. Many studies including a systematic review have
shown little if any benefit of preloading in preventing hypotension during obstetric regional anesthesia (19)
Coagulopathy and Platelet Counts
Despite years of concern and study, there is still no test of platelet function and no specific platelet count
that predicts bleeding into the neuraxis after regional anesthetic techniques. For patients with preeclampsia, many
anesthesiologists are comfortable with platelet counts as low as 75,000 provided the count is stable and not falling,
and that there are no signs of clinical bleeding at venipuncture sites, gums, etc. Thromboelastography (TEG) can
add information if the test is available, but there is still no cut-off value for any TEG variable that predicts
complications. Since pregnancy is a thrombophilic state, parturients have tremendous reserve before becoming
coagulopathic. A review of 1.7 million spinal or epidural blocks found that complications were more common after
epidural than spinal anesthetics, and that obstetric patients were less likely than surgical patients to have an injury
(1:25,000 obstetric patients versus 1:3600 after surgical epidurals in females). (20) There were 2 obstetric patients
in their series that developed a neuraxial hematoma, for an incidence of 1:200,000. One occurred after a spinal and
the other after epidural catheter removal; both patients had HELLP syndrome. This low incidence is reassuring, but
balance the risk-benefit ratio for each case and each patient.
Factors that might support using a regional technique even with borderline labs would include a worrisome
airway exam, the prospect of a lengthy induction of labor, and the rarity of an epidural hematoma. Factors that
would support avoidance of regional anesthesia and use of IV opioids or general anesthesia would be clinical signs
of bleeding, a rapidly worsening platelet count, the need for an urgent cesarean and a good airway. Even if you feel
that neuraxial analgesia is not appropriate, remember that anesthesiologists are consultants in pain management.
Our obstetric colleagues may appreciate help with an IV regimen for the patients labor analgesia. For example,
fentanyl can be used in an IV PCA as follows: give an IV bolus loading dose of 2-3 $g/kg to initiate analgesia. Set
the PCA pump for a 50 $g incremental bolus, 10 minute lockout interval and no basal rate. As labor progresses and
titration is needed, decrease the lockout from 10 to 5 minutes, then increase the bolus dose from 50 to 75 $g.(21)
Cesarean Anesthesia
The choices for cesarean anesthesia are epidural, spinal (or combined spinal-epidural) and general. In the
past, spinal anesthesia was avoided because of concerns that hypotension would be more severe and less treatable
than that seen after sympathectomy from an epidural anesthetic. However, a comparison of women with severe
preeclampsia to healthy women, all having cesarean delivery with a spinal anesthetic, found that preeclamptic
women actually had less hypotension (17% versus 53%) despite receiving less fluid preload and (by chance) a larger
dose of bupivacaine in their spinal.(22) A randomized comparison of spinal or epidural anesthesia for cesarean
delivery in women with severe preeclampsia found that although hypotension was more frequent after spinal and
required slightly more ephedrine, the duration of hypotension was short and neonatal outcomes were similar in both
groups.(23) A small study of stable eclamptic patients described their cesarean deliveries under spinal anesthesia
without intraoperative complications such as excessive hypotension or additional seizures.(24)
Regardless of the choice of neuraxial technique (spinal or epidural), pressors must be immediately available
to treat even mild hypotension since these fetuses may not tolerate any decrease in uteroplacental perfusion.
Clinical studies in humans have consistently shown that use of !-agonists such as phenylephrine produce better
umbilical pH values in the newborn than use of ephedrine.(25) A study randomizing women with severe
preeclampsia to spinal or general anesthesia for cesarean delivery for non-reassuring fetal heart tones found that
spinal anesthesia was associated with more acidotic fetal pH values and higher base deficits.(26) Maternal
hemodynamics were similar between groups, but the patients receiving spinal anesthesia received more ephedrine
(14 mg versus 3 mg) than those in the general anesthesia group. Phenylephrine was not used. Did the use of
ephedrine worsen fetal acidosis? If maternal heart rate is above 70, choose phenylephrine as the first-line pressor
agent.
If general anesthesia is chosen, focus on attenuating hypertensive responses during laryngoscopy and
intubation, managing a difficult edematous airway, and treating complications related to magnesium therapy such as
uterine atony and maternal weakness. A number of adjuncts to rapid sequence induction have been described and

412
Page 6
used successfully to control hypertension associated with laryngoscopy, e.g. esmolol, labetalol, lidocaine,
remifentanil and nitroglycerin. Include at least one as part of a rapid sequence induction, or have them immediately
available to treat hypertension if it occurs. Airway management may be difficult. Use of the laryngeal mask airway
(LMA) has been described in the setting of HELLP syndrome when there was inability to intubate or ventilate.(27)
Postoperatively, this patient was even ventilated for 8 hours in the ICU using the LMA.
Magnesium therapy has anesthetic interactions. Magnesium is a uterine relaxant, and additional oxytocics
such as Cytotec or Hemabate should be available to treat uterine atony after delivery in addition to the oxytocin
infusion. Magnesium also causes skeletal muscle weakness. If the mother exhibits muscle weakness prior to
induction (i.e., can she do a 5-second head lift before her anesthetic?), it may be best to discontinue the magnesium
sulfate infusion during the case and let her magnesium level decrease. Non-depolarizing muscle relaxants should be
avoided. If she cannot meet criteria for safe extubation at the end of the cesarean, she may require a brief period of
mechanical ventilation until she is strong enough to protect her airway.
Postpartum Care
Postpartum issues will require intense monitoring on L&D. If general anesthesia was used, consider
transversus abdominis plane (TAP) blocks to supplement analgesia.(28) The mother may need both acute and long
term blood pressure control with anti-hypertensives. Fluid mobilization will begin to occur during the first 24 hours
postpartum, and this is when she is most at risk for pulmonary edema. Monitor urine output, lung fields and pulse
oximetry. Thrombocytopenia may not resolve for several days. If she has an epidural catheter in place, decide
when removal is appropriate based on her platelet count and coagulation studies. About a third of eclamptic seizures
occur postpartum. A review of 89 cases of eclampsia found that 33% of seizures occurred postpartum and 79% of
those presented > 48 hours postpartum.(29) Most did not have an antepartum diagnosis of preeclampsia, but most
did have prodromal symptoms such as headache and visual changes. If the anesthesia team is called to evaluate a
headache, be vigilant and consider late-presenting preeclampsia in your differential diagnosis.
Prognosis After the Diagnosis of Preeclampsia
Does development of preeclampsia provide a marker for maternal disease risks later in life? A growing literature
indicates that pregnancy is a form of stress test that may predict later health issues in the mother. About 17% of
preeclamptic women will continue to be hypertensive based on risk factors, and the OR for recurrence in a
subsequent pregnancy is 4.3.(30) For example, post-menopausal women who had preeclampsia decades earlier were
57% more likely to have coronary calcification on CT.(31) A 22-year follow-up of formerly preeclamptic women
versus controls found hypertension present in 55% of the formerly preeclamptic women and only 7% of the
controls.(32) These studies all recommend better long term follow-up of preeclamptic women; the implications of
this disease do not end at delivery.

In Conclusion:
Be conservative with your fluid preload before neuraxial procedures.
Normalize low blood pressure with phenylephrine in preference to ephedrine.
The goal for management of hypertension is to keep maternal pressure close to her baseline to sustain
uteroplacental perfusion, but < 160 mmHg systolic to prevent maternal cerebrovascular
complications.
Use platelet count trends and your clinical judgment. There is no absolute platelet count or TEG
value to use as a cut-off for use of neuraxial anesthetic techniques.
Spinal anesthesia for cesarean delivery is safe. Limit fluid preload and treat hypotension
aggressively with !-agonist medications.
Participate as part of the L&D team when caring for high risk obstetric patients.(33)

412
Page 7
References
1. Obstet Gynecol 2010;116:1302
2. BJOG 2011;118:105
3. Am J Obstet Gynecol 2000;183:S1-23
4. Lancet 2005;365:785
5. Am J Obstet Gynecol 2012;206:58
6. Circulation 2011;124:940
10. Br J Anesth 2011;106:77
13. Lancet 2002;359:1877
14. NEJM 2003;348:304
19. Anesth Analg 2011;113:677
20. Anesthesiology 2004;101:950
21. Clin Obstet Gynecol 2003;46:616
22. Anesth Analg 2003;97:867
23. Anesth Analg 2005;101:862
24. J Clin Anesth 2011;23:202
25. Br J Anesth 2004;92:459
27. Anesth Analg 2004:98:1467
28. Int J Obstet Anesth 2012;21:112
31. Hypertension 2007;49:1
33. Anaesthesia 2012;67:1009
Disclosure
418
Page 1
Neonatal Resuscitation: What the Anesthesiologists Needs to Know
Valerie Arkoosh, M.D., MPH Philadelphia, Pennsylvania
Following birth, numerous physiologic changes must rapidly transpire in order for the fetus to successfully
make the transition to a neonate. Despite the complexity of this process, on average ten percent of newborns require
some assistance to begin breathing and only one percent of newborns require full resuscitation in the delivery room.
1

This percentage rises quickly, however, among newborns who weigh less than 1500 grams. Given the relative rarity
of the need for full resuscitation, it is optimal for all delivery room personnel to frequently review the neonatal
adaptations to extrauterine life, make provision for resuscitation, understand the predictors of need for resuscitation
and know how to respond appropriately.
Neonatal Adaptations to Extrauterine Life
2,3
The placenta is the organ for gas exchange in the fetus. A
substantial right-to-left shunt exists. The shunt persists due to high pulmonary vascular resistance (PVR) coupled
with low systemic vascular resistance (SVR). Ninety percent of right ventricular output shunts across the ductus
arteriosus. Forty percent of cardiac output flows to the low resistance placenta. During vaginal delivery,
compression of the infant thorax expels fluid from the mouth and upper airways. With crying, the lungs fill with air,
surfactant is released and oxygenation increased. In animal models, the presence of increased oxygen tension and
increased blood flow stimulate endothelial cells in the pulmonary vasculature to release nitric oxide ultimately
resulting in pulmonary vasodilatation.
4
These changes significantly decrease PVR. Simultaneously, clamping of the
umbilical cord removes the low resistance placental bed from the circulation, increasing SVR. Within minutes after
birth the right-to-left shunt across the foramen ovale and ductus arteriosus is substantially reduced. Transient
hypoxemia or acidosis is well tolerated by a normal newborn and prompt resuscitation usually prevents any
permanent physiologic alteration. Prolonged neonatal hypoxemia or acidosis impedes the transition from fetal to
neonatal physiology. The fetus/neonate initially responds to hypoxemia by redistributing blood flow to the heart,
brain and adrenal glands. Tissue oxygen extraction increases to the maximum extent possible. Eventually, as
additional oxygen extraction is unattainable, myocardial contractility and cardiac output decrease. Hypoxemia and
acidosis promote patency of the ductus arteriosus, counteracting the normal neonatal increase in pulmonary artery
blood flow. Blood flowing through a patent ductus arteriosus is not oxygenated, contributing to increasing
hypoxemia. Spontaneous ventilatory drive is reduced by both indirect central nervous system depression and direct
diaphragmatic depression. The net result of these physiological responses is a neonate with persistent pulmonary
hypertension and little or no ventilatory drive. Ideally, prompt resuscitation prevents these physiologic perturbations.
Preparation for Resuscitation Preparation for neonatal resuscitation is an ongoing activity on all labor and
delivery units. A number of tasks including acquisition and maintenance of the proper equipment, identification,
education and training of responding personnel and development of contingency plans for additional personnel if
418
Page 2
needed must be constantly monitored for completeness. Equipment and medications should be organized together in
one location in the delivery room, checked frequently for proper functioning and expiration date, and replenished
immediately after use (Table 1).
1

At least one person skilled in newborn resuscitation should attend every delivery. Additional personnel
should be available when a high-risk delivery is anticipated. The importance of trained personnel following protocol
driven maneuvers is critical. The need for anesthesia personal to participate in neonatal resuscitation is likely to
increase as pediatric residents
spend more time in primary
care training and less in
neonatology. A recent survey of
the proficiency of third year
pediatric residents at
performing neonatal
endotracheal intubation (n=131
observed intubation attempts)
found that intubation was
successful on the first or second
attempt by only 62% of these
residents.
5
The technical
competency of pediatricians at
performing neonatal
endotracheal intubation should
be assessed on an individual
basis and not assumed to be
present by the anesthesia team.
In determining need for personnel trained in neonatal resuscitation, anesthesiologists in the United States can refer to
Guideline VII of the American Society of Anesthesiology, Guidelines for Regional Anesthesia in Obstetrics. The
guideline states: "Qualified personnel, other than the anesthesiologist attending the mother, should be immediately
available to assume responsibility for resuscitation of the newborn. The primary responsibility of the
anesthesiologist is to provide care to the mother. If the anesthesiologist is also requested to provide brief assistance
in the care of the newborn, the benefit to the child must be compared to the risk to the mother."
Assessment of Risk By using ante- and intrapartum fetal assessment, the need for neonatal resuscitation can
be predicted in about 80% of cases. Antepartum assessment includes evaluation for major fetal anomalies and
identification of maternal factors that may influence fetal well being (Table 2).
1,2
Intrapartum events often predict
the need for neonatal resuscitation (Table 3).
1,6
Assessment must continue throughout labor as the clinical situation
can change rapidly. Intrapartum evaluation includes fetal heart rate monitoring with, when indicated, fetal scalp
stimulation or fetal scalp blood sampling for pH determination. Intrapartum fetal heart rate (FHR) monitoring is the
first line of fetal assessment.
7
FHR monitoring is most reliable in confirming fetal well-being and is more than 90%
accurate in predicting a 5 minute Apgar score greater than 7.
8,9
In predicting fetal compromise, however, FHR
monitoring has a false positive rate of at least 35-50%.
9,10
Even though an abnormal fetal heart rate trace may not
correlate well with a poor long-term prognosis, the presence of an abnormal tracing is highly correlated with the
need for neonatal resuscitation in the delivery room.
6
Additionally, it is important to remember that even in the
presence of a reassuring fetal heart rate trace nearly 50% of babies born by cesarean delivery will require some
active form of resuscitation.
6
Fetal pulse oximetry has been tested as a method of intrapartum fetal assessment.
Consensus from several large human trials is that normal fetal oxygen saturation is between 35% and 65% and that
metabolic acidosis develops after the fetal oxygen saturation is less than 30% for 10 to 15 minutes.
11-13
One
randomized study of 1010 patients found a >50% reduction in the number of cesarean deliveries performed for
nonreassuring fetal status when fetal pulse oximetry data was used compared with FHR monitoring alone but, no
difference in the overall cesarean delivery rate or neonatal outcome between the two groups.
14
A larger randomized
trial of 5341 nulliparous women found no difference in the cesarean delivery rate when clinicians had access to fetal
pulse oximetry data and no difference in neonatal outcome between the two groups.
15
Thus, there is no evidence to
support the clinical use of fetal pulse oximetry.
16

Table 1. Equipment & Medications for Neonatal Resuscitation
Suction Equipment
Bulb syringe
Mechanical suction
Suction catheters 5F - 10F
Meconium Aspirator
Bag & Mask Equipment
Neonatal resuscitation bag with pressure relief valve
Face masks - newborn & premature sizes
Oral airways
Oxygen with flowmeter & tubing
Intubation Equipment
Laryngoscope
Straight blades #0 and #1
Extra bulbs & batteries
Endotracheal tubes 2.5 - 4.0 mm
Stylet
Scissors & gloves
Medications
Epinephrine 1:10,000
Naloxone hydrochloride 0.4 mg/mL or 1.0 mg/mL
Volume expander
Sodium bicarbonate 4.2% (5 mEq/10 mL
Dextrose 10%
Sterile water & Normal saline
Miscellaneous
Radiant warmer
Stethoscope
ECG
Adhesive tape
Syringes & needles
Alcohol sponges
Umbilical artery catheterization tray
Umbilical tape
Umbilical catheters 3.5F, 5F
Three-way stopcocks
Feeding tube, 5F
418
Page 3
In the presence of a
non-reassuring fetal heart
rate trace, the practitioner
may wish confirmatory
studies of fetal well-being or
lack thereof. Digital
stimulation of the fetal scalp
will result in fetal heart rate
accelerations in a healthy,
non-acidotic fetus. Fetal
scalp pH determination can
confirm or exclude fetal
acidosis. A pH of less than
7.2 is considered abnormal
and if confirmed by a second
measurement may indicate
the need for delivery.
Predictors specifically of the
need for endotracheal
intubation include administration of general anesthesia to the mother and low infant weight.
17,18
In growth-restricted
infants, factors predicting low uterine artery pH and/or 5 minute Apgar score <7 include: preeclampsia, fetal
distress, breech delivery, forceps use, older maternal age, need for amnioinfusion, general anesthesia and nalbuphine
use during labor.
18

Response: Intrapartum Intrapartum resuscitation is attempted once fetal compromise is identified. Maternal factors
that may impair oxygen delivery to the fetus must be identified and corrected if possible. Considerations include
maternal hypotension or decreased cardiac output secondary to aorto-caval compression, sympathectomy,
hemorrhage or cardiac disease. Disease states that may interfere with maternal oxygenation such as asthma,
pneumonia, or pulmonary edema should be considered and if present, treated appropriately. Attention must also be
directed to the uterus where hyperstimulation, tetany, placental abruption or uterine rupture may interfere with blood
flow to the fetus. Stopping an oxytocin infusion or administering a tocolytic agent will reduce uterine tone and
potentially allow the fetus the opportunity to recover. Emergent delivery will be required if placental abruption or
uterine rupture are severe. Umbilical cord prolapse should always be considered if fetal heart rate changes are
sudden, severe and prolonged. Oligohydramnios is a risk factor for umbilical cord compression and variable
decelerations. Obstetricians may administer a saline amnioinfusion to try to alleviate cord compression.
19
Saline
amnioinfusion is performed by infusing warm saline into the uterus via an intrauterine pressure catheter. Saline
amnioinfusion, once frequently utilized in cases of thick meconium in an attempt to dilute the meconium, has been
shown to have no impact on the severity of meconium aspiration syndrome.
20

At Birth The American Heart Association/American Academy of Pediatrics recommends the neonatal resuscitation
protocol that follows. Updated protocol recommendations were released in late 2010.
21
The first 30 seconds of
neonatal resuscitation should include an assessment of the overall condition of the neonate and steps to minimize
heat loss (Figure 1). Depressed, asphyxiated infants often have an unstable thermal regulatory system. Cold stress
leads to hypoxemia, hypercarbia and metabolic acidosis, all of which will promote persistence of the fetal
circulation and hinder resuscitation. Within the first 20 seconds of birth, the newborn should be dried, placed under a
radiant warmer and evaluated for an open airway.
Table 2. Maternal & Fetal Factors Associated with Need for Resuscitation
Maternal diabetes
Pregnancy-induced hypertension
Chronic hypertension
Previous Rh sensitization
Previous stillbirth
Bleeding in the second or third trimester
Maternal infection
Lack of prenatal care
Maternal substance abuse
Known fetal anomalies
Post-term gestation
Pre-term gestation
Multiple gestation
Size-dates discrepancy
Polyhydramnios
Oligohydramnios
Maternal drug therapy including
Reserpine, lithium carbonate
Magnesium, adrenergic-blockers
Table 3. Intrapartum Events Associated with Need for Resuscitation
Cesarean delivery
Abnormal fetal presentation
Premature labor
Rupture of membranes > 24 hours
Chorioamnionitis
Precipitous labor
Prolonged labor > 24 hours
Prolonged second stage > 3-4 hours
Nonreassuring fetal heart rate patterns
General anesthesia
Uterine tetany
Meconium-stained amniotic fluid
Prolapsed cord
Abruptio placentae
Uterine rupture
Difficult instrumental delivery
Maternal systemic narcotics within 4 hours
of delivery
418
Page 4
Management of Meconium: A major
shift in thinking has occurred over
the last decade concerning the
management of meconium. In the
presence of meconium, routine
intrapartum oropharyngeal and
nasopharyngeal suctioning is no
longer recommended.
21,22

Additionally, routine endotracheal
intubation and suctioning are no
longer recommended. Even for
depressed infants born through
meconium stained fluid, the available
evidence does not support or refute
routine tracheal suctioning.
21,23-25

Following the first steps of
stabilization, further resuscitative
efforts should be guided by
auscultation of the heart rate.
21
Heart
rate is the primary vital sign by which
to judge the need for and efficacy of
resuscitation. For babies requiring
resuscitation or respiratory support
pulse oximetry should be used in
conjunction with auscultation of the
heart rate. Color has been removed as
an indicator of oxygenation or
efficacy of resuscitation. If the
neonate is gasping or apneic and/or
has a heart rate <100 bpm, begin
positive-pressure ventilation (PPV) at
a rate of 40-60 breaths per minute.
Peak inspiratory pressures of 30 to 40
cmH2O or higher may necessary for
initial lung expansion but should
quickly be reduced.
26
Ventilation that is adequate should promptly restore the heart rate to >100 bpm. The majority
of infants requiring any resuscitation will respond to these first two steps. Indications for endotracheal intubation
include ineffective bag and mask ventilation, anticipated need for prolonged mechanical ventilation, or as a last
resort route for administration of medicine.
1
With prolonged bag and mask ventilation, a nasal or oro-gastric tube
should be inserted to decompress the stomach.
Use of Oxygen The scientific basis for the use of 100% oxygen to resuscitate newborns has never been established.
Evidence is growing from both human clinical trials and animal models that resuscitation with oxygen may not be
optimal for all neonates.
27-36
Exposure to high concentrations of oxygen during resuscitation appears to promote the
formation of excessive levels of reactive oxygen intermediates in neonatal tissue, producing injury.
34
A recent meta-
analysis including randomized or pseudo-randomized trials of neonatal resuscitation with room air (n=881) versus
100% oxygen (n=856) found the following: overall neonatal mortality was 8.0 versus 13.0% in the 21 and 100%
groups, respectively (OR 0.57, 95% CI 0.42-0.78); neonatal mortality in term infants was 5.9 versus 9.8% in the 21
and 100% groups, respectively (OR 0.59 95% CI 0.40-0.87); for infants with a 1 minute Apgar score less than 1,
there was no difference between groups; Apgar score at 5 minutes and heart rate at 90 seconds were significantly
higher in the room air group; time to first spontaneous breath was significantly shorter in the room air group.
33
Study
of premature infants suggests that initiating resuscitation with less than 100% oxygen confers benefit in this patient
population, as well.
37
Data is accumulating from normal newborns not requiring resuscitation that normal neonatal
oxygen saturations are quite low during the first minute of age, ranging from 43% to 77%. At 3, 5, and 10 minutes
after birth, preductal mean values were 82%, 89% and 94%, respectively.
38,39
This data must be balanced with
concerns about tissue damage from prolonged asphyxia. The current guidelines reflect these concerns and
recommend beginning resuscitation with room air in term infants. If there is no increase in heart rate or SaO
2
use of
Figure 1.
418
Page 5
a higher concentration of oxygen should be considered.
21
For infants <32 weeks gestation resuscitation should begin
with either 30% or 90% oxygen then titrated to oxygen saturation. There is insufficient evidence to define a strategy
for infants between 32 and 37 weeks gestation.
Chest compressions are indicated for a heart rate < 60 bpm despite adequate ventilation with supplemental
oxygen for 30 seconds.
21
Neonatal cardiac arrest is generally secondary to respiratory failure producing hypoxemia
and tissue acidosis. The result of these metabolic changes is bradycardia, decreased cardiac contractility and
eventually cardiac arrest. Cardiac auscultation with a stethoscope should be used for the most accurate assessment of
the neonatal heart rate.
40
Chest compressions should be instituted at a rate of 90 compressions per minute. The
recommended ratio between chest compressions and ventilations is 3:1, producing 90 compressions and 30
ventilations each minute. In practice, this equals thirty, 2-second cycles/minute. A 2 second cycle consists of 3 chest
compressions in 1.5 seconds,
leaving 1/2 second for
ventilation. Compressions
should be delivered by the
two thumb encircling hands
technique and continue until
the spontaneous heart rate is
greater than 60 bpm.
21

Medications are
indicated if, after adequate
ventilation with 100%
oxygen and chest
compressions for 30 seconds,
heart rate remains below 60 beats per minute. Medications, doses and routes of administration are given in Table 4.
Epinephrine is the vasopressor of choice and can be repeated every 3 to 5 minutes until the heart rate is greater than
60 beats per minute. Intravenous administration of epinephrine is strongly preferred due to lack of evidence of
efficacy for the recommended dose given endotracheally.
1,21,41
While working to obtain IV access, epinephrine up to
0.1 mg/kg can be given via the endotracheal tube but the safety and efficacy of this practice has not been evaluated
in neonates.
21
Epinephrine is not indicated before adequate ventilation has been established because it will increase
myocardial oxygen consumption. In the absence of adequate oxygen, this will likely lead to myocardial damage.
Establish the airway first. The use of blood volume expanders is rarely indicated and may be detrimental.
42,43
Their
use should be restricted to situations in which there is evidence of acute blood loss, such as feto-maternal
hemorrhage, accompanied by lack of response to resuscitative efforts.
21,42,43
Volume expansion should occur over 5
to 10 minutes. Rapid expansion has been associated with intracranial hemorrhage. Naloxone hydrochloride is not
recommended as part of the initial resuscitative efforts; ventilation and heart rate must first be restored. The
preferred route is IV or IM. Keep in mind that no study has examined the efficacy of the recommended dose in
newborns. Naloxone should not be given to a neonate born of a narcotic addicted mother as this can precipitate acute
withdrawal and seizures in the neonate.
44
The use of sodium bicarbonate is not recommended during the initial
neonatal resuscitation. Sodium bicarbonate should be given only if ventilation is adequate (or respiratory acidosis
will replace metabolic acidosis) and metabolic acidosis is documented or presumed, or all other measures have been
unsuccessful.
26,45
Recent data from a small randomized trial suggests that sodium bicarbonate administered to
neonates still requiring positive pressure ventilation at 5 minutes of age had no impact on morbidity or mortality.
46

Table 4. Medications for Neonatal Resuscitation
Medication Concentration Dosage / Route Rate
Epinephrine 1:10,000 0.01 0.03 mg/kg
(0.1 0.3 mL/kg)
IV preferred
ET dose up to 0.1 mg/kg
Give rapidly
Flush catheter/ET tube
with saline
Volume expanders* Normal saline
O negative blood
10 mL/kg
IV (umbilical vein)
Give over 5 - 10 minutes
Naloxone
hydrochloride*
0.4 mg/mL 0.1 mg/kg
IV
Give rapidly
Sodium Bicarbonate* 0.5 mEq/mL
(4.2% solution)
2 mEq/kg
(4 mL/kg)
IV (umbilical vein)
Give slowly, over at
least 2 minutes
Give only if neonate is
effectively ventilated
*Rarely indicated; see text. ET = endotracheal, IV = intravenous
418
Page 6
Table 5. APGAR Score
Sign 0 1 2
Heart Rate Absent < 100 bpm > 100 bpm
Respiratory Effort Absent Slow, irregular Crying
Muscle Tone Flaccid Some flexion of extremities Active motion
Reflex Irritabililty No response Grimace Vigorous cry
Color Blue, pale Blue extremities Completely pink
Apgar Score (Table 5) Although 1 and 5 minute Apgar scores are recorded as one way of assessing neonatal
response to resuscitation, the practitioner should not wait for the 1 minute score to begin resuscitation. If the 5
minute score is less than 7, additional scores should be obtained every 5 minutes until 20 minutes have passed or
until 2 successive scores
are greater than or equal to
7.
47
In a study of stillborn
infants, 66.6% were
resuscitated and left the
delivery room alive.
48
Of
these, 39% survived
beyond the neonatal period. Survival is unlikely if the Apgar score is 0 at ! 10 minutes of age.
48
Current guidelines
now suggest that after 10 minutes of continuous and adequate resuscitative efforts, discontinuation of resuscitation
may be justified if there is no heart rate.
21
A recent retrospective cohort analysis of 151,891 live-born singleton
infants without malformations found that an Apgar score between 0 and 3 at 5 minutes was a better predictor of
neonatal mortality than the umbilical-artery blood pH value.
49

Laryngeal Mask Airway (LMA) The size-1 LMA has been used successfully to resuscitate newborns of both normal
and low birth weight requiring PPV at birth.
50-54
The size-1 LMA can be life-saving in neonates with Pierre-Robin
Syndrome or other conditions associated with a hypoplastic mandible in whom both bag and mask ventilation and
endotracheal intubation have failed.
55,56
The LMA should be considered when face mask ventilation is unsuccessful
and tracheal intubation is unsuccessful. The LMA may also be considered as an alternative to a face mask for
ventilation of newborns weighing >2000g or at !34 weeks gestation.
21

End-tidal CO
2
Detection Both infrared absorption and pediatric size colorimetric disposable devices are readily
available for the detection of expired carbon dioxide. Clinical trials have shown that both devices are reliable and
significantly more rapid than clinical exam in both confirming endotracheal intubation and detecting esophageal
intubation.
57,58
End-tidal CO
2
confirmation is the recommended technique to confirm intubation in neonates with
spontaneous circulation.
21

Neonatal Hypoglycemia Approximately 10% of healthy term neonates have transient hypoglycemia. Other neonates
at risk include those born of diabetic mothers or mothers who received a large amount of intravenous dextrose
during labor. If a dextrose strip glucose level is <40 to 45 mg/dl, the neonate should be treated either with oral
feedings (2-3 cc/kg D10% in water) or by intravenous infusion (8 mg/kg/min) with the goal of restoring glucose to
the normal range.
References
1. American Heart Association, American Academy of Pediatrics. 2005 American Heart Association (AHA)
Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric
and Neonatal Patients: Neonatal Resuscitation Guidelines. Pediatrics 2006;117:e1029-38.
2. Wimmer JE. Neonatal resuscitation. Pediatrics in Review 1994;15:255-65.
3. Ostheimer GW. Anaesthetists' role in neonatal resuscitation and care of the newborn. Can J Anaesth
1993;40:R50-R6.
4. Lakshminrusimha S, Steinhorn RH. Pulmonary vascular biology during neonatal transition. Clin Perinatol
1999;26:601-19.
5. Falck AJ, Escobedo MB, Baillargeon JG, Villard LG, Gunkel JH. Proficiency of pediatric residents in
performing neonatal endotracheal intubation. Pediatrics 2003;112:1242-7.
6. Posen R, Friedlich P, Chan L, Miller D. Relationship between fetal monitoring and resuscitative needs: fetal
distress versus routine cesarean deliveries. Journal of Perinatology 2000;20:101-4.
7. Guay J. Fetal monitoring and neonatal resuscitation: what the anaesthetist should know. Can J Anaesth
1991;38:R83-R8.
8. Krebs HB, Petres RE, Dunn LJ, Jordan HVF, Segreti A. Intrapartum fetal heart rate monitoring I.
Classification and prognosis of fetal heart rate patterns. Am J Obstet Gynecol 1979;133:762-72.
9. Schifrin BS, Dame L. Fetal heart rate patterns. Prediction of Apgar score. JAMA 1972;219:1322-5.
10. Tejani N, Mann LI, Bhakthavathsalan A. Correlation of fetal heart rate patterns and fetal pH with neonatal
outcome. Obstet Gynecol 1976;48:460-3.
11. Kuhnert M, Seelbach-Gobel B, Butterwegge M. Predictive agreement between the fetal arterial oxygen
saturation and fetal scalp pH: results of the German multicenter study. Am J Obstet Gynecol 1998;178:330-50.
418
Page 7
12. Seelbach-Gobel B, Huepel M, Kuhnert M, Butterwegge M. The prediction of fetal acidosis by means of
intrapartum fetal pulse oximetry. Am J Obstet Gynecol 1999;180:73-81.
13. Carbonne B, Langer B, Goffinet F, et al. Multicenter study on the clinical value of fetal pulse oximetry. II.
Compared predictive values of pulse oximetry and fetal blood analysis. The French study group on fetal pulse
oximetry. Am J Obstet Gynecol 1997;177:593-8.
14. Garite TJ, Dildy GA, McNamara H, et al. A multicenter controlled trial of fetal pulse oximetry in the
intrapartum management of nonreassuring fetal heart rate patterns. American Journal of Obstetrics and
Gynecology 2000;183:1049-58.
15. Bloom SL, Spong CY, Thom E, et al. Fetal pulse oximetry and cesarean delivery. New England Journal of
Medicine 2006;355:2195-202.
16. Greene MF. Obstetricians still await a deus ex machina. New England Journal of Medicine 2006;355:2247-8.
17. Parsons SJ, Sonneveld S, Nolan T. Is a paediatrician needed at all caesarean sections? J Paediatr Child Health
1998;34:241-4.
18. Levy BT, Dawson JD, Toth PP, Bowdler N. Predictors of neonatal resuscitation, low Apgar scores, and
umbilical artery pH among growth-restricted neonates. Obstet Gynecol 1998;91:909-16.
19. Sivan E, Seidman DS, Barkai G, Atlas M, Dulitzky M, Mashiach S. The role of amnioinfusion in current
obstetric care. Obstet Gynecol Surv 1992;47:80-7.
20. Fraser WD, Hofmeyr J, Lede R, et al. Amnioinfusion for the Prevention of the Meconium Aspiration
Syndrome. N Engl J Med 2005;353:909-17.
21. Perlman JM, Wyllie J, Kattwinkel J, et al. Neonatal Resuscitation: 2010 International Consensus on
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment
Recommendations. Circulation 2010;122[suppl 2]:S516-S38.
22. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal
suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomized
controlled trial. Lancet 2004;364:597-602.
23. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous meconium-
stained neonate: results of the multicenter, international collaborative trial. Pediatrics 2000;105:1-7.
24. Halliday HL. Endotracheal intubation at birth for preventing morbidity and mortality in vigorous, meconium-
stained infants born at term. The Cochrane Database of Systematic Reviews 2000;2.
25. Liu WF, Harrington T. Delivery room risk factors for meconium aspiration syndrome. Am J Perinatol
2002;19:367-77.
26. Leuthner SR, Jansen RD, Hageman JR. Cardiopulmonary resuscitation of the newborn. Pediatr Clin N Am
1994;41:893-907.
27. Ramji S, Ahuja S, Thirupuram S, Rootwelt T, Rooth G, Saugstad OD. Resuscitation of asphyxic newborn
infants with room air or 100% oxygen. Pediatr Res 1993;34:809-12.
28. Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or oxygen:
An international controlled trial: The Resair 2 Study. Pediatrics 1998;102:E1.
29. Vento M, Asensi M, Sastre J, Garcia-Sala F, Pallardo FV, Vina J. Resuscitation with room air instead of 100%
oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics 2001;107:642-7.
30. Saugstad OD, Ramji S, Irani SF, et al. Resuscitation of newborn infants with 21% or 100% oxygen: Follow-up
at 18 to 24 months. Pediatrics 2003;112.
31. Ramji S, Rasaily R, Mishra PK, et al. Resuscitation of asphyxiated newborns with room air or 100% oxygen at
birth: a multicentric clinical trial. Indian Pediatrics 2003;40:510-7.
32. Saugstad OD. The role of oxygen in neonatal resuscitation. Clin Perinatol 2004;31:431-3.
33. Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn infants with ambient air or pure oxygen:
a meta analysis. Biol Neonate 2004;87:27-34.
34. Kutzsche S, Ilves P, Kirkeby OJ, Saugstad OD. Hydrogen peroxide production in leukocytes during cerebral
hypoxia and reoxygenation with 100% or 21% oxygen in newborn piglets. Pediatric Research 2001;49:834-42.
35. Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn: A systematic review and meta-
analysis. Resuscitation 2007;72:353-63.
36. Higgins RD, Bancalari E, Willinger M, Raju TNK. Executive summary of the workshop on oxygen in neonatal
therapies: Controversies and opportunities for research. Pediatrics 2007;119:790-6.
37. Stola A, Schulman J, Perlman J. Initiating delivery room stabilization/resuscitation in very low birth weight
(VLBW) infants with an FiO2 less than 100% is feasible. Journal of Perinatology 2009;29:548-52.
38. Rao R, Ramji S. Pulse oximetry in asphyxiated newborns in the delivery room. Indian Pediatrics 2001;38:762-
6.
418
Page 8
39. Kamlin C, O'Donnell C, Davis P, Morley C. Oxygen saturation in healthy infants immediately after birth. J
Pediatr 2006;148:585-9.
40. Owen CJ, Wyllie JP. Determination of heart rate in the baby at birth. Resuscitation 2004;60:213-7.
41. Barber CA, Wyckoff MH. Use and efficacy of endotracheal versus intravenous epinephrine during neonatal
cardiopulmonary resuscitation in the delivery room. Pediatrics 2006;118:1028-34.
42. Saugstad OD. Practical aspects of resuscitating asphyxiated newborn infants. Eur J Pediatr 1998;157:S11-S5.
43. Roberton NRC. Use of albumin in neonatal resuscitation. Eur J Pediatr 1997;156:428-31.
44. Ginsberg HG, Goldsmith JP. Controversies in neonatal resuscitation. Clin Perinatol 1998;25:1-15.
45. Hein HA. The use of sodium bicarbonate in neonatal resuscitation: Help or harm? (letter). Pediatrics
1993;91:496-7.
46. Lokesh L, Kumar P, Murki S, Narang A. A randomized controlled trial of sodium bicarbonate in neonatal
resuscitation-effect on immediate outcome. Resuscitation 2004;60:219-23.
47. Jain L, Vidyasagar D. Controversies in neonatal resuscitation. Pediatric Annals 1995;24:540-5.
48. Jain L, Ferre C, Vidyasagar D, Nath S, Sheftel D. Cardiopulmonary resuscitation of apparently stillborn
infants: Survival and long-term outcome. J Pediatr 1991;118:778-82.
49. Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assessment of newborn
infants. N Engl J Med 2001;344:467-71.
50. Brimacombe J. The laryngeal mask airway for neonatal resuscitation (letter). Pediatrics 1994;93:874.
51. Paterson SJ, Byrne PJ, Molesky MG, Seal RF, Finucane BT. Neonatal resuscitation using the laryngeal mask
airway. Anesthesiology 1994;80:1248-53.
52. Gandini D, Brimacombe JR. Neonatal resuscitation with the laryngeal mask airway in normal and low birth
weight infants. Anesthesia and Analgesia 1999;89:642-3.
53. Trevisanuto D, Micaglio M, Pitton M, Magarotto M, Piva D, Zanardo V. Laryngeal mask airway: is the
management of neonates requiring positive pressure ventilation at birth changing? Resuscitation 2004;62:151-
7.
54. Zanardo V, Weiner G, Micaglio M, Doglioni N, Buzzacchero R, Trevisanuto D. Delivery room resuscitation
of near-term infants: Role of the laryngeal mask airway. Resuscitation 2010;81:327-30.
55. Baraka A. Laryngeal mask airway for resuscitation of a newborn with Pierre-Robin Syndrome (letter).
56. Denny NM, Desilva KD, Webber PA. Laryngeal mask airway for emergency tracheostomy in a neonate.
57. Repetto JE, Donohue PK, Baker SF, Kelly L, Nogee LM. Use of capnography in the delivery room for
assessment of endotracheal tube placement. Journal of Perinatology 2001;21:284-7.
58. Aziz HF, Martin JB, Moore JJ. The pediatric disposable end-tidal carbon dioxide detector role in endotracheal
intubation in newborns. Journal of Perinatology 1999;19:110-3.
Disclosure
504
Page 1
Postpartum Hemorrhage
Jill Mhyre, M.D. Ann Arbor, Michigan
The learner will: 1) Identify women at risk for major postpartum hemorrhage; 2) List options available to control
and mitigate the consequences of obstetric hemorrhage; 3) Discuss how contemporary transfusion practices apply in
the obstetric setting; and 4) Draw from published guidelines and protocols to inform both individual clinical practice
and systems solutions to prepare for these emergencies.
Definition
Hemorrhage is most commonly defined by estimated blood loss (EBL) !500 mL for vaginal delivery and !1000
mL for cesarean delivery.
1
However, blood loss estimation is notoriously inaccurate, bleeding may be concealed
within the uterus, the drapes, or in the retroperitoneal space, and the physiologic impact of hemorrhage depends on
the mothers initial blood volume, hematocrit, and the speed of blood loss.
2
Enhanced strategies to evaluate blood
loss in real time are described below.
Etiology
Primary postpartum hemorrhage develops within 24 hours of delivery and is due to uterine atony, retained
placenta, genital tract trauma, placenta accreta, increta and percreta, uterine inversion, or coagulopathy.
Coagulopathy may be inherited or result from a range of disorders in pregnancy, with amniotic fluid embolism being
the most severe.
3
Secondary postpartum hemorrhage is relatively infrequent, develops over 24 hours after delivery,
and is ascribed to subinvolution of the placental site, retained products of conception, infection, or inherited
coagulation defects.
Epidemiology
Maternal hemorrhage complicates approximately 3% of all deliveries. While the incidence of antepartum
hemorrhage appears to be relatively stable, postpartum hemorrhage (PPH) is increasing in developed countries
around the globe.
4-7

In the U.S., between 1994 and 2006, rates of PPH increased 30%, and the proportion of all U.S.
deliveries complicated by a blood transfusion increased 90% (from 2.4 to 4.6 per 1,000 deliveries) between 1998
and 2005.
7
These rising rates are almost entirely attributable to increases in abnormal placentation (placenta accreta,
placenta previa) and postpartum uterine atony. Hemorrhage-related morbidities include anemia, disseminated
intravascular coagulopathy (DIC), respiratory failure, renal failure, secondary surgical procedures, fertility loss, and
delayed postpartum functional recovery. Hemorrhage is the leading indication for intensive care unit admission in
obstetric patients.
8

Peripartum hysterectomy increased 15% in the U.S. between 1994 and 2007 up to a rate of 0.83 per 1,000
deliveries (1 in 1200).
9
Placenta accreta with or without placenta previa leads to approximately half of all peripartum
hysterectomies, and rates have increased in conjunction with the burgeoning population of pregnant women with
previous cesarean delivery.
9
Hysterectomy attributed to uterine atony more than doubled, and currently accounts for
one-third of all peripartum hysterectomies.
9
Infection and inflammatory findings in the placenta and uterus (e.g.,
chorioamnionitis, vasculitis, funisitis, endometritis, and cervicitis) are associated with hysterectomies performed for
intractable uterine atony, as opposed to other indications (e.g., suspected accreta, lacerations, leiomyomas), (45%
compared with 19%, P=.03).
10

The shift towards cesarean birth, from 21% of all births in 1997 to 32.3% in 2009,
11
underlies the increasing
rates of abnormal placentation, uterine atony, and PPH. Other factors contribute to the increasing risk of uterine
atony including: 1) increasing population rates of obesity, multiple gestation, and advanced maternal age; 2)
increasing rates of induction of labor
12
; and 3) increasing use of oxytocin for induction and/or augmentation of
labor. Prolonged exposure to oxytocin infusions down-regulate oxytocin receptors in the lower uterine segment,
13

and increase risk of PPH attributed to both uterine atony
14
and retained placenta.
15

504
Page 2
Historically, hemorrhage was the leading cause of maternal death in the United States, but is now tied with 7
other conditions, each contributing 10-13% of all deaths (i.e., hypertensive disorders of pregnancy, infection,
thrombotic pulmonary embolism, cardiomyopathy, cardiovascular conditions, and non-cardiovascular medical
conditions).
16
Over the past ~20 years, the hemorrhage-related maternal mortality ratio fell 30% from 2.6 to 1.8 per
100,000 live births, (comparing 1987-1990 with 1998-2005).
16

While hemorrhage is no longer the leading cause of maternal death, it remains among the most preventable.
17
In
California, between 2002 and 2003, hemorrhage accounted for just 10% of pregnancy-related deaths, but in 70% of
these cases improved clinical care had a good or strong chance to alter the fatal outcome.
2
This rate of potential
preventability was higher than any other condition, and established hemorrhage as a top priority for the California
Maternal Quality Care Collaborative (CMQCC). Consequently, CMQCC developed the Obstetric Hemorrhage
Toolkit and deployed a statewide campaign to improve California hospital capabilities and resources for
responding to obstetric hemorrhage by increasing the use of protocols and drills and by improving availability of and
training in standard and state-of-the-art medical, surgical and blood replacement options.
2

Anticipated Hemorrhage
Even with the physiologic anemia of pregnancy, a hematocrit less than 32% should be treated to reduce the risk
of peripartum blood transfusion (e.g., oral or intravenous iron, erythropoietin for select cases). In addition, three
groups need special antenatal preparation: 1) women with abnormal placentation; 2) those with inherited coagulation
disorders; and 3) those who refuse blood products. This section also discusses a risk-stratified algorithm to guide
blood product preparation.
Abnormal Placentation
With normal placentation, the chorionic villi grow into the uterine decidua and extravillous trophoblasts invade
uterine spiral arteries to establish the placental blood supply. At term, approximately 200 spiral arteries feed the
intervillous space, bathing the chorionic villi in 500-800 mL/min of maternal blood. Residual decidua forms the
basal plate, which then cleaves at delivery, creating the normal plane of placental separation, and the placenta is
delivered with the intravillous space intact. With placenta accreta, the decidua basalis (i.e., the decidual basal plate)
is absent, and the placenta adheres to a floor of uterine myometrium. With placenta increta, chorionic villi invade
into the myometrium, and with percreta, the placenta penetrates the uterine serosa, and may even grow into other
pelvic structures, most commonly the bladder. Estimated intrapartum blood loss has been reported as >2L in 66%,
>5L in 15%, and >10L in 6.5% of these cases.
18

Prior cesarean delivery, other uterine surgery, placenta previa, and maternal age !35 years are important risk
factors for placenta accreta. The incidence of a morbidly adherent placenta increases from 0.03% among primary
cesarean deliveries, to 0.2%, 0.3%, 0.6%, 2.1%, 2.3% and 6.7% after one, two, three, four, five and six or more prior
cesarean deliveries, respectively.
19
With placenta previa, the corresponding risks of a morbidly adherent placenta are
3%, 11%, 40%, 61%, and 67% with zero, one, two three, and four or more prior Cesarean deliveries, respectively.
19

Given the rising incidence and prevalence of cesarean birth, placenta accreta has increased from 0.8 per 1000
deliveries in the 1980s to 3 per 1000 deliveries in the past decade.
20

Antenatal recognition and controlled surgical delivery improve outcomes.
21-23
Recent evidence suggests that
maternal morbidity is reduced when women with placenta accreta deliver in tertiary care centers with a multi-
disciplinary care team.
24,25
The Society of Maternal-Fetal-Medicine recommends that women with a suspected
placenta accreta should be scheduled for delivery in an institution with appropriate surgical facilities and a blood
bank that can facilitate transfusion of large amounts of various blood products.
20
Nevertheless, placenta accreta
remains the leading indication for unplanned peripartum hysterectomy,
26
likely as a consequence of the limitations
of diagnostic accuracy.
Ultrasonography to locate the placenta and evaluate for markers of placenta accreta is recommended for every
woman who has undergone prior uterine surgery, or found to have a low-lying placenta on the routine first or second
trimester ultrasound.
20
Magnetic resonance imaging (MRI) may help to confirm the diagnosis when ultrasound is
inconclusive, and define the extent of invasion into surrounding organs in the case of placenta percreta.
20
Women
with a diagnosis of abnormal placentation based on ultrasonography are more likely to require blood transfusion and
peripartum hysterectomy, and require more units of blood products transfused, when compared with women without
definitive ultrasound findings.
27,28

In cases of extensive accreta, optimal surgical management is directed towards delivering the neonate, then
closing the uterus with the placenta left in situ, followed by planned peripartum hysterectomy. When the area of
accreta is small, a trial of spontaneous placental separation may be attempted followed by deep myometrial sutures,
a uterine compression suture (e.g., B-Lynch), and/or intrauterine balloon tamponade (e.g., with a Bakri balloon). For
placenta percreta, depending on the extent of placental invasion into surrounding organs, multidisciplinary surgical

504
Page 3
management may require gynecologic oncologists, general surgeons, urologists, interventional radiologists, and/or
vascular surgeons. For women who desire fertility preservation, uterine conservation techniques include
prophylactic uterine and hypogastric artery balloon catheters, stepwise uterine devascularization, pelvic vessel
ligation or embolization, uterine compression sutures, and/or postpartum methotrexate to facilitate placental
involution.
29

Optimal management by the anesthesiologist ensures sufficient intravenous access and blood products to
respond to massive hemorrhage, hemodynamic and hemostatic monitoring capability (e.g., central venous and
peripheral arterial access), compression stockings to prevent venous thromboembolism, padding and positioning to
prevent nerve compression injury, warming devices to ensure normothermia, standard preoperative antibiotic
prophylaxis in the hour prior to surgical incision and repeated if surgery is prolonged (i.e., !3 hours) or if heavy
bleeding occurs.
20
Given inaccuracy of models to predict total blood loss in these cases, the total number of
recommended blood products to prepare depends on institutional capacity to maintain ongoing supply in the face of
massive hemorrhage (Table 1).
28,30
Aggressive uterotonic administration, cell-saver auto-transfusion, massive
transfusion management, and electrolyte and hemostatic measurement and management are discussed below.
Combined spinal epidural (or standard epidural) anesthesia allows the mother to be awake for the delivery, and
may be extended for prolonged surgery. On the other hand, general anesthesia is preferred for cases with massive
transfusion in the event of airway edema, fluid overload with pulmonary edema, or transfusion associated lung
injury (TRALI). The decision about the primary anesthetic technique will weigh the magnitude of anticipated blood
loss, the extent of the operative plan, the availability of additional anesthesia staff to assist with an unplanned
conversion to general anesthesia, and the anticipated risk of a difficult airway.
Prophylactic embolization catheters may be inserted preoperatively into the anterior internal iliac or uterine
arteries to facilitate balloon inflation or embolization immediately following delivery of the infant.
31,32
Success rates
vary based on institutional experience; cesarean delivery in the interventional radiology suite may improve efficacy
of intra-arterial occlusion by avoiding catheter dislodgement.
33
While these catheters may be indicated for women
who desire fertility preservation, and in women with extensive or unrespectable placenta percreta, routine use is not
recommended by the Society for Maternal-FetalMedicine due to potential complications including insertion site
hematoma, abscess, tissue infection and necrosis.
20
Epidural anesthesia should be initiated prior to femoral sheath
insertion, to facilitate optimal positioning for both procedures and patient comfort.

Inherited Coagulation Disorders
Von Willebrand disease, hemophilia A and B, and factor XI deficiency account for approximately 90% of
inherited bleeding disorders.
34-36
Inherited platelet disorders (e.g., Bernard Soulier Syndrome, Glanzmann
thrombasthenia) are rare. Given the clinical heterogeneity within each diagnosis, consultation with a hematologist
and blood bank personnel will help to clarify optimal management for each patient. Sixteen percent of women who
have von Willebrand disease will experience PPH within 24 hours of delivery, and 29% will experience delayed
postpartum bleeding.
37
A familial history of inherited coagulopathy, postpartum or perioperative hemorrhage,
significant menorrhagia, gingivorrhagia or epistaxis may help to identify patients at increased risk for disordered
hemostasis with delivery.
35,37

Jehovahs Witnesses and other women who refuse blood products
Antepartum consultation should review a comprehensive list of blood products, alternatives, and blood
conservation strategies to determine acceptability of each intervention for the patient.
2
Antepartum iron and
erythropoietin are often acceptable ways to optimize hematocrit prior to delivery, aiming for a goal of 35-40%, and
may be continued postpartum in the event of significant blood loss.
38,39
Neuraxial anesthesia with a catheter-based
technique may be preferred for operative anesthesia because an awake patient may change her mind in the face of
impending death.
In the event of hemorrhage, permissive hypotension with a mean arterial blood pressure of 50 mmHg may help
limit blood loss following delivery of the fetus.
38
Volume replacement with crystalloid or colloid can decrease
viscosity of the blood and improve peripheral perfusion while maintaining oxygen delivery (by increasing oxygen
extraction in the periphery), and minimizing cardiac work. However, excessive fluid resuscitation can contribute to
dilutional coagulopathy and decreased oncotic pressure. Cell-saver autotransfusion is discussed below, and a
continuous circuit technique is often acceptable for patients who would otherwise refuse blood products.
39,40
In the
event of massive blood loss and profound anemia (hgb "4 g/dL) prolonged postoperative sedation, intubation,
thermoregulation, and paralysis may be required to limit oxygen consumption while erythropoietin and iron are used
to restore the patients red cell mass. Erythropoietin requires 48-72 hours for a significant reticulocyte response in
peripheral blood, and 10-14 days to increase hemoglobin levels. Laboratory testing should be minimized using
pediatric tubes and finger-stick testing where possible.
38

504
Page 4
Risk stratified blood product preparation
Patients usually receive a type and screen as part of routine prenatal care to determine blood type, the
requirement for RhoGAM
, and the presence of minor antibodies. This result in combination with antepartum risk
factors can help determine the optimal blood tests that should be submitted at the time of admission to the labor and
delivery unit. Risk-stratified blood testing has been shown to reduce excess cost associated with testing for low risk
women, and is also thought to focus attention and resources on high risk patients, and to reduce inconsistences in
transfusion ordering.
2,41
Nevertheless, specific algorithms vary among centers, and are largely based on expert
opinion supported by limited empirical data. Recommendations in Table 1 synthesize algorithms from the
CMQCC,
2,3
Stanford University,
41
Northwestern University (Cynthia Wong e-mail communication, October 2011),
and risk factors reported elsewhere in the literature.
39

Table 1. Blood product preparation based on the level of risk for blood transfusion
Risk level AND
Recommendations
Conditions
Low risk (~1/4000)
42

A clotted sample can be sent to the
blood bank at the time of admission
for delivery
Elective CD with no prior uterine surgery
Admitted for labor with fewer than 5 prior VB
No known bleeding disorder
No history of PPH
Risk < 5%
Either a type & screen or clot only,
depending on institutional resources
2
nd
through 4
th
elective CD
More than four prior VB
Multiple gestation
Prior PPH
Uterine fibroids
Fetal macrosomia
Maternal obesity
Unplanned CD in labor without additional risk factors
Risk 5 - 10%
At least a type & screen
Antenatal observation for placenta previa without active bleeding
Chorioamnionitis
Elective CD with prior myomectomy or fundal surgery
Trial of labor after any uterine surgery
A history of RhoGAM
therapy

Risk > 10%
Type and crossmatch
!2 units PRBC
Severe anemia (antepartum Hct <25%)
Mild anemia (Hct<30%) in the presence of other risk factors
Thrombocytopenia (platelets <100k)
Active bleeding on admission
Coagulation disorder including HELLP
Higher order CD (!5)
Positive antibodies on type and screen
CD for patients who have: placenta previa, intrauterine fetal
demise, placental abruption, uterine rupture, chorioamnionitis
Highest risk
Type and crossmatch
4-20 units PRBC
4-20 units FFP
4-20 platelets
A planned cesarean hysterectomy
Suspected: placenta accreta, placenta increta, placenta percreta
CD = cesarean delivery; FFP = fresh frozen plasma; Hct = hematocrit; PPH = post partum hemorrhage; PRBC =
packed red blood cells; VB = vaginal births;
The exact number of units determined by a patient-specific assessment of risk for massive blood loss, and
institutional resources to rapidly procure additional blood products.
28,30

Extra time is needed to discriminate between anti-D antibiodies due to RhoGAM
and any additional antibodies

that could interfere with a type and crossmatch.
43

504
Page 5

Unanticipated Postpartum Hemorrhage
System Factors
Clear multidisciplinary guidelines and regular skills training (multidisciplinary drills) reduce the incidence of
massive PPH,
44-46
and are recommended for all units by the Centre for Maternal and Child Enquiries in the United
Kingdom.
17
Simulation-based training for obstetric hemorrhage encounters can reveal specific management deficits,
and thereby facilitate targeted quality improvement and staff education.
47

Accumulating evidence suggests that treatment delays substantially increase risk for severe obstetric
hemorrhage and hemorrhage-related maternal death.
17,48,49
Calling for the obstetrician within 10 minutes, the
anesthesiologist within 10 minutes, administering oxytocin within 10 minutes, and exploring the uterus within 20
minutes each decrease the likelihood of severe obstetric hemorrhage from uterine atony following vaginal delivery.
49

Neuraxial labor analgesia reduces the risk-adjusted odds of severe atonic hemorrhage following vaginal delivery by
half, likely by facilitating rapid manual exploration and surgical repair.
49
Prompt placement of uterine compression
sutures within 1 hour of delivery decreases risk for peripartum hysterectomy.
50

Bundling personnel, equipment, and drug resources ensures rapid and reliable delivery to the bedside. For
example, group paging systems can simultaneously request an entire Obstetric Medical Emergency Team including
an attending obstetrician, critical care physician, anesthesiologist, respiratory therapist, and several nurses.
51

Likewise, an obstetric hemorrhage cart can be used to store essential equipment, including a laminated copy of the
institutional hemorrhage protocol, important phone numbers, equipment for lines, fluid resuscitation and serial
laboratory tests, and surgical equipment including a hysterectomy tray.
52
Lastly, an obstetric hemorrhage drug pack
containing fentanyl, oxytocin, methylergonovine, misoprostol, and carboprost allows for efficient retrieval in the
event of an emergency. (Manuel A. Vallejo, Jr., e-mail communication, May 2011)

The CMQCC Staged Approach
The CMQCC describes four stages of PPH, based on estimated blood loss, vital sign stability, need for
blood products, and interventions.

Stage O
Stage O begins with all deliveries, and focuses on ongoing risk assessment and active management of the third
stage of labor. This includes prophylactic oxytocin administration with delivery, vigorous fundal massage lasting at
least 15 seconds, and controlled cord traction to deliver the placenta.
53

Oxytocin is the preferred first line uterotonic, because it is clearly shown to decrease blood loss of the third
stage of labor,
53,54
and decreases need for additional uterotonics.
54
Rapid intravenous infusion of oxytocin may cause
peripheral vasodilation, hypotension, flushing, nausea, chest pain, myocardial ischemia, and in the face of
substantial hemorrhage, cardiovascular collapse.
55,56
Phenylephrine may be used to counteract the hemodynamic
effects of oxytocin.
57
As little as 0.35 IU is needed to initiate acceptable uterine tone in 90% of elective cesarean
delivery patients.
58,59
Three IU is effective to establish uterine tone in 90% of women undergoing cesarean in labor.
60

One of the cardinal recommendations from the CMQCC is to establish the standard of structured assessments of
blood loss, vital signs, fundal height, and uterine tone following all deliveries, and to define specific triggers for
action to limit the risk for denial and delay. Accurate blood loss estimation is improved by the use of calibrated
drapes and formal staff training in blood loss estimation.
2,61,62
Blood contained in absorbing materials (e.g., pads,
sponges) can be quantified by weight, subtracting the dry weight of each item, assuming 1 gm weight = 1 mL
blood.
2
Immediately following delivery, the team should routinely tabulate fluid volume in suction canisters,
calibrated drapes, and absorbing materials; any subsequent volume can be assumed to be blood, not amniotic fluid.
Because hemorrhage is so often concealed or underestimated, monitoring protocols with clear triggers for
escalating care are essential.
2,17
A Modified Obstetric Early Warning Scoring (MEOWS) system adapted from that

504
Page 6
published in the Saving Mothers Lives report is presented here.
63

Additional signs and symptoms of severe obstetric hemorrhage include narrow pulse pressure, pallor or
mottled appearance, cold and clammy extremities, oliguria (<0.5mL/kg/hr), anxiety, restlessness,
confusion, palpitations, dizziness, diaphoresis, and dyspnea or air hunger.
Stage 1: EBL>500 vaginal delivery, >1000 cesarean delivery, brisk gush or boggy uterus, or multiple clots
AND vital signs stable. At this point, both the anesthesiologist and the obstetrician should be requested to the
bedside. Monitoring intensity of both vital signs and EBL should increase. The patient likely requires additional
venous access, colloid or crystalloid resuscitation, active warming, a request to the blood bank to crossmatch at least
2 units packed red blood cells (PRBC), and analgesia for initial obstetric interventions to investigate and control the
source of bleeding. The initial diagnostic evaluation should address the five Ts: (1) Toneuterine atony; (2)
Traumalacerations or genital tract trauma; (3) Tissueretained placenta; (4) Thrombinabnormalities of
coagulation; and (5) Turned inside oututerine inversion.
Once oxytocin is infusing (500 mL/hr of 10-40 units/liter), administering a second uterotonic agent is more
effective than increasing the oxytocin infusion rate. Second line options include: 1) methergine 200 mcg if the
patient is not hypertensive, repeated every 2 hours; 2) carboprost 250 mcg IM every 15-20 minutes up to 8 total
doses (avoided in women with asthma); and 3) misoprostol 800-1000 mcg buccally, rectally, or vaginally.

Stage 2: Continued bleeding OR vital sign instability (change>20% from baseline of HR, SBP/DBP, or
HR>110, BP<85/45, SpO2<95%, RR>20, narrow pulse pressure) OR symptomatic (coldness or clamminess,
pale appearance, anxiety, restless, dizzy, short of breath, hunger for air, confusion) AND <1500 mL
cumulative blood loss. With Stage 2, it becomes very important to mobilize a full team, including: the charge nurse,
the blood bank, a second obstetrician, a second anesthesiologist, interventional radiologist if appropriate, the nursing
supervisor, and additional staff to communicate with the blood bank and to provide family support.
The patient should be moved to an operating room, large bore venous access secured, and a full panel of
laboratory values sent, most importantly Type and Cross, hematocrit, platelets, PT, and fibrinogen. Fibrinogen <2
g/L is an early predictor of the severity of subsequent PPH.
64-66
Ongoing uterotonics, thermoregulation, antibiotic
coverage, and venous thromboembolism prophylaxis should be addressed. Decisions about transfusion, requesting
additional blood products, activating a massive transfusion protocol, converting to general anesthesia, initiating cell
salvage, and establishing invasive hemodynamic monitoring depend on the ongoing state of the patient, the rate of
blood loss, and the degree to which obstetricians are effective in controlling the source of bleeding.
Following manual exploration and repair of lacerations, stepwise escalation of surgical therapy includes D&C,
intrauterine balloon (e.g., Bakri balloon), uterine compression suture (e.g., B-Lynch, OLeary, multiple squares),
selective embolization, peripartum hysterectomy, and abdominal packing. Uterine inversion requires anesthesia and
uterine relaxation to facilitate manual replacement.

Stage 3: EBL>1500, >2 u PRBC given, vital sign instability, evidence of coagulopathy, or ongoing bleeding.
Stage 3 qualifies as major obstetric hemorrhage. In the event of unanticipated massive hemorrhage, an interosseous
needle may be rapidly inserted in the proximal humerus and used to initiate fluid resuscitation while additional
intravenous access is established.
67
Temporizing maneuvers include leg elevation, manual compression of the aorta
at the umbilicus, and non-pneumatic anti-shock garments.
68
Permissive hypotension (MAP 50 mmHg) may help to
limit bleeding, but is not well studied in the postpartum patient.
38

Modified Early Obstetric Warning Scores
Contact a physician for early intervention if the patient scores !2 at any time.
Score 2 1 0 1 2
Pulse "40 41-50 51-100 101-120 or
10-20%
increase
>120 or
>20% increase
SBP "85 or
>20% decrease
85-100 101-150 151-160 >160
DBP <45 45-80 81-100 >100
SpO2 <90% 90-94% 95-100%
RR "10 11-20 21-30 >30
Temp "35.0 35.1-35.9 36.0-37.9 !38.0
CNS Normal Responds to
voice
Responds only to pain or
unresponsive

504
Page 7
While a hemoglobin transfusion threshold of 7 g/dL is generally appropriate, laboratory results are
inaccurate in the face of ongoing hemorrhage, and transfusion should proceed empirically without waiting for
laboratory results. Failure to maintain adequate hematocrit during acute obstetric hemorrhage has been associated
with end organ dysfunction.
69
Retrospective analyses suggest that hemostatic resuscitation with low transfusion
ratios (FFP: PRBC and Platelet: PRBC ratios of 1:1 to 1:2) may increase survival in massively transfused trauma
victims.
70
However, this evidence base suffers from survival bias. Furthermore, plasma and platelets are pro-
inflammatory, and may actually increase risk of TRALI and other morbidity among survivors.
71-73
Regardless, the
full panel of laboratory values (i.e., hematocrit, platelets, ionized Ca, K, PT, fibrinogen, ABG) should be sent every
30-60 minutes to establish trends. Serial coagulation tests are more helpful than single time point measurements in
assessing for development of coagulopathy.
5
Additional FFP may be needed to maintain the PT "1.5 times normal,
platelets to maintain the platelet count over 50 x 10
9
/L, and cryoprecipitate or fibrinogen concentrate 4 g to maintain
the fibrinogen over 2 g/L.
64-66
Central laboratory turn-around time within 20 minutes is possible.
74
Point-of-care
viscoelastic monitors are an alternate strategy to facilitate goal directed therapy.
75,76

Massive transfusion protocols can be established to treat life-threatening obstetric hemorrhage. At Stanford
University, upon activation of the massive transfusion protocol, the blood bank provides a standard pack to initiate
resuscitation (e.g., 6 units O negative blood, 4 units FFP, 1 apheresis platelet unit [5-pack]).
77,78
Subsequent matched
blood products are continuously prepared to maintain blood product availability, and the protocol is automatically
discontinued once additional blood products have not been requested for at least one hour.

Adjunctive agents: Cell salvageOver 400 published cases of obstetric patients have described auto-transfusion
with blood salvaged and processed from the surgical field. The technique is gaining acceptance as newer machines
in combination with leukocyte reduction filters have demonstrated effective clearance of fetal squamous cells,
phospholipid lamellar bodies, plasma heparin, cytokines, and other coagulopathic mediators. Cell-salvaged blood
does contain up to 2% fetal red blood cells; Rhesus-negative women require dose-adjusted RhoGAM

administration. Emergency cell salvage may be most appropriate in institutions where cell saver devices are
routinely used, and dedicated technicians are available to set up the equipment.
79

The anti-fibrinolytic agent tranexamic acid (1 g over 10 minutes Q 4-8 hr) improved survival in an
international randomized controlled trial of trauma patients with significant hemorrhage.
80
Although fibrinolysis
may be less important in the pathophysiology of PPH, the WHO recommends tranexamic acid when PPH continues
despite standard uterotonic agents.
81
A large trial in postpartum hemorrhage patients is currently ongoing.
82

Registries of recombinant factor VIIa report an overall 80% success rate to control hemorrhage when other
interventions have failed, with reported doses "90 mcg/kg.
83
Temperature, acidosis, calcium, platelets and
fibrinogen should be first optimized for maximal hemostatic effect. For women with refractory hemorrhage in the
setting of amniotic fluid embolism, recombinant factor VIIa has been associated with a high rate of devastating
thrombotic complications.
84

Lyophylized fibrinogen concentrate 2-4 g has been reported to be helpful in obstetric patients.
85
Although
derived from human serum, fibrinogen concentrate is pasteurized, available in a standard concentration, and may be
reconstituted and administered rapidly in a low volume.
86
The optimal amount of FFP to administer with fibrinogen
concentrate is unknown.

References
1. Obstet Gynecol 2006; 108:1039-48.
2. California Maternal Quality Care Collaborative. Available at: http://cmqcc.org/. Accessed June 7, 2011.
3. Thachil J et al.: Blood Rev 2009; 23:167-76.
4. Bateman BT et al.: Anesth Analg 2010; 110:1368-73.
5. Callaghan WM et al.: Am J Obstet Gynecol 2008; 199:133 e1-8.
6. Knight M et al.: BMC Pregnancy Childbirth 2009; 9:55.
7. Kuklina EV et al.: Obstet Gynecol 2009; 113:293-9.
8. Crozier TM et al.: Aust N Z J Obstet Gynaecol 2011; 51:233-8.
9. Bateman BT et al.: Am J Obstet Gynecol 2012; 206:e1-8.
10. Hernandez JS et al.: Obstet Gynecol 2012; 119:1137-42.
11. Hamilton BE et al.: National Vital Statistics Reports 2010; 59:1-29.
12. Al-Zirqi I et al.: Am J Obstet Gynecol 2009; 201:273 e1-9.
13. Phaneuf S et al.: J Reprod Fertil 2000; 120:91-7.
14. Grotegut CA et al.: Am J Obstet Gynecol 2011; 204:56 e1-6.
15. Endler M et al.: Obstet Gynecol 2012; 119:801-09.
16. Berg CJ et al.: Obstet Gynecol 2010; 116:1302-9.
17. Saving mothers lives 200608. Br J Obstet Gynecol 2011;118 (Suppl. 1):1203.

504
Page 8
18. Miller DA et al.: Am J Obstet Gynecol 1997; 177:210-4.
19. Silver RM et al.: Obstet Gynecol 2006; 107:1226-32.
20. Belfort MA et al.: Am J Obstet Gynecol 2010; 203:430-9.
21. Eller AG et al.: Br J Obstet Gynaecol 2009; 116:648-54.
22. Gonsoulin W et al.: Am J Obstet Gynecol 1991; 165:91-4.
23. Warshak CR et al.: Obstet Gynecol 2010; 115:65-9.
24. Eller AG et al.: Obstet Gynecol 2011; 117:331-7.
25. Wright JD et al.: Obstet Gynecol 2010; 115:1194-200.
26. Rossi AC et al.: Obstet Gynecol 2010; 115:637-44.
27. Weiniger CF et al.: Anaesthesia 2005; 60:1079-84.
28. Wright JD et al.: Am J Obstet Gynecol 2011; 205
29. Sentilhes L et al.: Obstet Gynecol 2010; 115:526-34.
30. Stotler B et al.: Transfusion 2011; 51:2627-33.
31. O'Rourke N et al.: Anesth Analg 2007; 104:1193-4.
32. Shih JC et al.: Am J Obstet Gynecol 2005; 193:1756-8.
33. Jeffrey A et al.: Curr Opin Anaesthesiol 2011; 24:439-44.
34. Chow L et al.: Hematol Oncol Clin North Am 2011; 25:425-43, ix-x.
35. Silver RM et al.: Clin Obstet Gynecol 2010; 53:252-64.
36. Singh A et al.: Anesth Analg 2009; 108:1882-5.
37. Pacheco LD et al.: Am J Obstet Gynecol 2010; 203:194-200.
38. Belfort M et al.: Am J Perinatol 2011; 28:207-10.
39. Barth WH et al.: New England Journal of Medicine 2011; 365:359-66.
40. Waters JH et al.: Anesth Analg 2000; 90:229-30.
41. Goodnough LT et al.: Transfusion 2011
42. Ransom SB et al.: Obstet Gynecol 1998; 92:493-5.
43. Cambic CR et al.: Can J Anaesth 2010; 57:811-6.
44. Grunebaum A et al.: Am J Obstet Gynecol 2011; 204:97-105.
45. Rizvi F et al.: Br J Obstet Gynaecol 2004; 111:495-8.
46. Skupski DW et al.: Obstet Gynecol 2006; 107:977-83.
47. Maslovitz S et al.: Obstet Gynecol 2007; 109:1295-300.
48. Bonnet MP et al.: Eur J Obstet Gynecol Reprod Biol 2011
49. Driessen M et al.: Obstet Gynecol 2011; 117:21-31.
50. Kayem G et al.: Obstet Gynecol 2004; 104:531-6.
51. Gosman GG et al.: Am J Obstet Gynecol 2008; 198:367 e1-7.
52. Shields LE et al.: Am J Obstet Gynecol 2011; 205:368.e1-68.e8.
53. Jangsten E et al.: Br J Obstet Gynaecol 2011; 118:362-9.
54. Elbourne DR et al.: Cochrane Database Syst Rev 2001:CD001808.
55. Dyer RA et al.: Int J Obstet Anesth 2010; 19:313-9.
56. Why mothers die 1997-1999. London: Royal College of Obstetrics & Gynaecologists; 2003.
57. Dyer RA et al.: Anesthesiology 2009; 111:753-65.
58. Butwick AJ et al.: Br J Anaesth 2010; 104:338-43.
59. Carvalho JC et al.: Obstet Gynecol 2004; 104:1005-10.
60. Balki M et al.: Obstet Gynecol 2006; 107:45-50.
61. Dildy GA, 3rd et al.: Obstet Gynecol 2004; 104:601-6.
62. Toledo P et al.: Am J Obstet Gynecol 2010; 202:400 e1-5.
63. Singh S et al.: Anaesthesia 2012; 67:12-18.
64. Charbit B et al.: J Thromb Haemost 2007; 5:266-73.
65. de Lloyd L et al.: Int J Obstet Anesth 2011; 20:135-41.
66. Cortet M et al.: Br J Anaesth 2012; 108:984-89.
67. Chatterjee DJ et al.: Anaesthesia 2011; 66:306-10.
68. Miller S et al.: BMC Pregnancy Childbirth 2010; 10:64.
69. O'Brien D et al.: Eur J Obstet Gynecol Reprod Biol 2010; 153:165-9.
70. Murad MH et al.: Transfusion 2010; 50:1370-83.
71. Inaba K et al.: J Am Coll Surg 2010; 210:957-65.
72. Sambasivan CN et al.: J Trauma Acute Care Surg 2011; 71:S329-S36.
73. Johnson JL et al.: Arch Surg 2010; 145:973-7.
74. Chandler WL et al.: Transfusion 2010; 50:2547-52.

504
Page 9
75. Schochl H et al.: Scand J Trauma Resusc Emerg Med 2012; 20
76. Huissoud C et al.: Br J Obstet Gynaecol 2009; 116:1097-102.
77. Burtelow M et al.: Transfusion 2007; 47:1564-72.
78. Gutierrez MC et al.: Int J Obstet Anesth 2012; 21:230-5.
79. McDonnell NJ et al.: Anaesth Intensive Care 2010; 38:492-9.
80. Shakur H et al.: Lancet 2010; 376:23-32.
81. WHO recommendations for the prevention of postpartum haemorrhage. Geneva: WHO; 2007.
82. Shakur H et al.: Trials 2010; 11:40.
83. Alfirevic Z et al.: Obstet Gynecol 2007; 110:1270-8.
84. Leighton BL et al.: Anesthesiology 2011; 115:1201-8.
85. Bell SF et al.: Int J Obstet Anesth 2010; 19:218-23.
86. Sorensen B et al.: Br J Haematol 2010; 149:834-43.

Disclosure

510
Page 1
Malpractice or Miscommunication? Lessons Learned to Improve Patient Safety on the
Labor and Delivery Suite.
David J. Birnbach M.D., MPH Miami, Florida
INTRODUCTION
Perceptions regarding the quality of healthcare in the US changed dramatically following the publication of Institute
of Medicine report titled To Err is Human: Building a Safer Health Care System in 1999 (1). Prior to that
publication, many patients and physicians did not realize that our healthcare system was often causing preventable
morbidity and mortality. We now know that many patients in the US die each year due to medical errors. A number
of changes have been advocated to improve patient safety, including mandating minimum nurse-to-patient ratios (2),
reducing working hours of resident physicians (3), and advances to the science of simulation and teamwork training
(4,5). This talk will review medical errors with an emphasis on the role of the anesthesiologist and also highlight
several modalities that can be used by labor and delivery personnel to improve communication and reduce risk to
patients. A recent review of patient safety in operating rooms offers recommendations based on the existing
evidence base that have potential to improve patient safety in the operating room and labor and delivery suite.(6)
PATIENT SAFETY IN OBSTETRICS
There has been a recent renewed interest in changing health care culture, so as to build safer systems, including
appropriate physical work environment, developing redundancies in safety procedures, having the ability to allow
health care workers to painlessly report their mistakes (including near misses) and to provide mechanisms to learn
from those experiences. Unfortunately, none of these systems will achieve the ultimate goal of patient safety
without the support from physicians as well as hospital leadership and administrators. Anesthesiologists may play a
vital role in this change in culture.
A recent American College of Obstetricians and Gynecologists (ACOG) Committee Opinion states that promoting
safety requires that all those in the healthcare environment recognize that the potential for errors exists and that
teamwork and communication are the basis for fostering change and preventing errors (7). The Committee
recommended the following seven objectives for safety:
1. Develop a commitment to encourage a culture of patient safety.
2. Implement recommended safe medication practices including improving legibility of handwriting and
avoiding use of non-standard abbreviations.
3. Reduce the likelihood of surgical errors.
4. Improve communication.
5. Identify and resolve system problems.
6. Establish a partnership with patients.
7. Make safety a priority in every aspect of practice.
MEDICAL ERRORS
The Institute of Medicine (IOM) has defined medical error as a failure of a planned action to be completed as
intended, or the use of a wrong plan to achieve an aim. Communication problems are consistently identified as a
510
Page 2
leading cause of medical errors in obstetrics (8) and the Joint Commission reports that lack of effective
communication is often the primary reason for sentinel events (9).
Traditional medical and nursing education has relied on the treatment of real patients in actual clinical settings.
There is a belief now that the current availability of medical simulations and the knowledge gained from the science
of team training may improve patient outcomes, and there is a paradigm shift occurring in many universities and
training programs. Many medical and nursing schools have purchased simulators and are increasingly using them in
undergraduate and graduate education.
TEAMS and TEAMWORK
Healthcare can be considered a team activity. Teams take care of hospitalized patients. Furthermore, healthcare
teams operate in an environment characterized by acute stress, heavy workload, and high stakes for decision and
action errors (10). Individuals have limited capabilities. When the limitations are combined with organizational and
environmental complexity, human error becomes virtually inevitable (11). The labor and delivery suite is a
particularly complex and stressful environment. In fact, the labor and delivery suite requires intense, error-free
vigilance with effective communication and teamwork between many different clinical disciplines who while
working together, have probably never trained together. The group includes obstetricians, midwives, labor nurses,
operating room staff, anesthesiologists, and pediatricians (12).
What is teamwork? It can be defined as a set of interrelated behaviors, actions, cognitions and attitudes that
facilitate the required task work that must be completed. (13) Lack of teamwork has been identified as leading
sources of adverse events in medicine. Team behavior and coordination, particularly communication or team
information sharing, are critical for optimizing team performance (14). Baker and colleagues have stated that to
work together effectively, team members must possess specific knowledge, skills and attitudes (KSAs) such as the
skill in monitoring each others performance, knowledge of their own and teammates task responsibilities, and a
positive disposition toward working in a team (15). These authors have described characteristics of effective teams,
which include team leadership, mutual performance monitoring, backup behavior, adaptability, shared mental
models, communication, team/collective orientation, and mutual trust. Moreover, effective team performance in
complex environments requires that team members hold a shared understanding of the task, their equipment, and
their teammates (16). Salas and colleagues (17) have defined the characteristics of effective teams, as highlighted in
Table 1.
Table 1
Characteristics of Effective Teams
Knowledge/Skills/Attitudes Characteristic of Team
Leadership Roles clear but not overly rigid
Team members believe leaders care about them
Backup Behavior Members compensate for each other
Provide feedback to each other
Mutual Performance Monitoring Members understand each others roles
Communication Adaptability Members communicate often, anticipate each other
Mutual trust Trust each others intentions
There is a clear difference between the leadership of individuals versus team leadership. One who is leading
independent individuals will diagnose a problem, generate possible solutions, and implement the most appropriate
solution. Team leadership, conversely, does not usually involve handing down solutions to individual team

510
Page 3
members, but rather defining team goals, setting expectations, coordinating activities, organizing team resources,
and guiding the team toward their goals (18).

Team leaders can improve team performance in many ways, such as by promoting coordination and cooperation.
These individuals must not only be technically competent, but they must also be competent in leadership skills (19).
But when do anesthesiologists and other physicians learn to be competent communicators and team leaders? If not
taught to undergraduate medical students, are these skills taught in residency programs? Unfortunately, the answer is
all too often a resounding no. Many of the tasks necessary can and must be learned during residency training.
Simulation therefore plays a key role in this education and may thus reduce errors (20). Team leadership training has
been developed to successfully train specific team leader behaviors. The implementation of these programs has been
shown to increase team performance (13). The Joint Commission has recommended a risk-reduction strategy for
decreasing perinatal death or injury. This strategy includes the implementation of team training and mock
emergency drills for shoulder dystocia, emergency cesarean delivery, and maternal hemorrhage (21).

The IOM has also recommended that team training and implementation of team behaviors could improve patient
safety (22). In a recent editorial, Murray and Enarson stated that when a crisis complicates patient care, teamwork
among healthcare professionals is frequently strained, resulting in more frequent as well as more serious failures in
managing critical events. (23) Team training promotes the acquisition of adaptive behaviors, shared cognitions and
relevant attitudes and is an instructional strategy that ideally combines practice-based delivery methods with realistic
events guided by medical teamwork competencies (i.e., the behaviors, cognitions, and/or attitudes).

TEAM TRAINING

Patient safety is predicated on trust, open communication, and effective interdisciplinary teamwork. (24) It is
often the interactions of healthcare workers that produce effective or ineffective performance (25). But where do
medical students, residents, attending physicians, nursing students, nurses, and midwives learn to work as team
members?

Thomas and colleagues conducted a qualitative assessment of teamwork and suggested that factors which influence
the ability to work together could be divided into 3 categories: (1) provider characteristics (personal attributes,
reputation, expertise); (2) workplace factors (staffing, work organization, work environment); and (3) group
influences (communication, relationships, and team) (26). These categories can be addressed, at least in part, by
working together in teams in a simulated environment and evaluating teamwork and human performance. Lyndon
has suggested that the application of human performance-based theory has demonstrated that communication
patterns, team function, workload, and coping mechanisms affect both individual and group ability to identify
evolving problems and make appropriate management decisions in complex decision-making situations (27).

Why is teamwork training important for Labor and Delivery personnel? As previously described, communication
problems are consistently identified as a leading cause of medical error. Many of these communication issues can be
addressed during team training. The recent Confidential Enquiry in Maternal Deaths in the UK has emphasized that
emergency drills for maternal resuscitation should be regularly practiced in clinical areas in all maternity units
(28). We know from research that when trainees have an opportunity to practice relevant competencies in a
structured scenario and get diagnostic feedback on their individual and collective performance, it works. A recent
review of a comprehensive obstetrics patient safety program which included labor and delivery team training
reported a decrease in number of sentinel events as well as a decrease in compensation payments (29).

SIMULATION-BASED TRAINING IN L&D
Do drills work? According to the Agency for Healthcare Research and Quality (AHRQ), drills that are carefully
planned can decrease medical errors by addressing unintended events that may result in injury to a patient arising
from unintentional actions, mistakes in judgment, or inadequate plans of action
http://www.qualityindicators.ahrq.gov). It has been suggested that simulation can be used as an educational tool to
assist in transfer of knowledge, practicing diagnostic skills, surgical skills training, emergency drill training, and
human factors and team training (30). Chopra and colleagues have reported that training with high fidelity
simulation improves the speed with which anesthesiologists respond to emergencies and the quality of their care
(31).

510
Page 4
Simulation of L&D events can range from high fidelity human simulators (often located off site) to low tech
simulations and drills, that can often be done in the L&D suite (32). L&D events that are commonly addressed
include maternal hemorrhage (antepartum as well as postpartum), failed intubation, failed neuraxial block,
eclampsia, cardiac arrest, anaphylaxis, cord prolapse, amniotic fluid embolism, and shoulder dystocia.

Obstetricians, anesthesiologists, pediatricians, labor nurses, midwives, and OR staff all work together as part of a
system and when an error occurs, it is usually associated with the system. Therefore, optimal simulation exercises
involve all these key players and evaluate not only their behaviors and communication skills, but also problems
within the system in which they work. Simulation allows the re-creation of a labor and delivery room or operating
room, where reality-based scenarios can be recreated allowing anesthesiologists, obstetricians, midwives, nurses,
and pediatricians to practice their roles and communication skills.

Both high tech and low tech approaches to simulation have been utilized for training Labor and Delivery staff.
Simulation centers often use high fidelity simulation with interactive computerized mannequins in a realistic
environment. The mannequin is quite realistic and has pulses, O2 saturation, heart and breath sounds, ventilatory
movements and electrocardiogram tracing. All vital signs can be adjusted via computer control, as can the ability to
intubate or ventilate. Not all simulation exercises and drills for obstetrics need to be performed in high fidelity
simulators and some authors have advocated classroom training as superior (33). The inability to arrange for staff of
several disciplines to be off the L&D floor simultaneously often precludes the use of high tech simulation and may
make on-site exercises advantageous (34).

Some authors believe that classroom training may be advantageous and it has been suggested that high fidelity
simulation is too expensive (35). Gaba, however, has countered by stating that simulation need not be cost-
prohibitive and that it provides the required real-life experience necessary for training of complex real-life
scenarios (36). Morgan et al have reported on an obstetric model that allowed a more realistic participation of real
surgeons (rather than actors playing the role of surgeons) in a simulated scenario (37).

There are several available options for teaching teamwork and crisis intervention in obstetrics. Multi-disciplinary
obstetric simulated emergency scenarios (MOSES) was first reported by the St. Bartholomew Hospital Group in
2002. (38) Obstetricians, anesthesiologists and midwives participated in team training on a high fidelity simulator.
MedTeams was developed by the US Armed Forces and Dynamics Research Corporation. Originally described in
Emergency Departments (39, 40) it has now been used for labor and delivery teams (12). AHRQ and the
Department of Defense have teamed to build a teamwork system termed Team Stepps to improve communication
and teamwork skills among health care professionals (41). This program has also become a popular tool for
obstetrics team training. A recent review on the use of simulation as part of a comprehensive patient safety program
concluded that following simulation-based training, the evidence is overwhelming that, with practice, obstetricians
improve their technical and communication skills (42).The same is no doubt true for anesthesiologists and labor
nurses, as well as for multi-disciplinary teams.

CONCLUSION

The data in support of the use of medical simulation and team training in Labor and Delivery is very encouraging.
These modalities improve teamwork and communication and allow recognition of potential areas of weakness.
Because of a growing body of evidence, many authors believe that team training is essential in the healthcare arena
(43, 44). It has recently been advocated that safety will be improved as a result of (i) embedding simulation into
clinical training and practice, (ii) standardization of skills and team assessment processes, (iii) investment in training
and quality assurance of senior faculty to train and mentor skills and teams, and finally (iv) a more thoughtful and
evidence-based approach to healthcare provider selection (6).

510
Page 5
References
1. Kohn LT, Corrigan JM, Donaldson MS, eds. Institute of Medicine. To err is human: building a safer health
system. Washington DC. National Academy Press, 2000.
2. Aiken LH, Clarke SP, Slonae DM et al. Hospital nurse staffing and patient mortality, nurse burnout and job
dissatisfaction. JAMA 2002;288:1987-1993.
3. Landrigan CP, Rothschild JM, Cronin JW et al. Effect of reducing interns work hours on serious medical
errors in intensive care units. N Engl J Med 2004;351:1838-48.
4. Gaba DM. Anaesthesiology as a model for patient safety in health care. BMJ 2000;320:785-88.
5. Salas E, Wilson KA, Burke CS, Priest HA. Using simulation based training to improve patient safety: what
does it take? Jt Comm J Qual Pat Saf 2005;31:363-71.
6. Sevdalis N, Hull L, Birnbach DJ. Improving patient safety in the operating theatre and perioperative care:
obstacles, interventions, and priorities for accelerating progress. Br J Anaesth 2012;109 Suppl 1:i3-16
7. ACOG Committee Opinion Number 286. Int J Gynaecol Obstet 2004;86:121-3.
8. Simpson KR, Knox GE. Adverse perinatal outcomes. Recognizing, understanding & preventing common
accidents. AWHONN Lifelines 2003;7:224-35
9. Joint Commission. Root cause of sentinel events, all categories: 1995-2004 http://www.jointcommission.org.
10. Salas E, Rosen MA, King H. Managing teams managing crises: principles of teamwork to improve patient
safety in the Emergency Room and beyond. Theoretical issues in Ergonomics Science 2007;8:381-94.
11. Wilson KA, Burke CS, {riest HA, Salas E. Promoting simulation-based training through high reliability
teams. Qual Saf Health Care 2005;14:303-9.
12. Nielsen PE, Goldman MB, Mann S et al. Effects of teamwork training on adverse outcomes and process of
care in labor and delivery. A randomized controlled trial. Obstet Gynecol 2007;109:48-55.
13. Salas E, Guthrie JW, Wilson-Donnelly KA, Priest HA, Burke CS. Modeling team performance: The basic
ingredients and research needs. Chapter 7. Organizational Simulation. Rouse WB ed. Wiley and Sons, NJ,
2005.
14. Blum RH, Raemer DB, Carroll JS, Dufresne RL, Cooper JB. A method for measuring the simulation-based
team training for improving communication skills. Anesth Analg 2005;100:1375-80
15. Baker DP, Day R, Salas E. Teamwork as an essential component of high reliability organizations. Health
Service Res 2006;4;1576-98.
16. Salas E, Rosen MA, Burke CS, Nicholson D, Howse WR. Markers for enhancing team cognition in complex
environments: the power of team performance diagnosis. Aviation Space Environ Med 2007;78:877-85.
17. Salas E, Sims DE, Klein C. Cooperation and teamwork at work. In Encyclopedia of Applied Psychology.
Vol1. Edited by Spielberger CD. P499-505. San Diego: Academic press. 2004
18. Salas E, Wilson-Donnelly KA, Sims, DE, et al. Teamwork training for patient safety: Best practices and
guiding principles. From: Teamwork Training for Patient Safety. Chapter 44.
19. Salas E, Rosen MA, King H. Managing .teams managing crises: principles of teamwork to improve patient
safety in the Emergency Room and beyond. Theoretical Issues in Ergonomics Science. 2007;8;381-94.
20. Birnbach DJ, Salas E. Can medical simulation and team training reduce errors in labor and delivery.
Anesthesiology Clinics 2008;26:159-168.
21. Joint Commission on Accreditation of Healthcare Organizations. JCAHO Sentinel Event Alert #30, 2004.
22. Committee on Quality Health Care in America. Crossing the quality chasm: a new health system for the 21st
century. Washington, D.C., National Academy Press, 2001.
23. Murray D, Enarson C. Communication and teamwork: essential to learn but difficult to measure.
24. Simpson KR, James DC, Knox GE. Nurse-physician communication during labor and birth: implications for
patient safety. JOGNN 2006;35:547-56.
25. Rosen MA, Salas E, Wilson KA, King HB, Salisbury M, Augenstein JS, Robinson DW, Birnbach DJ.
Measuring team performance in simulation-based training: adopting best practices for healthcare. Sim
Healthcare 2008;3:33-41.
26. Thomas EJ, Sherwood GD, Mulhollem JL, Sexton BJ, Helmreich RL. Working together in the neonatal
intensive care unit: provider perspectives. J Perinatol 2004;24:552-59.
27. Lyndon L. Communication and teamwork in patient care: how much can we learn from aviation? JOGNN
2006;35:538-46.

510
Page 6
28. RCOG. Why Mothers Die 2000-2002, the Confidential Enquiries into Maternal Deaths in the United
Kingdom. London, RCOG Press 2004, pp96-101.
29. Grunebaum A, Chervenak F, Skupski D. Effect of a comprehensive obstetric patient safety program on
compensation payments and sentinel events. Am J Obstet Gynecol. 2011;204(2):97-105.
30. Johannson H, Ayida G, Sadleer C. Faking it? Simulation in the training of obstetricians and
gynecologists.Current Opin Obstet Gynecol 2005;17:55-61.
31. Chopra V, Gesnik BJ, DeJong J, et al. Does training on an anaesthetic simulator lead to improvement in
performance? Br J Anaesth 1994;73:293-7.
32. Sorensen SS. Emergency drills in obstetrics: reducing risk or perinatal death or permanent injury. JONAS
Healthc Law Ethics Regul 2007:9;9-16.
33. Pratt SD, Sachs BP. Team Training: Classroom training vs. high fidelity simulation. Point Counterpoint.
AHRQ Web M&M March 2006. Accessed at:
http://www.webmm.ahrq.gov/perspective.aspx?perspectiveID=21.
34. Sorensen SS. Emergency drills in obstetrics: reducing risk of perinatal death or permanent injury. JONAS
Healthc Law Ethics Regul 2007:9;9-16.
35. Kurrek MM, Devitt JH. The cost for construction and operation of a simulation centre. Can J
Anaesth1997;44:1191-5.
36. Gaba DM. Two examples of how to evaluate the impact of new approaches to teaching.
Anesthesiology2002;96:1-2.
37. Morgan PJ, Pittini R, Regehr G, Marrs C, Haley MF. Evaluating teamwork in a simulated obstetric
environment. Anesthesiol 2007;106:907-15.
38. Davis C, Gregg A, Thornley D. Initial feedback on MOSES (multidisciplinary obstetric simulated emergency
scenarios): a course on team training, human behaviour and fire drills. Anesthesiol 2002;96:A
39. Morey JC, Simon R, Jay GD, et al. Error reduction and performance improvement in the emergency
department through formal teamwork training: evaluation results of the MedTeams Project. Health Serv Res
2002;37:1553-81.
40. Simon R, Salisbury M, Wagner G. MedTeams: teamwork advances emergency department effectiveness and
reduces medical errors. Ambul Outreach 2000;21-4.
41. http://teamstepps.ahrq.gov/index.htm
42. Argani CH, Eichelberger M, Deering S, Satin AJ. The case for simulation as part of a comprehensive patient
safety program. Am J Obstet Gynecol 2012;206:451-5.
43. Sundar E, Sundar S, Pawlowski J, et al. Crew Resource Management and Team Training. Anesthesiol Clin
2007;25:283-300)
44. Grogan EL, Stiles RA, France DJ, et al. The impact of aviation-based teamwork training on the attitudesof
health-care professionals. J Am Coll Surg 2004;199:843-8.

Disclosure

516
Page 1
Thrombocytopenia and Low Molecular Weight Heparin in the Parturient:
Implications for Neuraxial Anesthesia
Yaakov (Jake) Beilin, M.D.
New York, New York
Introduction
Neuraxial analgesia is routinely administered to the parturient. A devastating, albeit rare, complication of
neuraxial anesthesia is spinal or epidural hematoma, and primarily occurs in patients with disorders of hemostasis.
A parturient with a clinically active coagulation disorder, or someone with a history of easy bruising and/or
bleeding, is considered to have an absolute contraindication to regional anesthesia. However, many areas of
controversy exist. The concern most anesthesiologists have regarding thrombocytopenia is determining the lowest
platelet count at which it is still safe to perform a neuraxial anesthetic technique. In addition, an increasing number
of women are receiving anticoagulant medications during pregnancy and low molecular weight heparin (LMWH) is
a commonly used agent. During this lecture I will review the role of platelets in the coagulation process, the most
common disorders in pregnancy that lead to thrombocytopenia, the laboratory tests available to assess platelet
function and provide practical recommendations as to the anesthetic management of the parturient with
thrombocytopenia and one who is taking LMWH.
Thrombocytopenia and neuraxial anesthesia
Platelet counts generally decrease by approximately 20% during a normal pregnancy. This decrease is
usually not clinically significant and does not generally impact on the decision to place an epidural anesthetic.
However, approximately 7% of all parturients will present with a platelet count < 150,000!mm
-3
, and 0.5-1% will
present with a platelet count < 100,000!mm
-3
.
1

An epidural or spinal hematoma can be a catastrophic complication and can lead to permanent paralysis. In
1988, Cousins and Bromage recommended that one should not place an epidural catheter if the platelet count is less
than 100,000!mm
-3
.
2
Recently, their recommendation has been challenged, primarily because thrombocytopenia
occurs frequently during pregnancy
1
and neuraxial anesthesia is safer than general anesthesia for the parturient.
3
An
absolute platelet count below which a neuraxial anesthetic is considered unsafe would lead to more frequent use of
general anesthesia, which is far riskier in the parturient.
Hawkins et al.
3
reviewed pregnancy-related deaths in the United States between 1985 and 1990 and found
that the anesthesia-related maternal mortality rate was 32.3 deaths per million in parturients who had general
anesthesia for cesarean delivery, but only 1.9 deaths per million in women who had regional anesthesia. There is an
increasing trend to use regional anesthesia in the parturient, so an absolute conservative cut-off for a sufficient
platelet count is not prudent. Failure to provide neuraxial anesthesia during labor and delivery based solely on a low
platelet count commits the patient, at a minimum, to a painful labor. Furthermore, if the woman later requires a
cesarean delivery, perhaps emergently, the anesthesiologist may then be forced to administer an anesthetic under
less than optimal conditions.
Coagulation
Clotting can be thought of as occurring in two phases, primary and secondary hemostasis. Primary
hemostasis refers to the creation of the initial platelet plug and secondary hemostasis refers to the creation of the
stable fibrin clot. Platelets play an important role in both processes. Generally, blood vessels prevent platelet
adhesion by releasing a potent vasodilator, prostacyclin. After vessel wall injury, prostacyclin levels decrease
allowing platelets to adhere to the vessel wall. This adhesion leads to activation and degranulation of platelets with
release of adenosine 5-diphosphate (ADP), serotonin and thromboxane, which then leads to platelet aggregation.
Further aggregation leads to formation of a platelet plug. This plug is unstable and requires fibrin deposition to
make it more stable, which occurs by activation of the intrinsic and/or extrinsic coagulation system. Platelets
provide the phospholipid membrane on which the coagulation cascade occurs.
516
Page 2
Platelet abnormalities can be qualitative or quantitative and are the most common hematologic disorders
during pregnancy. Most cases (99%) of thrombocytopenia during pregnancy are related to one of three causes:
gestational thrombocytopenia (74%), hypertensive disorders such as preeclampsia (21%), and immune
thrombocytopenic disorders of pregnancy such as idiopathic thrombocytopenic purpura (ITP) (4%).
4
When
evaluating the parturient with thrombocytopenia, there are two specific issues to consider. The first concern is
whether the disorder is static or dynamic. If the disorder is static, as occurs during gestational thrombocytopenia or
ITP, the platelet count is usually stable. If the disorder is dynamic, as occurs during preeclampsia, the platelet count
may rapidly change and it is important to obtain serial platelet counts. The second issue is whether platelet function
is normal or abnormal. Platelet function is typically normal in gestational thrombocytopenia and ITP, and may be
abnormal in preeclampsia.
The parturient with thrombocytopenia is difficult to evaluate with standard laboratory tests because both
platelet quantity and quality must be assessed. Tests of platelet function have been criticized for being difficult to
perform, for lacking reproducibility and being of questionable clinical relevance. The ideal test should be easy to
perform, inexpensive, would not require specialized equipment and the results could be reproduced and correlated
with outcome. Bedside tests of coagulation include the bleeding time, thromboelastography (Haemoscope
Corporation, Skokie, IL), and the Platelet Function Analyzer, PFA-100 (Dade Behring, Newark, DE).
The bleeding time is a simple bedside test that evaluates both the quality and quantity of the platelets. A
small skin nick is made with a template on the volar surface of the forearm and the time until the blood clots is
calculated. A bleeding time of less than 10 minutes is considered normal. Anesthesiologists formerly used the
bleeding time to assess the safety of epidural or spinal placement. If the results of the bleeding time were normal,
they would proceed with neuraxial anesthesia, and if the results were abnormal, they would not. However, the
bleeding time is no longer recommended to determine the safety of epidural catheter placement because bleeding at
the test site does not necessarily reflect the risk of bleeding at other sites,
5,6
and there is also wide observer
variation.
7
OKelly et al.
7
asked twelve observers to assess the bleeding time on five separate volunteers and the
reliability of the measurements obtained was poor. Although no longer recommended, a survey by Beilin et al.
8
in
1996 found that 48% of anesthesiologists in academic practice and 76% in private practice still used the bleeding
time to assist them in deciding whether to place a neuraxial anesthetic in the parturient with thrombocytopenia.
The thromboelastogram (TEG) measures all phases of coagulation and fibrinolysis by using less than 1 mL
of a whole blood sample to measure the elasticity of clotting blood. Blood is placed in a cylindrical cup that
oscillates. A pin is then suspended in the blood by a torsion wire and is monitored for motion. The torque of the
rotating cup only affects the pin after fibrin-platelet bonding has linked the cup and pin together. The strength of the
developing clot affects the magnitude of the pin motion such that strong clots move the pin directly in phase with the
cup, and weak clots do not. The resulting profile is a measure of the time taken for the first fibrin strand to form,
and the kinetics, strength, and breakdown of the clot (Figure). The maximum amplitude (MA) has been found to
correlate best with platelet function.

516
Page 3
Orlikowski et al.
9
measured platelet counts, TEG parameters and bleeding time in healthy pregnant women
and in those with preeclampsia. They found that the MA remained normal (53 mm) until the platelet count
decreased to less than 54,000!mm
-3
(95% confidence limit 40-75,000!mm
-3
).

Based on their study, they suggested
that a platelet count of 75,000!mm
-3
should be associated with adequate hemostasis. However, there is no clinical
evidence that a normal MA correlates with safe epidural analgesia.
The PFA-100 is an intriguing test because it is specific to platelet function, the primary disorder in
preeclampsia. The machine simulates the in-vivo hemostatic mechanism of platelet function by accelerating citrated
whole blood through a small, 150 micrometer, aperture cut into a collagen membrane. The collagen membrane is
coated with one of two platelet activators, epinephrine or ADP. The collagen membrane cartridges are named for
the platelet activator that coats them, CEPI or CADP, respectively. The time taken for the aperture to close is called
the closure time (CT). This machine is commonly used by hematologists as a screening tool for patients who
present with unknown coagulopathies and is especially sensitive for the detection of Von Willebrand disease.
10

Some have found a correlation between an increasing CT and decreasing platelet count,
11
however, this has not been
confirmed in all studies.
12

The overall risk of epidural or spinal hematoma following neuraxial anesthesia is in the range of 1:150,000-
220,000.
13
Vandermeulen et al.
13
reviewed the literature and found 61 cases of anesthesia-related spinal hematoma.
Most (68%) occurred in patients with coagulopathies, and 75% of all cases had an epidural rather than a spinal
anesthetic. Of those who received an epidural anesthetic, 88% had an epidural catheter inserted and almost 50% of
those patients developed an epidural hematoma following catheter removal.
This author is aware of ten reports in the literature of neuraxial (spinal or epidural) hematoma occurring in
parturients and only one in a woman with preeclampsia with thrombocytopenia.
14-23
This woman had an epidural
anesthetic with 13 mL of bupivacaine 0.5% for uneventful cesarean delivery, but had a seizure in the recovery room
one hour after the procedure. It was noted that her legs did not move and a CT scan revealed an epidural collection
of fluid. A laminectomy was performed six hours after epidural catheter placement at which time four mL of blood
were drained. The patient recovered 72 hours later. Whether the four mL of epidural blood was sufficient to cause
her symptoms is unknown; it is possible that the symptoms were related to residual local anesthetic effects.
23

The origin of the recommendation to not place an epidural catheter if the platelet count is < 100,000!mm
-3

may be related to a study demonstrating that the results of the bleeding time are not prolonged until the platelet
count falls below 100,000!mm
-3
.
24
However, we are now aware that the bleeding time test is not reliable. The
safety of initiating an epidural anesthetic when the platelet count is < 100,000!mm
-3
is supported by the results of
three retrospective studies.
1,25,26
In the largest study, Beilin et al.
1
reviewed the medical records of 15,919
consecutive parturients during a three-year period. They found 80 women who presented with a platelet count <
100,000!mm
-3
, and thirty of these women received an epidural anesthetic without sequelae. None of these 30
women had a decreasing platelet count at the time of epidural catheter placement and none had clinical evidence of
bleeding. Five women were denied an epidural anesthetic because of decreasing platelet counts and two because of
clinical evidence of bruising. There is also one case report of a woman who safely received an epidural anesthetic
without prior knowledge of a platelet count of 2,000!mm
-3
.
27

Most authors do not define a minimum platelet count below which it is unsafe to perform an epidural
anesthetic. Indeed, each patient must be individualized and the responsible anesthesiologist must weigh the risks
versus the benefits. Based on the results of the survey by Beilin et al.
8
, most anesthesiologists (66% of those in
academic practice and 55% of those in private practice) will perform an epidural anesthetic when the platelet count
is between 80,000 and 100,000!mm
-3
. Below 80,000!mm
-3
,

most were unwilling to place an epidural catheter.

Practical recommendations
A routine platelet count is not necessary in the otherwise healthy parturient and should be drawn based on
patient history, physical examination and clinical signs.
28
If the platelet count is found to be low it is important to
confirm this finding since automated counters can be unreliable, especially at lower platelet counts. A manual count
should be undertaken as it is not uncommon to find the platelets are clumping and the count is really greater than
calculated.
29
The patient history and physical examination are key components when deciding whether to proceed
with a regional anesthetic in the parturient with thrombocytopenia. Consultation with a hematologist, preferably
prior to labor, can also help with assessing the etiology of thrombocytopenia and determining whether the platelets
are functioning adequately. If there is any history of easy bruising, or the patient has evidence of petechiae or
ecchymosis, regional anesthesia should not be offered. If the patient has no bleeding history, then our general
practice is to obtain at least one additional platelet count as close in time to epidural catheter placement as possible
to ensure that it is not decreasing further. This is especially important for disease processes that are dynamic, such

516
Page 4
as preeclampsia. We do not obtain any bed-side tests of platelet function nor do we have any absolute platelet count
cut-off. A patient with a stable platelet count of 50,000!mm
-3
, as seen in ITP, is probably at lower risk than one with
a platelet count of 75,000!mm
-3
that is rapidly decreasing, as seen in preeclampsia. In general this author will place
an epidural catheter in a woman with a stable platelet count of approximately 70,000-75,000 mm
-3
and some are
comfortable with lower platelet counts especially in women with ITP.
30
There is no absolute cut-off and the risks of
epidural placement versus general anesthesia has to be individualized and informed consent must be obtained.
If the decision is made to proceed with neuraxial anesthesia, a subarachnoid block using a small gauge
spinal needle may be preferable to epidural anesthesia. This is not always possible, especially for women in labor
who will require repeated doses of local anesthetic. If possible, the newer flexible soft-tip epidural catheters should
be utilized as they are associated with a smaller incidence of inadvertent placement into a blood vessel.
31
The
epidural catheter should be placed in the midline and analgesia produced with the lowest concentration of local
anesthetics, so as to preserve motor function. The patient should be examined periodically to assess the extent of the
motor block, and these examinations should continue until after the anesthetic has worn off and the catheter has been
removed. In this way, if the patient develops a motor block out of proportion to what one would expect, or if the
anesthetic has a prolonged duration of action, the patient can be immediately assessed with magnetic resonance
imaging (MRI) for the development of an epidural hematoma. Immediate evaluation is necessary because if the
patient has an epidural hematoma, an emergent laminectomy and decompression must be performed as soon as
possible, preferably within 8 hours, hours to preserve neurologic function.
13
If the patient has an epidural catheter in
situ and develops a coagulopathy, the catheter should be removed only after the coagulation status is corrected.
13

Low molecular weight heparin
The release of low molecular weight heparin (LMWH) for general clinical use occurred first in Europe in
1987, and then in the United States in 1993. From May 1993 to February 1998, there were over 40 reports of spinal
or epidural hematoma in conjunction with LMWH use in the U.S.
32
Emergency laminectomy was performed in 28
patients, and 16 of these patients suffered permanent paraplegia. The American experience contrasted sharply with
the 1992 European data where Bergqvist et al.
33
showed a greater margin of safety with LMWH. They reviewed
forty-four controlled studies involving LMWH and epidural analgesia and were not able to find any reported case of
spinal hematoma among 10,000 cases. Furthermore, they estimated that LMWH has been used in conjunction with
spinal/epidural anesthesia in almost one million patients and there is only one case report of an epidural hematoma.
34

These discrepancies prompted a reevaluation of the risks, benefits and uses of LMWH in conjunction with neuraxial
anesthesia.
Standard, unfractionated heparin (UH) is a mixture of linear polysaccharide chains, with a molecular
weight that ranges from 5,000 to 30,000 daltons. Heparin acts as an anticoagulant by binding to antithrombin III
and potentiates the inhibition of factors IIa (thrombin), IXa, Xa, XIa and XIIa. A specific pentasaccharide sequence
on the heparin chain has a high-affinity binding site for antithrombin III, but only about 30% of the heparin
molecule has this sequence. In order to catalyze inhibition of factor Xa, only the pentasaccharide binding sequence
is necessary. But to catalyze inhibition of factor IIa, a heparin molecule must contain both this high-affinity
pentasaccharide sequence and an additional chain of at least thirteen sugars.
35
UH is highly sulfated and negatively
charged; as a result, it has a great affinity for plasma proteins and vascular matrix proteins, and has less than a 30%
bioavailability.
LMWH is produced by chemical or enzymatic depolymerization of standard heparin, which produces
shorter polysaccharide chains of 13 to 22 sugars and a molecular weight of 4,000 to 6,000 daltons.
36
LMWH has the
same anti-Xa activity as standard heparin with less anti-IIa (thrombin) activity. The concentration of LMWH is
referred to in international standards and expressed as anti-Xa units per millimeter. The reduced molecular size
leads to lower binding to plasma and endothelial cell proteins. This results in greater than 90% bioavailability after
subcutaneous injection, a longer plasma half-life (4-6 hrs versus 0.5-1 hrs for standard heparin) and a predictable
and reproducible dose response.
37
Laboratory monitoring is not required. The peak LMWH anti-Xa activity occurs
3-4 hours after subcutaneous injection, and at 12-hour anti-Xa levels are approximately 50% of peak levels. LMWH
excretion is accomplished almost solely by the kidneys. Protamine sulfate is able to neutralize 100% of anti-IIa
activity but only 60-70% of anti-Xa activity, and therefore is not effective at neutralizing LMWH effects.
Pregnancy induces a hypercoagulable state. Although the incidence of thromboembolic complications is
rare, they are a major cause of maternal morbidity. Some parturients require anticoagulant medication during the
antepartum period, for example those with disorders of hemostasis or mechanical heart prostheses, or those at high
risk for venous thromboembolism. Additionally, anticoagulant medication is used in women with a history of fetal

516
Page 5
loss related to thrombophilia and hypercoagulable syndromes, such as antithrombin III deficiency, antiphosholipid
syndrome and protein C or S deficiency. Warfarin causes abnormal fetal development and congenital
malformations during the first trimester, such as nasal hypoplasia and skeletal dysplasias, and increases the risk of
maternal and fetal hemorrhage when given during the peripartum period. Unfractionated heparin and LMWH do not
cross the placenta and are not teratogenic. LMWH has gained widespread use in pregnancy, and has certain
advantages over unfractionated heparin. Both UH and LMWH have similar hemorrhagic complication rates and
antithrombotic efficacy; however, LMWH, unlike UH, does not require laboratory monitoring. Also, there is less
risk of serious complications with LMWH, such as heparin-induced thrombocytopenia and osteoporosis.
38

The release of LMWH for general use in the United States in May 1993 sparked a new challenge for
anesthesiologists. Previously, a spinal or epidural hematoma was a rather rare occurrence, reportedly less than 1 in
150,000-220,000.
13
Enoxaparin, the first LMWH to be approved by the United States Food and Drug
Administration (FDA), had been used for many years in Europe. However, the approved dosing schedule of
enoxaparin was 30 mg (3000 U) every 12 hours in the U.S. as opposed to 40 mg (4000U) once daily in Europe.
Within one year of its introduction in the U.S., two cases of epidural hematoma were voluntarily reported through
the Med Watch system. The warning section of the drug label was revised, a letter from the manufacturer and from
the FDA Health Advisory was issued to practitioners to alert them to the risk of spinal hematoma in patients
undergoing neuraxial anesthesia while receiving LMWH.
39

The actual risk of spinal or epidural hematoma in patients receiving LMWH while undergoing neuraxial
anesthesia is difficult to estimate. The reported incidences of spinal or epidural hematoma in patients receiving
LMWH may be as great as 1 in 3,000 for continuous epidural anesthesia and 1 in 40,000 for spinal anesthesia.
40
Of
the 40 cases of spinal or epidural hematoma associated with LMWH in conjunction with neuraxial anesthesia, two
patients received epidural steroid injections, six underwent spinal anesthesia, of which one was continuous spinal
anesthesia, 23 had continuous epidural anesthesia, six were unspecified techniques, and two had general anesthesia
after attempted or failed neuraxial anesthesia. Some of these patients had other risk factors for the development of
spinal or epidural hematoma, such as difficult needle placement or administration of antiplatelet or anticoagulant
medication. None of these patients was pregnant.
Neuraxial anesthesia can be safely administered to the patient receiving LMWH if certain guidelines and
precautions are met. The American Society of Regional Anesthesia (ASRA) formed a consensus committee on
neuraxial anesthesia in association with anticoagulation on May 2-3, 1998. The committee reconvened for a second
consensus conference in 2002 and a third meeting in 2009 with the findings published in 2010.
41
The findings are
summarized in the Table, but of note neuraxial anesthesia should be delayed by either 12 or 24 hours from the last
injection of LMWH depending on whether the patient is receiving low or high dose LMWH.

Conclusions
In summary, the parturient with coagulation defects, whether related to thrombocytopenia or to
anticoagulation therapy, presents a unique challenge to the anesthesiologist. The risk of spinal or epidural
hematoma in these patients has not been fully quantified, but is nevertheless a factor that one must consider on a
case-by-case basis in determining whether a neuraxial anesthetic is appropriate for the parturient. Following the
guidelines set forth in this lecture should help reduce the risk of spinal or epidural hematoma, without sacrificing the
quality of care provided to our patients.

516
Page 6
Table
Summary of the Recommendations of the consensus conference convened by the American Society of
Regional Anesthesia and Pain Medicine regarding anticoagulants and neuraxial anesthesia and analgesia
41

1. The decision to perform a neuraxial block when a patient is receiving LMWH must be made on an
individual basis by weighing the risk of spinal hematoma with the benefits of regional anesthesia for a
specific patient.
2. Monitoring of the anti-Xa level is not recommended, because it is not predictive of the risk of bleeding.
3. Concomitant medications known to potentiate bleeding, such as antiplatelet agents or oral anticoagulants,
create an additional risk for the development of spinal hematoma.
4. If blood is seen during needle or catheter placement, the first dose of LMWH should be delayed for 24
hours.
5. If a patient is receiving LMWH preoperatively, neuraxial anesthesia should occur at least 10-12 hours after
the last LMWH dose. Patients receiving high doses of LMWH, such as enoxaparin 1 mg/kg twice a day, or
enoxaparin 1.5 mg/kg daily will require waiting 24 hours.
6. The first dose of LMWH after surgery depends on the dosing schedule
a. Twicedaily dosing: The first dose of LMWH should be given no sooner than 24 hours
postoperatively. Indwelling catheters should be removed prior to initiation of LMWH, and the
first dose may be given two hours after catheter removal.
b. Single-daily dosing: The first dose of LMWH should be given 6-8 hours postoperatively. The 2
nd

dose should be given no sooner than 24 hours after the 1
st
dose. Indwelling catheters may be
maintained but should be removed 10-12 hours after the last dose of LMWH. Subsequent dosing
should occur two hours after catheter removal.

References:

1. Beilin Y, Zahn J, Comerford M. Safe epidural analgesia in thirty parturients with platelet counts between 69,000
and 98,000 mm
-3
. Anesth Analg 1997;85:385-388.
2. Cousins MJ, Bromage PR. Epidural neural blockade. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in
Clinical Anesthesia and Management of Pain, 2
nd
ed. Philadelphia: J.B. Lippincott Company, 1988:335-336.
3. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the United
States, 1979-1990. Anesthesiology 1997;86:277-284.
4. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med
1993;329):1463-6.
5. Channing Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost 1990;16:1-10.
6. Lind SE. The bleeding time does not predict surgical bleeding. Blood 1991;77:2547-2552.
7. O'Kelly SW, Lawes EG, Luntley JB. Bleeding time: Is it a useful clinical tool? Br J Anaesth 1992;68:313-315.
8. Beilin Y, Bodian CA, Haddad EM, et al. Practice patterns of anesthesiologists regarding situations in obstetric
anesthesia where clinical management is controversial. Anesth Analg 1996;83:735-741.
9. Orlikowski CE, Rocke DA, Murray WB, et al. Thrombelastography changes in pre-eclampsia and eclampsia. Br J
Anaesth 1996;77:157-161.
10. Favaloro EJ, Kershaw G, Bukuya M, et al. Laboratory diagnosis of von Willebrand disorder (vWD) and
monitoring of DDAVP therapy: efficacy of the PFA-100 and vWF:CBA as combined diagnostic strategies.
Haemophilia 2001;7:180-189.
11. Davies JR, Fernando R, Hallworth SP. Hemostatic function in healthy pregnant and preeclamptic women: an
assessment using the platelet function analyzer (PFA-100) and thromboelastograph. Anesth Analg 2007;104:416-20.
12. Beilin Y, Arnold I, Hossain S. Evaluation of the platelet function analyzer (PFA-100) vs. the
thromboelastogram (TEG) in the parturient. Int J Obstet Anesth 2005;15:7-12.
13. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg
1994;79:1165-1177.
14. Ballin NC. Paraplegia following epidural analgesia. Anaesthesia 1981;36:952-953.
15. Crawford JS. Some maternal complications of epidural analgesia for labour. Anaesthesia 1985;40:1219-1225.
16. Newman B. Postnatal paraparesis following epidural analgesia and forceps delivery. Anaesthesia 1983;38:350-1.

516
Page 7
17. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric practice. Br
J Anaesth 1990;64:537-41.
18. Jaeger M, Rickels E, Schmidt A, et al. Lumbar ependymoma presenting with paraplegia following attempted
spinal anaesthesia. Br J Anaesth 2002;88:438-40.
19. Roscoe MW, Barrington TW. Acute spinal subdural hematoma. A case report and review of literature. Spine
1984;9:672-5.
20. Esler MD, Durbridge J, Kirby S. Epidural haematoma after dural puncture in a parturient with
neurofibromatosis. Br J Anaesth 2001;87:932-4.
21. Lao TT, Halpern SH, MacDonald D, et al. Spinal subdural haematoma in a parturient after attempted epidural
anaesthesia. Can J Anaesth 1993;40:340-5.
22. Yarnell RW, D'Alton ME. Epidural hematoma complicating cholestasis of pregnancy. Curr Opin Obstet Gynecol
1996;8:239-42.
23. Yuen TS, Kua JS, Tan IK. Spinal haematoma following epidural anaesthesia in a patient with eclampsia.
24. Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med
1972;287:155-9.
25. Rasmus KT, Rottman RL, Kotelko DM, et al. Unrecognized thrombocytopenia and regional anesthesia in
parturients: a retrospective review. Obstet Gynecol 1989;73:943-6.
26. Rolbin SH, Abbott D, Musclow E, et al. Epidural anesthesia in pregnant patients with low platelet counts. Obstet
Gynecol 1988;71:918-208.
27. Hew-Wing P, Rolbin SH, Hew E, et al. Epidural anaesthesia and thrombocytopenia. Anaesthesia 1989;44:775-7.
28. Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists
Task Force on Obstetric Anesthesia. Anesthesiology 2007; 106:84363
29. Solanki DL, Blackburn BC. Spurious thrombocytopenia during pregnancy. Obstet Gynecol. 1985;65:14S-17S.
30. Douglas MJ. Platelets, the parturient and regional anesthesia. Int J Obstet Anesth 10:113-120,2001.
31. Banwell BR, Morley-Forster P, Krause R. Decreased incidence of complications in parturients with the arrow
(FlexTip Plus) epidural catheter. Can J Anaesth 1998;45:370-2.
32. Wysowski DK, Talarico L, Bacsanyi J, et al. Spinal and epidural hematoma and low-molecular-weight heparin.
N Engl J Med 1998;338:1774-5.
33. Bergqvist D, Lindblad B, Matzch T. Low molecular weight heparin for thromboprophylaxis and epidural/spinal
anaesthesia-is there a risk? Acta Anaesthesiol Scand 1992;36:605-9.
34. Tryba M. Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic
problems in regional anesthesia. Reg Anaesth 1989;12:127-31.
35. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis
regimens, and guidelines for regional anesthetic management. Anesth Analg 1997;85:874-5.
36. Cosmi B, Hirsh J. Low molecular weight heparins. Curr Opin Cardiol 1994;9:612-8.
37. Heit JA. Low-molecular-weight heparin: biochemistry, pharmacology, and concurrent drug precautions. Reg
Anesth Pain Med 1998;23:135-9.
38. Bazzan M, Donvito V. Low-molecular-weight heparin during pregnancy. Thromb Res 2001;101:175-86.
39. Horlocker TT. Low molecular weight heparin and neuraxial anesthesia. Thromb Res 2001;101:141-54.
40. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain
Med. 1998;23:183-189.
41. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT, Brown DL, Heit JA, Mulroy
MF, Rosenquist RW, Tryba M, Yuan CS. . Regional Anesthesia in the Patient Receiving Antithrombotic or
Thrombolytic Therapy. American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines
(Third Edition). Reg Anesth Pain Med 2010;35:64-101.

Disclosure

116
Page 1
Preoperative Evaluation, Premedication, and Induction of Anesthesia
in Infants and Children
Zeev N. Kain, M.D., MBA, Orange, California
A. Preoperative Evaluation
Preoperative evaluation and preparation of a child for anesthesia and surgery is an integral part of the process prior
to surgery. The preoperative evaluation should consist of birth and neonatal history, review of systems, physical
examination, height, weight and vital signs. Home use of medications such as bronchodilators, steroids and
chemotherapeutic agents has significant implications for the anesthetic management. A history of medical or
allergies should be elicited, including questions directed toward evaluating the presence of allergy to latex in
children at risk, notably those with meningomyelocele or urogenital anomalies, those who undergo bladder self-
catheterization, or those whose medical histories indicate frequent latex exposure in the past. Particular attention is
paid to previous anesthetics and problems encountered, the successful and unsuccessful techniques used in the past
for airway management. Anesthetic risks, anesthetic plans, recovery, postoperative analgesia, and discharge criteria
have to be discussed in during the preoperative evaluation process. The use of herbal medication and other
alternative and complementary medicine modalities has to be assessed as well as many herbal remedies have
anesthetic implications.
I. Underlying Conditions:
The Former Preterm Infant: When evaluating a former preterm infant one should take into consideration the
possible presence of BPD, anemia and the possibility of postoperative apnea. Perioperative complications from BPD
may involve reactivity of the airway and risk of severe hypoxia that can accompany bonchospasm episodes. Parents
should be questioned about the need for oxygen therapy at home and recent hematocrit data should be available.
Bronchodilators and inhaled corticosteroids should be continued up to and including the morning of surgery.
Upper Respiratory Infection: Several investigations have found that a child with a current URI or recovering from a
URI is at increased risk to develop laryngospasm, bronchospasm, oxygen desaturation and post-extubation croup.
While these complications typically do not cause significant morbidity in otherwise healthy children, they may be
significant in children with underlying conditions such as asthma, BPD, sickle cell disease, living in a household
which includes smoking parents and children who are to undergo surgery involving the airway. Children in these
categories should be carefully assessed and strong
consideration should be given to postponing elective
surgery. It is unclear how long surgery should be delayed
following an URI, however, because bronchial
hyperreactivity may exist for up to 6 weeks after a URI.
The final decision must take into account the risk-to-
benefit ratio of undergoing a surgical procedure in the
patients current and the likelihood of acquiring another
URI prior to rescheduled surgery. The technique used for
anesthesia may impact the number of airway issues
encountered. For example, LMA has been shown to be
associated with a lower rate of perioperative complications
as compared to endotracheal tube but higher risk as
compared to facemask.
Postoperative Apnea: Data indicates that former preterm
infants are more likely to develop postoperative apnea following general anesthesia. These data indicate that risk of
postoperative apnea is inversely related to postconceptional age and that infants with a history of apnea/bradycardia,
or mechanical ventilation may be at increased risk. The question as to which of these infants need to be admitted to
the hospital following general anesthesia is controversial. Theage is generally agreed to be less than 52 to 60 weeks

116
Page 2
postconceptual age. Arrangements for overnight
hospital monitoring following general anesthesia
should be made for any infant considered to be at
significant risk for postoperative apnea particularly
those with a history of previous problems with
apnea/bradycardia.
Obstructive Sleep Apnea: OSA patients are at risk for
airway obstruction with the use of preoperative
sedative predication and during the induction process.
Postoperatively, patients with severe OSA may exhibit
worsening of their obstructive symptoms secondary to
tissue edema and residual effects of anesthetic agents.
Children under 3 years of age are at particularly high
risk for respiratory complications. While most
children who undergo tonsillectomy and
adenoidectomy can be discharged home following 4
hours of PACU observation, children with severe OSA
require postoperative observation in the hospital. OSA is often accompanies obesity. All patients with markedly
elevated body mass index should be questioned about sleep apnea symptoms.
Asthma: It is well established that children with asthma should be optimelized prior to undergoing general
anesthesia and surgery and the more active the disease (as indicated by recent asthma symptoms, asthma medication
usage, and recent treatment in an emergency department) the greater probability of perioperative complications. All
oral and inhaled medications, such corticosteroids and beta agonists, should be continued up to and including the
day of surgery. Recent data has indicates that administration of inhaled short-acting beta agonists prior to induction
of anesthesia eliminates the increase in airway pressure that is typically associated with intubation in asthmatic
patients.
II. Laboratory Evaluation:
It is now well established that healthy children undergoing elective minor surgery require no preoperative laboratory
values, and thus can be spared the pain of routine blood drawing. Indeed, blood chemistry analyses are only
performed for specific indications, such as measurement of ionized potassium in children on digoxin or diuretics.
Hemoglobin measurement is not required for minor elective cases. For surgeries where significant blood loss may be
expected, a rather arbitrary value of 10 g ! dl1 has been cited as acceptable for infants older than 3 months or age..
For younger infants and neonates higher values may be desirable (depending on gestational age and general health
status). Patients with sickle cell anemia or other hemoglobinopathies require special preoperative preparation
including goal-directed transfusion. Routine chest x-rays and urinary analysis is unnecessary unless indicated by a
specific symptom or known coexisting illness. Laboratory testing of coagulation should only be considered in
selected situations including: 1) Children in whom either the history or medical condition suggests a possible
hemostatic defect. 2) Patients undergoing surgical procedures that might induce hemostatic disturbances (e.g.,
cardiopulmonary bypass). 3) Cases where an intact coagulation system is critical for adequate hemostasis 4) patients
for whom even minimal postoperative bleeding could be life threatening. It is also important to determine whether a
female patient is possibly pregnant before the administration of anesthesia. This may be a difficult task as a reliable
menstrual and sexual history may be difficult to obtain from an adolescent when a relationship of confidentiality
with medical personnel has not been previously established. In addition, parents (or patients) may decline a request
for a pregnancy test. At this point there are no clear national guidelines on the issue of pregnancy test screening of
all female patients of childbearing age before the administration of anesthesia. We submit that routine vs. selective
testing is a matter of policy at individual facilities.

116
Page 3
III. Preoperative NPO Status
The incidence of aspiration pneumonia in children is reported to be about 1 in 10,000. Studies indicate that the
outcome of children who developed aspiration pneumonia is excellent, unless these children had some major
underlying problem such as abdominal or thoracic trauma. In an effort to minimize aspiration injury, the American
Society of Anesthesiologists has issued practice guidelines regarding preoperative fasting. Solids are prohibited
within 6-8 hours of surgery (generally after midnight), formula within 6 hours, breast mild within 4 hours of surgery,
and clear liquids within 2 hours of surgery. Clear liquids such as apple or grape juice, flat cola, and sugar water may
be encouraged up to 2 hours prior to the induction of anesthesia as their consumption has been shown to decrease
the gastric residual volume. Some data obtained over the past few years indicates that perhaps the NPO times are
overly conservative as it relates to clear liquids, formula and breast milk. These data will be reviewed during the
refresher course.
B. Premedication
Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness
and worry, and may be expressed in many forms. Some children verbalize their fears explicitly while for others
anxiety is expressed only behaviorally. Coping with preoperative stress requires consistent communication between
the child, the parents and all health care providers involved in the preoperative process. Both behavioral and
pharmacological interventions can be used to address the issue of preoperative anxiety in children and their parents.
Behavioral interventions include tours of the operating room, written and audiovisual materials, coloring books, and
patient care representatives skilled in the preoperative preparation of children. Unfortunately, over the past decade
most hospitals have discontinued preoperative preparation programs for children who are about to undergo
outpatient surgery and instead rely on morning of surgery preparation by nurses and child-life specialists. Such an
approach is highly problematic, as recent research has indicated that a typical interaction of anesthesiologists and
nurses with children on the morning of surgery
lasts less than 5-minutes. Alternatives methods
such web based preparation should be
investigated. Some hospitals allow parents to be
present for the induction of anesthesia, but the
efficacy of this intervention is uncertain and the
availability of such programs is not universal.
Other non-pharmacological interventions such as
music, acupuncture, and hypnosis have been
shown to reduce the anxiety in perioperative
settings. It is important to note that the oral route
is by far the used and preferred route of sedative
administration for children. Nasal, rectal, and
intramuscular routes should be used only under
special circumstances such as cognitively
challenged children.
I. Orally Administrated Premedication:
Midazolam is the most commonly used sedative premedicant
used in the US. Over 90% of all preoperative sedation in the
US is performed using midazolam. It has rapid onset and
predictable effect without causing cardiorespiratory
depression. In a dose of 0.5-0.75 mg/kg, midazolam peaks
approximately 30 minutes after administration, and its effect
lasts approximately 30 minutes. While it is very effective in
the vast majority of children, about 14% of children may not
respond to a midazolam dose of 0.5 mg/kg. This
unresponsive group of children is reported to be younger, 2-3
years old and has high levels of preoperative emotionality.
Higher doses of midazolam (0.75 mg/kg) may be more
appropriate in these non-responders. While midazolam has a
short duration that generally does not delay emergence from
general anesthesia or discharge from PACU, some reports
indicate that the use of this agent with children undergoing ultra-short
Kain, Anesthesiology 1999

116
Page 4
procedures such myringotomies and endoscopy may delay hospital discharge. Midazolam has been shown to be
superior to parental presence in decreasing perioperative stress for patients and families although the addition of
parental presence will result in increased parental satisfaction from the overall perioperative experience. Midazolam
can be reversed with flumazenil, which antagonizes benzodiazepines competitively. Clonidine is an a2 agonist that
when given in combination with atropine produces satisfactory preoperative sedation, easy separation from parents
and mask acceptance within 45 minutes. Orally administrated clonidine in a dose of 4 ug/kg has been demonstrated
to reliably cause sedation, decrease anesthetic requirements and decrease requirement for postoperative analgesics. It
also attenuates the hemodynamic response to tracheal intubation. With the recommended dose, perioperative
hypotension is not observed. The major disadvantage of this sedative is slow onset as compared with midazolam.
Dexmedetomidine (DEX) a more selective " 2 agonist than clonidine, has gained some popularity as a preoperative
sedative for children. When used at 1mcg/kg transmucosally or 3-4mcg/kg orally, this drug has a similar sedative
and anxiolytic effect to Clonidine or Midazolam. Similar to Clonidine, DEX has the effect of lowering pain scores in
the post-anesthesia time frame. Oral ketamine has also been used as a sedation medication in doses of 56 mg ! kg1
for children 16 years of age. Maximal sedation occurred within 20 minutes. The combination of ketamine and
midazolam has also been utilized as an oral sedative premedication mixture. Funk et al. reported that the
combination of midazolam and ketamine administrated orally had a 90% success rate of satisfactory anxiolysis
compared to less than 75% with either drug alone. Nausea and vomiting rates were slightly increased in children
who received oral ketamine.
II. Other Routes Administrated Premedication:
Nasally: A major disadvantage of intranasally administered sedative medications is that many children cry upon
administration because it transiently irritates the nasal passages. Rapid absorption as well as avoidance of first pass
hepatic metabolism of medications are advantages of this route of administration. When required, midazolam can be
administered intranasaly in a dose of 0.2 mg ! kg1.
Rectaly: Rectal administration of midazolam in doses of 0.5-1.0 mg/kg effectively reduces the anxiety of children
prior to induction. Care must be taken, however, that the medication is not expelled immediately on placement.
BoOnset of sedation requires approximately 10 minutes. Respiratory depression and oxygen desaturation may occur
because of variable absorption of the medication in the rectum.
Intramuscularlly: Parenteral administration of sedation may be the only alternative in a child who refuses to
cooperate with other modalities. Intramuscular midazolam in a dose of 0.3 mg ! kg1 provides anxiolysis in 510
minute. Ketamine in an intramuscular dose of 34 mg ! kg1 provides a quiet, breathing, yet minimally responsive
patient in approximately 5 minutes.
C. Induction of Anesthesia
Mask induction of general anesthesia remains the most common induction technique for pediatric anesthesia the
United States. While there is no question that inhalation induction of anesthesia is safe, the incidence of bradycardia,
hypotension, and cardiac arrest during this form of induction is higher in infants younger than 1 year of age than in
older children and adults. This difference in outcome is due to the extremely rapid uptake of inhalation agents in
infants compared to adults as a result of the much greater ratio of alveolar ventilation to functional residual capacity
and the altered distribution of cardiac output. In light of these facts, mask induction of anesthesia in this age group
should be accompanied by monitoring of blood pressure, ECG, oxygenation and ventilation. The minimum alveolar
concentration (MAC) of anesthetic required in pediatric patients differs with age. There is actually a small increase
in MAC between birth and 2 to 3 months of age at which represents the age of highest MAC requirement. After that
time MAC slowly decreases with age. For sevoflurane the change in MAC is marked with a value of
approximately 2.5% for young infants compared to 2% for adolescents and adults. Children with unrepaired or
partially repaired congenital heart malformations may safely undergo inhaled induction of anesthesia. Although
intracardiac shunts can, in theory, alter the uptake of anesthetic agents and affect the speed of induction, this is
rarely clinically evident. A right-to-left shunt slows the inhaled induction of anesthesia because anesthetic
concentration in the arterial blood increases more slowly. A left-to-right shunt should have the opposite effect;
volatile agent induction is more rapid because the rate of anesthetic transfer from the lungs to the arterial blood is
increased.
I. Inhaled Agents: In the US, the only potent anesthetic agent currently in use that is compatible with an ideal
inhaled induction is sevoflurane. Its advantages (including rapid onset and low frequency of disrhythmias or
hypotension) allowed it to dominate the US market. Sevoflurane undergoes ex-vivo degradation reaction in the
clinical setting through direct contact with CO2 absorbents (i.e., soda lime or Baralyme) in the anesthesia circuit.
This reaction produces pentafluoroisopropenyl fluoromethyl ether (PIFE), also known as Compound A, and trace
amounts of pentafluoromethoxy isopropyl fluoromethyl ether (PMFE, Compound B). Mean maximum

116
Page 5
concentrations in pediatric patients with soda lime are about half those found in adults. While the level of compound
A at which toxicity occurs is not known, sevoflurane use
with fresh gas flows of 1L/min appears to be safe in children. Finally, while emergence from anesthesia is more
rapid with sevoflurane than with more soluble agents such as halothane or isoflurane, there is a growing literature
supporting the fact that agitation behaviors in children on emergence are more common with this agent. The exact
reason for this disturbance is not known but there is evidence that is may occur with or without pain as a factor. A
number of medications have been used to decrease the problem of emergence agitation after sevoflurane (including
midazolam, ketorolac, fentanyl, propofol, and dexmedetomidine). Careful attention to pain control and supportive
environments are indicated.
II. Sedative hypnotics: As with inhaled agents mentioned above, the doses of intravenous agents used in infants and
toddlers will often need to be increased by 25-40% in order to obtain the same level of sedation/anesthesia in
children as compared to adults. Propofol is the most widely used agent for induction and maintenance of anesthesia
or sedation in children. While its safety is well established, its use in children is limited to the operating room
environment and brief sedation outside the operating room. Prolonged infusion in the intensive care environment has
been linked to acidosis, heart failure, and a number of fatalities. Propofol induction doses range from 3-4mg/kg for
children younger than 2 years to approximately 2.5-3mg/kg for older children. Onset is rapid but may be
accompanied by some random movement and cough. Pain on injection of propofol is marked and this problem may
be minimized by infusing the largest vein possible and running carrier fluid as rapidly as possible. Lidocaine
preceding (or mixed with) the propofol bolus can be employed to decrease the pain with intravenous injection.
Propofol will cause mild to moderate decreases in blood pressure when used at recommended doses. The emergence
profile of propofol in children shows clear advantages over other intravenous agents and inhaled anesthetics.
Emergence from deep sedation/anesthesia is clearly faster than that from most other sedative agents and most
inhaled agents especially after prolonged administration. In addition, while time to awakening may not be faster than
sevoflurane or desflurane, the emergence from propofol is associated with less nausea and vomiting and it is
accompanied by less emergence agitation so readiness for discharge is at least as rapid. Although it was first
described 40 years ago, ketamine has been increasingly reported for use in anesthesia, procedural sedation, and
sedation the intensive care environment for children. It is the only intravenous agent that offers both potent hypnosis
and analgesia. Other unique aspects include the fact that ketamine preserves airway reflexes, maintains respiratory
drive, increases endogenous catecholamine release, and results in a small amount of bronchodilation. Induction
doses of 1mg/kg intravenously yields effective analgesia and sedation with rapid onset. Simultaneous administration
of an anticholinergic will minimize oral secretions. Emergence from ketamine sedation/anesthesia can be marked by
diplopia, occasional disturbing dreams, and nausea/vomiting, although these are less common in children than
adults. The use of concominant midazolam 0.3-0.50 mg/kg to decrease some of these side effects has a mixed record
of success and should not be considered reliable.
III. Muscle Relaxants:
Succinylcholine: This agent has been used as part of pediatric anesthesia and airway management for over 60 years.
When given in a dose of 1.5-2.0 mg/kg it produces excellent intubating conditions (reliably) in 60 seconds.
Recovery occurs in 6-7 minutes. Succinlycholine can also be given IM at 4mg/kg in emergencies when IV access is
not available. Its use is absolutely contraindicated in a variety of patients particularly in those with muscular
dystrophy, recent burn injury, spinal cord transaction and/or immobilization, as well as any child with a family
history of malignant hyperthermia because of the risk of rhabdomyolysis, hyperkalemia, masseter spasm, and
malignant hyperthermia. In addition, the drug is currently listed as relatively contraindicated for use in all children
by the FDA. This is due to the infrequent, but well reported cases where succinylcholine has been administered to
children with risk factors that are not clinically apparent or unappreciated. For all these reasons, succinylcholine can
only be recommended in situations where ultrarapid onset and short duration of action is of paramount importance
(laryngospasm) or when muscle relaxation required when IV access is not available and IM administration is
required.
Nondepolarizing Muscle Relaxants: All nondepolarizing muscle relaxants used in adults are effective for pediatric
patients.. In selecting a muscle relaxant, one must consider the possible side effects of each medication, its route of
metabolism, and the possible duration of action. For instance, pancuronium has a vagolytic effect which may be
desirable in many neonates. On the other hand it is dependent on renal excretion and therefore may have a markedly
extended duration of action in neonates where glomerular filtration rate is relatively decreased. Rocuronium has the
lowest potency and the fastest onset of action of the currently available non-depolarizing relaxants (60 seconds for a
1mg/kg dose) and is therefore the logical choice for rapid sequence intubation. Atracurium and Cisatracurium are
popular nondepolarizing muscle relaxants for children largely because they are eliminated by Hofmann elimination -
a process only dependent on pH and temperature. In fact the onset and offset of these drugs appears faster in
116
Page 6
neonates than in infants or children. 61 Cisatracurium is stereoisomer of Atracurium which has more specificity in
action and is associated fewer side effects related to histamine release.
** This refresher course is largely based on the chapter: Cravero J, Kain ZN. Pediatric Anesthesiology. In:
Barash PG, Cullen B, Stolting R (eds). Text Book of Clinical Anesthesia. Lippincott & Williams & Wilkins,
2008;1205-1218.
References
1. Schmidt AP, Valinetti EA, Bandeira D, Bertacchi. MF, Simoes. CM, JO A: Effects of preanesthetic
administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children.
Paediatric Anaesthesia 2007; 17: 667-74
2. Statham MM, Elluru RG, Buncher R, Kalra M: Adenotonsillectomy for obstructive sleep apnea syndrome in
young children: prevalence of pulmonary complications. Archives of Otolaryngology -- Head & Neck Surgery 2006;
132: 476-80
3. Setzer N, Saade E: Childhood obesity and anesthetic morbidity. Paediatric Anaesthesia.
2007; 17 321-6.
4. Maxwell L, Yaster M: Perioperative management issues in pediatric patients. Anesthesiology Clinics of North
America 2000; 18: 601-32
5. Gabriel P, Mazoit X, Ecoffey C: Relationship between clinical history, coagulation tests, and perioperative
bleeding during tonsillectomies in pediatrics. J Clin Anesth 2000; 12: 288-91
6. Kain ZN, MacLaren J, McClain BC, Saadat H, et al: Effects of age and emotionality on the effectiveness of
midazolam administered preoperatively to children. Anesthesiology
2007;107:545-52.
7. Mellon RD, Simone AF, Rappaport BA: Use of anesthetic agents in neonates and young children. Anesthesia &
Analgesia 2007 104 509-20
8. Woloszczuk-Gebicka B, Wyska E, Gabowski T: Pharmacokinetic-pharmacodynamic relationship of rocuronium
uncer stable nitrous oxide-fentanyl or nitrous oxide-sevoflurane anesthesia in children. Paediatric Anaesthesia 2006;
16: 761-768
9. Meakin G, Meretoja O, Perkins R: Comparison of atracurium-induced meruomuscular blockade in neonates,
infants, and children. British Journal of Anaesthesia 1988; 60: 171-175
10. Kain ZN, Caldwell-Andrews AA, Mayes LC, Weinberg ME, Wang S-M, MacLaren JE, Blount RL: Family-
centered preparation for surgery improves perioperative outcomes in children: a randomized controlled trial.
11. Blair JM, Hill DA, Bali IM, Fee JP: Tracheal intubating conditions after induction with sevoflurane 8% in
children. A comparison with two intravenous techniques. Anaesthesia 2000;
55: 774-76
12. Kain Z, Mayes L, Caldwell-Andrews A, Saadat S, McClain B, Wang S: Preoperative Anxiety and Postoperative
Pain and Behavioral Recovery in Young Children Undergoing
Surgery. Pediatircs 2006; 118: 651-8
13. Kain ZN, Caldwell-Andrews AA: Preoperative psychological preparation of the child for
surgery: any update. Anesthesiology Clinics of North America 2005; 23: 597-614
14. Cravero J, Surgenor S, Whalen K: Emergence agitation in paediatric patients after
sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatric Anaesthesia.
2000; 10: 419-24
15. Ibacache ME, Munoz HR, Brandes V, Morales AL: Single-dose dexmedetomidine reduces agitation after
sevoflurane anesthesia in children. Anesthesia & Analgesia 2004; 98: 60-3.
Disclosure
Merck, Consulting Fees
122
Page 1
Fast-tracking Pediatric Ambulatory Anesthesia: Challenges and Controversies
Linda J. Mason, M.D. Loma Linda, California
The Upper Respiratory Tract Infection Dilemma
Most anesthesiologists agree that the presence of an acute purulent upper respiratory tract infection (URI),
fever or any symptomatology of a lower respiratory infection would be sufficient grounds to postpone an elective
surgical procedure. However, the child with a nonpurulent active or recent URI (within 4 weeks) nearly always
presents a conundrum even for the most experienced anesthesiologists.
It has been documented that 20-30% of all children have a runny nose a significant part of the year. In the
preanesthetic evaluation we must rely on history, physical, and occasionally laboratory data to decide whether to
proceed with the anesthetic. A differential diagnosis of a child with a runny nose should include:
Noninfectious causes
Allergic Rhinitis: Seasonal, perennial
Vasomotor Rhinitis: Emotional (crying),
temperature
Infectious Causes
Viral infections
Nasopharyngitis (common cold)
Flu syndrome (upper and lower
respiratory tract)
Laryngotracheal bronchitis (infectious
croup)
Viral exanthems
Measles
Chicken pox
Acute bacterial infections
Acute epiglottitis
Meningitis
Streptococal tonsillitis
Previous studies have shown that children with a URI, particularly those less than 1 year of age, have an
increased risk of respiratory related adverse events intraoperatively and postoperatively.
1,2
Also symptomatic infants
with a URI have decreased time to desaturation during apnea.
2
Endotracheal intubation (ETT) has been shown to be
a major risk factor for hypoxemia, bronchospasm and atelectasis in children with a URI.
1-3
Temporary airway
hyperactivity is known to exist for 6 weeks after a viral infection.
4
One recent study looked at 2051 children of which 22.3% had symptoms of URI on the day of surgery,
45.8% had a cold in the preceding 6 weeks and 30% were asymptomatic controls.
5
Forty of the 2051 children did
not proceed to anesthesia and surgery on the basis of the preanesthetic consult. The nonanesthetized children were
more likely to have runny nose, cough, wheezing, malaise and fever and were said to have a cold by the parents.
There is some bias in this study first because the policy in this hospital is to reschedule elective cases with a URI if
they are under 12 months of age and require intubation and the second bias is the use of anesthesiologists to record
adverse events occurring during anesthesia rather than an independent observer who was blinded to the patients
perioperative condition.
Significant patient predictors were parental confirmation of the childs URI symptoms, presence of nasal
secretions, history of snoring, passive smoke exposure and sputum production. As far as anesthetic risk factors,
choice of airway management was identified as an independent risk factor for postoperative adverse events,
specifically the risk was higher with ETT than with LMA or face mask use respectively.
Thiopental for induction was associated with the highest probability of an adverse event followed by
halothane and sevoflurane with propofol having the lowest probability. Propofol depresses laryngeal reflexes and
may decrease airway responsiveness by relaxation of bronchial smooth muscle.
6,7
The administration of
neostigmine was the final predictor. Children who had muscle relaxants reversed had a lower probability of an
adverse event than those who did not. Residual neuromuscular blockade may have subtle effects on outcomes and
atropine administration with neostigmine may have the beneficial effect of decreasing secretions.
In conclusion, this study suggests children whose parents say they have a cold, who are snorers, passive
smokers, have nasal congestion or a productive cough have a higher risk of anesthetic complications. Intubation
increases the risk of complications and with LMA or face mask use the probability is decreased. Propofol is the
122
Page 2
safest intravenous induction agent and muscle relaxants should always be reversed. It is prudent to cancel non-
urgent surgery if the patient wheezes, is febrile, is suffering malaise or if the child is very young (<1 year of age).
In a prospective study with 1078 patients comprising roughly equal thirds having active URI symptoms,
recent URI symptoms within the previous 4 weeks, or no URI symptoms, respiratory adverse events were most
prevalent in the active URI group.
8
There was also a significantly higher incidence of desaturation in both the active
(15.7%) and recent (14.7%) URI groups versus the non-URI group. There was no statistically significant difference
in the incidence of bronchospasm or laryngospasm between groups. In this study only nine of 407 patients (2.2%)
with an active URI confirmed by the parent required succinylcholine for management of laryngospasm, and only
three children one with a recent URI and two with active URIs required unanticipated admission to hospital.
By employing logistic regression
8
in 1078 children with active, recent or no URI symptoms, patient risk
factors associated with adverse outcomes included copious secretions (P=0.0001), ex-premature infants (P=0.007),
nasal congestion (P=0.014), parental smoking (P=0.018), and reactive airway disease (P=0.028). ASA status did not
correlate with adverse outcomes.
The specific role age plays in the presence of URI has not been elaborated in all studies, but this study
6

showed that infants less than 6 months old with active URIs had a higher incidence of bronchospasm (20.8% versus
4.7%, P=0.08) than older children. This same study also showed that children under 2 years old had a higher
incidence of oxygen desaturation than older children (21.5% versus 12.5%, P=0.023).
Anesthetic risk factors identified ETT in children under 5 years of age as an independent risk factor for
postoperative respiratory adverse events (P=0.0002).
8
Of note, duration of anesthesia and awake versus deep
extubation were not identified as risk factors. Children with active URIs had the lowest incidence of problems when
induced and maintained with sevoflurane. There was a high incidence of adverse respiratory events in children
undergoing airway surgery eg. tonsillectomy and adenoidectomy, direct laryngoscopy and bronchoscopy in all 3
groups.
The conclusions of this study were children with active and recent URIs (within 4 weeks) are at increased
risk for adverse respiratory events particularly if they have a history of reactive airway disease, require surgery
involving the airway, have a history of prematurity, are exposed to environmental tobacco smoke, have nasal
congestion or copious secretions or require placement of an endotracheal tube.
Schreiner found URIs a predictor of increased risk of laryngospasm
9
while by Tait and Knights definition it
was not.
10,11
Risk of laryngospasm has been found to be 10 fold higher in children exposed to tobacco smoke.
12

Children with a URI within 30 days prior to surgery had a 2.3 fold higher risk of laryngospasm.
13
Comparison of
ETT with laryngeal mask airway (LMA) use in children with a URI showed a significant lower incidence of mild
bronchospasm, major desaturation events (oxygen saturation < 90%) and overall respiratory events with LMA use.
14
The incidence of laryngospasm was equal.
A study in 831 children (27% of whom presented with a recent URI within the last 2 weeks before
anesthesia) demonstrated that LMA use in children with a recent URI was associated with a higher incidence of
laryngospasm, cough and oxygen desaturation compared with healthy children. However, if anesthesiologists allow
a 2 week interval after a URI, the use of an LMA was confirmed to be a safe technique.
15

In 20 children age 1-6 undergoing elective surgery with tracheal intubation those with either a respiratory
tract infection in the past 2 weeks before surgery or asthma had an increase in airway resistance with desflurane as
opposed to sevoflurane or propofol, questioning the use of desflurane in children with airway susceptibility.
16

In afebrile ASA I or II children having either a URI within 6 weeks or an active URI disease undergoing
noncavitary, nonairway surgery for less than 3 hours, pretreatment with bronchodilators prior to anesthesia (either
inhaled ipratropium or albuterol) showed no decrease in adverse airway events.
17
A more recent article showed
preoperative salbutamol in children with a recent URI (<2 weeks) decreased the incidence of laryngospasm,
bronchospasm, oxygen desaturation (<95%) and severe coughing with LMA or endotracheal tube use.
18

In a risk assessment study, URI was associated with an increased risk for perioperative respiratory adverse
events only when symptoms were present or less than 2 weeks before the procedure.
19
However, in another study
assessing risk factors for adverse events in children with colds emerging from anesthesia a correlation with
respiratory adverse events occurred if peak URI symptoms have occurred within the preceding 4 weeks.
20
There is risk to anesthesia even in children without URIs. The child with a URI has an increased risk for
laryngospasm, bronchospasm, desaturation and postintubation croup especially if someone in the home smokes. Not
all children with a URI should be anesthetized but careful consideration should be given to severity of presenting
symptoms, a patients respiratory history, need for endotracheal intubation, choice of anesthetic agent and the
anesthesiologists overall comfort with anesthetizing children with URIs.
We must wait 4-6 weeks to decrease these risks as compared to the normal child. We can tailor our
anesthetic to decrease these risks (propofol, LMA or face mask instead of ETT) but they cannot be reduced to zero.
122
Page 3
Good judgment, common sense, clinical experience and informed consent of parents must be used when deciding
whether to cancel or proceed and discussions should be documented in the chart.
Obstructive Sleep Apnea
Sleep apnea is a sleep-related breathing disorder in children characterized by a periodic cessation of air
exchange, with apnea episodes lasting >10 seconds and an apnea/hypopnea index (AHI) total number of
obstructive episodes per hour of sleep >5.
21
Air flow cessation is confirmed by auscultation or oxygen desaturation
<92%. Types of sleep apnea include central (absent gas flow, lack of respiratory effort), obstructive (absent gas
flow, upper airway obstruction and paradoxical movement of rib cage and abdominal muscles) and mixed (due to
both CNS defect and obstructive problems). Diagnosis is made by clinical assessment (a history of snoring and
restless sleep), nocturnal pulse oximetry or polysomnography studies (PSG).
Obstructive sleep apnea syndrome (OSAS) is manifest by episodes that disturb sleep and ventilation. These
episodes occur more frequently during REM sleep and increase in frequency as more time is spent in REM sleep
periods as the night progresses. OSAS occurs in children of all ages (about 2% of all children) but more commonly
in children 3-7 years of age. It occurs equally among boys and girls but the prevalence may be higher in African
American individuals.
22
Childhood obesity is increasing in modern societies and OSAS is increased in children with
obesity. Signs of OSAS are sleep disturbances (including daytime sleepiness), failure to thrive from poor intake due
to tonsillar hypertrophy, speech disorders, and decreased size (decreased growth hormone release during disturbed
REM sleep). This syndrome can cause significant cardiac, pulmonary and CNS impairment due to chronic oxygen
desaturation. In children with OSAS and morbid obesity the incidence of hypertension and diabetes are seen at
much higher rates. Therefore it is important that prior to surgery that the cardiovascular status be evaluated in this
group of children. Although right ventricular dysfunction is classic, biventricular hypertrophy can develop. It is
more likely to be seen in patients with severe OSAS but has been reported in patients with only mild OSAS.
23
Pulmonary vasoconstriction can increase pulmonary vascular resistance with resultant decrease in cardiac output due
to cor pulmonale. Relief of the tonsillar/adenoidal obstruction can reverse many of these problems and prevent
progression of others (pulmonary hypertension and cor pulmonale). Cardiac evaluation is recommended for any
child with signs of right ventricular dysfunction, systemic hypertension or multiple episodes of desaturation below
70%. Electrocardiogram and chest radiograph are not sensitive tools; echocardiography is recommended.
24

Patients that are at high risk for postoperative upper airway obstruction after tonsillectomy and/or
adenoidectomy for OSAS include age < 2 yr, craniofacial anomalies, failure to thrive, hypotonia, morbid obesity,
previous upper airway trauma, cor pulmonale, a polysomnogram with a respiratory distress index (RDI) > 40 or O
2

saturation nadir <70% or patients undergoing an additional uvulopalato pharyngoplasty (UPPP).
25
If upper airway
obstruction occurs postoperatively in these patients, nasal CPAP/BIPAP should be considered as a therapeutic
intervention.
25

The American Academy of Pediatrics Clinical Practice Guidelines
22
give the following recommendations for
inpatient monitoring in patients at high risk for postoperative complications that have OSAS and are undergoing
adenotonsillectomy. These include:
Age younger than 3 years
Severe OSAS on polysomnography
Cardiac complications of OSAS (eg right ventricular
hypertrophy)
Recent respiratory infection
Craniofacial disorders
Neuromuscular disorders
Cerebral palsy
Down syndrome
Failure to thrive
Obesity
Prematurity
Sickle cell disease
Central hypoventilation syndromes
Genetic/metabolic/storage disease
Chronic lung disease

122
Page 4
As far as outpatient surgery for adenotonsillectomy in patients with OSAS, children age 1-18 years without
underlying medical conditions, neuromuscular disease or craniofacial abnormalities with mild sleep apnea (<15
obstructive events per hour) will have improvement of their airway obstruction documented by polysomnography
the night of surgery and do not need to be monitored intensively. In these patients a smaller number of obstructive
events and fewer severe oxygen desaturations occurred on the operative night.
26
Based on this and other studies it is
possible to consider discharge to home for children age 3-12 years if they meet these criteria. However, in children
with severe obstructive sleep apnea (AHI >16.4 events/hr, SaO
2
<85%) obstructive events occurred more frequently
on the first night after adenotonsillectomy suggesting overnight monitoring with pulse oximetry is indicated.
27

OSAS patients with preoperative nocturnal oximetry oxygen saturation of 80% or less had an increase from
20% of postoperative respiratory complications to 50%. Usually these children were younger (<2 years) and had an
associated medical condition.
28
Sixty percent of OSAS patients requiring urgent adenotonsillectomy had
postoperative respiratory complications. Risk factors for respiratory complications were again an associated
medical condition and preoperative nocturnal oxygen saturation nadir less than 80%. Atropine administration at
induction decreased the risk of postoperative respiratory complications. There was an 11.1% incidence of
reintubation and a 9.3% incidence of postoperative pneumonia in this urgent adenotonsillectomy group.
29

Children with severe OSAS who had adenotonsillectomy in the morning were less likely to have
postoperative desaturation than those who were operated in the afternoon.
30
The shortened time interval between
postoperative morphine dosing and bedtime may contribute to the incidence of postoperative desaturation because of
an exaggerated respiratory depressive response to opioids which has been reported in children with severe OSAS.
31

There is a strong possibility that the combination of opioids and sleep promote desaturation in these patients.
Children with OSAS in general may have a diminished ventilatory response to CO
2
rebreathing compared
with normal children.
32
Therefore drugs known to cause ventilatory depression (sedative hypnotics, anxiolytics,
narcotics and inhaled agents) must be used judiciously in these patients as they may be more sensitive to their
effects. Preoperative administration of midazolam 0.5 mg/kg in 70 children undergoing adenotonsillectomy for
OSAS (diagnosed as severe in 40% of subjects by polysomnography) resulted in 2 children having respiratory
events; one had a self limited desaturation event before surgery and one had a postoperative obstruction with
desaturation requiring a nasal airway.
33
Patients with OSAS can receive sedatives but require monitoring.
During inhalational induction of anesthesia, children with OSAS are at a high risk for airway obstruction due
to relaxation of the genioglossus muscle. Positioning in an upright or lateral position, use of jaw thrust maneuver,
delivery of positive pressure by face mask and placement of an oral airway may aid in relieving the obstruction.
34,35
Once anesthesia is induced and intravenous access is established, a single dose of IV propofol 1.5-2 mg/kg (lean
body weight) may facilitate tracheal intubation.
36

Children with OSAS usually need pain medication after surgery yet chronic hypoxemia renders them more
susceptible to the respiratory depressant effects of opioids.
37,38
Younger aged patients or those with preoperative
nocturnal oxygen saturation less than 85% had reduced morphine requirement possibly due to up-regulation of
central opioid receptors consequent to recurrent hypoxemia.
39
Children whose minimum nocturnal saturation was
less than 85% required one half of the dose of opioids for similar pain scores after T & A surgery compared with
children whose minimal saturation was 85% or greater.
40

One technique for opioid administration is that after tracheal intubation and spontaneous ventilation is
restored, small incremental aliquots of IV morphine (10-20 ug/kg) or fentanyl (0.2-0.5 ug/kg) can be administered.
If apnea occurs after the first aliquot of opioid, the child may be considered opioid sensitive. If they continue to
breathe additional increments up to the standard total dose of 50-100 ug/kg of morphine can be administerd.
36
Drugs
for pain management to decrease opioid use include ketamine 0.1 mg/kg
41
IV, or peritonsillar infiltration of
ketamine 0.5 to 1 mg/kg given 3 minutes before surgery
42
, dexamethasone 0.0625-1 mg/kg (maximum 25 mg) with
an average dose of 0.5 mg/kg and IV acetaminophen 15 mg/kg (maximum 75 mg/kg/d, children 2-12 years).
43-45

Concern over dexamethasone use in tonsillectomy patients in respect to postoperative bleeding was raised in
an article that compared three doses of dexamethasone 0.05 mg/kg, 0.15 mg/kg and 0.5 mg/kg. The primary
objective was a decrease in nausea and vomiting and the secondary objective was postoperative analgesia.
Regardless of the dose, children who received dexamethasone needed less rescue analgesia and antiemetics,
however the larger dose 0.5 mg/kg was associated with the highest decrease in postoperative nausea and vomiting
(PONV). Of concern was that both the 0.5 mg/kg dose and the 0.05 mg/kg dose of dexamethasone were associated
with a higher incidence of postoperative bleeding. The problem with this study was the lack of standardization of
surgeon, surgical technique and use of nonsteroidal antinflammatory drugs. This study has too many flaws to
change the practice of giving dexamethasone to tonsillectomy patients and needs to be repeated with bleeding as a
primary outcome in relation to dexamethasone use.
46
In a more recent retrospective review of 2788 children age 2-
122
Page 5
18 undergoing tonsillectomy were given either 0.5 mg/kg or 1.0 mg/kg of dexamethasone. The study was adjusted
for age, sex, primary diagnosis (sleep related disorder and infectious tonsillitis) and surgical technique, either
extracapsular electrosurgical tonsillectomy, extracapsular radiofrequency ablation tonsillectomy or intracapsular
microdebrider tonsillotomy. Perioperative dexamethasone administration was not associated with a dose dependent
elevation of postoperative hemorrhage.
47
A recent Cochrane review of 19 randomized placebo controlled, double
blinded studies conclude that children receiving a single intraoperative dose of dexamethasone (dose range 0.15-0.5
mg/kg) were half as likely to vomit in the first 24 hours and had less pain than the placebo group.
48
A recent report of adenotonsillectomy for children who demonstrated recurrent episodes of profound
hypoxemia (<80% saturation) during the perioperative sleep study demonstrated that a decrease in major medical
respiratory interventions by >50% was accomplished by administration of dexamethasone 0.3 mg/kg (maximum 10
mg) and the titration of morphine 0.02 mg/kg.
49

Nonsteroidal anti-inflammatory drugs (NSAIDS) have been avoided in post-tonsillectomy patients because of
reports of association postoperative bleeding. However, a systematic review did not find an increased risk of
reoperation for bleeding and found less vomiting when NSAIDS were part of an analgesic regimen.
50
The use of
NSAIDS after attainment of hemostasis is reasonable.
51

Emergence delirium may be decreased with a single IV bolus dose of dexmedetomidine 0.5 ug/kg given 5
minutes before the end of surgery thus providing a smoother transition to the post anesthesia care unit.
52
A
prospective study of 122 patients, age 2-10 years undergoing tonsillectomy with sevoflurane anesthesia received IV
dexmedetomidine 2 ug/kg over 10 min followed by 0.7 ug/kg/hr and were compared to a group receiving IV
fentanyl 1 ug/kg. The dexmedetomidine group needed less rescue analgesics with fentanyl, had a lower heart rate
and systolic blood pressure and also required less morphine in their postoperative period. Severe emergence
agitation on arrival to PACU was lower and the duration was shorter in the dexmedetomidine subjects.
53

After completion of the procedure patients should be awake and be able to maintain their upper airway
patency. Deep extubation is not recommended in patients with severe OSAS or those with comorbidities because
they are at risk of persistent OSAS after surgery. Before extubation a nasal airway can be placed in patients with
severe sleep apnea. The lateral decubitus or prone position can help relieve airway obstruction after extubation.
Postoperative intensive care unit admission is reserved for very severe OSAS, very young children, morbid
obesity (BMI >40) and those with comorbidities that cannot be managed in a regular unit.
54
Asthma is also
associated with an increased risk of respiratory complications after adenotonsillectomy and these children may need
a higher level of monitoring postoperatively.
55
Patients with mild to moderate obstructive disease (AHI <10) and no
comorbidities can usually be discharged home the same day if they are greater than 3 years of age.
However, there have been fatalities reported in children with OSAS given oral codeine for pain management
at home. These children may be part of a group of extensive or ultra rapid metabolizers that have a greater
production of potent morphine from its parent drug codeine. The genetic pattern occurs in 1-10% of individuals of
European descent but up to 30% of North African descendants and must be considered with codeine use.
56
Given
this data and the increased use of intravenous acetaminophen during the operative procedure, a safer drug to give in
the PACU before discharge maybe oxycodone elixir (1 mg/ml preparation), 0.1 mg/kg up to a maximum dose of 5
mg rather than acetaminophen with codeine. This also avoids the problem of acetaminophen excess in the
immediate postoperative period.
Although the respiratory distress index improves in children with severe sleep apnea and in obese children
with OSAS after adenotonsillectomy, OSAS may not resolve in the majority of these children. In addition, enlarged
lingual tonsils were found to contribute to persistent OSAS after adenotonsillectomy in children and was found to be
more prevalent in patients with Down syndrome.
57
It is important to realize that these children may have increased
anesthetic risk and need special care if they return for other surgeries.
What is the Youngest Age Appropriate for Outpatient Surgery?
Apnea Risk
There is little specific evidence of the risk of apnea in full term infants. There are facilities that feel
comfortable performing outpatient surgeries if the infant is born at greater than 37 weeks gestational age. However,
other ambulatory centers prefer to wait until the infant is 2-4 weeks of age to ensure decreased physiologic jaundice,
decreased pulmonary vascular resistance and to give time for the ductus arteriosus to close. As far as sudden infant
death syndrome (SIDS) there is no evidence anesthesia increases the risk.
58
However, if the patient has a sibling
with a history of SIDS or if the mother has abused drugs in her pregnancy the risk increases many fold. The infants
whose histories suggest a high risk for SIDS should be monitored closely for a longer perioperative period.
In the premature infant apnea is more likely to occur as well as other airway complications such as

122
Page 6
atelectasis, aspiration pneumonia, stridor and coughing with desaturation in infants undergoing inguinal
herniorrhaphy.
59
The best evidence based data is found in Cotes
60
combined analysis of 255 preterm infants
undergoing inguinal herniorrhaphy under general anesthesia. Apnea was defined as >15 seconds without
bradycardia or <15 seconds when accompanied by bradycardia. Apnea was strongly and inversely related to both
gestational age (GA) and post conceptual age (PCA), continuing apnea at home and anemia (<10 gm/dl). In the
nonanemic infant with a GA of 32 weeks and a PCA of 56 weeks or with a GA of 35 weeks and a PCA of 54 weeks,
the probability of apnea was less than 1%.
Caffeine has been shown to decrease the risk of apnea in preterm infants undergoing general anesthesia. In
32 preterm infants (37-44 weeks post-conceptual age) who received IV caffeine 10 mg/kg or placebo the caffeine
group had no postoperative bradycardia, prolonged apnea, periodic breathing or postoperative oxygen saturation
<90% while 81% of the patients in the control group had prolonged apnea at 4-6 hours postoperatively.
61
A
systematic review supported the evidence that caffeine administration reduces apnea risk.
62

Anesthetic Technique
Spinal anesthesia alone has been shown to have a lower incidence of postoperative apnea and bradycardia in
former premature infants when compared to spinal plus sedation or general anesthesia.
63
Also a decreased incidence
of oxygen desaturation and bradycardia has been seen.
64
Central apnea was not reduced so obstructive apnea may
play a role with sedation or general anesthesia.
65
Spinal anesthesia may be indicated in high risk infants. A
Cochrane review that was based on evaluating all the previous trials (which actually included only 108 patients)
stated there is not enough evidence to show whether or not spinal anesthesia improves outcomes for a preterm baby
having surgery for inguinal hernia and that a large well designed randomized control trial is needed.
66
Still the
chance for cardiopulmonary events are increased in these infants and the same postoperative monitoring as for
general anesthesia is indicated.
67,68
Patients less than 60 weeks post conceptual age for hernia repair had shorter times to extubation with no
postoperative apnea after thiopental or halothane induction with desflurane maintenance than either halothane or
sevoflurane for the entire anesthetic.
69
Avoidance of opioids where possible, using regional anesthetic techniques
and nonopioid systemic analgesics such as acetaminophen and nonsteroidal anti-inflammatory agents may decrease
the risk of apnea.

Recommendations
The recommendation for outpatient surgery in infants born before 37 weeks may be 50-52 weeks PCA as
long as there is no anemia, on going apnea or coexisting disease, if a risk of apnea in 5% of the patients is accepted.
However, looking at the evidence based literature to decrease the risk of apnea to <1%, patients should be greater
than 54 weeks PCA without anemia, ongoing apnea or other significant medical problems. Recent
recommendations are that infants with a PCA of less than 46 weeks should be admitted for continuous monitoring
for at least 12 h postoperatively. In infants with a PCA between 46 and 60 weeks with a history of apnea at home,
chronic lung disease, neurological disease or anemia, 12 h of respiratory monitoring is recommended. The
otherwise healthy infant in this PCA group should be monitored for 6 h postoperatively.
70
Postoperative monitoring
recommendations should include oxygen saturation, heart rate and impedance pneumography and that the infants are
apnea free before discharge.
Caffeine or spinal anesthesia may decrease the risk of apnea but patients should not be discharged if they are
not eligible for anesthesia on an outpatient basis by the previously stated criteria. Full term infants are acceptable
for outpatient procedures provided that they are otherwise healthy and the procedure is not likely to result in
significant physiologic changes or postoperative pain requiring opioid medication and the anesthetic is uneventful.
Even in term infants some facilities will not allow outpatient surgery until they are 44-46 weeks post conceptual age
or may require longer observation if younger e.g. 4 hours.

References
1. DeSoto H, Patel RI, Soliman IE, Hannallah RS. Changes in oxygen saturation following general anesthesia in children
with upper respiratory infection signs and symptoms undergoing otolaryngological procedures. Anesthesiology
1988;68:276-9.
2. Cohen MM, Cameron CB. Should you cancel the operation when a child has an upper respiratory tract infection? Anesth
Analg 1991;72:282-8.
3. Rolf N, Cote CJ. Frequency and severity of desaturation events during general anesthesia in children with and without
upper respiratory infections. J Clin Anesth 1992;4:200-3.
4. Aquilina AT, Hall WJ, Douglas RG Jr., Utell MJ. Airway reactivity in subjects with viral upper respiratory tract
infections: the effects of exercise and cold air. Am Rev Respir Dis 1980;122:3-10.
122
Page 7
5. Parnis SJ, Barker DS, Van der Walt JH. Clinical predictors of anaesthetic complications in children with respiratory tract
infections. Paediatr Anaesth 2001;11:29-40.
6. Ouedraogo N, Roux E, Forestier F, et al. Effects of intravenous anesthetics on normal and passively sensitized human
isolated airway smooth muscle. Anesthesiology 1998;88:317-26.
7. Cheng EY, Mazzeo AJ, Bosnjak ZJ, et al. Direct relaxant effects of intravenous anesthetics on airway smooth muscle.
Anesth Analg 1996;83:162-8.
8. Tait AR, Malviya S, Voepel-Lewis T, et al. Risk factors for perioperative adverse respiratory events in children with
upper respiratory tract infections. Anesthesiology 2001;95:299-306.
9. Schreiner MS, OHara I, Markakis D, et al. Do children who experience laryngospasm have an increased risk of upper
respiratory tract infection? Anesthesiology 1996;85:475-80.
10. Tait AR, Knight P. The effects of general anesthesia on upper respiratory tract infections in children. Anesthesiology
1987;67:930-5.
11. Tait AR, Knight PR. Intraoperative respiratory complications in patients with upper respiratory tract infections. Can J
12. Lakshmithapy N, Bokesh PM, Cowan DE, et al. Environmental tobacco smoke: a risk factor for pediatric laryngospasm.
13. Flick RP, Wilder RT, Pieper SF, et al. Risk factors for laryngospasm in children during general anesthesia. Pediatric
Anesthesia 2008;18:289-96.
14. Tait AR, Pandit UA, Voepel-Lewis T, et al. Use of the laryngeal mask airway in children with upper respiratory tract
infections: A comparison with endotracheal intubation. Anesth Analg 1998;86:706-11.
15. von Ungern-Sternberg BS, Boda K, Schwab C, et al. Laryngeal mask airway is associated with an increased incidence of
adverse respiratory events in children with recent upper respiratory tract infections. Anesthesiology 2007;107:714-9.
16. von Ungern-Sternberg BS, Saudan S, Petak F, et al. Desflurane but not sevoflurane impairs airway and respiratory tissue
mechanics in children with susceptible airways. Anesthesiology 2008;108:216-24.
17. Elwood T, Morris W, Martin LD, et al. Bronchodilator premedication does not decrease respiratory adverse events in
pediatric general anesthesia. Can J Anesth 2003;50:277-84.
18. von Ungern-Sternberg BS, Habre W, Erb TO, Heaney M. Salbutamol premedication in children with a recent respiratory
tract infection. Pediatric Anesthesia 2009;19:1064-9.
19. von Ungern-Sternberg BS, Boda K, Chambers NA, et al. Risk assessment for respiratory complications in paediatric
anaesthesia: a prospective cohort study. Lancet 2010;376:773-83.
20. Homer JR, Elwood T, Peterson DO, Rampersad S. Risk factors for adverse events in children with colds emerging from
anesthesia: alogistic regression. Pediatric Anesthesia 2007;17:154-61.
21. Warwick JP, Mason DG. Obstructive sleep apnoea syndrome in children. Anaesthesia 1998;53:571-9.
22. Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Section on
pediatric pulmonology, subcommittee on obstructive sleep apnea syndrome. American Academy of Pediatrics. Pediatrics
2002;109:704-12.
23. Amin RS, Kimball TR, Bean JA, et al. Left ventricular hypertrophy and abnormal ventricular geometry in children and
adolescents with obstructive sleep apnea. Am J Respir Crit Care Med 2002;165:1395-9.
24. Schwengel DA, Sterni LM, Tunkel DE, Heitmiller ES. Perioperative Management of Children with Obstructive Sleep
Apnea. Anesth Analg 2009;109:60-75.
25. Rosen GM, Muckle RP, Mahowald MW, et al. Postoperative respiratory compromise in children with obstructive sleep
apnea syndrome: can it be anticipated? Pediatrics 1994;93:784-8.
26. Helfaer MA, McColley SA, Pyzik PL, et al. Polysomnography after adenotonsillectomy in mild pediatric obstructive
sleep apnea. Crit Care Med 1996;24:1323-7.
27. Nixon GM, Kermack AS, McGregor CD, et al. Sleep and breathing on the first night after adenotonsillectomy for
obstructive sleep apnea. Pediatr Pulmonol 2005;39:332-8.
28. Wilson K, Lakheeram I, Morielli A, et al. Can assessment for obstructive sleep apnea help predict
postadenotonsillectomy respiratory complications? Anesthesiology 2002;96:313-22.
29. Brown KA, Morin I, Hickey C, et al. Urgent adenotonsillectomy: an analysis of risk factors associated with postoperative
respiratory morbidity. Anesthesiology 2003;99:586-95.
30. Koomson A, Morin I, Brouillette R, Brown KA. Children with severe OSAS who have adenotonsillectomy in the
morning are less likely to have postoperative desaturation than those operated in the afternoon.
Can J Anesth 2004;51:62-7.
31. Waters KA, McBrien F, Stewart P, et al. Effects of OSA, inhalational anesthesia, and fentanyl on the airway and
ventilation of children. J Appl Physiol 2002;92:1987-94.
32. Strauss SG, Lynn AM, Bratton SL, Nespeca MK. Ventilatory response to CO2 in children with obstructive sleep apnea
from adenotonsillar hypertrophy. Anesth Analg 1999;89:328-32.
33. Francis A, Eltaki K, Bash T, et al. The safety of preoperative sedation in children with sleep-disordered breathing. Int J
Pediatr Otorhinolaryngol 2006;70:1517-21.
34. Arai YC, Fukunaga K, Hirata S, Fujimoto S. The effects of chin life and jaw thrust while in the lateral position on stridor
score in anesthetized children with adenotonsillar hypertrophy. Anesth Analg 2004;99:1638-41.
35. Clarke MB, Forster P, Cook TM. Airway management for tonsillectomy: a national survey of UK practice. Br J Anaesth

122
Page 8
2007;99:425-8.
36. Lerman J. A disquisition on sleep-disordered breathing in children. Pediatric Anesthesia 2009;19 (Suppl 1):100-8.
37. Moss IR, Belisle M, Laferriere A. Long-term hypoxia in developing rat attenuates respiratory responses to subsequent
acute hypoxia. Pediatr Res 2006;59:525-30.
38. Moss IR, Brown KA, Laferriere A. Recurrent hypoxia in rats during development increases subsequent respiratory
sensitivity to fentanyl. Anesthesiology 2006;105:715-8.
39. Brown KA, Laferriere A, Moss IR. Recurrent hypoxemia in young children with obstructive sleep apnea is associated
with reduced opioid requirement for analgesia. Anesthesiology 2004;100:806-10.
40. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with increased analgesic
sensitivity to opiates. Anesthesiology 2006;105:665-9.
41. Elhakim M, Khalafallah Z, El-Fattah HA, et al. Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy.
Acta Anaesthesiol Scand 2003;47:604-9.
42. Honarmand A, Safavi MR, Jamshidi M. The preventative analgesic effect of preincisional peritonsillar infiltration of two
low doses of ketamine for postoperative pain relief in children following adenotonsillectomy. A randomized, double-
blind, placebo-controlled study. Paediatr Anaesth 2008;18:508-14.
43. Pappas AL, Sukhani R, Hotaling AJ, et al. The effect of preoperative dexamethasone on the immediate and delayed
postoperative morbidity in children undergoing adenotonsillectomy. Anesth Analg 1998;87:57-61.
44. Elhakim M, Ali NM, Rashed I, et al. Dexamethasone reduces postoperative vomiting and pain after pediatric
tonsillectomy. Can J Anaesth 2003;50:392-7.
45. Uysal HY, Takmaz SA, Yaman F, et al. The efficacy of intravenous paracetamol versus tramadol for postoperative
analgesia after adenotonsillectomy in children. J Clin Anesth 2011;23:53-7.
46. Czarnetzki C, Elia N, Lysakowski C, et al. Dexamethasone and the risk of nausea and vomiting and postoperative
bleeding after tonsillectomy: A randomized trial. JAMA 2008;300:2621-30.
47. Brigger MT, Cunningham MJ, Hartnick CJ. Dexamethasone administration and postoperative bleeding risk in children
undergoing tonsillectomy. Arch Otolaryngol Head Neck Surg 2010;136:766-72.
48. Steward DL, Grisel J, Meinzen-Derr J. Steroids for improving recovery following tonsillectomy in children. Cochrane
Database Syst Rev 2011(8):CD003997. Evidence-based recommendations for the use of dexamethasone in pediatric
adeontonsillectomy.
49. Raghavendran S, Bagry H, Detheux G, et al. An anesthetic management protocol to decrease respiratory complications
after adenotonsillectomy in children with severe sleep apnea. Anesth Analg 2010;110:1093- 101.
50. Cardwell M, Siviter G, Smith A. Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric
tonsillectomy. Cochrane Database Syst Rev 2005;CD003591.
51. Dsida R, Cote CJ. Nonsteroidal anti-inflammatory drugs and hemorrhage following tonsillectomy: do we have the data?
Anesthesiology 2004;100:749-51; author reply 751-2.
52. Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine reduces agitation and provides smooth extubation after
pediatric adenotonsillectomy. Paediatr Anaesth 2005;15:762-6.
53. Patel A, Davidson M, Tran MCJ, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation
in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg
2010;111:1004-10.
54. Leong AC, Davis JP. Morbidity after adenotonsillectomy for paediatric obstructive sleep apnoea syndrome: waking up to
a pragmatic approach. J Laryngol Otol 2007;121:809-17.
55. Kalra M, Buncher R, Amin RS. Asthma as a risk factor for respiratory complications after adenotonsillectomy in
children with obstructive breathing during sleep. Ann Allergy Asthma Immunol 2005;94:549-52.
56. Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities after tonsillectomy in North American children.
Pediatrics 2012;129:e1343-7.
57. Fricke BL, Donnelly LF, Shott SR, et al. Comparison of lingual tonsil size as depicted on MR imaging between children
with obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and normal controls. Pediatr Radiol
2006;36:518-23.
58. Steward DJ. Is there risk of general anesthesia triggering SIDS? Possibly not! Anesthesiology 1985;63:326-7.
59. Steward DJ. Preterm infants are more prone to complications following minor surgery than are term infants.
60. Cote CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former preterm infants after inguinal herniorrhaphy.
61. Welborn LG, Hannallah RS, Fink R, et al. High-dose caffeine suppresses postoperative apnea in former preterm infants.
62. Henderson-Smart DJ, Steer P. Prophylactic caffeine to prevent postoperative apnea following general anesthesia in
preterm infants. Cochrane Database Syst Rev 2001;4:CD000048.
63. Welborn LG, Rice LJ, Hannallah RS, et al. Postoperative apnea in former preterm infants. Prospective comparison of
spinal and general anesthesia. Anesthesiology 1990;72:838-42.
64. Somri M, Gaitin L, Vaida S, et al. Postoperative outcome in high-risk infants undergoing herniorrhaphy: Comparison
between spinal and general anesthesia. Anaesthesia 1998;53:762-6.
65. Krane EJ, Haberkern CM, Jacobson LE. Postoperative apnea, bradycardia, and oxygen desaturation in formerly

122
Page 9
premature infants: Prospective comparison of spinal and general anesthesia. Anesth Analg 195;80:7-13.
66. Craven PD, Badawi N, Henderson-Smart DJ, OBrien M. Regional (spinal, epidural, caudal) versus general anaesthesia
in preterm infants undergoing inguinal herniorrhaphy in early infancy (Review). Cochrane Database of Systemic
Reviews 2003, Issue 3. Art. No.: CD003669. DOI: 10.1002/14651858. CD003669.
67. Frumiento C, Abajian JC, Vane DW. Spinal anesthesia for preterm infants undergoing inguinal hernia repair. Arch Surg
2000;135:445-51.
68. Shenkman Z, Hopperstein D, Litmanowitz I, et al. Spinal anesthesia in 62 premature, former-premature or young infants:
Technical aspects and pitfalls. Can J Anaesth 2002;49:262-9.
69. OBrien K, Robinson DN, Morton NS. Induction and emergence in infants less than 60 weeks post conceptual age:
Comparison of thiopental, halothane, sevoflurane and desflurane. Br J Anaesth 1998;80:456-9.
70. Walther-Larsen S, Rasmussen LS. The former preterm infant and risk of post-operative apnoea: recommendations for
management. Acta Anaesthesiol Scand 2006;50:888-93.

Disclosure
206
Page 1
Controversies in Pediatric Anesthesia
Lena S. Sun, M.D. New York, New York
The Blackbox Warning
Use of Succinylcholine in Infants and Children
1. History of the Blackbox warning for SDC
2. MH and SDC
3. Myopathy and SDC
4. Use of SDC in rapid sequence induction
Anesthetic Agents and Blackbox Warning
Anesthesia Neurotoxicity-Evolution of Research and Clinical Updates
1. Overview of Pre-clinical Studies
I. Exposure:
Ex Vivo
In Vivo: Rodents and Non-human Primates
Anesthetic Agents: Single (ketamine, isoflurane, sevoflurane, desflurane, propofol)
Combination of agents
II. Outcomes:
Cellular Findings
Functional Outcomes
III. Window of injury vulnerability
IV. Mechanism of injury
V. Mitigating Factors
2. Human Studies
I. Birth cohort studies
II. Secondary analysis of two prospective cohort studies
III. Premature infants
3. Ongoing Studies
I. GAS
II. MASK
III. PANDA
Evidence for Changes in Anesthesia Practice?
Disclosure
210
Page 1
Practical Pediatric Anesthesia
Santhanam Suresh, M.D. Chicago, Illinois
Introduction: Regional anesthesia is experiencing resurgence in pediatric anesthesia. The use of ultrasound
guidance has increased the variety of blocks that can be performed in infants, children and adolescents. The
increased safety of performing blocks with US guidance has allowed the practitioner to attempt to perform more
difficult blocks compared to previously described using landmark techniques.
[1-3]
The use of ultrasound guidance
can also allow minimal use of local anesthetic solutions thereby decreasing the risk of toxicity.
[4]
In this lecture, a
variety of regional anesthesia techniques will be described that you can use in your everyday practice. Central
neuraxial as well as peripheral nerve blocks will be described with clinical techniques as well as images for
reference while performing these blocks. Large databases are now collecting prospective data on the feasibility and
complications associated with regional anesthesia in children.
[5]
Equipment: As the field of regional anesthesia is exploding, the use of ultrasound imaging is undergoing constant
improvement. Several ultrasound imaging machines with the capability of offering a variety of applications
including echocardiography have entered the market with greater emphasis on user-friendliness and portability.
This may be of greater importance in the pediatric population since most of these blocks are performed in the
operating room under general anesthesia. In children, it may be easier to perform regional anesthesia with deep
sedation or under general anesthesia.
[6]
US probes commonly used in children include a high frequency hockey
stick probe and a linear 25 mm high frequency probe. Since most of the neurovascular structures are located
superficially in children, visualization of neural structures is easier with a high frequency probe. The physics and
equipment descriptions can be found in textbooks on US guided regional anesthesia. US guidance can be used for
central neuraxial blocks as well as for peripheral nerve blocks. A brief description of each of these blocks will be
provided at this refresher course. In general, the use of curvilinear probes is limited to the use in older children and
obese individuals.
Central neuraxial blocks:
Epidural Analgesia:
Ultrasound imaging seems promising for use either pre-procedurally (prior to puncture) or during block performance
(US aided), although the latter may be most suitable in infants. The largely cartilaginous posterior vertebral column
of neonates and infants enables good US beam penetration to view the spinal structures and can in some cases
enable a view of the needle tip trajectory.
Techniques
Sonoanatomy:
A moderate-high frequency probe (hockey stick, 13-6 frequency probe) is utilized using a paramedian longitudinal
view. The window between the two spinous processes will allow the operator to visualize the anterior complex
(anterior duramater, and the posterior longitudinal ligament), the posterior duramater and the ligamentum flavum.
Our preference is to visualize the neuraxis using a paramedian approach. In a paramedian longitudinal view at the
thoracic spine, the spinous processes are represented by slanted hyperechoic lines beneath the homogeneous-
appearing paravertebral muscle mass. Dorsal shadowing will be apparent deep to the spinous processes and other
posterior vertebral elements. The highly hyperechogenic ligamentum flavum and dura mater are captured lying in
the alternate windows, and the underlying spinal cord appears largely hypoechoic with an outer bright covering of
the pia and a central line of hyperechogenicity (median sulcus).
[2]
In the first report of US imaging in central
blockade, Chawathe et al. performed a pilot study in 12 patients (1 day old to 13 months) to evaluate the possibility
of detecting catheters, and verifying their placement, within the epidural space after placement (within 24 hours) via
the direct lumbar route.
[7]
The important point from this paper is that US imaging (specifically using the midline
approach) of static structures such as catheters can be performed, yet only reliably in very young patients where
much of the posterior bony elements of the spinal column may exist as cartilage, thus allowing good US beam
penetration. An optimal angle of probe alignment needs to be evaluated in children and surrogate markers for
viewing needle and catheters may be necessary to facilitate a dynamic technique. Willschke et al placed epidural
210
Page 2
catheters under real-time US guidance using the paramedian longitudinal imaging plane in 35 neonates.
[8]
Needle
tip entry and the injection of local anesthetic solution within the epidural space were used to confirm epidural
placement; these parameters could be viewed in all neonates. Epidural catheters could only be identified via
surrogacy through tissue movement (i.e., anterior movement of the duramater) and fluid injection.
Caudal Needle Placement
Caudal blocks, including both single-shot caudal and lumbar or thoracic epidural catheters advanced from the caudal
epidural space (thus avoiding the spinal cord), is a commonly practiced regional anesthesia technique in children.
Although this technique is practiced with the identification of landmarks, there is a small, but not insignificant
chance for failure.
Sonoantomy: Ultrasound imaging at the midline using both transverse and longitudinal alignment of the probe
should be performed prior to needle placement in order to appreciate the patients anatomy and to identify the
sacrococcygeal ligament, dural sac and cauda equina. A linear high-frequency small footprint or hockey stick probe
is a suitable choice, although a larger footprint may be used when viewing the longitudinal axis to allow an adequate
field of view. Placing the probe initially in a transverse plane at the coccyx and scanning in a cephalad direction can
help with landmark identification particularly during training in sonoanatomy. This view allows a good delineation
of the sacral hiatus; the sacral cornua are viewed laterally (as humps) and the sacral hiatus is located between an
upper hyperechoic line representing the sacrococcygeal membrane/ligament and an inferior hyperechoic line
representing the dorsum of the pelvic surface (base) of the sacrum. Placing the probe longitudinally between the
sacral cornua will capture the dorsal surface of the sacrum, the dorsal aspect of the pelvic surface of the sacrum and
the sacrococcygeal ligament. The sacrococcygeal ligament covers the sacral base beyond the end of the dorsum of
the sacrum. It appears as a relatively thick linear hyperechoic band, sloping caudally. The sacral hiatus is identified
as a hypoechoic space located between the dorsum of the sacrum and the dorsal side of the pelvic surface of the
sacrum. In older patients where the structures may be ossified at the midline, the paramedian longitudinal view may
be necessary since it will allow the US beam to penetrate the spaces on either side of the spinous processes. This
paramedian view would allow appreciation of the ventral movement of the duramater during fluid injection, but
would not allow a real-time view of the needle along its axis.
Technique: During or after skin puncture with the needle, both transverse and longitudinal sonographic planes can
be used for confirming caudal epidural needle placement. Roberts at al. published a prospective observational
study of 60 children, in which they determined whether a saline test bolus could be reliably imaged with US in order
to confirm cannula placement in the caudal epidural space.
[9]
While transverse imaging was performed in the pre-
puncture scan to help visualize the neuraxial structures (there was no mention of measurements or skin markings),
longitudinal imaging (approximately 1 cm above the cannula insertion site) was used during the saline test bolus of
0.2-0.3 ml kg
-1
to view the anterior displacement of the posterior dura mater. The longitudinal plane may allow a
view of the long axis of the needle as it penetrates the sacrococcygeal ligament. This technique may be particularly
beneficial to allow adjustments in needle angle to ensure adequate length of advancement and depth of penetration
without intraosseous placement. The optimal angle for needle insertion during caudal block has been evaluated
using US, since many of the previous recommendations include multiple angles, necessitating needle manipulations,
including a steep initial angle, which may increase the incidence of bony puncture. When introducing a catheter into
the caudal space to reach the lumbar or thoracic spine, similar technique to the above is used for cannula placement
and the catheter is viewed during advancement using US imaging at the level of the spine above the sacrum. The
above section describing intervertebral epidural catheter placement can be referred to for imaging techniques when
viewing the spinal column.
Epidural Analgesia:
- US-guided technique does not preclude continuous testing for loss of resistance.
- The limitation of the technique is that the needle shaft and tip may be hard to localize with the
tangential relationship of the needle (midline) and the probe (paramedian longitudinal).
- An assistant (2
nd
set of hands) is required during catheter placement in order to perform the imaging
real-time for US aided catheter placement. It is important to use saline for LOR to facilitate US
imaging.
210
Page 3
Head & Neck Blocks: Head and neck blocks are often performed in infants and children for managing pain in the
postoperative period. Although these blocks are simple and easy to use, the prevalence of their use has been lower
than expected due to inexperience as well as the need for education of surgeons regarding their use. Two common
blocks that we use in our practice are the infraorbital nerve blocks and the superficial cervical plexus block.
Infraorbital nerve blocks: The infraorbital nerve is the terminal branch of the trigeminal nerve (V1). This nerve, as
it exits the maxillary foramen supplies the sensory innervation to the upper lips, the maxillary sinus area and parts of
the nasal septum. We have used it successfully for infants undergoing cleft lip repair as well as in sinus surgery.
Technique: The upper lip is everted, using a 27_G needle, it is advanced towards the infraorbital foramen, and after
careful aspiration 1 mL of 0.25% bupivaciane is injected. The area is gently massaged to allow easy spread of the
local anesthetic solution.
Adverse effects: The upper lip remains numb after the block and some children may find it distressing. In addition,
a small hematoma can develop at the site of injection.
Superficial cervical plexus block: The superficial cervical plexus is derived of the cervical nerve roots and supply
the pain fibers for the neck, the pinna and the mastoid area. The superficial cervical plexus wraps around the belly
of the sternocleidomastoid to supply the anterior neck as well as the mastoid area with its branches, the great
auricular, the lesser occipital, the transverse cervical and the supraclavicular.
Technique: Using a sterile technique, the sternocleidomastoid is identified at the level of the cricoid cartilage (C6),
a 27- g needle is inserted along the posterior border of the sternocleidomastoid, after careful aspiration, 2 mL of
0.25% bupivaciane is injected to provide pain relief. We have used this technique for children undergoing mastoid
surgery repair as well as for cochlear implants.
Adverse effects: Serious adverse effects can be seen from injection into a blood vessel but with superficial injection,
there is little chance for major problems.
Upper Extremity Blocks
The most common approach to the brachial plexus in infants and children is the axillary approach and the
supraclavicular approach. With the advent of US guidance, the interscalene approach has resurfaced as a viable
technique for placement of a catheter.
Interscalene Block
Sonoanatomy: A small footprint hockey stick probe will allow optimal recognition of the superficial structures in
this region for infants and small children. In a transverse oblique plane at the level of the cricoid cartilage and at the
posterolateral aspect of the sternocleidomastoid muscle, the superficially-located sternocleidomastoid muscle
appears triangular in shape and overlies the internal jugular vein and common carotid artery. In small infants, the
US probe footprint is wide enough to capture the great vessels along the brachial plexus in the same image screen.
Lateral to the vessels and deep to the sternocleidomastoid muscle lays the anterior scalene muscle, and more
posterolaterally, the middle and posterior scalene muscle (the latter two often appearing as a single mass). The
hyperechoic (bright)-appearing tissue forming a lining around the muscles is presumably the fibrous tissue of the
Caudal Needle Placement
- Initially use a transverse plane of imaging to identify the sacral hiatus located between the cornua; the
sacral hiatus is located between an upper hyperechoic line representing the sacrococcygeal
membrane/ligament and an inferior hyperechoic line representing the dorsum of the pelvic surface
(base) of the sacrum.
- Rotate the probe to the longitudinal plane (a paramedian plane may be required in older children) to
capture the sacrococcygeal membrane, a relatively thick linear hyperechoic band, sloping caudally.
- Insert the needle under either plane of view, although a longitudinal view may allow for optimal
viewing along the needle. A transverse view can be used after needle placement within the epidural
space, in order to view the spread of local anesthetic (as dilation of the caudal space and localized
turbulence).

210
Page 4
interscalene sheath. Brachial plexus trunks and/or roots in this sagittal oblique section are usually visualized as three
(or more) round or oval-shaped hypoechoic (grey or dark) structures, lying between the scalenus anterior and medius
muscles.
[10]
Continuous interscalene blockade was performed for a 10-year old girl in the Philippines during a
plastic surgery medical mission with an intravenous catheter.
[11]
Without the availability of perineural catheters as
well as stimulating needles, a 22 gauge angiocatheter was used for the block, utilizing an in-plane alignment to the
posterior edge of the probe using the US equipment from the obstetric suite. This case demonstrates the ubiquitous
nature of US equipment in most medical centers across the globe.
Supraclavicular Block
Sonoanatomy: The probe is placed along the upper border of the clavicle. The carotid and the internal jugular vein
are recognized. The probe is moved laterally while looking for the pulsation of the subclavian artery. The
supraclavicular brachial plexus is located lateral to the artery and appears hyperechoic mixed with hypoechoic
shadows in a grape like fashion surrounding the artery.
Technique: The supraclavicular block is performed using a high frequency hockey stick or linear probe. The
subclavian artery to identified, inferior to it is the dome of the pleura and lateral and inferior to it is the 1
st
rib. The
plexus can be accessed using an in-plane approach from laterally. Nerve stimulation can be used in conjunction
with US guidance for this block.
Comment: When performing a supraclavicular block there is a greater risk of pneumothorax as the cupola of the
lung lies just medial to the first rib, not far from the plexus; the distance of the plexus from the lung being especially
short in children. It is critical to ensure that clear visibility of the needle shaft and tip is obtained by aligning the
needle in-plane to the ultrasound probe at all times. Single injection techniques are generally sufficient; however
multiple injections of local anesthetic can be performed if needed with the needle redirected to ensure sufficient
circumferential spread around the plexus. However, care should be taken to avoid intravascular injection of the
surrounding vessels (including the transverse colli artery located cephalad to the plexus). Auscultation of the lungs
should be performed before and after performance of the block as well as prior to discharge to detect clinical signs
of pneumothorax. A simple method to
recognize the viability of the radial median and ulnar nerve can be performed by a thumbs up sign radial nerve;
flexion of PIP (median nerve) and scissoring of the fingers (ulnar nerve) prior to performance of the block to
recognize prior injury.
[12]

Axillary Block
Sonoanatomy: With the probe placed perpendicular to the anterior axillary fold, a short-axis view of the
neurovascular bundle can be obtained; the biceps brachii and coracobrachialis muscles are seen laterally; the triceps
brachii muscle is medial and deep to the biceps brachii muscle. The anechoic and circular pulsating axillary artery
lies centrally, adjacent to both the biceps brachii and coracobrachialis muscles, and is surrounded by the nerves. The
median nerve is typically located superficial and between the artery and biceps brachii muscle, the ulnar nerve is
commonly located medial and superficial to the artery and the radial nerve often lies deep to the artery at the
midline. At this level, the musculocutaneous nerve is located between the biceps brachii and coracobrachialis
muscles.
Technique: The terminal nerves are visualized in an axial plane, the probe is placed in the axillary fold. A needle is
placed in an in-plane approach to access the median, radial and ulnar nerves individually. Local anesthetic solution
is placed to surround the plexus in its entirety to provide an adequate blockade. We feel that the use of ultrasound
may allow reduction in dosing for the block although further studies are required to prove the pharmacodynamic
ability of US guidance with lower volumes for axillary blocks in children.
Comment: Multiple injections and needle redirections are commonly required to ensure circumferential spread of the
local anesthetic around each of the individual nerves. Since there is an abundance of vessels in this region, complete
avoidance of vessel puncture can be a challenge even when utilizing ultrasound imaging. It is important to
Clinical Pearls - Supraclavicular block
- Place a linear probe superior to the clavicle scanning lateral to the great vessels
- Notice the 1
st
rib and the subclavian artery
- The supraclavicular plexus is seen surrounding the subclavian artery as a bunch of grapes
- Using an in-plane approach, place the needle below the plexus, injection of 0.3mL/kg of local
anesthesia will produce adequate analgesia.
- Stay away from using a medially positioned needle due to close proximity to the pleura.

210
Page 5
understand that the plexus remains very close to the surface and hence the needle should be directed cautiously
while this block is attempted. Smaller doses can be used to provide an adequate blockade of this plexus in infants
and children.

Lower Extremity Block
Femoral Nerve Block
Sonoanatomy: Similar to using conventional technique, arterial pulsations of the femoral artery is the key landmark
when using US guidance for femoral nerve blockade. With the probe placed at the level of and parallel to the
inguinal crease, the nerve appears lateral to the large, circular and anechoic femoral artery (color Doppler may be
used to identify the femoral artery and vein). The nerve often appears triangular in shape and may be variable in
size. The fascia lata (most superficial) and iliaca (immediately adjacent to the nerve and in fact separating the nerve
from the artery) are seen superficial to the femoral nerve and often appear as bright and longitudinally angled
echogenic signals.
[13]

Technique: A linear high frequency US probe is placed at the level of the inguinal crease and using an in-plane
approach, the femoral nerve is accessed from the lateral aspect. Once the needle enters the fascia iliaca
compartment, local anesthetic solution is injected to envelope the nerve entirely. If a nerve stimulator is used
adjunct, quadriceps contraction is elucidated. Although one cannot be sure about intraneural injection while using
US guidance, it may be prudent to place the needle in the fascia iliaca compartment and not place it directly into the
neural plexus.

Lateral Femoral Cutaneous Block:
Sonoanatomy: The lateral femoral cutaneous nerve is located at the lateral aspect of the insertion of the Sartorius
and medial to the tensor fascia lata. The nerve is located between the fascia lata and the fascia iliaca. This supplies
the lateral aspect of the thigh and can be used for providing analgesia for surgery to the lateral aspect of the thigh
including muscle biopsies
[14]
and for percutaneous hip pinning.
Technique: A finger is placed to identify the ridge between the tensor fascia lata and the Sartorius. A linear probe
is placed straddling the tendinous ridge. The fascia between the tensor fascia lata and the Sartorius houses the
lateral femoral cutaneous nerve. After sterile preparation, a 22-G needle is inserted through the fascia lata, after
aspiration, 5 to 10mL of local anesthetic solution is injected.
Complications: Rare, bruise at the site of injection.
Sciatic Nerve Block:
Sonoanatomy: The sciatic nerve block is commonly used in children for providing analgesia for lower extremity
surgery. We use it in combination with a femoral nerve block for providing analgesia for knee surgery. The sciatic
nerve is usually scanned at the level of the popliteal crease. The biceps femoris tendon is identified. The popliteal
artery is identified with the popliteal vein on top of the artery. Immediately above that is the tibial nerve. On
scanning further laterally, the common peroneal nerve can be located.
Technique: In the supine or prone position, the popliteal fossa crease is identified; a linear US probe is placed at the
level of the popliteal crease. The popliteal artery is identified; the popliteal vein deeper to it and deep to that
structure is the tibial nerve. The US probe is moved laterally to visualize the common peroneal nerve. The probe is
advanced cephalad to where the common peroneal and tibial nerves coalesce to form the single sciatic nerve. A
Axillary Block
- Place a hockey stick probe or a linear small footprint probe in the axilla as proximal as possible.
- The needle is directed from superior to inferior using an in-plane approach.
- The structures are superficial and hence are located fairly superficial and can be easily identified.
- Color Doppler can be used to recognize the vascular structures.
- Local anesthetic solution is injected to surround the cords.
Femoral Nerve Block
- Place a linear probe along the inguinal/femoral crease.
- Place a needle in an in-plane approach.
- The local anesthetic is injected to surround the nerve.
- The needle has to be placed inside the fascia iliaca compartment and the local anesthetic is seen
surrounding the nerve bundle.

210
Page 6
needle is placed in an in-plane orientation; the sciatic nerve can be stimulated if a stimulating needle is used to elicit
inversion or eversion of the foot.

Blockade of the Anterior Trunk
Among many blocks performed at the anterior trunk, ilioinguinal/iliohypogastric nerve blockade is one of the most
commonly performed blocks for surgery in the inguinal region and may be one of the most common peripheral
nerve blocks in children. (Pediatric Regional Anesthesia Network PRAN, personal communication Dr. Suresh)
Various other nerve blocks are also becoming popular to provide analgesia for procedures in the umbilical or
epigastric regions. Ultrasonography can be particularly beneficial for truncal blocks in children due to the close
anatomical relations between the nerves and various critical abdominal structures.
Ilioinguinal/Iliohypogastric Nerve Block
Sonoantomy: A linear high frequency probe is placed immediately medial to the superior aspect of the anterior
superior iliac spine (ASIS) to capture a short-axis view of the ilioinguinal nerve sandwiched between the internal
oblique abdominal and transverse abdominal muscles. The ASIS appears hypoechoic (due to dorsal shadowing
beyond the highly-reflective periosteum) and nodular-shaped at the lateral edge of the screen. The lateral abdominal
muscles will appear with multiple hyperechoic dots within a hypoechoic background.The nerve can be identified as
an elliptical-oval shaped structure with a hyperechoic film surrounding a hypoechoic core.
[15, 16]

Technique: A hockey stick probe will be suitable for many infants and younger children, since the nerves are closely
situated beneath the skin (8 mm on average) and medial (7 mm on average) to the ASIS. The probe is placed with
the direction pointed towards the umbilicus. A needle is inserted in an in-plane approach to place in between the
internal oblique and the transversus abdominis muscle. Local anesthetic solution is injected to hydro-dissect
between the two layers thereby providing a blockade of the L1 nerve root. We use a volume of 0.1mL/kg with a
total maximum volume of 5mL for this blockade.

Sciatic Nerve Block at the Popliteal Fossa
- Place a linear probe in the popliteal fossa at the crease at the knee.
- Look for the popliteal artery.
- The popliteal vein is noted above the artery.
- The tibial nerve is often located in close proximity to the popliteal artery.
- The common peroneal nerve is located lateral to the tibial nerve.
- A linear probe is gently moved cephalad until the two branches confluence; the nerve will diverge from
the vessels.
- Using an in-plane approach, a needle is placed in close proximity to the sciatic nerve and local
anesthetic solution is injected to surround the nerve.
Ilioinguinal Nerve Block
- Place a linear probe or a hockey stick probe along the ASIS with the probe oriented towards the
umbilicus.
- The three layers of the abdominal wall muscles can be recognized.
- The ilioinguinal nerve and iliohypogastric nerves are seen as 2 hypoechoic structures between the
internal oblique and transversus abdominis muscles.
- Using an in-plane approach, a 27-Gauge needle is advanced and placed between the internal oblique
abdominal and the transversus abdominis muscle.
- After aspiration, 0.1mL/kg of local anesthetic solution is injected.

210
Page 7
Rectus Sheath Block

Sonoantomy: The rectus sheath is located between the rectus abdominis muscle and the posterior rectus sheath. A
small footprint probe will be suitable for viewing unilateral anatomy. The anterior and posterior aspects of the
rectus sheath and the enclosed rectus abdominis muscle are visualized. The sheath appears hyperechoic with
multiple linear layers, lying on the anterior and posterior aspects of the rectus muscle.
Technique: A linear high frequency probe is placed on the abdominal wall lateral to the umbilicus. Using an in-
plane approach and coming in from laterally, a needle is inserted posterior to the rectus abdominis muscle but
anterior to the posterior rectus sheath. Superior displacement of the rectus abdominis muscle is seen with injection
of the local anesthetic solution. This block can be used for umbilical hernia repairs as well as most midline
abdominal surgeries involving the T10 distribution.
[17]

Transversus Abdominis Plane (TAP) Block
Sonoantomy: The layers of the abdominal wall can be easily distinguished using ultrasonography. The thoraco-
lumbar nerve roots (T10 to L1) provide the sensory supply to the abdominal wall. The nerves run in a plane
between the internal oblique and transversus abdominis muscle, hence referred to as the transversus abdominis plane
or TAP. A linear probe placed along the lateral aspect of the abdomen can distinguish the various layers of the
abdomen including from superficially, fascia/fat, external oblique, internal oblique and the transversus abdominis
muscle. A blockade at this level can provide analgesia for anterior abdominal wall surgery. This may be especially
useful in infants and children who may have underlying coagulopathy, spinal dysraphism or as a rescue block
following a failed neuraxial blockade. The block has been demonstrated to be effective for abdominal surgery in the
adult population.
[18]

Technique: A simple step by step approach to this block has been recently described.
[19]
A linear high frequency
probe or a hockey stick probe is used for the procedure. Recognize the various layers of the abdomen. A needle is
inserted in the in-plane technique to enter the plane between the transverses abdominis and the internal oblique.

Local anesthetic solution (0.2mL/kg) is injected. The downward movement of the transverses abdominis signifies
correct placement of the needle in the TAP plane.

Rectus Sheath Block
- A linear high frequency probe or a hockey stick probe is placed at the level of the umbilicus.
- The rectus abdominis muscle is identified along with the anterior and posterior rectus sheaths.
- Using an in-plane technique, a 27-gauge needle is advanced until it penetrates the space between the
rectus abdominis and the posterior rectus sheath.
- 0.1mL/kg of local anesthetic solution is injected into the potential space between the posterior rectus
sheath and the rectus abdominis muscle.
- Hydro-dissection can be used to find the exact plane since the space is small and may need exact
localization.
Transversus Abdominis Plane Block
- A high frequency linear probe or a hockey stick probe is placed lateral to the umbilicus.
- Sliding the probe laterally, the three muscle layers of the abdominal wall are recognized (external and
internal oblique abdominal and transverse abdominal).
- In the mid-axillary line, using an in-plane approach, place a needle between the internal oblique and the
transverse abdominal muscles.
- As local anesthetic is injected, the plane is seen to expand with posterior movement of the transversus
abdominis muscle.

210
Page 8
Conclusion: US guidance for peripheral and central neuraxial blocks are becoming the mainstay of regional
anesthesia in children. As equipment improves and becomes more cost-effective, the use of US guidance may
become the norm rather than the exception. Multiple hands-on workshops offered by the ASA, ASRA and SPA
may shed greater insight into some of the common techniques. The steep learning curve for US guidance can be
offset by offering it as routine curriculum for training residents and fellows in anesthesia training programs. A
block-rotation (as offered by the fellowship program at Childrens Memorial Hospital in Chicago) can improve and
reinforce the use of regional anesthesia in infants, children and adults. Ongoing data is being collected prospectively
by the Pediatric Regional Anesthesia Network (PRAN), a consortium of pediatric hospitals. As more data is
collected, we will be able to provide a more meaningful insight into adverse effects, dosing and pharmacodynamics
of regional anesthesia in infants, children and adolescents.

Figure-1: Epidural

Figure-2: Supraclavicular Figure 3:Axillary block

Figure 4: Femoral Block Figure-5: Popliteal Fossa Block

210
Page 9
Figure-6 Ilioinguinal N Block Figure-7 TAP block

[1] C. Frigon, R. Mai, T. Valois-Gomez, J. Desparmet, Bowel hematoma following an iliohypogastric-ilioinguinal
nerve block, Paediatr Anaesth, 16 (2006) 993-996.
[2] B. Tsui, S. Suresh, Ultrasound imaging for regional anesthesia in infants, children, and adolescents: a review of
current literature and its application in the practice of extremity and trunk blocks, Anesthesiology, 112 473-492.
[3] B.C. Tsui, S. Suresh, Ultrasound Imaging for Regional Anesthesia in Infants, Children, and Adolescents: A
Review of Current Literature and Its Application in the Practice of Extremity and Trunk Blocks, Anesthesiology,
112 473-492.
[4] H. Willschke, A. Bosenberg, P. Marhofer, S. Johnston, S. Kettner, U. Eichenberger, O. Wanzel, S. Kapral,
Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal
volume?, Anesth Analg, 102 (2006) 1680-1684.
[5] D.M. Polaner, A.H. Taenzer, B.J. Walker, A. Bosenberg, E.J. Krane, S. Suresh, C. Wolf, L.D. Martin, Pediatric
Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of
pediatric regional anesthesia, Anesth Analg, 115 (2012) 1353-1364.
[6] C.M. Bernards, A. Hadzic, S. Suresh, J.M. Neal, Regional anesthesia in anesthetized or heavily sedated patients,
Reg Anesth Pain Med, 33 (2008) 449-460.
[7] M.S. Chawathe, R.M. Jones, C.D. Gildersleve, S.K. Harrison, S.J. Morris, C. Eickmann, Detection of epidural
catheters with ultrasound in children, Paediatr Anaesth, 13 (2003) 681-684.
[8] H. Willschke, A. Bosenberg, P. Marhofer, J. Willschke, J. Schwindt, M. Weintraud, S. Kapral, S. Kettner,
Epidural catheter placement in neonates: sonoanatomy and feasibility of ultrasonographic guidance in term and
preterm neonates, Reg Anesth Pain Med, 32 (2007) 34-40.
[9] S.A. Roberts, V. Guruswamy, I. Galvez, Caudal injectate can be reliably imaged using portable ultrasound--a
preliminary study, Paediatr Anaesth, 15 (2005) 948-952.
[10] M.J. Fredrickson, C.M. Ball, A.J. Dalgleish, A.W. Stewart, T.G. Short, A prospective randomized comparison
of ultrasound and neurostimulation as needle end points for interscalene catheter placement, Anesth Analg, 108
(2009) 1695-1700.
[11] E.R. Mariano, B.M. Ilfeld, G.S. Cheng, H.F. Nicodemus, S. Suresh, Feasibility of ultrasound-guided peripheral
nerve block catheters for pain control on pediatric medical missions in developing countries, Paediatr Anaesth, 18
(2008) 598-601.
[12] S. Suresh, J.P. Sarwark, T. Bhalla, J. Janicki, Performing US-guided nerve blocks in the postanesthesia care
unit (PACU) for upper extremity fractures: is this feasible in children?, Paediatr Anaesth, 19 (2009) 1238-1240.
[13] U. Oberndorfer, P. Marhofer, A. Bosenberg, H. Willschke, M. Felfernig, M. Weintraud, S. Kapral, S.C.
Kettner, Ultrasonographic guidance for sciatic and femoral nerve blocks in children, Br J Anaesth, 98 (2007) 797-
801.
[14] R.M. Maccani, D.J. Wedel, A. Melton, G.A. Gronert, Femoral and lateral femoral cutaneous nerve block for
muscle biopsies in children, Paediatr Anaesth, 5 (1995) 223-227.
[15] H. Willschke, P. Marhofer, A. Bosenberg, S. Johnston, O. Wanzel, S.G. Cox, C. Sitzwohl, S. Kapral,
Ultrasonography for ilioinguinal/iliohypogastric nerve blocks in children, Br J Anaesth, 95 (2005) 226-230.
210
Page 10
[16] N. Jagannathan, L. Sohn, A. Sawardekar, A. Ambrosy, J. Hagerty, A. Chin, K. Barsness, S. Suresh, Unilateral
groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the duration of
analgesia of a single-shot caudal block?, Paediatr Anaesth, 19 (2009) 892-898.
[17] B. de Jose Maria, V. Gotzens, M. Mabrok, Ultrasound-guided umbilical nerve block in children: a brief
description of a new approach, Paediatr Anaesth, 17 (2007) 44-50.
[18] J.G. McDonnell, B. O'Donnell, G. Curley, A. Heffernan, C. Power, J.G. Laffey, The analgesic efficacy of
transversus abdominis plane block after abdominal surgery: a prospective randomized controlled trial, Anesth
Analg, 104 (2007) 193-197.
[19] S. Suresh, V.W. Chan, Ultrasound guided transversus abdominis plane block in infants, children and
adolescents: a simple procedural guidance for their performance, Paediatr Anaesth, 19 (2009) 296-299.
216
Page 1
Anesthesia For the Patient With Congenital Heart Disease For Noncardiac Surgery
Dean B. Andropoulos, M.D., M.H.C.M. Houston, Texas
Introduction
Congenital heart disease (CHD) is present in 9 per 1000 live births in the United States, making it the most common
congenital defect requiring invasive treatment in the first year of life. With the current mortality for all congenital
cardiac operations less than 5%, an increasing number of these patients survive, and it is currently estimated that
there are between 650,000 and 1.3 million adults and children in the U.S. living with congenital heart disease. Of
these, approximately 55% have simple lesions, 30% have moderately complex lesions, and 15% have complex
lesions. The learning objectives of this lecture are: 1) Understand the pathophysiology of common congenital heart
diseases and its impact on anesthetic management for non-cardiac surgery; 2) Understand the most common non-
cardiac surgical procedures in patients with congenital heart disease; 3) Understand the updated SBE prophylaxis
guidelines from the American Heart Association.
Basic Approach to Congenital Cardiac Lesions
One practical approach to assessing patients with CHD is to ask the following questions: 1. Is the patient cyanotic,
with either obligatory right-to-left intracardiac shunting, or mixing lesions? And if cyanotic, does the patient have a
functional single ventricle? If acyanotic is this a left-to-right shunting lesion, or an obstructive lesion? 2. Has the
patient undergone corrective or palliative surgery, and if so, what is the resulting anatomy and residual defects? 3.
What is the patients current status: well compensated with no limitations, moderately well compensated with few
limitations, or poorly compensated with significant limitations? 4. What is the proposed procedure and what
anticipated effects will the procedure and anesthetic management have on the patients pathophysiology? 5. Does
this patient need infective endocarditis prophylaxis?
Pathophysiology of Common Cardiac Lesions
The common complex and moderately complex cardiac lesions include: Tetralogy of fallot (incidence 9-14% of
CHD), transposition of the great arteries (10-11%), atrioventricular septal defects (4-10%), coarctation of the aorta
(8-11%), hypoplastic left heart syndrome (4-8%), and ventricular septal defects (VSD)(10-20%). All of these
lesions, with the exception of transposition of the great arteries, have a wide range of anatomical abnormality
ranging from relatively mild, to severe, which must be assessed and which have great influence on the patients
symptomatology and anesthetic considerations.
Tetralogy of Fallot
Tetralogy of fallot (TOF) consists of 1) large subaortic VSD, 2) right ventricular outflow tract obstruction/
pulmonary stenosis, 3) right ventricular hypertrophy, 4) right sided aortic arch (present in 25% of patients). In the
unrepaired TOF patient, pathophysiology depends on the degree of right ventricular outflow tract (RVOT)
obstruction. With significant RVOT obstruction, infundibular spasm constricts the RVOT, limiting blood flow into
the pulmonary artery, forcing blood right to left across the VSD and resulting in significant arterial desaturation, or
Tet spells. These spells are incited by catecholamine release due to pain, stress, light anesthesia, and emotional
upset in the infant. Many of these patients receive oral propranolol to prevent these spells. Treatment involves
intravascular volume administration to increase RV stroke volume, increasing sedation or anesthesia, avoidance of
exogenous catecholamines, increasing FiO
2
, and increasing systemic vascular resistance to force blood left-to-right
across the VSD and out the RVOT, increasing pulmonary blood flow and thus oxygenation. Surgical treatment of
TOF with pulmonary atresia or significant pulmonary stenosis with spells involves either placing a systemic to
216
Page 2
pulmonary artery shunt in early infancy followed by a complete anatomic repair at 6-12 months, or complete repair
in early infancy. Patients without cyanotic spells are normally repaired at 6-12 months. It is important to note that
repaired TOF patients often have residual defects, usually involving varying degrees of pulmonary insufficiency, or
residual RVOT obstruction. Assessment of these patients with periodic echocardiography or cardiac MRI is
important, and planning the anesthetic should involve review of these data. Teenage or adult TOF patients may have
RV dilation and are prone to ventricular arrhythmias.
D-Transposition of the Great Arteries
In this lesion the great arteries fail to rotate and the aorta and coronary arteries arise from the right ventricle, and the
pulmonary artery from the left ventricle. D- refers to dextro- meaning the aorta is rightward and anterior to the
pulmonary artery. About 85% of these patients have an intact ventricular septum and 15% have a VSD. Since the
systemic venous blood is recirculated to the RV and the aorta and is not oxygenated by this pathway, adequate
arterial saturation depends on mixing between right and left sides of the heart, either at the VSD level, atrial septal
defect level, or patent ductus arteriosus. For this reason, neonates with significant desaturation undergo a balloon
atrial septostomy, which creates a much larger communication at the atrial level and normally increases oxygen
saturation to the 80-90% range. Standard surgical treatment since the mid-1980s has been the arterial switch
operation, which includes translocation of the coronary arteries and leaves the normal physiology. The vast majority
of infants do very well and have little if any residual defect, and thus can be treated as a well-compensated,
corrected CHD patient. Residual problems might include coronary artery ischemia due to anatomic problems with
the re-implanted coronary arteries, or regurgitation or stenosis in the neo-artic root. Older patients with D-TGA
repaired before the mid-1980s most often had the Mustard or Senning operations, which both re-routed the blood
flow at the atrial level, leaving the aorta arising from the RV and pulmonary artery from the LV. These patients are
now adults, and most have significant problems including systemic ventricle failure, as the RV is inadequate as a
systemic pump; and frequent significant atrial arrhythmias from the atrial suture lines. These patients require
thorough preoperative evaluation by a cardiologist addressing ventricular function and arrhythmias.
Atrioventricular Septal Defects
Atrioventricular septal defects (AVSD) are classified as partial, intermediate or transitional, and complete. AVSD
are also known as atrioventricular canals (AVC), and derive from a deficiency or absence of the endocardial cushion
during cardiac development. Partial AVC consist of a primum atrial septal defect, no VSD, and separate
atriventricular valves with a cleft mitral valve. These defects have pathophysiology similar to that of a large atrial
septal defect (ASD), and thus are rarely symptomatic in infancy, and are usually repaired at age 2-4 years. Residual
mitral stenosis or regurgitation may be encountered. Intermediate or transitional AVC has a primum ASD, common
single atrioventricular valve, often with regurgitation, and a small or absent VSD component. These patients are also
usually not symptomatic in infancy and are repaired at 2-4 years of age, and also may have residual mitral valve
disease. Complete AVC have both a large primum ASD, and VSD component and common atrioventricular valve.
These patients have very large left-to-right shunts in infancy, and develop congestive heart failure that necessitates
repair before 6 months of age. Residual mitral or tricuspid valve regurgitation may be problematic for these patients.
The majority of CAVC patients also have Trisomy 21, and these patients develop severe pulmonary hypertension
earlier than patients with CAVC and normal chromosomes. If these patients are not repaired in the first several years
of life, the high pressure and flow in their pulmonary arteries may result in significant muscular development in
smaller and more distal pulmonary arteries, and then produce severe pulmonary hypertension, that is equal to or
even higher than systemic pressures. This results in right-to-left shunting, increasing cyanosis, and eventually results
in Eisenmengers Syndrome, which denotes irreversible, fixed pulmonary hypertension. These patients are at high
risk for anesthesia for any procedure. With early repair of CAVC that is offered to all patients, this syndrome is seen
much less frequently over the past two decades.
Coarctation of the Aorta
Coarctation is a narrowing of the aorta most commonly in the juxtaductal area, or opposite the insertion of the
ligamentum arteriosum near the left subclavian artery. As with nearly all congenital defects, there is a wide range of
anatomy and patients may present as neonates in cardiovascular collapse when their patent ductus arteriosus closes
if they have a very tight coarctation, or may not present until later in childhood with milder forms of coarctation.
Later presentation is usually with hypertension in the right upper extremity; patients may also have a soft systolic

216
Page 3
murmur, or continuous murmur over the back due to development of extensive arterial collaterals which form to
increase blood flow to areas below the coarctation. Repair is normally done as soon as the coarctation is diagnosed,
usually via left thorocotomy by direct end-to-end anastomosis after resection of the coarctation segment. Residual
coarctation may occur and is usually treated with balloon angioplasty and stenting in the cardiac catheterization
laboratory. Patients may have residual hypertension, and adults with late treatment of coarctation often have severe
coarctation, early coronary artery disease, and are prone to cerebral vascular accidents. Most repaired patients,
however, have essentially normal cardiac function when presenting for non-cardiac procedures.

Hypoplastic Left Heart Syndrome

This syndrome (HLHS) has varying degrees of underdevelopment of the left ventricle, and has either significant
stenosis, or atresia of both the aortic and mitral valves, resulting in very limited or no flow through the left ventricle
and aortic valve. At birth systemic blood flow is dependent on a patent ductus arteriosus (maintained by
prostaglandin E1 infusion) to supply blood flow to the lower body, and to augment blood flow to the brain and
coronary arteries in a retrograde manner. Since the mid 1980s these patients have survived in increasing numbers,
and now there are teenagers and even young adults with HLHS presenting for anesthesia for non-cardiac procedures.
The initial surgical palliation involves reconstruction of the aorta by using the native pulmonary valve, native aorta,
and augmenting the repair with a cryopreserved homograft patch to create a neo-aorta to provide systemic blood
flow, which arises from the single right ventricle. An atrial septectomy must be performed to allow unimpeded flow
of blood from left atrium to right atrium to bypass the hypoplastic left heart. And, since the pulmonary valve has
been used to construct the neo-aorta, a new source of pulmonary blood flow is provided, either a small 3-4 mm
systemic to pulmonary artery shunt, or a larger right ventricle to pulmonary artery shunt. In either case, the single
systemic RV in parallel with the pulmonary circulation, bridged by a shunt, is inherently unstable, and
hemodynamic stability depends on balancing pulmonary to systemic flow ratio to approximately 1:1. Excessive
pulmonary vasodilation with high FiO
2
, or low PaCO
2
will steal flow from the systemic and coronary circulations,
often resulting in myocardial ischemia and a vicious cycle ending in cardiac arrest. These patients are most
precarious after the neonatal Stage I Norwood palliation, and unfortunately often need non-cardiac procedures such
as fundoplication and gastrostomy tube, during this period. These patients must be managed carefully during non-
cardiac procedures, and should be cared for in an intensive care setting after most procedures.

The second stage of the palliation sequence for HLHS is a bidirectional cavopulmonary connection done at 2-6
months of age, where the systemic-pulmonary, or RV-pulmonary shunt is replaced by direct anastomosis of the
superior vena cava to the right pulmonary artery. This greatly stabilizes the circulation by unloading the systemic
single ventricle by diverting SVC flow directly to the lungs, resulting in much improved myocardial function.
Although the balance of pulmonary to systemic flow is still a consideration at this stage, and hyperventilation will
result in hypocarbia, decreased cerebral blood flow and thus decreased SVC and PA flow which results in arterial
desaturation, it is after the bidirectional cavopulmonary connection that elective non-cardiac procedures should be
performed. These may include procedures such as cleft lip and palate repair, craniosynostosis repair, or other
common procedures.

The third stage of HLHS palliation is the Fontan operation, whereby the inferior vena cava blood is routed to the
pulmonary arteries, bypassing the right ventricle to form a total cavopulmonary connection, either intracardiac
(lateral tunnel Fontan), or by an extracardiac conduit. This is normally performed at 18 months-4 years of age and
results in a patient with a completely unloaded systemic single right ventricle, and no pumping chamber for the right
side of the heart. Instead, blood flow into the thorax and out through the pulmonary arteries depends on the small
transpulmonary pressure gradient from the vena cavae into the pulmonary arteries, across the lungs, and into the
pulmonary veins. This flow is augmented by normal breathing and its negative thoracic pressure augmenting the
transpulmonary pressure gradient. After the Fontan operation, signs and symptoms of right sided cardiac failure may
occur, such as pleural effusions, ascites, and lower extremity edema. Although after the Fontan the patient may no
longer be cyanotic, because of the high right sided pressures a 3-5 mm fenestration is often created in the Fontan
tunnel, to lower right sided pressures. Systemic cardiac output is augmented at the expense of a small amount of
right to left shunting, producing patients with varying degrees of desaturation. It is important to determine if the
patient has a fenestration when presenting for an anesthetic. After the Fontan operation, patients may be intolerant
of excessive positive pressure ventilation as commonly perfomed during general endotracheal anesthesia, because it
reduces the transpulmonary pressure gradient and thus flow into the Fontan circuit, resulting in low cardiac output.

216
Page 4
In addition, hypovolemia from prolonged fasting, third space loss, or blood loss is not well tolerated. These patients
merit careful evaluation and planning for anesthesia, and should be monitored postoperatively in an intensive care
setting after major interventions.

Other forms of single ventricle such as tricuspid atresia have been treated with the Fontan operation since the
1970s. These patients are often adults with the older Fontan configurations, such as a direct atriopulmonary
connection between the right atrial appendage and the pulmonary artery. These patients often have severe refractory
atrial arrhythmias and signs of significant right heart failure. Before anesthesia these patients need careful
evaluation, and many undergo Fontan conversion to a more hemodynamically favorable arrangement, or heart
transplant.

Ventricular Septal Defects

VSDs are the most common single isolated defect, and are a component of many more complicated defects as well.
In isolation, VSDs range from tiny asymptomatic muscular VSDs seen at birth that close spontaneously, to large or
multiple Swiss cheese defects in the ventricular septum that produce severe symptoms and signs of congestive
heart failure in early infancy. The degree of left to right shunting depends on the size of the defect, and the relative
ratios of pulmonary to systemic pressure and resistance and the compliance of right and left ventricles. Neonates and
infants with large unrepaired defects may have significant cardiomegaly and myocardial dysfunction, and in addition
if intubated and hyperventilated with high FiO
2
may deteriorate further from increased pulmonary blood flow, steal
from the systemic blood flow, and further increases in end-diastolic volume. Patients with large defects who are
unrepaired can progress to Eisenmenger Syndrome. Patients with smaller defects are much more hemodynamically
stable, and patients with repaired VSDs and no residual defects most of ten have normal myocardial function and
can be treated as corrected well compensated patients for non-cardiac procedures.

Common Simple Lesions

Atrial Septal Defect

This common lesion may be essentially asymptomatic and not diagnosed until adulthood in some patients. The three
major types are: 1. primum ASD which is low in the atrial septum and usually associated with atrioventricular canal
and repaired in the first five years of life; 2. secundum ASD in the center of the atrial septum, often closed in the
cardiac catheterization laboratory with ASD closure devices; 3. sinus venosus ASD, high in the atrial septum near
the superior vena cava and most often associated with partial anomalous pulmonary venous return. The latter two
types of ASD may be undiagnosed until adulthood; pulmonary vascular disease usually will not develop until the 4
th

or 5
th
decade or later. These patients may come to medical attention because of transient ischemic attacks or strokes
due to right to left movement of platelet fibrin thrombi during valsalva maneuver. If unrepaired, besides assessment
for cardiac symptoms, meticulous attention needs to be paid to avoid introduction of air via intravenous infusion, or
during the surgical procedure itself.

Patent Ductus Arteriosus

A small patent ductus arteriosus (PDA) is usually asymptomatic, and may not warrant treatment. Larger PDA
produce significant left to right shunting, and are closed, often in the cardiac catheterization laboratory with PDA
closure devices. Large PDA are often components for more complex cardiac lesions and are addressed during
surgery. If isolated and not suitable for catheterization laboratory closure, they are closed via left thoracotomy, and
the patient is treated as a well compensated simple cardiac patient for future anesthetics. If a PDA is large, and not
closed in childhood, pulmonary vascular disease and even Eisenmenger Syndrome can develop, and these patients
are approached with great caution.

Preoperative Evaluation

A thorough history and physical examination, focusing on cardiac signs and symptoms, previous surgical and
catheterization procedures, and available data such as recent echocardiograms, is important for all patients with
CHD presenting for non-cardiac procedures. Cardiac rhythm status is important to determine, especially in older
patients with residual defects or in single ventricle patients. Common medications in the CHD population include

216
Page 5
ACE inhibitors for single ventricle patients, or those with significant CHF or mitral regurgitation; beta blockers for
TOF patients or those with atrial arrhythmias such as paroxysmal supraventricular tachycardia; amiodarone for
patients with significant atrial or ventricular arrhythmias; and diuretics for patients with CHF. Digoxin is rarely used
in the modern era because of its lack of effectiveness in either the adult or pediatric population. Endothelin
antagonists, phosphodiesterase-5 inhibitors, or prostaglandin analogs are used in pulmonary hypertensive patients.
Many patients with CHD are taking aspirin or other antiplatelet therapies to decrease risk of thrombus formation in
shunts or conduits. Finally, some patients are taking coumadin for mechanical cardiac valves, which will merit
careful planning of perioperative anticoagulation regimens. Many patients, particularly adults with CHD will have
implanted transvenous or epicardial pacemakers or automated defibrillators, and it is critical to understand the
patients underlying cardiac rhythm, the reason for placement of the device, and the current modes and settings of
the device.

Echocardiography is the mainstay of diagnostic testing in the CHD population, and the latest echocardiography
results should be reviewed. If there is any history of cardiac rhythm abnormality a recent ECG or Holter
examination should be reviewed. Cardiac catheterization is most often performed for interventional procedures, but
valuable diagnostic data is also available from this modality. Cardiac MRI has assumed an increasingly important
role to assess anatomy, function, and progression of pathophysiology, and results should be reviewed.

A frequent question in the preanesthetic evaluation of the CHD patient for non-cardiac procedures is whether the
patient should be evaluated by their cardiologist prior to the procedure. In general, if the patient has a simple or
moderately complex lesion that has been completely corrected and is well compensated and so is followed by their
cardiologist on an infrequent basis, a standard preanesthetic visit without a cardiology consultation is appropriate. A
patient with a moderately complex lesion who is not well compensated, any cyanotic or single ventricle patient or
patient with a complex lesion needs a recent cardiology evaluation that usually includes at least an echocardiogram,
within no more than 3-6 months before the surgery. If the patients condition has changed significantly since the last
evaluation, they should be seen again by the cardiologist.

In general, all cardiac medications should be continued through the perioperative period for most types of surgeries.
Low dose ASA use is not a contraindication for most simple, superficial surgeries, but if the surgery is major,
including intracranial, a discussion with the patients cardiologist and surgeon should take place and ASA is usually
stopped 7-10 days preoperatively. Standard NPO orders apply to the CHD population including clear liquids up to 2
hours before anesthesia, breast milk up to 4 hours before, and infant formula, milk, or solids up to 6 hours before. It
is critically important that patients with cyanotic lesions, shunt-dependent patients, and those with outflow tract
obstruction are not left NPO for long periods of time. Hypovolemia can be a critical problem for these patients,
especially with induction of anesthesia and institution of positive pressure ventilation. These patients should be
scheduled early in the day, and if there are delays should be fed clear liquids until 2 hours before induction.

Conduct of Anesthetic

The setting for the non-cardiac procedure for the well compensated patient with a simple or moderately complex
lesion can be in a normal well equipped and staffed community hospital setting. However, with less well
compensated patients and complex and single ventricle patients, the procedures should be done in centers with
expertise in CHD, and necessary backup support in case these patients deteriorate. In general, the more complex
patients can have outpatient surgery, but admission to the hospital must be readily available. For complex patients
having major surgery, postopertative care in an ICU is essential and must be planned in advance.

Standard monitors including ECG, non-invasive blood pressure, pulse oximetry, and capnography are essential for
all procedures, including diagnostic imaging procedures, where end-tidal CO
2
can be monitored via a nasal cannula
for sedation procedures. The decision to institute more invasive monitoring such as invasive arterial pressure, central
venous pressure, continuous central venous oxygen saturation monitoring, or cerebral/somatic near-infrared
spectroscopy for brain and tissue oxygenation, is anesthesiologist-dependent to a large extent and depends on the
assessment of the potential for hemodynamic and respiratory instability due to the patients pathophysiology and the
invasiveness of the planned procedure. Patients with significant baseline myocardial dysfunction, pulmonary
hypertension, or cyanosis often benefit from preoperative intravenous access if possible.

216
Page 6
Any anesthetic and sedation technique may be used in CHD patients, with careful attention to the particular
pathophysiology of the patient and the desired hemodynamic goals. Premedication, often with oral midazolam, is
well tolerated. Since halothane is no longer available, inhalation induction with sevoflurane is appropriate and well
tolerated for many CHD patients. Propofol may be used for induction and maintenance in CHD patients, with
careful attention to veno- and vasodilation produced by this agent. Ketamine, either IM or IV, is a very useful agent
for many of these patients, preserving myocardial function and providing sedation and analgesia. Etomidate has little
effect on myocardial contractility and hemodynamics, and is an excellent agent for the patient with impaired
myocardial function. Dexmedetomidine is increasingly used for sedation in patients with CHD, and is usually well
tolerated if the patient can withstand the bradycardia, and hypotension that sometimes results from the use of this
agent. Any opioid can be used, and single shot caudal and nerve block techniques can also be used, even with low
dose ASA use. Major neuraxial techniques, i.e. lumbar/thoracic epidural and spinal are best avoided with ASA use.

Airway management may range from sedation with spontaneous respiration, to mask or LMA general anesthesia, to
endotracheal anesthesia, again being mindful of the effects of hyper- or hypocarbia, and postive pressure ventilation
for the individual patient. With endotracheal anesthesia, the decision to extubate at the end of the procedure of
course must take into account the severity of the underlying pathophysiology, and the magnitude of the surgical
procedure. In single ventricle infants undergoing major abdominal procedures, for example, it is very often prudent
to ventilate the patient in the early postoperative period.

Pacemakers and defibrillators must be interrogated before the procedure, and a discussion held with the patients
cardiologist as to the underlying cardiac rhythm and reason for placing the device. In general, the pacemaker should
be converted to asynchronous mode just before the surgery, to avoid electrocautery interference inhibition of the
pacemaker in demand mode. The defibrillator function must also be turned off, and external defibrillator capability
immediately available. The device settings are restored as soon as possible after the completion of the procedure.

Common Non-Cardiac Procedures

Although CHD patients may undergo any surgical or diagnostic procedure, there are several common procedures
that merit discussion. Young CHD patients often present for dental restorations and extractions under general
anesthesia, due to the need for excellent dental hygiene to prevent infective endocarditis. A thorough preoperative
evaluation is essential, and these procedures must be performed in the hospital setting with adequate expertise and
backup in case of decompensation. Laparoscopic procedures such as fundoplication and gastrostomy tube, and
cholescystectomy, are performed in CHD patients, but careful attention must be paid to the effects of CO
2

insufflation on PaCO
2
, and increased intra-abdominal pressure. The combination of acute hypercarbia and decreased
venous return is not well tolerated by single ventricle infants and patients with a Fontan circulation, and careful
monitoring, or consideration for an open procedure are important. Scoliosis surgery is often done in patients with
CHD, and must be very carefully planned, especially in patients with the Fontan circulation, who do not tolerate
hypovolemia and hypotension. Careful monitoring, blood and volume replacement, and careful consideration of
anesthetic technique in light of the need for spinal cord monitoring must be performed for these complicated
patients. Craniofacial surgery, especially cleft lip and palate, and craniosynostosis repair, are done in the CHD
population, with careful consideration for prevention of air embolus, and monitoring and replacing blood loss. As
noted above, in single ventricle infants, elective surgery is best performed after the cavopulmonary connection,
which yields a much more stable circulation to withstand the stresses of major surgery. Diagnostic imaging
procedures, especially MRI, are commonly performed in the CHD population, and either sedation or general
anesthesia techniques can be used, again with careful attention to the hemodynamic and respiratory goals of each
individual patient.

Infective Endocarditis Prophylaxis

The American Heart Association significantly changed its guidelines for prevention of infective endocarditis (IE) in
2007, resulting in a narrowing of the indications for administering IE prophylaxis. This has resulted in confusion for
patients, parents, surgeons, and even cardiologists, and it is important to understand the new indications, which were
based on an extensive review of the data and discussions among a large panel of experts. The patient must have
BOTH a cardiac indication, and a surgical/procedural indication. The major cardiac indications are: 1. prosthetic
cardiac valve or material; 2. previous IE; 3. congenital heart disease, but ONLY a) unrepaired cyanotic CHD
including palliative shunts and conduits; b) completely repaired CHD with prosthetic material or device during the

216
Page 7
first 6 months after the procedure; c) repaired CHD with residual defects at or near the site of a prosthetic patch or
device; 4. cardiac transplant recipients who develop valvulopathy. The surgical/procedural indications are 1. all
dental procedures that involve manipulation or the gingival tissue or perforation of the oral mucosa; 2. respiratory
tract procedures or procedures on infected skin, or musculoskeletal tissue. IE prophylaxis is not recommended for
simple gastrointestinal or genitourinary procedures where the mucosa is not incised, i.e. simple endoscopy and
cystoureteroscopy, but is recommended for surgery where mucosa is incised. For dental prophylaxis, a single dose
of ampicillin 30-60 minutes before the procedure, or as soon as IV access is obtained, is the recommended regimen,
with clindamycin, cefozolin, or ceftriaxone acceptable for penicillin allergic patients.

Summary

The large and growing population of patients who are living with CHD requires anesthesia care for the same types
of non-cardiac surgeries and other procedures as the non-CHD population, and anesthesiologists will increasingly
care for these patients in a variety of settings. Knowledge of the pathophysiology of the common CHD lesions, as
well as careful preoperative assessment and preparation, and communication with the patients cardiologist and
surgeon, are essential to provide optimal care in the best setting for these patients.

Bibilography

1. Baum VC, Barton DM, Gutgesell HP. Influence of congenital heart disease on mortality after noncardiac surgery
in hospitalized children. Pediatrics 2000; 105: 332-5.
2. Ramamoorthy C, Haberkern CM, Bhananker SM, et al. Anesthesia-related cardiac arrest in children with heart
disease: data from the Pediatric Perioperative Cardiac Arrest (POCA) registry. Anesth Analg. 2010;110:1376-82.

3. Diaz LK, Andropoulos DB. New developments in pediatric cardiac anesthesia. Anesthesiol Clin North America.
2005;23:655-76.

4. Diaz LK, Hall S. Anesthesia for non-cardiac surgery and magnetic resonance imaging. In, Andropoulos DB,
Stayer SA, Russell IA (eds.) Anesthesia for Congenital Heart Disease. Blackwell-Futura Publishing, Malden MA,
2005, pp. 427-52.

5. Dorfman AL, Odegard KC, Powell AJ, et al. Risk factors for adverse events during cardiovascular magnetic
resonance in congenital heart disease. J Cardiovasc Magn Reson. 2007;9:793-8.

6. Friesen RH, Williams GD. Anesthetic management of children with pulmonary arterial hypertension. Paediatr
Anaesth. 2008 Mar;18(3):208-16.

7. Williams GD, Maan H, Ramamoorthy C, et al. Perioperative complications in children with pulmonary
hypertension undergoing general anesthesia with ketamine. Paediatr Anaesth. 2010;20:28-37.

8. Hedequist DJ, Emans JB, Hall JE. Operative treatment of scoliosis in patients with a Fontan circulation. Spine.
2006 Jan 15;31:202-5.

9. Hennein HA, Mendeloff EN, Cilley RE et al. Predictors of postoperative outcome after general surgical
procedures in patients with congenital heart disease. J Pediatr Surg 1994;29: 866-70.
10. Kipps AK, Ramamoorthy C, Rosenthal DN, et al. Children with cardiomyopathy: complications after noncardiac
procedures with general anesthesia. Paediatr Anaesth. 2007;17:775-81.

11. Roger VL, Go AS, Lloyd-Jones DM,et al. Heart disease and stroke statistics--2012 update: a report from the
American Heart Association. Circulation. 2012;125:188-97.
216
Page 8
12. Prez-Caballero C, Sobrino E, Vzquez JL, et al.Complication of surgery for scoliosis in children with surgically
corrected congenital cardiac malformations. Cardiol Young. 2009 ;19:272-7.
13. American Society of Anesthesiologists. Practice advisory for the perioperative management of patients with
cardiac implantable electronic devices: pacemakers and implantable cardioverter-defibrillators: an updated report by
the american society of anesthesiologists task force on perioperative management of patients with cardiac
implantable electronic devices. Anesthesiology. 2011;114:247-61.
14. Slater B, Rangel S, Ramamoorthy C, et al. Outcomes after laparoscopic surgery in neonates with hypoplastic
heart left heart syndrome. J Pediatr Surg. 2007;42:1118-21.
15. Stayer SA, Andropoulos DB, Russell IA. Anesthetic management of the adult patient with congenital heart
disease. Anesthesiol Clin North America. 2003;21:653-73.
16. Warner MA, Lunn RJ, OLeary PW et al. Outcomes of noncardiac surgical procedures in children and adults
with congenital heart disease. Mayo Clin Proc 1998; 73: 728-34.
17. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with
congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines. J Am Coll Cardiol. 2008;52:e1-121.
18. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American
Heart Association. Circulation. 2007;116:1736-54.
19. Shukla AC, Almodovar MC. Anesthesia considerations for children with pulmonary hypertension. Pediatr Crit
Care Med. 2010 Mar;11(2 Suppl):S70-3.
20. van der Griend BF, Lister NA, McKenzie IM, et al. Postoperative mortality in children after 101,885 anesthetics
at a tertiary pediatric hospital. Anesth Analg. 2011;112:1440-7.
21. Galante D. Intraoperative management of pulmonary arterial hypertension in infants and children--corrected and
republished article. Curr Opin Anaesthesiol. 2011;24:468-71.
22. Seal R. Adult congenital heart disease. Paediatr Anaesth. 2011;21:615-22.
Disclosure
220
Page 1
Anesthetizing the Neonate for Surgical Emergencies: Avoiding Common Errors
Samuel H. Wald , M.D. Los Angeles, California
What are the Surgical Emergencies?
Congenital Diaphragmatic Hernia (CDH)
CDH most often occurs as a postero-lateral Bochdalek hernia requiring emergent surgical closure. The
compressive effects of abdominal viscera in the chest cavity impede cardiopulmonary development. The transition
from fetal to neonatal circulation may be affected as lung growth is harshly reduced. The degree of hypoplasia of
the lung is inversely related to the gestational age of the presence of the hernia. With delivery of the neonate, acute
and extreme respiratory distress is almost always present because of the pulmonary hypoplasia.
Specific concerns include those related to the management of viscera in the chest cavity and poor
pulmonary structure and function. Mask ventilation should be avoided in order to reduce the risk of insufflating the
stomach and abdominal contents. Low peak pressures should be used for ventilation in order to avoid
pneumothorax. ECMO may need to be instituted depending on the response to intubation and ventilation as may
Nitric Oxide therapy for pulmonary hypotension.
Tracheoesophageal Fistula (TEF)/Esophageal Atresia (EA)
TEF/EA may be associated with other congenital anomalies and EA is almost always accompanied by TEF.
One group of abnormalities is the VACTERL complex: Vertebral, imperforate Anus, Congenital heart disease, TEf,
Renal and Limb. The repair may be completed in one surgical procedure or staged. In the staged procedure, a
gastrostomy tube is placed first with a later repair of the fistula.
Specific concerns include the limitation of further insufflation of the stomach (increasing the risk of
aspiration) and proper placement of an endotracheal tube. The goal is to minimize positive pressure ventilation
before the fistula is ligated. This is accomplished by intubation with spontaneous ventilation (sedated or general
anesthesia) and placement of the endotracheal tube with the tip below the fistula, but above the carina (if possible).
Multiple techniques using a vented gastrostomy tube, auscultation and rigid or flexible bronchoscopy can be used.
After the repair the benefit of decreased intra-tracheal pressure with early extubation must be balanced with the risk
of re-intubation and rupture of the surgical repair of the tracheal or esophagus.
Gastroschisis/Omphalocele
The neonate with gastroschisis presents with the abdominal viscera herniated and exposed to air after
delivery and is usually and isolated lesion. Omphalocele is associated with other anomalies including, cardiac,
genetic, urologic and metabolic (Beckwith-Wiedermann) and viscera are covered with a sac.
Specific considerations are directed at maintaining perfusion of the bowel, fluid resuscitation and careful
staging of reduction with pulmonary function. Surgical closure of the abdominal contents must be carefully
monitored with changes in pulmonary compliance in order to prevent an abdominal compartment syndrome.
220
Page 2
Intestinal Obstruction/Atresia/Nectrotizing Enterocolitis (NEC)
Intestinal obstruction and atresia may be associated with other anomalies and prematurity. As noted above,
imperforate anus may be part of the VACTERL constellation of abnormalities. Bowel obstruction requires
consideration of aspiration precautions with induction of anesthesia and intubation. NEC is more likely to occur in
premature neonates and may have associated septic phenomena and coagulation disorders requiring aggressive
management. Fluid resuscitation is also an important aspect of the care of these neonates especially those with
gastric losses.
Meningomyelocele
Meningomyelocele is a defect in the spine with both CSF and spinal tissue. Associated hydrocephalus and
Chiari malformation is also common. The emergent nature is to reduce the risk of infection.
The specific considerations include the positioning of the neonate for induction and intubation and the
avoidance of latex. Latex precautions are taken because of the high likelihood of a neurogenic bladder and the need
for frequent exposure to medical procedures and daily bladder catheterization. Intubation may be performed in the
supine position with protection of the defect and contents or in the lateral decubitus position.
Teratoma
Teratomas may be highly variable in size and location containing both solid and cystic components. The
morbidity is related to high output cardiac failure, airway obstruction/mass effect and blood los during resection.
Considerations include the possibility of a difficult airway or a difficult intubation due to positioning and a
high risk of massive blood loss.
General Considerations for Care of the Neonate
Over the past 50 years, major improvements have been made in the overall survival of neonates requiring
emergency surgery. This is likely due to the presence of neonatal surgeons and their dissemination of knowledge
and the parallel growth of pediatric anesthesia. Besides the technological advances, it is the understanding of
neonatal physiology that has allowed for the enhanced care of this special population of patients. In 1949, the
surgical mortality in neonates was 72% and now after the year 2000, survival rates are in the range of 85-95%. For
example, esophageal atresia has changed from 100% mortality to an 80% survival rate due to the modern
perioperative management of high-risk neonate. Gastroschisis carried a 100% mortality now with a staged closure
has a 90% survival. The growth of pediatric anesthesia has played a role in these advances.
In order to care for any neonate and understanding of neonatal physiology is essential and the constant
feature is change. The neonatal period is a time of physiologic translational tasks, which may acutely change during
the peri-operative period. The premature infant has not yet finished development and must now more rapidly
complete the transition.
Physiology Matters
Temperature
Both term and premature neonates are thermogenically active. In order to maintain constant temperature,
infants exposed to a cold environment increase their metabolic activity and heat production without shivering. This,
however, has high energy and oxygen costs. Heat loss is favored due to the neonatal body habitus of reduced
subcutaneous fat and large surface area to body ratio. Neonates have limited shivering and non-shivering
thermogenesis (brown fat) at high risk for temperature losses in the peri-operative period. Survival of premature
neonates is directly related to ambient temperature.
The goals should be a neutral thermal environment. This is facilitated by use of heated transport, warm
solutions, warm blood, heated mattress, radiant warmer and forced air hearting
220
Page 3
Oxygen
Neonates are characterized by a high consumption of oxygen, low Functional Residual Capacity (FRC),
immature airway and respiratory structures. The chest is highly compliant with weak musculature. They are
extremely sensitive to any impediment of diaphragmatic movement. Their immature response to hypoxia means that
they have unstable respiratory control and are prone to apnea. In contrast to older infants and adults they will
decrease their respiratory rate in response to hypoxia. This paradoxical response to hypoxia is exacerbated by
hypothermia and they also have a poor response to carbon dioxide. Too much oxygen is also a consideration for the
prevention of Retinopathy of Prematurity (ROP). ROP is progressive vascular overgrowth of the retinal vessels and
may lead to intraocular hemorrhage, retinal detachment and blindness. It is recommended to minimize inspired
oxygen up to infants until they are 46 weeks in post-conceptual age.
Cardiac Function
The transitional circulation is a mix of the adult series circulation and fetal parallel circulation due to the
Patent Ductus Arteriosus and the possible presence of a Patent Foramen Ovale. The conversion complete series
circulation may be disrupted by hypoxia, hypercarbia, acidosis, hypothermia, stress and prematurity. It is therefore
important to avoid and of these disturbances as much as possible during transport and surgery.
Specific attention should be paid the balance of Systemic Vascular Resistance and Pulmonary Vascular
Resistance. Imbalances in either direction will change the course of flow and amount of shunt. Left to right shunt
will result in pulmonary edema and a low-cardiac output state. Right-to-left shunt will produce cyanosis and
acidosis potentiating further interruption of complete transition.
The cardiac muscle is immature which results in limited cardiac compliance and rate dependence for
cardiac output. Steps to prevent bradycardia are needed in the care of the neonate. The autonomic nervous system
is also immature at birth.
Fluid Management
The neonatal renal system is limited in the ability to concentrate urine, but able to dilute urine. This results
in excess sodium and free water losses. Glomerular Filtration Rate (GFR) is significantly decreased, but increases
over the first 4 weeks of life. There is therefore delayed excretion of drugs that are dependent on GFR. Surgical
losses are isotonic (blood and insensible) so using hypotonic replacement will lower serum osmolality.
Neonates and premature infants are at specific risk for hypoglycemia. There are no glycogen stores until
beyond the neonatal period. The guideline from the American Academy of Pediatrics is to maintain glucose levels
above 45 mg/dl. If glucose supplementation is needed, D10W in a 1-2ml/kg bolus can be given.
Assessment of intravascular volume should be continuous. If the heart rate is persistently elevated vs.
variance with surgical stimulation this may indicate intravascular hypovolemia. Other indicators are a narrow pulse
pressure, blood pressure variability with positive pressure, cool extremities and poor capillary refill in addition to
decreased urine output. An initial maneuver would be to check response to a fluid bolus of 10-20 ml/kg.
Coagulation studies including INR/PT/PTT are abnormal at baseline in the neonate. The PT and PTT are
prolonged due to vitamin K deficiency. Fibrinogen and Factor V are at adult levels at birth. However, acute illness
such as a surgical emergency may present with hemorrhagic bleeding. Also, premature infants at increased risk for
intraventricular hemorrhage. In general blood volume estimations are as follows:
Premature Infant-100ml/kg
Term Infant-90 ml/kg
Comorbidities such as cyanotic heart disease and prematurity may require a higher hemoglobin than other
neonates for a similar procedure due tan in increased metabolic demand are the dilution of oxygen content sue to
right-to-left shunt. Transfusion will easily result in calcium deficiency due to citrate. Blood storage results in
potassium release from red blood cells, which increases with the age of the unit. Hyperkalemia is a well-known
complication of transfusion in neonates and infants and the use of washed red-blood cells should be considered.
220
Page 4
Pharmacology and the Neonate
When compared to adults the action of anesthetics may be different due to the immature Blood Brain
Barrier (BBB). Permeability to large molecules in similar, however small molecules may be more permeable to the
fetal and neonatal BBB which changes through gestation and the first weeks of life. By two months of age, the
permeability is similar to adults. Overall, the effect is increased potency of opioids in neonates.
The absorption and distribution of pharmacologic agents is affect by the total body water, total body fat and
the total protein. Because neonates have large total body water content, water-soluble drugs such as the non-
depolarizing muscle relaxants will have a larger volume of distribution. The premature infant body weight is 80%
water, the term neonate is 75% and adults are 50-55% water. It is the extracellular compartment that is
disproportionately larger rather than the intracellular one. Onset will occur faster from a small initial dose, but bolus
doses will have a prolonged effect. Of note, preterm infants less than 32 weeks post-conceptual age have a reduced
train-of-four response at baseline. Full-term neonates may have a fourth twitch at 95% as the myoneural junction is
just maturing at one month with no fade at two months (full-term). So, there is an overall sensitivity to
neuromuscular blockade. Neonates have a risk of residual block due to the three factors of the immature
neuromuscular junction, reduced type I ventilator fibers and an increased elimination half-life.
The smaller total body fat affects the lipid soluble drugs in the central nervous system and the periphery in
neonates, which does not increase until three to six months of age. Lastly, the relatively low amount of total body
protein will increase the bioavailability of protein-bound substances. Neonates have less albumin and less alpha-1
glycoprotein. This is a consideration for the use of bupivacaine if an epidural is used in the post-operative period.
Also, the threshold for bupivacaine cardiac toxicity is lower and may occur simultaneously with central nervous
system symptoms.
The hepatic enzymes involved in phase one hepatic biotransformation are at 20-50% of adult levels
depending on the specific cytochrome. The phase two enzymes are also at low levels and both increase during
childhood. Excretion is facilitated by increasing the water solubility, but because of the low GFR, may be limited to
10% of adult levels.
SELECTED REFERENCES
Adamkin DH, Committee on Fetus and Newborn, Clinical report-postnatal glucose homeostasis in late-preterm and
term infants, Pediatrics, 2011;127:575-580.
Brusseau R, McCann ME, Anaesthesia for urgent and emergency surgery, Early Human Development, 2010;86:703-
714.
Davis, PJ, Perioperative crystalloid and colloid fluid management in children: where are we and how did we get
here? Pediatric Anesthesiology, Anesthesia and Analgesia, 2010;110:375-390.
Liu LMP, Pang LM, Neonatal surgical emergencies, Anesthesiology Clinics of North America, 2001(June);19(2):1-
17.
Mellor DJ, Lerman J, Anesthesia for neonatal surgical emergencies, Seminars in Perinatology,
1998(October);22(5):363-379.
Murat I, Humblot A, Girault L, Piana F, Neonatal fluid management, Best Practice & Research Clinical
Anaesthesiology, 2010;24:365-374.
Rowe MI, Rowe SA, The last fifty years of neonatal surgical management, American Journal of Surgery,
2000;180:345-352.
Disclosure
327
Page 1
A Child with a Difficult Airway: Succeed with the Tricks of the Trade
Paul Reynolds M.D. Ann Arbor, Michigan
Introduction
Pediatric airway management can be challenging. Even though difficult airways in children are a relatively
rare phenomenon compared to adults, children with normal airways can pose problems to clinicians unaccustomed
to managing small children. A study of closed anesthesia malpractice claims suggests a higher incidence of cardiac
arrest due to loss of airways in normal children, especially less than 1 year of age (1). This may be due to the
anesthesia care providers unfamiliarity with anatomical differences between the adult and pediatric airway, as well
as the physiological and metabolic differences.
Differences between the adult and pediatric airways
Anatomical differences
Successful management in children, especially under 1 year of age, requires the anesthetist to understand
both anatomical and physiological differences between adults and children. A childs airway typically becomes
anatomically adult after 6 to 8 years of age. For maximum differentiation, I compare a neonates airway (children
under 1 month of age), to an adult. Neonates are obligate nasal breathers. Nasal obstruction for prolonged periods of
time (e.g. choanal atresia) can be fatal. Neonates also have much more narrow nares compared to adults. This can
make passage of nasotracheal tube more difficult. The nasal opening may be smaller than the laryngeal opening,
leading to a large airway leak unless a cuffed nasotracheal tube is used. Unlike an adult, the neonates tongue rests at
the roof of the mouth during quiet respiration. The tongue is also large in relation to the mouth, making both mask
ventilation and oral intubation more difficult. The neonates head is large in relation to their body. During mask
ventilation or laryngoscopy, the goal is to align the oral, tracheal and pharyngeal axis (sniffing position). In an
adult, this is accomplished by placing a pillow behind the head. However, in the neonate or infant, because of
relatively large head, a pillow should be placed behind the shoulders. The larynx is higher in the neck of a neonate
(C 3-4) when compared to an adult (C 4-5). This, in combination with a shorter neonatal neck can lead to more
difficult laryngeal visualization during direct laryngoscopy. In addition, the small mouth of a neonate requires the
use of a straight laryngoscope blade to visualize the laryngeal opening. The epiglottis in adults is broad, with its
axis parallel to the trachea, while a neonates epiglottis is long, narrow and floppy, angulated away from the axis of
the trachea. During laryngoscopy, the tip of the neonates epiglottis is lifted by the laryngoscope for glottic
visualization. Adults vocal folds are perpendicular to the axis of the trachea, while the vocal folds of a neonate have
a lower anterior attachment to the glottis than posteriorly. This can sometimes lead to difficulty in passing the
endotracheal tube through the neonates glottis.
It has been often stated the narrowest portion of the neonatal airway is at the level of the cricoid ring, as
compared to the adult, where the laryngeal opening is the narrowest. Thus, the immature larynx has a funnel shape,
compared to the cylindrical shape of the adult larynx. This is part of the rationale for the use of uncuffed
endotracheal tubes in children less than 6 years of age. If the narrowest portion of the pediatric airway is the cricoid
ring, being perfectly circular, an uncuffed tube is ideal. Conversely, the narrowest portion of the adult airway, at the
level of the vocal folds, an irregular shape, requires a cuffed endotracheal tube. Evidence of laryngeal shapes in
children was based on an article in Anesthesiology published in 1951 by Eckenhoff (2), not by a study of his own,
but an examination of 15 plaster casts made from cadaveric larynxes preserved from children, ages 4 months to 14
years, who died in 1897 (3). A study, published in Anesthesia & Analgesia by Dalal et.al (4). examined 135
anesthetized children, aged 6 months to 13 years of age, using video bronchoscopy to measure laryngeal dimensions.
The authors concluded the glottis, rather than the cricoid, was the narrowest potion of the pediatric airway. Thus,
327
Page 2
the shape of the pediatric airway was cylindrical, similar to the adult shape. This study leads to the discussion of
cuffed vs. uncuffed endotracheal tubes in children. The advantages of an uncuffed endotracheal tube include a
larger internal diameter, lower resistance to airflow, and avoidance of trauma to the subglottic region. Advantages
of cuffed endotracheal tubes include lower fresh gas flow, reduced air pollution, less inhalational agent used,
reduced risk of aspiration, avoids multiple intubations, and improved ventilation and end-tidal CO2 monitoring (5).
In a review of the current literature, Taylor et.al. (6) conclude there is strong evidence to support the use of cuffed
endotracheal tubes in children.
Physiologic differences
Neonatal oxygen consumption, as well as metabolic rate, is much higher in than in adults. To compensate,
neonatal cardiac index as well as minute ventilation are 2 to 3 times that of adult. Functional residual capacity
(FRC), is the volume of air in the lungs at the end of expiration, and is dependent on size of patient, the elasticity of
the chest wall, and inward recoil of the lungs. Neonates are smaller and have more compliant chest walls. Under
anesthesia, neonatal FRC approaches closing volumes, causing more atelectasis in a shorter period of time. These
differences in physiology translate to shorter periods of apnea tolerated in neonates before oxygen desaturation
occurs. In addition, because of the inability of children to cooperate with preoxygenation, desaturation with rapid
sequence induction can occur much quicker. The laryngoscopist not skilled in pediatric airway management has an
even shorter time to secure an airway.
What makes a pediatric airway difficult?
There are many causes for difficult airways in pediatric patients. Congenital abnormalities, such as Pierre
Robin syndrome, Goldenhars and Treacher Collins Syndrome are all examples of syndromes associated with
difficult airways. Facial or airway trauma, burns, surgical scarring or radiation therapy can all cause difficult
airways in children. Inflammatory processes such as infections or rheumatoid arthritis can predispose to airway
problems. Other diseases, including neoplasms or metabolic diseases (Mucopolysaccharidosis) can be challenging.
Obesity may also contribute to difficulty masking children. Nafiu et.al. found a positive correlation between large
neck circumference in children and upper airway obstruction both in the operating room and recovery room (7). The
goal of direct laryngoscopy is to allow a line of site from the teeth or alveolar ridge to the laryngeal opening. The
blade of the laryngoscope displaces the soft tissue in the mandible into a potential space encompassed (and
potentially restricted) by an incomplete bony ring bound posteriorly by the hyoid bone, laterally by the rami of the
mandible, and anteriorly by the mentum of the mandible. Any alteration in the shape or size of these bony structures
results in a decrease in this space that the laryngoscope can displace the soft tissues, (e.g.; Pierre Robin, Treacher
Collins). Alternatively, an increased amount of soft tissue in the area of the tongue will have the same effect, (e.g.;
macroglossia, cystic hygromas).
Diagnosis of a difficult airway
A careful history, and detailed airway examination should be obtained prior to anesthetizing a child with a
difficult airway. One should suspect a difficult airway in a child if any of the following history is elicited: noisy
breathing or stridor, variable airway related to position, problems with feeding, leading to severe coughing and
cyanosis. Additionally, an infant or child who has airway problems associated with either URI or feeding will
probably have the same problems when given sedatives or narcotics, or after induction of anesthesia. Extra
precaution should be taken if the child has a history of difficult intubation in the past. Every attempt should be made
to obtain previous anesthetic records. The physical examination of a child with a suspected difficult airway should
begin with a careful inspection of the face, looking for asymmetry, dysmorphism, or any other unusual features.
The ears, mandible and the larynx are all formed during the 9
th
week of gestation, from the same group of branchial
arches. Abnormal ears shapes may be associated with airway malformations. Nasal patency should be checked
bilaterally. The mouth opening should be assessed, as well as the size of the tongue, and Mallampatti score noted.
Mandibular size and mobility should be assessed, as well as flexion, extension and rotation of the neck. Ideally,
diagnostic studies can be performed prior to induction of anesthesia. Simple x-rays of the head and airways, as well
as CT scans can be helpful for determining boney abnormalities. MRIs are useful for imaging soft tissues;
however, the duration of the exam usually requires sedation or anesthesia in small or uncooperative children.

327
Page 3

Management of a difficult airway

If a child requires intubation, and has a known difficult airway, a well thought out plan, with alternative
measures for intubation should be planned. ASA Practice guidelines for management of the difficult airway (8) note
the pediatric patient may limit options for airway management (awake fiberoptic intubation), necessitating deep
sedation or, more commonly, general anesthesia for securing the childs airway. A survey of pediatric
Anesthesiologists in Canada (9) found inhalational anesthesia the preferred technique for pediatric patients with
difficult airways. If general anesthesia is chosen for securing the airway, one option is to induce the child with
sevoflurane, and 100% oxygen. After intravenous access is secured, oxymetazoline (Afrin nasal spray) 0.05%
solution, is sprayed into both nares to prevent epistaxis. A nasal airway with an endotracheal tube connector is
placed, and high concentrations of sevoflurane and oxygen are insufflated into the childs hypo pharynx via this
connection. A fiberoptic scope, fitted with an appropriate sized endotracheal tube, is then introduced either into the
opposite nares, or the oropharynx to facilitate tracheal intubation. If the scope has a suction channel, either suction
or a second oxygen source is attached to the channel. It is quite helpful if an assistant gently pulls the patients
tongue forward with gauze or a ringed forceps to open the pharyngeal space, and enhance visualization. A small
dose of 1 % lidocaine (less than 5 mg/kg) may be injected into the suction port of the fiberscope after it has been
positioned over the laryngeal inlet to prevent cough when inserting the endotracheal tube.

Airway devices

A number of supraglotic airways can be used to secure the airways of children with difficult airways, or
facilitate intubation of the airway. Laryngeal Mask Airways (LMA Intavent Orthofix) were invented By Dr. Archie
Brain and first used in humans in 1981. LMAs are often used to facilitate tracheal intubation in children with
difficult airways in conjunction with fiberoptic scopes (10). Since the introduction of the LMA, several other
supraglotic devices have been introduced and have been used in children with both normal and difficult airways
(11). The Proseal LMA (PLMA Intavent Orthofix) is a second generation LMA with an esophageal drain and an
integrated bite block, comes in both pediatric and neonatal sizes.

A number of airway devices have been used in children to facilitate intubation and are useful as an
alternative to direct laryngoscopy or fiberoptic intubation in children with difficult airways. A review article by
Holm Knudsen (12), compared four commercially available devices current used in the pediatric population. The
Airtraq (Prodol Meditec) is a single use device which uses an eye piece or light weight video monitor instead of line
of site between the user and laryngeal opening (as in the case of laryngoscopy). Pediatric and neonatal sizes are
available. The Glidescope Video Laryngoscope (Verathon) works on the same principal as the Airtraq, (indirect
laryngoscopy) but uses a video monitor, had disposable blades, and comes in pediatric and neonatal sizes. The
Stortz DCI Video Laryngoscope (Karl Stortz) can be used for both direct and indirect laryngoscopy has 2 Miller like
blades, sizes 0 and 1. I personally have found this device extremely helpful while intubating neonates with Pierre
Robin syndrome. The Trueview PCD Infant (Truphatek) is a reusable indirect laryngoscope with an eyepiece
(adaptable to a videocamera) with a wide magnified laryngeal view. It also has an adapter for insufflation of
oxygen. The authors conclude fiberoptic intubation is still the gold standard for pediatric difficult airways. The
Shikani Optical Stylet (SOS, Clarus Medical) has also been used to intubate children with difficult airways. Shukry
et.al. describe 3 children with difficult airways, who were successfully intubated with this device(13). The SOS
combines the benefits of a lightwand and a rigid bronchoscope.

Unexpected difficult airways

Although rare, unexpected difficult intubation in children can be devastating. As mentioned earlier, a study of
closed anesthesia malpractice claims suggests a higher incidence of cardiac arrest due to loss of airways in normal
children, especially less than 1 year of age (1). Weiss et.al. proposed an simple algorithm based on the adult
Difficult Airway Society protocol, adapted for the pediatric population (14). In addition to the algorithm, the
authors recommend each department have a pediatric airway trolley/bag, where specialized equipment is available to
manage airway emergencies in children. Rarely, a patient may deteriorate to a point where the clinician may not be
able to ventilate or secure an airway (cannot intubate/cannot ventilate). In this instance surgical airway must be
secured in rapid fashion. Cote et.al. reviewed a number of techniques and devices designed for the anesthesiologists
use in children in this scenario. They concluded the appropriate sized equipment should be utilized, and that
327
Page 4
cricothyrotomy in a neonate or small infant is extremely dangerous. Intravenous catheter devices are recommended
in infants, as anesthesiologists are much more comfortable with IV catheters than scalpels (15).
References
1. Morray JP, Geiduschek JM, Caplan RA, Posner KL, Gild WM, Cheney FW, A Comparison of Pediatric
and Adult Anesthesia Closed Malpractice Claims, Anesthesiology, 1993;78:461-467.
2. Eckenhoff JE, Some Anatomic Considerations of the Infant Larynx Influencing Endotracheal Anesthesia,
Anesthesiology The Journal of the American Society of Anesthesiologists, Inc, 1951;12(4):401-409.
3. Motoyama EK, The Shape of the Pediatric Larynx: Cylindrical or Funnel Shaped?, Anesthesia &
Analgesia, 2009;108(5):1379-1381.
4. Dalal PG, Murray D, Messner AH, Feng A, McAllister J, Molter D, Pediatric Laryngeal Dimensions: An
Age-Based Analysis, Pediatric Anesthesiology 2009;108(5):1475-1479.
5. Bhardwaj N, Review Article: Pediatric cuffed endotracheal tubes, Journal of Anaesthesiology Clinical
Pharmacology, 2013;29(1):13-18.
6. Taylor C, Subaiya L, Corsino D, Pediatric Cuffed Endotracheal Tubes: An Evolution of Care, The Ochsner
Journal, 2011;11:52-56.
7. Nafiu OO, Burke CC, Gupta R, Christensen R, Reynolds PI, Malviya S, Association of Neck
Circumference with Perioperative Adverse Respiratory Events in Children, Pediatrics, 2011;127(5).
8. American Society of Anesthesiologists: Practice guidelines for management of the difficult airway: An
Updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult
Airway, 2013;C118(2):1-20.
9. Brooks P, Ree R, Rosen D, Amsermino M, Canadian pediatric anesthesiologists prefer inhalational
anesthesia to manage difficult airways: a survey, Obstetrical and Pediatric Anesthesia, Can J Anesth,
2005;52(3):285-290.
10. Reynolds PI, OKelly SW, Fiberoptic Intubation and the Laryngeal Mask Airway, Anesthesiology,
1993,79:1144.
11. White MC, Cook TM, Stoddart PA, Review article: A critique of elective pediatric supraglottic airway
devices, Pediatric Anesthesia, 2009;19(1):55-65.
12. Holm-Knudsen R, Review Article: The difficult pediatric airway a review of new devices for indirect
laryngoscopy in children younger than two years of age, Pedaitric Anesthesia, 2011;21:98-103.
13. Shukry M, Hanson RD, Koveleskie JR, Ramadhyani U, Case report: Management of the difficult pediatric
airway with Shikani Optical Sylet
TM
, Pedaitric Anesthesia, 2005;15:342-345.
14. Weiss M, Engelhardt T, Proposal for the management of the unexpect4ed difficult pediatric airway,
Pediatric Anesthesia 2010;20:454-464.
15. Cote CJ, Hartnick CJ, Review article: Pediatric traqnstracheal and cricothyrotomy airway devices for
emergency use: which are appropriate for infants and children? Pediatric Anesthesia 2009;19(1):66-76.
Disclosure
333
Page 1
Common Pediatric Emergencies
Randall P. Flick, M.D. Rochester, Minnesota
Introduction
The practice of pediatric anesthesia is highly variable and as a consequence the type of emergency that may be
encountered in the community hospital will differ from that which may be routinely encountered in a childrens
hospital. This lecture is intended to provide guidance to the generalist practicing in a non-pediatric hospital and will
be presented as case based discussions. Each of the cases describe a situation that may be encountered in any acute
care hospital and include some of the following. Those that have been presented in previous years have been
updated with new information and insight. In order to ensure that the lecture contains new information for
repeat attendees I will abbreviate some areas of the discussion so that scenarios can be added that will cover
common urgent or emergent condition that may be encountered in daily practice. These may include;
laryngospasm, sudden cardiac arrest, post obstructive pulmonary edema, vomiting and aspiration,
malignant hyperthermia or others.
1. The toddler with a suspected aero-esophageal foreign body
2. The school age child with a bleeding tonsil
3. An infant with fever and severe stridor
4. A young child with massive trauma presenting to the emergency department.
5. The neonate with pyloric stenosis
Each of these cases could be encountered in any practice. I have tried to include cases involving children of a
variety of ages. However young children are emphasized as they pose the greatest challenge in the community
setting given that emergencies in this age group are less common and less familiar to the generalist.
Case #1
The toddler with a suspected foreign body is one of the most common cases that one encounters on-call in a
childrens hospital. Suffocation related to aspiration is among the most common causes of death among children
under the age of five years. These cases are extremely challenging as they usually involve a toddler who is very
anxious uncooperative and who may have some degree of airway compromise. Although most of cases involve a
coin lodged in the esophagus some may actually involve the airway and others may involve a foreign body that is
not radio-opaque and cannot be easily localized. The first task for the team caring for a child that is suspected of
aspirating or swallowing a foreign body is differentiating aspirated foreign bodies from those that are swallowed. In
the case of the typical coin this is relatively easily and simply requires a plain radiograph of the chest and neck with
inclusion of the abdomen to ensure that a coin that has passed into the stomach is not missed. Coins that are seen on
face in an antero-posterior view are virtually by definition esophageal whereas those seen on edge in that view must
be suspected of being lodged in the airway. In both cases the child may have stridor as esophageal foreign bodies
rapidly produced edema of the esophageal wall which in turn encroaches on the membranous trachea causing a
narrowing of the subglottic airway and resulting stridor.
Removal of tracheal foreign bodies represents an enormous challenge requiring close teamwork between the
procedural team and the anesthesiologist.
1,2
Controversy exists as to the proper induction technique (mask versus
intravenous), whether ventilation should be controlled or spontaneous and whether rigid or flexible bronchoscopy is
most appropriate. In the case of esophageal coins the technique used for removal remains controversial as in some
institutions these children are managed in the radiology suite using a foley catheter to remove the coin under

333
Page 2
intravenous sedation. I will discuss both the approach to the esophageal and airway foreign bodies in this lecture
including my thoughts on the various areas of controversy.
3,4

Case #2
The case of a child with a bleeding tonsil is a classic problem in the care of children. Tonsillectomy is the second
most common procedure performed under anesthesia in children after myringotomy and in about 1% of cases there
will be bleeding in the postoperative period. A recent study has suggested that the use of steroids may increase the
risk of bleeding in the perioperative period.
5
A finding not confirmed in other studies.
6
Most of these bleeding
episodes will occur in the first 24 hours although a significant number will occur 5 to 7 days after the procedure and
are related to the sloughing of the eschar. Although most cases of bleeding after tonsillectomy are relatively minor
and do not present a major challenge those associated with younger children and or those with significant bleeding
represent one of the most challenging cases encountered in any setting. As in the case of the airway foreign body,
close cooperation with the surgical team is an imperative in the safe management of these children. In this lecture
we will discuss risk factors for bleeding, the evaluation of the child with the bleeding tonsil as well as the approach
to ensuring that intravascular volume is sufficient and the airway is secured.
7,8

Case #3
Since before the middle of the last decade children have been vaccinated against Haemophilus influenza B and as a
consequence the frequency of epiglottitis has declined dramatically. However, these cases still do occur although
rarely. More common are the children that present with severe viral croup or the more serious disorder, bacterial
tracheitis. Bacterial tracheitis has replaced epiglottitis as the most common infectious airway emergency in children
occurring slightly more commonly than sever viral croup.
9-11
Typically caused by Staph or Strep, the presentation of
bacterial tracheitis is dramatic and often emergent airway management is lifesaving. The approach to the young
child with bacterial tracheitis and severe viral croup are similar to the approach most of us learned for epiglottitis.
As with epiglottitis, the management of tracheitis requires close cooperation between the surgical team and the
anesthesiologist. Important differences exist between the treatments of the various causes of acute infectious airway
obstruction in children. These will be discussed in this section.

Case #4
Trauma, usually blunt force associated with motor vehicle crashes, is by far the most common cause of death in all
ages of children (except neonates) making it important for all anesthesiologists to be familiar with some of the basic
principles of initial management of these kids. The evaluation and care of the traumatized child is an enormous
topic and cannot be adequately covered in this refresher course lecture. Therefore, in this section I intend to focus
only on the initial management primarily of the airway as this is the role that most community anesthesiologists are
likely to assume in this setting. Anesthesiologists responding to the emergency department must be alert to the
frequent errors that occur in the field management of the pediatric airway as well as the difficulty and common
complications associated with vascular access in the young child. Important differences in the pediatric airway,
cervical spine response to hemorrhage will be emphasized as will common pitfalls that one is likely to encounter in
the chaotic environment of the emergency department.
12,13

Case #5
Care of the neonate presents obvious challenges especially for those who only occasionally care for infants. The
most common call case among neonates is most probably pyloric stenosis. Pyloric stenosis results from
hypertrophy of the muscle surrounding the gastric outlet and presents classically in first born males with a history of
projectile vomiting in an otherwise vigorous neonate that continues to have an interest in feeding. Hypovolemia as
well as electrolyte abnormalities including hypochloremia, hypokalemia and metabolic alkalosis are frequently
encountered. Although most texts continue to admonish the anesthesia practitioner not to be convinced by an
impatient surgeon to take these babies to the operating room until they have had several hours of intravenous
rehydration (usually overnight) those cases that are diagnosed early can be safely taken to the operating room for
pyloromyotomy as soon as the electrolytes have been confirmed to be normal and the child has received a modest
amount of isotonic fluid. The need for prolonged rehydration and electrolyte correction and other aspects of the
care of the neonate with pyloric stenosis remain controversial.
14

15,16
Perioperative management will be outlined
including advice for those uncomfortable with the care of neonates who may wish to limit their groups practice to
older children.

333
Page 3

Each of the cases outlined above have potential pitfalls and controversies that could easily occupy more than the
time allotted for this refresher course lecture. I will therefore cover as much of the material as time allows and
provide the audience with an opportunity to help choose the cases that are of the greatest interest.

1. Litman RS: Anaesthesia for bronchial foreign body removal: what really matters? Eur J Anaesthesiol
2010; 27: 928-9
2. Fidkowski CW, Zheng H, Firth PG: The anesthetic considerations of tracheobronchial foreign bodies
in children: a literature review of 12,979 cases. Anesth Analg 2010; 111: 1016-25
3. Waltzman ML: Management of esophageal coins. Curr Opin Pediatr 2006; 18: 571-4
4. Soprano JV, Mandl KD: Four strategies for the management of esophageal coins in children. Pediatrics
2000; 105: e5
5. Beutner D, Koll C: Dexamethasone and postoperative bleeding after tonsillectomy in children. JAMA
2009; 301: 1764; author reply 1765-6
6. Brigger MT, Cunningham MJ, Hartnick CJ: Dexamethasone administration and postoperative bleeding
risk in children undergoing tonsillectomy. Archives of Otolaryngology -- Head & Neck Surgery 2010;
136: 766-72
7. Fields RG, Gencorelli FJ, Litman RS: Anesthetic management of the pediatric bleeding tonsil. Paediatr
Anaesth 2010; 20: 982-6
8. Czarnetzki C, Elia N, Lysakowski C, Dumont L, Landis BN, Giger R, Dulguerov P, Desmeules J,
Tramer MR: Dexamethasone and risk of nausea and vomiting and postoperative bleeding after
tonsillectomy in children: a randomized trial. JAMA 2008; 300: 2621-30
9. Graf J, Stein F: Tracheitis in pediatric patients. Semin Pediatr Infect Dis 2006; 17: 11-3
10. Sendi K, Crysdale WS, Yoo J: Tracheitis: outcome of 1,700 cases presenting to the emergency
department during two years. J Otolaryngol 1992; 21: 20-4
11. Hopkins A, Lahiri T, Salerno R, Heath B: Changing epidemiology of life-threatening upper airway
infections: the reemergence of bacterial tracheitis. Pediatrics 2006; 118: 1418-21
12. Bankole S, Asuncion A, Ross S, Aghai Z, Nollah L, Echols H, Da-Silva S: First responder
performance in pediatric trauma: A comparison with an adult cohort. Pediatr Crit Care Med 2010
13. Ehrlich PF, Seidman PS, Atallah O, Haque A, Helmkamp J: Endotracheal intubations in rural pediatric
trauma patients. J Pediatr Surg 2004; 39: 1376-80
14. Cook-Sather SD, Tulloch HV, Cnaan A, Nicolson SC, Cubina ML, Gallagher PR, Schreiner MS: A
comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis. Anesth
Analg 1998; 86: 945-51
15. Willschke H, Machata AM, Rebhandl W, Benkoe T, Kettner SC, Brenner L, Marhofer P: Management
of hypertrophic pylorus stenosis with ultrasound guided single shot epidural anaesthesia--a
retrospective analysis of 20 cases. Paediatr Anaesth 2011; 21: 110-5
16. Allan C: Determinants of good outcome in pyloric stenosis. J Paediatr Child Health 2006; 42: 86-8

Disclosure

428
Page 1
Sedation for Diagnostic and Therapeutic Procedures in Children
Outside the Operating Room: Rules of The Road
Joseph P. Cravero, M.D. Boston, Massachusetts
This lecture will review logical methods for assuring safe and effective sedation for children. It will consider issues
around how to assess the safety of various techniques of sedation. As evidence we will consider several of the
guidelines that have been produced and literature that has been published around the general topic of sedation
provision for children.
Rules:
A. CMS Guidelines: The Centers for Medicare and Medicaid Services (CMS) has issued clear directives on the
nature of the responsibilities that Anesthesia Departments have in assuring safe sedation is a facility:
1. They define types of anesthesia services as ranging from minimal sedation to general anesthesia.
2. All services along this continuum must be organized under a single Anesthesia Service which must be
directed by a qualified physician. (Logically the Chair of Anesthesiology but not required to be an
anesthesiologist). Standards of care must be consistent across all areas where the sedation or anesthesia is
delivered.
3. Hospitals must ensure that procedures are in place to rescue patients whose level of sedation becomes
deeper than initially intended.
4. The anesthesia service is responsible for developing policies and procedures governing the provision of all
categories of anesthesia services including the category of practitioner who is permitted to provide
anesthesia services that are not subject to the anesthesia administration requirements.
5. The administration of anesthesia must be by a qualified anesthesiologist, a doctor of medicine or
osteopathy, dentist, oral surgeon, CRNA, or anesthesia assistant. In this case the requirement does not
apply to local anesthesia, minimal or moderate sedation.
6. Medical staff bylaws must include criteria for determining the anesthesia service privileges to be granted to
an individual practitioner.
7. Delivery of anesthesia services must be consistent with recognized standards for anesthesia care including
patient consent, infection control, safety practices, reporting requirements, documentation, and equipment
requirements.
B. AAP Guidelines: The most useful contribution to the outline of safe sedation practice has come from the AAP
guidelines written by Dr. Charles Cote and the Committee on Drugs of the AAP. There have been several
iterations of these guidelines and, just as the technology has evolved, so have the AAP sedation guidelines.
This first monitoring guideline was written in collaboration with the American Academy of Pediatric Dentistry
(AAPD) and the American Society of Anesthesiologists (ASA).
1
It emphasized concepts that had been well
established as promoting safety in the field of anesthesiology. This document addressed the need for informed
consent, appropriate fasting intervals, regular charting of vital signs, the availability of age and size appropriate
equipment, the use of physiologic monitoring, the need for basic life support skills, and proper
recovery/discharge procedures. As had been accepted in anesthesia care, the concept of an independent
observer whose only responsibility was to monitor the patient was introduced for deeply sedated pediatric
patients. These guidelines also addressed the equipment needs for sedation, as well as basic information on the
various drug interactions that can impact the safety of sedation. The original guidelines defined three terms for
depth of sedation: conscious sedation, deep sedation, and general anesthesia. These terms became ingrained in
the lexicon of sedation provision for children and subsequent iterations of these guidelines have sought to refine
and improve these categories.
428
Page 2
In 1992, the Committee on Drugs of the AAP (primary author Dr. Cot) revised the 1985 guideline.
2
The
statement was careful to point out how a patient could readily progress from a given level of sedation to another
without warning. It also emphasized the fact that the practitioner should be prepared to increase vigilance and
the level of monitoring if a deeper level of sedation is attained. Pulse oximetry was widely available and was
recommended for all patients undergoing sedation.
Another amendment to this guideline was produced in 2002.
3
Perhaps most importantly, this time the use of the
term conscious sedation (and its inherent contradiction in terms) was eliminated in favor of moderate
sedation. The guidelines now unified the terminology used for levels of sedation as minimal sedation,
moderate sedation, deep sedation and anesthesia. This terminology is still accepted by the AAP, AAPD,
ASA, and The Joint Commission.
4
The authors also clarified the fact that these guidelines apply to any location
where children are sedated in or out of the hospital (including dental offices and similar free standing
locations).
The most recent version of the guidelines published in 2006.
5
In terms of depth of sedation, this iteration
states that any child under age 6 must be assumed to be deeply sedated. Given the increased use of potent
sedation agents such as propofol and dexmedetomidine, the guidelines require that the sophistication of the
monitoring and the skills of the sedation provider must match this level of sedation. It moved us closer to using
the term procedural sedation to encompass the entire spectrum of the level of sedation in the pediatric
population. By doing this, it unified the approach so that all patients receiving any type of sedative agent for
procedures should undergo the same evaluation, preparation, monitoring, and recovery regarding the agent or
agents used. It advises that all providers must have advanced airway management skills so as to be able to
rescue the child from unintended deep sedation or general anesthesia where native airway reflexes and tone may
be lost. The routine use of capnography was "encouraged" as this technology had become widely available and
had proven beneficial in the anesthesia operating room environment. Finally the guideline stressed the
importance of recent advances in human simulation for training sedation providers and the collection of quality
improvement data.
Any rules of the road for safe sedation should start with these guidelines. Specific questions such as which
providers should administer potent sedatives (e.g. propofol) should be entertained only after basic monitoring,
personnel, and equipment issues have been addressed.
The Nature of Pediatric Sedation Literature:
We must recognize that the current state of the sedation literature and the reports that are routinely published on
pediatric sedation rarely help us understand the safety or effectiveness of the practice. Specifically, the papers
published on pediatric sedation are almost always small 50-300 patients. They are generally retrospective in
nature or (at best) prospective and observational. Generally they come from one institution. No one publishes a
negative study, so the reports always end with the sentence that we found that technique X is safe and effective for
procedure(s) y. We should also recognize that often times these papers are published under the heading of
sedation when, in fact, they describe anesthesia level of care. A study typical of this literature is that produced
by Vardi et al .
6
This study looked at a comparison of the use of propofol vs. a combination of
ketamine/midazolam/fentanyl for elective oncology procedures performed in the ICU. There were significant rates
of respiratory depression and the need for rescue in both cohorts. A total of 108 procedures were evaluated and the
conclusions of the authors was that propofol and ketamine based sedation were effective and that the care should be
provided in a monitored environment.
A subsequent study published in the Annals of emergency medicine evaluated the use of propofol by ED physicians
for elective oncology procedures.
7
The study looked at a total of 393 patients and had fairly good outcomes. This
study was accompanied in the same journal by an editorial that stated the work by Bassett et. al. had proven the
safety and effectiveness of propofol sedation in the ED and that larger studies were unnecessary and impractical.
428
Page 3
Dartmouth Projects Alternatives for Evaluating Sedation Practice:
With support from the National Patient Safety Foundation we undertook a study of the process of pediatric sedation
at the Childrens Hospital at Dartmouth using a human factors approach. We started by videotaping 40 procedural
sedation events. We then had experts review the tapes and describe the nature of the work, the tools used, the
environment and the critical elements of the timing of this work. Using this input, a scale (Dartmouth Operative
Conditions Scale (DOCS)) (Figure 1.) was developed to grade the conditions under which each sedation was
performed. This scale is meant not just to categorize the level of sedation for each procedure, but rather to measure
how well the goals of sedation were met. We have subsequently validated this scale for inter-rater reliability,
criterion validity, and construct validity.
8,9

It is important to recognize that the goals for sedation may be met with a child wide awake but distracted by a
video or a calming voice. This scale defines a zone between scores of 2 and +2. In this zone, the patient is not
agitated or out of control and is not experiencing side effects from excessive sedation.
Subsequently one hundred and ten procedures performed by various providers throughout the Childrens Hospital at
Dartmouth were videotaped and viewed by one of two trained graders. The graphical DOCS data is superimposed
with the time of the actual procedure that was being performed during the sedation to allow measurement of the fit
of the sedation for the procedure. The results of our objective analysis showed huge variations in practice from one
location/provider to another. (Figure 2.)
1. The medications (tools) used by different providers led to widely differing efficiency of sedation work.
Time to accomplish sedation varied from 1 minute to 63 minutes.
2. There were significant differences in the efficiencies of the systems under which procedures were
performed. The time from accomplishing sedation to starting the procedure varied from 2 minutes to 83
minutes.
3. Post-procedure (wake-up) time varied from 2 to 136 minutes. Notable were 5 chloral hydrate sedations
where over 100 minutes of sedation was provided for CT scans which took approximately 6 minutes.
4. Failure to achieve sedation rate was 5%. 0% with anesthesia sedation providers.
5. Six of the one hundred tapes were noted to have over-sedated states. Most consisted of prolonged oxygen
desaturation with partial airway obstruction.
6. Of note was a seventh tape where a neurologically normal child was discharged while still appearing
sedated and with poor muscle tone against the policies of our hospital.
7. Undersedated states were extremely prevalent. 68% of the videos reviewed showed a significant interval of
agitation as defined by a DOCS score of greater than 2 for at least 5 minutes.
Figure 1. D.O.C.S. (Dartmouth Operative Conditions Scale)
CONDITIONS RATING
Pain/Stress
0= Eyes- Calm Expression
1= Grimace; Frown; Tears
2= Crying; Sobbing; Screaming
Movement
0= Still
1= Random minor movement
2= Major Purposeful Movement
3= Thrashing; Kicking; Biting
Level of Consciousness
0= Eyes Open
-1= Ptosis; Dysarthria; >Low Tone
-2= Eyes Closed
Respiratory Side Effects
-1= Pulse Ox <92
-1= Respiratory Noise (Snoring)
-1= Pauses-Apnea
-1=Bradycardia < 5
th
Percentile
-1= BP < 5
th
Percentile
428
Page 4
Figure 2. Graphical representation of DOCS data over time:
Simulation Work:
Full function patient simulators have gained a great deal of interest over the last 5 years. They are widely used for
training of individuals who need to resuscitate patient and for those who are involved in anesthesia delivery. Some
institutions have broadened their use to teaching medical students cardiac and respiratory physiology. We received
permission from our institution to call a code as needed for resuscitation without telling the code team that the
simulator was the patient. We then had the departments give sedation as per their usual routine and we created an
apnea event simulating a laryngospasm episode in the patient. The resuscitation was videotaped and the data on
what was happening physiologically with the patient was recorded on the simulator software. At a later time the
simulator data and the video data were evaluated in tandem to produce a graphic representation of the performance
of the resuscitation team in each instance. An example of this data is displayed in figure 3.
10

Analysis of the data we have generated reveals significant differences in the time to respond to the apneic event
between providers at different locations. In addition we have shown that the computer modeled duration of hypoxia
and acidosis varies greatly from one site to another. In some cases providers were unable to use basic resuscitation
equipment correctly because they were unfamiliar with the resuscitation bags and masks that were provided. In
other cases the providers were simply unfamiliar with exactly what they should do for the given scenario.
Most importantly analysis of our video and simulator data has shown that there were some instances of poor
response for the ultimate rescue or backup airway providers because of communications problems and other
systems related difficulties. In one instance the designated code airway provider showed up 15 minutes after the
code was called because of difficulties with the paging system within the hospital.
Video #1; CT scan
(Medication = Chloral hydrate, 75mg/kg dose)
-5
-4
-3
-2
-1
0
1
2
3
4
5
0 5
1
0
1
5
2
0
2
5
3
0
3
5
4
0
4
5
5
0
5
5
6
0
6
5
7
0
7
5
8
0
Time (minutes)
S
u
m

D
O
C
S
Start Time
Sedation Lag Time
Procedure Start Time
Procedure End Time
Intra-procedure Period
Post-procedure Period
Pre-procedure Delay Period
Completion Time
428
Page 5
Figure 3. Graphical representation of video and simulator data:
Simulator Work Conclusions:
As has been well established in other high risk low error tolerance fields, sedation systems need to be tested for
capability to rescue patients from rare events using high fidelity simulation. Changes in systems should be based on
this objective data and detailed analysis of system function.
Pediatric Sedation Research Consortium (PSRC):
The Pediatric Sedation Research Consortium is a consortium of hospitals and medical centers dedicated to sharing
information on sedation work in an effort to understand better what works and what does not work for sedation of
children. This group is made up of a variety of pediatric specialists from 30 institutions in the United States and
Canada. Data is entered over the web and stored on servers at Dartmouth College. Information for each sedation
from selected sites at each participating institution is collected this includes demographic data, procedure,
coexisting illness, provider of sedation, drugs used, monitors used, outcomes of the sedation etc. To date after 8
years we have over 300 thousand records in the database. Our goal will be to evaluate practice at participating
institutions, identify best practice and emulate this work at other sites.
In Sept 2006 Pediatrics published the first paper from the PSRC describing the types of adverse events and
unexpected airway management issues that were encountered during the first 30,000 sedations collected in this
consortium.
11
Notable for the purposes of training and credentialing is the incidence of airway interventions that
were not expected (Table 1.).
Given the rates of intervention, we feel our data indicates clearly that recognition of apnea, airway insertion, and the
provision of positive pressure ventilation are critical competencies that must be present for providers of
moderate/deep sedation in children. As a consortium, we feel this data can/could be used to define (more generally)
critical competencies for sedation delivery.
Simulated Apnea Event (Emergency Medical Team)
0
20
40
60
80
100
120
140
160
0
:
0
4
0
:
0
5
0
:
0
6
0
:
0
7
0
:
0
8
0
:
0
9
0
:
1
0
0
:
1
1
0
:
1
2
0
:
1
3
Time (minutes)
U
n
i
t
s

(
B
P
M
,

m
m
H
g
,

%
)
Spont. RR
SaO2
HR
SBP
start apnea event
ketamine
Severe Hypoxia and Hypotension
(5 minutes and 45 seconds)
Bag-mask started
Respiratory therapist
connects oxygen hose
Stable
428
Page 6
Table 1: Adverse Events rates are expressed as number of events per 10,000 sedations
A subsequent paper was published in Anesthesia and Analgesia in 2009 titled The incidence and nature of adverse
events during pediatric sedation/anesthesia with propofol for procedures outside the operating room report from
the Pediatric Sedation Research Consortium.
12
This paper discussed evaluated data from 49,836 sedation
encounters utilizing primarily propofol. Data were evaluated for complications and effectiveness of sedation. The
incidence and nature of unexpected airway management is displayed below Table 2:
Table 2. Airway interventions for Propofol sedated patients.
Table 3. Data on effectiveness of care revealed outstanding general performance
Adverse Events During Pediatric Sedation
Table 12: Complications rates are expressed as number of events per 10,000 sedations
Adverse Events
Incidence per 10,000 N 95% CI
Death 0.0 0 ( 0.0-0.0)
Cardiac Arrest 0.3 1 ( 0.0- 1.9)
Aspiration 0.3 1 ( 0.0- 1.9)
Hypothermia 1.3 4 ( 0.4- 3.4)
Seizure (unanticipated) During Sedation 2.7 8 ( 1.1- 5.2)
Stridor 4.3 11 ( 1.8- 6.6)
Laryngospasm 4.3 13 ( 2.3- 7.4)
Wheeze (new onset during sedation) 4.7 14 ( 2.5- 7.8)
Allergic Reaction (rash) 5.7 17 ( 3.3- 9.1)
Intravenous Related Problems/complication 11.0 33 ( 7.6- 15.4)
Prolonged Sedation 13.6 41 ( 9.8- 18.5)
Prolonged Recovery 22.3 67 ( 17.3- 28.3)
Apnea (unexpected) 24.3 73 ( 19.1- 30.5)
Secretions (requiring suction) 41.6 125 ( 34.7- 49.6)
Vomiting During Procedure (non-GI) 47.2 142 ( 39.8- 55.7)
Desaturation below 90% 156.5 470 ( 142.7-171.2)
Total Adverse Events 339.6 (1 per 29) 1020 ( 308.1- 371.5)
Unplanned Treatments
Reversal Agent Required - unanticipated 1.7 5 ( 0.6- 3.9)
Emergency Anesthesia Consult for Airway 2.0 6 ( 0.7- 4.3)
Admission to Hospital unanticipated
(sedation related)
7.0 21 ( 4.3- 10.7)
Intubation Required - unanticipated 9.7 29 ( 6.5- 13.9)
Airway (oral) (unexpected requirement) 27.6 83 ( 22.0- 34.2)
Bag-mask Ventilation (unanticipated) 63.9 192 ( 55.2- 73.6)
Total Unplanned Treatments 111.9 (1 per 89) 336 ( 85.3 130.2)
Conditions Present During Procedure
Inadequate sedation, could not complete 88.9 (1 per 338) 267 ( 78.6-100.2)
428
Page 7
Once again we conclude that the practice described here does not prove the general safety and effectiveness of
propofol sedation, but rather it gives us an idea of what high performance systems can do with propofol sedation,
and the kinds of adverse events that can be expected with this care. The paper reinforces the need for providers of
propofol sedation to have excellent airway management skills. It documents the outstanding effectiveness of this
sedative.
The PSRC has subsequently published several papers analyzing the incidence of severe adverse events between
different providers of sedation, with obese patients undergoing sedation, among emergency medical physicians
using propofol for sedation, and the use of monitors by sedation providers. The PSRC project emphasizes the utility
of large data analysis in evaluating pediatric sedation provision safety and the need to evaluate data from multiple
specialties that are involved in this specialty care.
Training and Credentialing -Human Patient Simulation:
The best method for assuring safety and effectiveness in sedation is to provide outstanding training and credentialing
for providers. There is no absolute standard in this field, but there some trends are becoming clear. Optimal
training for sedation is made up of several components:
1. Didactic training through the use of online or hardcopy materials that stress basic knowledge of physiology,
pharmacokinetics, and pharmacodynamics.
2. Hands on training that emphasizes core competencies such as the recognition of apnea, opening of a
blocked airway, and effective bag-mask ventilation techniques.
3. A period of monitored or proctored care. Observation of somewhere between 10 to 30 cases in various
settings.
An example of curriculum as presented by the Society for Pediatric Sedation is presented in Figures 4 and 5.
In terms of practical training in sedation, the field of Human Patient Simulation (HPS) continues to grow and will
doubtless change the nature of medical education (in general) in the near future. Adult sedation literature has
indicated a role for HPS in training for sedation
13
, but the literature on the use of HPS related to pediatric sedation is
just now beginning to join this vanguard. Shavit, et al. demonstrated improved sedation safety performance in a
cohort of pediatrician sedation providers who had been trained with HPS when compared to a cohort of providers
who had not received simulation training.
14
While the study was small, it is the first to attempt to validate this form
of training and its contribution of sedation provider skills. Another study led by Keidan used human patient
simulation to document the effect of supplemental oxygen on the ability of pulse oximetry to detect apnea and
confirmed the long-held physiology-based axiom that patients on oxygen will be delayed in experiencing oxygen
desaturation.
It is clearly too early to report that HPS is revolutionizing pediatric sedation, it deserves mention as a technology
with the potential to radically change the way in which we train, credential, and test the readiness of sedation
providers and systems.
428
Page 8
Figure 4. Sedation Provider Course Curriculum Lectures
Pre-Sedation Phase -
Sedation Risk
Assessment
Describes conducting the pre-sedation risk assessment including performance of a
patient history and physical exam with focus on the upper airway, respiratory,
cardiovascular and neurological status.
Procedural Sedation
Phase Sedative Drugs
and Procedures
Explains the general approach to procedural sedation including sedative
pharmacology and a rationale for matching a particular sedative drug(s) with
specific patients and/or procedures.
Sedation Related
Adverse Events
Identifies the most common complications occurring during sedation, contributing
factors, and management.
Sedation Monitoring Explains the effects of sedation on cardiorespiratory function, monitoring
requirements and the principles and applications of common monitoring tools (e.g.
pulse oximetry, end tidal CO
2
monitoring)
Post-Sedation Phase -
Sedation Recovery and
Discharge
Discusses a systematic approach to patient recovery and discharge following
sedation.
Figure 5. Skill and Core Case Simulation Sessions and Small Group Discussion
Skill Simulation
Scenarios (4)
Apnea Hypoventilation
Upper Airway Obstruction
Secretions / Aspiration with laryngospasm
Hemodynamic Changes
Core Case Simulation
Scenarios (2)
Invasive Procedures - Students work with other team members to prepare and
sedate a child for a painful procedure (e.g. bone marrow procedure).
Non-invasive Procedures - Students work with other team members to prepare
and sedate a child for a non-painful procedure (e.g. MRI scan).
Tailoring Sedation Small
Group Session
Instructors use an open discussion format and present various sedation scenarios
to students to work through as a team.
Safety Summary
Pediatric sedation safety involves a systematic approach.
1. Recognize that there are clear guidelines for appropriate oversight and organization of sedation services
from regulatory bodies such as CMS.
2. Guidelines from the AAP (in particular) provide a helpful roadmap to appropriate components of sedation
provision.
3. In order to understand the true nature of sedation provision, a detailed analysis of practice is required with
an emphasis on evaluation of objective standards and outcomes.
4. Systems must be tested to detect latent vulnerabilities and assure appropriate rescue capability.
5. Large database analysis and sharing of data will allow us to better understand the incidence and nature of
sedation problems.
6. Well designed and executed training programs for sedation are critical to safe sedation delivery and care.
428
Page 9
References:
1. Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric
patients. Pediatrics 1985;76:317-21.
2. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic
and therapeutic procedures. Pediatrics 1992;89:1110-5.
3. Guidelines for monitoring and managemet of pediatric patients during and after sedation for diagnostic and
therapeutic procedures: addendum. Pediatrics 2002;110:836-8.
4. Joint Commission on Accredidation of Healthcare Organizations. Sedation and Anesthesia Care Standards. .
Oakbrook Terrace, IL: Joint Commission on Accredidation of Healthcare Organizations; 2003.
5. Cote CJ, Wilson S. Guidelines for Monitoring and Management of Pediatric Patiens During and After
Sedation for Diagnostic and Therapeutic Procedures: An Update. Pediatrics 2006;118:2507-602.
6. Vardi A, Salem Y, Padeh S, Paret G, Barzilay Z. Is propofol safe for procedural sedation in children? A
prospective evaluation of propofol versus ketamine in pediatric critical care. Critical care medicine
2002;30:1231-6.
7. Bassett KE, Anderson JL, Pribble CG, Guenther E. Propofol for procedural sedation in children in the
emergency department. Ann Emerg Med 2003;42:773-82.
8. Cravero JP, Blike GT. Review of pediatric sedation. Anesth Analg 2004;99:1355-64.
9. Cravero JP, Blike GT, Surgenor SD, Jensen J. Development and validation of the Dartmouth Operative
Conditions Scale. Anesth Analg 2005;100:1614-21.
10. Blike GT, Christoffersen K, Cravero JP, Andeweg SK, Jensen J. A method for measuring system safety and
latent errors associated with pediatric procedural sedation. Anesth Analg 2005;101:48-58, table of contents.
11. Cravero JP, Blike GT, Beach M, et al. Incidence and nature of adverse events during pediatric
sedation/anesthesia for procedures outside the operating room: report from the Pediatric Sedation Research
Consortium. Pediatrics 2006;118:1087-96.
12. Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH. The incidence and nature of adverse events
during pediatric sedation/anesthesia with propofol for procedures outside the operating room: a report from
the Pediatric Sedation Research Consortium. Anesth Analg 2009;108:795-804.
13. DeMaria S, Jr., Levine AI, Cohen LB. Human patient simulation and its role in endoscopic sedation
training. Gastrointestinal endoscopy clinics of North America 2008;18:801-13, x.
14. Shavit I, Keidan I, Hoffmann Y, et al. Enhancing patient safety during pediatric sedation: the impact of
simulation-based training of nonanesthesiologists. Archives of pediatrics & adolescent medicine
2007;161:740-3.
"#$%&'$()*
"#$% %&'()'* #(% $+,$-(.', .#(. #' /* %#' #(% +/ %$0+$1$-(+. 1$+(+-$(2 *'2(.$/+%#$& 3$.# .#' 4(+51(-.5*'* /1 (
-/44'*-$(2 &*/,5-. /* &*/6$,'* /1 ( -/44'*-$(2 %'*6$-' .#(. 4(7 8' ,$%-5%%', $+ .#$% &*'%'+.(.$/+9
434
Page 1
New Guidelines: Pediatric Advanced Life Support for the Anesthesiologist 2013
Jayant K. Deshpande, M.D., M.P.H. Little Rock, Arkansas
This refresher course will provide the anesthesiologist a) a summary of the American Heart Association
guidelines for pediatric life support and b) a discussion on management of perioperative cardiac arrest
resulting from selected causes.
Capsule of the Current AHA Guidelines for Pediatric Resuscitation
Pediatric Basic Life Support
CHANGE IN CPR SEQUENCE (C-A-B replaces A-B-C): Start with chest compressions instead
of rescue breaths. Start CPR with 30 compressions (one rescuer) or 15 compressions with two
providers, instead of with two rescue breaths.
Chest compression depth: Appropriate depth for chest compressions is at least 1/3 of the anterior-
posterior chest diameter, or approximately 1! inches (4 cm) for infants; 2 inches (5 cm) for children.
Just open the airway - No need to Look, Listen, and Feel for Breathing.
Pulse check de-emphasized: In the unresponsive infant or child who is not breathing or only
gasping, if a pulse is not apparent, chest compressions should be initiated. Time is wasted (almost 10
seconds) trying to find pulse.
Defibrillation and use of the AED in infants: For infants, use a manual defibrillator instead of an
AED. If manual defibrillator is not available, use AED with a pediatric dose attenuator. If neither is
available, use AED without the pediatric dose attenuator.

434
Page 2

Perioperative cardiac arrest progressively has become less of a concern over the past two decades. Yet when it
occurs is a traumatic event for the anesthesiologist and perioperative care team. Knowledge of the epidemiology of
pediatric cardiac arrest and of current resuscitation techniques may further reduce the associated morbidity and
mortality. Recent studies of pediatric cardiac arrest (Flick et al 2007;Bhananker et al 2008) indicate that the
principal causes of perioperative arrest have remained fairly consistent throughout the years. In decreasing order
these are cardiovascular, respiratory, medication, equipment, combination of events and other miscellaneous causes.
Intraoperative arrests often are related to the cardiovascular system while respiratory events are more likely to cause
postoperative arrests. Higher ASA physical status and emergency procedures have the highest association with
perioperative cardiac arrest in children.

Epidemiology
Cardiac arrest in infants and children who are in-hospital or in the perioperative setting may occur from various
causes. Causes include Respiratory failure, Sepsis, Drug toxicity or overdose, Metabolic disturbances and
Dysrhythmias. Perioperative cardiac arrest may occur because of cardiovascular reasons; respiratory obstruction or
failure; medication overdose or adverse reactions; equipment failure or malfunction; a combination of events.
The causes of cardiac arrest are different for the different phases of care. In the presurgical setting, cardiovascular,
respiratory and medication related events are equally likely as the underlying cause of cardiac arrest.
Intraoperatively, the precipitating cause most likely is a cardiovascular event. Post-operatively, respiratory causes
account of the majority of cases, followed by cardiovascular events. The anesthesiologist must be cognizant of the
common causes in the different phases of surgical experience in order to properly treat the patient in a timely
manner. (Bhananker et al 2007; Christensen et al 2013)

Pediatric Advanced Life Support
Monitor exhaled CO2: In addition to clinical assessment, use exhaled CO2 detection (colorimetry
or capnography) to confirm tracheal tube position for patients with a perfusing rhythm in all settings
and during interhospital/intrahospital transport. Continuous monitoring, when available, can be
beneficial during CPR to gauge effectiveness of chest compressions.
Defibrillation energy doses: Initial dose is 2-4 J/kg. For refractory VF, dose may be increased start
with 4 J/kg (biphasic) up to but not to exceed 10 J/kg (maximum dose 360 J monophasic).
After resuscitation, limit supplemental oxygen to minimum levels needed: use 100% FiO2 for
resuscitation. Avoid hyperoxia after resuscitation. Oxyhemoglobin saturation (SpO2) should be
monitored following return of circulation. Titrate the FiO2 to maintain SpO2 " 94%.
Resuscitation of infants and children with congenital heart disease: The guidelines include
resuscitation measures for cardiac arrest in infants and children with single-ventricle anatomy,
Fontan or hemi-Fontan / bidirectional Glenn physiology, and pulmonary hypertension.
Medications during cardiac arrest and shock: The routine use of calcium during pediatric
cardiopulmonary arrest is not recommended. Calcium may be used to treat documented
hypocalcemia, calcium channel blocker overdose, hypermagnesemia, or hyperkalemia. In septic
shock, etomidate is not recommended.
Post-cardiac arrest care: Therapeutic hypothermia (32C-34C) may provide benefit for
adolescents who remain comatose after resuscitation following sudden witnessed out-of-hospital VF
cardiac arrest. Therapeutic hypothermia may also be beneficial for patients remaining comatose
after resuscitation from cardiac arrest.
A rapid response system in the inpatient setting may beneficial to reduce rates of cardiac and
respiratory arrest and in-hospital mortality.
Evaluation of sudden cardiac death victims: Past medical and family history, as well as review of
previous ECGs may point to the cause of sudden, unexplained cardiac death in a child or young
adult. When possible, tissue from the patient should be analyzed for the presence of channelopathy.

(adapted from Gooden CK. SPA News, Society for Pediatric Anesthesia, 24(1), Spring 2011
and Kleinman et al Circulation October 2010)

434
Page 3
The American Heart Association (AHA) Committee on Pediatric Resuscitation completed an exhaustive process of
evidence review and expert consensus development to revise and update the guidelines for resuscitation of children.
This process culminated in the dissemination of the new AHA guidelines in November 2010 and significant
modification of the AHA Pediatric Advanced Life Support (PALS) course.

Cardiorespiratory arrest in infants and children is an infrequent phenomenon as compared to adults. In the majority
of cases the etiology is respiratory distress and failure which can lead to cardiac arrest if not treated and reversed in a
timely manner. Primary cardiac events leading to arrest are rare in infants and children, whereas in adults cardiac
arrest may be the primary event resulting from dysrhythmias, which can quickly deteriorate to a non-perfusing state.

Out-of-hospital arrests have a poor prognosis, with less than 9% survival to hospital discharge. For in-hospital
arrest, CPR is successful in restoring spontaneous circulation in over 60% of patients. However, the rate of survival
to discharge decreases rapidly to approximately 15% or less.

Respiratory Failure
Successful cardiorespiratory resuscitation of infants and children begins with early recognition and reversal of
respiratory distress or shock.

Respiratory distress may be characterized by tachypnea, increased respiratory effort, nasal flaring, intercostal,
subcostal or substernal retractions, and stridor or grunting. Lethargy in a child with respiratory distress is a bad sign
indicating impending respiratory failure and requires immediate treatment. Other signs include inadequate or low
respiratory rate, decreased unilateral or bilateral breath sounds and pallor or cyanosis. Untreated, the patient will
suffer respiratory failure defined as inadequate ventilation and possibly respiratory arrest.

Shock
Shock is defined as blood flow and oxygen delivery that is inadequate to meet metabolic demands. During the early
stage of compensated shock, tachycardia and peripheral vasoconstriction may sustain systemic blood pressure and
vital organ perfusion at marginally adequate levels. When the bodys ability to compensate is exceeded,
decompensated shock leads to rapid deterioration reflected as systemic hypotension and weak central pulses.
Because the normal values for vital signs vary with age, signs of compensated or decompensated shock may be easy
to miss. Bradycardic shock or arrest in infants and children is characterized by a heart rate significantly lower than
expected (usually under 100) in the presence of other signs of circulatory failure.

Airway
Airway problems are a leading cause of respiratory distress and failure in children. Young infants are obligate nose
breathers who may develop significant distress which may be relieved by suctioning of the nostrils. The infant
anatomy may contribute to airway obstruction because of the relatively large tongue, rostrally placed larynx (more
anterior) and large occiput. Proper positioning of the head and neck or placement of an oral airway may relieve an
apparent airway obstruction. Airway adjuncts including laryngeal mask airway and endotracheal intubation should
be used as appropriate.

Oxygen
Standard recommendations for resuscitation include the use of 100% oxygen. This recommendation is classified as
Indeterminate because of the possible adverse effects of 100% inspired oxygen. These effects include increased
cerebrovascular resistance, oxidative stress on lung, cardiac and other tissues, and atelectasis. Once the patient has
been resuscitated, the FiO2 should be decreased to a level sufficient to maintain adequate systemic oxygen levels.

Ventilation
Manual ventilation during resuscitation often results in significant overventilation. Overexpansion of infant lungs
may result in barotrauma and even pneumothorax, and impede proper venous return and affect cardiac output.
Hypocapnia may exacerbate brain hypoperfusion. Therefore, care should be used to provide ventilation that is
adequate to inflate the lungs while avoiding overdistention.

434
Page 4
Cuffed Versus Uncuffed Tubes
Both cuffed and uncuffed tracheal tubes are acceptable for infants and children.If cuffed tracheal tubes are used,
avoid excessive cuff pressures. Appropriately sized endotracheal tubes should be used and care should be taken to
minimize glottic and subglottic trauma. Tube size can be approximated as (age in years/4) + 4 for uncuffed tubes
and (age in years/4) + 3 for cuffed tubes. Even in emergency situations, tube placement should be confirmed by
chest auscultation and by detection of exhaled CO2.

Vascular Access
PALS guidelines emphasize the need for timely vascular access. If peripheral access is not obtained within 90
seconds, intraosseous (I/O) needle placement is advised. All resuscitation carts and operating rooms should have
access to I/O needles. Experienced providers may be able to place a central line for more secure access, but the
procedure may impede the ability to perform adequate chest compressions during cardiac arrest. In the absence of
IV or I/O access, most emergency medications may be administered via the endotracheal route but will require
higher doses than with the IV or I/O route.

Cardiac Arrest
Pulseless arrest requires both ventilatory support and effective chest compressions. The likelihood of effective
resuscitation and return of spontaneous circulation improves with starting timely and adequate chest compressions.
The goal is to achieve longer periods of diastolic pressure sufficient to perfuse the coronaries. Therefore, the
pediatric recommendations are similar to those for adults. For single rescuer, 2 breaths are given after each 30
compressions. The two rescuer method involves a ratio of 15 compressions to 2 manual ventilations. Compressions
should be of sufficient depth (1/3 to 1/2 of the anterior-posterior chest diameter) and allow full recoil of the chest.
The compression rate for all ages is 100/minute. Chest compression often is inadequately performed (Niles et al
2012).

Fluids and Medications
Dosing of fluids and medications in children is based on the childs weight. Patients in hospital should have a
recently measured weight and pre-calculated doses of emergency medications available at the bedside. If the childs
weight is unknown, length-based tape measures with pre-calculated doses have been validated and are commercially
available.

Isotonic crystalloid solutions should be used for resuscitation. Glucose containing solutions are not recommended
for routine use. Because infants are at high risk for developing hypoglycemia, blood glucose should be measured
early during the resuscitation.

Resuscitation medications for children are similar to those used in adults. When indicated in pulseless cardiac
arrest, the standard dose of epinephrine IV is 0.01 mg/Kg. The higher dose may in fact have significant adverse
effects including worse outcomes, such as hypertension, ventricular ectopy, myocardial necrosis and prolonged
myocardial dysfunction.

Defibrillators in Pediatric Resuscitation
Because most pediatric arrests are a result of respiratory events, the most common dysrhythmias in children are
asystole and bradycardia with a wider QRS complex. Sudden cardiac arrest in children may result from ventricular
fibrillation (VF) or pulseless electrical activity (PEA). For children with VF, defibrillation may be a life-saving
intervention with the chance of survival approaching 20%. Out-of-hospital pediatric arrests are associated with 5-
15% incidence of VF. For these children, especially those with witnessed sudden cardiac arrest, defibrillation has
resulted in rapid resuscitation and functional survival. Because of the significant benefit of automated external
defibrillators (AEDs), many communities have instituted Public Access Defibrillator (PAD) programs.

Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in children may be associated with a pulseless
state or pulses may be present. For the pulseless patient, treatment should be instituted according to the cardiac
arrest guidelines. If pulses are present, treatment should include oxygen and airway support and assessment of the
underlying cardiac rhythm. Narrow QRS complexes likely represent supraventricular tachycardia which may be
treated progressively with vagal stimulation, intravenous adenosine, and electrocardioversion. Amiodarone or
procainamide may be needed if the SVT is unresponsive to other treatments or the rhythm relapses. These
medications prolong the QT interval and therefore should be used with caution. Wide complex tachycardia may

434
Page 5
represent SVT with aberrant conduction or VT. This rhythm may respond to electrocardioversion but often requires
amiodarone or procainamide as well.

Torsade de Pointes
This is a polymorphic form of VT in children which may be congenital in origin or occur because of toxicity of
certain antiarrhythmics, antidepressants, or drug interactions. Intravenous magnesium sulfate is the treatment of
choice for torsade of any etiology. The initial dose of magnesium is 25 - 50 mg/Kg IV.

Duration of CPR
Recently Matos et al reported that CPR duration was inversely associated with survival to hospital discharge and
neurological outcome, even after adjustment for confounding factors. Surgical cardiac patients had improved
outcomes compared with patients in all other illness categories. Importantly, the study suggests that a some
children who might die without CPR survive with a favorable neurological outcome even after prolonged CPR.

Rapid response ECMO (RR-ECMO)
In some centers extracorporeal membrane oxygenation (ECMO) is available and has been used for rescue after
cardiac arrest. Turek et al reviewed 3 years experience from several center and found that pediatric RR-ECMO
program for venoarterial ECMO initiation was associated with reduced neurologic complications. But RR-ECMO
did not improve survival during the first 3 years of program implementation.

Miscellaneous
Cardiorespiratory arrest in children may occur as a result of toxic ingestion. A focused history and rapid diagnostic
tests may indicate the specific causative toxin or medication. Treatment of the systemic effects depends on the
ingested drug or toxin. Tricyclic antidepressants, !-blockers, calcium channel blockers, methamphetamine and
cocaine pose additional challenges.

Post-Resuscitation Neuroprotection
Preservation of brain function and prevention of secondary brain injury is an important goal of resuscitation.
Hyperventilation and hypocapnea should be avoided as there is no demonstrated benefit. Severe hypocapnea may
cause cerebral ischemia and myocardial dysfunction. Maintaining a normal body temperature is a foundational
practice in pediatric anesthesia. However, hyperthermia can have deleterious effects on brain recovery. Rapid
rewarming of a child during and after resuscitation is not necessary as it may result in hyperthermia. In patients who
remain comatose, therapeutic hypothermia (32oC-34oC) may improve brain recovery.

Family Presence During Resuscitation
Patient families may have a strong desire to be present during resuscitation. Although not practical in the operating
room, it may be possible to have family members present in the emergency department or hospital bedside during
the resuscitation. For children with chronic conditions, family members may be able to provide useful information
about the childs history and clinical conditions. The healthcare team is encouraged to consider allowing families to
be present during resuscitation and to have a team member assigned to support the family.

Cardiac Arrest in the Perioperative Setting
Several special circumstances related to anesthetic management and surgery warrant mention. These will be
discussed in more detail during the Refresher Course. Anesthetic agent related effects include overdose of
Intravenous or Inhalation anesthetic. A high neuraxial block may result in near-total sympathectomy. Unsuspected
malignant hyperthermia or drug administration errors may result in circulatory compromise. Hypoxemia, auto
PEEP, or acute bronchospasm may go undetected or untreated. Cardiovascular effects of interventions under
anesthesia may result cardiac arrest or circulatory compromise. Infants and young children with high
parasympathetic tone may experience severe bradycardia induced by Vasovagal reflex. Other conditions that can
result in arrest include hypovolemic and/or hemorrhagic shock, tension pneumothorax, anaphylactic reaction,
transfusion reaction, acute electrolyte imbalance (high K) particularly after succinylcholine administration, severe
pulmonary hypertension, increased intraabdominal pressure (e.g., laparoscopy) and known or unrecognized
prolonged q-t syndrome, pulmonary embolism, gas embolism.

434
Page 6
Anaphylaxis
Common causes include IV contrast agents, latex, beta lactam antibiotics, non-depolarizing neuromuscular blockers.
The management of the patient with anaphylaxis consists of measures to interrupt the reaction and support the
patient. Surgery should be interrupted when feasible and the patient should be immediately supported with IV fluid
and vasopressors. It is imperative to remember that the Epinephrine administered to patients with anaphylaxis is
intended to interrupt the reaction, and not support the circulation. Thus it should always be given and at the full
recommended dose (0.01 mg/kg, or approximately 1mg in most adults).

Complications of Central Venous Access
Pneumothorax is a well described and relatively rare complication of central line placement in perioperative
patients. Most practitioners astutely suspect this complication in patients who become unstable after undergoing
central venous cannulation. More recent analysis from the closed-claims database suggests that both hemo-
pneumothorax and tamponade may be important and sometimes unrecognized fatal complications of patients who
undergo attempts at central venous cannulation. In those instances where a patient deteriorates following central line
placement, echocardiography should be considered in addition to chest radiography.

Local Anesthetics
Risk of local anesthetic toxicity is difficult to predict. In general, local anesthetics depress the heart in a dose
dependent fashion. Of the local anesthetics in widespread clinical use, bupivacaine is the most potent myocardial
depressant and most often associated with cardiac arrest. Most children receive local anesthetic blocks while they
are under general anesthesia. Therefore, clinical symptoms that may presage cardiac arrest in this setting are usually
masked. Signs of local anesthetic toxicity include PVCs, wide QRS complex EKG which can subsequently
deteriorate into EMD/PEA or asystole (bupivicaine), bradycardia or atrioventricular block (lidocaine and
etidocaine). Treatment includes stopping the administration of local anesthetic, CPR as indicated (pulseless for >10
sec), Epinephrine 10 mcg/Kg, tracheal intubation and ventilation with 100% oxygen. Intralipid (20%) 1.5ml/Kg IV
load, then 0.25ml/Kg/hr IV may be lifesaving. Sodium Bicarbonate should be used to maintain a pH >7.25. Other
treatment may include H1 and H2 blockers, transcutaneous or intravenous pacemakers for all bradycardic rhythms.
Continue CPR for at least 60 minutes, as very good neurologic recovery has been reported in patients after very
prolonged cardiac arrests from local anesthetic overdoses.

Summary
The guidelines for pediatric advanced life support emphasize early recognition and treatment respiratory failure and
shock. In cases where IV placement is difficult rapid placement of an intraosseous needle is recommended for
venous access. Vagal maneuvers are a first line intervention for SVT with progressive advancement to adenosine
and cardioversion, if the patient fails to improve. Amiodarone is recommended as the first-line treatementfor most
dysrhythmias, especially VT. Epinephrine remains a crucial medication in resuscitation. The standard dose of 0.01
mg/Kg is recommended; while the high-dose (0.1 mg/Kg) may actually cause harm. AEDs are recommended to
treat children >1 year of age; their effectiveness in infants <1 year of age is unclear. Chest compressions during
CPR should be hard and fast maintaining a ratio of 15 compressions to 2 manual ventilations. Therapeutic
hypothermia may be neuroprotective. Family presence during resuscitation should be considered.

434
Page 7
Table 2. Summary of Selected Doses in Pediatric Resuscitation
"#$%&' (#))'*+
,-'*#$.*' 0.1 - 0.2 mg/kg Sv1
,).#-%/#*' 3 mg/kg
(up Lo 3 doses)
v1 or Sv1
01.*'12/.*' 0.01 mg/kg ulseless or 8radycardlc
ArresL
3%&*'$.4) 23 - 30 mg/kg 1orsade de olnLes
(%/-.#5'/$.#* 0.3 - 1 [oule/kg Sv1
"'6.7/.88%+.#* 2 [oules/kg
(max 4 [oules/kg)
venLrlcular flbrlllaLlon
,0" 9,4+#)%+.: 0;+'/*%8
"'6.7/.88%+.#*<
AdulL dose > 8 yoa
edlaLrlc aLLenuaLor
< 8 yoa
Sudden Collapse
ulseness
v1/vl

See Circulation October 2010 for detailed guidelines and precautions.

Recommended Reading:

Aufderheide T, Lurie KG: Death by hyperventilation: a common and life-threatening problem during
cardiopulmonary resuscitation. Crit Care Med 2004; 32[Suppl]:S345-351.

Berg RA, Otto CW, Kern KB et al: A randomized, blinded trial of high-dose epinephrine versus standard-dose
epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med 1996, 24:1695-1700.

Bhananker SM, Ramamoorthy C, Geiduschek JM, Posner et al: Anesthesia-related cardiac arrest in children: update
from the pediatric perioperative cardiac arrest registry. Anesth Analg 2007;105:344 50.

Boudreaux ED, Francis JL, Loyacano T: Family presence during invasive procedures and resuscitations in the
emergency department: a critical review and suggestions for future research. Ann Em Med 2002; 40:193-205.

Christensen R, Voepel-Lewis T, Lewis I, et al: Pediatric cardiopulmonary arrest in the postanesthesia care unit:
analysis of data from the American Heart Association Get With The Guidelines() -Resuscitation registry. Paediatr
Anaesth. 2013 Jun;23(6):517-23. doi: 10.1111/pan.12154. Epub 2013 Apr 1.

Turek JW, Andersen ND, Lawson DS, et al: Outcomes Before and After Implementation of a Pediatric Rapid-
Response Extracorporeal Membrane Oxygenation Program. Ann Thorac Surg. 2013 Mar 15. pii: S0003-
4975(13)00222-1. doi: 10.1016/j.athoracsur.2013.01.050. [Epub ahead of print].

Davis PG, Tan A, ODonnell CPF et al: Resuscitation of newborn infants with 100% oxygen or air: a systematic
review and meta-analysis. Lancet 2004; 364:1329-1333.

Flick RP, Sprung J, Harrison TE, et al: Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary
referral center. Anesthesiology 2007; 106:22637.

434
Page 8
Gabrielli A, OConnor MF, Macchioli GA. Anesthesia Advanced Circulatory Life Support. American Society of
Anesthesiology Committee on Critical Care Medicine and American Society of Critical Care Anesthesiology.
February 2008. Downloaded May 2010 from <http://asahq.org/clinical/Anesthesiology-CentricACLS.pdf>.

Gooden CK. 2010 Update: American Heart Association guidelines for pediatric resuscitation. SPA News, Society
for Pediatric Anesthesia, 24(1), Spring 2011.

Hazinski MF, Nolan JP, Billi JE, Bttiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW,
Jacobs I, Kleinman ME, Kloeck W, Koster RW, Lim SH, Mancini ME, Montgomery WH, Morley PT, Morrison LJ,
Nadkarni VM, O'Connor RE, Okada K, Perlman JM, Sayre MR, Shuster M, Soar J, Sunde K, Travers AH, Wyllie J,
Zideman D. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122(16 Suppl
2):S250-75.

Kleinman ME, de Caen AR, Chameides L, et al (2010) Pediatric Basic and Advanced Life Support Chapter
Collaborators. Part 10: Pediatric basic and advanced life support: 2010 International Consensus on
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Circulation122(16 Suppl 2):S466-515.
Perondi M, Reis A, Paiva E, et al: A comparison of high-dose and standard-dose epinephrine in children with
cardiac arrest. N Engl J Med 2004; 350:1722-1730.

Matos, R. I., R. S. Watson, et al. (2013). "Duration of Cardiopulmonary Resuscitation and Illness Category Impact
Survival and Neurologic Outcomes for In-hospital Pediatric Cardiac Arrests." Circulation 127(4): 442-451. [doi:
10.1161/CIRCULATIONAHA.112.125625].

Niles DE, Nishisaki A, Sutton RM, et al: Comparison of relative and actual compression depths during cardiac arrest
in children, adolescents and young adults. Resuscitation 2012; 83:320-326.

Ramamoorthy C, Haberkern CM, Bhananker SM, Domino KB, Posner KL, Campos JS, Morray JP. Anesthesia-
Related Cardiac Arrest in Children with Heart Disease: Data from the Pediatric Perioperative Cardiac Arrest
(POCA) Registry. Anesth Analg 2010; 110:1376-1382.

Reis AG, Nadkarni V, Perondi MB, et al: A prospective investigation into the epidemiology of in-hospital pediatric
cardiopulmonary resuscitation using the internation Utstein reporting style. Pediatrics 2002, 109:200-209.

Spittler KL: Family presence during CPR and invasive procedures. Pulmonary Reviews.Com 2006; 11(3). accessed
07/06/08 at [http://www.pulmonaryreviews.com/mar06/family.html].

Young KD, Gausche-Hill M, MCClung CD et al: A prospective population-based study of the epidemiology and
outcome of out-of-hospital pediatric cardiopulmonary arrest. Pediatrics 2004;114:157-164.

Disclosure

204
Page 1
Building a Quality Management System for Meaningful Use
John Allyn, M.D. Portland, Maine
I. Introduction
This lecture will discuss how to build a Quality Management System (QMS) to demonstrate and improve the value
of anesthesia care provided to patients (meaningful use). This lecture will not discuss meaningful use as defined by
the HIPPA of 2005 that allowed physicians and health systems to gain financial support for implementing and using
information technology. Before beginning to build a QMS, the principles that should guide the design and
management of the QMS will be reviewed. The structure of the QMS and methods of data collection, analysis, and
feedback will be discussed along with examples and present concerns.
II. Frame of Reference and Disclosure
Maine Medical Center (MMC) has approximately 32 anesthetizing locations on its main campus, 2 of which are
dedicated to obstetrics and 6-7 are located off-site or outside the operating room (ex. endoscopy suite). There is a
separate outpatient surgery center that has 10 operating rooms. On any given day 21 anesthesiologists, at least 6
anesthesiology residents and 36 CRNAs, staff these 42 anesthetizing locations. The anesthesiologists are employed
by Spectrum Medical Group (private practice) which markets a quality improvement product FIDES. Additional
figures and the entire slide set for this RCL will be available from: [email protected]
III. Background and Resources Available
The history of quality assurance or quality improvement is beyond the scope of this RCL; however, the foundations
for this work, the principles guiding the structure and management of a QMS, were provided by individuals such as
Shewhart and Deming. They introduced control charts and the Plan-Do-Study/Check-Act cycle. For those
interested, links to more information about Shewhart and Deming and other topics (ex. Root Cause Analysis, RCA)
are provided at the end of this lecture. Directors of anesthesia services are constantly asked to provide provider-
specific quality outcome data to justify hospital privileges whether for the Center for Medicare and Medicaid
Services (CMS) or an entity with deemed authority for accreditation for CMS (ex. Joint Commission (JC) or Det
Norske Veritas (DNV)). Why this request should be denied and the focus maintained on a providers participation
in a registry, your QMS, which continues to learn and improve patient outcomes will be discussed later, but links to
more information about CMS Conditions of Participation (COPs), JC, DNV, and ISO 9001 including information
about the JCs Ongoing Professional Practice Evaluation (OPPE) are also provided at the end of this lecture. The
ASA and AQI provide resources to help build and maintain a QMS; links to this information are provided. Finally,
the safety culture of the QMS will be strengthened when providers understand the state and federal protection
afforded for this work. Links to information about Patient Safety Organizations (PSOs) are also provided.
IV. Why Have a QMS?
First, quality improvement work is required by CMS (COP 482.21) and most likely is also required by your state
regulations and hospital by-laws. For practices with anesthesiology residents, the ACGMEs Clinical Learning
Environment Review (CLER) and Next Accreditation System Milestones require residents to participate in a QMS
(1). More importantly, for anesthesiology practices, there is a growing need to demonstrate value within the health
care system. The only way to do this is to build a system that will allow for data capture and analysis of the quality
and cost of care provided to patients. Finally, working in a culture of safety and building high performing teams
results in higher professional satisfaction, work becomes fun.
204
Page 2
V. Guiding Principles
A. QMS and Provider Privileging are Separate Systems.
To achieve quality outcomes two separate systems are required, one assures quality providers, and the other assures
quality systems. Assuring that quality of the providers working within the system is the responsibility of the
provider-privileging process. The quality system is the QMS.
1. Why keep provider privileging (ex. OPPE) and the QMS separate?
Both JC and DNV require provider-specific measures to justify granting hospital privileges to providers and suggest
possible measures to for this purpose. However, any measure used to assess hospital privileges by its very nature
has potential negative consequences (i.e. an unsatisfactory measure could mean loss of hospital privileges).
Providers will not participate in a QMS by self-reporting data and openly discussing concerns if their reporting or
reviews might adversely affect their or their colleagues ability to practice (privileges). However, directors of
anesthesia services are required to perform both functions. Health care quality leaders and the airline industry have
recognized this conflict between provider privileging and a QMS. The Institute of Medicine concludes: there is a
role both for mandatory, public reporting systems and voluntary, confidential reporting systems. However, because
of their distinct purposes, such systems should be operated and maintained separately.(2) The Agency for
Healthcare Research and Quality also concludes, The ability of health care organizations to replicate the successes
of other industries in their use of incident reporting systems will undoubtedly depend in large part on the uses to
which they put these data. Specifically, success or failure may depend on whether health care organizations use the
data to fuel institutional quality improvement rather than to generate individual performance evaluations.(3) The
airline industry maintains two systems. For the pilot privileges, the National Transportation Safety Board (NTSB)
administers a potentially punitive accident and event investigation process that might involve judgment(s) regarding
pilot competency and punitive actions such as pilot sanctions and fines. At the same time, to enhance the systems
performance, the Federal Aviation Administration (FAA) operates the Aviation Safety Reporting System (ASRS)
through NASA, a voluntary, confidential, non-punitive reporting system for the purpose of collecting, analyzing,
and responding to voluntarily submitted aviation safety incident reports in order to lessen the likelihood of aviation
accidents (aviations QMS).
2. How do we operate our privileging (OPPE for our hospitals) and QMS separately?
We developed a template for our OPPE measures that includes metrics in all six of the ACGMEs core
competencies.(4) Data for each OPPE metric is gathered outside of our QMS. For the provider specific outcome
data that JC requires we report each providers participation rates in the QMS which is neither self-reported nor
subject to patient or surgery related factors (i.e. no risk adjustment is needed). The importance of focusing on a
providers registry participation (participation rate) instead of the providers outcome measures has been adapted by
the ASA. In a recent letter to the CMS, ASA president Zerwas emphasizes the importance of registry participation
for individual providers and groups and that this alone would be a meaningful PQRS measure.(5) Additional OPPE
measures include data from reviews performed outside of the QMS, such as sentinel event reviews and malpractice
cases, and feedback received (praise or complaints). We rely greatly on the 360 reviews included in our OPPE
process. We measure anesthesiologists participation in evaluating their peers (% reviews complete). In addition,
360 reviews of each anesthesiologist by CRNAs have been very valuable. The final determination of privileges is
based on a subjective assessment of these largely qualitative data by a committee separate from the QMS and is
based on observed trends in their professional performance. We find this to be a robust process that identifies
deficiencies, resulting in recommendations and actions for individual providers that lead to successful remediation
of those deficiencies.
B. Focus on Systems.
Focusing on the systems performance should be the goal of any QMS. Deming estimated that 94% of performance
issues were the result of system issues and only 6% were due to a special cause (human error or machine failure).(6)
Therefore it should be expected that focusing on the performance of individual providers (peer review) will do little

204
Page 3
to improve the systems overall performance. Removal of a few bad apples (subpar providers) does little to
improve the overall average performance of the system. In contrast, education of all providers in the system (ex.
adopting a new protocol) may greatly enhance the systems performance, improving care provided to all patients.

C. We are human.

As humans, we will make mistakes. Reason points out that our fallibility is predictable and rooted in the essential
and adaptive properties of our cognition. Human errors are the penalties, the debt side of the cognitive balance
sheet, for our remarkable ability to handle complex problems.(7) Human errors are not intentional, the individuals
involved should not be judged, but rather consoled, and the system assessed and modified to prevent future errors.
Other factors that may affect system performance are at-risk and reckless behaviors; individuals should be held
accountable for the latter behavior. At-risk behavior may not reflect the desired performance of a team member, but
rather a learned behavior in response to the existing environment. Our primary goal must be patient safety, but at
times efficiency, a secondary goal, may obscure this primary goal. An example would be rushing to set up a room
to decrease turnover time and neglecting a safety check. At risk behaviors should be addressed with coaching.(8)

D. Culture eats strategy for lunch.

Integrity and trust must define the foundation of the groups culture and be demonstrated continuously by leaders of
both the group and the QMS. Providers must feel safe when reporting concerns. Providers should not feel they are
reporting themselves, but rather are highlighting a safety concern for the entire group. Defects are treasures and
without a robust reporting culture, becoming a strong learning organization is not possible.(9,10) Consequently,
without learning, resources would be wasted attempting to design an effective strategy for improving the care of
patients. Ongoing education about measurement is needed to support the groups safety culture. When an audience
hears that there is a difference in outcome between individual anesthesia providers, the assumption is often that this
difference represents a disparity in the quality of care provided. We remind providers that because of a lack of clear
data definitions, robust risk adjustment, and chance, we do not have the ability to assign a variance in a provider-
specific outcome measure to a deficiency in the quality of anesthesia care provided by an individual. This last point
cannot be over-emphasized. To strengthen our culture, we are constantly protecting principle A above. Accrediting
organizations, such as the JC, will ask to see quality data that is provider-specific. We respond to this request by
providing our OPPE (or Focused Professional Practice Evaluation, FPPE) data that includes provider specific
participation rates in the QMS. This latter measure does not need risk stratification, is entirely under the control of
the provider, and can be assessed in a statistically meaningful manner. We then demonstrate the improvements in
patient outcomes that our QMS has produced over time with this high level of participation. We also re-state the
reasons outlined above that we keep our QI data separate from provider privileging data (OPPE). Finally, we point
out the existence of separate successful confidential reporting systems (QMS) and public reporting systems
(privileging) used by the airline industry as discussed in detail above. We believe this dialogue strengthens our
culture and thus improves our QMS.

E. The goal may not be zero.

There are frequently unintended consequences of quality improvement work, not the least of which is resource
consumption. The consequence of aiming to reduce hospital readmission rates to zero may be added expense for a
long hospital stay. In addition, when provider-specific outcome measures are made public, high-risk patients may
be denied care.(11,12) Certainly challenging your QMS to eliminate central line associated blood steam infections
(CLABSIs) makes sense; however, labeling a pediatric oncologist as subpar when his/her patients continue to
have CLABSIs may not be fair. The patient factors presented by this pediatric oncology patient population
including maintenance of the central line outside the hospital may be well outside the scope of the resources the
pediatric oncologist is provided to influence this outcome.

F. QMS takes resources.

Over a decade ago, the Institute of Medicine recognized the importance of resource allocation for a successful QMS.
The IOM states: reporting systems without adequate resources for analysis and follow-up action are not useful.
Reporting without analysis or follow-up may even be counterproductive in that it weakens support for constructive
responses and is viewed as a waste of resources.(13) We have had experiences in our own practice that reinforce

204
Page 4
this message. One of our greatest challenges is creating communication that provides effective education and then
serves as a future reference for all members of the perioperative team. We can attempt to communicate at grand
rounds or morbidity and mortality conferences; however, not all anesthesia providers are present at these
conferences

(vacations, working at different sites, conflicting meetings, on call etc.). We supplement this by sending emails with
educational content as well as posting new guidelines and protocols on our groups resource web site
(theapms.com). Despite our efforts, we continue to make repeated errors. At one institution we were forced to
repeat a RCA surrounding a medication error, a medication error that had occurred in the same way, on the same
unit, but with different providers, two years earlier. In addition, when on-boarding employees it is important to
include prior communication and education about patient safety concerns. How your department and hospital, or
system, manages these educational efforts can either help or hurt your QMS. The harm to your QMS occurs, in part,
when individuals spend valuable hours creating educational content that is not distributed effectively to produce a
system change and takes these same providers away from productive work for the QMS. As mentioned above, the
Accreditation Council for Graduate Medical Education (ACGME) focuses heavily on residents participating in
patient safety and quality improvement work. The CLER Program assesses the sponsoring institution in six focus
areas, two of which are patient safety and quality improvement. For patient safety, the organization must
demonstrate opportunities for residents to report errors, unsafe conditions, and near misses, and to participate in
multidisciplinary teams to promote and enhance safe care.(1) Within quality improvement, how the sponsoring
institution engages residents in the use of data to improve systems of care, reduce health care disparities, and
improve patient outcomes will be assessed. The draft milestones for anesthesiology residents within the practice-
based learning and improvement competency require a junior resident to select a topic for a quality improvement
project, a mid-level resident to develop an implementation plan, and a senior resident to implement a plan for a
quality improvement project. Certainly inclusion of learners in the QMS must happen for the system to perform at
its highest level; however, simply creating a program requirement for residents to create or participate in a QI
exercise during their training may put the department or institutions QMS at risk. Each resident designing a QI
project will need resources, including mentorship and data, to be successful. In addition, these resident QI projects
must be collaborative and coordinated. If the end result for your institution is that you have both a pediatric and an
anesthesiology resident working independently on crisis checklists for managing the perioperative care of neonates,
individuals in both departments are likely to become frustrated, valuable resources will be lost, and the performance
of the QMS will suffer.

VI. Structure of QMS

The department or service lines QMS should be structured to align with hospital or health system priorities.
Specifically, how a safety concern (ex. possible sentinel event) can be communicated reliably and efficiently to the
hospitals patient safety officer should be defined; in turn the QMS may be asked to review concerns identified by
hospital leadership. Today we lack a robust inter-departmental quality and safety communication structure, but are
working to build this within a new service line structure. Originally our departments Quality Improvement
Committee (QIC) consisted only of anesthesiologists. Over time, we have continued to learn the value of including
all members of the perioperative team. Today, the committee includes all types of anesthesia providers, anesthesia
techs, perioperative nurses, and surgical techs. At one time we included a representative nurse from one of the busy
postoperative hospital floors; however, we struggled to create content that made monthly attendance valuable for
this individual. The wide representation on the committee enhances the QMS ability to capture and respond to
safety concerns while challenging the QIC to make valuable use of each members time. Presently, the QIC is
working on the systems best response to an operating room (OR) code roles for responders to an OR code are
presently being discussed after the QIC conducted a mock OR code with the help of our simulation center team.
Our QIC meets monthly and administrative support is provided to keep minutes; these minutes provide the
foundation for the next meetings agenda and assure that concerns are not lost. The QIC has one subcommittee,
the Critical Incident Committee (CIC), which reviews all critical events (ex. perioperative cardiac arrest). The CIC
is made up of anesthesia providers only. Members are assigned cases to review prior to meetings and a structured
form is used to review each case. Periodically the CIC provides reports to the QIC and may also provide education
to the department if specific concerns/trends are identified. New members of the department (anesthesiologists) are
required to attend these meetings for one year.

204
Page 5
VII. Data Capture

The QMS needs reliable and sufficient data to function. To acquire this data, the QMS must have a protected and
efficient means for providers, recovery room nurses, and perhaps others to provide the desired information. Both
paper and electronic reporting forms can be used. These forms will need constant review, and education about data
field definitions needs to occur periodically. The intraoperative indicators for MMCs QMS are shown in the table
below; those also collected by the AQI or the Anesthesia Business Group (ABG) are noted in the left-hand columns.
The data entered by providers or recovery room nurses is linked to data already in our billing data base (ex.
procedure) to decrease the amount of data providers must enter, but also strengthen the scope of questions the QMS
is able to address. For certain sites of service, our QMS has specific forms to improve efficiency and performance:
specific patient type forms (ex. obstetrical patients) or procedure type forms (ex. ECT) allow for a focused
simplified data set in these areas.

Intraoperative Quality Indicators

ABG AQI Indicator
X X No Listed Observations
Other Major Morbidity/Mortality

X
X
Blue button/STAT page
Death
Airway/Respiratory
X

X

X
X
X
X
X

X

X
X
X

X
Unable to intubate
Expected Difficult Intubation
Unexpected Difficult Intubation
Difficult mask airway
Reintubation in OR
Unable to extubate in OR
Desaturation <90% for >3 min. or <80% for >1 min
Narcan/Flumanzenil given
Pulmonary edema
Bronchospasm
Laryngospasm
Pneumothorax
Suspected aspiration
CardioVascular

X
X
X
X

X
X
X
Arrhythmia
Myocardial infarction
Myocardial ischemia
Cardiac arrest
Hypotension (requiring vasopressor infusion)
Neurologic

X
X Seizure
Central nervous system injury/Ischemia
Head/Neck Trauma
X Tooth damage
Regional/Procedural
X

X
X
X
X
X
X
X
X
Failed regional (requiring GA or repeat for any reason)
High spinal (requiring airway management)
Local anesthetic toxicity
Unintended dural puncture/wet tap
Vascular access complication
Pharmacy/Blood Bank
X

X
X
X
X
Medication event
Unexpected drug reaction
Malignant hyperthermia
Received blood transfusion

204
Page 6
Patient Safety
X
X

X
X
X
X

X
X
Incorrect surgical site, side, patient, procedure, implant
Equipment malfunction
Near miss/Safety concern
Patient Burn/Fire
Patient Fall
Discharge/Planning

X

X
Case canceled in OR
Unplanned ICU admit
Miscellaneous
X Other

VIII. Data Analysis and Feedback (with examples)

Quality improvement is not achieved by collecting data or sending data to a registry. MMCs program began in this
manner, but we now better understand the investment needed for data analysis and we are constantly learning to
provide feedback in a manner that more easily supports further dialogue and leads to improvements in patient care.
Early reports generated by our QMS were not always easy for individual providers to interpret and we implemented
very few quality improvement tests of change. Today we track high frequency events such as first temperature on
arrival to PACU or recovery room nausea or vomiting rates using trend graphs. Our QIC reviews these trends every
3-6 months. We have learned that it may take several years for us to demonstrate a sustained change or to recognize
a variance. For some of this data we have explored use of a statistical process control chart. For low frequency
events, such as desaturation in the operating room or recovery room, we group these data elements into categories
(ex. desaturation would be grouped with difficult intubation and reintubation). Each category of low frequency
events (equipment, hemodynamics, etc.) is then assigned to one anesthesiologist to review. Periodically, the
anesthesiologist assigned to review each category reports to the QIC and discusses any concerning trends in need of
further investigation.

The QMS also supports ad hoc analysis. As part of this analysis, even if the QMS is performing well on average for
all patients, we have learned from analysis of failures. Two examples are provided below. Additional examples will
be provided in the lecture.

A. Temperature and hip replacement patients:
The majority of our patients arrive in our recovery room with a temperature of greater than 36C and this trend
continues to increase. However, when we looked at the population of patients who failed to meet this metric, we
discovered that this group contained an over-representation of one surgeons patients having hip replacements. Our
observation of these cases led us to believe that positioning of these patients delayed the application of a forced air
warming blanket, and when applied this blanket was felt to provide suboptimal coverage. We instituted a test of
change and began warming these patients preoperatively. Our measurements for these patients, reported quarterly
over the past two years, demonstrate a steady decline in the percentage of patients arriving in the recovery room
hypothermic.

B. Patient Satisfaction:
On average, our outpatients are very satisfied with their anesthesia care when asked as part of a postoperative phone
call (POD #1) by a preoperative nurse. As with the example above, our QIC chair tried to understand better how we
might be failing to meet some patients expectations. A preliminary analysis demonstrated that two of our
anesthesiologists were more likely to have patients that were dissatisfied with their anesthesia care. We lack the
ability today to risk adjust this measure, but we discovered as part of this analysis that patients receiving care at one
of our facilities were more likely to be dissatisfied and in fact, they were more likely to be cared for by a particular
group of surgeons that practice at that facility. The two individual anesthesiologists identified in the initial analysis
as having higher rates of patient dissatisfaction practice more frequently at this facility and with these surgeons.
Feedback to this individual surgery practice has resulted in a decrease in the in the rate of patients dissatisfaction
with their anesthesia care at this facility and thus also for these two anesthesiologists.

204
Page 7
Feedback to Individual Providers for Self-Reflection:
Our QMS lacks adequate risk adjustment tools and adequate numbers of cases to identify a statistically sound
difference in the quality of anesthesia care delivered by two providers. As stated previously, we believe utilizing QI
data for such purposes would also inevitably lead to under reporting and undermine our safety culture. We have
thus chosen not to use clinical outcome measures to judge our providers; however, we do provide feedback reports
to each individual provider in our practice for self-reflection; no one else reviews these individual reports. These
reports allow the individual provider to see their own outcome rates (ex. recovery room nausea and vomiting) as
well as the groups averages for these same data elements. We encourage providers to evaluate any variance in their
rate from the groups average and consider possible hypotheses for the variance in light of their subjective
assessment of risk adjustment and their understanding of possible factors associated with the outcome, and
implement tests of change in their own practice. We believe dialogue about these variances also strengthens our
culture. An example of self-reflection leading to improvement would be a provider noting that his recovery room
nausea and vomiting rates were higher that the groups average for patients cared for at an outpatient facility; a small
subset of providers work at this facility and the patients and procedures at the facility are relatively homogeneous.
After comparing his practice with his peers working at this facility, this provider implemented a change in his
practice and reduced his rate of recovery room nausea and vomiting to the groups average for that facility.

The QMS also provides many types of reports. At times specific proceduralists will ask for data on their patients.
In addition, the QMS may respond to help confirm resident case numbers or compliance with SCIP measures (for
example). At times a query of our QMS will be the first step for the hospital when a process of care is being
evaluated. Finally, annual reports are provided to the group and the hospital.

IX Next steps

MMC recently adopted a service line structure and given the multi-disciplinary representation on our QIC, we feel
this committee is well positioned to serve the Surgical Services Service Line. The committee presently has two
multi-disciplinary projects: operating room codes and the use of crisis checklists. Both of these projects will take
considerable resources to develop and implement, we are approximately six months into the operating room codes
project and just starting to work on crisis checklists. Lastly, we feel we are only beginning to understand what
patients mean when they answer that they are satisfied or dissatisfied with their anesthesia care. Presently we only
capture this data in a reasonably robust manner for outpatients; our data for inpatients is suboptimal, and we need to
continue to work on both.

References:
1. ACGME. Clinical Learning Environment Review (CLER) Program. 2013; http://www.acgme-
nas.org/cler.html. Accessed 4/25/2013.
2. Kohn LT, Corrigan J, Donaldson MS. To err is human: building a safer health system. Washington, D.C.:
National Academy Press; 2000. Page 10
3. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical near miss reporting
systems. BMJ. Mar 18 2000;320(7237):759-763.
4. ACGME. Program Requirements for Graduate Medical Education in Anesthesiology. 2008.
5. Zerwas JM. Re: CMS-3276-NC Medicare Program; Request for Information on the Use of Clinical Quality
Measures (CQMs) Reported under the Physician Quality Reporting System (PQRS), the Electronic Health
Record (EHR) Incentive Program, and Other Reporting Programs. 2013.
6. Deming WE. Out of the crisis. 1st MIT Press ed. Cambridge, Mass.: MIT Press; 2000. Page 315
7. Reason JT. Human error. Cambridge England; New York: Cambridge University Press; 1990. Page 17
8. Wack-a-mole Page 55
9. Just Culture and its Critical Link to Patient Safety (Part 1). 2012;
http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=22. Accessed 4/25/13, 2013.
10. Just Culture and its Critical Link to Patient Safety (Part 2). 2012;
http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=26. Accessed 4/25/2013.
11. Lee TH, Torchiana DF, Lock JE NEJM 2007;357:111-3
12. Moscucci et al. Public Reporting and Case Selection for Percutaneous Coronary Interventions. J Am Coll
Cardiol 2005;45:1759-65.
13. Kohn LT, Corrigan J, Donaldson MS. To err is human: building a safer health system. Washington, D.C.:
National Academy Press; 2000. Page 100
204
Page 8
Resources:
1. Shewart: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464836/
2. Deming: Deming Institute: https://deming.org/theman/overview
3. Donabedian: The quality of medical care. Science. May 26 1978;200(4344):856-864. (introduced structure,
process, and outcome measures)
4. Root Cause Analysis (RCA): http://psnet.ahrq.gov/primer.aspx?primerID=10
5. Failure Mode Effect Analysis: Description and example from Institute of Safe Medical Practices (ISMP):
http://www.ismp.org/tools/FMEA.asp
6. Lean Manufacturing discussion: Lean Manufacturing discussion:
http://mti.mercubuana.ac.id/wp-content/uploads/2010/10/holweg-2007-history-of-lean-prod.pdf
7. Centers for Medicare and Medicaid Services (CMS): CMS defines Conditions of Participation (COP) for
payment for anesthesia services. (REF) These COP require QI work. In addition, never evens ex. Lack of
payment for complications secondary to CLASBI or readmissions force hospitals to improve their quality of
care to avoid these complications.
8. Never Events: http://psnet.ahrq.gov/primer.aspx?primerID=3
9. Physician Quality Reporting System (PQRS): http://www.cms.gov/Medicare/Quality-Initiatives-Patient-
Assessment-Instruments/PQRS/index.html?redirect=/pqri/. More from the ASA on PQRS in the members only
section: http://www.asahq.org/
10. The Joint Commission (JC). In 1910 Ernest Codman proposed that hospitals standardize and track patient
outcomes. When the American College of Surgeons (ACS) was founded in 1913, this principle was adopted
and the ACS began to inspect hospitals. In 1951, the American College of Physicians (ACP), the American
Hospital Association (AHA), the American Medical Association (AMA), and the Canadian Medical
Association (CMA) joined with the ACS as corporate members to create the an independent, not-for-profit
organization, The Joint Commission on Accreditation of Hospitals (JCAH), whose primary purpose is to
provide voluntary accreditation. (http://www.jointcommission.org/about_us/history.aspx) The JC publishes
standards that hospitals must meet to maintain accreditation. The JC has an entire chapter dedicated to
Performance Improvement. Most of the JC material must be purchased. More information is available at:
http://www.jointcommission.org/. Recently JC incorporated ISO 9001 standards as well
(http://www.jointcommission.org/assets/1/18/hospital_accreditation_1_31_11.pdf). In 2007, JC introduced two
new privileging concepts, Ongoing Professional Practice Evaluation (OPPE) and Focused Professional Practice
Evaluation (FPPE) that require provider-specific measurements as part of the hospital privileging process. (ex.
Joint Commission Hospital Accreditation Standards. MS.08.01.03)
11. Det Norske Veritas (DNV) was established in 1864, initially as a company that would inspect and evaluate
merchant vessels. They are relatively new to healthcare in the USA. DNV uses ISO 9001 for the design and
maintenance of a QMS. More information about DNV is available at:
http://www.dnv.com/moreondnv/profile/about_us/ and
http://www.dnv.com/industry/healthcare/quality_management/dias/index.asp. More information about ISO
9001 is available at: http://www.iso.org/iso/home.html
12. ASAs MADOM The American Society of Anesthesiologists Quality Management and Department
Administration Committee maintains a Manual for Anesthesia Department Organization and Management,
which provides guidance for building and managing a QMS. This is available (free to members) at:
https://ecommerce.asahq.org/p-154-madom-2010-manual-for-anesthesia-department-organization-and-
management.aspx
13. The Anesthesia Quality Institute (AQI) website offers guidance in building and maintaining a QMS. In
addition, the website provides definitions for the measures collected by AQI, how to join AQI and obtain
assistance moving data to AQI. Recently the ASAs Closed Claims Database became part of AQI. More
information at: http://www.aqihq.org
14. Patient Safety Organization: Patient Safety and Quality Improvement Act, Public Law 109-41, 924 (2005).
More information at: http://www.pso.ahrq.gov/psos/overview.htm
15. Patient Safety Culture see references 9 and 10
Disclosure
Spectrum Medical Group - FIDES, Self, Ownership

209
Page 1
Chemical Dependency and Anesthesiology
John Tetzlaff, M.D. Cleveland, Ohio
The discovery of anesthesia and addiction to the drugs used to provide anesthesia have a common origin. Cocaine
had a social use profile before its incidental discovery as a topical anesthetic. Experiments with injection of cocaine
to anesthetize plexus and peripheral nerves led to addiction of early 20
th
century master surgeons, such as Halsted,
who performed the experiments.
(1)
Early experimentation with ether, nitrous oxide and chloroform also caused
psychological and even physical addiction. It is not surprising, therefore, that addiction to anesthetic drugs and
anesthesiology remain linked and that addiction remains the most prevalent, serious occupational health risk
associated with anesthesia. Because of the morbidity, much is known.
Scope of the Problem
Although addiction to anesthetic drugs has become a prominent issue for anesthesiology in the United States, this
issue is neither new nor restricted to the USA. In an early report, Bruce
(2)
reported on the mortality and causes of
death of anesthesiologists, noting lower death rates in most categories, except suicide, which was three times the rate
for other physicians (1947-66). Lew
(3)
reported similar data (1954-76), with lower overall age-adjusted mortality,
except for 6.2% suicide (2 times normal) and 6.9% accidental. Although the suicide rate is higher in general for
physicians
(4)
, suicide in anesthesia providers is highly associated with addiction.
(5)
Ward
(6)
surveyed residency and
nurse anesthesia programs for 10 years prior to 1982. With a 74% response rate, the incidence of addiction was 1%
per year of giving anesthesia for the first five years. Gravenstein
(7)
reported the same 1% addiction rate with an
alarming mortality of 7 providers out of 44 reported. The issue is also not restricted to the United States. Berry
(8)

survey 304 departments of anesthesia in the United Kingdom and Ireland and found cases in this interval (1990-99)
in 39% of departments reporting (71.7% response rate) and drew the remarkable conclusion that one anesthesia
provider per month in the United Kingdom was disabled by addiction. Weeks reported a comparably high incidence
for Australia and New Zealand
(51)
. The risk is not limited to physician anesthesiologists, with comparable or higher
rates in CRNAs, with as high as 10% risk for a full career.
(9)

Even though the issues are now well known and education/prevention steps are widely in use, the incidence has not
seemed to change. Booth
(10)
surveyed 133 programs in 1997, achieved a 93% response rate, and reported 1.6%
addiction rate in residents and 1.0% in faculty, despite 47% of respondents reporting increased education and steps
to prevent diversion of controlled drugs. Collins
(11)
surveyed 176 programs (M.D. and D.O.), achieving a 66%
response rate, with 80% of responding programs reporting at least one incident in the interval (1991-2001) with 19%
reporting mortality. If anything, the mortality may actually be increasing, by comparison of the Collins
(11)
data for
the 1990s with the 10% mortality reported by Spiegelman.
(12)

Speculation about the Cause
While there will never be absolute proof, there is a consensus that a variety of issues combine to create a high risk of
addiction. These include exposure to the drugs, familiarity with their pharmacology, access, stress and the uniquely
addictive properties of anesthetic drugs. Prior addictive and high risk behaviors seem to be highly associated.
Chemical experimentation in medial students has been reported
(13)
be 30-50%, and several reports have suggested
that prior illicit drug use may motivate (consciously or unconsciously) the individual to choose anesthesia.
(11, 14)
In
a large series, high risk behavior was found to be highly predictive of addiction.
(15)

Occupational exposure seems to be a clear association. As previously mentioned, early experiments to create safe
anesthesia techniques (nitrous oxide, ether, chloroform, cocaine) created victims of addiction in the investigators.
The high incidence identified is even more remarkable when the early presentation of addiction is considered. In
209
Page 2
both physicians and CRNA, the incidence of addiction is highest during the first 5 years of giving anesthesia.
(6, 16, 17,
18, 52)
There is other suggestive evidence that the risk is giving anesthesia. Oral surgery residents in some
maxillofacial residency programs receive extensive training (often from anesthesiologists) in giving anesthesia, and
they report the same incidence of addiction proportionate to time in anesthesia with the same drug profile.
(17)
The
converse is equally true- physicians who do not practice anesthesia (internists) have a lower rate of addiction and
suicide compared to an age and gender matched cohort of anesthesiologists
(53)
.
Simply experiencing clinical anesthesia alone is too simple of an explanation for the risk of addiction. Gold has
presented a provocative hypothesis that aerosol contact with fentanyl during opening of fentanyl ampoules
(1)
or from
exhaled breath of patients
(72)
or contact with fentanyl or propofol from working surfaces within the operating room
(77)
may cause neurochemical changes in the brain that predispose some providers to become addicted
(73)
. They
confirmed this hypothesis by detecting fentanyl and propofol in the air in several locations within active operating
rooms
(78)
. The ASA Committee on Occupational Health has responded with the observation that exposure to
fentanyl as a cause is preliminary data that should be further evaluated, citing a variety of methodological issues.
(57)
The neurochemistry of addiction is becoming well understood, with chemical changes in the reward centers leading
to exaggerated need for drug acquisition, and exaggerated reward from experience with the drug.
89
Another possible
explanation is a lower density of dopamine receptors in reward centers, resulting in less reward from natural
reinforcers.
91, 92
In adults with addiction to gambling, increased activity in the reward center in response to gambling
prompts is detected by functional MRI, compared to controls
(101)
. A molecular mechanism for the sensitization has
been suggested by Kovacic, who reports that addictive substances have in common the ability to create reactive
oxygen species (ROS) that result in electron transfer that activates brain reward centers
(80)
. Further work has
established that metabolites of propofol and fentanyl create these ROS messengers
(81)
.
Other elements of anesthesia practice that contribute to addiction are less objective but undisputed. The anesthesia
provider is unique in organized medicine in providing start-to-finish administration of controlled substances.
Even the most junior resident will obtain-fentanyl, draw it up, decide to inject, observe the effect, chart the
intervention and handle the accounting of waste, often without any observed assistance. No other resident routinely
has this experience or possesses these skills. New anesthesia providers also rapidly learn the clinical pharmacology
of these substances by observation, reading and trial and error. This creates both the skill for self-medication, and
the more ominous skill to achieve painless suicide. Self-medication may be an occupational hazard of the operating
room related to stress and lack of positive reinforcement. New anesthesia providers get a disproportionate level of
the work, their skill level is lower and as a result, their efficiency is low. And the operating room is rough on
newcomers. These factors, combined with some natural curiosity about the drugs being used, create an unfortunate
propensity for anesthesia newcomers to self-mediate. They know how, what to use, and the fallacy in the highly
educated provider is that they can control the experience. Unfortunately, this initiates a cascade of use and addiction
that accelerates at a very rapid rate. Gold
(1)
reports a case where a single experiment with intranasal accelerated to
injection of 30mL/day of sufentanil within 30 days. In the context of high stress, reduced self-esteem and
availability of synthetic opioid, Ward
(18)
states that control is gone after the first self-medication even though the
individual doesnt know it. Farley
(19)
identifies other unique element of anesthesia practice, including a chemical
solution to solving problems, and the isolated nature of anesthesia practice. Moleskin
(20)
further speculates that
routine use of controlled substances minimizes the importance of tight accounting, desensitizing the individual to its
relevance.
Other features may be triggering events for the subset of providers. Prior experience with substance abuse or high
risk behavior has been previously identified. A prior history of psychiatric illness (contributory or coincident) can
be contributory in the addicted anesthesia provider.
(15, 16, 21)
Personality disorders
(74)
and primary psychiatric
diagnoses
(75)
are commonly found in addicted physicians, and self-medication may represent a response to these
symptoms.
(76)
Depression is known to be associated with suicide, and although complicated, may be linked to self-
medication and addiction
(82)
. There is strong evidence for a genetic susceptibility to addictive behavior, especially
the transition from abuse to dependency.
88
Drugs Involved in Addiction for Anesthesiologists
From the substance abuse literature, the progression of substance (ETOH to marijuana to cocaine) is a common
observation. Addiction within anesthesiology does not follow this pattern. Although the incidence of addiction to
drugs used in anesthesia is alarmingly high, the incidence of abuse of illicit drugs (alcoholism, THC, cocaine) is
low. Addiction within anesthesia has always focused on anesthetic drugs. Prior to 1980, the drugs involved were

209
Page 3
meperidine, diazepam, and barbiturates.
(22.23)
After 1980, addiction has been heavily concentrated in the fentanyl
family
(6,10,17,19)
Although parenteral fentanyl is the rule, severe addiction to oral fentanyl has been reported,
although the victim was a nursing supervisor who lacked some of the parenteral administration skills.
(24)
Although
rapid metabolism would seem to make parenteral remifentanil abuse seem unlikely, intranasal self-administration
has been reported as the entry point to a fentanyl addiction
(79)
. Midazolam
(17)
and ketamine
(25)
have been reported in
addiction cases, as has nitrous oxide
(54)
and potent inhalation agents, such as enflurane.
(26)
In a survey of academic
departments, 22% reported at least one incident with an inhaled agent with less than half of the individuals involved
entering rehabilitation, less than 30% return to practice, and a 26% mortality rate.
(64)
Propofol is the newest player
on the scene with one case report
(27)
involving injection to unconsciousness up to 15 times per day. In a survey of
academic anesthesiology programs from 1995-2005, Wischmeyer reported 18% of programs had a propofol abuse
incident with 28% of the cases detected by death.
(71)
Repeated, prior exposure to propofol may be causative, with
experience of the euphoria leading to intense craving and psychological dependence.
94, 95, 96

The addiction potential with anesthetic drugs has been reviewed. Propofol has been tested in volunteers and found
to have properties associated with addiction,
(27)
although the pharmacokinetics predict a difficult abuse pattern,
requiring either pump infusion or frequent, intermittent injection. The addictive potential for other uncommon
substance has been predicted based on the side effect profile,
(28)
including local anesthetics (dysphoria), cocaine
(euphoria, stimulation), anticholinergics (psychotomimetic), antihistamines (sedation) and ephedrine (stimulant).
Ketamine has an obvious role in those with prior psychotropic drug use, such as LCD, or PCP.
(25, 29)

Detection
Unfortunately, self-reporting of serious addiction is uncommon. Direct observation of abuse and audits that confirm
suspicion are the most common means of detection. Unfortunately, suicide, accidental death and coma combined
are more common than self reporting.
(19)
Suicide during evaluation of possible addiction is a serious issue.
(30)

Intervention must be conducted carefully, with the goal of getting the suspected addict into a safe treatment facility,
using progressively increasing motivators like reporting, termination, and as a last resort, police involvement. In
one case, the cause of death was determined to be propofol by hair analysis where blood and urine toxicology were
negative.
(31)
In cases where suspicion is high and urine toxicology is repeatedly negative, hair analysis has
detected addiction to fentanyl, sufentanil, and alfentanil
(55)
. Detection of drugs with brief half-lives such as
ketamine, midazolam and propofol are difficult or impossible in routine toxicology
(27,32)
and may require either
observed abuse and rapid for cause screening, or hair analysis.
(33,55)
The fentanyl family is especially difficult to
detect because of the brief plasma half-life and non-detection of metabolites.
(24,34)
A computer profile of drug use to
detect outliers might be a better approach.
(35)
Epstein has prospectively applied this computer profile, and
demonstrated that it detects diversion months before clinical detection, although its sensitivity needs to be refined
before it becomes a first line tool, due to false positives.
87
Another electronic approach, using run charts comparing
individual use against time to identify upward trends in individuals, also shows promise.
90
A promising opportunity
for detection of propofol abuse is a urine assay for detection of the glucuronide metabolites of propofol, present in
the urine for up to 3 days after exposure.

The urgency for detection of diversion of substances has never been low, but it has increased dramatically with the
disclosure that individuals involved in diversion have used techniques that have resulted in injury to patients.
Clusters of hepatitis infection have been traced to diversion practices of an infected health care provider
(98)
.
Irresponsible handling of diverted substances and/or equipment presents a risk to all other health care workers
(99)
.
The risk is particularly relevant given the variable level of prevention of diversion from institution to institution and
state to state
(100)
.

Re-entry
Addiction is a disease as well as a federally protected disability, as long as the addict remains in treatment.
(67)

Treatment only succeeds when evaluation reveals addiction and the victim is able to fully acknowledge their
addiction. This is rarely (if ever) successful without in-patient treatment, graded re-entry with a contract, handling
of addictive substances by other providers, and random testing, including periodic hair samples.

Even with the risk, a simple majority of providers will want to re-enter anesthesia. The outcome, however, is not
always promising. In general physicians have a better outcome in rehabilitation from addiction than non-physicians

(36)
even from opioid (prescription) abuse.
(60)
The California Physician Diversion Programs data suggests that this
also applies to addiction involving anesthesiologists, although their definition of recovery may be very generous.
(37)

209
Page 4
Some other data is in agreement,
(38)
however there is also evidence that re-entry is both ineffective and risky.
Collins reports a 40% failure rate with re-entry of residents and 9% mortality. Re-entry for student nurse
anesthetists has the same poor prognosis.
(39)
Merk reports 34% successful re-entry for residents with 13 having the
first presentation of relapse as death.
(40)
Bryson
(58)
reported a graded re-entry of residents involving work in a
simulation center for the first 12-15 months prior to re-entry. The value of this approach has been challenged
(59)
in
light of the 60% relapse rate they report, and there remains a serious doubt that re-entry is ever the right choice for a
resident
(67)
. The failure rate, the cost to the department with attempted re-entry, and the mortality rate led Berge
(68)
,
in an editorial in Anesthesiology, to advocate one strike and youre out, a universal prohibition to re-entry.
Oreskovich
(69)
and others responded to this strong position with circumstances where this would be excessive and
highlighted the role of the highly effective state Physician Health Committees (PHC). It may be that the resident
failure rate is related to the less universal role of PHC in the re-entry of residents.

Hedberg
(41)
has attempted to quantify the process by defining criteria that predict success and failure with re-entry.
He has divided anesthesia providers in rehabilitation into three categories based on specific criteria, with category
two needing delay and re-evaluation after one to two years and category three being individuals who should never
practice anesthesia. Domino reports greatly increased risk of relapse when there is a coexisting psychiatric disorder,
family history of substance abuse, or in those addicted to opioid, with the increase even greater if more than one of
these risk factors is present
(56)
. Re-entry may actually oppose the process of recovery by re-exposing the addict to
the visual, olfactory or physical cues to the emotions that triggered self-medication, and also may explain why
delayed re-entry is required
(65)
. If re-entry is attempted, the focus should be on prevention of relapse
(84)
. There is
even risk of relapse from subsequent required medical care, if exposure to triggering substances (opioids, propofol)
is required for medical or surgical care.
93

Prevention

There is universal agreement that mandatory education about the risk of substance abuse, stress and fatigue
management should be a part of all anesthesia training programs at the entry point and regularly thereafter. There is
also general agreement that this education process should continue beyond residency, although this is less
universally applied. Despite evidence that the majority of training programs have increased their education
programs, Booth
(10)
reports no change in the incidence of substance abuse. Previous reports of inadequate education

(42)
have created the education but not decreased the risk. Increased effort to prevent the diversion of controlled
substances has also been instituted in a majority of programs
(10, 43)
including locked boxes, dispensing machines,
video surveillance and satellite pharmacies. Some effect has been observed, including reduced controlled substance
discrepancy.
(20)
Electronic data analysis can reveal average user profiles, and provide detection via outliers.
(20, 35)

The subject of random drug testing is controversial
(83)
. The almost infinite number of ways to tamper with urine
toxicology screening must be considered.
(70, 86)
Although a promising avenue in the future, detection of anesthesia
drugs in oral fluid is not possible at this time
(85)
. In responses to the survey of Booth,
(10)
a majority of chairs favored
random testing, although only two programs outside the military have instituted such a program. Fitzsimons
(61)

presents the first five years of one of these programs designed to prevent addiction which includes a random testing
element, and reports no addicted providers detected. The Department of Transportation (DOT) has had a random
screening program for almost two decades for commercial drivers, railroad and airline pilots. Industry has followed,
with more than 90% of companies with more than 5000 employees having some kind of testing.
(44)
Random testing
programs have been shown to reduce positives
(45)
and save health care dollars. Mike Scott, previous council to the
ASA, has written a review of random testing,
(46)
in which he identifies the AMA endorsement of for cause testing
and discusses the unresolved legal issues with random testing. Although random testing is prohibited in 12 states,
there are exceptions for industry involved in safety. Concerns by the AMA are expressed in an editorial which
discusses privacy, handling of false positives, confidential records and the approaches to randomization.
(47)
DOT
rules have created the need for the role of a Medical Review Officer, a physician with specific training to handle the
initially positive screen.
(48)
All recovering physicians are subject to random screening during recovery and any
failure or absence requires action.
(49)
Collins
(11)
data reveals a slightly higher rate of pre-employment screening
(16%) and pre-employment toxicology screening. Based on the kind of data in Mens Health
(50)
( the Junkie in the
OR) and two recent cases that made headline news in the press on the East Coast, the lay public may begin to
demand random screening. It is clear that detection during residency training is a responsibility of the residency
program.
(62)
Failure to report provider impairment may incur legal liability for the anesthesia department, the

209
Page 5
hospital or anesthesia groups who know.
(63)
Regardless of the legal risk, protocols for handling of impairment and
substance abuse should be present in every department.
(66)

Conclusion
Substance abuse is the most serious occupational safety hazard for anesthesiology. Causing devastating
consequences to the career, morbidity, personal stress and death, it is a high attractive target for prevention. The
nature of anesthesia (working alone, production pressure, isolation) and the handling of highly addictive drugs are
contributors. Up to 1% per year of residents may become addicted. The mortality rate of relapse may approach 9%.
Prevention by education, tight control of controlled substance use, profiling for outliers and possibly random urine
toxicology may be needed to arrest this serious hazard of providing anesthesia.

References
1. Gold MS, Byars JA, Frost-Pineda K. Occupational exposure and addictions for physicians: case studies and
theoretical implications. Psychiatr Clin N Am 2004;27:745-53.
2. Bruce DL, Eide KA, Linde HW, Eckenhoff JE. Cause of death among anesthesiologists. Anesthesiology
1968;29:565-9.
3. Lew EA. Mortality experience among anesthesiologists. Anesthesiology 1979;51:195-9.
4. Williams SV, Munford RS, Colton T, et al. Mortality among physicians: a cohort study. J Chronic Dis
1971;24:393-401.
5. Blachy PH, Osterud HT, Josslin R: Suicide in professional groups. N Engl J Med 1963;268:1278-82.
6. Ward CF, Ward GC, Saidman LJ. Drug abuse in anesthesiology training programs. JAMA 1983;250:922-5.
7. Gravenstein JS, Kory WP, Marks RG. Drug abuse by anesthesia personnel. Anesth Analg 1983;62:467-72.
8. Berry CB, Crome IB, Plant M, Plant M. substance misuse amongst anaesthetists in the United Kingdom
and Ireland. Anaesthesia 2000;55:946-52.
9. Bell DM, McDonough JP, Ellison JS, et al. Controlled drug misuse by certified registered nurse
anesthestists. AANA J 1999;67:133-40.
10. Booth JV, Grossman D, Moore J, Lineberger C, Reynolds JD, Reeves JG, Sheffield D. Substance abuse
among physicians: a survey of academic anesthesiology programs. Anesth Analg 2002;95:1024-30.
11. Collins GB, McAllister MS, Jensen M, Gooden TA. Chemical dependency treatment outcomes of residents
in anesthesiology: results of a survey. Anesth Analg 2005;101:1457-62.
12. Spiegelman WG, Saunders L, Mazze RI. Addiction and anesthesiology. Anesthesiology 1984;60:335-41.
13. Epstein R, Eubanks EE. Drug use among medical students. N Engl J Med 1984;311:923.
14. Gallegos KV, Browne LH, Veit FW, Talbott GD. Addiction in anesthesiologists: drug access and patterns
of substance abuse. QRB 1988 (April)116-22.
15. Yarborough WH. Substance use disorders in physician training programs. J Oklahoma State Med Assoc
1999;92:504-7.
16. Talbott GD, Gallegos KV, Wilson PO, Porter JL. The medical association of Georgias impaired physician
program: review of the first 1000 physicians. Analysis by specialty. JAMA 1987;257:2927-33.
17. Rosenberg M. Drug abuse in oral and maxillofacial training programs. J Oral Maxillofac Surg
1986;44:458-62.
18. Ward CF. Substance Abuse (Editorial). Anesthesiology 1992;77:619-22.
19. Farley WJ, Talbott GD. Anesthesiology and addiction. Anesth Analg 1983;62:465-6.
20. Moleski RJ, Easley S, Barash PG, Primer G, Shier NQ, Schrier RI. Control and accountability of controlled
substance administration in the operating room. Anesth Analg 1985;64:989-95.
21. Flaherty JA, Richman JA. Substance use and addiction among medical students, residents and physicians.
Psyche Clin N Amer 1993;16:189-97.
22. Hughes PH, Brandenberg N, Baldwin DC, Storr CL, Williams KM, Anthony JC, Sheehan DV. Prevalence
of substance use among US physicians. JAMA 1992;267:2333-9.
23. Hughes PH, Baldwin DC, Sheehan DV, Conard S, Storr CL. Resident physician substance use by specialty.
Am J Psychiatry 1992;149:1348-54.
24. Hays LR, Stillner V, Littrell R. Fentanyl dependence associated with oral ingestion. Anesthesiology
1992;77:819-20.
25. Moore NN, Bostwick JM. Ketamine dependence in anesthesia providers. Psychosomatics 1999;40:35609.
26. Musshoff F, Junker H, Madea B. An unusual case of driving under the influence of enflurane. Forensic Sci
Int 2002;128:18709.

209
Page 6
27. Zacny JP, Lichtor JL, Thompson W, Apfelbaum JL. Propofol at subanesthetic dose may have abuse
potential in healthy volunteers. Anesth Analg 1993;77:544-52.
28. Zacny JP, Galinkin JL. Psychotropic drugs used in anesthesia practice: Abuse liability and epidemiology of
abuse. Anesthesiology 1999;90:269-88.
29. Dalgarno PJ, Shewan D. Illicit use of ketamine in Scotland. J Psychoactive Drug 1996;28:191-9.
30. Crawshaw R, Bruce JA, Eraker PL, Greenbaum M, Lindemann JE, Schmidt DE. An epidemic of suicide
among physicians on probation. JAMA 1980;243:1915-17.
31. Iwersen-Vergmann S, Rosner p, Kuhnau HC, Judge M, Schmoldt A. Death after excessive propofol abuse.
Int J Legal Med 2001;114:248-51.
32. Council on Scientific Affairs: Scientific issues in drug testing. JAMA 1987;257:3110-4.
33. Cirimele V, Kintz P, Doray S, Ludes B. Determination of chronic abuse of the anaesthetic agents
midazolam and propofol as demonstrated by hair analysis.
34. Henderson GL. The fentanyls. Am Assoc Clin Chem 1990;12:7-14.
35. Epstein RH. Development of a scheduled drug diversion surveillance system based on an analysis of
atypical drug transactions. Anesth Analg 2007;105:1053-60.
36. Morse RM, martin MA, Swenson WM, Niven RG. Prognosis of physicians treated for alcoholism and drug
dependence. JAMA 1984;251:743-6.
37. Pelton C, Ikeda RM. The California physician diversion programs experience with recovering
anesthesiologists. J Psychoactive Drugs 1991;23:427-31.
38. Paris RT, Canavan DI. Physician substance abuse impairment: anesthesiologists vs. other specialties. J
Addict Dis 1999;18:1-7.
39. Luck S, Hedrick J. The alarming trend of substance abuse in anesthesia providers. J Perianesthesia Nursing
2004;19:308-11..
40. Merk EJ, Baumgarten RK, Kingsley CP, Culling RD, Middaugh R. Success of re-entry into anesthesiology
training programs by residents with a history of substance abuse. JAMA 1990;263:3060-2.
41. Hedberg EB. Anesthesiologists: addicted to the drugs they administer. ASA Newsletter 2001;65:14-16
42. Lutsky I, Abram SE, Jacobsen GR, Hopwood M, Kampine JP. Substance abuse by anesthesiology
residents. Acad Med 1991;66:164-6.
43. Klein RL, Stevens WC, Kingston HGG. Controlled substance dispensing and accountability in United
States anesthesiology residency programs. Anesthesiology 1992;77:806-11.
44. Zwerling C. current practice and experience in drug and alcohol testing in the workplace. Bull Narc
1993;45:155-96.
45. Pent MA. Financial viability of screening of drugs of abuse. Clin Chem 1995;41:805-8.
46. Scott M. Legal aspects of drug testing. ASA Newsletter 2005;69:25-8.
47. Orenlicher D. Drug testing of physicians (editorial). JAMA 1990;264:1039-40.
48. Clark HW. The role of physician as medical review officers in workplace drug testing programs. West J
Med 1990;152:514-24.
49. Canavan DI. Screening: urine drug tests. Maryland Med J 1987;36:229-33.
50. McDougall CM. The Junkie in the O.R. Mens Health 2006;11:186-93.
51. Weeks AM, Buckland MR, Morgan EB, Myles PS. Chemical dependence in anaesthetic registrars in
Australia and New Zealand. Anaesth Intens Care 1993;21:151-5.
52. Clark GD, Stone JA. Assessment of the substance abuse curriculum in schools of nurse anesthesia. J
Addiction Nursing 1999;11:123-35.
53. Alexander BH, Checkoway H, Nagahama SI, Domino KB. Cause-specific mortality risks of
anesthesiologists. Anesthesiology 2000;93:922-30.
54. Suruda AJ, McGlothlin JD. Fatal abuse of nitrous oxide in the workplace. J Occup Med 1990;32:682-4.
55. Kintz P, Villain M, Dumestre V, Cirimele V. Evidence of addiction by anesthesiologists as documented by
hair analysis. Forensic Sci International 2005;153:81-4.
56. Domino KB, Horbein TF, Polissar NL, Renner G, Johnson J, Alberti S, Hankes L. Risk factors for relapse
in health care professionals with substance abuse disorders. JAMA 2005;293:1453-60.
57. Polk SL, Katz JD, Berry AJ, McGregor DG, Arnold WP. Does ambient fentanyl enhance the susceptibility
of anesthesiologists to addiction. ASA Newsletter 2007;71:18-19.
58. Bryson EO, Levine A. One approach to return to residency for anesthesia residents recovering from opioid
addiction. J Clin Anesth 2008;20 397-400.
59. Tetzlaff JE, Collins GB. Reentry of anesthesiology residents after treatment of chemical dependency- is it
rational? J Clin Anesth 2008;20: 325-27.

209
Page 7
60. Merlo LJ, Gold MS. Prescription opioid abuse and dependency among physicians: hypothesis and
treatment. Harv Rev Psychiatr 2008;16:181-94.
61. Fitzsimons MG, Baker KH, Lowenstein E, Zapol WM. Random drug testing to reduce the incidence of
addiction in anesthesia residency: preliminary results from one program> Anesth Analg 2008;107:630-5.
62. Aach RD, Girard DE, Humphrey H, McCue JD, Reuben DB, Smith JW, Wallenstein L, Ginsburg J.
Alcohol and other substance abuse and impairment among physicians in residency training. Ann Int Med
1992;116:245-54.
63. Liang BA. To tell the truth: potential liability for concealing physician impairment. J Clin Anesth
2007;19:638-41.
64. Wilson JE, Kiselanova N, Stevens Q, Lutz R, Mandler T, Tran ZV, Wischmeyer PE. A survey of
inhalational anaesthetic abuse in anesthesia programmes. Anaesthesia 2008;63:616-20.
65. Wilson H. Environmental cues and relapse: an old idea that is new for reentry of recovering anesthesia
professionals. Mayo Clin Proc 2009;84:1040.
66. Berge KH, Seppala MD, Schipper AM. Chemical dependency and the physician, Mayo Clin Proc
2009;84:625-31.
67. Bryson EO, Silverstein JH. Addiction and substance abuse in anesthesiology. Anesthesiology
2008;109:905-17.
68. Berge KH, Seppala MD, Lanier WL. The anesthesiology communitys approach to opioid and anesthetic-
abusing personnel: time to change course. Anesthesiology 2008;109:762-4.
69. Oreskovich MR, Caldeiro RM. Anesthesiologists recovering from chemical dependency: can they safely
return to the operating room? Mayo Clin Proc 2009;84:576-80.
70. Jaffee WB, Trucco E, Levy S, Weiss RD. Is this urine really negative? A systematic review of tampering
methods in urine drug screening and testing. J Substance Abuse Treatment 2007;33:33-42.
71. Wischmeyer PE, Johnson BR, Wilson JE. A survey of propofol abuse in academic anesthesia programs.
Anesth Analg 2007;105:1066-71.
72. Gold MS, Meljer RJ, Dennis DM, Morey TE, Bajpain LK, Pomm R, Frost-Pineda K. Fentanyl abuse and
dependence: further evidence for the second hand exposure hypothesis. J Addict Dis 2006;25:15-21.
73. Mohar AR, Yao WD, Caron MG. Genetic and genomic approaches to reward and addiction.
Neuropharmacology 2004;47:101-10.
74. Nance EP, Davis CW, Gaspart JP. Axis II co-morbidity in substance abusers. Am J Psychaitr
1991;148:118-20.
75. Udel MM. Chemical abuse/dependence: physicians occupational hazard. J Med Assn GA 1984;73:775-8.
76. Markov A, Kosten TR, Koob GF. Neurobiological similarities in depression and drug dependence: a self
medication hypothesis. Neuropharmacology 1998;18:135-74.
77. Merlo LJ, Goldberger BA, Kolodner D, Fitzgerald K, Gold MS. Fentanyl and propofol exposure in the
operating room: Sensitization hypotheses and further data. J Addict Dis 2008;27:67-76.
78. McAuliffe PF, Gold MS, Bajpain L, Merves ML, Frost-Pineda K, Pomm RM, Goldberger BA, Melker RJ,
Cendan JC. Second-hand exposuere to aerosolized intravenous anesthetics propofol and fentanyl may cause
sensitization and subsequent opiate addiction among anesthesiologists and surgeons. Medical Hypotheses
2006;66:874-82.
79. Levine AI, Bryson EO. Intranasal self-administration of remifentanil as the foray into opioid abuse by an
anesthesia resident. Anesth Analg 2010;110:524-5.
80. Kovacic P. Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine
and glutamate mediators: electron transfer and reactive oxygen species. Medical Hypothesis 2005;65:90-6.
81. Kovacic P. Unifying electron transfer mechanism for addiction involvement by the anesthetic propofol.
Med Hypotheses 2010;74:206.
82. Rose GL, Brown RE. The impaired anesthesiologist: not just about drugs and alcohol anymore. J Clin
Anesth 2010;22:379-84
83. Donohoe M. Urine trouble: Practical, legal, and ethical issues surrounding mandated drug testing of
physicians.
84. Carcini AJ, Christo PJ. Physician impairment: is recovery feasible? Pain Physician 2009;12:487-91.
85. Pil K, Verstraete A. Current developments in drug testing in oral fluids. Ther Drug Monit 2008;30:196-202.
86. Dasgupta A. The effects of adulterants and selected ingested compounds on drug-of-abuse testing in urine.
Am J Clin Pathol 2007;128:491-503.
87. Epstein RH, Gratch DM, McNulty S, Grunwald Z. Validation of a system to detect scheduled drug
diversion by anesthesia care providers. Anesth Analg 2011;113:160-4.
209
Page 8
88. Hiroi N, Agatsuma S. Genetic susceptibility to substance dependence. Mol Psychiatry 2005;10:336-44.
89. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharacology 2010;35:217-38.
90. Chisholm AB, Harrison MJ. Opioid abuse amongst anaesthetists: a system to detect personal usage.
Anaesth Intensive Care 2009;37:267-71.
91. Volkow ND, Fowler JS, Wang GJ. The addicted human brain: insights from imaging studies. J Clin
Investig 2003;111:1444-51.
92. Volkow ND, Fowler JS, Wang GJ. The addicted human brain viewed in light of imaging studies: brain
circuits and treatment strategies. Neuropharmacology 2004;47:3-13.
93. Hamza H, Bryson EO. Exposure of anesthesia providers in recovery from substance abuse to potential
triggering agents. J Clin Anesth 2011;23:552-7.
94. Welliver M. Propofol alert. Gastrointestinal Nursing 2011;34:398-99.
95. Koopmann A, von der Goltz C, Hermann D, Keifer F. Propofol addiction initiated by anesthetic use. Am J
Psychiatry 2011;168:211-12.
96. Megarbane B. The tragic end of the king of pop: an exceptional example of pharmcodependence to
propofol. Reanimation 2010;19:601-4.
97. Bryson EO, Hamza H. The drug seeking anesthesia care provider. Int Anesth Clinics 2011;49:157-71.
98. Hellinger WC, Bacalis LP, Kay RS, Thompson ND, Xia GL, Lin Y, Khudyakov YE, Perz JF. Health care-
associated hepatitic C virus infection attributed to narcotic diversion. Ann Int Med 2012;156:477-82.
99. Berge KH, Dillon KR, Sikkink KM, Taylor TK, Lanier WL. Diversion of drugs within health care
facilities, a multiple-victim crime: Patterns of diversion, scope, consequences, detection, and prevention.
Mayo Clin Proc 2012;87:674-82.
100. McClure SR, ONeal BC, Grauer D, Couldry RJ, King AR. Compliance with recommendations for
prevention and detection of controlled-substance diversion in hospitals. Am J Health-Syst Pharm
2011;68:689-94.
101. van Holst RJ, Veltman DJ, Buchel C, van den Brink w, Goudriaan AE. Distorted expectancy coding in
problem gambling: Is the addictive in the anticipation? Biol Psychiatry 2012;71:741-8.
Disclosure
229
Page 1
The Art and Science of Disclosing Adverse Events to Paitents:
An Anesthesiologists Perspective
Allen N. Gustin, Jr., M.D., F.C.C.P. Chicago, Illinois
Introduction: Disclosure is defined as the act of making secret information known. This concept has gained
enormous attention in healthcare over the years. Since the 1999 landmark Institute of Medicine report To Err is
Human, evolving healthcare innovations have intended to reduce harmful patient events through education and
systems improvement.
1
In 2001, the Joint Commission instituted Standard 2.90 R.I. (Rights of the Individual),
requiring the disclosure of all unanticipated outcomes to patients.
2
Following this requirement, many states
mandate the disclosure of unanticipated outcomes and almost forty states have encouraged disclosure by providing
legal protection for portions of what information is disclosed to patients. Further encouragement for disclosure
continued with the 2009 update for the National Quality Forum which linked disclosure of unanticipated outcomes
to patient-centered care.
3
Other national guidelines (including the American Medical Association and the
American College of Chest Physicians) have issued recommendations that disclosure of unanticipated outcomes
should be done. The Full Disclosure Working group of the Harvard Hospitals (2006) and the Institute for
Healthcare Improvement (2010) also advocate for the disclosure of all unanticipated outcomes.
4,5
All of these
groups recognize advocate for disclosure but recognize that these disclosure conversations are difficult for
healthcare practitioners. Disclosure to patients has been deemed an uncomfortable experience by physicians and
many are unable to carry out disclosure discussions effectively.
6
Emphasizing this issue, ongoing research efforts
have shown that marked differences exist in how patients and physicians perceive disclosure conversations. One
study by Gallagher found that patients rated the quality of the disclosure poor in 40% of cases while the majority
of the physicians rated the disclosure experience as being very positive.
7
Previous work indicates that when
healthcare workers do disclosure adverse events to patients, critical portions of the unanticipated outcome (why the
adverse event happened and what is being done to prevent it from occurring again) are not disclosed. All physicians
(from surgeons to anesthesiologists) must be skilled in communication strategies when delivering disclosure
conversations to patients. The phrase unanticipated outcome is a term that Joint Commission uses to refer to
outcomes of care that are different from what healthcare workers and patients expect.
8
Unanticipated outcomes are
essentially synonymous with adverse events. An adverse event is best defined as an injury that is caused by medical
management that results in measurable disability. It is important to recognize that the occurrence of an
unanticipated outcome or an adverse event does not necessarily mean that there was a breakdown in the process of
delivering healthcare. Research suggests that the vast majorities of unanticipated outcomes are not due to errors,
thus are not preventable. A medical error is defined as an inaccurate or incomplete diagnosis and/or treatment of a
disease. A medical error (as opposed to an unanticipated outcome or adverse event) is viewed as a breakdown in the
process of delivering healthcare and suggests that someone should be held accountable.
The Near Miss: The near miss is an unplanned event that does not result in injury, illness, or damage; but has the
potential to do so. Near misses are usually not disclosed but should alert healthcare practitioners to potential system
issues that may lead to adverse events later. Ethicists have debated the issue of disclosing near misses to patients.
At the moment, many ethicists fear that the disclosure of a near miss might render more psychological suffering to
the patient and thus, do not recommend disclosure in these circumstances. However, some institutions are currently
disclosing each near miss to their patients.
Barriers to Disclosure: Physicians fear that disclosure will lead to litigation. Imbalances exist between the push for
full transparency in healthcare and the risk management approach to minimizing liability. Ethicists and many
professional organizations agree that unanticipated outcomes associated with healthcare should be disclosed to
patients. Multiple studies confirm that unanticipated outcomes are common and that disclosure of these events to
patients is frequently inadequate. While historically, the disclosure literature has focused primarily on the potential

229
Page 2
impact of disclosure on litigation, recent standards such as the National Quality Forum Safe Practice on Disclosure
and the Harvard Working Groups White Paper on disclosure emphasizes that effective disclosure is a fundamental
component of patient-centered care.
3,4
The risk management aspects of disclosure are now viewed only as secondary
considerations. The other issues associated with not wanting to do disclosure: physicians fear of litigation, loss of
reputation, feelings of shame and embarrassment, insufficient tools and training in disclosure, and a perceived lack
of support form the healthcare system where the physicians practice.
9

Facilitators to Disclosure: Patients report that full disclosure of an unanticipated outcome, especially those due to
a medical error, increases their satisfaction with care, reinforces trust in their physician, and results in more positive
emotional response to the event.
6
Many of the studies have surveyed patients and found that patients desire a
consistent set of information after an unanticipated outcome that results from a medical error.

This set of
information includes the following: an explicit statement that an error occurred, what the error was, why the error
happened, how any recurrence of that error will be prevented, and an apology for the unanticipated outcome.
6

Failed Disclosures (Discussions That are Poorly Delivered): Failed disclosures can have a wide range of
consequences. Failed disclosures can impair patients decision-making capacity, reduce a patients trust in
healthcare, and decrease patients satisfaction with any healthcare received. For patient autonomy to be respected,
disclosure must be performed.
10
Disclosure supports the right of patient decision making.
11

Patients Needs: Patients surveyed from a general sample say that when things go wrong with health care, they need
disclosure, an apology, information about what happened, and how it can be prevented from happening again.
10

Thus, these are the key elements of an effective disclosure conversation: 1. disclosure of the events of the
unanticipated outcome, 2. how it happened, 3. how it can be prevented in the future, and 4. an apology. These
findings suggest that for errors resulting in harm, breakdown in access to and the relationships with the clinician
may be more troubling to a patient than any technical error in diagnosis and/or treatment. The studies that
considered patient perspectives either pre- or post-injury included reviews of patient complaints, hospital records,
plaintiffs depositions, criminal prosecutions, malpractice claims, and general patient surveys/interviews
with/without the use of scenarios. The degree of emotional stress and emotional trauma seemed to vary according to
the characteristics of the communication between provider and patient. Patients who felt good about the
communication (respect, active listening, caring, etc.) with their provider experienced less emotional trauma.
Literature exists concerning the importance of an apology. Some participants mentioned that apologies did not
routinely happen, but an apology remained important to their resolution process. The nature of the communication
appeared to predict whether the patient continued a relationship with the provider after an event. That patient who
experienced a good communication process with their provider also perceived a no fault event and was more
likely to call these events mistakes or complications. Few studies (if any) have focused specifically on
participant perspectives after the injury. Disclosure and apology, if done well, should not increase potential liability.
On the other hand, disclosure and apology done in an insensitive manner, or not at all, may ultimately result in
deterioration or destruction of trust between the patient and the healthcare practitioner.

The Apology/Im Sorry Law: Fear of lawsuits by healthcare providers is a major factor which acts as a barrier
to disclosure. Two national surveys designed to assess attitudes toward disclosure revealed that fear of litigation was
the primary reason for both physician and hospital reluctance to disclose errors and unanticipated outcomes.
13

Lawyers and insurance companies have long warned against apologizing in order to avoid litigation, even though
many states now prohibit a doctors expressions of remorse, fault, or causality from being used in court as evidence
of their guilt. This body of legislation, referred to as Im sorry or apology laws, encourages full disclosure of
mistakes or errors in judgment by eliminating the physicians and the hospitals fear that any apology admission will
be used against them in a court of law. Im sorry laws are a marked change from existing American law: under the
Federal Rules of Evidence and analogous state provisions, apologies are ordinarily admissible in civil court to prove
liability (Federal Rules of Evidence 801(d)). A final warning regarding an apology law, not all apology laws are
created equal! Before assuming that an apology law in your state covers any expression of apology, each
practitioner should evaluate the apology law in his/her state before proceeding with an apology during any
disclosure conversation.

Not Only What You Say, But Also How You Say It! Most doctors are uncomfortable explaining the
circumstances surrounding avoidable complications. For clinicians overwhelmed by self-recrimination, discussing
any adverse event or medical error can be hard. Openness, humility, and conceding medicines imperfections are

229
Page 3
considered new concepts in health care. Studies point to poor patient provider communication, inadequate
delivery of information, and negative interactions with the provider as leading causes of increased litigation. It is
best to maintain the physician/patient relationship, encourage open and honest communication including disclosure
of unexpected medical outcomes, encourage expressions of concern including an apology when appropriate, and
attempt to support the patients emotion during this stressful time. Face-to-face discussions, communicating openly
and honestly, and active listening to the patient and patients family are further examples of skills that need to be
developed by clinicians for effective communication during disclosure conversations.
11
Clinicians are also
encouraged to express concern, empathy, or other appropriate emotions without defensiveness. A clinician may find
that keeping his or her feelings in check and attempting to understand the patients perspective is very valuable
during a disclosure conversations. The guidelines go on to state that a physicians concern about legal liability that
might result from full disclosure should not affect a physicians decision to deal candidly with a patient.

The Pioneers. Have Organizations Who Routinely Disclose Adverse Events Experienced More Litigation?
The answer is NO! Having realized the benefits of apologizing, several hospital systems throughout the country (in
conjunction with their attorneys and insurance carriers) have implemented full disclosure policies. A disclosure
policy is a procedure that is carried out when an unanticipated outcome occurs. These organizations have trained
their staff and their health care professionals in how to apologize and engage in early settlement offers. The VA
Medical Center in Kentucky was the first medical center to adopt a disclosure policy. After two lawsuits with large
judgments against the medical center, the VA Medical Center in Kentucky mandated that all adverse events be
disclosed to their Veterans. The facility shifted its strategy in dealing with adverse events from deny and defend
to disclose, compensate, and apologize. Many speculated that lawsuits against this VA Medical Center would rise
in number when in actuality, no increase in awards or number of suits ever occurred.
16
Since the University of
Michigan Health System adopted its program in 2002, the number of medical malpractice claims has dropped each
year, their attorney fees have declined significantly, and the university has reduced its claims-processing period by
more than 50 percent.
17
McDonald at the University of Illinois at Chicago has found that when disclosure of
unanticipated outcomes occurs routinely, then patients are less likely to sue and actually are far more forgiving
toward the healthcare provider/facility.
18

Lessons Learned from Healthcare Systems with Active Disclosure Practices. Adopted from the Lecture
Disclosing Medical Errors: Best Practices from the Leading Edge
19
Virginia Mason Medical Center
(VMMC), Seattle, Washington, adopted the Toyota Lean model as the basis for its healthcare center operations. The
Toyota Lean focuses on transparency and visibility. VMMC turned the medical centers into a system where:
everyone is considered a safety inspector, anyone can report a safety concern (and the process stops immediately),
and the system is continuously mistake proofing. When VMMC introduced the Toyota Lean Model, the medical
center averaged thee patient safety alerts a month and now they average well over 300 reports a month. Lessons
learned include the following: the VMMC staff see that the nature and number of errors that occur and the staff
knows what to expect when an adverse event occurs. VMMC shared stories in order to overcome fear by being
transparent. VMMC felt that too many physicians and other VMMC staff ware faltering and had too many excuses.
Now, the medical center feels that they have buy in from the entire clinical staff of the medical center. University of
Illinois at Chicago Medical Center (UIC), Chicago, Illinois. UIC developed a process where an investigation beings
after an unanticipated outcome in order to determine whether a further investigation is warranted. If the error and
the case meet criteria for an apology with full disclosure, then the apology is delivered. If a remedy is offered, a
liaison is created between the patient, the family, and the claims department. If the claim is large, then the
organization must decide how to the claim will travel through he administrative approval process. The UIC
outcomes: family who experienced an error at UIC continued to seek care in that facility, patient safety has overall
improved, and the time it takes for clinicians to receive critical test results has been reduced. Overall, the lessons
learned at UIC: persuade your lawyers that disclosure is the right thing to do ethically, legally, and financially. UIC
recognizes that shifting the culture of an organization is not easy and it can take time. University of Michigan
Health System (UMHS), Ann Arbor, Michigan. Boothman and colleagues developed a system based on the
following guiding principles: compensate patients and families when UM has made an error, fight to defend
themselves when their care was reasonable, and systematically use mistakes as tools for learning along with making
any needed changes to their system. Michigan Compiled Law 600.2912 stipulates that before a claim can be filed
against any health practitioner or facility in Michigan, the patient is required to present details of their claim in
writing. This allows UMHS time to review the claims within three months or less. Then, UMHSs Medical
Liability Review Committee reaches conclusions about the reasonableness of the care delivered and its impact on
the patients outcome. UMHS is able to handle many of these claims long before the claim might enter into the

229
Page 4
legal system. UMHSs lessons learned: hospital leaders wont easily embrace this unquestioningly, start with small
successes and publicize them widely in order to gain the confidence of the leadership, have courage and appreciate
the significance of what you are asking people to do, be willing to hold the line both ways, and sometimes you need
to tell patients that they wont be compensated because the care was reasonable. Kaiser Permanente Healthcare
System. Developed a six-step statement principle to guide physicians in communicating with patients and their
families after an adverse outcome or medical error. Step 1: Always care for the patient. Step 2: Communicate
about the unanticipated adverse outcome. Step 3. Report to appropriate parties. Step 4. Check the medical record.
Step 5. Follow-up and provide closure. Step 6. Support the patient care team (physicians, nurses, pharmacists,
etc.). Kaiser created the healthcare ombudsman/mediator. This is a person that is specially trained in disclosure and
is an internal/neutral/confidential line of communication between the family/patient and the healthcare system.
Kaisers lessons learned: treat staff as respectfully as you would treat your patients, engage your leaders in the
process, and teach others who may have been involved in the medical errors to respond as part of the team.
Geisinger Health System, a Pennsylvania healthcare system, covers patient care in 41 counties. In 2002, the
Pennsylvania state passed the Medical Care Availability and Reduction of Error Act. This law requires that a patient
who sustained injury as a result of medical negligence by a health are provider must be afforded a prompt
investigation and fair compensation. Every effort must be made to reduce the errors by identifying the problem and
implementing solutions that promote patient safety. Geisinger developed a process that should make such
disclosures routine throughout the health system. Since they implemented their process, they have experienced a
increase in the reporting of serious events and an increase in number of disclosure conversations between physicians
and patients. They have had fewer claims filed than the national average. They recommend adopting a patient
centered practice rather than a legalistic philosophy toward disclosure. COPIC Insurance Company, a Colorado-
based physician-led malpractice carrier, has openly communicated medical errors to patients since October 2000.
The company felt that the tort system destroys the relationship between physicians and patients. The COPIC system
developed the no fault 3Rs program with stands for the following: Recognize an unanticipated event, Respond
soon after the event occurs, and Resolve any related issues. The 3Rs program was partially successful given that
Colorado has a very strong apology law. Overall, the lessons learned are the following: nurturing good
relationships with patients is essential, develop strong relationships with senior management, and have faith in a
patients ability to forgive their physician when adverse events or medical errors occur.

There are many other medical facilities/healthcare systems that have had great success with disclosing unanticipated
outcomes and medical errors to patients. This above list is not meant to be all-inclusive, but rather an attempt to
offer a sample of those healthcare systems that have experienced success.

Whats the Next Step for Disclosure? Disclosure practice tends to be transitioning from the individual practitioner
focus to the team based focus. Emphasis is removed from a single healthcare provider managing the issues of
disclosing unanticipated outcomes to placing more emphasis on the team or the organization as a whole managing
any issues of disclosure. This is best identified by one concept called TeamSTEPPS. Released by the Agency for
Healthcare Research and Quality (AHRQ), TeamSTEPPS outlines a training methodology to train healthcare
institutions to assume team based behaviors, including the management of disclosure converstations and disclosure
policies. Training modules for TeamSTEPPS can be readily accessed from AHRQs website: www.ahrq.gov. For
anesthesiologists, the team model can be quite beneficial. The operating room can be a source of conflict and
differences of opinion regarding the occurrence of unanticipated outcomes can easily occur. Conflicts or differences
of opinion can be mitigated when team based approaches have been adopted in healthcare environment. Team
based approaches to disclosure can provide support to all members of the operative team along with support for the
patient (and the patients family).
19

Conclusion: Disclosure of unanticipated outcomes is mandated by the Joint Commission and supported by multiple
national organizations. Barriers and facilitators to disclosure exist and can influence a healthcare practitioners
willingness to engage in a disclosure conversation. Physicians may not have any experience with disclosure
conversations or with how to effectively engage in these conversations with patients. Resources are available
(national meetings, learning modules, etc.) that allow for physicians to gain experience with disclosure
conversations. Disclosure continues to be patient centered care and professionalism standards support the
disclosure practices as endorsed by national organizations.

229
Page 5
References:

1. Kohn LT< Corrigan J, Donaldson MS. To err is human: building a safe health care system. Washington,
DC; National Academy Press. 2000.
2. Lamb RM, Studdert DM, Bohmer RM, Berwick DM, Brennan TA. Hospital disclosure practices: results
of a national survey. Health Affairs 2003 (22): 73-83.
3. National Quality Forum. Safe Practices for Better Healthcare- 2009 Update: A Consensus Report.
Washington, DC: National Quality Forum, 2009.
4. The Full Disclosure Working group. When Things Go Wrong: Responding to Adverse Events. A
Consensus Statement of the Harvard Hospitals. Boston, MA: Massachusetts Coalition for the Prevention of
Medical Errors, 2006
5. Conway J, Federico F, Stewart K, Campbell M. Respectful management of serious clinical adverse events
IHI Innovation series white paper. Cambridge, MA: Institute for Healthcare Improvement, 2010
6. Gallagher T, Studdert D, Levinson W. Disclosing Harmful medical Errors to Patients. New England
Journal of medicine 2007; 356 (2): 2713-19.
7. Chan DK, Gallagher TH, Reznick R, Levinson W. How surgeons disclose medical errors to patients: A
study using standardized patients. Surgery. 2005; 138(5): 851-858.
8. Trombly ST. Dealing with adverse Events, Anesthesia Patient Safety Foundation, Accessed on May 3,
2012: http://www.apsf.org/resource_center/newsletter/2006spring/01adverse_event.htm
9. White A, Waterman A, McCotter P, Boyle D, Gallagher T. Supporting healthcare workers after medical
errors: considerations for health care leaders. J Clin Outcomes Manag 2008;15:240 7
10. Lo B. Resolving Ethical Dilemmas: A Guide for Clinicians. 3rd ed. Philadelphia, PA: Lippincott Williams
& Wilkins, 2005
11. Wu AW, Cavanaugh TA, McPhee SJ, Lo B, Micco GP. To tell the truth: ethical and practical issues in
disclosing medical mistakes to patients. J Gen Intern Med 1997;12:7705
12. The Patient Safety Handbook by Barbara J Youngberg, Martin J. Hatlie Published by Jones and Bartlett
Publishers, 2003, page 552.
13. Gallagher TH, Denham DR, Leape LL, Disclosing unanticipated outcomes to patients: the art and practice,
J Patient Safety 2007 3(3): 158-65.
14. Dulcos C, Eichelr M, Taylor L, Quintela J, Main D, Pace W, Staton E. Patient perspectives of patient
provider communication after adverse events. International Journal for quality in Healthcare Care. 2005:
17(6); 479-486.
15. Mazor KM, Simon SR, Gurwitz JH. Communicating with patients about medical errors. Archives of
Internal medicine, 2004 146; 1690-1697.
16. Gallagher TH, Denham C, Leape L, Amori G, Levinson W. Disclosing unanticipated outcomes to patients:
the art and the practice. J of Patient Safety. 2007; 3(3): 158-165.
17. Kachalia A, Kaufman SR, Boothman R, Anderson S, Welch K, Saint S, Rogers MA. Liability claims and
costs before and after implementation of a medical error disclosure program. Ann Intern Med
2010;153:21321.
18. Helmchen LA, Richards MR, McDonald TB. How does routine disclosure of medical error affect patients
propensity to sue and their assessment of provider quality? Evidence from survey data. Med Care, 2010
Nov; 48 (11): 955-961.
19. Souter KJ, Gallagher TH. The Disclosure of Unanticipated Outcomes of Care and Medical Errors: What
Does This Mean for Anesthesiologists? Anesthesia and Analgesia 2012;114(3): 615-621.

Disclosure

"#$
Page 1
Tired of Not Being Taken Seriously?
Professionalism and How It Affects You
Saundra Curry, M.D. New York, New York
In 2002 the European federation of Internal Medicine, the American College of Physician s-American Society
of Internal Medicine (ACP-A SIM) and American Board of Internal Medicine (ABIM) collaborated to write
Medical Professionalism in the New Millennium: A Physician Charter'. This charter laid out three
fundamental principles and ten commitments all which encompass the basis of medicine's contract with
society. The ASA, the ABA and some 130 other societies worldwide have endorsed this charter, but there is
precious little in the l iterature about how practitioners are and should be applying this charter to their everyday
work lives. As yet there is no definition of professionalism that everyone agrees upon.Differing specialties
view professionalism through their own eyes
2
which is appropriate since we all have different types of
interaction s with patients and colleagues. But professionalism in anesthesia is still not well defined, an
unfortunate situation, because it impacts us at ever y level in our daily working lives. Each paragraph of
the chatter can be applied to what we do.
TENETS
Principles
Principle of primacy of patient welfare: There can be no argument about the importance of this statement.
We care for patient s at their most vulnerable moments. They are ill, frightened, and for the most part,
unconscious. We as anesthesiologists are patient advocates and protectors in operating room and critical care
environments. Nothing should interfere with this duty to altruism.
Principle of patient autonomy: Again, we are protector s of patient tights. We have a duty to present the
option s patients have for their care and cannot force them to have any type of anesthesia. They rely on us to
use our best judgment to provide the best of care, given the surgical situation. We can't force regional or
general on them, but can only present the best options available to them. This also applies to DNJ/DNR
scenarios.
Principle of social justice: This principle may seem removed from the operating room,but in fact appears
more often than one would think. We take all comers to the operating room, and should delegate care based
only on the basis of the medical status of the patient, not their ability to pay, their standing in the community,or
any other soci al characteristic.
Commitments
Commitment to professional competence: The decisions made over ten years ago to require recertification
on a regular basis satisfies this commitment. And the recent changes to MOCA , requi ring life long learning
and maintenance of clinical skills show the world at large that we acknowledge that modem medicine is an ever
changing field. Practicing with the skills learned long ago is not enough. Best practice requires keeping up to date in
everything.

"#$
Page 2
Commi tment to honesty with patients: Lying to patients about thei r care can only lead to disaster. Medical
errors need to be acknowledged so patients can be properly cared for. Patients suspect many things are done to
them while under anesthesia that they don 't know about and might not approve of. If students, vendors, etc.
are going to be around this needs to be agreed to ahead of time and then followed through. If a patient refuses
this sort of contact, that wish must be honored. If it can 't be, they must be told.

Commitment to patient confidentiality: No one wants to hear about their case in elevator discussions.
Electronic media make this commitment even harder to adhere to. However, it again is our duty to protect
our patients' medical information, which extends from the type of surgery they are having to their diagnoses
and genotype.

Commitment to maintaining appropriate relation s with patients: Expl oitation of any sort by
practitioners of their patient s is wrong and cannot be tolerated.

Commitment to improving quality of care: Anesthesiologists have always been leaders in quality
and safety. This extends from maintaining competence, reducing errors and collaborating with other
specialties to optimize clinical outcome s.

Commitment to improving access to care: We need to strive to improve access to the best possible care
that our patients can receive. This includes supporting efforts to improve public health, such as the ASA's
initiative to stop smoking.

Commitment to a just distribution of finite resources: As anesthesiologists we can aid in this
commitment by avoiding waste and applying the best cost effective care possible.

Commitment to scientific knowledge: This commitment may be one of the easier ones for
anesthesiologists to understand. Scientific research is the way our specialty will move forward.Not everyone
is cut out to be a researcher , but we can all read about and apply the advances shown to be improvements to
patient care. We can also support those who do research with time and money.

Commitment to maintaining trust by managing conflicts of interest: Full disclosure i s the only way
to go with this commitment. Anesthesia is a specialty that draws clever people who are interested in new
product and drug development and who also know how to pursue these interests to potential financial markets.
We need their know-how, we and our patients just need to be clear that it is the patients best interest that is
being maintained, not just the bottom line of any new company.

Commitment to professional responsibility: This final commitment encompasses many duties, including
promoting the specialty, maximizing excellent patient care, self-regulate, respect one another, set educational
standards, as well as support organizations that promote the specialty on a national level. Much of how we
practice can be mandated at a national level and we need to be involved in those processes.

ADVERSE CONSEQUENCES TO PATIENTS

What happens if we don 't adhere to the principles and commitments? The consequences of not adhering to
these tenets may be easier to see than their daily application.

Patient welfare can be easily compromised if their best interest is not placed paramount. We could leave
patients alone under anesthesia. Anesthesia is so safe these days nothing would happen, right?

Patient autonomy is paramount. As an example, the DNR debate over the last 20 years has shown that
patient s want their rights acknowledged and respected. Not to do this leads to patient mistrust and potential law
suits.

Social injustice gives good care only to those who can afford it or to those we happen to like because of their
race, ethnic background, religion, or political affiliation.

"#$
Page 3
Professional incompetence means that your colleague who hasn't read a journal or attended an educati onal
meeting for the last ten years might be giving you anesthesia in an emergency. Or perhaps he has a substance
abuse problem ...

Dishonesty with patients means that if a mi stake was mad e and not reported,the mistake may be repeated
(drug reaction s) or the pati ent may not get the appropriate care to rectify the new problem.

Lack of confidentiality - means that the world can hear about a patient's issues. This can lead to job
consequences, marital discord, and other topics that are none of anybody else's business.
Inappropriate relations with patients can l ead to wrong care, bullying, and professional blackmail.

Not improving the quality of care means we are taking care of today 's problems with yesterday's
solutions. This may work for a while, but is doomed to failure eventually.

Not improving access to care means we end up having to care for sicker patients than we have to. If they
don't have access to good primary care, our job is that much more difficult.

Unjust distribution of finite resources means that those who need care the most won't get it when
they need it.

Lack of scientific discovery - mean s that we never advance the specialty and cannot improve patient
outcomes.

Not managing conflicts of interest means that we lose the public trust. This is another form of altruism
where the public needs to know that we are putting their needs above our own, not vice versa.

Not taking professional responsibilities seriously means no one else will either. If we don't care
enough to support our major organizations as they fight for our rights in Congress, for example, why should
Congress listen?

PERSONAL AND DAILY APPLICATIONS

Swick et.al.
3
point out that one of the flaws of the Charter is that i t concentrates on duties and not on values
that are virtue based. Their theory is that duties without values are very hard to stick to and one needs to
absorb. Virtues have the benefit of being inherent in people and not externally driven. Therefore they have
better chance of sticking. The other important benefit is that virtues are what people bring to any situation
regardless of the context. The operating rooms are inherently stressful with different groups of people working
together. Each has their own agenda. If everyone concentrates on the patient as being the key element that
has brought them all together, focus can be maintained on the only important person in the room. One of the
common grumbles of anesthesiologists is that they don 't get enough respect from surgeons and nursing staffs
or even patients. Respect i s earned, not automatically granted. It is true that patients do not come to the
hospital to get anesthesia. Surgeons bring them in so there is an inherent dichotomy for everyone to deal with.
However, it is unlikely that patients would come for surgery if they thought they were not getting any of the
services we provide, i.e., analgesia, amnesia, and maintenance of life. Lesser et.al.
4
bring up a slightly
different emphasis. They focus on behaviors of individual s and organizations because attitudes (values and
virtues) are very hard to adjust. Behaviors are teachable, learnable and can be assessed. Quoting Aristotle,
"Excellence is an art won by training and habituation. We do not act rightly because we have virtue or
excellence but rather we have those because we have acted rightly. We are what we repeatedly do.
Excellence then is not an act but a habit. " It is virtually impossibl e to change other people. One can only
work on oneself. Here's an approach that encompasses the some of the tenets of the Charter, incl udes
personal virtues and behaviors.

"#$
Page 4
I will place patient welfare above all else. I will have carefully planned my anesthetic for the case at band,
having discussed the surgeon's needs with him/her ahead of time. I will discuss plans and goals with the
patient at a level they can understand.
I will listen to the patient. Their concerns and desires are important in my plan for how I care for this
patient. I will show them compassion for their concerns. To do this every day but this may be the patient's
first encounter with the OR's.
I will give them the best care, regardless of their place in society.
I will strive for excellence in my profession, not just competence. That means that every day there is
someth ing to learn and improve upon. My board certification was just a large stepping stone in my drive to
become an outstanding and expert clinician. Lifelong l earning and professional development will be my tools.
I will be honest in my dealings with all maintaining integrity and accountability. This includes,
patients, OR staff, surgeons and consu lts. Honesty about mistakes, errors in judgment, as well as thoughts on
chances of success in a particular procedure will gain me the confidence of those with whom I work. I will
also honor myself and not abuse myself with drugs, lack of sleep, etc. which may compromise my ability
to care for my patient s.
I will maintain the confidentiality of my patients and thus they will know they can count on me.
I will maintain strictly appropriate behavior with my patients.
I will take my professional responsibilities seriously. This includes supporting my national
organizations who speak for me to the public. But it also means treating colleagues of all specialties
with the respect I expect from them. I will confer with my surgical colleagues about upcoming
cases so that an appropriate care plan can be established. If I suspect a colleague in any specialty i s
behaving inappropriately (drugs, alcohol, behavior) I will make sure it gets reported to the
appropriate authorities. This shows compassion for the person and care of any patients that may be
in harm 's way.
Ultimately by adhering to these duties, virtues and responsibilities and acting on them we will earn the
respect of all with whom we work, take great care of our patients and honor our specialty and ourselves.
REFERENCES
1. Medical Professionalism in the New Millennium: A Physician Charter. Ann Int Med 2002;
136: 243-246
2. Garfield JM, et al. Doctors in acute and longitudinal specialties emphasize different
professional attributes: implications for training programs. Med Ed 2009; 43:749-756.
3. Swick HM, Bryan C, Longo LD. Beyond the physician charter. Perspectives in Bio and Med
2006; 49(2):263-275.
4. Lesser CS, et al. A behavioral and systems view of professionalism. JAMA 2010; 304(24):
2732-2737
Disclosure
303
Page 1
Using Information Systems to Manage Departmental Staff,
Hospital Administration, and Payers
David L. Reich, M.D. New York, New York
There are many commercial products that are marketed as anesthesia information management systems
(AIMS) in the United States (US) and worldwide. Despite incentives to adopt electronic health records and their
various benefits, there was low penetration into the U.S. market in a recent years (<10% of academic anesthesia
practices in 2007). Adoption by smaller anesthesia practices is likely much lower. When surveyed as to why an
AIMS had not been adopted, commonly cited reasons were cost, perceived medicolegal risk, and inertia.
1

With meaningful use incentives stemming from the ARRA funds and future penalties for lack of adoption
of meaningful use standards, many institutions are now purchasing enterprise electronic medical records (EMR)
with an anesthesia/perioperative module. Thus, it is likely that many anesthesiology departments have recently
implemented or will be implementing AIMS in the near future. A detailed summary of the process of choosing and
implementing an AIMS was the subject of a recent multi-center publication by Muravchik et al.
2
There is a major
opportunity to use the data from AIMS and perioperative information systems to manage many aspects of anesthesia
and hospital practice. This Refresher Course outline will review the literature on management applications of AIMS
and also provide detail regarding the utility of specific analytical reports that are created from AIMS and related
information systems data. A partial list of the regular reports that support departmental and other hospital
departmental functions at the authors institution is detailed in Table 1.
Table 1. AIMS-Based and Associated Scheduling System Reports
1. Financial
a. Automatic anesthesia billing
i. OR billing records creation
ii. Missing data report
iii. Updates monitoring and reporting
iv. Pain and ICU billing
v. Real-time notification of missing data elements
vi. Reports for administrative assistant to follow up
b. Faculty compensation program
i. Web display and emails
ii. Resident bonus pay
2. Administrative
a. ACGME report automatic generation
b. EPIC interface
c. Tracking system
i. OR Control Desk
ii. Family Waiting Room
iii. Assessment Area
iv. PACU
v. Bed assignment unit
vi. Cardiac White Board
vii. Events Notification: Surgeons, Anesthesia attendings, and residents
d. Scheduling system
e. Daily assignments
f. Night and weekend calls
g. Time off
h. Web displays and reports
i. Personnel system
303
Page 2
3. Quality
a. Return to OR
b. Anastomotic leak
c. Surgical operation log
d. PACU statistics and pain level upon discharge
e. Second operations in same hospitalization
f. 48 hour post-anesthesia mortality
g. Postop complications (standard CMS list)
h. Central Line Associated Blood Stream Infection (CLABS) prevention program compliance
i. Central line education report
j. OR utilization reports
k. Fairness of assignment report (Anesthesia Attendings)
MANAGING THE DEPARTMENT
Improving Clinical Documentation
Several investigators have assessed the impact of an AIMS on the quality of clinical documentation. One
study comparing AIMS-produced records to completely manual records showed that AIMS records required less
practitioner time (both absolute time and percentage of case time), recorded more vital signs and clinical notes, had
a similar number of artifacts, and fewer illegible entries.
3
Another study concluded that missing or erroneous data
occurred more frequently in handwritten records, especially during the first 15 minutes and last 10 minutes of a case,
when greater attention to patient care is typically required which detracts from attention to documentation.
4

Accuracy of physiologic (i.e., vital sign) data was also found to be more accurate (or at least more variable) in AIMS
records compared with manual records.
5
AIMS records are still imperfect. Additional studies have shown that
information may be incomplete even in an AIMS record secondary to a dependence on free text remarks an inability
to automatically present entries in logical sequences consistent with workflow, and because practitioners
deliberately smooth variability and extreme values in automatically acquired physiologic data in AIMS records.
6
,
7

Overall, the improvement realized after AIMS implementation is supported by several surveys that showed that the
majority of users, both in OR and obstetric settings, were satisfied with their AIMS and would not want to return to
a completely manual system.
8,9,10,11

Enhancing Performance Improvement and Patient Safety
In addition to providing better documentation of clinical care, AIMS have the potential to improve quality of care.
Several studies using simple reminders in an AIMS showed that this intervention could significantly improve
compliance with prophylactic antibiotic administration timing.
12 ,13 ,14
Another group used a computer-generated
reminder to enhance rates of re-dosing of antibiotics.
15
In addition to the contemporaneous reminders, data from
AIMS may be extracted and analyzed to generate daily reminders for US Physician Quality Reporting Initiative
reports and communication with practitioners encouraging them to improve their performance.
Another use of an AIMS is to provide decision support, such as for determining completeness of the
anesthesia record. In one study, an AIMS-based algorithm that alerted the clinician if a patient had multiple risk
factors for post-operative nausea/vomiting nearly doubled the use of antiemetic prophylaxis for these high-risk
patients.
16
Using an AIMS to screen for intraoperative markers of complications may also be helpful in identifying
cases for quality assurance reviews. Electronic screening yielded many more cases of interest than voluntary
reporting by clinicians.
17,18
A comparative effectiveness outcomes trial of an AIMS-based decision support system
suggested that lower rates of intraoperative awareness may have occurred.
19
Overall, the evidence in the literature is
just emerging, but the trend towards pay-for-performance and other quality measurement efforts will provide further
impetus to foster information systems that help health care practitioners adhere to guidelines and to adopt decision
support tools proven to enhance patient safety.
Technologies in common use in other industries are also beginning to be used in healthcare and integrated
into AIMS. Use of barcodes on medication labels in conjunction with a special scanning device may decrease
medication errors and improve documentation.
20,21,22
Barcodes and radiofrequency identification tags can also be
used to verify patient identity, locate patients and vital equipment, and ensure blood product compatibility.
Other areas of potential improvement with AIMS include: 1) the capacity to retrieve records of prior
anesthesia encounters to identify previous problems; 2) an improvement of summary documentation for transfer of
care (i.e., handoffs); 3) guidance during emergencies (e.g., malignant hyperthermia or cardiac arrest); 4) laboratory
data interfaces that report and record pertinent lab values when they become available; 5) alerts to worrisome trends
303
Page 3
in physiologic values beyond the simple limit alarms built into monitors; and 6) the ability to monitor cases remotely
by accessing live AIMS records from a remote workstation or personal digital assistant (PDA).
The possibility that an AIMS could actually jeopardize patient safety has been considered. With clinicians
free of the need to record vital signs manually, there is potential for inattention to the vital signs that are both
measured and recorded automatically. This issue was addressed in two studies that concluded that the use of an
AIMS did not decrease vigilance.
23,24

Enhancing Professional Billing Metrics and Clinical Productivity
Use of an AIMS creates opportunities to improve the economics of practice. In addition to recording the
clinical documentation that is needed to support billing, the AIMS can function as a point-of-care charge capture
system as well. A complete AIMS record can contain all of the necessary patient information, procedure, time, and
special technique information that, in combination with other patient insurance information, can be used to create a
bill of service by a billing provider. Using an AIMS to drive billing can eliminate the need for paper billing
vouchers and can reduce charge lag, clerical and processing costs, lost bills, days in accounts receivable, and
practitioner paperwork burden.
25
Using automatic electronic mail and PDA alerts to practitioners about deficiencies
in the AIMS record, so that they can be expeditiously corrected, has also led to improved billing metrics.
26

AIMS can also increase revenue by helping to identify potentially reimbursable items. One study showed
that screening AIMS records for presence of vital signs from an invasive monitor but without supporting
documentation of placement of that monitor (necessary for billing) identified a significant source of missed revenue
that could be corrected.
27
Another study showed that use of an AIMS-based pre-operative evaluation system by
hospital coders resulted in additional abstracted diagnoses that increased hospital revenue under the diagnosis-
related-group (DRG) system.
28

Not only does an AIMS allow for documenting anesthesia care, but it has potential applications for
monitoring and incentivizing practitioner activities. One report demonstrated a role for using an AIMS as the basis
of a productivity-based compensation system for faculty and house staff in an academic anesthesia practice.
29

Another study found that an AIMS-based cost-analysis was helpful in implementation of practice guidelines
regarding anesthetic drug usage, and could lead to significant cost savings.
30
Also reported is the use of an AIMS to
help identify practitioners who may be diverting controlled substances.
31

Good communication with anesthesia providers is a key to realizing productivity gains with an AIMS.
Table 2 demonstrates an excerpt from a weekly report to an anesthesia provider. Note that one case did not have a
postoperative note documented within 48 hours and was subjected to a 10% case points penalty. Figure 1
demonstrates the marked effect of the postoperative note points penalty in achieving extremely high compliance
with postoperative note documentation guidelines.
Table 2. Example of a Daily Faculty Productivity Report with Penalty for Late Postoperative Note
Case
Number
Start Time End Time Points
Concurrency
Adjustment
PostOp
Adjustment
for Lateness
Call
Related
Completeness
Adjustment
Final Points
Cardiac 1 N/A 450
Worked
Pre-Call
N/A 450
1 9:28 10:34 195 0.97 1 1 190
2 20:00 23:24 310 N/A after 1800 1 1 310
3 9:00 10:43 255 0.97 1 1 248
4 17:45 18:00 27 0.97 1 1 27
4 18:00 21:28 378 N/A after 1800 1 1 378
5 11:10 15:25 420 0.97 1 1 409
6 15:50 18:00 206 0.97 0.9 1 181
6 18:00 20:15 214 N/A after 1800 0.9 1 193
Total 2836

303
Page 4
Figure 1. Hours between End-Anesthesia Time and Postoperative Note Entry

Conducting Clinical Research
Continued use of an AIMS leads to accumulation of large amounts of clinical data that can be used for
research purposes. These data can mined (extracted) and used to generate hypotheses prior to planning prospective
studies, to study rare events, or questions that cannot be ethically or practically studied prospectively. There is also
opportunity to combine the electronic records created by AIMS from multiple centers, allowing multicenter
retrospective analyses. Such efforts are hindered, however, by the lack of standardization of structure and
terminology in electronic medical records. Multiple efforts are underway to create such standards.
32
For
prospective studies, an AIMS can be configured to collect necessary data elements, and an AIMS-based pre-
operative evaluation can be used to screen patients for inclusion in research protocols.
The AIMS data structure can also be modified to include additional variables of interest that will facilitate
future studies. Since the standards for controlled anesthesia terminologies have only begun to be incorporated by
the AIMS vendors, there is very limited exchange of clinical data among AIMS in different institutions, though it
can be still be accomplished with manual mapping of variables between each system.
33

Whenever possible, data should be acquired from anesthesia practitioners in a structured format. Although
it is easier for practitioners to enter the operation performed as a free text field rather than choosing from a long list
of current procedural terminology (CPT) or international classification of diseases (ICD)-10 codes, the quality
improvement and research tasks will be much simpler with the database-generated list. Free text fields are very
difficult to search, and the variability of spacing, abbreviations, and misspellings greatly complicates the task,
compared with the ease of searching across ranges of numerical codes.
34
For US practice, surgical CPT codes are
preferable to anesthesia CPT codes for many reasons, but mainly because it is possible map one or more surgical
CPT codes to a single anesthesia code using the American Society of Anesthesiologists (ASA) Crosswalk Program
(ASA, Chicago, IL), but the reverse is not possible.

External Databases
One of the greatest challenges in AIMS-based research is the merging of data from separate databases. In
the process of conducting evidence-based patient safety research, it is inevitable that hospital, surgical, and
governmental databases will be used at some point for collecting demographics, process and outcome variables that
are not present in the anesthesiology database. For example, length of hospital stay and co-morbid conditions
leading to prolonged hospital stays are data that are not routinely found in the anesthesiology database. In the
reconciliation of databases, it is often critical to use multiple identifiers for patients, including medical record
numbers, hospital account numbers that are specific to each hospital encounter, dates of surgery, etc. This is
necessary in order to positively identify the data (e.g., a postoperative infection) that coincides with the hospital
encounter of interest (e.g., an abdominal surgical operation).

!
#!
$!
%!
&!
'!!
'#!
'$!
(
)
*
+
!
,

-
)
.
+
!
,

-
)
/
+
!
,

(
0
1
+
!
,

2
3
4
+
!
,

5
6
7
+
!
,

(
)
*
+
'
!

-
)
.
+
'
!

-
)
/
+
'
!

(
0
1
+
'
!

2
3
4
+
'
!

5
6
7
+
'
!

(
)
*
+
'
'

-
)
.
+
'
'

-
)
/
+
'
'

(
0
1
+
'
'

2
3
4
+
'
'

5
6
7
+
'
'

(
)
*
+
'
#

-
)
.
+
'
#

-
)
/
+
'
#
!
"
#
$

&
'
(
)
*

+'*,'- .'," /#,"$01
303
Page 5
MANAGING THE HOSPITAL
Dexter et al
35
implemented an automatic method to estimate the times remaining in OR cases. Instant
message dialogs appearing on AIMS workstations were used to elicit estimates of times remaining from anesthesia
providers, with acknowledgment occurring on average within 1.2 min. For cases taking nearly as long as or longer
than scheduled, each 1 min progression of OR time reduced the median time remaining in a case by <1 min. Based
upon historical surgeon performance, they demonstrated more accurate automated calculation of times remaining for
every case occurring at a 29 OR hospital. Table 3 below is an example of a PACU length-of-stay analysis.
Table 3. Post-Anesthesia Care Unit Length of Stay Data by Type of Anesthetic
General MAC Spinal Non-Spinal Regional
Number of Patients 1266 553 84 87
5th Percentile (min) 40 30 76 47
Mean SD (min) 13589 2052025 209148 11363
MAC = monitored anesthesia care
The lecture will demonstrate how many of the reports detailed in Table 1 are used to manage hospital administrative,
operational and quality needs.
MANAGING THE PAYERS
Although an AIMS is not required to manage a billing operation and payers, the authors institution noted a
decrease of 6-7 days in charge lag that was associated with a switchover to electronic billing voucher creation for
OR anesthesia.
25
Vigilant review of charge lag metrics are an excellent surrogate for front-end problems in the
billing operation for the various anesthesia departmental business lines.
Table 4. Excerpt of Charge Lag Metrics Monthly Report
Location Data Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12
OR Avg Lag
SESM%
Claims
SESM Current
Mode
10
67%
4413
79%
8
10
75%
4259
86%
8
10
75%
4057
75%
8
9
71%
4486
78%
8
9
72%
4852
80%
8
9
66%
4039
71%
9
Amb Suite Avg Lag
SESM%
Claims
SESM Current
Mode
10
71%
141
83%
8
10
74%
108
77%
8
14
76%
123
71%
8
9
70%
149
76%
8
8
76%
144
81%
8
10
60%
128
63%
9
Acute Pain Avg Lag
SESM%
Claims
SESM Current
Mode
28
22%
1107
0%
21
31
13%
991
0%
20
29
47%
793
0%
16
22
55%
667
0%
16
18
42%
587
0%
23
19
38%
760
0%
15
SESM = Same entry, same month
303
Page 6
Figure 2 demonstrates an analysis of accounts receivable that is particularly useful for managed care organizations.
Even with a contracts management module, underpayments require appeal and resubmission. The effect of a special
project are evident in the oldest service dates payments that were received in March and April of 2012.
Figure 2. One Managed Care Payers Performance by Date of Service
Conclusion
The extensive functionality of AIMS and custom add-on systems in many of the early adopter centers
developed over many years. Such systems are likely to be implemented more rapidly in the future by others. This
process most often begins with the deployment of a standard commercial AIMS software package, which is then
extensively configured to meet the individual departmental needs. Significant additional programming resources
and initiative are needed for a full exploitation of the potential of an AIMS. Control of extensive perioperative
information resources is an intangible but real return on investment.
303
Page 7
References
1. Egger Halbeis CB, Epstein RH, Macario A, Pearl RG, Grunwald Z. Adoption of anesthesia information
management systems by academic departments in the United States. Anesth Analg. 2008 Oct;107(4):1323-9.
2. Muravchick S, Caldwell JE, Epstein RH, Galati M, Levy WJ, O'Reilly M, Plagenhoef JS, Rehman M, Reich DL,
Vigoda MM. Anesthesia information management system implementation: a practical guide. Anesth Analg. 2008
Nov;107(5):1598-608.
3. Edsall DW, Deshane P, Giles C, Dick D, Sloan B, Farrow J. Computerized patient anesthesia records: less time
and better quality than manually produced anesthesia records. J Clin Anesth. 1993;5:275-83.
4. Lerou JG, Dirksen R, van Daele M, Nijhuis GM, Crul JF. Automated charting of physiological variables in
anesthesia: a quantitative comparison of automated versus handwritten anesthesia records. J Clin Monit 1988;4:37-
47.
5. Reich DL, Wood RK Jr, Mattar R, Krol M, Adams DC, Hossain S, Bodian CA.Arterial blood pressure and heart
rate discrepancies between handwritten and computerized anesthesia records. Anesth Analg. 2000;91:612-6.
6. Driscoll WD, Columbia MA, Peterfreund RA. An observational study of anesthesia record completeness using an
anesthesia information management system. Anesth Analg. 2007;104:1454-61.
7. Wax DB, Beilin Y, Hossain S, Lin HM, Reich DL. Manual editing of automatically recorded data in an
anesthesia information management system. Anesthesiology. 2008;109:811-5.
8. Eden A, Grach M, Goldik Z, Shnaider I, Lazarovici H, Barnett-Griness O, Perel A, Pizov R. The implementation
of an anesthesia information management system. Eur J Anaesthesiol. 2006;23:882-9.
9. Coleman RL, Stanley T 3rd, Gilbert WC, Sanderson IC, Moyer GA, Sibert KS, Reves JG. The implementation
and acceptance of an intra-operative anesthesia information management system. J Clin Monit. 1997;13:121-8.
10. Quinzio L, Junger A, Gottwald B, Benson M, Hartmann B, Jost A, Banzhaf A, Hempelmann G. User acceptance
of an anaesthesia information management system. Eur J Anaesthesiol. 2003;20:967-72.
11. Beilin Y, Wax D, Torrillo T, Mungall D, Guinn N, Henriquez J, Reich DL. A survey of anesthesiologists' and
nurses' attitudes toward the implementation of an Anesthesia Information Management System on a labor and
delivery floor. Int J Obstet Anesth 2009;18:22-7.
12. O'Reilly M, Talsma A, VanRiper S, Kheterpal S, Burney R. An anesthesia information system designed to
provide physician-specific feedback improves timely administration of prophylactic antibiotics. Anesth Analg.
2006;103:908-12.
13. Wax DB, Beilin Y, Levin M, Chadha N, Krol M, Reich DL. The effect of an interactive visual reminder in an
anesthesia information management system on timeliness of prophylactic antibiotic administration. Anesth Analg.
2007;104:1462-6.
14. St Jacques P, Sanders N, Patel N, Talbot TR, Deshpande JK, Higgins M. Improving timely surgical antibiotic
prophylaxis redosing administration using computerized record prompts. Surg Infect (Larchmt). 2005;6:215-21.
15. Zanetti G, Flanagan HL Jr, Cohn LH, Giardina R, Platt R. Improvement of intraoperative antibiotic prophylaxis
in prolonged cardiac surgery by automated alerts in the operating room. Infect Control Hosp Epidemiol. 2003;24:13-
6.
16. Kooij FO, Klok T, Hollmann MW, Kal JE. Decision support increases guideline adherence for prescribing
postoperative nausea and vomiting prophylaxis. Anesth Analg 2008;106:893-8.
17. Sanborn KV, Castro J, Kuroda M, Thys DM. Detection of intraoperative incidents by electronic scanning of
computerized anesthesia records. Comparison with voluntary reporting. Anesthesiology. 1996;85:977-87.
18. Benson M, Junger A, Fuchs C, Quinzio L, Bttger S, Jost A, Uphus D, Hempelmann G. Using an anesthesia
information management system to prove a deficit in voluntary reporting of adverse events in a quality assurance
program. J Clin Monit Comput 2000;16:211-7.
19. Mashour GA, Shanks A, Tremper KK, Kheterpal S, Turner CR, Ramachandran SK, Picton P, Schueller C,
Morris M, Vandervest JC, Lin N, Avidan MS. Prevention of intraoperative awareness with explicit recall in an
unselected surgical population: a randomized comparative effectiveness trial. Anesthesiology. 2012;117:717-25.
20. Merry AF, Webster CS, Mathew DJ. A new, safety-oriented, integrated drug administration and automated
anesthesia record system. Anesth Analg 2001;93:385-90.
21. Webster CS, Merry AF, Gander PH, Mann NK. A prospective, randomised clinical evaluation of a new safety-
orientated injectable drug administration system in comparison with conventional methods. Anaesthesia.
2004;59:80-7.
22. Nolen AL, Rodes WD 2nd. Bar-code medication administration system for anesthetics: effects on documentation
and billing. Am J Health Syst Pharm 2008;65:655-9.

303
Page 8

23. Allard J, Dzwonczyk R, Yablok D, Block FE Jr, McDonald JS. Effect of automatic record keeping on vigilance
and record keeping time. Br J Anaesth 1995;74:619-26.
24. Loeb RG. Manual record keeping is not necessary for anesthesia vigilance. J Clin Monit 1995;11:5-8.
25. Reich DL, Kahn RA, Wax D, Palvia T, Galati M, Krol M. Development of a module for point-of-care charge
capture and submission using an anesthesia information management system. Anesthesiology. 2006;105:179-86.
26. Spring SF, Sandberg WS, Anupama S, Walsh JL, Driscoll WD, Raines DE. Automated documentation error
detection and notification improves anesthesia billing performance. Anesthesiology 2007;106:157-63.
27. Kheterpal S, Gupta R, Blum JM, Tremper KK, O'Reilly M, Kazanjian PE. Electronic reminders improve
procedure documentation compliance and professional fee reimbursement. Anesth Analg 2007;104:592-7.
28. Gibby GL, Paulus DA, Sirota DJ, Treloar RW, Jackson KI, Gravenstein JS, van der Aa JJ. Computerized pre-
anesthetic evaluation results in additional abstracted comorbidity diagnoses. J Clin Monit 1997;13:35-41.
29. Reich DL, Galati M, Krol M, Bodian CA, Kahn RA. A mission-based productivity compensation model for an
academic anesthesiology department. Anesth Analg 2008;107:1981-8.
30. Lubarsky DA, Sanderson IC, Gilbert WC, King KP, Ginsberg B, Dear GL, Coleman RL, Pafford TD, Reves JG.
Using an anesthesia information management system as a cost containment tool. Description and validation.
31. Epstein RH, Gratch DM, Grunwald Z. Development of a scheduled drug diversion surveillance system based on
an analysis of atypical drug transactions. Anesth Analg 2007;105:1053-60.
32. Warner MA, Monk TG. The impact of lack of standardized definitions on the specialty. Anesthesiology.
2007;107:198-9.
33. Monk TG, Sanderson I. The development of an anesthesia lexicon. Seminars in Anesthesia Perioperative
Medicine and Pain. 2004;23:938.
34. Levin MA, Krol M, Doshi AM, Reich DL. Extraction and mapping of drug names from free text to a
standardized nomenclature. AMIA Annu Symp Proc 2007;11:438-42.
35. Dexter F, Epstein RH, Lee JD, Ledolter J. Automatic updating of times remaining in surgical cases using
Bayesian analysis of historical case duration data and "instant messaging" updates from anesthesia providers. Anesth
Analg 2009;108:929-40.

Disclosure
Covidien, Self, Funded Research

310
Page 1
Safety and Human Factors in Anesthesia Practice
Keith J Ruskin, M.D. New Haven, Connecticut
Introduction
Effective decision-making, risk management, and teamwork are essential components of patient safety.
Anesthesiologists were among the first to adopt human factors, industrial engineering, and operations research as
part of clinical practice, but other specialties soon followed. A recent editorial highlighted the growing body of
human factors articles in the medical literature (over 140 papers on crisis resource management [CRM]),
demonstrating the growing level of interest in this topic.[1] Research in the fields of safety and human factors
continues to evolve, and current interests include the early detection of error-producing situations and the design of
error-resistant systems.[2] Using tools for risk assessment, judgment, and decision-making may help to improve
patient safety in the perioperative period.
Safety
The operating room is a complex environment in which critical events can happen without warning. The
operating room is a complex environment in which even seemingly insignificant errors can have potentially life-
threatening consequences. Large interprofessional teams with varying levels of training care for patients with
multiple comorbidities while they are subjected to a range of physiologic stresses and surgical insults.
Anesthesiologists must manage large quantities of rapidly changing information while sharing it with the rest of the
team. They are frequently required to make decisions quickly, with incomplete information, in an environment that
is intolerant of errors. At any time, one or more factors, including patient illness, the surgical procedure, or
equipment malfunction, may combine to cause a life threatening condition. Although accidents and near misses in
the operating room are relatively uncommon on an individual scale, thousands of adverse events occur throughout
the United States annually. Effective decision-making, risk assessment, and risk management are therefore essential
components of patient safety.
Deviations from safe practice can be divided into errors, which are unintended, and violations, which are
deliberate. Errors can be caused by unfamiliarity with a given task, external pressures such as production pressure,
or systemic problems such as a poor human-system interface or fatigue due to extended work hours. Errors can
occur as a result of improperly formed plans (mistakes) or while implementing plans (slips of action or lapses of
attention). Systemic failures, or latent errors, may go undetected for months or years. Latent errors can be caused by
failures in equipment design and maintenance, staffing shortages or inappropriate staffing, communication failure,
and lack of training. Improperly developed procedures (for example, a poorly developed time out that does not
specifically address the laterality of the surgery) may ultimately result in an adverse event. Latent errors may be the
result of conflicting institutional, surgical, and anesthetic goals. This may be due to improper planning and
organization, or from simply not having an anesthesiologist on the appropriate hospital committee. For example, the
nursing staff or surgeon may pressure the anesthesiologist to bring the patient into the operating room on time,
which prevents the anesthesiologist from verifying that the necessary patient workup has been completed.
Violations in the operating room are usually the result an attempt to achieve a goal that is incompatible
with safe practice. Although it is tempting to dismiss violations as the actions of someone else, even the most
dedicated physician may deviate from safe practice for a seemingly plausible reason. Skipping a few tasks on the
anesthesia machine checkout in order to get a case started on time, for example, might please the hospital
administration but increases the risk of an equipment malfunction at a critical point in the procedure. In some cases,
violation of poorly designed existing procedures may even be required to solve a clinical problem. Violations may
be caused by inadequate supervision, workplace conflicts, poor morale, a perceived lack of concern by supervisors,
and the lack of an institutional safety culture.
310
Page 2
Production pressure and fatigue are examples of systemic problems that affect patient safety. In one study,
647 California anesthesiologists were asked how production pressure affected their practice. Nearly all reported that
there was an overt pressure to proceed with cases, while 49% admitted to making errors as a direct result of
production pressure. Errors included inadequate monitoring, elective surgery without an appropriate patient workup,
and surgery despite contraindications.[3] Fatigue plays a role in both violations and errors. Simply being tired
predisposes to mistakes. In one study, surgical residents were asked to perform both cognitive and motor tests using
a laparoscopic surgical simulator. Residents who had been on call the night before had a significant decline in motor
skills and made a significant number of cognitive errors. EEG monitoring revealed objective evidence of a
significant decline in performance. Working overnight has been associated with a significant increase in the risk of
percutaneous needle injuries. Fatigue and lapses in concentration were the two most commonly cited risk factors.[4]
Physicians who have gone 24 hours without sleep experienced degradation in judgment that is equivalent to that of a
person with a blood alcohol concentration of 0.1%; this meets the legal definition of impaired driving in many
states. Another study suggests that eliminating extended-duration work shifts (defined as greater than 24 hours) may
significantly reduce the risk of medical errors.[6]
Human Factors in Clinical Practice
Over the past 20 years, there has been an increased emphasis in implementing human factors and systems-
oriented approaches to organizational safety in health care. Relatively simple interventions can produce significant
improvements in patient safety. For example, a time-out procedure assures that all personnel agree on the surgical
procedure and operative site and that everyone is aware of the critical components of the procedure.
Recommendations for improving safety in the operating room include minimizing the number of handoffs during the
procedure so that information is not lost during transfers of care.[7] Effective communication is critical to
perioperative safety; steps include team training, making the electronic health record available in the operating
room, and using video cameras to improve situational awareness.[7] Standardizing procedures and minimizing the
variety of drugs and equipment where possible help to create an environment that is resistant to error by limiting the
number of choices that a provider must make. Forcing functions (which prevent personnel from taking an action
without conscious consideration), automation, and checklists and double-check systems all help to reduce the
number of errors made in the operating room.
High Reliability Organizations (HROs) have an exceedingly low rate of accidents or incidents despite
accomplishing technically challenging tasks with a high level of intrinsic hazard. Classic examples of HROs include
aircraft carrier flight operations and nuclear power plants. HROs maintain safe operation because of systems that are
designed to maximize a climate of safety.[8] Shared values of safety begin with senior management and are
transmitted throughout the workforce. There is ongoing monitoring of performance with frequent, candid
communication among all workers. Instead of being hidden, errors are viewed as an indication of a potential
weakness of the entire system. Failures are reported and extensively discussed, enabling new processes to be
developed that make the entire system more resistant to failure. Although there is no simple recipe for creating an
HRO within the healthcare environment, Christiansen et al have identified several key processes: HROs use failures
as a way to gain insight into the weaknesses of the entire system. They do not simplify or explain away a failure.
They try to understand how all components of the operation fit together and can interact to cause problems. HROs
are resilient; processes are designed to recover from unexpected failures. Lastly, decisions about how to deal with
failures (or potential failures) are made by personnel with expertise in that specific aspect of the operation.[8]
Becoming an HRO is not the product of a single decision, but rather a coordinated effort that involves a significant
change in organizational culture that must be embraced by everyone from senior management to individual staff.
Anonymous or confidential reporting of critical incidents can detect latent failures that impact safety. The
Anesthesia Quality Institute was created several years ago to create a National Clinical Outcomes Registry in order
to track anesthesia outcomes nationwide. The collected data is used for benchmarking, quality improvement,
research, and eventually maintenance of certification. AQI also developed a near miss registry called the Anesthesia
Information Reporting System (www.aqiairs.org) that allows either anonymous or confidential reporting of near
misses in the operating room. In order to protect contributors from legal action, AQI is now classified as a Patient
Safety Organization. This gives information submitted to AIRS the same legal protections as that discussed at
quality improvement conferences. Cases submitted to the database is studied and reported, with selected cases
appearing as part of a recurring feature in the ASA Newsletter.

310
Page 3
Anesthesia Decision Making
Crisis Resource Management is a series of techniques for managing critical events in the operating room
that was developed by Gaba et al over 20 years ago.[9] It is based on Crew Resource Management techniques
originally developed by the airlines, and stresses management and use of collective resources that are readily
available. Operating room resources include personnel, equipment, and cognitive aids such as the medical record,
handbooks, and online references. A well-formulated anesthetic plan as well as generalized plans for critical events
can help to guide initial management of a problem. Checklists may be used to increase certainty that critical steps
are not missed. Team training is essential to improve communication and the ability to work together when things
are not going well. Whenever possible, the team leader should delegate tasks in order to avoid becoming fixated on a
single component of patient management. Although the team leader is ultimately responsible for making decisions,
other people in the room may have critical information. The leader should therefore solicit information from other
team members whenever possible. All communication should flow through the leader. For example, if a person is
unable to complete an assigned task, that person should inform the leader, and not simply ask another person (who
might have a critical task) for help.
Vigilance is the motto of the American Society of Anesthesiologists, and anticipating critical events before
they occur will make successful resolution more likely. Situational awareness can be defined as maintaining
awareness of the entire environment while attending to a single problem.[10] It can also defined as knowing where
you are, where you are going, and everything that is going on around you. In the operating room, this means being
aware of the surgeons actions and the most likely complications of the procedure at that moment, the nurses
actions, the equipments status and function, and, most importantly, the patients condition. Situational awareness is
a skill that can be taught. Carbo et al reported a Code Blue simulation in which the providers became so focused
on the patients tachycardia that the airway was neglected. The debriefing from this simulation stressed the
importance of a shared mental model that would allow team members to divide tasks and more efficiently coordinate
their actions.[10]
Although anesthesiologists are told early in their training to maintain vigilance, few if any receive formal
training on how to maintain rapidly evaluate a situation and make the best decision. Human factors specialists
working with the Federal Aviation Administration have developed a series of practical decision-making and risk
management tools for pilots. These thought process checklists can be applied to many elements of clinical
practice. One such model is called 3P, for Perceive, Process, Perform. The 3P model is a structured, efficient, and
systematic way to identify hazards, assess risk, and implement risk controls that are effective. Using this model, one
first perceives that there has been a change in the patients course. He or she then processes the information to create
a strategy to eliminate or mitigate the hazard. The last step is to perform the actions necessary to solve the problem.
At that point, one returns to the Perceive step to determine whether the intervention worked. By constantly
following these steps, an anesthesiologist can detect a problem, take the steps to solve it, and then, most importantly,
determine whether the solution actually fixed the problem.[11]
The ability to constantly evaluate and manage risk is critical to patient safety, but anesthesiologists receive
little training in risk assessment. Risk can be defined as the exposure to the possibility of loss, injury, or other
adverse circumstance. (Oxford English Dictionary) This definition can be further expanded to include the
probability and severity that an injury will occur because of an exposure to a given hazard. Risk management is a
formal method of evaluating the probability that a given hazard will occur and then formulating a strategy for
minimizing the exposure, decreasing the possibility or severity of an adverse outcome, or making a decision to avoid
the hazard altogether.[12] The PAVE tool, also adopted from aviation, can help a clinician to perform a structured
risk analysis. The elements that are considered as part of PAVE include Patient comorbidities, the Anesthesiologists
knowledge base and technical skills, the enVironments special characterists, and External pressures.
Communication is critical to safe patient care. Unfortunately, the traditional medical hierarchy creates an
environment in which lower ranking members of the team (e.g., junior residents and medical students) are reluctant
to speak when they see a problem. In one case series, for example, medical students who were in a position to
prevent medical errors sometimes hesitated to identify the hazard to operating room personnel. Mistakes seen by
medical students and missed by residents or attending staff included contamination of a sterile field, medication
errors, and a failure to implement respiratory precautions in a patient with a presumed diagnosis of tuberculosis. In
some of these cases, the medical student who observed the error was afraid to speak up for fear of retribution.[13]
Reports such as these underscore the importance of listening carefully to all members of the team and creating an
environment where team members will call attention to problems.

310
Page 4
A variety of tools are used to improve team communication. One such model is SBAR, which stands for
Situation, Background, Assessment, Recommendation. Using this paradigm, a provider can briefly state the
situation (The patient is hypotensive and tachycardic.), background (The surgical blood loss is greater than
anticipated.), assessment (I believe that the patient is hypovolemic.), and recommendation (We should
administer additional fluids and check a hematocrit.). Although the effectiveness of this technique has not been
studied in the operating room, it has been shown to improve the effectiveness of communication on a busy pediatric
service that included a general ward, a labor and delivery suite, and a pediatric intensive care unit.[14] United
Airlines developed a critical language program called CUS, which stands for I am concerned. I am
uncomfortable. This is a safety issue! These phrases are used to point out threats that present an immediate
hazard instead of using indirect language that may not emphasize the importance of a serious problem. The use of
critical language allows all members of the team to express concern about a safety issue in a manner that is
understood by everyone.[15]

Simulation
Simulation training, which is now a part of the Maintenance of Certification program, is of particular
benefit to personnel who work in an operating room. The operating room is a dynamic, complex environment staffed
by a large, interdisciplinary team with varying levels of training whose members may not work together frequently.
Simulation has been shown to improve interactions between team members and facilitate exchange of
information.[16] Although high-fidelity mannequin simulators can be used to recreate critical events, it is also
possible for team members to improve their interaction skills using role-playing either in an operating room or
around a table. This technique has been used to teach assertive communication and also to plan complex surgery.
The most critical part of simulator training is the debriefing process after the simulation is complete. During this
process, which is essential to the learning process, team members discuss what happened openly and honestly.

Threat and Error Management
Phipps et al have creating a systematic description of anesthetic practice. Creating such a taxonomy can
potentially allow prediction of the points at which errors and violations can occur. After creating a hierarchical task
analysis, they then applied a human error taxonomy to each step, creating descriptions of the errors that could take
place.[17] The study used two specific frameworks to determine the type of information that an anesthesiologist
would need in order to complete a task, and to analyze the cognitive activity that takes place during the planning and
delivery of an anesthetic. This information can then be used to predict situations in which errors could potentially
occur. The authors hypothesize changes in training or workflow could then potentially reduce errors.
Threat and error management (TEM) suggests that most adverse events can be described in terms of risks
or challenges present in an operational environment (threats) and the actions of specific personnel that potentiate or
exacerbate those threats (errors). If unchecked, errors can produce an undesired state. The goal of this technique is to
identify threats that are likely to be present in the operating environment, mitigate those threats, and trap and correct
any erroneous actions by team members. TEM has been widely applied in the aviation industry and suggests that
some risks are constant, but many others are contingent upon situation and vary by phases of activity. This regularity
may be used to predict and prevent error. The utility of TEM has been demonstrated for analyzing accidents,
incidents and safety reports. It has also been adapted for developing training programs that allow pilots, dispatchers,
and mechanics to identify and mitigate threats before a hazardous situation can occur. Helmreich proposed the
technique for aviation but then suggested that TEM might also be applied to medical practice, suggesting that it
could be used to analyze a catastrophic event.[18]

Conclusions
Effective decision-making, risk management, and teamwork are essential components of patient safety.
Errors can be caused by unfamiliarity with a given task, misperception of risk, latent errors, and systemic problems
such as production pressure and fatigue. Fortunately, accidents and near misses in the operating room are
relatively uncommon, and adopting techniques that improve risk assessment, judgment, and decision-making will
make our patients safer.

310
Page 5

References
1. Gaba, D.M., Crisis resource management and teamwork training in anaesthesia. Br J Anaesth, 2010.
105(1): p. 3-6.
2. Kontogiannis, T., A systems perspective of managing error recovery and tactical re-planning of operating
teams in safety critical domains. J Safety Res, 2011. 42(2): p. 73-85.
3. Gaba, D.M., S.K. Howard, and B. Jump, Production pressure in the work environment. California
anesthesiologists' attitudes and experiences. Anesthesiology, 1994. 81(2): p. 488-500.
4. Kahol, K., et al., Impact of fatigue on neurophysiologic measures of surgical residents. J Am Coll Surg,
2011. 213(1): p. 29-34; discussion 34-6.
5. Ayas, N.T., et al., Extended work duration and the risk of self-reported percutaneous injuries in interns.
JAMA, 2006. 296(9): p. 1055-62.
6. Barger, L.K., et al., Impact of extended-duration shifts on medical errors, adverse events, and attentional
failures. PLoS Med, 2006. 3(12): p. e487.
7. Schimpff, S.C., Improving operating room and perioperative safety: background and specific
recommendations. Surg Innov, 2007. 14(2): p. 127-35.
8. Christianson, M.K., et al., Becoming a high reliability organization. Crit Care, 2011. 15(6): p. 314.
9. Howard, S.K., et al., Anesthesia crisis resource management training: teaching anesthesiologists to handle
critical incidents. Aviat Space Environ Med, 1992. 63(9): p. 763-70.
10. Carbo, A.R., et al., Developing a high-performance team training framework for internal medicine
residents: the ABC'S of teamwork. J Patient Saf, 2011. 7(2): p. 72-6.
11. Stiegler, M.P. and K.J. Ruskin, Decision-making and safety in anesthesiology. Curr Opin Anaesthesiol,
2012. 25(6): p. 724-9.
12. Haimes, Y.Y., Systems-Based Guiding Principles for Risk Modeling, Planning, Assessment, Management,
and Communication. Risk Anal, 2012.
13. Seiden, S.C., C. Galvan, and R. Lamm, Role of medical students in preventing patient harm and enhancing
patient safety. Qual Saf Health Care, 2006. 15(4): p. 272-6.
14. Beckett, C.D. and G. Kipnis, Collaborative communication: integrating SBAR to improve quality/patient
safety outcomes. J Healthc Qual, 2009. 31(5): p. 19-28.
15. Leonard, M., S. Graham, and D. Bonacum, The human factor: the critical importance of effective teamwork
and communication in providing safe care. Qual Saf Health Care, 2004. 13 Suppl 1: p. i85-90.
16. Moorthy, K., et al., A human factors analysis of technical and team skills among surgical trainees during
procedural simulations in a simulated operating theatre. Ann Surg, 2005. 242(5): p. 631-9.
17. Phipps, D., et al., Human factors in anaesthetic practice: insights from a task analysis. Br J Anaesth, 2008.
100(3): p. 333-43.
18. Helmreich, R.L., On error management: lessons from aviation. BMJ, 2000. 320(7237): p. 781-5.

Disclosure
Masimo Corp., Self, Consulting Fees

315
Page 1
Disaster Preparedness: Yourself, Your Family, Your Department
Joseph McIsaac, M.D., MS Avon, Connecticut
Disaster Preparedness: Yourself, Your Family, Your Department
Disaster Epidemiology
Disasters seem to be increasing infrequency and severity. Whether this is due to real forces, such as climate change,
or merely a perception due to our increasingly connected world is not known. What is known, is that preparedness
can markedly reduce the impact of a disaster on those affected.
Hazards and HVA
A hazard can be modified or prevented and its probability of occurring represents a risk. Once the event occurs, its
impact on the affected population depends on their ability to absorb, buffer and respond. Collectively, this is called
resilience. When local resources are insufficient to respond appropriately and outside help is needed, the event
becomes a disaster
1
. (See figure 1.) Disasters can be man-made or natural. Weather, seismic, and cosmic events
represent natural disasters. Acts of war, terrorism, and technological failure are clearly man-made. All hospitals in
the US are required to perform a Hazard Vulnerability Analysis
2
. A grid is prepared analyzing the likelihood of a
particular event occurring vs its impact. This is then used to prioritize resources and training. Geographic weather
patterns are the prime drivers of this template.
Hospital Preparedness: Are we ready?
Certainly, the world has changed much since 2001. Hospitals now undergo twice yearly preparedness drills and the
Hospital Incident Management System
3
(HICS) has been widely adopted. Medical staff preparedness is more
difficult to ascertain. This is the result of individual, team, and department training and exercises. The FEMA
Preparedness site is a great place to start
4
. The ASA Committee on Trauma and Emergency Preparedness (COTEP)
website is another useful resource
5
. It is imperative to run team and department wide simulations to practice your
plans and identify problems that can be corrected. Be sure to have a branching phone tree or automatic paging
system that can rapidly contact staff.
Family Preparedness
It is well accepted that staff members will not report during a disaster if they perceive that their families are at risk.
It is imperative that everyone have a Family Preparedness Plan
6
. This includes food, medication, and supplies for
sheltering in place for up to 3 weeks. (Dont forget about pets) Have a prearranged meeting place and an evacuation
plan. Go bagsprepacked backpacks with survival essentials, medications, and critical paperwork make for an
easier exit during an emergency. Be sure to question school and public officials about school plans and whether
there is a place of refuge available.
Terrorism
Guns and bombs are still the favorite means for creating terror. They are readily available and easy to use. All
medical personnel should review the principles of first aid and trauma care. The Department of Health and Human
Services maintains an extensive but easy to use set of online preparedness references
7
. There are several excellent
texts on trauma anesthesia
8,9
. The SALT triage system is an easy to use way to sort and prioritize mass casualty
victims. This can be found on the REMM website or through the National Disaster Life Support Foundation which
also runs several excellent courses
10,11
.
Familiarity with the management of explosive injuries, gunshot wounds, and burns is essential
12
.

315
Page 2
CBRN
CBRN preparedness, while thought to be less likely than ordinary mass trauma requires ready access to appropriate
references. All anesthesiologists should be familiar with chemical toxidromes, the management of radiation
casualties, bioterrorism agent syndromes, and the principles of isolation, decontamination, and the use of personal
protective devices. Again, HHS has assembled a set of references and playbooks on the web
13
.

Austere Medicine
Our fall-back position for maintaining resilience is to learn the principles of austere medicine and be prepared to
practice in spite of limited resources. Many books and courses on wilderness medicine and anesthesia for relief
missions can provide this knowledge
14,15
.

Figure 1. The Utstein disaster framework. Reproduced with permission from Sundnes and Birnbaum, 2003.

315
Page 3
References

1
Sundnes. KO and Birnbaum,ML, HEALTH DISASTER MANAGEMENT GUIDELINES FOR EVALUATION
AND RESEARCH IN THE UTSTEIN STYLE, VOLUME I. CONCEPTUAL FRAMEWORK OF DISASTERS,
PREHOSPITAL AND DISASTER MEDICINE VOLUME 17/SUPPLEMENT 3, p 35.
2
http://training.fema.gov/EMIWeb/downloads/UNTServiceLearning.pdf
3
http://www.hicscenter.org/
4
http://www.fema.gov/preparedness
5
http://www.asahq.org/For-Members/About-ASA/ASA-Committees/Committee-on-Trauma-and-Emergency-
Preparedness.aspx
6
http://www.ready.gov/make-a-plan
7
http://www.phe.gov/emergency/pages/default.aspx
8
Varon, AJ and Smith, CE, Essentials of Trauma Anesthesia, Cambridge University Press, 2012.
9
Smith, CE, Trauma Anesthesia, Cambridge University Press, 2008.
10
http://www.remm.nlm.gov/salttriage.htm
11
http://www.ndlsf.org/Courses
12
http://emergency.cdc.gov/masscasualties/essentialspro.asp
13
http://www.phe.gov/emergency/terroristthreats/Pages/default.aspx
14
http://www.wilderness-medicine.com/
15
http://www.ucsfcme.com/2013/courseDetails/MMJ13012/MMJ13012.pdf

Disclosure
US DHHS, Self,Salary ; Mountain Laurel Biomedcal, LLC, Self, Spouse_Partner, Ownership, Equity Position;
Hartford Anesthesiology Inc., Salary, Ownership

325
Page 1
Hospital Accreditation: What are My Choices and How Will It Affect Me?
Robert S. Lagasse, M.D. New Haven, Connecticut
So why do we care about performance measurement?
We should care about performance measurement because it is required by several accrediting and regulatory
agencies. These include, most notably, the Joint Commission and other accrediting bodies like DNV Healthcare, a
Norwegian Company that applies the ISO 9001 standards for many industries and has recently gotten involved with
healthcare in the US. Other accrediting agencies include AAAHC and AAAASF for ambulatory facilities and many
regulatory agencies also require performance measurement. The regulatory agencies include your state Department
of Health and the Centers for Medicare and Medicaid Services. And finally, the American Board of Anesthesiology
requires performance measurement for Maintenance of Certification in Anesthesiology.
Other organizations allow voluntary participation in their performance measurement activities, but if your hospital
or group has chosen to participate, you may not have a choice. These voluntary projects include the Surgical Care
Improvement Project and the American College of Surgeons National Surgical Quality Improvement Project. And
at the physician level voluntary programs include the Physicians Quality Reporting Initiative. Some of the specialty
societies also maintain outcome databases. The most notable of these is the Society of Thoracic Surgeons database
for cardiac surgery outcomes, and of course the relatively new Anesthesia Quality Institute. Needless to say, I have
only mentioned a few of the hundreds of performance measurement sets that are available. These come from quality
improvement organizations, insurers, consumer advocacy groups, and, in the near future, Accountable Care
Organizations.
The Joint Commission
So, lets look at some of the details. The Joint Commission, for example, has performance improvement standards
that require hospitals to collect data to monitor performance. This data must be compiled and analyzed, and
information from the data analyses must be used to make changes that improve performance. Also, the leadership
standards require each organization to have an organization-wide, patient safety program. The Joint Commission
assesses compliance with these standards by looking for specific Elements of Performance (EPs). The EPs for the
standard that says that the hospital must collect data to monitor its performance specify exactly what data should be
collected. This includes performance improvement priorities identified by leaders, operative or other procedures that
place patients at risk of disability or death, adverse events related to using moderate or deep sedation or anesthesia,
use of blood and components, all confirmed transfusion reactions, the results of resuscitation, significant medication
errors, significant adverse drug reactions, and patient perception of safety and quality. It is easy to see that many of
these measures relate directly to what anesthesiologists do for a living.
The Joint Commission also requires us to monitor and evaluate each practitioners professional practice. The
Medical Staff standards require Ongoing Professional Practice Evaluation (OPPE). As the name implies, OPPE must
be continuous and must be factored into decisions regarding clinical privileges. Focused Professional Practice
Evaluation is slightly different in that it is time limited and triggered by specific criteria, such as being newly hired.
TJC does not specify which performance measures need to be used, only that they should be developed by the
individual departments and approved by the organized medical staff.
ORYX is the Joint Commissions performance measures database. The Joint Commission requires accredited
hospitals to collect and transmit data to The Joint Commission for a minimum of four core measure sets through an

325
Page 2
approved ORYX vendor. Of note, the current ORYX measure sets include the Surgical Care Improvement Project
measures, which are relevant to anesthesiologists.

The Surgical Care Improvement Project

The Surgical Care Improvement Project (SCIP) began as a national quality partnership of 10 organizations,
including the American College of Surgeons, VAs National Surgical Quality Improvement Project, and the ASA
along with the Centers for Medicare and Medicaid Services and the CDC to reduce surgical complications by 25%.
That project currently involves process measures in 4 target areas where there is some evidence that outcomes can
be improved. These include surgical wound infection, cardiac morbidity, thrombophlebitis and ventilator associated
pneumonia. Many of these processes are under the control of the anesthesiologist, such as selection of antibiotics,
timing of antibiotics, maintenance of normothermia, and glucose control to prevent surgical site infection. Similarly,
anesthesiologists can reduce the incidence of perioperative MI by appropriate administration of B blockers. At the
outset of SCIP, the recommendations were thoughtfully based on Level 1 evidence with particular attention to the
applicable patient populations, but that is changing as performance measurement becomes more closely related to
reimbursement. For example, the normothermia measure was expanded beyond the scope of colorectal surgery,
where most of the evidence lies. Other examples of process measures getting ahead of the evidence can be seen with
the use of perioperative beta blockers. The Joint Commission does not have the ability to react to the rapidly
changing evidence regarding the use of perioperative beta blockers and the possibility that current recommendations
may increase the risk of stroke and, possibly, death.

Centers for Medicare and Medicaid Services

CMS also has federal regulatory requirements for performance measurement. The Medicare Prescription Drug,
Improvement and Modernization Act of 2003, provided a financial incentive for hospitals to report quality of care
data for release to consumers. There were 10 measures for 3 medical conditions that included MI, CHF, and
pneumonia. Reporting was voluntary, but if the hospital didnt report, their annual market basket update from
Medicare was reduced by 4 tenths of a percentage point. Interestingly, for 4/10ths of a percentage point, over 99%
of hospitals participated. Amendments to Deficit Reduction Act upped the ante for hospitals in 2007 from 0.4% to
2%. They also established procedures for making the reported data available to the public through Health and
Human Services.

The latest in this evil progression appeared in the Federal Register in May of 2007. For discharges occurring on or
after October 1, 2008, hospitals could no longer receive additional payment for certain high cost, high volume DRGs
if they represented conditions that were not present on admission. In other words, the hospital is paid as though the
secondary diagnosis was not present, even though it must be reported, because these complications, in the eyes of
the federal government, should never happen. These so-called never events include catheter-associated urinary
tract infections, pressure ulcers (decubitus ulcers), foreign object retained after surgery, air embolism, blood
incompatibility, and staphylococcus aureus septicemia. Clearly, we can take steps to reduce these complications, but
we will never reduce the incidence to zero.

National Surgical Quality Improvement Project

One of the more complex models of performance measurement is the VAs National Surgical Quality Improvement
Project. NSQIP has developed and validated separate risk adjustment models for 30-day morbidity and for 30-day
mortality after major surgery in eight surgical subspecialties and for all operations combined. Trained chart
abstracters review medical records for complications and for several patient characteristics that are used for risk
adjustment.

325
Page 3
But this modeling comes with a pretty high price tag. The cost of data collection and analysis has been quoted at
approximately $38 per case. The VA database is expanding by approximately 100,000 cases annually and currently
has over 1 million cases. So the cost to date has been over $38 million dollars; yet private sector hospitals are still
lining up to participate as the American College of Surgeons moves this project into the private sector. Each
hospital pays about 35 thousand dollars annually, plus the cost of a trained nurse data collector, which would
probably be around $50,000. The VA made this investment because of a 1986 congressional mandate to compare
their outcomes to the national benchmarks following accusations of substandard care for our veterans. But what
motivates the private sector to want to spend this kind of money?

Return on investment motivates the private sector. In NSQIPs first ten years, the 30-day postoperative mortality
decreased by 27%. Beginning with a 30-day mortality of 3.1% for major surgery in 1991, it decreased to 2.2% in
2002. But there is a definite slowing of this improvement. This is even more dramatic when you look at
postoperative morbidity. The number of patients undergoing major surgery in the NSQIP who experienced one or
more of 20 predefined postoperative complications decreased from 17.8% to 9.8% over ten years. At the same time,
the median length of stay declined by five days. Although unpublished, NSQIP administrators feel that these results
justify the cost. That may be true, but the real question is whether continued costs can be justified. When compared
to 15 academic centers in the private sector, the VA showed comparable morbidity and mortality rates, but that was
after the VA had maximized their improvement. Maybe continued improvement is no longer possible.

Physicians Quality Reporting Initiative

Lets shift to physician level measurement. CMS has a pay for reporting program known as the Physicians Quality
Reporting Initiative, or PQRI, which was established by the Tax Relief and Health Care Act of 2006. In 2007,
eligible professionals who successfully reported a designated set of quality measures earned a bonus payment from
Medicare of up to 1.5% of total allowed charges for covered Medicare physician fees. Unlike hospitals, the majority
of physicians did not feel that the bonus payment offset the data burden, so they did not participate. Also, the
majority of physicians who did participate did not earn their bonus because of the quirky accounting methodology.
That is all going to change because the Patient Protection and Affordable Care Act, often referred to as just the
Affordable Care Act, is transitioning PQRI incentives to payment withholds which were so effective on the hospital
side of reporting. That will amount to a 2% reduction by 2016. We can only hope that it doesnt progress to never
events as it did on the hospital side.

This change in the incentive program is likely to push all physicians to participate. In 2007, PQRI had 74 quality
measures. In 2012, this number has more than tripled. There are three measures applicable to anesthesiologists and
you can probably guess that they are antibiotic timing, CVC insertion protocols, and normothermia, which, as I
mentioned earlier, is being expanded in scope. You should also know that the ABA has also proposed Maintenance
of Certification in Anesthesiology as a PQRI measure.

If you were board certified in the last two decades, the ABA requires that you maintain your certification through
participation in their Maintenance of Certification in Anesthesiology, or MOCA program. If you enter the MOCA
program after January 2008, unless you hold a non-time limited certificate, you will be required to participate in
Practice Performance Assessment and Improvement or PPAI. PPAI is a three-part program that includes: 1)
simulation education, 2) patient safety education, and 3) case evaluation. The MOCA Case Evaluation is a 4-step
process in which the diplomate must: 1) collect performance data over an extended period of time, 2) compare
outcomes with practice guidelines, explicit expert consensus, or to peer data, 3) design and implement a plan to
improve outcomes using clinical reminders, education, system/process changes, or clinical pathways, and, then, 4)
collect new data, compare the latest outcomes to the chosen guidelines, and determine the amount of improvement
since the original assessment with goal being to improve or maintain a high standard of practice. The development
and implementation of a practice improvement plan may be an individual or a group effort. If the group approach is
used, it must be possible to extract the individual diplomates data from the group data. Sample case evaluations
covering the following topics can be found on the ASA Web site: nausea and vomiting, surgical site infections,
hypothermia, and perioperative beta adrenergic blockade.

325
Page 4
Data Collection

So thats a very quick overview of why we need to collect performance data, the next section reviews methods to
collect data. At my institution, we review all adverse events and I believe it is the responsibility of every provider to
report all adverse events. For the purpose of our quality management program, an adverse event is defined as any
event that you would not want to happen to a family member. This takes the judgment out of the reporting process.
If it seems badreport it. I also get adverse events reported from other sources, but anesthesiologists are the most
important source. Thats because physician self-reporting is a more sensitive means of detecting cases meeting
indicator criteria. I expect 85-90% of all adverse events to be reported by a member of our Department and
physician self-reporting is not biased by severity of the outcome or involvement of human error. Cases detected by
concurrent chart reviewers are more specific for outcomes involving death or permanent injury and staff using
hospital incident reports are six times more likely to report a case involving human error.

In Demings book, Out of the Crisis, he describes 14 points necessary for the transformation of American industry to
a more effective management style. Point number 8 is to drive out fear, so that everyone can work effectively for
the company. Bceause our department looks at system errors as critically as human errors, they share the
responsibility for quality care with management, thus making peer review less threatening. In the first year at my
current institution, self-reporting increased from 65% to over 90%. This phenomenon has occurred in every
institution in which I have instituted this peer review process. Of particular note, the self-reporting of cases
involving human error is also over 90%.

So how do you drive out fear? Some people fear a peer review model that openly discusses human errors because of
the fear of malpractice litigation, but that fear is unfounded. In fact, I looked at the relationship between malpractice
and human errors while at SUNY, Stony Brook. Out of 38,000 anesthetics performed, 13 cases were judged by peer
review to involve a human error by the anesthesia provider that led to a disabling patient injury. During that same
time period, 18 cases involved malpractice litigation defined as a letter of intent, claim, or closed claim in which
money changed hands. Anyone want to guess at how many cases overlapped? None! There is absolutely no
relationship between malpractice litigation and human errors.

Some people also fear that having a human error in their credentialing file is somehow going to make them standout
from their peers. So, I looked at the statistical power of human error rates for judging clinical competence. During
the study period, 323,879 anesthetics were administered and 104 adverse events were attributed to anesthetist error
for a rate of 3.2 per 10,000 anesthetics. According to a survey conducted at the same time, the median number of
human errors by an anesthetist felt to be indicative of the need for remedial training and suggestive of incompetence
were 10 and 12.5, respectively. What I found was that if we were willing to be wrong about 1 out of 100
anesthesiologists judged to be incompetent (alpha error 0.01) and 1 out 20 anesthesiologists judged to be competent
(beta error 0.05), then sample sizes of 21,600 anesthetics per anesthesiologist would be required. Even at these
unacceptably high levels of alpha and beta error, an appropriate sample size could require over two decades to
collect. Therefore, the concept of utilizing human error rates to judge clinical competence is not feasible. This has
implications for database registries designed for this purpose.

Peer Review

The peer review model that we use is a structured review process that has several important components that are
necessary to improve the interrater reliablity. Interrater reliability is important because, in order for physicians to
make improvements in care, they have to agree on what needs to be changed. In order to increase interrater
reliability amongst reviewers, you need to have a stable pool of multiple reviewers who share an area of expertise,
are aware of the outcome, and meet to discuss the case using a structured review process.

The structured review process has been shown to focus the reviewers task and prevent them from fixating on a
single error. We have talked about fixation errors in clinical care, but they can also exist in peer review. For
example, if you were reviewing a case of esophageal intubation, you might want to focus on the human factors that

325
Page 5
resulted in missing the diagnosis, and not discuss the system factors that have to do with why monitors fail to alert
providers to the diagnosis, how the alarms can be disabled, or why calling for help doesnt result in resolution of the
problem. Structured peer review forces you to look at system factors as critically as human factors. The human
factors are fairly self-explanatory and something that you are all probably quite used to considering. They include:

Improper Technique : leaving a short IV catheter in a jugular vein
Operator Error: neglecting to perform an appropriate machine check
Data Disregarded: failure to avoid a known drug allergen
Inadequate Data Sought: failure to check appropriate extubation criteria resulting in respiratory failure
Inadequate Knowledge: incorrect interpretation of hemodynamic variables resulting in pulmonary edema
Supervision of Residents or CRNAs: not performing your supervisory function in the prescribed manner
Communication Error: improper sign-out during transfer of care results increased patient risk
Lack of Professionalism: lack of professionalism by an anesthesiologist that adversely affects patient care
You can see that human factors cover the six core competencies that one expects to see in an anesthesiologist

System factors are a little less intuitive, but it is consideration of these factors that is most likely to result in
performance improvement. They include:
Technical Accident: wet tap while performing an epidural with an appropriate loss of resistance technique.
Equipment Failure: equipment failure despite appropriate checks and maintenance
Limitation of Therapeutic Standards: the ten year old that gets hit by a bus and is not resuscitatable
Limitation of Diagnostic Standards: the undiagnosed IHSS becomes symptomatic after a spinal anesthetic
Limited Resources Available: could be anything from blood products to equipment
Limited Supervision: an attending supervising two locations and cant be in both places at once
Communication Failure: failed communication despite following the proper lines of communication
Lack of professionalism: lack of professionalism on the part of someone other than an anesthesia provider

When you employ this peer review model, you get a distribution of contributing factors that looks something like
Figure 1. You can see that most adverse outcomes are not the result of human factors, but overwhelmingly due to
system factors. The most common system factors leading to adverse events are limitations of our standards of care
and, therefore, represent unavoidable events. When I first looked at this distribution, human factors contributed to
about 8% of adverse events reported. In the eight or so hospitals where I have instituted this model, the human error
has contributed to 3.5 to 11% of the adverse events reported.

325
Page 6

I believe that this peer review model has face validity because the error distributions that it yields are similar to error
distributions in other industries. W. Edwards Deming, who is often credited for transforming Japanese industry after
WWII, said that I should estimate that in my experience most troubles and most possibilities for improvement add
up to proportions something like this: 94% belong to the system (system errors are the responsibility of
management) 6% special (human errors are the workers responsibility)

After peer review is completed, final changes will be made to the database and the data will be used for several
purposes. These include Ongoing Professional Practice Evaluation and MOCA, statistical process control and
quality improvement, clinical research, regulatory and accrediting requirements, and resident evaluation as part of
the ACGME outcomes project. We are also currently working on an export of data to AQI from our new automated
information management system.

Maintenance of Certification in Anesthesiology

So, lets just look at a few examples of the database output. With regard to MOCA PPAI, I have a few examples, but
they do raise some questions for the Board. This is a run chart of the reintubation rate at my last place of
employment. We decided that this rate was too high by comparing it to data from another institution where I had
implemented this model. There is no evidence to support the idea that a reintubation rate of 1 in 1,000 cases is too
high. Some argue that if the reintubation rate is too low, then you may leaving too many endotracheal tubes in place
unnecessarily. In any event, we started to focus our peer review on specific extubation criteria and established a
standard within the Department. This standard was in part supported by the literature, though no practice guideline
exists. Not following these criteria results in the assignment of a human error in the event of a reintubation. You can
see that change has been slow overall, with a decrease in reintubation from 1 in 1,000 to about 1 in 2,000, but some
members of the Department made dramatic improvements.

325
Page 7
Questions are raised by looking at the individual provider reintubation rates, especially for providers with the
highest reintubation rates. For example, one provider clearly satisfied his case evaluation criteria by participating in
a performance improvement project and showing a rapid improvement to a level better than the Departmental
average. Another provider also demonstrated significant improvement, but maintains a rate about twice the
Departmental average. Does this satisfy the PPAI requirement for MOCA? And finally, what about the provider
who participates in a performance improvement project, but continues to show a great deal of variability in his
practice? For the purposes of MOCA, this provider could select specific data points and demonstrate improvement,
but has he really changed his practice. These are real situations and I believe they represent real questions for the
ABA.

Outcomes Research

With regard to research output from this database, having real numbers lets you question the literature. For example,
the 1999 Institute of Medicine (IOM) report entitled To Err is Human said that 44-98,00 Americans die each year
as a result of medical errors. That same report, however, held anesthesiology up as a model of safety and said
today, anesthesia mortality rates are about one death per 200,000300,000 anesthetics administered, compared with
two deaths per 10,000 anesthetics in the early 1980s. Unfortunately, the reference cited is an article from the Joint
Commission Journal of Quality Improvement that contains no references and no author. The report then went on to
attribute these impressive gains in patient safety to improved monitoring techniques, the development and
widespread adoption of practice guidelines, and other systematic approaches to reducing errors. Now I had used this
quality management program at two university hospital networks prior to 1999 and had demonstrated an anesthesia-
related mortality rate of about 1 in 13,000. Not exactly the model of anesthesia safety.

So I decided to take a look at the literature. I queried the Medline and HealthStar databases using keywords
anesthesia and mortality in order to identify anesthesia-related mortality studies in general patient populations.
In other words, I excluded studies that were restricted to certain age groups, anesthetic techniques, or disease states.
This query identified 23 anesthesia-related mortality studies covering periods between 1955 and 1992: overall
perioperative mortality ranged from 1 death in 53 anesthetics to one in 5,417 anesthetics (a difference of two orders
of magnitude), while anesthesiarelated mortality ranged from 1:1,265 anesthetics to one in 85,708 anesthetics.
When the data is plotted on a run chart, you see tremendous variability and no clear trend over time. In fact, only
six data points are within three standard deviations of the mean of 3.34 anesthesia-related deaths per 10,000
anesthetics. The highest reported mortality rate was in 1992 by McKenzie and one of the lowest was in 1962 by
Kubota. Clearly, with this amount of variability, one cannot choose single data points for comparison. Most
anesthesiologists have been presented with data from the mid-sixties, seventies, and eighties and led to believe that
anesthesia-related mortality is declining. If that were acceptable, however, one could easily start in the early
eighties and suggest that anesthesia related mortality has increased dramatically. Both of these assumptions ignore
the variability in the data.

So, what led to the anesthesia-related mortality rate of 1 in 200-300,000 that was quoted by the IOM did not appear
in my data. I believe that the IOM was referring to a study from the Harvard hospitals in Massachusetts. In this study
John Eichhorn looked at the anesthesia-related mortality in over 1 million patients. He found five deaths in his
sample for an anesthesia-related mortality of 1 in 200,200, which came to be quoted as 1 in 200 300,000. But, to
be included in the Harvard study, the patients needed to be healthy (ASA PS 1 or 2), they needed to die on the
operating room table, and the death needed to involve litigation against the anesthesiologist who was felt to be solely
responsible.

Believe it or not, my anesthesia-related mortality rate of 1/13,000 is consistent with Eichhorns 1:200,000 when
similar definitions are applied. Of the 14 anesthesia-related deaths in my dataset, only 4 were the result of major
contributions from the anesthesia personnel, or 1 per 46,118 anesthetics. Of the four deaths with major contributions
by the anesthetist, only 1 occurred in a patient with an ASA Physical Status of 1 or 2 and resulted in litigation over
the eight-year period in which 184,472 anesthetics were performed. Interestingly, this death did not occur
intraoperatively and would have been excluded by Dr. Eichhorns criteria.

325
Page 8
Morbidity, like mortality, lacks uniformity in its definitions. In one study from the Mayo Clinic, investigators looked
at 518,294 patients to determine predictors of survival following cardiac arrest in patients undergoing non-cardiac
surgery. They found a frequency of 4.3 cardiac arrests per 10,000 anesthetics and felt that 0.5 were attributable to
anesthesia. Looking at survival of these cardiac arrest patients then led them to report a mortality caused by arrests
attributable to anesthesia as a rate of 1 in 100,000 anesthetics. This report drew closer scrutiny from me when they
went on to say that recent studies found somewhat higher rates of anesthesia-attributable mortality and one of those
studies was mine. Upon a closer look, I found that Sprung defined cardiac arrest as an event requiring closed chest
compressions or open cardiac massage. Also, unstable patients whose arrest occurred after an anesthetic induction
agent was given, were not considered as having had an anesthesia-attributable cardiac arrest, regardless of the fact
that anesthesia may have contributed.

So, lets perform the same exercise for cardiac arrest that we just did for mortality using data from my institution. In
my last institution, where we had an anesthesia-related mortality rate of 1:13,000, we had 253 deaths within 48
hours of 180,000 anesthetics. Only 110 involved a cardiac arrest during anesthesia care and only five were judged
by our peer review process to involve human error. This gives us a rate of 1:36,000 deaths caused by anesthesia-
related cardiac arrests. Not quite as good as the Mayo clinic until I exclude the three patients who were unstable
prior to induction, then my rate is nearly identical to that of the Mayo Clinic.

Another area of the literature that I believe lies in question is the closed-claims analyses. The Closed Claims Project
began in 1985 under the auspices of the ASA Committee on Professional Liability. The current database consists of
nearly 9000 claims and is expanded by approximately 300 claims annually. Despite the fact that this is a very small
percentage of the total litigation brought against anesthesiologists in the United States and that there is no
relationship between malpractice litigation and quality of care, the ASA Closed Claims project has drawn several
conclusions from their data and published them in the medical literature.

For example, one publication in Anesthesiology is a review of claims centering on problems with equipment used in
anesthesia gas delivery systems and concludes that Misuse of equipment is more common than equipment failure,
and most of these equipment problems result in death or brain damage. Using a clinical outcome database and a
structured peer review model for anesthesiologist you might come to a different conclusion. For example, we
identified 161 equipment problems from 1995 to 2003 at Montefiore Medical Center. Like other error types,
approximately 89% were due to system errors and 11% due to human errors when judged by anesthesiologists.
Most of these adverse outcomes resulted in increased care or risk without any functional deficit to the patient.
Seventeen were specifically related to the gas delivery systems and showed identical error distributions and outcome
severity.

So, I would like to leave you with a final thought. If anesthesia is not as safe as the IOM suggested, how effective
are the mechanisms to which the IOM attributed our success? We will leave this topic for another time, but I will tell
you that two Cochrane reviews have been unable to demonstrate the effectiveness of monitors as revered as pulse
oximeters, there is very little evidence behind our practice guidelines, and some of that evidence is a moving target,
as we have seen for the use of perioperative beta blockers.

Disclosure

330
Page 1
Compemnsations for Service-When Revenues Dont Support the Expectations
Asa C. Lockhart, M.D., M.B.A Tyler, Texas
COMPENSATION FOR SERVICES
Developing a Strategy for Success
Stable anesthesia groups have a good payor mix, efficiently run operating rooms, an equitable compensation model,
and a sound internal professional and business infrastructure. While severe problems can overwhelm a group with a
strong infrastructure, relatively minor issues can engulf a group that has not invested in strategic and business
planning. If any of the above elements are missing or diminished, the initial warning signs of retention and
recruiting instability brought on by below-market compensation and lack of patient access to surgical services can
quickly erode a practice. These confounding factors justify compensation for service (CFS) arrangements between
anesthesia groups and hospitals, but the days of merely asking hospital administrators to stabilize an anesthesia
group by giving them an unsubstantiated stipend are gone. Therefore, reframe the negotiation process from a
simple request for money into a concept that more accurately reflects the driving forcecompensation for the
desired level of anesthesia services requested by the hospital not supported by the revenue generated from clinical
activities due to poor operating room efficiency, surgeon practice patterns, utilization, and/or payor mix. If your
group determines that a CFS is required, you must develop a strategy for a successful negotiation.
You cannot manage what you cannot measure. In order to have a winning strategy, one must define the stakeholders
and their expectations, evaluate the data, convert the data to information, the information to knowledge, and develop
a fact-based story. The internal and external stakeholders include patients, surgeons, anesthesiologists,
proceduralists, obstetricians, perioperative staff members, and hospital administrators. A benefit, either real or
perceived, must exist to motivate the various stakeholders who require, utilize, or provide anesthesia services to take
action. Each stakeholder group has its own goals and deliverables that may or may not conflict, and which other
stakeholders may or may not understand. Most anesthesia groups want to maximize efficiency while most surgeons,
proceduralists, obstetricians, and administrators want to maximize access and market share. As stated above, patient
access to surgical services is the basic justification for a CFS agreement. If there is a threat to access due to
anesthesia recruitment and retention deficiencies, there will be a greater sense of urgency from multiple stakeholders
for a successful CFS negotiation. It is also important to evaluate the practice patterns and customer service
philosophies of all of the anesthesiologists and their employees to determine if there will be pushback from external
stakeholders if the hospital agrees to a fair-market value CFS agreement.
When preparing a strategy for a contract negotiation that requires a CFS, it is important to include the following
steps: (1) identify the appropriate staffing utilizing a staffing grid (SG), (2) evaluate operational and practice
performance against national benchmarks, (3) quantify the OR utilization metrics, and (4) embrace strategic
planning concepts. The goal is to develop a logical sequence of events that results in a story of why the group cannot
provide the desired level of access of anesthesia services with its native revenue stream.
Staffing
The OR is an inherently interdependent environment and demands a four-way conversation to develop an optimal
staffing configuration. Surgeons/proceduralists, anesthesiologists, hospital administrative, and OR nursing
representatives should develop the SG in conference so that there are no misunderstandings of the coverage
expectations; two-way conversations may not reflect the needs of the missing stakeholders resulting in a patchwork
or inadequate plan. This process permits the adjudication of conflicts in real time. The ability to perform a surgical
procedure requires a functional and synchronized unita surgeon/proceduralist/obstetrician, patient,
anesthesiologist/anesthetist, nursing staff, and an operating roomotherwise someone is wasting resources. The

330
Page 2
proceduralists and obstetricians are included since out-of-OR (OOOR) sites are the fastest growing service lines
requiring anesthesia, and these services are often not represented on the OR Committee. All sites requiring
anesthesia must be included in the Staffing Grid to determine the number of anesthesiologist and anesthetist FTEs
that are required. There should be a consensus among all stakeholders that the grid is a just-say-yes grid. If the
hours are on the grid, anesthesia services will be available and reflected in the budget. It should specify the hours
per day, number of days per week, and personnel configuration for each potential location. Additionally, there must
be appropriate administrative, vacation, and day-after-call (DAC) allowances. All potential anesthetizing locations
should reflect either dedicated, cross (or best efforts) coverage, flip rooms, and closed rooms. Best efforts coverage
is coverage that is not included in the budget or guaranteed contractually but may be provided with slack capacity or
DAC personnel. A flip location is a second dedicated clean room that would permit a rapid turnover for a surgeon,
but would not duplicate anesthesia personnel; duplicated personnel would require two locations on the staffing grid.
A closed location is a room: (1) that lacks the necessary equipment and is not functionally available at anytime, or
(2) one closed for a defined period (hours or days) with no assigned personnel. (See Figure 1)

Evaluate the Data
In preparation for CFS negotiations, it is important to see where your group fits in the local and national
marketplace. Remember that you are not asking for an undefined amount of money, you are developing a strategy
with concrete data to present to the hospital administration. For operational trending purposes, three years or two
years plus year-to-date (YTD) performance data will provide staffing, collection, business cost, and productivity
metrics. The basic benchmark data utilized in this process are charges, contractual adjustments/allowances/refunds,
revenue, cases, full-rate or undiscounted conversion factor (CF), and physician/anesthetist full time equivalents
(FTEs). Adjustments include contractual allowances and refunds. The contractual allowances represent the
difference between the full charge and the allowable charge (i.e., Medicare or managed care). Charges should be at
the full-undiscounted rate or they may later understate the relative performance of the group relative to benchmarks.
The question of what represents an FTE varies greatly by group. For fractional FTEs, they may represent a relative
percentage of days worked, hours worked, or relative percentage of compensation compared to full time personnel.

The Medical Group Management Association (MGMA) represents business managers for all specialties, and the
Anesthesia Administrators Assembly (AAA) represents anesthesia and pain management practices. The MGMA
produces a number of publications, including those formulated by AAA, that are useful in benchmarking your
practice. Other organizations produce salary surveys, but most of their surveys do not make a distinction between
the salary of a new hire and a partner, and some of their sample sizes are not statistically significant relative to the
number of anesthesia personnel in represented in a survey that may have over 1,000 responses for all physicians and
physician extenders. Executive search firms produce some of the surveys and tend to have lower numbers; this is
not surprising given their population, which occasionally makes them a popular resource during negotiations even
though they may not reflect the true market value for services rendered.

There is statistically significant compensation survey data for the country as a whole as well as well as geographic
sections in the annual MGMA Compensation and Productivity Survey. The geographic sections are Eastern,
Midwest, Southern, and Western. On the disc version only, there are minor regions as well. They are Northeast,
North Atlantic, Mid-Atlantic, CA-AK-HI, Eastern Midwest, Lower Midwest, Northwest, Rocky Mountain,
Southeast, and Upper Midwest. Since the relevant markets often extend beyond the minor regions, most clients use
either the geographic sections or national data points. Although not always present in the printed survey, the data
may permit the calculation of demographic, capitation, and multi-specialty differentials; it was available on the most
recent DVD. The compensation categories are anesthesiologists, pediatric anesthesiologists, pain medicine, and
anesthetists. Since anesthesiologists historically average 44 weeks of productivity per year, this translates into eight
weeks of vacation and CME. By calculating an adjustment/vacation modifier if the group takes a different time than
benchmark, neither the group nor the hospital are penalized for the variation. Most groups fall between a 6- and 10-
week range. Most anesthetists are around six weeks with a much smaller variation. By factoring in these variables,
the calculation will reflect similar practice comparables. The hours per week is no longer shown, but it has
historically been around 45 for median, 50-53 for the 75
th
percentile, and 57-60 for the 90
th
percentile. Trending and
confounding factor explanations build an even more compelling story.

330
Page 3
Data to Information Information to Knowledge
Tabulate the basic and derived data and convert it to information with the derivation of other key performance
indicator (KPI) metrics. The derived data provides the basis for the calculations that yield information but in and of
themselves do not provide a context for the determination of fair-market value (FMV). These include the average
charge per case, the average revenue per case, the average units per case, cases per FTE, FTEs per 1000 cases,
average charges per physician, compensation to gross charges ratio, average or aggregate conversion factor, and
total group units generated, and per FTE average. However, from an administrative viewpoint, the most important
KPI metrics are the net collection percentage (NCP), bad debt percentage based on total charges or revenues, benefit
costs, units per physician FTE, and billing and administrative costs.

Additionally, to demonstrate the billing and revenue-cycle management efficiency, evaluate the accounts receivable
(A/R). With the A/R, it may be necessary to evaluate it with adjustments for accounts that are greater than 180 days
since many practices roll those accounts into bad debt or suspended accounts (e.g., auto accident where the account
may not be adjudicated for several years). It is also important to know whether accounts have been re-aged; the
desired methodology is not to re-age the accounts. One can better evaluate A/R performance based on date of
service or date of posting as opposed to date of payment. Date of insurance payment is important in evaluating
prompt pay from the insurance company. However, except for the group inserting language into their contracts and
enforcing the provision, practice managers have little control over this metric. The calculation of an aggregate or
average conversion factor (CF) demonstrates the groups economic potential and may be useful in evaluating the
billing performance. Another major determinant for a viable practice is the public payor mix (i.e., Medicare,
Medicaid, Workers Comp, and Tri-Care). Due to the disproportionate impact of Medicare and Medicaid relative to
other specialties and facilities, the public payor mix is a key factor in an anesthesia groups economic potential
making the aggregate CF benchmark determination an important part of the story. This will allow the
administration to appreciate the performance trends of the practice. As one compares the practice information to
benchmarks, there is a transformation from information to knowledge. With benchmarks in anesthesia, it is
important to know when to use All Respondents data and when to use mode of practice data. If the mode of
practice is material to the metric, use the By Staffing Model section; otherwise, use the All Respondents section
data since it will have a higher number of responses. Full charges and revenue per unit, A/R, and payor mix are
examples that are appropriate for All Respondents metrics. The productivity per FTE will vary significantly
between practice modes such as personally provided, anesthetist-to-physician ratio of <1:1, and anesthetist-to-
physician ratio of >1:1. Avoid using the All Respondents data for productivity related metrics since it does not
accurately portray any of the specific practice modes, and the billing/administrative overhead is very practice mode
sensitive (See Figure 2). Having calculated the above data, benchmarking against national databases will build your
story.

The development of a budget summary sheet based on projected revenues and expenses will display the financial
impact of the group-facility relationship. Unless a substantial change is expected, the previous years revenues are
the basis for the following years revenue projection; as one passes midyear, year-to-date (YTD) calculations may be
used. However, one must be careful to avoid extrapolating data points that do or do not include unusual or onetime
events (e.g., lump sum adjudication from previous year accounts or lump sum professional liability premiums and/or
retirement contributions paid at the end of the year). The expenses will be the number of anesthesiologists and
anesthetists required multiplied by the salary and benefit costs, billing and administrative costs, and other
professional overhead (OPOH). The OPOH represents professional overhead that is not discretionary, which
includes FICA, Medicare tax, various unemployment taxes, professional liability insurance, dues and subscriptions,
CME allowances, business and occupational taxes, and miscellaneous items. Other than CME, these costs are
essential professional overhead categories that are non-negotiable and mandatory. The net income of revenue less
expenses may justify a CFS if it is negative and the hospital is requesting a level of coverage not supported by the
net income.

Once there is a validation of sound business practices, assess whether the practice is above, at, or below market
since a CFS can only be justified if a practice is materially below market. Two common methods for determining
CFS are net income guarantees pegged to a commonly accepted benchmark such as the MGMA Compensation
Survey and guaranteed units per location per day that result in a targeted income. As stated above, these levels will
vary with acuity, geographic location (Eastern, Southern, Midwest, and Western), number of vacation/CME weeks,
and demographic category. Anesthesia departments within multi-specialty clinics require further adjustments. One
basis for selecting the appropriate compensation survey percentile (25
th
, 50
th
, 75
th,
and 90
th
) is the relative practice
acuity, but it may also reflect local/regional competitors to avoid defections in a retention-based strategy. Some

330
Page 4
consultants will use an average of several performance metrics. These metrics may include information such as call
frequency and acuity that are material considerations, but they may not carry equal weight with potential recruits.
This method may skew the FMV if one of the metrics is unusually low where one is only averaging a handful of
numbers. The FMV must ultimately reflect the percentage of the workforce that is able to meet the clinical
expectations and willing to make the lifestyle sacrifice required by the position.

Utilization
The nationally accepted utilization benchmarks are 70% without turnover time and 80% with turnover time.
Suboptimal utilization of operating rooms can be attributed to a silo culture, pre-admission testing (PAT) strategies,
block posting policies without discipline, high cancellation rates, and physician referral patterns. By far, the major
opportunity for stabilization is block postingif there are consequences for poor citizenship. An anesthesia group
cannot sustain itself if the surgeons and proceduralists operating patterns leave large blocks of time in the daily
schedule and then insist on adding patients to the evening schedule. Even though it is clear that utilization is the key
to a self-sufficient anesthesia group, many administrators are not willing to eat the political fire by telling the
surgeons they must be more efficient, which may be a legitimate strategic consideration to retain market share in
very competitive markets. That business decision is another reason for a CFS agreement. In the post-health system
reform world, these considerations will become even more significant.

Strategic Planning
The cornerstones of strategic planning are a S-W-O-T Analysis and Business Plan that includes an Action Plan. A
S-W-O-T analysis identifies the groups internal Strengths and Weaknesses and external Opportunities and Threats.
The planning process is most successful when utilizing a survey instrument that is enhanced through group
discussion after the results have been tabulated. Running a medical practice like a business is not only helpful
internally, it strengthens the groups position with the hospital if there is a partnership element to the negotiations.
Deliverables might include improved on-time starts, group discipline, and champions for improved utilization and
perioperative redesign. The focus is to determine what issues enhance or diminish utility. The goal is to develop a
win-win scenario where both organizations reinforce their relative strategic plans in a mutually beneficial
relationship on a functionally unified balance sheet.

Develop and Execute Your Story
Your success will depend upon your ability to convert information into knowledge in an impactful, organized
manner. Additionally, it is crucial that a decision-making committee and negotiating team be empowered to affect
change in order to assess the achievable goals and implement them to the benefit of the anesthesia group and/or
various stakeholders. Mere discussion and vetting of the issues does not achieve the goal of correcting the
underlying factors that led to the stated difficulties. There must be an alignment of incentives with a clear
understanding that CFS is not the same as Pay for Performance (P4P), nor is it an annuity. It is essential that the
practice data be in the same format as the benchmark (i.e., the number of time units per hour) and presented in a
tabular, trended format to optimize the visual impact. Benchmark the KPI against the Medical Group Management
Association (MGMA) Anesthesia Cost Survey results, published every other year, to assess the relative efficiency
and productivity of your organization. As noted earlier, one must be cautious in using the generic MGMA Cost
Survey that is produced annually and cannot be used for data points impacted by mode of practice.

Since failure to implement the required changes is the most common reason for a failed result, adequate time and
resources should be devoted to this aspect of the process. Once a consensus is reached, the formal implementation
phase should begin immediately. Although the appropriate plan will give the stakeholders a sense of well-being, it
is the implementation, and not the plan itself, that ultimately solves the problems and meets expectations.
Persistence is the key!

While the numbers tell the story, they tend to be arcane and confusing to hospital administrators and their
consultants if they the lack anesthesia experience. The goal is to develop an easy to follow story utilizing a logical
sequence of information that explains outliers and anticipates potential flashpoints. For instance, assigning revenue
and expenses to a responsibility center such as OB may explain why OB places undue pressure on a group since
fully staffed in-house OB coverage may easily consume 40% of the gross revenues of a small anesthesia practice.
Another example would be a primary-care physician hospital board member who would have to be educated in
advance regarding anesthesiologist and anesthetist salaries since primary care salaries tend to be unfairly low and

330
Page 5
could result in a disruptive or subversive position in closed-door facility board of director meetings.
Anesthesiologist salaries do not surprise them, but many are justifiably incensed that a nurse out earns them!

Depending on the level of trust and market knowledge of the key stakeholders, it is important not to create a
perception that this exercise is only to guarantee high levels of income to the anesthesiologists. There is a higher
chance of success if framed in the context of stabilizing the anesthesia platform when it is requested to provide a
level of service that is not supported by the revenue stream generated. Recruitment, retention, and stability are the
desired goals.

Your presentation/story should flow in a logical and believable manner that demonstrates an alignment of incentives
between the group, hospital, and community as well as providing the desired level of access. Assess the political
timing before scheduling your first hospital meeting to make sure that this is the right moment in time to raise the
question. It must pass the smell test internally before being presented externally. If the objective assessment is
that there is not a satisfactory answer to these issues/questions, then the negotiation is not ready for prime time.

New Options and Current Trends
In the survey realm, the 2010 MGMA Compensation and Productivity Survey in the electronic format added the
Health and Human Services (HHS) Regions One through Ten as another option in addition to the previously
mentioned Major and Minor Regions as well as state specific data on 26 states. Although there is much crossover
with the Minor Regions, they are somewhat different. Some may feel that the existing options are not representative
of their practice setting. Depending on the scope of the data request and the content of their data repository, MGMA
may be able to run a custom report for your project for a region of the state or several adjoining states if there were
not enough respondents from your particular state.

In the past, coverage alone may have provided justification for a CFS. However, as the levels have grown both in
magnitude and prevalence, facilities are questioning what they are getting for their money. They seek to align the
incentives between the group, facility, and other stakeholders such as surgeons, hospital staff, and patients on
quality, performance, OR utilization, and/or other local issues. As evolving health system reform develops (e.g.,
Perioperative Surgical Home, clinical integration, accountable care organizations), their facets will introduce
additional mitigating factors in the negotiations.

Quality metrics often focus on Physician Quality Reporting Initiatives (PQRI) and Surgical Care Improvement
Program (SCIP) measures such as timely antibiotic administration, prevention of catheter-related bloodstream
infections, and normothermia. Local issues drive other requested metrics such as acceptable patient and/or surgeon
satisfaction scores, medication management (e.g., charge capture and controlled substance documentation), and
clinical adverse events. Jerry Stonemetz, MD, who was the National Medical Director, Anesthesia Services,
Clinical and Physician Services Group for HCA, advocates putting some portion of the CFS at risk with assignment
of weighted values to each metric with a sliding scale allocation depending upon the level of performance (e.g., 20%
potential on timely antibiotic administration with 100% payment for >95% compliance, 75% payment for 91-95%
compliance, 50% for 80-90% compliance, and zero for <80%).

Common performance metrics include assessment of on-time first-case-of-the-day (FCD) starts, timely pre-op
assessments, acute pain blocks, case delays, cancellation rates, turn-over-time (TOT), PACU sign-outs, and other
throughput process steps. The key point for a fair and meaningful assessment is the degree to which anesthesia has
control over the activity. Global metrics should be avoided since they may fail to meet expectations through no fault
of anesthesia. With FCD, it is fair to set a time certain where anesthesia is expected to be dressed and ready to work
(e.g., arrive by 0645 for 0715 in-room cases) and receive credit for an on-time arrival. However, if a patient enters
the room at 0735 due to a delayed surgeon arrival, patient site-marking, or missing lab results/instruments,
anesthesia should not be penalized since these delays would be beyond their control.

While an emergency room or primary care physician may have control over their productivity per unit of time, an
anesthesiologists productivity is more likely to be related to the requested number of simultaneous sites. The
conundrum is access versus efficiency, which are diametrically opposed. However, the group may be able to
position itself in a favorable light by providing accurate utilization numbers and suggestions on how the schedule
might be reasonably adjusted. Many productivity metrics are particularly risky since some of the more popular
facility options are beyond the control of their anesthesia department (e.g., units or cases per anesthesiologist). This

330
Page 6
risk will increase with evolving payment reforms, so groups must be prepared to articulate a reasonable response.
On the other hand, groups do have control over many elements that drive their financial efficiency performance so
long as they are reasonably adjusted for payer mix as discussed earlier in the section on benchmarks such as net
collection percentage or overhead. One must remember to use the appropriate benchmark for any metric driven by
mode of practice (e.g., units or cases per anesthesiologist); the facilitys consultant may not understand the nuance.

Local issues vary greatly. They are often related to problems with citizenship and professionalism. It may reflect
past or present conflicts and general attitudes of individual members or the group culture as a whole such as dress, or
personal interactions with surgeons, patients, and/or staff. The failure to discipline unruly members is one of the
most common, if not leading, factors for a group to lose a contract for non-economic reasons. This facet tends to be
very fact specific with much emotion and passion that at times may defy logic in relative terms.

Health system reform has impacted CFS arrangements in several ways. Hospitals on average will face a $2.5
million Medicare cut in the new payment paradigms with PPACA. This does not include other potential cuts in
revenue due to excess readmissions and an expanding list of never event penalties. Accountable care
organizations (ACO) and bundled payments give hospitals a sense of empowerment since they are better positioned
with capital to fund new initiatives. Closely related is the push towards physician employmentthe ultimate CFS!

Showtime
Lastly, it is important to determine the groups organizational BATNA or best alternative to no (or negotiated)
agreement. The BATNA determines when to walk away from the negotiation, and group members must be
intellectually honest in determining what they are willing to accept or not accept. One should never walk out of the
room unless they are willing to stay out until the other party blinks. Be cautious in asking the consultant what they
would do; they are not the one who has to relocate if things do not work out to the groups preference! If the
hospital administration senses a weakness in the groups resolve, they will make the most of it since that is their
fiduciary responsibility to their organization. Our economic system is built on a price-quantity combination between
two willing partiesnothing mandates that both, or either, are happy with the outcome! The best plan in the world
is worthless unless implemented. Once the strategic analysis indicates that the presentation is ready for primetime,
execute it!

Conclusion
Determine the critical success and critical failure factors, objectively assess your reasonable needs, assets, and
liabilities, and then synchronize your requests with the institutional objectives as well as your mutual key
stakeholders. View the current chaos and uncertainty with health system reform as an opportunity but also respect it
as a threat. The result should be a fair-market value proposition that truly benefits the community by providing a
stable and sustainable anesthesia platform. Persistence is the key!

903-521-6728
[email protected]

Sources
MGMA Compensation and Productivity Survey published annually
MGMA Cost Survey for Anesthesia and Pain Management Practices published every other year
MGMA Cost Survey published annually
Jerry Stonemetz, MD, Past National Medical Director, Anesthesia Services, Clinical and Physician Services Group
for HCA Personal communication

330
Page 7
Figure 1
STAFFING GRID EXAMPLE

Reprinted with permission from Golden Caduceus Consultants. 2013.

Figure 2
EXAMPLES OF DATA POINTS FROM COST SURVEY for ANESTHESIA and PAIN MANAGEMENT
PRACTICES: 2011 Report based on 2010 Data
Data: Median

Note that per physician data points vary by mode of practice while those that are independent of mode of practice
have less variation.
Data used with permission from the MGMA-ACMPE, 104 Inverness Terrace East, Englewood, Colorado 80112.
877.ASK.MGMA. www.mgma.com. Copyright 2011!

Disclosure
Golden Caduceus Consultants, Self, Spouse_Partner, Ownership
331
Page 1
50 Facts in 50 minutes: An Update from the Anesthesia Quality Institute
Richard P. Dutton, M.D., M.B.A. Park Ridge, Illinois
Introduction
Anesthesiology is the safest of all medical disciplines, with a failure rate of fewer than 1 in 1,000 cases and a
history of interest in patient outcomes that dates back more than a century. Landmarks include Rovenstines
promulgation of collected anesthesia case records in the 1930s,
1
Beecher and Todds examination of perioperative
mortality in the 1950s,
2
and creation of the Anesthesia Patient Safety Foundation, the Foundation for Anesthesia
Education and Research and the Anesthesia Closed Claims Project in the 1980s. In 1999 the Institute of Medicine
published To Err is Human, calling attention to preventable errors in healthcare and initiating a focused effort to
improve the quality of medicine in America.
3
Anesthesiology was singled out as the medical discipline which had
done the most to improve patient safety. In 2009 the American Society of Anesthesiologists took another step
forward by founding the Anesthesia Quality Institute (AQI). The AQIs mission is to improve patient outcomes
through development of a national anesthesia registry.
4

The AQI created the National Anesthesia Clinical Outcomes Registry (NACOR) in 2010 to capture basic data on
every case, every day from participating practices. A second registry, the Anesthesia Incident Reporting System
(AIRS) was created in 2011 to capture detailed information from individual cases of interest. Data is collected from
anesthesia practices of all types and sizes and aggregated to create benchmarks for clinical outcomes. The collected
data encompass all aspects of anesthesia quality including operational efficiency, safety, and patient experience.
Practices contributing to the AQI receive continuous online access to dozens of reports on their data. NACOR
reports show trends over time and how the practice compares to the rest of NACOR. Electronic tools allow for most
reports to be sub-divided by facilities in the practice, individual providers, and specific surgical procedures. NACOR
reports are designed to facilitate practice management, and to address burgeoning regulatory requirements from the
federal government and the Joint Commission.
Aggregated information from NACOR and AIRS describes the practice of anesthesiology in the United States, and
is distributed to ASA and subspecialty society leaders; Anesthesia in the US 2012 is available for download from the
AQI website at www.aqihq.org. AQI maintains dashboards of key indicators for ASA leaders, subspecialty
societies such as the Society for Obstetrics and Perinatology, and select ASA Committees. This Refresher Course
Lecture will provide a brief overview of the structure, mechanics and current status of the AQI, NACOR and AIRS,
and will present some snapshots of aggregated national data.
Data Acquisition
The AQI gathers information about the specialty of anesthesiology. This includes published reports in the scientific
literature, business articles and reports, and internal ASA communications. The most important sources of data,
however, are NACOR and AIRS. Participation in the AQI is open to every anesthesiology practice in the United
States, and any provider in the world can submit case reports to AIRS. There is no requirement for a minimum
level of technology or the use of software from any specific vendor. ASA members receive a substantial discount
for participation in NACOR.
Practices wishing to join the AQI begin by signing a Business Associate agreement that outlines the extent of
information to be shared and the rights and responsibilities of both parties towards that data. The AQI is accredited

331
Page 2
as a Patient Safety Organization by the Agency for Healthcare Research and Quality (AHRQ), and the
confidentiality of data contributed to the AQI is protected by both federal law and the Illinois Medical Studies Act.
The AQI collects all data in de-identified form, and is further bound by its practice agreements to preserve the
confidentiality of all patients, facilities, providers and groups.

NACOR is designed to accumulate data through periodic electronic reporting. Participating practices complete an
online demographic survey that describes their organization, the facilities they work in, and the members of the
group. This provides context for all subsequent case-specific data. AQI works with the practice to build links
between their existing software (billing systems, hospital systems, QM programs) and NACOR. The goal is to
collect whatever case-specific electronic data exists, without requiring new data entry by working anesthesiologists.
Data contributed to the AQI is entirely deidentified. Patient names and numbers are removed, and facilities and
providers are recorded by code numbers.

At present, every anesthesia practice uses electronic billing software, and the AQI works with vendors of these
products to enable periodic reporting. A participating practice is NOT required to have an anesthesia information
management system (AIMS). It is expected that electronic anesthesia records will advance over time, and AQI is
aiming for a future state in which a large amount of case-specific data is available through such systems. In the
meantime, the AQI is working with practices and vendors to design, improve and deploy electronic systems to
facilitate the aggregation of clinical data. One function of AQI is to develop consensus-based standards for defining
and reporting relevant outcomes in anesthesiology, and to share these with the healthcare information technology
industry. A second important function is to advise anesthesia practices on which elements of patient care are most
important to measure, and make them aware of technologies that may facilitate electronic data collection.

The AQI began recruiting participant practices in late 2009, and as of June 1, 2013 has signed agreements with 247
groups. These practices represent the breadth of anesthesiology in the United States, including a mix of academic
and private groups, large and small practices and both single-center and multi-hospital corporations. Forty-two out
of fifty states are represented, and these practices include more than 17,000 anesthesia providers working in more
than 1800 surgical facilities.

NACOR began collecting case data on January 1, 2010, and currently includes records on more than 10 million
cases. Information available from every case includes the date, location and duration of surgery; the specific
surgical and anesthesia procedures performed; the patients age, sex and primary diagnosis; the anesthesia coverage
model; and the specific providers involved. Many AQI Participant Practices contribute further electronic
information based on their local software systems. Additional data may include quality improvement forms (safety
and complications), patient experience (nausea and vomiting, pain management, satisfaction), operational efficiency
(length of stay, readmission or upgrades of care) and detailed information about the case itself (medications used,
procedures performed, patient vital signs, fluid management). Departments of Anesthesiology that are contributing
AIMS data to the Multicenter Perioperative
Outcomes Group (MPOG;
http://mpog.med.umich.edu/) can arrange to have
this same data transmitted simultaneously to
NACOR, thus reaping both research and quality
management benefits from the same information.

Reporting

AQI reports data to a variety of stakeholders
(Figure 1). AQI participating practices receive
quarterly online reports from NACOR which
include their own submitted data (trended over
time) and aggregated national benchmarks.
Features of the reports allow the practice to slice
and dice their data to examine specific facilities,
providers, cases or patient types. Reports can be
constructed out of multiple variables, and
displayed to the level of the individual

331
Page 3
practitioner. This allows the practice to use NACOR data for federal and hospital requirements (such as PQRS
submission and for the Joint Commission), and allows individuals to use NACOR data for maintenance of
certification and licensure. Outcome benchmarks can be created based on the peer groups of greatest relevance (for
example: hospital-affiliated surgery centers in the Southeast US). Member practices can construct reports on their
own, or can request specific reports and analysis from the AQI. In 2013 the AQI has begun publishing a
Participant User File (PUF) as a tool for academic research by anesthesiologists in AQI-participant practices. The
PUF includes cleaned, de-identified, case-level data from each full year of NACOR accumulation, as well as a data
dictionary that specifically describes the meaning and context of each field. Access to the PUF is available by
completing an application on the AQI website.

AQI is working with ASA Committees and anesthesia subspecialty societies to provide custom aggregate data
reports. Collaborations with AQI can take many forms, but one model is illustrated by the relationship between the
AQI and the Society for Ambulatory Anesthesia (SAMBA). Anesthesia practices with a large proportion of
ambulatory cases can contract with SAMBA to receive ambulatory-specific reports based on data collected in
NACOR that offer greater granularity for this subspecialty area. SCOR is a software front-end offered by
SAMBA that facilitates rapid collection of case data at the point of care and submission to NACOR. Groups
participating with both AQI and SAMBA will gain added value in understanding the ambulatory component of their
practice. More information is available at http://www.sambahq.org/.

Limitations of NACOR

In reviewing the data that follows, the reader should remember that garbage in = garbage out. Data in NACOR is
accumulated from hundreds of facilities, each with its own unique mix of patients, operations and providers. Data
transmission is through dozens of different electronic systems, many of which use unique definitions for outcomes
of interest. The greatest value of NACOR data to an individual practice is examination of their own outcomes over
time. Development of benchmarks requires unification of disparate data without full knowledge of its heterogeneity,
and interpretation of benchmark data should be undertaken with a grain of salt.
5
This is why the demographic
information collected from each practice is so important: it allows an understanding of the context of data collection
at individual sites. For some common elements NACOR data is highly reliable (e.g. surgical case times). For other
elements, such as the occurrence of postoperative nausea and vomiting, there are no standard definitions to draw on
and many different ways of collecting the data. Benchmarks in this area will be less solid, although trends over time
within a single practice sharing a common definition and level of risk will remain useful.

Another concern is the potential bias among practices that are participating in NACOR. It is likely that early
adopters are those groups which already put significant value on data collection and analysis, and are best able to
apply the quality management lessons learned. This might bias NACOR towards better performing groups and
lower aggregated rates of major complications.

Anesthesiology as a Specialty

The American Medical Association reports 42,000 anesthesiologists in its records, but does not report how many of
them are engaged in full-time clinical practice. Of these, more than 80% are ASA members. These providers work
in more than 40,000 ORs in 5,000 acute care hospitals and countless ambulatory surgery centers and physician
offices. At least 62% of all operations are performed on an ambulatory basis, with variable participation of an
anesthesiologist based on local history and economics. There are regions of the country in which less than 5% of all
endoscopies are done under monitored anesthesia care, and other areas where this number approaches 100%. (As an
aside, this appears to be driven more by the efficiency which anesthesia management brings to an endoscopy
practice than by fee-for-service billing.)

The average practicing anesthesiologist in the US is 50 years old. 25% of anesthesiologists in NACOR are women,
but this percentage increases in more recent graduating classes; 40% of PGY-1 residents are women. 73% of
anesthesiologists in NACOR are certified by the American Board of Anesthesiology. 85% report working full-time,
for an average of about 50 hours per week. Recent work force projections suggest an ongoing nationwide shortage
of anesthesiologists through 2020, as a slight decline in discretionary surgery due to the deflated economy is

331
Page 4
balanced by those leaving practice.
6
Surgical volume has increased a steady 3-4% per year for the past two decades,
and this is unlikely to change in the years ahead. There will be continued need for our services.

More than 5000 anesthesiology residents are currently in training at 131 accredited programs. More than 50% will
continue into fellowships this year (a substantial increase over the previous year), with the last available numbers
showing 292 pain fellows, 153 cardiothoracic fellows, 185 pediatric anesthesia fellows, and 104 critical care
fellows. Others are pursuing extra training in obstetrics, transplant, trauma and other disciplines that are non-
ACGME approved. It is not known how many are pursuing bench research or supplemental training in public
policy, statistics, business or epidemiology.

Demographics of Anesthesia Practice

Participating practices in the AQI range from one person private practices up to groups which include more than 100
anesthesiologists. Mean practice size is 37 physicians and 20 nurse anesthetists. While the majority of NACOR
practices are private corporations, at least 30 academic departments are current participants. Approximately 50% of
AQI anesthesiologists report some time spent teaching residents, student nurses, or anesthesiologist assistants.

65% of providers in NACOR are
anesthesiologists and 35% are nurse
anesthetists. This represents a bias in NACOR
relative to the approximately 50:50 nationwide
ratio of these professions. 63% of the practices
in NACOR work with NAs and 10% with AAs;
the remainder are physician-only groups. The
care team model of one physician medically
directing some number of residents, AAs or
NAs is dominant in NACOR, representing
more than 75% of all cases.

On average, practices in NACOR report
deriving 7% of their income from direct
contracts with a hospital, 5% from self-pay
patients, and 56% from Medicare or Medicaid.
There is substantial variability in these numbers
from group to group, however. 42% of
practices report operating an acute pain management service.

Thirty-eight percent of NACOR facilities are medium community hospitals (100-500 beds), accounting for almost
half of all the cases reported (Figure 2). 25% of facilities are freestanding ambulatory surgery centers and another
15% are hospital associated outpatient surgery facilities; these two groups account for 22% of all cases. Large
community and university hospitals represent only 10% of all NACOR facilities, but perform 24% of all cases.

Demographics of Anesthesia Cases

Approximately 10% of all patients in
NACOR are 18 years or younger; 38%
are aged 19-49; 26% are 50-64; 19%
are 65-79; and 7% are 80 years or
older. The average anesthesia practice
will soon see far more geriatric than
pediatric patients. Figure 3 shows the
distribution of male and female
patients by age in NACOR.

331
Page 5
Two thirds of the cases in NACOR were performed under
general anesthesia, 22% as monitored anesthesia care, and 10%
with spinal or epidural (Figure 4). Peripheral nerve block was
the primary anesthetic in less than 5% of cases. It is possible that
these numbers will shift as ultrasound-guided regional techniques
become more popular.

ASA physical status increases with age (Figure 5). One third of
50 year old patients are ASA III or greater. This proportion rises
to more than 60% by age 80.

Clinical Outcomes

One or more measures of clinical quality are reported by about three-quarters of NACOR participants, representing
more than 80% of cases. The most common outcome measures are the procedure codes for timely administration of
antibiotics, observation of sterile precautions during central line placement, and maintenance of intraoperative
normothermia. These measures incentivized by the Center for Medicare and Medicaid Services in the Physician
Quality Reporting Systemare reported by more than three quarters of NACOR participants, with a generally low
rate of failure.

About 25% of AQI practices collect and report detailed clinical outcomes, using a variety of different information
technology platforms and varying
definitions for the measures
themselves. An illustration of the
risks and benefits of these data can
be seen in Figure 6, which shows
the aggregated rate of
postoperative nausea and vomiting
(PONV), by patient age, for more
than a million cases from several
dozen practices which report this
complication. Looking at the data,
one might imagine that the
aggregate national rate of PONV is
about 6%, but this would be an

331
Page 6
erroneous assumption because of the different definitions used at the practice level. Some practices gather this
information subjectively from the PACU nurse, some from the anesthesiologist during patient sign-out, and some
from the objective administration of an anti-emetic medication. Each of these differing definitions will lead to a
different PONV rate, and aggregating this bushel basket of apples and oranges to arrive at a single national
benchmark is statistically fraudulent. Further, there has been no attempt to risk adjust this data. Some of these
practices perform large numbers of cases in adolescents and young women, while others do very few. So why show
the graph?

The answer is that within each practice a common definition and common case-mix risk applies. So the observation
that teenagers have a higher rate of PONV than octagenarians is perfectly valid. In other words, the shape of the
graph is likely correct, but the y-axis scale is not accurate. A second observation, that men and women have nearly
identical risk at each age, is harder to explain. Looked at within any given practice there is no reason to think that a
bias exists in how the data is collected for different genders. Looking at the literature, female sex is well established
as a risk factor for PONV. So the curves should diverge in magnitude, but dont. Why this is so is not clear, but is a
topic for ongoing investigation. One hypothesis is that women receive more aggressive prophylaxis against PONV
than men, and thereby arrive at the same relative risk. In the long run this is a question that NACOR data will help
answer, but in the short run it remains a mystery.

Serious adverse events, defined as those that cause patient harm or serious risk of harm, have been reported in about
0.5% of the approximate million-plus cases done by the groups that have electronic reporting of these occurrences.
Definitions of these are relatively standardized, based on the recommendations of ASAs Committee on
Performance and Outcome Measures. Serious adverse events range from dural puncture headache to peripheral
nerve injury to stroke and myocardial infarction. Perioperative deaththe ultimate adverse eventis reported by
these same groups, and provides a crude all-cause mortality of 0.05%, or about 1 in 10,000 anesthetics.

The AQI took a step this year towards increasing the capture of serious complications, and improving the
consistency of definitions. With MPOG, AQI hosted the First Annual Conference on Standard Definitions in
Anesthesia (DefCon 1) in April, 2013. Participants included anesthesiologists with an interest in electronic data,
patient safety, and anesthesia practice management, as well as representatives from a number of anesthesia software
vendors. Working together, a consensus document was developed that recommends a core set of outcome
measures to capture during the perioperative, recovery and post-recovery periods of any anesthetic. This document
is available on the AQI site at http://www.aqihq.org/files/Outcomes_of_Anesthesia_Summer_2013.pdf and is
available to any company developing software in this area, and to any anesthesia practice working to improve their
quality management program.

As yet the number of serious adverse events captured in NACOR is too small for statistical analysis, other than
making the observation that anesthesia is generally very safe. Serious adverse events or mortality have occurred in
fewer than 8 cases per 1,000 in NACOR, with the leading subcategories being the need for upgraded care (ICU
admission or hospital admission of an outpatient) and the need for resuscitation (variable definitions apply). While
committed to the long-term development of outcome benchmarks, the AQI intends to move cautiously in reporting
them. Because the frequency is so low, and the consequences of disclosure are serious, any public reporting of
major adverse events will require unified definitions, risk adjustment across reporting locations, and selected
auditing of submitted data. For the time being, detailed reports about major adverse outcomes will be confined to
the private quality management reports shared between the AQI and participating practices. In the long run,
however, it is likely that NACOR will become the definitive reference for outcome data about our profession.

Future Initiatives of the AQI

The primary mission of AQI will remain expansion of NACOR. This will occur through ongoing recruitment of
new practices and increasing the quantity and depth of data collected from current participants. As technology
advances, the NACOR model of continual passive collection of existing clinical data will become progressively
more powerful. The AQI works with more than two dozen information technology vendors to develop reporting
bridges between their software and NACOR. Many anesthesia billing systems and AIMS already include standard
AQI reporting routines. The ongoing dialog between vendors and anesthesia practices will lead to gradual and
incremental standardization of anesthesia outcomes, data formats, and reports; the AQI is perfectly positioned to

331
Page 7
facilitate this discussion, and the AQI website has already become an important resource for software developers
and hospital quality managers.

AQI will encourage increased understanding of patient outcomes beyond the usual horizon of PACU discharge. The
adequacy of pain management and the incidence of nausea following discharge after ambulatory surgery are
important to patients, and will be of increasing interest to external regulators. Thirty-day post-procedure mortality is
a standard in many other specialties, and the increasing scientific interest in longer-term outcomes such as cognitive
function or cancer recurrence will drive a demand for this kind of data. At present there are no software systems in
place that can track these outcomes, but the AQI is committed to their development. Alternatively, the AQI will
work collaboratively with other registries such as NSQIP (the National Surgical Quality Improvement Program) to
combine our wealth of process information with their long-term patient outcomes.

The Anesthesia Incident Reporting System

A nationwide benchmarking registry such as NACOR is the ultimate example of top-down quality management, but
there is value in bottom-up reporting as well. Discussion of interesting cases is the cornerstone of the morbidity
and mortality conference, and remains a powerful educational tool. This explains AQIs creation of the Anesthesia
Incident Reporting System (AIRS). The object is to collect unusual cases and events directly from the point of care.
The mechanism is a simple online form that can be submitted confidentially from any internet-capable computer.
Submission to AIRS is protected from legal discovery by AQIs status as a Patient Safety Organization, and all
reports are stored in a de-identified format. Case submissions are periodically reviewed by a committee of experts.
Cases with unique teaching potential are fictionalized and presented monthly in the ASA NEWSLETTER. All cases
are periodically analyzed for common features, and aggregated to identify trends in patient safety. AIRS currently
includes sub-modules for reporting postoperative respiratory depression, incidents related to drug shortages, and
pediatric incidents. More modules are under development. AIRS can be accessed at: https://www.aqiairs.org.

In the first full year of operation, AIRS has collected hundreds of incidents from practitioners across the United
States and Canada. Reported events have ranged from cardiac arrest due to air embolus in ERCP to minor case
disruptions caused by the lack of needed equipment. Published case studies from AIRS have covered topics
including anaphylaxis, medication errors, the hazards of neuro-monitoring, and bullying behavior in the operating
room. Recurring themes such as the potential for electronic record-keeping to disrupt patient care are aggregated
and shared with vendors and other organizations to seek common solutions. Specialty-specific problems like
medication shortages inspire custom-built report forms in AIRS that enable AQI to collect structured data focused
on those events; these reports can be turned into useful fodder for advocacy at the state and federal level.

Summary

The AQI is an important resource for anesthesiologists and their practices. Data from AQI helps shape ASA
committee work, educational products and advocacy efforts. The goal of NACOR and AIRS is nothing less than a
complete picture of anesthesia practice in the United States, empowering anesthesiology as the leader in patient
safety. More information on the AQI, including educational material on quality management and anesthesia
information technology, can be found on its website at www.aqihq.org.

331
Page 8
References

1. Rovenstine EA. A method of combining anesthetic and surgical records for statistical purposes, Part IV,
Chapter 3 in Baehne GW (ed) Practical applications of the punched card method in colleges and universities.
New York: Columbia University Press, 1935, pps 301-8.

2. Beecher HK, Todd DP. A study of the deaths associated with anesthesia and surgery: based on a study of 599,
548 anesthesias in ten institutions 1948-1952, inclusive. Ann Surg. 1954;140:2-35.

3. Kohn LT, Corrigan JM, Donaldson MS (eds). To Err is Human: Building a Safer Health System. Washington:
National Academies Press, 1999.

4. Dutton RP. Pro: The AQI model for data collection. ASA Newsletter, May, 2010.

5. Dutton RP, Dukatz A. Quality improvement using automated data sources: the anesthesia quality institute.
Anesthesiol Clin. 2011 29(3):439-54.

6. Glance LG, Neuman M, Martinez EA, Pauker KY, Dutton RP. Performance Measurement at a "Tipping Point"
Anesth Analg. 2011; 112; 958-966.

7. The Anesthesia Quality Institute. Anesthesia in the US 2012, available online from
https://ecommerce.asahq.org/p-556-anesthesia-in-the-united-states-2012.aspx?

Disclosure

335
Page 1
Occupational Health for Anesthetic Practice
Jonathan D. Katz, M.D. New Haven, Connecticut
INTRODUCTION
Employment as a health care provider can be hazardous to ones health. The health care industry ranks among the
highest workplaces in the frequency of occupational injuries and illnesses sustained by their workers. Endemic
hazards in the high intensity environment of the operating room potentially expose anesthesia personnel to a number
of occupational illnesses or injuries, such as accidents, fires, or explosions. Specific workplace hazards include
exposure to waste anesthetic gases, ionizing radiation, and to a wide array of infectious agents. Additionally,
anesthesia personnel are susceptible to emotional and psychological disorders such as burnout and substance abuse
engendered at least in part by the high stress inherent in their work. Many of these concerns are especially
challenging to the aging anesthesiologist.
In the following discussion we will consider the etiologies of many of these illnesses and practical means of
avoidance and treatment. We will also discuss the growing awareness of the importance of preventative strategies
that encourage wellness among our colleagues.
PHYSICAL HAZARD
Accidents: Accidents are the most common source of injury to anesthesia personnel in the operating room.
However, these injuries are rarely reported and much of the information on accidents comes from anecdotes or
incident reports.
Needle stick injury is the most frequent accident suffered by anesthesiologists. The majority of needle stick injuries
occur during use, but many occur during recapping and disposal after use. Needle stick injuries are potentially lethal
and completely preventable.
Ionizing Radiation: A growing concern within modern operating suites is exposure of personnel to radiation as a
result of the increasing number and complexity of procedures requiring x-ray imaging.
The biologic consequences of radiation vary depending on age, gender, and specific organ site of exposure. The
deterministic effects of radiation result in cell death and organ injury and are cumulative in a dose related fashion.
Common examples of deterministic injuries include skin damage, infertility, and certain types of cataracts.
Stochastic effects of radiation are those that result in DNA damage and the development of cancer. There is a long
latency period between exposure and the clinical presentation of an induced neoplasm and no known threshold
below which the risk of developing these consequences completely disappears.
The Occupational and Safety Heath Administration (OSHA) has set an annual limit for workers who are exposed to
ionizing radiation of 5 Rems and a life time limit of (N-18) x 5 Rems (where N is the age in years). Early studies
found the exposure to radiation among anesthesia personnel to be safely below these limits. However, more recent
studies, conducted subsequent to the increased utilization of ionizing radiation in operating rooms, cardiac
catheterization labs and interventional radiology suites, have revealed a trend towards increased exposure among
anesthesia personnel. In one study, the mean radiation exposure for members of a department of anesthesiology
doubled (to almost 500 mRem on an annualized basis) in the six months after a new electrophysiology service was
introduced. (1) A similar study reported a significant level of exposure to anesthesiologists during endoscopic
retrograde cholangiopancreatography (ERCP) and cardiac catheterization. (2) In both of these studies, exposure
remained well below the annual limit of 5 Rem. However, it must be appreciated that many of the diseases
associated with radiation exposure exhibit a direct dose response relationshipmaking as low as reasonably
practical (ALARP) the safest practice.
Preventative strategies for anesthesiologists to limit their radiation exposure include decreasing the exposure time,
distancing oneself from the source of the radiation, and using maximal shielding from both primary and scattered
sources of radiation.

335
Page 2
A second form of radiation with potential health consequences comes in the form of chronic exposure to low-
frequency electromagnetic fields such as those emitted by MRI equipment. (3) It is often necessary for the
anesthesia care provider to remain in close proximity to the patient, and thus the magnet during MRI studies. Data
are not yet available to determine the safety of long-term exposure to high-intensity magnetic fields. Therefore, until
such time that safety thresholds have been determined for this type of exposure, anesthesiologists should obey the
general admonition regarding all radiation exposure-as low as reasonably practical.
Noise: Noise levels in a modern operating room frequently exceed established limits for safe noise exposure and
pose a potential health hazard. OSHA has determined that the maximum level for safe noise exposure is 90 dB for 8
hours. Each increase in noise of 5 dB halves the permissible exposure time. Ventilators, suction equipment, music,
and conversation commonly produce background noise in operating rooms to a level of 75 to 90 dB. Sporadic
noises caused by dropped equipment, surgical saws and drills, and alarms can elevate these noise levels to greater
than 100 dB with peak levels in excess of 120 dB. These are the noise levels produced by a busy freeway or a rock
and roll band.
Excessive levels of noise can diminish an anesthesiologists mental efficiency, short-term memory, and ability to
multitask. Noise also interferes with the ability to hear crucial verbal communications and equipment alarms. There
are also health ramifications of long-term exposure to excessive noise. Chronic exposure has been associated with
elevated levels of endogenous catecholamines and heightened levels of stress, increased irritability, and elevated
blood pressure.
Ultimately, exposure to excessive noise levels will result in hearing loss. Although no direct connection has been
established with noise levels in operating rooms, it is interesting to note that more than 50% of anesthesiologists
have a substantial hearing deficit and 7% have deficits that potentially interfere with their ability to hear operating
room alarms. (4)
The role of one form of background noise, music, remains controversial. Self-selected background music can
contribute to reducing autonomic responses and improving performance of selected technical functions among
operating room personnel. These beneficial effects are lost when a third party chooses the music. A recent report
points out the detrimental effect of music on the ability to communicate vital information in the task dense
environment of an operating room. (5) The selection of music, and the volume at which it is played, should be by
mutual agreement of all parties present in the operating room.
Infectious Agents: The risk to anesthesia personnel of acquiring infections in their workplace continues to increase
due to the growing number of antimicrobial resistant bacteria, and the frequent necessity of surgery among immune-
compromised patients who might serve as vectors for resistant and opportunistic organisms. Additionally, diseases
that were once thought to be noninfectious are now understood to be long-term consequences of infection, making
occupational health precautions even more important. Examples are; peptic ulcer disease (Heliobacter pylori),
invasive cervical cancer (human papillomavirus), Kaposis sarcoma (human herpesvirus type 8) and certain
lymphomas (Epstein-Barr virus).
Immunity against some viral pathogens, such as hepatitis B (HBV), can be obtained through vaccination.

Although
vaccines do not yet exist for other common blood-borne viruses, such as hepatitis C (HCV) and human
immunodeficiency virus (HIV), the risk of transmission can be minimized by rigorously applying Standard
Precautions as detailed by the Centers for Disease Control and Prevention (CDC). These precautions include the
appropriate use of hand washing, personal protective equipment (PPE), and respiratory hygiene/cough etiquette. The
selection of specific PPE can be as basic as wearing gloves for some patient contacts, or as complicated as
employing advanced personal protection gear, such as gown, mask, and face shield or respirator for many invasive
procedures.
In addition to CDC guidelines, standards have been developed by OSHA designed to help protect employees from
occupational exposure to blood-borne pathogens. Among other requirements, these standards require that an
employer encourage strategies to reduce blood exposures, furnish appropriate PPE, and provide an annual
educational program focused upon employees risk of blood-borne infection. In addition, the institutions employee
health service is required to maintain protocols for workers exposed to contagious diseases such as Tuberculosis,
HIV or hepatitis.
Case reports of occupationally acquired infection have appeared for virtually every communicable disease.
Pathogens of special concern for anesthesiologists include: influenza types A B and C, human respiratory syncytial
virus, SARS-associated coronavirus, norovirus, c. difficile , herpes simplex viruses, Epstein-Barr virus , rubella,
rubeola, hepatitis virus A B and C, human immunodeficiency virus, methicillin resistant staphylococcus aureus, and
tuberculosis.
In the event of exposure to a pathogenic microorganism, the incident should immediately be reported to the
employee health service. Post- exposure treatment is optimally initiated within 2 to 4 hours of the exposure.

335
Page 3
Detailed recommendations for post- exposure prophylaxis to many potential pathogens can be obtained at the CDC
website.
Waste Anesthetic Gases: Potential health hazards from waste anesthetic gases have been a concern since the
introduction of inhalation anesthetics into clinical practice. Extensive investigation has failed to identify any link
between the low level of exposure to trace gases that anesthesiologists receive in a modern, scavenged operating
room and adverse health effects. (6) The importance of effective scavenging of waste gases is demonstrated by
reports of reduced fertility and elevated spontaneous abortion among female dental assistants and veterinarians
working in unscavenged operating rooms. (7)
Work Hours, Night Call, and Fatigue: Inadequate sleep resulting from any number of factors, including
obstructive sleep apnea or disruptive work schedules, can contribute to illness and have deleterious effects upon
work practices. Workers who are sleep deprived suffer a decrement in performance and are at greater risk of
committing workplace errors and to suffer work related injuries. The impairments associated with sleep deprivation
bear a striking similarity to that seen with alcohol intoxication.
The contribution of sleep loss and fatigue to accidents has been documented in many well-publicized industrial
catastrophes, including those that occurred at Chernobyl, Three Mile Island, Exxon-Valdez, and the Challenger
space shuttle disaster.
A number of reports have identified sleep deprivation as a causative factor in errors occurring in the health care
industry. Friedman and colleagues reported that interns made almost twice as many errors reading
electrocardiograms after an extended work shift than after a night of sleep. (8) In a study among emergency room
physicians, intubation skills were reduced among those working night shifts when compared with others working
days. (9) Physicians in both groups were more likely to commit errors during a simulated triage test towards the end
of their work shifts. And in a study that examined the management of medical admissions provided by interns,
35.9% more medical errors were committed while working 24 plus hour work shifts than while working a schedule
that eliminated extended shifts and reduced the number of hours worked per week. (10)
Sleep deprivation can adversely impact an anesthesiologists ability to conduct a safe anesthetic. Changes include;
impairment of mood, alertness, short term memory and cognition, prolonged reaction time, compromised clinical
decision making, and reduced attention, vigilance and performance.
The precise role of sleep deprivation specifically on clinical outcomes remains unclear. While some studies have
demonstrated a detrimental effect on patient outcomes, others have shown no evidence of suboptimal clinical
management or poor outcomes from sleep deprived clinicians.
Practicing anesthesiologists continue to work long hours. An unintended consequence of the restrictions on trainees
duty hours has been a shift of work from residents to faculty. Attending anesthesiologists and nurse anesthetists still
commonly work 10- to 12-hour workdays and 24 hour on-call shifts. Gravenstein et al reported that the average
anesthesiologists work week was 56 hours and that 74% of the respondents had worked without a break for longer
periods than they personally thought was safe. (11)
Medicine remains significantly behind other industries in regulating work hours.

The Accreditation Council for
Graduate Medical Education (ACGME) established the first set of standards to limit resident duty hours in 2000,
which were revised in 2011. However, these restrictions on duty hours apply only to trainees and work hours in
medical practice remain largely unregulated.
Impairment and Disability: Impairment and disability can result from physical, mental, emotional, sensory or
developmental etiologies. The onset can be sudden, as occurs with injury or acute illness, or more gradual, as is the
case with many chronic diseases. Many cases of physician impairment are the result of substance abuse.
Unwillingness or inability to keep up with current literature and techniques can also be considered a form of
impairment.
Depression is often the presenting finding among impaired physicians. Unfortunately, many of the personality traits
that serve as risk factors for depression are the same as those found in many successful physicians, such as self-
sacrifice, achievement orientation, and intellectualization of emotions. Observations of alcoholic physicians offer
examples of the potential association between excessive achievement orientation and emotional disturbance.
Several studies have reported that frequently students who have identified themselves as alcohol abusers are among
those with higher grades and scores on standardized examinations such as the National Board Examinations.
It can be very challenging to appropriately respond to all of the problems created by an impaired or unsafe
colleague. Management protocols for dealing with the impaired physician are covered in a series of articles by
Canavan. (12)

335
Page 4
EMOTIONAL HAZARDS
Stress: Mild, brief, and controllable episodes of occupational stress are unavoidable and can serve as an impetus to
personal achievement. On the other hand, extreme degrees of chronic stress are harmful and can contribute to a wide
range of mental and physical illnesses. Stress-related outcomes in the workplace include industrial accidents,
absenteeism, decreased productivity and increased disability.
The work environment of an anesthesiologist contains many of the features of a classically defined stressful
workplace. The background of chronic, low-level stress is frequently punctuated by intermittent episodes of extreme
stress. Many of the clinical demands are externally paced and unpredictable in timing or urgency. Habituation to the
ever changing demands is difficult. Finally, failure to meet the demands imposed by the workplace can result in
serious consequences.
Certain specific stressors are commonly reported by anesthesiologists. These include the unpredictability of the
work, the need for sustained vigilance during long intervals, production pressure, fear of litigation, difficult
interpersonal relations, and economic uncertainties.
To many who work in the operating room, interpersonal relationships and conflict are the greatest source of
workplace stress. Conflict can easily occur where overlapping areas of professional responsibility exist, as routinely
occurs in the operating room, where surgeon and anesthesiologist simultaneously share patient responsibility. Recent
work has focused upon applying the principles of Crisis Resource Management, first developed in the aerospace
industry, to improve communication and team work in the operating room. (13)
Catastrophic intraoperative incidents, bad patient outcomes and the accompanying threat of litigation are frequent
sources of stress to anesthesiologists. Many anesthesiologists experience long lasting emotional disturbances after
being involved in a catastrophic incident in the operating room. In a recent survey, 84% of anesthesiologists
admitted to being involved in a serious or fatal incident and greater than 70% reported that they experience lingering
guilt, anxiety or a sense of personal responsibility for the patient's injury or death. (14) Few departments offer
formal debriefing programs or counseling services to provide support in the event of a catastrophic outcome.
Burnout: Burnout is characterized by physical and emotional exhaustion, poor judgment, cynicism, guilt, feelings
of ineffectiveness, and a sense of depersonalization. Unfortunately, many of the attributes desired in health care
providers, such as idealism, perfectionism, and a heightened sense of responsibility, can also make these individuals
more vulnerable to feelings of inadequacy if their high standards are unmet.
Physicians suffering from burnout are prone to medical errors and malpractice lawsuits. Burnout has also been
shown to contribute to various illnesses, including cardiovascular disease and substance abuse.
Significant degrees of burnout have been identified among anesthesiologists. Greater than 50% of American
academic chairs meet the criteria for high or moderate degrees of burnout. (15)
Commonly cited causes of burnout among anesthesiologists are production pressure, excessive regulation, long
hours of work, lack of control of ones schedule, decreasing reimbursement, a rapidly expanding base of medical
knowledge and difficulty balancing personal and professional lives.
Substance abuse: Substance abuse occurs when an individual repeatedly abuses a drug despite significant adverse
consequences, such as the need for larger amounts of the substance, unsuccessful attempts to control its use, the
necessity of spending greater amounts of time seeking the substance, and symptoms of withdrawal.
The prevalence of alcoholism and substance abuse is approximately equal for physicians and the general population.
However, physicians are less likely to abuse tobacco or illicit drugs and more likely to self-medicate with
prescription drugs. A growing number of medical centers require drug screening as a pre-condition to employment
or procurement of hospital privileges.
Several studies have reported a disproportionately high prevalence of substance abuse among anesthesiologists as
compared to other physicians. Additionally, these reports demonstrate that anesthesiologists are more likely to
become addicted to potent intravenous drugs such as opioids or propofol that are potentially lethal. As a result, many
authorities now consider substance abuse to be the number one occupational hazard of anesthesiology.
One particularly troubling aspect of this problem is the persistently high incidence of substance abuse among
anesthesiology residents. In one of the most frequently cited studies, anesthesiology residents constituted 33.7% of
the resident population of the treatment group in the Medical Association of Georgia Disabled Doctors Program,
despite representing only 4.6% of the overall resident population. (16) The incidence of controlled substance abuse
within anesthesiology training programs continues to run close to 2% despite increased emphasis on substance abuse
educational programs and more stringent accounting of controlled substances.(17)
Addiction is a chronic progressive disease that, if untreated, is frequently fatal. Alexander et al calculated a relative
risk of 2.79 for drug related deaths among anesthesiologists compared to a matched cohort of internists.(18) Re-
entry into clinical practice after rehabilitation is a particularly vulnerable period, with an alarmingly high relapse and
death rate reported among clinicians re- entering practice after treatment for chemical dependency.

335
Page 5
There is an ongoing debate about the ultimate career path of the anesthesiologist in recovery. Reports have ranged
from very pessimistic to more optimistic regarding the ability of recovering anesthesiologists to successfully return
to practice. The most recent report found that 76% of anesthesiologists who had successfully completed
rehabilitation in a state run physician health program remained in practice at 5 year follow up.(19) There was no
difference between anesthesiologists and non- anesthesiologists with regard to rates of relapse, mortality or
disciplinary action. Guidelines from physician treatment centers may be helpful to assist in the difficult decisions
surrounding re-entry.

THE AGING ANESTHESIOLIOGIST
Important physiologic changes can impact an older anesthesiologists ability to administer a safe anesthetic.
Commonly observed physiological changes include impairments in hearing, vision, short term memory, and
problem-solving abilities. Intellectual quickness, learning, and reaction time all slow. These changes have the
potential to limit the older anesthesiologists ability to rapidly process information, assimilate and apply new
knowledge, make complex decisions and initiate a proper response.
Age related changes in the cardiovascular and musculoskeletal systems can make it more difficult for older
anesthesiologists to sustain the long, demanding work shifts common in anesthetic practice. Older individuals are
particularly sensitive to disturbances of the sleepwake cycle and are less well suited to night time work. Night call
has been identified as the most stressful aspect of practice and most frequently cited impetus toward retirement
among older anesthesiologists. (20)
On the other hand, normal aging also imparts advantages, such as wisdom, judgment, and the experience acquired
by a lifelong practice of the specialty. There is a strong positive correlation between experience and performance of
many tasks required for administration of a safe anesthetic.
Anesthesiology is often regarded as a young persons profession. Anesthesiologists tend to retire at a younger age
than many other physicians. The decision to retire from anesthesiology is frequently precipitated by concerns about
deteriorating clinical skills and the growing burdens of night call.

MORTALITY AMONG ANESTHESIOLOGISTS
A number of studies have examined mortality among anesthesiologists and arrived at different conclusions
regarding the average life expectancy. The most recent study found that the average age at death among
anesthesiologists was 78 years, the same as the national average for all Americans. (21)
Inconsistent findings have also been reported about the most common causes of death among anesthesiologists.
Earlier work found an increased incidence of certain types of cancer. More recent reports have failed to find any
increase in cancer risk but a consistent finding of increased numbers of drug related deaths and suicide.

Malpractice law suits and substance abuse are two precursor events that have a strong association with suicide
among anesthesiologists. One study reported that 4 of 185 anesthesiologists being sued for medical malpractice
attempted or committed suicide. (22) And in Alexanders study, drug abuse was the most frequent method of
suicide among anesthesiologists. (18)

WELLNESS
It is estimated that half of the mortality in the US is premature. Many of these lives could have been preserved with
the modification of just 10 behaviors - tobacco use, dietary pattern, physical activity level, alcohol consumption,
exposure to microbial agents, exposure to toxic agents, use of firearms, sexual behavior, motor vehicle crashes, and
illicit use of drugs.
One of the greater challenges for busy anesthesiologists is to balance the demands and stress of practice with the
time necessary for wellness maintenance. A recent article describes the value of a proactive wellbeing program
towards decreasing stresses and improving coping in a group of anesthesia residents. (23)
The importance of wellness has also been recognized by the ASA . The ethical guidelines of the ASA state that
anesthesiologists are obliged to maintain their physical and mental health and special sensory capabilities. With
this in mind, the ASA has developed a Health and Wellness in Action initiative whose primary mission is to
promote the health and welfare of ASA members.

335
Page 6
BIBLIOGRAPHY
1) Katz JD: Radiation exposure to anesthesia personnel: the impact of an electrophysiology laboratory. Anesth
Analg 2005; 101: 1725-6
2) Ismail S, et al.:Radiation exposure to anaesthetists during interventional radiology. Anaesthesia 2010; 65:
54-60
3) Roh JH,et. al: Intensity of extremely low-frequency electromagnetic fields produced in operating rooms
during surgery at the standing position of anesthesiologists. Anesthesiology 2009; 111:2758
4) Wallace MS, et al: Hearing acuity of anesthesiologists and alarm detection. Anesthesiology 1994; 81: 13-
28
5) Way, TJ, et al: Effect of Noise on Auditory Processing in the Operating Room. J Am Coll Surg
2013;216:933- 8
6) McGregor DG: Occupational exposure to trace concentrations of waste anesthetic gases. Mayo Clin Proc
2000; 75: 273-7
7) Shirangi A, et al: Associations of Unscavenged Anesthetic Gases and Long Working Hours With Preterm
Delivery in Female Veterinarians. Obstet Gynecol 2009;113:100817
8) Friedman RC, et al: The intern and sleep loss. N Engl J Med 1971; 285: 201- 203
9) Smith-Coggins R,et al: Relationship of day versus night sleep to physician performance and mood. Ann
Emerg Med 1994; 24: 928-34
10) Landrigan CP, et al: Effect of reducing interns' work hours on serious medical errors in intensive care units.
N Engl J Med 2004; 351: 1838-48
11) Gravenstein JS, et al: Work and rest cycles in anesthesia practice. Anesthesiology 1990; 72: 737- 742
12) Canavan DI, Baxter LE, Sr.: The twentieth anniversary of the Physicians' Health Program of the Medical
Society of New Jersey. N J Med 2003; 100: 27-9
13) Gaba DM: Crisis resource management and teamwork training in anaesthesia. Br J Anaesth 2010; 105: 3-6
14) Gazoni FM, et al: The impact of perioperative catastrophes on anesthesiologists: results of a national
survey. Anesth Analg 2012; 114: 596-603
15) De Oliveira GS,et al: High incidence of burnout in academic chairpersons of anesthesiology: should we be
taking better care of our leaders? Anesthesiology 2011; 114: 181-93
16) Talbott GD, et al: The Medical Association of Georgia's Impaired Physicians Program. Review of the first
1000 physicians: analysis of specialty. JAMA 1987; 257: 2927-30
17) Collins GB, et al: Chemical dependency treatment outcomes of residents in anesthesiology: results of a
survey. Anesth Analg 2005; 101: 1457-62
18) Alexander BH: Cause-specific mortality risks of anesthesiologists. Anesthesiology 2000; 93: 922-30
19) Skipper GE, et al: Anesthesiologists with substance use disorders: a 5-year outcome study from 16 state
physician health programs. Anesth Analg 2009; 109: 891-6
20) Orkin FK, et al: United States Anesthesiologists over 50. Retirement Decision Making and Workforce
Implications. Anesthesiology 2012; 117:95363
21) Katz JD, Slade MD: Anesthesiologists are living longer: mortality experience 1992 to 2001. Journ Clin
Anesth 2006; 18 (6): 405- 408
22) Birmingham PK, Ward RJ: A high-risk suicide group: the anesthesiologist involved in litigation. Am J
Psychiatry 1985; 142: 1225-6
23) Saadat H, et al: Wellness program for anesthesiology residents: a randomized, controlled trial. Acta
Anaesthesiol Scand 2012; 56(9):1130-8

Disclosure

403
Page 1
How to Avoid Recruiting the Problem Employee (and What to Do Once You Have One)
Catherine M. Kuhn, M.D.
Durham, North Carolina
Introduction and Pre-Recruitment Considerations
The goal for any anesthesiology practice, academic or private, should be to add partners and employees who
improve the function and value of the group. Hiring an underperforming employee immediately decreases the
productivity of the organization. Managers quickly realize that they spend most of their time dealing with their
underperforming employees, at a cost to their groups. The best employees require relatively little effort from
managers once established in the group. This seems obvious--how is it, then, that nearly every organization at some
point fails to hire the best person for its needs?
All physicians are products of standardized education processes, with rigid timelines and criteria for application for
training positions. Residency and fellowship programs across the country spend enormous amounts of time and
money trying to recruit the best students into their training programs, and have the advantage of standardized, online
applications, defined recruitment cycles and primary source verification through the Electronic Residency
Application System (ERAS) and the National Resident Matching Program (NRMP). Every academic
anesthesiology department has infrastructure and resources dedicated to the process of recruiting trainees into their
programs. Despite this, not all medical students succeed in their training programs, and both trainees and their
programs are often surprised that the outcome was not predicted during the recruitment process. The application
and interview process as it exists for undergraduate and graduate medical education is imperfect. (1,2)
Is there any evidence that recruitment for the next level of employment, i.e., anesthesiology faculty appointments or
positions in a private practice, offers better success? There is no standardized process for that recruitment and even
state licensure and hospital accreditation practices vary considerably. Adding to the problem, people looking for
faculty or attending jobs are often hopeful to find a stable position for the long term, with compelling reasons to do
so. The stakes are much higher for a successful job search, and for the employer, the stakes are equally high.
Despite this, departments vary tremendously in the resources allocated to the recruitment and retention of physicians
and other employees.
Organizational Self-Assessment
Before considering the quality or suitability of candidates for a practice, it is important to take some time to define
what success means for a particular group. What are the essential characteristics all employees require to uphold
the core values of the practice? What character traits and behaviors are essential? A clear definition of the purpose
for hiring new employees should be articulated. Are there particular clinical needs? Does the group need
subspecialty expertise or generalists? Is the group engaged in new business practices that require partners with
management experience? Does the group employ an anesthesia care team model or provide solo anesthesia care? Is
there a preference for hiring into a partnership track or an employee track? For academic groups, is there a specific
research or educational requirement that needs to be met? These considerations may help refine the criteria used
during the recruitment process. The recruitment process should be developed to optimize the likelihood of hiring
the type of physician who will most likely advance the goals of the group. Finding candidates whose career goals
are aligned with those of the group minimizes the likelihood of disappointment for either party. Similarly, the
available resources of the group should be considered when considering a successful hire. For example, a group that
has limited pediatric case volume may not be able to accommodate the desires of a newly-minted graduate of a
pediatric fellowship who wants to practice as much pediatric anesthesia as possible, while still allowing
opportunities for other group members to maintain their pediatric anesthesia skills.

403
Page 2
Another useful exercise is to review the history of the hires in the group, and consider the attributes of the most
successful, as well as those who struggled. Although every individual is different, there may be some hints about
the type of physician who thrives in the environment of the group, and targeting candidates with those skills might
be productive.

It is important to predict the short- and long-term needs of a group when making hiring decisions. Some candidates
may be unable to commit to an indefinite term of employment due to spousal careers or other considerations. It is
important to consider the structure that will work best for a particular group, so that honest discussions are held
during the interviews. If hiring this person meets an important practice goal, how will the group manage after the
short-term hire leaves the group? Can the recruit enhance the practice quickly and train a replacement? Conversely,
filling a position with a less desirable candidate simply to accommodate burdensome short-term clinical needs
deprives the group of the possibility of hiring a more attractive candidate for the long term, so decisions about hiring
must balance the current demands on the group with its future desires for growth and accomplishment.

Application Materials

An application can provide useful information about candidates and if reviewed carefully, can be used by employers
to identify potential problems. Many employers discover too late, after being faced with a problem employee that
there were predictors of problems in the application materials and application process.

Cover letters: Although viewed as a less important part of the application, review of the cover letter can glean some
information about the candidates previous experience and plans for the future. This can provide pre-interview
insight into the alignment of the applicants interests with opportunities available within the enterprise. Measures of
creativity and the candidates ability to communicate in writing are also addressed. The care with which a candidate
puts together his or her application and documentation (e.g., spelling, typographical errors) may be relevant for a
detail-oriented specialty such as anesthesiology. Promptness of responses and interaction with department staff
prior to interviews are also worthy of attention.

Letters of Recommendation: Many letters of recommendation are unhelpful in providing meaningful information
about a candidates performance. Particularly with difficult employees, former employers may be hesitant to
commit negative information in writing. Instead, a bland report of facts about employment dates and other similar
demographic information is provided. There are, however some important considerations about letters of
recommendation. The names of the letter writers should be correlated against the list of referees the candidate
provided. Discrepancies should be explained; was the candidate shopping for the best letter possible? Letters
from family members, friends or former students are less objective and valid. Were the letters provided by the
candidate, or were they mailed directly from the source? Do the letters address cognitive, technical and
interpersonal attributes or one area exclusively? In reviewing letters, what isnt said is at times more important than
what is said (3). Any letter that seems cautionary or incomplete should be followed up with a phone call to the
referee. Indeed, prior to offering a position to a candidate, it is advisable to contact all letter writers, to validate their
information and provide an opportunity for the letter writer to add additional useful information which might not
have been included in the letter. Every recommendation letter can be turned into a reference check. One important
question to ask is whether the candidate is eligible to be rehired by the group (4).

Standardized Test Scores: (United States Medical Licensing Examination (USMLE), Comprehensive Osteopathic
Medical Licensing Examination (COMLEX), Intraining Examinations). After successful completion of American
residency training, it is likely that applicants have passed all steps of the USMLE or COMLEX, as this is a
requirement for entrance into the American Board of Anesthesiologys examination system. All states require
passage of Steps 1, 2 and 3 of the USMLE for licensure. A candidate who is not a part of the American board
examination process may have comparable examination scores from another country. Although a group may rely on
the fact that a physician has completed his or her residency program successfully, and therefore may discount
examination scores, the examination history and scores may provide useful information, particularly if the candidate
is newly graduated from a training program and is not yet board certified (5). It is assumed that achieving diplomate
status with the American Board of Anesthesiology is a desired goal for all members of a practice, especially as
licensure and credentialing requirements have become stricter. Of note, the American Board of Anesthesiology
currently limits the use of the term board eligible to candidates who are active in the examination process, whereas
in the past anyone who completed a residency program could identify themselves as board-eligible. Board

403
Page 3
eligibility implies that the candidate has unrestricted medical licensure and has met other important qualifying
characteristics.

Employment History: When reviewing applications, particular attention should be paid to information about gaps in
training, gaps in employment and negative administrative action. A single gap may be easily explained, but a
pattern of frequent job changes and numerous gaps in employment should generate concern. A candidate with
medical licenses in many more states than s/he has practiced in may have had issues with licensure, and this should
be pursued and explained.

It is also important to consider the trajectory of the applicants career thus far. Simply stated, trajectory refers to the
rate and progress of accomplishment in a career. Is the candidate on a pathway that shows growth and
improvement, stasis, or backsliding? Is s/he considering your practice because of new opportunities or because of
problems with the former group? What unmet needs could be achieved in your group?

Honorary society selection: It is generally believed that Alpha Omega Alpha (AOA) selection is indicative of higher
achievement in medical school. Although it would seem that AOA selection should predict future success in
residency and beyond, this has not been a universal finding in all specialties. This may relate to the criteria used to
determine AOA eligibility, which at times are largely focused on cognitive accomplishments (6, 7, and 8).
Recently, many schools have formed chapters of the Gold Humanism Honor Society (GHHS) (9). Students are
selected by their peers and faculty for membership based on humanistic traits such as altruism, professionalism, and
interpersonal skills. The intent of the Arnold P. Gold Foundation in establishing these societies is to honor and
celebrate the non-cognitive aspects of medical practice. Whether selection to GHHS will predict success in
residency training, much less eventual practice remains to be seen. The importance of selection to honorary medical
societies generally indicates that the candidate was a high achiever in medical school or residency, but may not
predict success as a faculty member or member of an anesthesiology practice. Again, careful consideration of the
core values of the practice and focus on the likelihood that the candidate possesses these values is most critical in
making good hiring decisions.

The Interview

As illustrated above, traditional residency application materials are not sufficient to use as the sole source of
information about candidates for residency programs (7, 8). A number of studies have suggested that the residency
interview is a more effective mechanism for discovering candidates who are best suited for training in a specialty
(10, 11). It could be extrapolated that the same consideration would be important for permanent employment
decisions. The interview process is time-consuming and expensive for both candidates and groups. At its worst, an
interview is reduced to an opportunity for candidates to meet prospective colleagues, as well as to see their work
environment. At its best, the interview experience can be structured in a way to provide both candidates and the
group with more useful information about the job and mutual suitability. Is there a way to use the interview and
related activities more productively?

Most interviews include a combination of opportunities for potential recruits to meet physicians in the group, to tour
the facilities where they would work, and to learn incremental information about the clinical practice, finances,
business arrangements and potential salaries enjoyed by group members. Often social activities such as dinners
with business partners and spouses are arranged as well. Structured, formal interviews have been shown in other
settings to be useful in distinguishing the attributes of candidates (11). However, they are rarely used for medical
job interviews. In most settings, interviews are either semi-structured, or unstructured, and the combined
information gathered by the interviewers is often incomplete, or duplicative. Many inexperienced interviewers
spend time educating the candidate about the practice, rather than asking questions. In general, an interviewer
should aim to spend 80% of the time listening, and 20% talking. Rather than accepting broad statements, follow-up
questions should be asked to validate the assertions the candidate makes. (12)

However, the practical reality is that most employers use, and will continue to use, semi-structured interviews.
Semi-structured interviews can be more reliable if attention is paid to the way they are conducted. Consideration
should be given to including non-departmental members in the interview process at some point, to emphasize that
team work and relationships are important. It is ideal if some subset of the organization interviews most if not all of
the candidates being considered for a position. This gives the group a better sense of the range of the applicants and

403
Page 4
will lead to more careful discrimination of who might be the best candidate (4). Second, asking each interviewer to
use consistent questions for each applicant will also provide some additional perspective for comparison. This can
be facilitated by drafting some sample topics for each interviewer to cover, and will potentially reduce redundancy
in the questions for the candidate. Lastly, in business and other industries, the use of behavior-based, or Behavior-
Descriptive Interviewing (BDI) has been shown to improve the selection process (11, 12, and 13, 14). The premise
of BDI is that past behavior is the best predictor of future behavior. Traditional BDI questions include a main
question, followed by probing questions to elaborate upon the described behavior and help gather more information
about non-cognitive competencies. A grading scale can be applied to the answers received. Conducting an entire
interview with behavior-based questions may be laborious, and would require a large investment in training the
interviewers. However, utilizing one or two behavior based questions, even without a formal grading scale, if
applied consistently to all candidates, can be quite illustrative. Some typical questions used by the author for
residency applications, and the attribute of interest are listed below:

Give me an example of a time when you went above and beyond expectations to help a friend. (altruism)
Tell me about a situation where you disagreed with the suggestion of your supervising resident. (conflict
resolution)
Tell me about the hardest thing youve ever accomplished (work ethic)
Give me an example of a time when you exceeded your own expectations (ambition)

These questions can easily be modified to reflect important elements of success within an academic department or
private practice, for example:

Give me an example of your most frustrating day at work. (adaptability)
Tell me about a time when you and your surgical colleague really disagreed over a patients management.
(conflict resolution)
How would you handle a colleague who makes inappropriate comments to the nursing staff?
(professionalism)

As one gains experience using these questions, differences in candidates become apparent. Additionally, candidates
do not typically expect these questions, and are less likely to have a prepared answer ready. This allows some
opportunity to see how well a candidate thinks on his or her feet, and is a better test of communication than the
standard questions about why a candidate is interested in your practice, their strengths and weaknesses, etc. These
traditional questions typically yield only predictable answers which provide very little useful information upon
which to distinguish candidates, unless further probing questions are employed. It is important to not settle for the
candidates assurance that they possess admirable traits; instead, interviewers should ask for evidence from the
candidates experience that this is the case. In the internet era, problems with plagiarism in application materials
have been found, and BDI or modifications can be used to validate the information included in a job application.
(16) Although the tone of a formal interview can be friendly and include some social elements, savvy interviewers
should be looking for reasons not to hire a candidate. Once these concerns are raised, they should be considered
carefully and discussed with the candidate. Good candidates will not be put off by a challenging but fair interview
and recruitment process. Such a process demonstrates that the organization values the job highly and places
emphasis on hiring the right person for it (4). It also sets the tone for the values and work culture in the department.

Another important suggestion for interviewers is to refrain from dominating the conversation. Often well-
intentioned interviewers spend so much time providing a candidate with information about the practice, community,
school systems, etc., that the candidate is not given much opportunity to speak. This deprives the interviewer from
getting a better sense of the character of the candidate. Allowing the candidate time to speak can provide insight
into whether he or she is a problem identifier or solver, an optimist or a pessimist, etc.

The Problem Employee

Despite all caution and efforts, anesthesiology groups will inevitably recruit an employee who presents problems in
the work place. This is one of the most challenging tasks for department leaders, and can require an enormous
amount of time, effort and hard work to diagnose the problem, and then implement a plan to help the employee.

403
Page 5
The first aspect of dealing with a problem employee is identifying exactly what the problem is. This is more easily
identified when performance standards and policies are clearly defined, agreed upon by the group members, and
communicated clearly to the entire group. Having standards established makes it easier to determine when an
employees behavior is problematic. Problem employees can manifest in many ways, but can be categorized in
one of three domains. However, it is important to realize that it is rare for a struggling employee to have problems
limited to one domain. Typically even if one domain predominates, there is impact in the other domains.

The Employee with a Cognitive Problem: Cognitive problems are less likely than affective problems, but still
manifest themselves, even at the level of practicing physicians. An anesthesiologist may have poor learning and
studying habits, or may even have learning disabilities for which they have compensated quite well. A graduated
resident who is a memorizer may finally reach his or her limits as the volume of material to learn increases, and may
fail to pass the ABA examination (17). Other group members may not have the initiative to prioritize continuing
education. This can be problematic for some groups or institutions which require board certification or maintenance
of certification for credentialing, and will be an increasing potential issue as one-time certification is replaced by
Maintenance of Certification in Anesthesiology. Additionally, physicians who have not developed a system for
continued learning will become outdated in their practice and this can pose a problem for the smooth functioning of
the group.

The Employee with an Affective Problem: This is probably the most common problem encountered by leaders of
medical groups and can be the most difficult to solve. Affective problems tend to lead to more problematic
outcomes with medical boards and other organizations (19, 20). Examples of problems in this domain include:

Work ethic
Compliance with requirements: e.g. HIPAA, supervision
Compassion
Respect for others
Fairness
Impairment
o Substance abuse
o Medical illness
o Psychiatric illness
o Disruptive behavior

The Employee with a Psychomotor Problem: This type of problem is less common in anesthesiology, but does
occur. There can be some overlap between Affective and Psychomotor problems. Some examples include problems
with:

Stamina
Eye-hand coordination
Technical skills
Pace of practice

Diagnosing the type of problem is the first important part of finding a solution. Once a plausible sense of the
problem is identified, it is then appropriate to meet with the employee to try to establish a plan of action for
improvement. The goal is to try to help the individual achieve success. Leaders of departments must define what
resources they are willing to commit to helping individuals who are struggling, and weigh this against the expense
and time of recruiting another employee. At a certain point, a decision to terminate the employment might be
reached, particularly if resources are not available to remediate the problem.

Affective problems seem to be the major category of issues program departmental leaders deal with. The effective
management of these problems can be difficult, as physicians are often uncomfortable giving a colleague feedback
about affective problems, and frequently there is little objective information to support the concerns. The key to
approaching affective issues is to describe them in behavioral terms. For example, an anesthesiologist who is
termed lazy, disinterested, difficult, etc. will almost certainly set up a defensive posture, making further
dialogue about the problem difficult. If however, using lazy as an example, the problem is described by the

403
Page 6
doctors arrival time each day, versus the expected standard, the message is less emotional and cant be argued about
as easily. Describing the problem in behavioral terms with nouns and verbs rather than adverbs also makes it easier
to define the expected outcomes to help the individual achieve the goal more readily (17, 18).

Meetings to address these issues should be carefully planned. The goal is to help the employee accept the problem,
and be willing to engage in the solution. For some individuals, the transition from resident to attending level
responsibility is difficult, but even experienced but new-to-the-practice employees may need specific guidance and
instruction to help them adjust to the practice setting. In short, the idea is to help the individual understand the
consequences of the undesired behavior. In the setting of a potentially permanent job, the specter of unemployment
can motivate some individuals quite well.

The expense in time and effort of hiring a good employee is tremendous. Good departments will create an
environment that assists new employees with the transition to the practice. Establishing a trial period of
employment, which includes careful scrutiny of the new employee, feedback and opinions from other members of
the group, surgeons/obstetricians, other consultants, nursing staff and departmental staff, may help. This can include
formal 360 degree assessments, observation of clinical practice, and monitoring of compliance with departmental
policies. A similar, but perhaps less intense model should be applied to all department members, as problems may
develop long after an initial provisional employment period.

Each state and institution has policies regarding due process and appeals of negative administrative employment
decisions. Good employment contracts also specify the expectations and rights of the employee, and if a decision
has been made to terminate an employee, it is important to consult with all entities including legal counsel about the
appropriate process and procedures. The importance of keeping appropriate documentation to support any adverse
decision cannot be overemphasized.

In summary, even the most careful application and interview process cannot guarantee that a problem employee will
never be hired. Additionally, group members can change over time in their capabilities, adaptability and reactions to
a stressful work environment. Thoughtful leadership includes the development of a highly selective hiring process,
creation of a supportive environment for the transition of new employees into the organization, and appropriate
feedback about performance. Implementation of these strategies should increase the likelihood of success for the
employee and the group.

References:

1. Ferguson E, James D, and Madeley L. Factors associated with success in medical school: systematic review of
the literature. BMJ (324) 952-7, 2002.
2. Ferguson E, Sanders A, OHehir F et al. Predictive validity of personal statements and the role of the five-
factor model of personality in relation to medical training. J Occ Org Psychol (73) 321-44, 2000.
3. Lurie SJ, Lambert DR, Grady-Weliky TA. Relationship between deans letter rankings and later evaluations by
residency program directors. Tch Learn Med (19) 251-6, 2007.
4. www.pbpexecutivesummaries.com Accessed June 10, 2010.
5. Wenghofer E, Klass D, Abrahamowicz M et al. Doctor scores on national qualifying examinations predict
quality of care in future practice. Med Educ (43) 1166-73, 2009.
6. Crane JT and Ferraro CM. Selection criteria for emergency medicine residency applicants. Acad Emerg Med
(7) 54-60, 2000.
7. Fine PL, and Hayward RA. Do the criteria of resident selection committees predict residents performances?
Acad Med (70) 834-838, 1995.
8. Brown E, Rosinski EF, and Altman DF. Comparing medical school graduates who perform poorly in residency
with graduates who perform well. Acad Med (68) 806-808, 1993.
9. http://www.humanism-in-medicine.org/ accessed 6/10/2010.
10. Brothers TE and Wetherholt S. Importance of the faculty interview during the resident application process. J
Surg Educ (64) 378-385, 2007.
11. Altmaier EM, Smith WL, OHalloran CM et al. The predictive utility of behavior-based interviewing
compared with traditional interviewing in the selection of radiology residents. Invest. Radiol (27) 385-389,
1992.

403
Page 7
12. Herrenkohl E. How to interview candidates, not educate them. http://hiring.monster.com/hr/hr-best-
practices/recruiting-hiring-advice/interviewing-candidates/how-to-interview.aspx accessed 5/29/2013.
13. Easdown LJ, Castro PL, Shinkle EP et al. The behavioral interview, a method to evaluate ACGME
competencies in resident selection: A pilot study. JEPM (7) 1-10, 2005.
14. Prager JD, Myer CM, Hayes KM et al. Improving methods of resident selection. Laryngoscope (120) 2391-
2398, 2010.
15. Wood PS, Smith WL, Altmaier EM et al. A prospective study of cognitive and noncognitive selection criteria
as predictors of resident performance. Invest Radiol (25) 855-9, 1990.
16. Segal S, Gelfand BJ,, Hurwitz S et al. Plagiarism in residency application essays. Ann Int Med (153) 112-120,
2010.
17. Willenkin RL. Helping residents with cognitive learning problems. Int Anes Clinics (46) 41-54, 2008.
18. Willenkin RL. Helping residents with affective learning problems. Int Anes. Clinics (46) 55-66, 2008.
19. Papadakis MA, Teherani A, Banach MA et al. Disciplinary action by medical boards and prior behavior in
medical school. NEJM (353) 2673-82, 2005.
20. Papadakis MA, Arnold GK, Blank LL et al. Performance during internal medicine residency training and
subsequent disciplinary action by state licensing boards. Ann Intern Med (148) 869-76, 2008.

Suggested Additional Readings:

Baker JD, Bailey MK, Brahen NH et al. Selection of anesthesiology residents. Acad Med (68) 161-163, 1993.

Leichner P, Eusebio-Torres E, and Harper D. The validity of reference letters in predicting resident performance. J
Med Educ (56) 1019-1021, 1981.

Wagoner NE, and Suriano JR. Recommendations for changing the residency selection process based on a survey of
program directors. Acad Med (67) 459-465, 1992.

Wagoner NE, Suriano JR, and Stoner JA. Factors used by program directors to select residents. J Med Educ (61)
10-21, 1986.

Powis DA, Neame RLB, Bristow T et al. The objective structured interview for medical student selection. Br Med
J (296) 765-768, 1988.

Friedman RB. Fantasy Land. N Engl J Med (308) 651-653, 1991.

Young TA. Teaching medical students to lie. The disturbing contradiction: medical ideals and the resident-
selection process. Can Med Assoc J (156) 219-222, 1997.

Metro DG, Talarico JF, Patel RM et al. The resident application process and its correlation to future performance as
a resident. Anesth Analg (100) 502-5, 2005.

Berner ES, Brooks CM, Erdmann JB. Use of USMLE to select residents. Acad Med (6) 753-5, 1993.

Disclosure

405
Page 1
Mindfulness and Anesthesiology
Robert S. Holzman M.D., M.A. (Hon.), FAAP Boston, Massachusettes
Why is it that a 4 year old can answer this question with a single word, and a computer would try to fill in the blank
for hours?
The giraffe had a very long ____.
Humans care about whats probably right. Inductive reasoning is called into action when we hear a strange noise in
the house at 3 a.m. and call the cops. It is the basis for reaching for the roller clamp on the IV with tachycardia,
hypotension and a narrow pulse pressure, pending further considerations. Humans formulate nearly instantaneous
beliefs and take action. Although inductive reasoning may generate conclusions that arent necessarily true, they are
probabilistically true and therefore, possibly false.
My thesis will be that our capacity to err is inextricable from what makes the human brain so swift, adaptable, and
intelligent. Mindfulness is an essential component to best practice in anesthesiology, but our professional milieu is
increasingly conducive to mindlessness. Mindlessness is real, it exists, it is insidious, and it is sneaking into your
operating room and your anesthetic environment. Moreover, it is seductive, biological, and neurochemically
enticing. Finally, it is altogether natural, and ironically, that is why we can understand it and improve upon it.
Mindfulness is not vigilance (therefore mindlessness is not lack of vigilance)
Vigilance, or sustained attention, is the ability to maintain
attention and alertness over prolonged periods of time. The
study of vigilance has expanded since the 1940s mainly due
to the increased interaction of people with machines. As we
use what sociologist Daniel Bell has called our intellectual
technologies - the tools that extend our mental rather than
our physical capacities - we take on the qualities of those
technologies.
2
Bell devoted his career to examining the
influence that post-industrial society had on human thought,
including early suggestions that increasing technology could
promote vigilance decrement yet he was far from the first
to suggest advancing technologys adverse effects.
Vigilance decrement is deterioration in the ability to remain
vigilant for critical signals with time, as indicated by a
decline in the rate of the correct detection of signals.
3
While
early vigilance studies assumed that successive discriminations impose a greater workload than simultaneous
discriminations, starting in the 1990s, neuroimaging techniques such as Positron Emission Tomography (PET),
functional Magnetic Resonance Imaging (fMRI) and Transcranial Doppler sonography (TCD) were added to the
investigation of brain activation and mental workload during vigilance experiments, and linked increases in mental
workload and allocation of attentional resources with increased activity in the prefrontal cortex. Studies employing
PET, fMRI and TCD revealed a (logical) decline in activity in the prefrontal cortex with vigilance decrement.
4

However, if vigilance decrement were only the result of less brain activity rather than more, vigilance tasks could
not be expected to be stressful. Subjects performing vigilance tasks exhibit elevated levels of epinephrine and
norepinephrine, consistent with high stress levels and indicative of a significant mental workload. Although early
theories of vigilance explained the vigilance decrement as a result of neural habituation due to repeated stimulation,
The clock, which came into common use in the 14th
century, provides a compelling example. Mumford
described how the clock disassociated time from
human events and helped create the belief in an
independent world of mathematically measurable
sequences. The abstract framework of divided time
became the point of reference for both action and
thought.
1
But it also took something away. In
deciding when to eat, work, sleep, and wake up, we
stopped listening to our senses and started obeying the
clock. People began thinking of their brains as
operating like clockwork. Today, we have come to
think of them as operating like computers. But the
changes go much deeper than metaphor. Thanks to our
brains plasticity, the adaptation also occurs at a
biological level.

405
Page 2
there is no decline in N100 amplitude when performance declines during a vigilance task.
5
Vigilance tasks may
therefore be assumed to be stressful, recruitment-related hard mental work.
6,7
Vigilance decrement may be reduced
by amphetamines, practice, performance feedback, and rest, without reducing sensitivity.
8-10

Mindfulness is not concentration (therefore mindlessness is not lack of concentration)

Dont confuse concentration with mindfulness. Concentration is a tool. It powers mindfulness, but mindfulness is a
broader and larger function than concentration. Concentration is exclusive, and mindfulness is inclusive. The best-
known study of this phenomenon was conducted by Simons and Chabris, in which two groups of people (wearing
black and white t-shirts) pass a basketball around. The subjects are told to either count the number of passes made
by one of the teams or to keep count of bounce passes vs. aerial passes. In different versions of the video a man
walks through the scene carrying an umbrella, or wearing a full gorilla suit. After watching the video the subjects are
asked if they saw anything out of the ordinary. In most groups, 50% of the subjects did not report seeing the
gorilla.
11
While concentration provides the power to acquire information, it restricts contextual perception.

Multitasking and Mindlessness

Nass and co-workers have been looking at this issue in modern society, and concluded in a seminal paper in
Proceedings of the National Academy of Sciences that multitasking was not exactly all it was supposed to be. Heavy
media multitaskers (HMMs) are distracted by the multiple streams of media they are consuming. Low media
multitaskers (LMMs) have a greater tendency for top-down attentional control, and thus may find it easier to focus
on a single task in the face of distractions. HMMs are more likely to respond to stimuli outside the realm of their
immediate task, and thus may have a greater tendency for bottom-up attentional control. With larger computing
screens supporting multiple windows and browsers, chat, and SMS, and portable media coupled with social and
work expectations of immediate responsiveness, media multitasking quickly became ubiquitous in the business
world. These changes placed new demands on cognitive processing and attention allocation.

Working memory (WM) capacity and the ability to ignore interference increase during childhood development. In
order to retain information in WM, it is necessary to ignore interfering stimuli from the surroundings. High WM
capacity is also essential for the ability to differentiate between relevant and irrelevant information. The larger
frontal activation in response to distracters presented during the delay may explain why children are more
susceptible to interfering stimuli.
12
When people perform two tasks simultaneously, the tasks are often executed
slower and with more errors than when they are carried out as single tasks. Concurrently performed visual and
somatosensory reaction time tasks engage almost identical volumes of cortical and subcortical motor structures.
Dual reaction time tasks engage additional cortical regions that are not activated by the component tasks had they
been performed as single tasks.
13
Performance of dual reaction time tasks activates cortical regions in excess of
those activated by the performance of component single tasks. When attention needs to be divided between two
concurrent processes there is a performance cost, which is elicited as an increased reaction time. If the brain were
truly a parallel processor, like a computer, the shared cortical fields should not lead to interference, nor should there
be interference-specific cortical activity.

It is fascinating to see how the business world rapidly shifted from job requirements that required ability to
multitask, listed prominently 15 years ago, to ability to concentrate and focus starting about 5-7 years ago. The
most rapidly growing position at leading companies now is envisioning officer.

What does it mean if multitaskers are actually fooling themselves into believing they are competent when they are
really not? Some studies show they are worse at analytic reasoning. It isnt simply a matter of having impaired
performance and vigilance decrementwe simultaneously think and feel that we're invincible. And that attitude has
massive carryover into real life, because we are wired to respond that way.

The Biological Basis of Increasing Mindlessness

Like almost all activities we find compulsive, gaming induces our bodies to produce elevated levels of dopamine
within the nucleus acumbens.
14
Certain kinds of games are, however, especially adept at elevating levels of

405
Page 3
dopamine over long periods of time via their combination of structured tasks and varied, regular rewards. In this
regard, the operating room is very reminiscent of a casino.

As our ability to gather information became more sophisticated, so did the data we could acquire. Still, the physician
remained the primary collector, assessor, and interpreter of tests and their results. Individual physicians would spin

urine and examine the sediment, perform blood smears, and even examine tissue samples for pathology. This was a
manageable task for the physician because the number of tests was small, and the interpretation of results was fairly
straightforward. Today tests and the ways we can interpret them are both more numerous and more complicated.
How can we manage all of this information?

In the world of the operating room and intensive care unit, most current physiological monitoring systems are not
intelligent. The alarm systems are based on upper and lower thresholds. Furthermore, alarms seldom localize
problems; they do not provide predictive information and the diagnostic process is still left to the practitioner. As
physiological rhythms fluctuate and the acceptable range varies for each individual, false alarms are inevitable.
When combined with clinical interventions and other artifacts, the high false-positive rate renders alarms ineffective
- so that they are frequently ignored, in an attempt to cope with attention overload. The current visual and auditory
displays have become ineffective monitoring systems that amplify demands on human attention. As our ability to
gather information became more sophisticated, so did the data we could acquire. As the volume of data increases, so
does the likelihood that a piece of important data will be missed.

Have you ever found yourself reading the same paragraph in the medical record over and over again, because
auditory processing interfered with the processing of the visual input? Interference is often worst if simultaneous
activities are very similar, suggesting competing demands on shared processing or neural systems.

Mindlessness and Burnout

Physician burnout has been recognized for years; in anesthesiology practice, it has been explored thoughtfully by
Jackson within the context of stress.
15
It starts early. Burnout was associated with self-reported unprofessional
conduct and less altruistic professional values among medical students at 7 US schools. In a survey of almost 2,700
medical students attending 7 US medical schools in 2009, more than half self-reported findings consistent with
burnout. Cheating/dishonest academic behaviors were rare (endorsed by10%) in comparison to unprofessional
conduct related to patient care (endorsed by up to 43%). Students with burnout were more likely to report engaging
in 1 or more unprofessional behaviors than those without burnout (35.0% vs. 21.9%). After multivariate analysis
adjusting for personal and professional characteristics, burnout was the only aspect of distress independently
associated with reporting 1 or more unprofessional behaviors (OR=1.76) or holding at least 1 less altruistic view
regarding physicians responsibility to society (OR=1.65).
16

In our evolving group care model, when patients are evaluated preoperatively by one doctor, have their anesthetic
administered by another, and are discharged by a third there may be a tendency to see ones role as mechanical.
Under the imprimatur of the 80-hour rule, mandatory departures from work have been recognized as (potentially)
promoting a shift-worker system based more on rules than values. Few studies exist to examine the learning
consequences of the night float system, but at least one has raised the question of adverse effects on the acquisition
of surgical experience (vs. the perioperative care of surgical patients.)
17
An essay from Slate magazine in 2008
posed the intriguing question The Nightmare of Night Float: Is an ignorant doctor really better than a tired one?
18

Mindfulness: Recognizing and Fixing the Gaps Between Knowledge, Values, and Actions

Mindlessness may be a root cause for many deviations from professionalism.
19
Reporting findings that were not
actually observed, or failure to seek remediation for errors are actions that deviate from professional knowledge and
values. These may be due to concerns about efficiency, a desire to please supervisors, embarrassment, and being
overwhelmed.
20-23

It is not hard to find accounts of improved practice within the mindfulness context. A pilot study found a reduction
in medication errors after implementation of the program at a single hospital.
24
Groopman suggests that most
misdiagnoses do not result from lack of knowledge but from faulty thinking, including anchoring errors (snap

405
Page 4
judgment), attribution errors (stereotyping), and other cognitive traps.
25
He proposes that these cognitive errors can
be avoided by paying attention to the process of thinking, a metacognitive practice of self-reflection - mindfulness.

Mindfulness as a Cognitive Lens

Clinical judgment is based on explicit as well as
tacit knowledge. While explicit knowledge can be
quantified, communicated, and easily formed into
clinical practice guidelines, seasoned practitioners
also employ skills, values, and experiences that are
not explicitly stated by or known to them. This
knowledge may constitute a different kind of
evidence, which also has a strong influence on
medical decisions. During this process, the brain
rapidly scans perceptions, prioritizes conspicuous
features, and submerges other information in the
background, all before the content of the perception
is analyzed. Clinical skills, such as the manipulation of the fetal head during a delivery, the realization that a patient
has given sufficient information to diagnose major depression and turning the APL valve slightly during the
excitement phase of an inhalation induction or when observing paradoxical chest wall movement, all involve tacit
knowledge and preattentive processing probabilistic reasoning.

The goals of mindful practice are to become more aware of ones own mental processes, listen more attentively,
become flexible, and recognize bias and judgments. Mindful practice involves a sense of unfinishedness, curiosity
about the unknown and humility in having an imperfect understanding of anothers suffering. It has been described
as having a beginners mind open and allowing for new possibilities whereas the experts mind narrows the
possibilities.
26
Uncertainty is welcomed. Difficult patients might then become interesting patients; unsolvable
problems might become avenues for research. Mindfulness is the opposite of multitasking, the obverse of
concentration, and energy-restoring, unlike vigilance.

There are neurohumoral correlates as well. Using electroencephalogram (EEG), Lutz et al found that during
meditation, highly experienced Buddhist monks produced long-distance phase synchrony (suggestive of large-scale
neural coordination) and gamma activity with a higher amplitude than any reported in a state of health.
27
Tang et al
reported that undergraduates in a Chinese university randomly assigned to a mind/body intervention that included
mindfulness showed lower salivary cortisol and higher salivary IgA concentrations in response to psychological
stress (mental arithmetic task) compared with control students who were given an intervention of equal intensity that
focused on relaxation.
28

Mindfulness an Antidote to Burnout?

A mindfulness program was initiated among family practitioners affiliated with the University of Rochester and
reported in 2009 in JAMA
29
with an accompanying editorial.
30
The one year program consisted of an intensive phase
(8 weekly 2.5-hour sessions, plus an all-day 7-hour session) and a maintenance phase (10 monthly 2.5-hour sessions
following the eighth weekly session) with the hypothesis that intensive training in attention, awareness, and
communication skills would increase physician well-being, reduce psychological distress and burnout, and promote
positive changes in physicians capacity to relate to patients as indicated by increased empathy and patient- centered
orientation to care. Over the course of the program and follow-up, participants demonstrated improvements in
mindfulness (raw score=45.2 to 54.1; 95% CI=7.0-10.8); burnout (emotional exhaustion, 26.8 to 20.0; 95% CI=4.8
-8.8; depersonalization, 8.4 to 5.9; 95% CI=1.4-3.6; and personal accomplishment, 40.2 to 42.6; 95% CI=1.2-3.6);
empathy (116.6 to 121.2; 95% CI=2.2-7.0); physician belief scale (76.7 to 72.6; 95% CI=1.8-6.4); total mood
disturbance (33.2 to 16.1; 95% CI=11-23.2), and personality (conscientiousness, 6.5 to 6.8; 95% CI=0.1-5 and
emotional stability, 6.1 to 6.6; 95% CI=0.3-0.7). Improvements in mindfulness were correlated with improvements
in total mood disturbance, physician empathy, burnout (emotional exhaustion and personal accomplishment
subscales) and personality factors. Participation in a mindful communication program was associated with short-

405
Page 5
term and sustained improvements in well-being and attitudes associated with patient-centered care. The intervention
was also associated with increased trait emotional stability (i.e., greater resilience). Most importantly, these salutary
effects on burnout, well-being, and empathy occurred in the absence of systems changes. Although the study was
done in volunteers (who may have been disposed to more mindful practice in any event) and was limited to primary
care physicians, it provided a model for constructing and measuring such an approach.

Mindfulness training has been shown to help promote well-being, as summarized in a recent review of the research
literature,
31
with neuroimaging studies suggesting possible mechanisms of action.
22,32
Two studies on nursing
students add credence to the theory that more mindful health care workers provide better health care.
33,34

Mindfulness leads to Wisdom

Mindful practice extends beyond examining the
affective domains and involves critical reflection on
action, tacit personal knowledge, and values in all
realms of clinical practice, teaching, and research.
Mindfulness is a discipline and an attitude of mind.
It requires critical informed curiosity and courage to
see the world as it is rather than how one would
have it be. Mindful practitioners tolerate making
conscious their previously unconscious actions and
errors. The goal of mindfulness is compassionate
informed action in the world, to use a wide array of
data, make correct decisions, understand the patient,
and relieve suffering. Mindful practice requires
mentoring and guidance. Recognition of ones
limitations and areas of incompetence can be
emotionally difficult and can invite avoidance in
even highly motivated practitioners. Although
mindfulness is an individual and subjective process,
each of us can identify practitioners who embody these attributes, learn from them, and identify unique ways of
being self-aware. Educators can take on the task of helping trainees become more mindful by explicitly modeling
their means for cultivating awareness. Professionals can learn to articulate their personal knowledge by observing
their own actions reflective practice.

We can also improve our self-control with practice; there is emerging evidence that specific training will result in an
increase in brain activity related to working memory in the middle frontal gyrus and superior and inferior parietal
cortices. This can take place over an 18 day 5 week period, resulting in an improved specific performance and a
generalization of the training effect to nontrained tasks related to working memory. In debriefing, most of the
subject reported using chunking as a strategy.
12,35
Cognitively, mindfulness appears to improve working memory
capacity
36
and possibly lead to an increase in gray matter.
37

Conclusions

Mindlessness is one of the most ubiquitous and pervasive of all cognitive phenomena. It often occurs
unintentionally, without awareness, occupies a substantial proportion of our day, and leads to failures in task
performance. It is particularly challenging now because of technology-intensive interactions in the workplace,
especially among millennial generation workforce members. Moreover, there may be a substantial biological
(pleasure-reward center) basis for the response to that technology.

Physicians in the United States will face a host of new challenges over the next decade as the nation reforms its
health care system. This restructuring will likely result in reduced physician compensation and autonomy, increased
time pressure, and myriad new administrative challenges. These changes have the potential to increase the already
epidemic levels of burnout among physicians and to overwhelm those currently near their limits. Although many
physicians may be tempted to respond to this challenge by retreating from work (e.g., more time off, reduced scope
In his description of Socrates speech to the court while on trial
for impiety and corruption:
If I tell you that I would be disobeying the god
and on that account it is impossible for me to keep
quiet, you wont be persuaded by me, taking it that
I am ironizing. And if I tell you that it is the
greatest good for a human being to have
discussions every day about virtue and the other
things you hear me talking about, examining
myself and others, and that the unexamined life is
not livable for a human being, you will be even
less persuaded.
Plato details why Socrates felt it impossible to go into exile and
keep his opinions to himself. The paraphrase of this statement
became the Socratic dictum The unexamined life is not worth
living.
Plato: Apology. Thomas Library, Bryn Mawr College, 1989.
Sect. 38

405
Page 6
of practice, retirement), the study by Krasner and colleagues demonstrates that training physicians in the art of
mindful practice has the potential to promote physician health through work.
29

References

1. Mumford L: Technics and Civilization. New York, Harcourt, Brace & Company. Translated by: 1934.
2. Bell D: The Coming of Post-Industrial Society. New York, Harper Colophon Books,. Translated by: 1974.
3. Parasuraman R: Vigilance, Monitoring and Search, Handbook of Human Perception and Performance.
Edited by Boff J, Kaufmann L, J.P. Thomas J. New York, Wiley, 1986, pp 411 - 41-49
4. Parasuraman R, Caggiano G: Neural and genetic assays of mental workload, Quantifying Human
Information Processing. Edited by McBride D, Schmorrow D. Lanham, Maryland, Rowman and Littlefield, 2005,
pp 123155
5. Parasuraman R: Sustained attention: a multifactorial approach, Attention and Perormance. Edited by Posner
M, O Marin O. Hillsdale NJ, Lawrence Erlbaum, 1985, pp 493-511
6. Lundberg U, Frankenhaeuser M: Pituitary-adrenal and sympathetic adrenal correlates of distress
and effort (Report 548). Stockholm, Sweden, University of Stockholm, 1979
7. Warm, J, Parasuraman, R, Matthews G: Vigilance Requires Hard Mental Work and Is Stressful. Human
Factors 2008; 50: 433-441
8. Kerkhoff G, van der Schaaf T, Korving H: Auditory Signal Detection: Effects of long-term practice and
time on task. Perception and Psychophysics 1980; 28: 79-81
9. Mackworth J: Performance Decrement in Vigilance, Threshold, and High-Speed Perceptual Motor Tasks.
Canadian Journal of Psychology 1964; 18: 209-223
10. Mackworth J: The effect of amphetamine on the detectability of signals in a vigilance task. Canadian
Journal of Psychology 1965; 19: 104-117
11. Simons D, Chabris C: Gorillas in our midst: sustained inattentional blindness for dynamic events.
Perception and Psychophysics 1999; 28: 1059-1074
12. Olesen P, Macoveanu J, Tegne J, Klingberg T: Brain activity related to working memory and distraction in
children and adults. Cerebral Cortex 2007; 17: 1047-1054
13. Herath P, Klingberg T, Young J, Amunts K, Roland P: Neural correlates of dual task interference can be
dissociated from those of divided attention: An fMRI study. Cereb Cortex 2001; 11: 796805
14. Koepp M, Gunn R, Lawrence A, Cunningham V, Dagher A, Jones T, Brooks D, Bench C, Grasby P:
Evidence for striatal dopamine release during a video game. Nature 1998; 393: 266-8.
15. Jackson S: The role of stress in anaesthetists' health and well-being. Acta Anaesthesiologica Scabndinavica
1999; 43: 583-602
16. Dyrbye L, Massie Jr F, Eacker A, Harper W, Power D, Durning S, R. M, Moutier C, Satele D, Sloan J,
Shanafelt T: Relationship Between Burnout and Professional Conduct and Attitudes Among US Medical Students.
JAMA 2010;; 304: 1173-1180
17. Kelly RJ, Senkowski C: Effect of the night float system on operative case volume for senior surgical
residents. J Surg Educ 2009; 66: 314-8
18. Jauhar S: The Nightmare of Night Float: Is an ignorant doctor really better than a tired one?, Slate, The
Washington Post Company, 2008
19. Lovas J, Lovas D, Lovas P: Mindfulness and Professionalism in Dentistry. Journal of Dental Education
2008; 72: 998-1009
20. Balint M: The Doctor, His Patient and the Illness. London, England, Pitman. Translated by: 1964.
21. Christakis D, Feudtner C: Ethics in a short white coat. Acad Med 1993;; 68: 249-254
22. Davidson R, Kabat-Zinn J, Schumacher J, Rosenkranz M, Muller D, Santorelli S, Urbanowski F,
Harrington A, Bonus K, Sheridan J: Alterations in brain and immune function produced by mindfulness meditation.
Psychosom Med 2003; 65: 56470
23. Feudtner C, Christakis D, Christakis N: Do clinical clerks suffer ethical erosion: students perceptions of
their ethical environment and personal development. Acad Med 1994; 69: 670-679
24. Jones J, Barge B, Steffy B, Fay L, Kunz L, Wuebker L: Stress and medical malpractice: organizational risk
assessment and intervention. J Appl Psychol 1988; 73: 727-735
25. Groopman J: How Doctors Think. Boston, MA, Houghton Mifflin. Translated by: 2007.
26. Suzuki S: Zen Mind, Beginners Mind. New York, NY, Weatherhill. Translated by: 1980.

405
Page 7
27. Lutz A, Greischar L, Rawlings N, Ricard M, Davidson R: Long-term meditators self-induce high-amplitude
gamma synchrony during mental practice. Proc Natl Acad Sci U S A 2004; 101: 16369-16373
28. Tang Y, Ma Y, Wang J, Fan Y, Feng S, Lu Q, Yu Q, Sui D, Rothbart M, Fan M, Posner M: Short-term
meditation training improves attention and self-regulation. Proc Natl Acad Sci U S A 2007; 104: 17152- 17156

29. Krasner M, Epstein R, Beckman H, Suchman A, Chapman B, Mooney C, Quill T: Association of an
Educational Program in Mindful Communication With Burnout, Empathy, and Attitudes Among Primary Care
Physicians. JAMA 2009; 302: 1284-1293
30. Shanafelt T: Enhancing Meaning in Work: A Prescription for Preventing Physician Burnout and Promoting
Patient-Centered Care. JAMA 2007; 302: 1338-40
31. Brown K, Ryan R, Creswell J: Mindfulness: theoretical foundations and evidence for its salutary effects.
Psychol Inquiry 2007; 18: 21137
32. Farb N, Segal Z, Mayberg H, Bean J, McKeon D, Fatima Z, Anderson A: Attending to the present:
mindfulness meditation reveals distinct neural modes of self-reference. Social Cognitive Affective Neurosci 2007; 2:
31322
33. Beddoe A, Murphy S: Does mindfulness decrease stress and foster empathy among nursing students? J
Nurs Educ 2004; 43: 30512
34. Mackenzie C, Poulin P, Seidman-Carlson R: A brief mindfulness-based stress reduction intervention for
nurses and nurse aides. Appl Nurs Res 2006; 19: 1059
35. Olesen P, Westerberg H, Klingberg T: Increased prefrontal and parietal activity after training of working
memory. Nat Neurosci. 2004; 7: 7579
36. Mrazek M, Franklin M, Phillips D, Baird B, Schooler J: Mindfulness Training Improves Working Memory
Capacity and GRE Performnce While Reducing Mind Wandering. Psychological Science 2013; 24: 776-81
37. Hlzel B, Carmody J, Vangel M, Congleton C, Yerramsetti S, Gard T, Lazar S: Mindfulness practice leads
to increases in regional brain gray matter density. Psychiatry Res 2011; 191: 36-43

Disclosure

411
Page 1
Mythbusters Episode: Anesthesia Economic Issues
Amr Abouleish, M.D., MBA Galveston, Texas
Healing is an Art, Medicine is a Science, and Healthcare is a Business
Author Unknown
Objectives: By the end of the presentation, you should be able to
1. Determine if the myths discussed are Confirmed, Plausible, or Busted
2. Discuss different strategies to improve OR throughput
3. Explain how anesthesia care is billed and paid and how surgical duration affects the charges
4. Show how comparing simply yearly compensation of different anesthesia providers results in wrong
conclusions of the cost of care
5. Show why using per provider measurements can lead to inaccurate benchmarking of clinical
productivity.
Myths of Anesthesia Economics
On the Discovery Channels MythBusters TV Show (http://dsc.discovery.com/tv-shows/mythbusters), the hosts
examine different myths (from social media, entertainment, internet, and folklore). They develop scientific
experiments to test these myths, and by the end of an episode, they determine if a myth is Confirmed, Plausible,
or Busted.
In a similar way, in todays presentation, I will examine 4 myths of anesthesia economics and try to determine if
they are true (confirmed), possible (plausible), or wrong (busted). The myths that will be discuss are the following:
Focusing on turnover time will improve OR throughput.
Because anesthesia revenue includes time, anesthesia providers prefer longer surgeries.
Going from physician-only staffing to medical direction staffing will reduce staffing costs.
Using per provider (aka FTE) measurements allow for accurate benchmarking of productivity.
Focusing on turnover time will improve OR throughput.
More frequently, you will hear the complaint If turnover time was shorter, wed do more cases! My first response
to this statement is Stop beating a dead horse! Research has established the fact that further reducing reasonable
turnover times will not increase the number of cases that can be done in a workday.(1,2) For instance, for an OR in
a non-ambulatory surgical center hospital, a reasonable maximum turnover time between procedures might be 35
minutes. Reducing this number by 20% would only result in a 7-minute time saving between cases. If 3 cases were
done per OR, this would mean a 14-minute saving. Compared to the average surgical duration of ones hospital,
reducing turnover time by 20% will not allow for one more surgical case to be done. Obviously, in an OR where
more cases are being done in a day (e.g., 7-10 cataract or pediatric otolaryngology surgeries), reducing turnover time
by 7 minutes per case may be significant. But in these specific ORs, the turnover time will already be much lower
than in the rest of the ORs (e.g., 15-20 minutes) and further reduction may not be possible.
In contrast, focusing on reducing any delaysdefined as a turnover time greater than the reasonable maximum
turnover timewill result in large time savings. For instance, if a turnover time is 90 minutes in an OR with a the
maximum time set at 35 minutes, then a 55-minute delay has occurred. Focusing on the etiologies of this type of
delay could result in a reduction of 55 minutes per occurrence.

411
Page 2
Finally, anesthesiologists should point out that they cannot bill for turnover time and therefore are also interested in
decreasing it. Although decreasing the downtime will not allow an anesthesiologist to bill more per OR for that day
(because of the previously mentioned inability to perform even one more case in a regular day); such efforts may
result in the anesthesia provider(s) going home earlier, which can reduce overtime payments.

Traditionally, OR throughput improvement initiative has been to focus on how to have current number of people
work more efficiently. (3,4) An interdisclipinary work flow assessment and redesign has been to work. It is
important to note that all the efforts must include all participants, including surgeons. Further, anecdotal experience
is that the initiatives work as long as there is a focus on the effort. After people are not looking at, old habits will
come back into existence. So the major lessons from this traditional approach is that one must include everyone and
that the initiative must be publicized every 3 months to remind workers that it is still important.

In additional, traditional methods have a limited potential improvement. On the other hand, three studies published
in Anesthesiology (August 2005 issue) describe successful attempts at redesign the non-surgical time.(5-7) Each
study examined the movement of non-surgical time from series to parallel processing that is moving from
performing all activities in the OR where the surgery is done to performing some or all the non-surgical activity in
another room while the surgery from the previous case is ongoing. In this way, turnover time activities are not
reduced but done at another time. In all three studies, more staff (anesthesia and non-anesthesia) were required. This
process is not new. In the past, ORs use to provide two ORs for fast surgeons that is two complete OR teams for
one surgeon. Presently, this is not as common, but with the emergence of preoperative regional block rooms, a
form of parallel processes already exist in some OR suites. A form of parallel processing (either block room or ones
described in the studies) makes economic sense if the increased costs is offset by increased revenue (i.e., more
cases) (which is dependent on payer mix and staffing costs (as described in the previous section) or a reduction in
overtime staffing costs.

In July 2008 Anesthesiology, Smith et. al. showed how parallel processing and the use of regional anesthesia
successfully allowed for an increase in OR throughput over a several year period.(8) As noted in the accompanying
editorial (9), several important factors contributed to this success including (a) commitment of increased staff (both
anesthesiology and nursing, especially an extra surgical technician), (b) commitment of increased facilities (no new
ORs were built, but a place to set-up the equipment for total joint replacements was provided outside the actual OR),
and (c) patient selection bias (not all patients were done in the high volume rooms).

To put it all together, Cima et al. from the Mayo Clinic presented their experience at improving OR efficiency and
throughput.(10) I strongly recommend this paper as pre-reading for any committee or group that wants to do this at
their own institution and the committee or group should begin any discussion by looking at Table 1 of this paper
describing the 5 key work stream issues focused on in the improvement projects are
1. Unplanned surgical volume variation
2. Streamlining the preoperative process
3. Reducing non-operative time
4. Reducing redundant information collection
5. Employee engagement

Myth Buster Decision: Plausible. It is possible to improve OR throughput, but one must focus on the whole
perioperative experience, like described by Cima et al. If one only looks at turnover time, then this myth would
be busted!

Because anesthesia revenue includes time, anesthesia providers prefer longer surgeries.
Charges for anesthesia care differ from those of other medical specialties, in that time directly influences the amount
charged. For instance, surgeons bill for cholecystectomies using relative value units (RVUs) independent of case
duration of the surgery. In contrast, as noted above, anesthesiologists bill using ASA units, including time units.
Thus, anesthesiologists do bill more for longer cases than shorter ones.

At first glance it would appear to be in the best financial interests of an anesthesiologist to have longer cases because
he or she could bill more per case. Upon further analysis, it becomes clear that longer cases are not financially
beneficial. Anesthesiologists actually bill more providing care for many short cases than for a few long cases.

411
Page 3
Instead of examining billed units per case, one should evaluate the hourly billing productivity (defined as total ASA
units billed per hour of care = tASA/h).(11-14) This measurement is calculated by dividing the sum of total base
units and total time units by the total hours of care (for 15-minute time units, hours of care will equal time units
divided by 4). For instance, if one assumes that 8 billed hours of care are provided to 2 different surgeons, then the
difference in hourly productivity (tASA/h) is dependent solely on the basic units billed. The basic units billed for
these 8 hours is related to the number cases done and the base units per case. Therefore, for similar cases, a greater
number of cases that can be done in 8 hours will result in more billed units. In other words, the shorter the case
duration, the more advantageous it is for an anesthesiologist. Hence, there is actually an incentive to work faster!

A further incentive for wanting surgical cases to be shorter is that for most anesthesiology groups, the revenue from
the additional surgical time does not cover the staffing costs for that time. In particular, the cases that finish after
regular hours result in a net loss to the anesthesiology group due to the higher staffing costs.(14) That is the situation
of finishing the same number of cases, but finish at 6 PM or 5 PM. If the difference is delays, then it is a no-
brainer since any delay of a case is non-billable and the revenue is identical but the anesthesiologist is leaving the
hospital an hour later. On the other hand, lets examine the situation where the additional hour is intraoperative time
and hence an additional hour of billed time. So there is a difference in revenue, but only for an hour of billed time
and no difference in base units since the same number of cases are done. Therefore the difference is revenue can be
calculated by multiplying the conversion factor for one unit by 4 (assuming 15-min time units). Calculating a
weighted average depending on payer mix, the results are shown in Table 1 and range from $80 (poor payer mix) to
$176 (good payer mix).

Table 1: Hourly Revenue due to Time
Commercial MediCAID MediCARE Indigent Ave CF
Hourly Revenue
(CFx4)
CF $55.00 $15.50 $18.50 $0.00
Good 71% 2% 24% 3% $44 $176
Average? 44% 20% 32% 4% $33 $132
Poor 15% 35% 32% 18% $20 $80

The next step is to ask if this increase revenue is worth it. That is if the revenue covers staffing costs, then the
answer is yes, it makes sense to want to stay an extra hour. On the other hand, if the staffing costs are more than
the revenue, then it makes economic nonsense to want an extra hour.

We originally did using 2001 compensation data (14). Since then, compensation for both anesthesiologist and nurse
anesthetists have changed, I will use an estimate of staffing costs. Note that since the hour being considered is after
hours, there needs to be a increase costs. In studies, this increase is a multiplier of 1.75 to cover direct costs (actual
payments out) and indirect costs (cost of poor moral and need to recruit new members). Using an estimate of
working 44 weeks a year (that is 2 weeks holiday, 4 weeks vacation, and 2 weeks meeting) and an average of
working 50 hours a week, an estimate of an average anesthesiologist works 2200 hours per year. In Table 2, the
staffing cost per hour and per after hour is shown.

Table 2: Staffing Costs per Hour Estimate
Yearly Compensation Hourly
Cost
After-Hourly Costs (1.75x)
$400,000 $182 $318
$300,000 $136 $239
$250,000 $114 $199
$160,000 $73 $127

Comparing revenue expected (Table 1) for additional time with staffing costs (Table 2), it is easy to understand why
for most groups, additional time in the OR does not pay for itself, especially for cases that run beyond regular hours.

411
Page 4
Simply stated, from an anesthesiology perspective, the provider would rather go home sooner than work the
additional time (that is go home at 5 PM rather 6 PM).

Therefore, we do have an incentive to work faster and have an interest for the surgeon to work faster as well!

Myth Buster Decision: Busted.

Going from physician-only staffing to medical direction staffing will reduce staffing costs.

For a full discussion, please see the December 2010 ASA Newsletter article by A.Abouleish, S.Stead, and N.Cohen,
entitled Myth or Fact? Nurse Anesthetists cost less than anesthesiologists. Available on the ASA website,
www.asahq.org (15).

Costs can be compared either using Cost-effectiveness or Cost-minimization analysis. In a cost-effective
analysis, the underlying principle is that two items being compared do different functions or provide different
benefits. Therefore, a item that costs more might be the better option because of the additional benefits. In a cost-
minimization analysis, the underlying principle is that both items being compared do the same function or have the
same benefits. Therefore, the best option is the lowest cost item.

In the case of staffing models, the correct analysis should be cost-effectiveness analysis because physicians
(anesthesiologists) can provide additional functions and expertise than advanced nurse practioners (CRNAs). These
include consultations, providing independent medical care and expertise, call and evening duties, additional training,
acute pain and chronic pain expertise, and management of postoperative patients as well as medical staff committee
membership work. In addition, in all states, physicians can work independently which allows for more efficient
staffing in remote settings. Finally, in academics, physicians can provide clinical and didactic educational duties of
residents. The full discussion of this analysis is beyond the time allowed in this presentation.

On the other hand, if the move from physician-only staffing to medical direction results in more costs than a cost-
minimization analysis would show this. Hence, in any situation, the first thing is to do a cost-minimization.
Unfortunately, this is often done incorrectly. Simply comparing costs of providers by yearly compensation will lead
to inaccurate conclusions of staffing costs. On average, an anesthesiologist works 55 hours per week clinically, and
a CRNA works 40 hours a week clinically. Further, the additional 15 hours the physician works is done after regular
hours (evenings, nights, and weekends) which needs to valued per hour more than work done during regular hours.

Myth Buster Decision: Busted. Simply moving to medical direction staffing model does not necessarily mean
reduction in staffing costs.

Using per provider (aka FTE) measurements allow for accurate benchmarking of
productivity.
Hospital administrators or medical school deans who make this statement are mistakenly trying to apply outpatient
clinic logic to anesthesia staffing. For instance, the administrator might use 30 patients a day as a benchmark for
how many patients a pediatrician should see in one day. Thus, if there are 300 patients to be seen each day, then one
needs 10 pediatricians to staff the clinic each day.

Unfortunately, as anesthesiologists well know, this logic does not work for determining staffing needs for operating
rooms. The primary determinants of the number of anesthesia providers needed each day for a particular department
are a) the number of clinical sites or ORs to be staffed; b) the staffing ratio (i.e., concurrency); and c) the numbers of
persons both on-call and post-call.(16) What is not a direct determinant of anesthesia staffing is any type of
productivity benchmark. Simply put, if the administrator wants the anesthesiology group to cover 20 ORs, then the
group will need the same number of providers whether the cases finish at noon or 3 PM.

In addition, the logic applied by the administrator in this situation compares anesthesiology group productivity using
per anesthesiologist (i.e., per FTE or full time equivalent) measurements. However using per FTE

411
Page 5
measurements to compare anesthesiology groups with different staffing ratios leads to inaccurate conclusions.(17)
An example in see when comparing a physician-only group and a group that uses anesthesia care team model
(medical direction). When comparing tASA per FTE, the medical direction groups appears to be more productive.
But when the comparison is done by per OR site, one finds that the physician-only group is identical to the
medical direction group. (See Table 3) Administrators can more meaningfully compare anesthesia care done by
groups (or by hospitals in which they work) by using tASA/hr and per OR site measurements.(12,18-19)

Table 3. Comparing Group Productivity
Physician Only Medical Direction
Cases
Per FTE 907 1653
Per OR 933 915
tASA
Per FTE 8,769 16,647
Per OR 9,157 9,323
tASA = total ASA units per FTE, from MGMA 2011 Cost Survey of Anesthesia Groups

Myth Buster Decision: Busted. Using per FTE measurements will lead to misleading conclusions if there
are differences in the staffing models/ratios.

References
1. Dexter F, Macario A. Decrease in case duration required to complete an additional case during regularly
scheduled hours in an operating room suite: a computer simulation study. Anesth Analg 1999;88:72-76.
2. Dexter F, Abouleish AE, Epstein RH, et al. Use of operating room information system data to predict the impact
of reducing turnover times on staffing costs. Anesth Analg 2003;97:1119-1126.
3. Overdyk FJ, Harvey SC, Fishman RL, Shippey F. Successful strategies for improving operating room efficiency
at academic institutions. Anesth Analg 1998; 86;896-906.
4. Cedan JC, Good M. Interdisciplinary work flow assessment and redesign decreases operating room turnover
time and allows for additiona caseload. Arch Surg 2006; 141:65-69.
5. Sandberg WS, Daily B, Egan M, Stahl JE, et al. Deliberate perioperative systems design improves operating
room throughput. Anesthesiology 2005; 103:406-418.
6. Hanns R, Buttgereit B, Tonner PH, Bein et al.. Overlapping induction of anesthesia: An analysis of costs and
benefits. Anesthesiology 2003; 103:391-400.
7. Torkki PM, Marjamaa RA, Torkki MI, et al.. Use of anesthesia induction rooms can increase the number of
urgent orthopedic cases completed within 7 hours. Anesthesiology 2005; 103:401-405.
8. Smith MP, Sandberg WS, Foss J, et al.. High-throughput Operating Room System for Joint Arthroplasties
Durably Outperform Routine Processes. Anesthesiology 2008; 109-25-35.
9. Abouleish AE. Increasing Operating Room Throughput: Just Buzzwords for This Decade? Anesthesiology
2008; 109:3-4.
10. Cima RR, Brown MJ, Hebl J et al. Use of lean and six sigma methodology to improve operating room
efficiency in a high volume tertiary care academic medical center. J Am Coll Surg 2011;213:83-94
11. Abouleish AE, Prough DS, Zornow MH, et al.. The impact of longer-than-average anesthesia times on the
billing of academic anesthesiology departments. Anesth Analg 2001;93:1537-43.
12. Abouleish AE, Prough DS, Barker SJ, et al.. Organizational factors affect comparisons of clinical productivity
of academic anesthesiology departments. Anesth Analg 2003;96:802-812.
13. Abouleish AE, Prough DS, Whitten CW, Zornow MH. The effects of surgical case duration and type of surgery
on hourly clinical productivity of anesthesiologists. Anesth Analg 2003;97:833-838.
14. Abouleish AE, Dexter F, Whitten CW, et al. Quantifying net staffing costs due to longer-than-average surgical
case durations. Anesthesiology 2004;100:403-412.
15. A.Abouleish, S.Stead, and N.Cohen. Myth or Fact? Nurse Anesthetists cost less than anesthesiologists. ASA
Newsletter 2010 (December);74:30-32
16. Abouleish AE, Zornow MH. Estimating How Many Anesthesia Providers Do Our Group Needs? American
Society of Anesthesiologists Newsletter 2001;65:14-16.

411
Page 6
17. Medical Group Management Association. Cost Survey of Anesthesia Practices (2011 Report Based on 2010
Data). Engelwood, CO.
18. Abouleish AE, Prough DS, Whitten CW, et al. Comparing clinical productivity of anesthesiology groups.
19. Abouleish AE, Prough DS, Zornow MH, et al. Designing meaningful industry metrics for clinical productivity
for anesthesiology departments. Anesth Analg 2001;93:309-312.

Disclsoure
ECG Consultants, Consulting Fees

415
Page 1
Ethics in the Real World
Jeffrey Jacobs, M.D. Weston, Florida
Bioethics vignettes classically involve end-of-life, consent, and Jehovahs Witness challenges, but there are many
other situations that affect the practicing anesthesiologist. Some of these topics involve clinical practice, some deal
with professional relationships, and others revolve around national and political issues. The unique feature of these
is their removal from the usual doctor-patient interaction. The goal of is to outline two of these unusual bioethical
issues and help formulate a strategy for addressing them.
Protecting the Patient from Incompetence
How many times has an anesthesiologist heard the question, my surgeon is good, right, coming from a
preoperative patient? What happens if the answer is no? This section will explore the issues that surround the
answer to this question.
Importance
In this era of health care reform, one of the missing pieces of the puzzle from the physicians perspective is
tort reform: i.e.: medical malpractice reform. In fact, the American Medical Association produced a white paper
regarding the topic
16
. One of the sticking points with tort reform is the claim by personal injury attorneys that the
public needs to be protected from bad doctors. The claim is that physicians do a poor job of policing themselves.
Just as important is the idea of patient protection from these subpar physicians. It is indisputable that
anesthesiologists have led all other medical specialties in the category of patient safety initiatives. There is no
reason that safety stops with technology, physiology, and pharmacology.
Epidemiology
Is there a problem with self-policing in the house of medicine? In 1998, more the 4500 medical
malpractice cases were filed against physicians in Texas
17
. Seven hundred fifty resulted in payments. Of the closed
claims, only 121 were investigated by the state board of medicine. Of those cases investigated only three resulted in
discipline (Figure 2). Over a 5 year period in Texas, there were 18 medical license revocations, but none due to
medical errors. In Minnesota over a 20 year period, of the 35,000 doctors with five or more malpractice claims
against them, only 13% were disciplined by the state
18
. In Florida over a 12 year period, of the 23 doctors with TEN
or more judgments against them, only 12 were disciplined by the State
19
. In the August 10, 2011 edition of the LA
Times, the lack of physician discipline was a lead story
20
.
According to the National Practitioner Data Bank, 5% of the doctors account for more than ! of all
malpractice payouts. Furthermore, there is no interstate mandatory data sharing. In other words, one physician
could practice terribly in one state, lose his license, move to another state and start all over. Additionally, nearly !
of doctors have witnessed a serious medical error but have not reported it
21
. Its possible the attorneys have a valid
point (Figure 3).
Ethical Discussion
Considering the above information, is there an ethical obligation to protect patients from bad physicians?
According to the AMA, the answer is yes. Code E-9.031 addresses the requirement to report impaired, incompetent,
or unethical colleagues
22
.The principle of beneficence dictates that in order to do whats in the patients best
interestan incompetent physician should be reported. At a minimum, a patient should be protected from a physician
who is working above his/her skill level. To protect society from a dangerous physician, the principle of utility is
invoked. Whose happiness and safety is more important: the incompetent physicians or societys? The principle of

415
Page 2
nonmaleficence dictates that a physician must not do harm to patient. Undoubtedly, there is compelling ethical
evidence to support protecting patients from an incompetent physician.
One of the finest examples of protecting patients on ethical grounds came from the Manitoba Pediatric
Cardiac Surgery Inquest
23
. The anesthesia group of the only hospital providing pediatric cardiac surgery in the
Province of Manitoba, Canada recognized that the new (and only) heart surgeon was taking much longer on most
operations than the norm, making more intraoperative errors, and his patients were suffering significant morbidity
and mortality. The cardiac group went to the chief of their anesthesia group and ultimately to the hospitals chief
with this information and with their refusal to provide services to this surgeon. A moratorium was placed on the
program, and an inquest was held reviewing all of his cases. His care was deemed substandard, and he was
mentored with a contraction of his privileges. When his bad outcomes continued, he was fired. This group of
anesthesiologists had nothing to financially gain from this, and quite possible stood to suffer a significant financial
loss, yet they opted for patient protection.

Barriers
Despite the undeniable ethical justification for protecting patients, it is rarely done. Why does this not
happen with more frequency? Some quote the Golden Rule: do unto othersMany believe that something bad will
eventually happen to every provider including themselves, and therefore they would want the benefit of the doubt.
Others plead ignorance stating that they werent present or dont have all of the facts. Many claim that the outcome
to the patient will not change, and therefore why go through all of those unpleasant steps for nothing. Some are
afraid they might become a target as a whistleblower and this could cause career suicide. Courageous anesthetist
Stephen Bolsin from England spent five years battling the unsatisfactory performance of the pediatric heart surgeons
at the Bristol Royal Infirmary. Despite two surgeons and the chief executive being found guilty of serious
professional misconduct, Dr. Bolsin moved to Australia after being ostracized by the local medical community.
Since that time, the United Kingdom passed a new law protecting whistleblowers
24
. While these are all theoretical
reasons, there are safeguards in place to protect physicians who take the high road. More importantly, there are
legal precedents that protect reporting physicians.

Legal Discussion
From the institutional point of view, it is a breach of duty for a hospital to permit a physician on its staff
that the hospital knows or should know is negligent. Additionally, a credentialing body must truthfully respond to
inquiries about a practitioner. In KadlecMedicalCenter v. Lakeview Anesthesia Associates
25
, the group of
anesthesiologists lost a lawsuit when they failed to fully answer a credentialing inquiry by a new hospital. The
group had terminated a prior anesthesiologist for failing to respond to his pager and diversion of a controlled
substance, but when questioned about his competence, they only responded that he was a former employer and could
not supply the other information due to a large volume of requests. This anesthesiologists intraoperative
impairment resulted in brain damage to a patient under his care.
When protecting patients, are anesthesiologists protected from litigious surgeons? In one of the earliest
legal cases addressing this topic, Locksley v. Anesthesiologists of Cedar Rapids
26
, a group of anesthesiologists
refused to continue providing anesthetics for a specific neurosurgeon. His operations included wrong-sided
procedures, clipping incorrect vessels, and multiple bad outcomes. Despite peer-review by two other hospitals
finding him not medically incompetent, the group refused to work with him. The neurosurgeon sued the group for
putting him out of business, but the Supreme Court of Iowa found in the anesthesiologists favor.
In one landmark case, Mansmith v. Hameeduddin
27
, a primary care physician referred a patient with chronic
back pain and a herniated disc to a spine surgeon. The spine surgeon operated on the wrong level. The patient
returned with continued symptoms, and despite noticing the discrepancy about the MRI findings and the operative
report, did not inform the patient, but instead sent the patient to a pain specialist. After a lumbar epidural steroid
injection, the patient developed sepsis from an abscess, and ultimately died. The primary care physician lost the suit
for failing to notify the patient of the wrong-site surgery and failing to protect the patient from further harm.

State Boards
The purpose of state medical boards is to ensure the quality of licensed practitioners to the public. One of
their rules is often the demand that physicians police themselves and their colleagues. In Florida, the Board of
Medicine requires that failure to report to the Department of Health any person who the licensee knows is in
violation of this chapter [Ground for Disciplinary Action]
28
can result in disciplinary action. In other words, if a
licensed physician observes another licensed physician committing malpractice and fails to report him/her, the
observer can be punished. While this sounds ideal, over a 14-year period, only four doctors were punished under

415
Page 3
this rule, and this infraction was always grouped with more serious charges. No physician has ever been sanctioned
solely for this. Most states have rules similar to Floridas with similar experiences.

How to Report
Before reporting someone, it is crucial to discriminate between medical incompetence and a bad outcome.
If true medical ineptitude exists, reporting should be factual, objective, and unemotional. There are many options of
where to report, and the dynamics of each practitioners institution should be taken into account when deciding.
Possibilities include reporting to the chief of anesthesia, administration, or the credentialing department. If there is a
hostile environment, anonymous reporting to the State Medical Board is another option. There is always the
possibility of retribution, but the law usually prevails. In perhaps the most egregious example of this, Winkler
County Texas v. Anne Mitchell
29
, a nurse reported a physician to the State Medical Board for falling below the
standard of care in many instances. In the past, the physician had successfully treated both the county sheriff and
the local district attorney (DA), and in a cruel twist, the DA charged the nurse with misuse of official information.
Unsurprisingly, the nurse was acquitted.
The goal of reporting incompetence should never involve personal retribution, business-related issues, or
getting rid of someone. The objective should be to protect future patients from someone who is potentially
dangerous. Ideally, with remediation, refresher courses, and further education, the incompetent physician can be
reinstated to full practice. If not, a limitation of privileges is another viable and reasonable option. A license
revocation should be the last resort.

Summary
There are compelling ethical reasons to protect patients from medical incompetence. Additionally, there is
case law that suggests this act is required. Furthermore, there are closed cases that adjudicate on the side of
protecting those who protect patients. The role of the anesthesiologist is not just limited to protecting a patient
during an operation or procedure, but sometimes extends to guarding future patients before they even get through
the door.

Practical Considerations with Drug Shortages

Anesthetic drug shortages have become widespread over the past several years, and these shortages have
impacted nearly every practicing physician at one time or another. The causes of drug shortages have been
explained by everything from civil war in the region from where the raw materials come to misguided legislation
leading to a failed market. Whether the cause is either of these, both of them, or due to factors completely unrelated,
most physicians are only concerned with, how do I deal with these shortages when it comes to patient care? There
are many facets to shortages when it comes to clinical work, patient care, and simply acting as a responsible
physician.

Is it our responsibility to worry about shortages?
Drug shortages affect the way we care for our patients to such an extent that some may refer to shortages as
a public health crisis. In many situations we are forced to use medications with which we are not accustomed to use,
and in some circumstances, we need to use medications that may result in less than optimal outcomes for our
patients. There is no question that anesthesiologists have an ethical responsibility to participate in the
development of solutions to this societal problem.

Do we always have to provide an anesthetic if a drug shortage might negatively impact the patients outcome?
Of course not. Part of our duty as a physician is to protect the patient by using sound medical judgment to
decide appropriateness of care. As an extreme example, suppose the facility in which one practiced was out of
oxygen. There would be no question that business as usual would stop until the situation was rectified. The effects
of some drug shortages can be mitigated with alternative medications, but some medications do not have a suitable
substitute. Its up to each individual provider, working with the surgeon or proceduralist, and taking into account
the patients procedure and health status to decide whats safe. Anesthesiologists, as well as surgeons and other
proceduralists, should consider postponing an elective procedure when the risks of proceeding might
outweigh the risks of using medications that are alternative to those in short supply or unavailable.

415
Page 4
Assuming there are drug shortages in my operating room, do I need to tell the patient about this?
Some medication shortages may have a definite and profound impact on the patients experience. For
example, some medications are associated with an increased risk of postoperative nausea and vomiting as compared
with others. Some medications have a longer half-life, which might lead to greater than normal effects. On the
other hand, some medications may be seamless substitutes for the usual drug. In general, if the anesthesiologist
judges the risk of increased morbidity or mortality by using alternative medications to be negligible, then
there is no need to discuss this issue when obtaining informed consent. However, if the anesthesiologist
judges the added risk to be significant, then the discussion of alternative plans should be part of the informed
consent process.

If my patient suffers as the result of a medication shortage, should I keep it to myself?
Part of the solution to drug shortages comes from the ability to track bad outcomes and complications due
to the lack of a medication or from the use of a substitute. If nobody were to report bad outcomes, there may be a
misperception that the shortages are having no impact on patient safety. One such place to report is to the
Anesthesia Quality Institute (AQI), which is a Federally Designated Patient Safety Organization. This means
anything reported to them is anonymous, confidential, and not discoverable based on Federal law
(https://www.aqihq.org/airs/airsIntro.aspx). In general, the collection of adverse events occurring as a result of
drug shortages provides important information useful in the pursuit of a solution. Anesthesiologists should
report these events to the appropriate entities for this purpose.

Is there anything I can do to make my supply last longer?
The first thing every anesthesiologist should evaluate is his/her normal pattern for medication usage. In the
face of shortages, it may be reasonable to question whether all possible emergency drugs need to be drawn into
syringes (as opposed to having them available in their original packages). It may be reasonable to use smaller vials
of medications, when available, to minimize wastage. It is never reasonable, however, to create your own rules
when it comes to dividing ampules or bottles of medications in order to share the drugs among multiple patients.
There are strict guidelines for how this should be accomplished, and if the rules do not make sense, anesthesiologists
should advocate for amending them. In summary, in the face of specific drug shortages, anesthesiologists should
reassess customary practice patterns of drug usage to minimize drug wastage and safely maximize any
limited supply.

Could I have contributed to the problem?
Theoretically, yes! Because of the training an anesthesiologist undergoes (which includes medical school),
anesthesiologists have the understanding and ability to develop suitable and safe alternative plans when a medication
goes into a short supply. While this is appreciated by the institution and allows for safe patient care, it downplays
the actual problem. For example, if drug x is in short supply, so anesthesiologists decide to substitute drug y,
eventually drug y could undergo a shortage. What if there is no substitute for y? Therefore, flexibility and
adaptability in patient care may obscure the reality of potential harm created by drug shortages and should
not be a substitute for pursuing a permanent solution.

Must I deal with this issue alone?
Of course not. You should work in partnership with all involved stakeholders to develop safe plans within
your institution as well as discuss solutions with your professional society and your elected officials.
Anesthesiologists should collaborate with colleagues, pharmacists, appropriate committees, institutional
administrators, professional societies, and government agencies to manage issues, policies, and procedures
related to drug shortages.

Is it okay to order lots of extra medications that are in short supply so my facility has enough?
Probably not. While having plenty of medication x is great for one institution, if that drug is in short
supply, then it follows that other facilities will not have any, which could potentially inconvenience or harm other
patients. The distinction between preparedness and hoarding with regard to medications is unclear. In general, if
you have boxes of a medication stored away while your competitor has none, its unethical. Some might say, thats
good business, but because this particular business involves peoples health, it crosses a line. In summary, while
stockpiling medications may be beneficial for a given institution, excessive accumulation and storage of drugs
can result in shortages to other institutions and may be unethical.

415
Page 5

Should my medical societies be doing anything about this?
Yes. Because of the complexity of the issue and the widespread affect drug shortages have, professional
societies are in the unique position to identify and advocate for statutory and legislative changes that will ameliorate
this problem. One significant issue is that current rules exist that, while likely well-intended, are not evidence-
based. Because of the intellectual capital a professional society holds, rational alterations in rules and laws may be
possible. In general, professional medical organizations should identify statutes, regulations, and guidelines
that impact the adequate supply of medications, and to advocate for appropriate evidenced-based changes
that would optimize their availability.

Summary

Drug shortages are a complex, but critical problem facing health care, and there are no simple solutions.
However, anesthesiologists are uniquely positioned to aid in the solution both on the front line as well as behind the
scenes.

Disclosure

421
Page 1
Important Health Care Industry Megatrends and Implications for Anesthesiologists
Thomas R. Miller, M.D. Washington, D.C.
Introduction
It seems that one of the primary reasons to predict the future is to build a compelling case for (or against) change.
The primary problem with predictions is that humans, even experts, tend to be very poor at them. For example,
Philip Tetlock conducted an experiment in which 284 experts made 82,361 predictions about political and economic
trends.
1
In a summary of Tetlocks findings, Donaldson et al. noted the following trends:
simple extrapolation using mathematical models typically does better than human predictors,
education and popularity increase the predictors confidence but not their accuracy,
prognosticators over predict change and under predict the status quo,
extremists predict worse than moderates, and
some people predict better than others, and their superiority is not limited to their area of expertise.
2
Even relatively short five-year predictions by academic surgeon leaders on the growth of minimal invasive therapy
(MIT) gave evidence to our poor prognostic abilities and the challenges faced. Bloom and colleagues found that the
experts overestimated the rate of MIT diffusion and its effect on length of stay for most operations and
underestimated the extent of diffusion for two procedures.
3
The authors note that unexpected consequences occur
when one or a few parts of complex systems are changes
4
an observation relevant for almost all predictions about
the health care industry.
When it comes to the future practice of anesthesiology, however, excellent groundwork has been laid in the past five
to eight years by Kapur,
5
Miller,
6
and Warner
7
. Each of these leaders has described how anesthesiologists might
manifest the oft-quoted saying that the best way to predict the future is to create it. The need for anesthesiologists to
remain broadly capable, be willing to transform, and move aggressively into the new opportunities
8
is
certainly motivated by the likely future of health care delivery; and, importantly, this call to action is not likely to
waiver regardless of the plausible futures that lie before us.
Economics will be the Key Driver of Change
In 2014, national health expenditures (NHE) are projected to rise 7.4%, or 2.1 percentage-points faster than in the
absence of reform, as coverage expansions from the Affordable Care Act (ACA) are expected to result in 22 million
fewer uninsured people. Because the newly insured populations are anticipated to be relatively younger and
healthier than currently insured individuals they are expected to devote a greater proportion of their spending to
prescription drugs and physician and clinical services, rather than inpatient hospital stays.
9

Between 2014 and 2021, NHE are projected to grow at an average annual rate of 6.2%, reflecting the net effect of
the aging of the population, provisions of the ACA, and improving economic conditions. Figure 1 depicts NHE and
NHE as a percentage of U.S. Gross Domestic Product (GDP) between 2006 and 2021.
10

Economic forecasts can certainly be off the mark. In 1992, NHE in the U.S. were projected to reach $7.8 trillion
and represent 26.5% of the GDP by 2020.
11
Current forecasts for 2020 are substantially less, at $4.5 trillion and
18% of the GDP.
12
Regardless of the forecast du jour, continued economic pressures will foster disruptive
innovation and change in the health care industry.

421
Page 2

Demographics and Health Status Drive Demand for Medical Care

Did you hear the one about the Baby Boom? Of course you have; the baby boomers are persons born roughly
between 1946 and 1964. Economists and demographers have been tracking the baby boomers since the 1970s and
have tried to estimate their impact on the U.S. economy and health care system. Figure 2 depicts the 20-year spike
in births after World War II associated with the baby boomers.
13

In 2010, an estimated 10 million baby boomers lived with multiple chronic conditions. By 2020, this number is
expected to rise to almost 24 million and by 2030 to 36 million.
14
By 2030, treatment costs for preventable obesity-
related diseases are expected to add $48 billion to $66 billion to current costs that are estimated between $147
billion and $210 billion. Related economic productivity losses are estimated to be between $390 billion and $580
billion by 2030.
15

Figure 1. National Health Expenditures (NHE; billions) and NHE as percentage
of Gross Domestic Product, U.S., actual and projections 2006 2021.
Source: Center for Medicare & Medicaid Services, Office of the Actuary.
Figure 2. Live births and fertility rates: U.S. 1920-2010.
Source: CDC/NCHS, National Vital Statistics System.

421
Page 3
The Quest for Value will Continue, Relentlessly

Value is often referred to as that elusive relationship between quality and cost. Rewarding value-based services is
the goal of myriad new payment models being tested by the Centers for Medicare & Medicaid Services (CMS),
private payers, and integrated delivery systems. The March 2013 Report of The National Commission on Physician
Payment Reform simply and emphatically states, Our nation cannot control runaway medical spending without
fundamentally changing how physicians are paid.
16

Conrad and colleagues recently described eight early stage projects testing value-based payment but were unable to
report conclusive findings on the effectiveness of these models. There identified, however, a few key lessons and
implications: (1) the process of payment reform is ill-defined, (2) delivery system design can facilitate payment
reform, (3) accurate and timely data are critical, and (4) design and implementation need to be undertaken with the
objective of developing evidence of effectiveness of the new payment model.
17

As we look to the future, there will be a few key trends concerning payment, quality, and value that are probably
sure bets:

A variety of payment models will be implemented and many will succeed. Despite the popular belief that fee-
for-service (FFS) medicine will see its demise, FFS will continue to play an important role to encourage
productivity among providers and facilitate systems for cost accounting and analysis of resource use.
A primary objective of the changing payment methods is to shift the financial risk and responsibility from the
payer to the provider; while not going too far as to make the payer superfluous.
Defining quality will continue to be troublesome. Data will improve, but standardization and sharing across a
health system will continue to be problematic. Risk adjustment methodologies will advance; however, none will
satisfy all subsets of providers and poor adjustment will continue to be a rationale for why some providers
have lower quality metrics reported compared to other providers.
The patient is becoming more knowledgeable about health care and provider quality, or at least more inquisitive;
and this may impact the demand for and productivity of certain types of providers.
18

The value formula will not be unraveled in the next 10 years; however the quest must continue. For anesthesiology,
defining value will be even more challenging and the demand for joint accountability for quality and costs with the
surgeons and other care team members will increase substantially. In any event, Value in Health Care will be a
topic at ANESTHESIOLOGY 2025.

Horizontal and Vertical Integration will Continue and Mature, Along with Some Dis-Integration

Coordinated care and integrated (bundled) payment will motivate continued integration among providers and further
development of integrated delivery systems. Hospitals will continue to acquire health plans and take on insurance
roles; health plans will buy physician groups; physician groups will get larger; mini-Kaisers will develop, and
merger activity among hospitals and health systems will continue. These headlines are not too dissimilar as those in
the early 1990s, amidst capitation-phobia and preceding the Health Security Act of 1993 submitted by President
Clinton. Accountable Care Organizations (ACOs) are for the most part Accountable Health Plans with the
providers, rather than the payers, theoretically in charge. This push towards integration and accountability is
supposed to work this time because of better data and because the focus is on altruistic providers rather than
greedy health plans. And, as in the 1990s, not all integration efforts will succeed or even last long-term.

Regina E Herzlinger, a professor at the Harvard Business School, believes that ACOs and Patient-Centered Medical
Homes (PCMHs) are unlikely to succeed.
19
..The primary reasons are that electronic health record systems dont talk
(well) with each other and Health Information Exchanges are largely a dream. Organizational core competencies
required to manage a population, as is necessary for an ACO, are quite different than the competencies needed to
manage patients (i.e., a sick subpopulation). ACOs centered on provider-based health systems must undergo a
substantial culture change.

421
Page 4
Still, moving in the direction of an ACO-type model(s) is probably warranted. And the potential disappointment in
primary-care focused ACOs and PCMHs may prove to be a stimulus for specialty-based integration efforts to
facilitate initiatives such as the perioperative surgical home,
20
Enhanced Recovery After Surgery (ERAS),
21
and
other programs focused on improving quality of care and efficiency of delivery for one or more specific types of
surgical patients.

Forecasting Manpower Requirements and Technology Advances is Always Tricky

Many have predicted a shortage of physicians; often exacerbated by the ACA (Figure 3).
22
Economist Uwe
Reinhardt of Princeton describes the complexity and nuanced methodologies intrinsic in forecasting the supply of or
demand for physicians.
23
He not only questions what is actually meant by a shortage but whether the process of
forecasting manpower needs is worth the trouble.
24

Indeed, one must proceed cautiously with any forecast and understand the potential implications for, and
interpretations by, policymakers and other external stakeholders. For instance, suppose we project a shortage of
anesthesiologists. If we are confident in these forecasts, then such knowledge should inform graduate medical
education resource needs. However, such a forecast also paves the way for labor and technological substitution to
provide anesthesia services to solve the physician shortage problem. On the other hand, if we project a surplus of
anesthesiologists, an economist might argue that the market price (anesthesiologists compensation) is too high
and clearly above the equilibrium price.

Technology predictions may be more amenable to the crystal ball, and technology-related forecasting errors in either
direction are likely relatively innocuous. As described previously, experts tend to overestimate the impact (or its
timing) of new technology. Still, articulating assumptions about what new technology may be coming on line and
how it will impact the practice of anesthesia is a worthwhile exercise. For example, what are the implications of
increasing rates of outpatient hip and knee replacement surgery; or of medical devices to facilitate patient-controlled
analgesia; or the use of robotic intubation?
25

Figure 3. Projected physician shortages with and without ACA.
Source: Kirch DG. Physician workforce projections in an era of health care reform.
Annu Rev Med 2012, 63:435-445; p. 436.

421
Page 5
Will advances in information technology (IT) and big data solve the challenges of measuring and rewarding value
in health care?
26
Technology is but one important consideration; others include organizational structure,
infrastructure capabilities, interpersonal relationships, and market dynamics. Therefore, the answer is likely to be a
resounding No; however, there will continue to be advances and improvements in IT and the use of big data; and
we can look forward to additional discussions on this topic during ANESTHESIOLOGY 2025.

So What? From Group Think to Individual Relevance

For an individual or organization to transform or engender effective change, at least three conditions must be met.
First, there must be (perceived) a compelling reason to change; second, there must be a common vision of the
direction of change; and third, the individual or organization must have the capacity to change. Clearly, economics
will be at the forefront in driving future change in the practice and role of anesthesiology. Achieving a common
vision and developing the capacity to change will be an individual or organization-specific journey.

Kapur highlights the need for anesthesiologists to expand their portfolio of skills and prepare for a future
diversified practice model.
27
Seim and Sandberg urge anesthesiologists to create more headroom between costs
and revenues to sustain the academic vigor and creativity required to create better clinical practice.
28
Similarly,
surgeons
29,30
and hospitalists
31
will seek to take leadership roles in the transformation of surgical care delivery and
payment models.

Rather than focusing on what anesthesiology should do or what anesthesiologists in general need to do, the
consideration of and response to major health care industry trends should first be addressed by the individual
physician. In essence, each physician should undertake an individual professional strategic planning exercise. With
thoughtfulness and rigor, each physician should develop a personal white paper and answer the following questions:

Is there a compelling call to action? What are my planning assumptions about the future that will drive change?
If the demand for anesthesia services dropped 20% in the next five years, how well am I positioned? What
should or would I do differently tomorrow?
If payment (per unit) for anesthesia services dropped 20% in the next five years, how well am I positioned?
What would or should I do differently tomorrow?
Do I have the breadth of clinical skills that I think will be required in five years? If not, should I acquire them;
and, if so, how?
How relevant do I think leadership skills will be over the next 5 to 10 years for success? What leadership
qualities do I have? What qualities do I need to strengthen to be an exceptional leader within my health care
organization?
How will I increase my value to my health care organization? To my employer? To the payers?

421
Page 6

References

1. Tetlock P: Expert political judgment: How good is it? How can we know? Princeton University Press, 2009.
2. Donaldson H, Doubleday R, Hefferman S, Klondar E, Tummarello K: Are talking heads blowing hot air? An
analysis of the accuracy of forecasts in the political media. (2011) p.5. Retrieved May 12, 2013 from
http://www.hamilton.edu/documents/An-Analysis-of-the-Accuracy-of-Forecasts-in-the-Political-Media.pdf
3. Bloom BS: Surgeon predictions on growth of minimal invasive therapy: the difficulty of estimating technologic
diffusion. Health Policy 2000, 54(3):201.
4. Ibid. p. 202.
5. Kapur PA: The future practice of anesthesiology. CSA Bulletin Summer 2008; 30-35.
6. Miller RD: Anesthesiologys choices for the next century. ASA Newsletter. 2005 Special Commemorative
Issues. http://www.asahq.org/Newsletters/2005/Centennial/miller100.html
7. Warner MA: Who better than anesthesiologists? The 44
th
Rovenstine Lecture. Anesthesiology 2006; 104:1094-
1101.
8. Kapur PA: The future practice of anesthesiology. CSA Bulletin Summer 2008; 30-35, p. 35.
9. Centers for Medicare & Medicaid Services. National health expenditure projections 2011-2021. CMS Office of
the Actuary. Retrieved May 12, 2013 from http://www.cms.gov/Research-Statistics-Data-and-
Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/Proj2011PDF.pdf
10. Ibid.
11. Burner ST: National health expenditures projections through 2030. Health Care Financ Rev 1992, 14(1):1-29.
12. Centers for Medicare & Medicaid Services: National health expenditure projections 2011-2021. CMS Office of
the Actuary. Retrieved May 12, 2013 from http://www.cms.gov/Research-Statistics-Data-and-
Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/Proj2011PDF.pdf
13. Martin J, Hamilton B, Ventura S, Osterman M, Wilson E, Mathews T: Births: Final data for 2010. In: National
Vital Statistics Reports. vol. 61: U.S. Department of Health and Human Services, Centers for Disease Control
and Prevention, National Center for Health Statistics; 2012.
14. FCG and American Hospital Association: When Im 64: How Boomers will change health care. Retrieved May
12, 2013 from http://www.aha.org/content/00-10/070508-boomerreport.pdf
15. Voelker R: Escalating obesity rates pose health, budget threats. JAMA 2012, 308(15): 1514.
16. The National Commission on Physician Payment Reform: Report of the The National Commission on Physician
Payment Reform. 2013. Retrieved May 12, 2013 from http://physicianpaymentcommission.org/wp-
content/uploads/2012/02/physician_payment_report.pdf
17. Conrad D: A report on eight early-stage state and regional projects testing value-based payment. Health Aff
(Millwood) 2013, 32(5):998.
18. Shih YT, Tai-Seale M: Physicians perception of demand-induced supply in the information age: A latent class
model analysis. Health Economics 2012; 21:252-269.
19. Health Plan 2020: Herzlinger predicts ACOs, PCMHs will fail. December 4, 2012. Retrieved May 12, 2013
from http://www.managedcaremag.com/print/archives/1204/1204.healthplan2020_herzlinger.html
20. Vetter TR: The Perioperative Surgical Home: how can it make the case so everyone wins? BMC Anesthesiol
2013, 13:6.
21. Ren L, Zhu D, Wei Y, Pan X, Liang L, Xu J, Zhong Y, Xue Z, Jin L, Zhan S et al: Enhanced Recovery After
Surgery (ERAS) program attenuates stress and accelerates recovery in patients after radical resection for
colorectal cancer: a prospective randomized controlled trial. World Journal of Surgery 2012, 36(2):407-414.
22. Kirch DG: Physician workforce projections in an era of health care reform. Annu Rev Med 2012, 63:435.
23. Reinhardt UE: From physician glut to physician shortage. The New York Times. August 31, 2012. Retrieved
May 12, 2013 from http://economix.blogs.nytimes.com/2012/08/31/from-physician-glut-to-physician-shortage/
24. Reinhardt UE: Health manpower forecasting: the case of physician supply. In Health Services Research: Key to
Health Policy. E Ginzberg, Editor. 1991. Harvard University Press: Cambridge, MA. p.234-379.
25. Hemmerling TM: First robotic tracheal intubations in humans using the Keplar intubation system. British
Journal of Anaesthesia 2012, 108(6): 1011-1016
26. Groves P, Kayyali B, Knott D, Van Kuiken S: The 'big data' revolution in healthcare: Accelerating value and
innovation. Edited by McKinsey&Company , Business Technology Office; 2013.
27. Kapur PA: The future practice of anesthesiology. CSA Bulletin Summer 2008; 30-35, p. 35.

421
Page 7

28. Seim AR, Sandberg WS: Shaping the operating room and perioperative systems of the future: innovating for
improved competitiveness. Current Opinion in Anesthesiology 2010, 23:765-771.
29. Muoz E: National and surgical health care expenditures, 2005-2025. Ann Surg 2010, 251(2):195-200.
30. Leichtle SW: Physician leadership and the future of surgical practice. Bull Am Coll Surg 2012, 97(5):15.
31. Society of Hospital Medicine: 2013 Media Kit. Retrieved May 12, 2013 from
http://www.hospitalmedicine.org/Content/NavigationMenu/Media/MediaKit/SHM_MediaKit2013.pdf

Disclosure

422
Page 1
A Fire in the Operating Room: It Could Happen to You
Jan Ehrenwerth, M.D. New Haven, Connecticut
In the days when flammable anesthetic agents were frequently used, fire and explosion hazards were of paramount
importance to the anesthesiologist. Although most operating room personnel do not consider fires a major safety
hazard, in reality many fires occur in the operating room every year. It has been estimated by the ECRI (Emergency
Care Research Institute) that there are approximately 500-600 operating room fires every year in the United States.
About 10% of these produce serious injury to patients or operating room personnel. Therefore, it is incumbent upon all
those who work in the operating room to be aware of how to prevent fires and what to do if one should occur.
The Fire Triad
In order for a fire to occur, three elements must come together at the same time. These elements are known as the fire
triad. They include; (1) heat, or an ignition source; (2) fuel; and (3) an oxidizer. In the operating room, the heat source
is commonly the electrosurgical unit (ESU), a laser, or a fiberoptic light cord. There are many elements that can
provide fuel for an operating fire. These include paper drapes, plastics, gauze dressings, endotracheal tubes, the
patients hair, linens and gel mattress pads. The common oxidizers in the operating room are oxygen, air and nitrous
oxide.
A fire is actually the chemical reaction of fuel rapidly combining with oxygen with the resultant release of heat and
light energy. Prevention is clearly better than extinguishing a fire. Fires can be prevented by isolating the various legs
of the fire triad. This can be done by minimizing the amount of oxygen or nitrous oxide that is delivered to the patient.
It should be remembered that oxygen and nitrous oxide support combustion equally well. Therefore, a mixture of 50%
nitrous oxide and 50% oxygen is virtually the same as 100% oxygen. Oxygen and nitrous oxide are oxidizers and not
explosive gases. Examples of explosive gases are cyclopropane, hydrogen and methane.
Keeping heat sources away from flammable materials is another important safety precaution. It should be remembered
that an ESU tip remains hot for a few seconds after the instrument has been deactivated. Similarly, ends of fiberoptic
cables can retain significant amounts of heat after being disconnected from their light source. Therefore, it is important
to be careful where one places the end of a fiberoptic cord. Lasers should be immediately placed in standby mode and
ESUs placed in an appropriate holder when they are not in use. Finally, volatile liquids must be allowed to dry since
the vapors can be quite flammable.
There are many dangers from a fire. Obviously, heat can cause burns to the patient or operating room personnel. Of
great importance is that smoke from the fire can necessitate that the room be evacuated. Depending on what is burning,
toxic products can be given off by the combustion of various materials. Many of these products such as carbon
monoxide, ammonia, cyanide, isocyanates and hydrogen chloride are quite toxic. They can cause chemical and
physical irritation to the tracheal-bronchial system but more important, they can cause asphyxia.
Being prepared for a fire and knowing what to do if one should occur are key elements of a fire safety program.
Knowing the location of fire extinguishers and having fire drills will enable all operating room personnel to become
familiar with proper procedures. Operating room personnel should be familiar with the location of alarm boxes, gas
shut-offs, and fire extinguishers. People should realize that it is important to immediately call for help, decide who is
going to fight the fire, when it will be appropriate to leave the room and how to care for the patient during the fire. If
drapes are burning, they must be removed as most OR paper drapes are impervious to water. Therefore, the fire will
burn on the underside and dousing them with water will not extinguish the fire. Having sources of battery powered
portable lighting available is also extremely important.

422
Page 2
Types of OR Fires
Operating room fires can be classified into two types: those that occur in the patient and those that occur on the
patient. Fires that occur
in the patient would include airway fires such as ignition of an endotracheal tube or a fiberoptic bronchoscope or an
intra-abdominal fire. Fires occurring on the patient include ignition of drapes or surface fires that are fueled by
supplemental oxygen.

One of the ignition sources in the operating room is the laser. Laser is an acronym for Light Amplification by
Stimulated Emission of Radiation. The laser light is produced when energy is aimed at the "lasing medium". The
lasing medium then becomes the name of the laser. For instance, electrical energy aimed at carbon dioxide molecules
is a carbon dioxide laser. The light produced by a laser is known as coherent radiation. Coherent light can be focused
into very small spots with a very high power density.

There are a number of different types of lasers. These include the argon laser which is used in eye and dermatologic
procedures. The energy produced by this laser is absorbed by hemoglobin and melanin and has a tissue penetration of
0.5 to 2.0mm. The KTP (frequency doubled YAG) laser produces energy that is absorbed by hemoglobin and has a
tissue penetration of 0.5 to 2.0mm. The dye laser has wave lengths that are tunable for different applications. The
Nd:YAG laser has tissue penetration of 2-6mm and can be used for tumor debulking particularly in the tracheal-
bronchial tree. Its energy can be transmitted through a fiberoptic cable which enables it to be used in a "contact" mode.
The CO
2
laser produces energy that is absorbed by water. It is used where precision is needed and has negligible tissue
penetration. Also there is minimal heat dissipated to the surrounding tissues. The helium neon laser (He-Ne) is a very
low power laser. Its red light is used for aiming the CO
2
and the Nd:YAG lasers.

Fires in the Patient
The most serious fire in the patient is an endotracheal tube fire. Although the ET tube can be ignited by electrocautery,
it is more common for a fire to occur as a result of it being struck by a laser. Wolf and colleagues showed that the red
rubber, the polyvinyl chloride (PVC), and the silicone endotracheal tubes all have a flammability index of less than
25% oxygen. Therefore, these tubes are not appropriate when doing surgery in and around the airway.

Before specific laser resistant tubes were developed, many practitioners wrapped endotracheal tubes with various
kinds of foil or copper tape. Today, this is a dangerous practice and should be avoided. There are many complications
associated with wrapping tubes which include kinking of the tube and having unprotected parts of the tube exposed
where layers of tape fail to overlap. In the event that an endotracheal tube should be set on fire, it is important to
immediately disconnect the tube or the inspiratory hose from the anesthesia machine. This will usually result in the fire
going out since the oxidizer has been removed from the fire. Simultaneously the surgeon should remove the ET tube,
and saline or water poured into the airway. The patient is mask ventilated and then reintubated. Next, bronchoscopy is
performed so that the airway can be inspected and any pieces of foreign material removed. These fires can be quite
devastating as an endotracheal tube ignited by a laser with high concentrations of oxygen essentially turns into a "blow
torch" with resultant burns to the lungs, trachea, and esophagus.

Upper Airway Surgery
When anesthetizing patients for upper airway surgery, a number of anesthetic techniques are possible. One can use jet
ventilation either through a metal bronchoscope or a catheter inserted through the cricoid membrane. In this
circumstance, there is no tracheal tube in the airway to burn. However, the FIO
2
is not controllable as it is dependent
on a venturi mechanism that entrains room air which is delivered to the patient. Complications of this technique
include hypoventilation, barotrauma and aspiration. The surgery can also be performed using an endotracheal tube that
is specifically resistant to the type of laser being used. The tube should have two cuffs and they should be filled with
saline that has been colored with methylene blue. This allows the surgeon to know when one of the cuffs has been
ruptured.

If the carbon dioxide laser is being used, then the LaserFlex (Mallinkrodt) ET tube is an excellent choice. The tube
consists of a double cuff and a flexible metal shaft that is highly resistant to the CO
2
laser. This tube, however, is not
resistant to the Nd:YAG laser. If the Nd:YAG laser is to be used in the upper airway, then a special laser resistant tube
called Lasertubus (Rusch, Inc.) can be used. The Lasertubus consists of a soft rubber shaft that is covered by a
corrugated silver foil which is then covered by a Merocel sponge covering. The Merocel
TM
when moistened with
saline will consume laser energy if it is struck. It also dissipates the laser light and the silver foil prevents the laser

422
Page 3
light from penetrating the shaft of the tracheal tube. It is critical that the Merocel
TM
covering be kept moist at all times.
This tube also consists of a double cuff design. Only a portion of the tube is laser resistant and it is important that this
part of the tube always remains in the surgical field.

The electrocautery can also be a source of ignition during upper airway surgery. A typical example would be during a
tonsillectomy on a child with an uncuffed tracheal tube. The anesthetic mixture, which may contain oxygen and
nitrous oxide, can readily leak around the tracheal tube and be present in sufficient concentrations that the
electrocautery could cause a fire at the operative site. In these cases, it is recommended that oxygen be mixed with air
and the FIO
2
be kept as low as possible. The surgeon can also put wet pledgets around the tracheal tube; however, it
must be remembered that if the pledgets dry out they can also be a source of fuel for a fire.

Lower Airway Surgery
When doing surgery on the lower airway, the Nd:YAG laser is frequently employed. The surgeon usually passes a
laser fiber through the suction port of the fiberoptic bronchoscope. This bronchoscope may then be passed either
through a PVC tracheal tube or through a rigid metal bronchoscope. If the fiberoptic bronchoscope is passed through a
tracheal tube a PVC tube can be used. There is no special tube for this type of surgery. Indeed the fiberoptic cable
passes through the inside of the tracheal tube. Therefore, it is essential to keep the inspired oxygen as low as possible
(preferably <30%) and titrate the oxygen saturation to between 90-95%. Also, the endotracheal tube should be placed
just below the vocal cords so that the tip is as far away from the operative site as possible.

If the rigid metal bronchoscope is used, then obviously there is no tracheal tube in the airway. The patient is then
ventilated with a form of venturi which will entrain room air. Therefore, the inspired oxygen is not precisely
controllable. The FIO
2
will usually vary between 40-60%. It should be remembered that in either circumstance, the
cover of the fiberoptic bronchoscope is plastic and can easily burn especially in an oxygen enriched environment.

Laser Safety
There are other safety considerations when using the laser. Reflected laser light can cause retinal damage. The patient's
eyes should be covered with wet eye packs and all personnel in the room must wear goggles that are specific for the
laser being used. These goggles frequently have a color tint, which may make it difficult to monitor skin color
changes. Also, all windows should be covered with black window shades and warning signs should be posted on all
doorways to the operating room. There is also potential damage to the respiratory track from vaporized tissue which
may contain chemical toxins or virus particles in the laser "plume". It is recommended that special (high filtration)
masks be worn by OR personnel during these types of procedures.

Another place where a fire could occur in the patient is during laparoscopic surgery. Even though the abdomen is
inflated with CO2, after about 30 minutes of nitrous oxide anesthesia, the N2O can diffuse into the abdomen and reach
levels that could support combustion. Neuman et al studied this phenomenon and found that at 30 minutes the mean
nitrous oxide concentration was 36%. However, in certain patients, the nitrous oxide concentration was as much as
47%. Bowel gas contains two potentially flammable gases. These are methane and hydrogen. The reported maximum
concentration of methane in bowel gas is 56% and hydrogen 69%. 56% methane would require 47% nitrous oxide in
carbon dioxide to support combustion. Since that was the maximum concentration found in the study, this presents a
relatively small hazard. However, 69% H
2
will burn in concentrations of nitrous oxide of 29% or greater. Therefore, if
the surgeon should accidentally enter the bowel during laparoscopy which contained a high percentage of hydrogen, a
fire could occur. The nitrous oxide would support combustion, the hydrogen would be the fuel, and the electrocautery
would provide the heat source. Greilich et al reported a fire in which a tank of 14% carbon dioxide and 86% oxygen
was accidentally used to inflate the abdomen instead of pure carbon dioxide. When the surgeon activated the
electrocautery, a fire ensued. The pin index for tanks with 100% CO
2
is the same for any tank with greater than 7%
CO
2
.

Another kind of fire that occurs in the patient is the ignition of a tracheal tube during a tracheostomy. A critically ill
intubated patient will be receiving supplemental oxygen. A surgeon may use the electrocautery to enter the trachea.
This is an extremely dangerous practice since the tracheal tube is frequently in the field while supplemental oxygen is
being delivered to the patient. The ESU then provides a source of heat and a number of fires have resulted. Decreasing
the inspired oxygen would obviously be a safety factor; however, this may not be possible in this patient population.

422
Page 4
Also, unless the patient is ventilated with decreased inspired oxygen content for at least a minute, the higher
concentration of oxygen will continue to be present in the trachea. It is far better that the surgeon use a scalpel or
scissors to enter the trachea, instead of the ESU. This will greatly reduce the risk of a tracheal fire.

Fires on the Patient
The other type of operating room fire is one that occurs on the patient. Most commonly these are associated with
monitored anesthesia care (MAC) for head and neck cases where the patient is administered supplemental oxygen
either by a face mask or a nasal cannula. The surgeon then drapes the field such that there is a build up of 100%
oxygen under the drapes and in close proximity to the operative site. This oxygen, in certain circumstances, can then
diffuse directly into the operative site so that when the electrosurgery pencil or the laser is used, a fire can be started.
There are many potential objects that could provide fuel for the fire. These include paper drapes, gauze sponges,
plastic tubing from the oxygen mask, and even the patients facial hair. It is important to remember that oxygen is a
drug. Therefore, the need for supplemental oxygen as well as the concentration of oxygen needs to be titrated in each
patient. Frequently, by reducing the amount of sedation given to the patient, the use of supplemental oxygen can be
eliminated. The oxygen can be diluted with room air and titrated to keep the patients oxygen saturation between 90-
95%. The drapes should be arranged so that the oxygen does not build up underneath the operative site. The drapes
should be arranged in a fashion that forms an open tent so that the oxygen will be diluted with room air. Since oxygen
is slightly heavier than room air, as long as there is some way for the oxygen gas to get in and out, it will tend to flow
towards the ground.

Another potential strategy to minimize the risk of fire is to discontinue the use of supplemental oxygen several minutes
before the surgeon uses the laser or the ESU. This will give any oxygen that has built up time to dissipate which would
greatly reduce the risk of fire. However, this may be difficult to do if there is frequent use of the ESU or laser. Also, it
is difficult to predict how long it would take for the oxygen to dissipate. Therefore, the newest recommendation from
the Anesthesia Patient Safety Foundation and the ECRI Institute, is to secure the airway with an LMA or endotracheal
tube when the patient needs supplemental oxygen for a head and neck procedure. There are a few exceptional cases
when there is a need to communicate with the patient (i.e. awake craniotomy or carotid endarectomy). In these cases
the FiO
2
should be less than 30 percent.

Volatile prep solutions provide another potential source of fuel for a fire. Solutions such as isopropyl alcohol are
frequently used by surgeons as skin prep. These solutions could pool in certain areas and remain liquid for a
considerable period of time. Additionally, these solutions will vaporize and the resulting vapor, especially in an
oxygen enriched atmosphere, is highly flammable.
DuraPrep is a skin prep that is very popular in many hospitals. It consists of Iodofor and 74% isopropyl alcohol. It
appears that the very high concentration of alcohol is not appreciated by many surgeons and operating room personnel.
If the solution is not allowed to dry completely before beginning surgery, then the alcohol will provide a potential fuel
for a fire. In 2001, Barker & Polson reported on just such a case. A patient was having a burr hole craniotomy under
MAC anesthesia. The patient was receiving supplemental oxygen and the head was prepped with the Iodofor and
alcohol solution. When the surgeons made the skin incision, the electrosurgical unit was activated and a "pop" sound
was heard. In very short order, smoke and a ball of flames engulfed the patient's head and shoulders. The fire was
quickly extinguished, but the patient suffered burns to the face and neck area. In a laboratory re-creation of the event,
Barker and Polson discovered some interesting facts. By duplicating the setup in the operating room, they were able to
re-create the fire. However, if there was no flow of supplemental oxygen, there was no fire. If the alcohol-based prep
solution was not used, again there was no fire and finally, if the closed space where the oxygen was allowed to build
up was not present, again there was no fire. This illustrates an essential fact, that although operating room fires are a
rare event, when the key elements come together at precisely the same time, a fire is easily started. Also, in the
presence of an oxygen enriched atmosphere, the fire will spread almost instantaneously.

In 2004 four cases of fires in the CO
2
canister of the anesthesia machine were reported. These canisters have melted or
actually caught on fire. In at least one case there was a serious patient injury. The common elements included use of a
CO
2
absorbent that was desiccated (Baralyme), Sevoflurane
TM
, and low O
2
flows. Apparently a breakdown of
Sevoflurane
TM
occurred, and there was a very exothermic reaction, which caused a fire. Laster et.al. demonstrated that
when desiccated Baralyme
TM
interacts with Sevoflurane
TM
there is a sustained temperature increase to 200 degrees C,
and in one case to over 300 degrees C. In contrast, with Isoflurane
TM
and Desflurane
TM
there was only a transient
increase in temperature to 100 degrees C. Amsorb
TM
is a newer CO
2
absorbent that does not contain strong alkali, and
does not react with Sevoflurane
TM
. Therefore, it would not pose a fire hazard.

422
Page 5

In 2010 Laudanski and colleagues reported two cases of a ventilator circuit that caught on fire. This was associated
with a wire that was used to heat the gases in the circuit. In this type of circuit this is a risk of melting wires,
insulation, and/or tubing that can lead to a fire.

Extinguishing a Fire
If a fire should develop, it is important to know how to extinguish it as rapidly as possible. Breaking the fire triad is
extremely important. Therefore, removing the oxidizer by disconnecting the oxygen or the circuit from the patient, will
frequently extinguish the fire. Burning drapes should be removed as quickly as possible and once on the floor, they can
then be extinguished. It should be remembered that impervious paper drapes will repel water and the fire will actually
burn on the underside of the drapes. Therefore, attempting to throw water on these burning drapes would be useless.
Although most operating rooms have a sprinkler system, the sprinklers are usually not activated in cases of OR fires.
This is because the sprinklers are rarely located over the operating room table, and they are also heat activated. OR
fires tend to give off a lot of smoke and toxic products of combustion, but not necessarily enough heat to activate the
sprinklers.

It is important that all operating room personnel are familiar with fire extinguishers. They are classified into three
basic types. Class A is used for wood, paper, cloth and plastics. Class B is used to extinguish flammable liquids or
grease, and Class C are used for energized electrical equipment. Many fire extinguishers are classified to be used in
two or all three types of fires. Halon is a fire extinguisher commonly found in operating rooms. It is a
bromofluorohydrocarbon and can be used on Class B & C fires and on many Class A fires as well. It is a highly
effective fire extinguisher and can be used safely around electronic equipment. However, because it is a fluorocarbon,
it is no longer being manufactured. Newer, environmentally friendly substitutes are now available. Carbon dioxide
fire extinguishers are useful for Class B & C fires and can also be used in Class A fires. The blast of carbon dioxide
gas has liquid and solid components that rapidly vaporize, which leads to a cooling and smothering of the fire. Carbon
dioxide extinguishers do not leave a residue which could damage electronic equipment, but the cold may cause
freezing if it came into contact with exposed skin. Pressurized water can be used in hand held fire extinguishers or
from the large fire hoses located in the operating room corridors. If a corridor fire hose is used, it can deliver up to 50
gallons of water a minute. These devices are best used by the fire department unless a patient or OR personnel is in
need of immediate rescue. Obviously, these devices would cause extreme damage to electronic equipment. All fire
extinguishers have advantages and disadvantages. When considering all of these factors, the CO
2
fire extinguisher is
probably the best for an operating room fire.

When using a fire extinguisher, the acronym "PASS" should be remembered. This stands for Pull the pin to unlock the
handle of the fire extinguisher; Aim the nozzle of the fire extinguisher at the base of the fire; Squeeze the handle to
activate the fire extinguisher and release the agent; Sweep the stream of the extinguisher over the base of the fire.

Case Studies
A couple of case scenarios of actual OR fires will help to illustrate some of the points that have been made. In one
instance during a neurosurgical procedure, the laser and the electrosurgery unit were both in use during the case. The
surgeon picked up the ESU while the laser was lying on the drapes. He mistakenly stepped on the laser pedal which
immediately ignited the drapes and subsequently the mattress and gel pad. A fire was started which produced very
toxic smoke and forced all of the OR personnel to leave the OR. They subsequently had to crawl back into the room,
disconnect the patient from the anesthesia circuit and pull the patient and the table out of the room. This case
illustrated the value of being absolutely certain of which pedal activates which device. Also, when a laser is in use,
once it is set down, the laser should be put in the standby mode immediately. Similarly, when an electrosurgery unit is
not in use, the pencil should be placed in a plastic holder.

Another case involved a trauma patient for an exploratory laparotomy. The electrosurgical pencil became draped over
the side of the table and the button was inadvertently activated. This immediately set the drapes on fire. Although
initially the fire appeared small, within a few seconds the flames had engulfed the left side of the patient. Attempts by
the OR staff to extinguish the fire were unsuccessful and the fire department arrived approximately 15 minutes later
and extinguished the fire. A review of the incident revealed that the OR staff had no plan for dealing with the situation,
they couldn't find the fire extinguishers, the fire cabinets were blocked by equipment and the OR sprinkler system was
not activated. Once again, the fact that the ESU pencil was not placed in the holder contributed significantly to this
fire.

422
Page 6

ASA Practice Advisory Recommendations

The ASA practice advisory makes a number of recommendations on the prevention of OR fires. First the OR team
must determine if a high risk situation exists. If there is a high fire risk then each person is given a specific task on how
to prevent a fire, and what they will do in the event a fire occurs. All fire management equipment must be readily
available. Prevention is the most important part of the equation. The anesthesiologist and the surgeon must collaborate
during the procedure to minimize an oxygen rich environment. The drapes must be configured to avoid oxidizer
buildup, and flammable skin preps must be dry before draping. Many institutions have instituted a prep time out to
insure that all flammable solutions have dried and there is no pooling of prep solutions. This must be completed prior
to draping the patient. The surgeon should be notified if an oxidizer and ignition source are in proximity, and time
allowed for the oxidizer to dissipate before using the ESU or laser.

The team should be aware of early signs of a fire such as a pop, flash, or smoke. If these occur, the surgery must be
stopped immediately, and everyone carries out their assigned task. If it is an airway fire, then simultaneously stop the
flow of gases and remove the ET tube. Saline is poured in the airway and burning materials are removed. If the fire is
on the patient, then the fire is extinguished with water or saline, and the burning drapes are removed and thrown on the
floor. The patient is then given supportive care, and the degree of injury is assessed. Finally, the scene is preserved,
and hospital and local regulatory reporting requirements are followed.

All OR personnel must be vigilant to potential operating room fires. Clearly, prevention is better than trying to deal
with an established fire. It is however, incumbent upon OR personnel to be prepared. This includes fire drills, being
familiar with the type and location of fire extinguishers, having an evacuation plan, knowing where gas and electrical
shutoffs are located, and being able to rapidly call for help, sound a fire alarm and communicate with other OR
personnel. Only by working together to keep all three legs of the fire triangle from coming together, can OR fires be
prevented.

REFERENCES

1. Abbott Laboratories: Dear Healthcare Provider( letter) Nov 17, 2003
[www.fda.gov/medwatch/SAFETY/2003/ultane_deardoc.pdf].
2. Aly A, McIlwain M, Ward M. Electrosurgery- induced ET tube ignition during tracheotomy. Ann Otol Rhinol
Laryngol 1991; 100:31-33
3. Anesthesia Patient safety Foundation: Prevention and Management of Operating Room Fires (Video).
Apsf.org. 2010.
4. Barker SJ, Polson JS. Fire in the operating room: A case report and laboratory study. Anesth Analg 2001; 93:
960-965
5. Bruley ME, Lavanchy C. Oxygen-enriched fires during surgery of the head and neck. In: Symposium on
Flammability and sensitivity of Material in Oxygen-Enriched Atmospheres, ASTM STP 1040. Philadelphia,
American Society for Testing and Materials. 1989, p. 392
6. Burgess GE, LeJeune FE. Endotracheal tube ignition during laser surgery of the Larynx Arch Otolaryngol
1979;105:561-562
7. Cameron BG, Ingram GS. Flammability of drape materials in. Anaesthesia 1971;26:281-288
8. Caplan RA, Barker SJ, Connis RT, Cowles C, de Richemond AL, Ehrenwerth J, Nickinovich DG, Pritchard D,
Robertson D, Wolf GL. Practice Advisory for the Prevention and Management of Operating
Room Fires.
Anesthesiology 2008;108: 786-801
9. Caplan RA, Barker SJ, Connis RT, Cowles C, de Richemond AL, Ehrenwerth J, Nickinovich DG, Pritchard D,
Robertson D, Wolf GL. Practice Advisory for the Prevention and Management of Operating
Room Fires. Anesthesiology 2013;118: 271-290
10. Casey KR, Fairfax WR, Smith SJ, et al. Intratracheal fire ignited by the Nd:YAG laser during treatment of
tracheal stenosis. Chest 1983;84:295-296
11. Castro BA, Freedman LA, Craig WL, Lynch C. Explosion within an anesthesia machine: BaralymeR , high
fresh gas flows and sevoflurane concentration. Anesthesiology 2004; 101:537-39.
12. Cozine K, Rosenbaum LM, Askanazi J, et al. Laser induced endotracheal tube fire. Anesthesiology
1981;55:583-584

422
Page 7
13. Di Pierro GB,Besmer I,Hefermehl LJ,et al. Intra-abdominal Fire Due to Insufflating Oxygen Instead of Carbon
Dioxide During Robot-Assisted Radical Prostatectomy: Case Report and Literature Review. European Urology
2010;58:626-628

14. de Richemond AL, Bruley ME. Head and Neck Surgical Fires. In: Complications in Head and Neck Surgery.
Ed: Eisele DW. Mosby, St. Louis, 1993
15. de Richemond AL. Laser resistant endotracheal tubes - protection against oxygen-enriched airway fires during
surgery? In: Stoltzfus JM, McIlroy K (eds). Flammability and Sensitivity of Material in Oxygen-Enriched
Atmospheres, vol 5, ASTM STP 1111. Philadelphia, American Society for Testing and Materials. 1991, p. 157
16. de Richemond AL. The patient is on fire! Health Devices 1992;21:19-34
17. ECRI. Airway fires: reducing the risk during laser surgery. Health Devices 1990;19:109-111
18. ECRI. A clinicians guide to surgical fires: how they occur, how to prevent them, and how to put them out.
Health Devices 2003;32:5-24.
19. ECRI. Laser-resistant tracheal tubes (evaluation). Health Devices 1992;21:4-14
20. ECRI. Lasers in medicine - an introduction. Health Devices 1984;13:151-178
21. Ehrenwerth J, Seifert HA: Electrical and Fire Safety in Clinical Anesthesia, Edited by Barash PG, Cullen BF,
Stoelting RK, Cahalan MK, Stock MC, 7
th
Edition, Lippincott, Williams & Wilkins; Philadelphia 2013.
22. Ehrenwerth J: A Fire in the Operating Room: It Could Happen to You. ASA Refresher Courses in
Anesthesiology; 40(1): 26-31, Lippincott, Williams and Wilkins; Philadelphia 2012.
23. Ehrenwerth J, Seifert HA: Electrical and Fire Safety in Anesthesia Equipment: Principles and Applications,
Edited by Ehrenwerth J, Eisenkraft J, and Berry J, 2
nd
edition, Elsevier, Philadelphia. 2013.
24. Fatheree RS, Leighton BL. Acute respiratory syndrome after an exothermic baralymeR-sevoflurane reaction.
25. Geffin B, Shapshay SM, Bellack GS, et al. Flammability of endotracheal tubes during Nd:YAG laser
application in the airway. Anesthesiology 1986;65:511-515
26. Greilich PE et al. Intraabdominal fire during laparoscopic cholecystectomy. Anesthesiology 1995; 83:871-874,
27. Gupte SR. Gauze fire in the oral cavity: a case report. Anesth Analg 1972;51:645-646
28. Hirshman CA, Smith J. Indirect ignition of the endotracheal tube during carbon dioxide laser surgery. Arch
Otolaryngol 1980;106:639-641
29. Johnson RM, Smith CV, Leggett K. Flammability of disposable surgical drapes. Arch Ophthalmol
1976;94:1327-1329
30. Krawtz S, Mehta AC, Weidemann HP, et al. Nd:YAG laser-induced endobronchial burn. Chest 1989;95:916
31. Laster M, Roth P, Eger EI. Fires from the interaction of anesthetics with desiccated absorbent. Anesth Analg
2004; 99:769-7
32. Laudanski K, Schwab WK, Bakuzonis CW, Paulus DA. Thermal damage of the humidified ventilator circuit in
the operating room: An analysis of plausible causes. Anesth Analg 2010;111:1433-6
33. Lew EO, Mittleman RE, Murray D. Tube ignition by electrocautery during tracheostomy: case report with
autopsy findings. J Forensic Sci 1991;36:1586-1591
34. Marsh B, Riley DH. Double-lumen tube fire during tracheostomy. Anesthesiology 1992;76:480-481
35. Moxon MA. Fire in the operating room. Anaesthesia 1986; 41:543-46,
36. Murray JM, Renfrew CW, Bedi A et al. Amsorb: A new carbon dioxide absorbent for use in anesthetic
breathing systems. Anesthesiology 1999; 91:1342-48.
37. Neufeld GR. Fires and explosions. In: Orkin K, Cooperman LH (eds). Complications in Anesthesiology.
Philadelphia, JB Lippincott., p. 671
38. Neuman GG, Sidebotham G, Negoianu E, et al. Laparoscopy Explosion Hazards with Nitrous Oxide,
Anesthesiology, 1993; 78:875-879
39. Ponath RE. Preventing surgical fires. JAMA 1984;252-1762

40. Patel R, Chavda KD, Hukkeri S. Surgical field fire and skin burns caused by alcohol-based skin preparation. J
Emerg Trauma Shock 2010 Jul;3(3):305.

41. Ramanathan S, Capan L, Chalon J, et al. Mini-environmental control under the drapes during operations on eyes
of conscious patients. Anesthesiology 1978;48:286-288
42. Rampil IJ: Anesthetic considerations for laser surgery. Anesth Analg 74:424-35, 1992.
43. Seifert HA. Fire Safety in the Operating Room. In: Progress in Anesthesiology, Ed: Eisenkraft JB, W.B.
Saunders, Philadelphia, 1994.
422
Page 8
44. Simpson JI, Wolf GL. ET tube fire ignited by pharyngeal electrocautery. Anesthesiology 1986;65:76-77
45. Simpson JI, Wolf GL: Flammability of esophageal stethoscopes, nasogastric tubes, feeding tubes, and
nasopharyngeal airways in oxygen- and nitrous oxide-enriched atmospheres. Anesth Analg 1988;67:1093-1095
46. Snow JC Norton ML, Saluja TS, et al. Fire hazard during CO2 laser microsurgery on the larynx and trachea.
Anesth Analg 1975;55:146-147
47. Vickers MD. Fire and explosion hazards in operating theatres. Br J Anaesth 1978;50:659-664
48. Wolf GL, Simpson JI. Flammability of ET tubes in O2 & N2O enriched atmosphere. Anesthesiology
1987;67:236-239
49. WuJ, Previte JP, Adler E et al. Spontaneous ignition, explosion and fire with sevoflurane and barium hydroxide
lime. Anesthesiology 2004; 101:534-37.
Disclosure
427
Page 1
New Findings from the ASA Closed Claims Project and Its Registries
The ASA Professional Liability Committee oversees a number of ongoing projects that promote a better
understanding of anesthesia risk and associated opportunities for risk reduction. In this lecture, we will review and
update four current areas of work: the ASA Closed Claims Project, focused studies of claims for chronic pain
management, the Postoperative Visual Loss Registry, and the Anesthesia Awareness Registry.
CLOSED CLAIMS PROJECT OVERVIEW
Since 1985, the ASA Committee on Professional Liability has conducted a detailed analysis of closed anesthesia
claims. This undertaking is called the ASA Closed Claims Project. The Closed Claims database is a standardized
collection of information about adverse anesthetic outcomes, retrieved from the closed claims files of 37 medical
liability insurance carriers. In aggregate, these carriers provide coverage for approximately 14,500 (36%) of
anesthesiologists in the United States. The current database contains over 9,800 cases. Claims for dental injury are
not included in this project.
Demography and Case Characteristics. Claims in the database represent the full spectrum of anesthesia care
including surgical (73%), obstetric (12%), chronic pain management (9.5%), acute pain (4%) and intensive care
(1.5%). Most cases involve healthy adults undergoing non-emergency surgery with general anesthesia (93% age
>16, 78% non-emergency, 62% ASA I or II, 69% general anesthesia, 59% female). The database is not a collection
of medically or surgically compromised patients in whom the underlying disease plays a major role in the outcome.
For this reason, the Closed Claims database offers an important opportunity to discern how the process of care
contributes to the genesis of adverse outcomes.
Damaging Events and Adverse Outcomes. Claims are characterized according to two basic features: damaging
events and adverse outcomes. The damaging event is the specific incident or mechanism (e.g., airway obstruction)
that leads to an adverse outcome. The adverse outcome is the injury (e.g., brain damage) sustained by the patient.
Overall, there are fewer damaging events than adverse outcomes
because some patients display injuries for which a specific
damaging event cannot be identified in the records. Damaging
events and adverse outcomes both show tight clustering in a small
number of specific categories. For example, just 3 categories -
death, nerve damage, and brain damage - account for more than half
(58%) of all adverse outcomes. Recurring mechanisms or cluster of
injury are findings of fundamental importance, because they suggest
that research and risk management strategies targeted at specific
aspects of clinical practice can result in significant improvements in
safety and professional liability. The ASA has successfully used
this approach with its Basic Monitoring Standards and Practice
Parameters.
Karen B. Domino, M.D., M.P.H
Robert A. Caplan, M.D.
Lorri A. Lee, M.D.
Edward Michna, M.D.
Seattle, Washington
Seattle, Washington
Seattle, Washington
Boston, Washington
427
Page 2
Analysis of Recurring Patterns of Injury
The in-depth examination of adverse outcomes with a common theme can reveal previously unappreciated
relationships or patterns of injury. This section gives an overview of key findings.
Adverse Respiratory Events. Since the inception of the Closed Claims Project, adverse respiratory events have
constituted the single largest source of injury (excluding chronic pain management).
1
In claims for events occurring
in the year 2000 or later (Fig. 1, n=409), just four mechanisms of injury accounted for 80% of all claims for adverse
respiratory events. These mechanisms were inadequate ventilation (28% of cases), difficult intubation (24%),
pulmonary aspiration (18%), and premature extubation (10%). Respiratory-related claims were characterized by a
high frequency of severe outcomes (74% death or brain damage) and costly payments (median $366,000 in 2012
dollar amounts). A study of difficult airway claims by Peterson
2
and colleagues provides a welcome indication that
the liability profile associated with respiratory events is improving.
Nerve Injury. Nearly one-fifth (19%) of all claims in the Closed Claims database arise from damage to discrete
parts of the peripheral nervous system or spinal cord, with approximately one-third of these nerve injuries
characterized as permanent disabling injuries.
3,4
An in-depth analysis of 610 claims for nerve injury was reported in
1999.
4
Just three specific distributions - ulnar nerve, brachial plexus, and lumbosacral root - accounted for more
than half of all claims for peripheral nerve damage. The 1999 report contributes to a well-established body of
evidence that peripheral nerve injury often occurs under conventional conditions of positioning and padding. Ulnar
nerve injury is notable for a preponderance of claims involving males (75%), and because the mechanism of injury
is evident in <10% of cases.
4
The most notable change in nerve injury claims involves the
spinal cord. In claims for events that occurred in 2000 or
later (Fig. 2, n=426)), nearly half (49%) of nerve injury
claims involve injury to the spinal cord. In comparison,
spinal cord injuries accounted for about 25% of nerve injury
claims in the 1990s, 10% in the 1980s, and 5% in the
1970s. Spinal cord injuries occurred most often in
conjunction with chronic pain procedures (61%), surgical
anesthesia care (24%), acute pain management (11%), or
(4%) obstetric anesthesia care. The most common cause of
spinal cord injury in cases involving regional anesthesia was
spinal or epidural hematoma (43/103 cases; 41%).
5
Of these
cases, 32 (74%) were associated with an abnormal
coagulation state, either from anticoagulant therapy (30
cases) or intrinsic coagulopathy (2 cases). The most
common sites of peripheral nerve injury in claims occurring in 2000 or later were the brachial plexus (15%), ulnar
nerve (6%), and median nerve (5%).
In the past two decades, nerve blocks have become increasingly common in perioperative care. Claims occurring
from 1990-2010 were recently studied by Lee
6
and colleagues to understand the liability associated with peripheral
nerve blocks used for surgical anesthesia and acute pain management. In this time period, 189 patients (2%) had
block-associated events in a database of 8954 claims. The primary purpose of the block was surgical anesthesia in
71% of claims, and acute pain management in 29%. Four-fifths of the claims were associated with just 3 blocks
interscalene (42%), axillary (26%), and intravenous anesthesia (11%). The most commonly injured nerves were the
brachial plexus (38%), median nerve (21%), ulnar nerve (16%), and phrenic nerve (8%). Slightly more than half
(53%) of all peripheral nerve injury claims were regarded as block-related. Two-thirds of peripheral nerve block
injuries were temporary and non-disabling, and the remaining were evenly divided between permanent or disabling
injuries (16%), and brain damage or death (16%). Local anesthetic toxicity was considered a cause of injury (brain
damage or death) in 7 claims, and was most often associated with axillary blocks. Administration of a wrong-sided
block was the basis for another 7 claims. Recent clinical advances such as lipid emulsion for rescue of local
anesthetic toxicity, pre-procedure timeouts, and ultrasound guidance all have the potential to improve the safety
regional anesthesia. It will be interesting to see if the peripheral nerve blocks exhibit a more favorable liability
profile in future years.

427
Page 3
Emerging Concerns

Operating room fires. Operating room fires have received attention for decades, but continue to occur at a national
rate of about 11 per week.
7
These events pose a serious threat to the safety of patients, operating room staff, and
occupants of health care facilities. A recent
study by Mehta
7
and colleagues revealed 103
claims for operating room fire out of a total of
9536 database claims. Electrocautery was the
ignition source in 90% of fires. About four-
fifths of fire claims (83%) occurred during
monitored anesthesia care (MAC) or sedation
for regional anesthesia (RA). Supplemental
oxygen was used in virtually all claims (99%)
involving electrocautery-induced fire. An
open oxygen delivery system (nasal cannula
or face mask) was used in about 90% of cases.
Plastic surgery procedures on the face
accounted for more than half of the fires
(64%) occurring during MAC or RA.
Electrocautery fires that occurred during
general anesthesia (17%) were associated with
tonsillectomy or tracheostomy, and were attributed to leaks or ruptures of an endotracheal tube cuff. A small
proportion of fire claims (10%) were associated with ignition by lasers or a defibrillator. In 8 of the 9 laser-related
fires, the inspired oxygen concentration was >30%. A troubling finding was that claims involving electrocautery
fire increased from <1% of surgical claims in 1985-1989 to 4.4% of surgical claims in 2000-2009 (Fig. 3).
Fortunately, excellent educational resources on fire prevention are now available. These include the ASA Practice
Advisory for the Prevention and Management of Operating Room Fires,
8
the Anesthesia Safety Foundation Fire
Safety Video (www.apsf.org/resources), and the FDA Safety Communication: Preventing Surgical Fires
(www.fda.gov/MedicalDevices/AlertsandNotices/.ucm275189.htm.)

Respiratory depression during acute pain management. In recent years, several national organizations (Anesthesia
Patient Safety Foundation, Institute for Safe Medication Practice, Joint Commission) have called attention to the risk
of opioid-induced respiratory depression in the postoperative period. Lee
9
and colleagues recently studied closed
claims from 1990-2000 in which respiratory depression occurred in association with acute postoperative pain
management. The intent was to identify contributing factors that might lead to better preventive strategies. A total
of 341 claims related to acute pain management were identified. One-fourth were associated with respiratory
depression. The three most common characteristics of claims involving respiratory depression were respiratory
depression occurring during the first day or night of surgery (87%), multimodal pain therapy (51%), and
somnolence (60%). Other interesting associations included evidence of sleep apnea (40%), use of non-opioid
sedatives (38%), and more than 1 physician prescribing opioids or non-opioid sedatives (34%). Because timing of
respiration depression (the first day or night of surgery) was the most commonly shared characteristic, the authors
suggested that novel preventive strategies should focus on the first 24 hours after surgery. In addition, the authors
suggested a fundamental shift in the preventive strategy - rather than focusing on some patients with a high-risk
patient profile, it may be more effective to focus on all patients during a high-risk period.

Liability associated with trauma care. Outcomes in trauma care can be improved by using organized trauma centers
and trauma systems.
10
Physicians are sometimes reluctant to participate in such systems because of the challenges
associated with trauma care one of these being the perception that trauma care is associated with increased
professional liability. Olivar
11
and colleagues examined claims from 1980-2005 to determine if the liability profile
for claims arising during trauma surgery (n=395) differed from that of claims arising during non-trauma surgery
(n=5820). Not surprisingly, death was more common in trauma claims, and temporary injury was more common in
non-trauma claims. Beyond this expected difference, trauma and non-trauma claims were mostly similar in terms of
specific outcomes and damaging events. Furthermore, there was no significant difference between trauma and non-
trauma claims in the proportion of claims with substandard care, frequency of payment to the plaintiff, or median
payment. These findings not only provide reassurance, but are notable because they run counter to the conventional

427
Page 4
observations that severe injuries are more likely to be associated with judgments of substandard care
12
and a higher
frequency of payments to the plaintiff.
13

Favorable Trends and Future Directions

The severity of injury in the Closed Claims database appears to be decreasing over time.
14,15
Death and brain
damage accounted for 56% of all claims in 1975, and then decreased approximately 1% per year to 27% of total
claims in the year 2000. In particular, the contribution of respiratory events to death and brain damage is
diminishing. From 1975 to 1986, adverse respiratory events accounted for 50% or more of all claims for death or
brain damage, decreasing to 28% in 2000.
In terms of challenges, the database shows a continued increase in the proportion of claims arising from acute and
chronic pain management. In the 1980s, surgical anesthesia accounted for 80% of claims, while claims arising
from acute and chronic pain were rare. Since 2000, claims associated with surgical anesthesia have declined to about
65% of the database, but claims associated with acute and chronic pain management have increased to 25%. A
notable increase has also been observed for claims associated with MAC. The proportion of claims associated with
MAC was 2% in the 1980s, 5% in the 1990s, and 10% in first decade of 2000.

From the perspective of risk management, two future directions are easy to identify. First, we must maintain and
extend the favorable trends in respiratory risk. And second, we must focus investigative resources and preventive
strategies on mechanisms of injury that make an increasing contribution to anesthesia liability - particularly pain
management.

POSTOPERATIVE VISUAL LOSS REGISTRY UPDATE

Postoperative Visual Loss

Since the mid to late 1990s, postoperative visual loss (POVL) has received focused attention from anesthesiologists,
ophthalmologists, and spine surgeons. Progress elucidating the etiology, prevention, or treatment of ION has been
difficult because of its low incidence (highest estimates at 1 in 1000 for spine operations).
16-21
Although
hypotension, anemia, and many other factors have been proposed as contributing to this complication, none have
been causally linked in clinical studies with detailed perioperative information. The ASA POVL Registry was
established in July of 1999 and findings from this database have significantly contributed to our understanding of
this perioperative complication. Results from the first study from the ASA POVL Registry in 2006 demonstrated
that the most common type of POVL injury after spine surgery, ischemic optic neuropathy (ION), occurs in the
absence of pressure on the globe even when the head is suspended in air in Mayfield pins.
22
Dispelling this
common misperception about the etiology of ION resulted in increased receptiveness to new theories and research
regarding causation. Though we still lack definitive evidence on the precise pathophysiology of ION after spine
surgery, findings from the recent multicenter case-control study using the ASA POVL Registry data identified six
risk factors associated with this complication (discussed later in this section).
23

Most Common POVL Diagnoses

POVL is most commonly associated with cardiac bypass procedures, spine surgery in the prone position, and head
and neck operations.
17
The most frequently encountered perioperative ophthalmologic injuries to consider are 1)
central retinal artery occlusion (CRAO); 2) anterior ischemic optic neuropathy (AION); 3) posterior ischemic optic
neuropathy (PION); and 4) cortical blindness. Findings consistent with CRAO on physical exam include an absent
pupillary reflex or relative afferent pupillary defect, and typically, unilateral, total, and permanent loss of vision.
Fundoscopic exam usually reveals a cherry red spot at the macula, narrowed retinal arterioles, and a pale and
edematous retina. Etiologies proposed for CRAO with respect to spine surgery include external globe compression,
emboli, hypotension, venous congestion, or vasculitis.
17
However, the frequent occurrence of accompanying
ipsilateral periorbital trauma implicates pressure on the globe as a common etiology. Many of the earlier case reports
with CRAO occurred with use of the horseshoe headrest and globe compression, though it can occur with soft foam
cushions as well.
24
This complication is also known as the Hollenhorst or headrest syndrome.

ION is the most common diagnosis for POVL associated with spine surgery in the prone position. Pupillary light
reflexes in ION are either absent or delayed. Loss of vision can include total blindness, altitudinal field cuts (loss of

427
Page 5
upper or lower visual fields), or scotoma (blind spots-usually central). Early fundoscopic exam in AION is
remarkable for the presence of disc edema, vascular attenuation, and frequent peripapillary flame-shaped
hemorrhages. The disc edema and hemorrhages are later replaced by permanent optic disc pallor one or more weeks
from the time of injury. Early fundoscopic exam of PION is completely normal, but also develops permanent optic
disc pallor one or more weeks after the injury. AION and PION may be difficult to distinguish from one another
because of subtleties of the early fundoscopic exam, and the fact that both lesions are identical several days to weeks
after the event with optic nerve pallor. It is currently unclear if these two lesions represent a continuum of the same
disease or not when associated with spine surgery. PION is more commonly associated with spine surgery and
bilateral head and neck dissections, whereas AION is more commonly associated with cardiac bypass procedures
and other miscellaneous cases in the supine position such as major vascular procedures. Both AION and PION have
poor recovery of vision.

Proposed, but unproven, risk factors for ION include hypovolemia, hypotension, anemia, venous congestion, edema,
adverse drug effects, and individual patient variation in anatomy and physiology of the optic nerve blood flow. This
lesion, in isolation, is not associated with external pressure on the globe. Similarly, embolic causation is thought to
be less likely with this lesion because of the lack of any retinal findings of emboli. The leading theory regarding the
etiology of ION is thought to be the development of a compartment syndrome of the optic nerve caused by a long
duration in the prone position with large fluid shifts that promote edema formation.

Cortical blindness may present with hemianopsia or complete blindness. Both the pupillary light reflex and
fundoscopic exam are normal. It is typically associated with states of profound hypotension such as cardiac arrest or
cardiac bypass procedures where emboli are common. Of the 4 ophthalmologic injuries discussed, cortical blindness
has the best chance for recovery.

The ASA Postoperative Visual Loss Registry: 2006 Findings

The ASA Committee on Professional Liability established the ASA POVL Registry in July 1999 to collect detailed
perioperative data on all cases of POVL after non-ocular surgery. Submission of cases is voluntary and anonymous.
Results from the ASA POVL Registry demonstrated that 87% of 93 spine cases in the database were diagnosed with
ION (23% AION, 67% PION, 10% unspecified).
22
CRAO was diagnosed in only 11% of cases.
22
No cases of
cortical blindness associated with spine surgery were submitted to the Registry.

Central Retinal Artery Occlusion (CRAO) Registry Cases Associated with Spine Surgery
CRAO was associated with 10 of 93 spine cases in the Registry.
22
Associated ipsilateral features such as extraocular
muscle paresis (ophthalmoplegia), bruising, marked periorbital edema, or proptosis implicate external globe
compression as the causative factor in CRAO, and were present in 70% of the 10 CRAO cases from the POVL
Registry. Blood loss and duration of surgery for patients diagnosed with CRAO were significantly less compared to
patients diagnosed with ION. Moreover, all of the CRAO cases were unilateral, whereas two thirds of the 83 ION
cases were bilateral. These findings are consistent with the proposed etiology of CRAO with the head slipping off
the headrest, resulting in unilateral globe compression. The high proportion of bilateral lesions in ION cases is more
consistent with a systemic insult. Because CRAO still occurs secondary to external globe compression, careful and
frequent eye checks in the prone position with documentation is recommended. Mayfield pins are an alternative to
the horseshoe headrest when the eyes cannot be adequately protected or frequently checked during the procedure.
However, Mayfield pins will not prevent the occurrence of ischemic optic neuropathy (ION).

Ischemic Optic Neuropathy: Combined AION and PION Registry Cases Associated with Spine Surgery
Mean age of the ION patients associated with spine surgery was 50 14 years, with the youngest patient being 16
years of age.
22
Almost two thirds of the ION patients were relatively healthy, ASA physical status I-II. Mayfield
pins were utilized in 16 of 83 spine cases with ION from the Registry, proving that ION occurs in the absence of
pressure on the globe. The high preponderance of male gender (72%) in the ION cases

is reminiscent of similar
findings for perioperative ulnar neuropathy,
25
leading to speculation that there may be some protective effect of
female gender for both nerve lesions. Some recovery occurred in approximately 40% of ION patients, but vision
rarely returned to baseline, and recovery was as small as being able to see hand motion.
22

The ION cases from the ASA POVL Registry were primarily multi-level instrumented operations in the lumbo-
sacral region associated with an anesthetic duration of 9.8 3.1 hours.
22
Almost all ION cases (94%) had an

427
Page 6
anesthetic duration of 6 or more hours (Fig. 4). Not surprisingly, these long anesthetic times were associated with
large intraoperative blood loss (median 2.0 liters), and 82% of the ION cases had an estimated blood loss of 1000 ml
or more (Fig. 5).
22
Anemia has frequently been implicated as a contributory factor for ION and the mean nadir
hematocrit for these ION cases was 26 5%. However, 17% of ION cases had a nadir hematocrit ! 30%.
22

Approximately one quarter of the ION patients from the ASA POVL Registry were treated with deliberate
hypotension to reduce blood loss. Blood pressure management was variable with 6% of cases maintaining their
lowest mean arterial pressure within 20% of baseline, indicating that ION can occur in the absence of hypotension.
However, the majority of cases (approximately 60%) had their lowest blood pressure kept within 20-39% of baseline
values, and the remainder of cases had their lowest blood pressure 40% or more below baseline.

The occurrence of this complication in children and in relatively healthy young adults,
22,26
and the relative absence
of other associated end-organ ischemic damage in these cases, suggests that ION is brought about by abnormal
physiologic changes during prone spine surgery in a uniquely vulnerable organ.
27
Atherosclerosis and other vascular
disease is not a prerequisite for its development. Moreover, the etiology appears to be multi-factorial because there
are many ION case reports which lack hypotension, anemia, operative time > 5 hours, or use of vasopressors.
Patient-specific factors that are not readily detectable such as anatomic and physiologic variations in the optic nerve
blood supply are also likely to contribute to ION. These inter-patient differences may account for similar anesthetic
management in patients resulting in different outcomes.

National Database and Single Institutional Studies

Three noteworthy studies on perioperative ION were published several years later in 2008 and 2009. The first study
examined the Nationwide Inpatient Sample (NIS) database for associations between POVL and perioperative factors
for spinal fusion surgery.
28
They identified hypotension (odds ratio, OR 10.1), peripheral vascular disease (OR 6.1)
and anemia (OR 5.9) as the strongest risk factors for the development of ION. The retrospective nature of the NIS
database, and the way the information is entered into the database, makes interpretation of these data used in this
manner difficult. Data entry with ICD-9 codes is typically done by staff hired to search the records for specific ICD-
9 codes for the purposes of increasing the acuity of care for outcomes adjustment and for reimbursement. Therefore,
unvalidated diagnoses may be entered as ICD-9 codes by staff uninvolved in the patients care. Further, events such
as hypotension that are not typically mentioned in the absence of complications will be over-represented in affected
cases of POVL. This misrepresentation results from a more thorough review of cases with adverse events than in
cases without adverse events. For example, it is unlikely that a patient who had no complications after spinal fusion
surgery would even have the anesthetic record examined for blood pressure management. Therefore, there is uneven
examination of records and diagnoses made.

The second study on perioperative ION by Holy and colleagues was based on a single institution experience.
29
This
group analyzed various types of surgical procedures (n = 17) associated with ION including cardiac bypass, spine
surgery, orthopedic operations, and miscellaneous procedures. They found no association with any perioperative
hemodynamic variables or preoperative co-existing diseases and ION. Possible limitations of this study were the

427
Page 7
small number of cases examined and inclusion of different procedures, with different physiologic perturbations,
associated with ION into one group for analysis.
30

The last study by Shen and colleagues utilized the NIS database to examine rates and associated factors for POVL.
30

Their methodology was more rigorous than Patils study, examining only variables that were collected routinely for
all cases. Their data confirmed the highest risk of POVL was associated with cardiac and spine surgery.
Additionally, they found an elevated risk of POVL for hip and femur surgery, and for knee arthroplasty, compared
to abdominal surgery. Other notable findings from their study included a greatly increased risk of POVL for children
after spinal fusion (OR 18.3) and all surgical procedures (OR 6.9), and for cortical blindness in children after all
procedures (OR 64). The authors also demonstrated a decreased prevalence of POVL in their study period of 1996
through 2005.

The ASA POVL Registry: Multicenter Case-Control Findings

Early in 2012, results of a multicenter case-control study utilizing 80 ION cases associated with spinal fusion
surgery from the ASA POVL Registry identified six risk factors for this complication.
23
These ION cases were
matched 1:4 to controls undergoing similar surgery in 17 different academic medical centers. This study was unique
because of the large number of ION cases collected after one type of procedure with detailed perioperative data.
Potential bias and other limitations were introduced by the retrospective collection of data and occurrence of ION
cases at institutions different from control cases. After stepwise multivariate analysis, six risk factors were
independently and significantly associated with development of ION after spinal fusion surgery: male sex, obesity,
use of the Wilson surgical frame, longer anesthetic duration, greater estimated blood loss, and a lower percentage of
colloid in the non-blood volume administration. With the exception of male sex, these risk factors are congruent
with the most popular theory of pathophysiology of this complication involving venous congestion and interstitial
edema formation around the optic nerve as important contributory factors to optic nerve ischemia. As with most
models of risk, it did not account for all ION cases, leaving open the likely possibility of other unidentified risk
factors such as unique patient vulnerabilities.

The Updated ASA Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery

Prior to the publication of the multicenter case-control study, the ASA Task Force on Perioperative Visual Loss
updated the practice advisory for perioperative visual loss associated with spine surgery.
31
These recommendations
do not differ from the initial practice advisory published on this topic in 2006. Recommendations from the original
practice advisory and this update are consistent with the multicenter case-control study findings, though lacking
comment on avoidance of specific surgical frames that place the head significantly below heart level. Major
recommendations for the high risk patient for POVL include considering consent of patients for this complication,
continually monitoring blood pressure, using colloids along with crystalloids for volume replacement, keeping the
head neutral with or above heart level, and considering staging high risk procedures.

POVL and Robotic Surgery

More recently, concern has been raised regarding the potential risk of ION with robotic prostatectomy surgery.
32

The prolonged duration in steep Trendelenburg position results in significant venous congestion of the head similar
to the prone position. To date, the Registry contains 3 cases of ION occurring after robotic prostatectomy surgery
with a duration of 7.9 or more hours.
33
This number of cases so early in the introduction of this procedure may
signify a heightened risk. Despite marginal benefits compared to open prostatectomy, the popularity of this
procedure is rapidly increasing nationally. A larger denominator of cases in the future may be more revealing
regarding any association with ION.

Risk factors for ION and other forms of POVL continue to be elucidated which give rise to new theories on
causation. Basic science research with creation of an animal model for ION and validation of current risk models are
needed before effective preventative strategies and treatment can be identified.

427
Page 8
THE ANESTHESIA AWARENESS REGISTRY

Recall during general anesthesia (GA) remains a small but consistent source of medical liability for
anesthesiologists, representing approximately 2.5% of surgical and obstetric general anesthesia claims since 1980.
To put this into perspective, GA Recall is similar in claims frequency to wrong side surgery (2%), burns (3%),
myocardial infarction (3%), and stroke (3.5%).
Approximately half (52%) of GA recall claims resulted
in some payment to the patient (Fig. 6). Payment
amounts have remained fairly consistent over time,
with a median payment of $64,000 (in 2012 dollar
amounts), and an interquartile range of $26,000 to
$127,000 (Fig. 6).

Among 2034 surgical or anesthesia claims with MAC
or regional anesthesia, there were 91 claims (4%) for
inadequate anesthesia. These claims involved pain
during the procedure with significant emotional
distress. Payment was made in 41% of these claims,
with median payment of $51,000 (interquartile range
$21,000 - $161,000). These trends have remained
consistent over time.

Anesthesia Awareness Registry

The Anesthesia Awareness Registry was created in October 2007 in an attempt to improve patient education and
intervention strategies in the event of recall during general anesthesia. Following University of Washington IRB
approval, subjects were recruited to the Anesthesia Awareness Registry through the Registry website
(www.awaredb.org). The inclusion criteria were 13 years or older and explicit recall during general anesthesia for
surgery. Subjects completed a short questionnaire about their anesthesia awareness experience, including procedure,
date of surgery, specific recollections during surgery, satisfaction with care, and psychological sequelae. A second
survey was added in October 2011 to explore with more depth psychological sequelae. This survey (Survey 2)
contains a number of validated physical and mental health scales. Medical records were also requested.

As of May 1, 2013, 277 subjects had enrolled in the Registry, with 291 awareness experiences. We have also
collected 96 Survey 2. For enrolled subjects (25% males and 75% females), the surgical years ranged from 1952-
2013, with 201 cases (69%) since 1990 and 147 cases (51%) since 2000. The most common surgical procedures
were intra-abdominal (23%), obstetrics (19%), orthopedics (18%), and non-OR (12%). Of 291 experiences reported,
84% experienced tactile sensations and 70% had pain or burning. Eighty-seven percent felt paralyzed/unable to
move and 89% felt anxiety, fear, or panic.

A review of the Anesthesia Awareness Registry was recently conducted to assess the psychological impact of
unexpected explicit recall of events occurring during surgeries performed under sedation, regional anesthesia, and
general anesthesia.
34
A total of 83 cases from 1990-2010 for whom medical records had been received were
identified for inclusion. Most (n=56) had received general anesthesia, but some subjects had received MAC (n=10),
regional anesthesia (n=7), and sedation without an anesthesia provider (n=10). Six GA awareness cases were
excluded from analysis based on the awareness incident occurring before induction or during emergence. Patients
reported experiencing a range of sensations during the explicit recall experience including paralysis (96% GA, 76%
non-GA), pain (78% GA, 65% non-GA), paralysis with pain (76% GA, 44% non-GA), distress (94% GA, 78% non-
GA), and auditory/tactile sensations (2% GA, 19% non-GA). Most respondents had psychological sequelae related
to awareness regardless of anesthetic type, with 82% of respondents who received GA and 59% of non-GA
reporting feelings of anxiety, chronic fear or phobias, avoiding crowds or noise, dreams or nightmares, flashbacks,
trouble sleeping, increased fatigue, or depression. Both groups had continuing persistent psychological sequelae
with 82% of GA and 63% of non-GA patients reporting they were still experiencing weekly symptoms at the time of
filling out the survey. Both groups reported being very upset about the awareness experience at the time of filling
out the survey (47% GA, 33% non-GA).

427
Page 9
Our data suggest that a patients understanding of intraoperative awareness may differ from that of an
anesthesiologist, and that the disparity of expectations may lead to considerable patient distress. Improved
communication and patient education may be helpful.

CHRONIC PAIN MANAGEMENT CLAIMS

The ASA began collecting data on closed malpractice claims in the 1980s. Due to the lag time between when the
care alleged to be negligent occurred and when the malpractice claim closed, the events involved in the claims
occurred as early as the 1970s. The newest claims in the database are for events in 2010. Malpractice claims in the
ASA Closed Claims Database are divided into four types: obstetric, acute pain, chronic pain, and surgical claims.
The proportion of claims in each of these categories has changed between the 1970s and the most recent claims
collected (Fig. 7, p < 0.001). Of the 670 claims
where the event occurred in the 1970s, 84%
were for anesthesia provided for non-obstetric
surgical claims. By the 1990s, 72% of the
anesthesia malpractice claims (n = 3,864) were
for surgical procedures and in the 2000s, 65%
of anesthesia claims (n = 2,187) were for
surgical procedures. Obstetric claims have also
declined over the last 40 years from 14% of all
claims to 9% of all claims in the database.
Until the 1990s, acute pain claims comprised
less than 1% of all claims, but by the 2000s,
acute pain claims make up 8% of the database.
Chronic pain claims made up less than 3% of
all the claims before 1990, but in the 2000s,
they make up 18% of all claims. This increase
in chronic pain malpractice claims coincides
with the establishment of formal accredited
fellowship training programs in pain medicine
in 1993. As more and more anesthesiologists began to enter this new specialty, an increase in malpractice claims
related to the management of chronic pain is not surprising.

Not only have the percentage of malpractice
claims for chronic pain increased, the types
of chronic pain management have also
changed since the 1970s. In the 1970s and
1980s, 80 to 85% of all chronic pain
malpractice claims (n = 110) were for non-
lytic blocks and injections, but for events that
occurred since 2000, only 53% of all claims
(n = 382) were for non-lytic blocks (Fig. 8, p
< 0.001). Until the mid-1990s, less than 3%
of all chronic pain claims were for
medication management, but since 2000,
19% of all chronic pain claims are for
medication management (p < 0.001).
Implanting, managing, and removing
devices, e.g., pumps and stimulators, were
less than 3% until 1990, but are 16% of all
chronic pain claims since 2000 (p = 0.016).

Although non-lytic blocks have always comprised the largest category of chronic pain claims, the types of blocks
and injections in malpractice claims have also changed over the last 40 years. Lumbar epidurals comprised just
under 35% of all non-lytic injections and blocks through the mid-1980s and peaked at 49% of all claims by the early

427
Page 10
1990s (Fig. 9, p < 0.001). Since 2000, they have
only comprised 29% of all non-lytic injections and
blocks (p < 0.001). In contrast, cervical epidurals
made up 6% of non-lytic injection and block
claims until the mid-1990s, but since 2000,
cervical epidurals comprise 41% of all non-lytic
block and injection malpractice claims (p < 0.001).
Stellate ganglion blocks have declined from 18%
in the 1970s and 1980s to 3% of all non-lytic
injections and blocks since 2000 (p = 0.002).
Intercostal blocks comprised 19% of all non-lytic
blocks prior to 1985, but only 1% of all non-lytic
blocks since 2000 (p < 0.001)

The first report on chronic pain related claims
from the ASA Closed Claims Database was
published in 2004, detailing claims that occurred
between 1970 and 1999.
35
Nerve injury and
pneumothorax were the most common outcomes.
Serious injuries, involving brain damage or death, occurred with epidural steroid injections when local anesthetics
and/or opioids were used and with maintenance of implantable devices.

The information gleaned from the early analysis of chronic pain claims was limited by the data collection tools used,
which had been designed for analysis of intraoperative claims, and limited by the closed claims reviewers
themselves, many without any expertise in the management of chronic pain. By 2005, a group of chronic pain
experts had joined the Closed Claims project and redesigned the data collection tool to collect detailed information
pertinent to the management of chronic pain. Reviewers using this form all had some expertise in managing chronic
pain. With expanded information relevant to managing chronic pain now an integral part of the Closed Claims
database, in late 2009 an overall analysis of the expanding collection of claims related to chronic pain was
undertaken. Two new trends appeared: claims related to management of chronic pain with medications had
increased compared with a decade earlier, as had claims related to procedures carried out at the level of the cervical
spine. Both of these trends have continued in claims collected since 2008 (Figs. 8 and 9).

Malpractice Claims Associated with Medication Management for Chronic Pain

Medication management is an integral part of chronic pain management. Medication management represented 17%
of 295 chronic non-cancer pain claims collected from 2005 to 2008.
36
Compared with other chronic pain claims,
medication management patients tended to be younger men (p<0.01) most often with back pain. Most patients were
prescribed opioids (94%) and also additional psychoactive medications (58%). Eighty percent of patients had at least
one factor commonly associated with medication misuse
and 24% had ! 3 factors. The most common factors were
a history of depression (45%), obtaining medications
from multiple providers (35%), history of drug or
alcohol problems (35%), or current illicit drug or alcohol
abuse. The main underlying event in 82% of claims was
that the patient did not cooperate in the care plan and/or
there was inappropriate medication management by the
pain management anesthesiologist, or both (Fig. 10). In a
total of 69% of claims, the patient did not cooperate in
the care plan; in 59%, there was inadequate or
inappropriate medication management by the pain
management anesthesiologist. Other complaints included
inadequate pain relief, adverse drug reaction, failure to
diagnose, wrong dosage dispensed, and accidental
patient overdose. There were three claims associated
with the patients underlying co-morbid conditions, and

427
Page 11
one unexplained death. Death was the most common outcome in medication management claims (57% vs. 9% in
other chronic pain claims, p<0.01). Factors associated with death included use of long-acting opioids, additional
psychoactive medications, and ! 3 factors commonly associated with medication misuse. Alleged addiction from
prescribed opioids was the complaint in 24% of claims. Appropriateness of care and payments were similar for
medication management versus other chronic pain claims. Thus, most anesthesia malpractice claims for problems
with medication management involved patients with a history of high-risk behaviors commonly associated with
medication misuse. Malpractice claims arising from medication management had a high proportion of deaths, with
both patient and physician contributions to the outcome.

Injury and Liability Associated with Cervical Procedures for Chronic Pain

!"#$%& ()"#*)+ *, -)(.$-#" $/*)(.)/*$,/& ()0()&)/*)+ 112 34561758 ,9 -:(,/$- 0#$/ *()#*%)/* -"#$%& -,"")-*)+
9(,% ;#/<#(= >? 1@@A *, B)-)%C)( D>? 1@@EF
DG
H#*$)/*& I:, </+)(I)/* -)(.$-#" 0(,-)+<()& I)() :)#"*:$)(
3J%)($-#/ K,-$)*= ,9 J/)&*:)&$,",L$&*&M &-,() ,9 >N1O 0P@F@@>8 #/+ I)() %,() ,9*)/ I,%)/ 30Q@F@>>8F R9 *:)
0#*$)/*& I:, </+)(I)/* # -)(.$-#" 0(,-)+<()? A72 )S0)($)/-)+ &0$/#" -,(+ +#%#L) -,%0#()+ I$*: >>2 ,9
0#*$)/*& I$*: ,*:)( -:(,/$- 0#$/ 30P@F@@>8? I$*: +$()-* /))+") *(#<%# #& *:) 0()+,%$/#/* -#<&) 3D>28F
H#*$)/*& I:, </+)(I)/* -)(.$-#" 0(,-)+<()& I)()
%,() "$T)"= *, :#.) &0$/#" -,(+ $/U<(= #/+ ")&& "$T)"=
*, +$) *:#/ ,*:)( -:(,/$- 0#$/ -"#$% 0#*$)/*& 3V$LF >>
W0P@F@> #/+ WW0P@F@@>8F X,&* &0$/#" -,(+ $/U<($)&
3EG28 I)() 0)(%#/)/*? ,/) 0#*$)/* I$*: # &0$/#"
-,(+ $/U<(= #9*)( # -)(.$-#" 0(,-)+<() +$)+F Y)/)(#"
#/)&*:)&$# ,( &)+#*$,/ I#& <&)+ $/ 4G2 ,9 -)(.$-#"
0(,-)+<() -"#$%& #&&,-$#*)+ I$*: &0$/#" -,(+
$/U<($)& C<* $/ ,/"= >72 ,9 -)(.$-#" 0(,-)+<() -"#$%&
/,* #&&,-$#*)+ I$*: &0$/#" -,(+ $/U<($)& 30P@F@@>8F
R9 *:) 0#*$)/*& I:, </+)(I)/* -)(.$-#" 0(,-)+<()&
#/+ :#+ &0$/#" -,(+ $/U<($)&? 1A2 I)()
/,/()&0,/&$.) +<($/L *:) 0(,-)+<() -,%0#()+ I$*:
A2 ,9 *:) 0#*$)/*& I:, </+)(I)/* -)(.$-#"
0(,-)+<()& #/+ +$+ /,* :#.) &0$/#" -,(+ $/U<($)&
30Z@F@A? "Q@FA18F [:<&? $/U<($)& ()"#*)+ *, -)(.$-#"
$/*)(.)/*$,/#" 0#$/ *()#*%)/* I)() ,9*)/ &).)() #/+ ()"#*)+ *, +$()-* /))+") *(#<%# *, *:) &0$/#" -,(+F
[(#<%#*$- &0$/#" -,(+ $/U<(= I#& %,() -,%%,/ $/ 0#*$)/*& I:, ()-)$.)+ &)+#*$,/ ,( L)/)(#" #/)&*:)&$# #/+
$/ *:,&) I:, I)() </()&0,/&$.) +<($/L *:) 0(,-)+<()F V<(*:)( &*<+$)& #() -(<-$#" *, +)9$/) *:) <&)9<"/)&& ,9
-)(.$-#" $/*)(.)/*$,/& #/+ *, $%0(,.) *:)$( &#9)*=F

REFERENCES

1. Caplan RA, Posner KL, Ward RJ, et al. Adverse respiratory events in anesthesia: a closed claims analysis.
2 Peterson GN, Domino KB, Caplan RA, Posner KL, Lee LA, Cheney FW. Management of the Difficult Airway:
a closed claims analysis. Anesthesiology 2005; 103:33-39.
3. Kroll DA, Caplan RA, Posner K, et al. Nerve injury associated with anesthesia. Anesthesiology 1990;73:202-7.
4. Cheney FW, Domino KB, Caplan RA, et al. Nerve injury associated with anesthesia: a closed claims analysis.
5. Lee LA, Posner KL, Domino KB, Caplan RA, Cheney FW: Injuries associated with regional anesthesia in the
1980s and 1990s: a closed claims analysis. Anesthesiology 2004;101:143-52.
6. Lee LA, Posner KL, Kent CD, Domino KB. Complications assoicated with peripheral nerve blocks: lessons
from the ASA Closed Claims Project. Int Anesth Clinics 2011; 49:56-67.
7. Mehta SP, Bhananker SM, Posner KL, Domino KB. Operating room fires: a closed claims analysis.
8. Practice advisory for the prevention and management of opreating room fires. A report by the American
Society of Anesthesiologists Task Force on Operating Room Fires. Anesthesiology 2008; 108: 786-801.

427
Page 12
9. Lee LA, Domino KB. Factors associated with postoperative respiratory depression: from the ASA Closed
Claims Analysis. ASA Newsletter 2013; 77 (5):34-6.
10. MacKenzie EJ, Rivara FP, Jurkovich GJ, Nathens AB, Frey KP, Egleston BL, Salkever DS, Scharfstein DO. A
national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006;354:36678
11. Olivar O, Sharar SR, Stephens LS, Posner KL, Domino KB. Similar liability for trauma and nontrauma surgical
anesthesia: a closed claims analysis. Anesth Analg 2012; 115:1196-203.
12. Caplan RA, Posner KL, Cheney FW. Effect of outcome on physician judgments of appropriateness of care.
JAMA1991; 265:1957-60.
13. Brennan TA, Sox CM, Burstin HR. Relationship between negligent adverse events and the outcomes of
medical-malpractice litigation. N Engl J Med 1996: 335:1963-7.
14. Cheney FW, Posner KL, Lee LA, Caplan RA, Domino KB: Trends in anesthesia-related death and brain
damage. Anesthesiology 2006;105:1081-6.
15. Metzner J, Posner KL, Lam, MS, Domino KB. Closed claims analysis. Best Practice & Research Clinical
16. Myers M, Hamilton S, Bogosian A, et al. Visual loss as a complication of spine surgery. Spine 1997;22:1325-9.
17. Roth S, Gillesberg I. Injuries to the Visual System and Other Sense Organs. In Benumof J, Saidman L, eds.
Anesthesia and Perioperative Complications. St. Louis: Mosby, 1999; pp. 377-408.
18. Sadda S, Nee M, Miller N, et al. Clinical spectrum of posterior ischemic optic neuropathy. Am J Ophthalmol
2001;132(5):743-50.
19. Warner M, Warner M, Garrity J, et al. The frequency of perioperative vision loss. Anesth Analg 2001;
93:1417-21.
20. Dunker S, Hsu H, Sebag J, et al. Perioperative risk factors for posterior ischemic optic neuropathy. J Am Coll
Surg 2002;94(6):705-10.
21. Stevens W, Maj M, Glazer P, et al. Ophthalmic complications after spinal surgery. Spine 1997; 22(12):1319-24.
22. Lee LA, Roth S, Posner KL, et al. The American Society of Anesthesiologists Postoperative Visual Loss
Registry: Analysis of 93 Spine Surgery Cases with Postoperative Visual Loss. Anesthesiology 2006;105:652-9.
23. The Postoperative Visual Loss Study Group. Risk factors associated with ischemic optic neuropathy after spinal
fusion surgery. Anesthesiology 2012; 116:15-24.
24. Hollenhorst R, Svien H, Benoit C. Unilateral blindness occurring during anesthesia for neurosurgical
operations. A.M.A. Arch Ophth 1954; 52:819-30.
25. Warner MA, Warner ME, Martin JT. Ulnar Neuropathy: Incidence, outcome, and risk factors in sedated or
anesthetized patients. Anesthesiology 1994;81:1332-40.
26. Chang SH, Miller NR. The incidence of vision loss due to perioperative ischemic optic neuropathy associated
with spine surgery: The Johns Hopkins Hospital Experience. Spine 2005;30:1299-1302.
27. Lee LA, Deem S, Glenny RW, et al. The effects of anemia and hypotension on porcine optic nerve blood flow
and oxygen delivery. Anesthesiology 2008;108:864-72.
28. Patil CG, Lad EM, Lad SP, Ho C, Boakye M. Visual loss after spine surgery: a population- based study. Spine
2008;33:1491-6.
29. Holy SE, Tsai JH, McAllister RK, Smith KH. Perioperative ischemic optic neuropathy: a case control analysis
of 126,666 surgical procedures at a single institution. Anesthesiology 2009;110:246-53.
30. Shen Y, Drum M, Roth S. The incidence of perioperative visual loss in the United States: a ten year study from
1996 to 2005 of spinal, orthopedic, cardiac, and general surgery. Anesth Analg 2009;109:1534-45.
31. American Society of Anesthesiologists Task Force on Perioperative Visual Loss. Practice advisory for
perioperative visual loss associated with spine surgery: an updated report by the American Society of
Anesthesiologists Task Force on Perioperative Visual Loss. Anesthesiology 2012;116:274-85.
32. Weber ED, Colyer MH, Lesser RL, Subramanian PS. Posterior ischemic optic neuropathy after minimally
invasive radical prostatectomy. J Neuroophthalmol 2007;27:285-7.
33. Lee LA, Posner KL, Bruchas R, Roth S, Domino KB: Visual loss after prostatectomy. Proceedings of the 2010
Annual Meeting of the American Society of Anesthesiologists: A1132, 2010.
34. Kent CD, Mashour GA, Metzger NA, Posner KL, Domino KB. Psychological Impact of unexpected recall of
events during surgery performed under sedation, regional anaesthesia, and general anaesthesia: Data from the
Anesthesia awareness registry. BJA 2013; 110(3):381-387.
35. Fitzgibbon DR, Posner KL, Domino KB, et al. Chronic pain management: American Society of
Anesthesiologists Closed Claims Project. Anesthesiology 2004;100:98-105.
36. Fitzgibbon DR, Rathmell J, Michna E, et al. Malpractice claims associated with pain management for chronic
pain. Anesthesiology 2010;112:948-56.

427
Page 13
37. Rathmell JP, Michna E, Fitzgibbon DR, et al. Injury and liability associated with cervical procedures for
chronic pain. Anesthesiology 2011;114:918-26.

Disclosure

435
Page 1
Cognitive Errors In Anesthesiology:
Making Mistakes Even When You "Know" Better
Marjorie Podraza Stiegler, M.D. Chapel Hill, North Carolina
"I never make stupid mistakes. Only very, very clever ones." ~John Peel
Introduction
What does it feel like to be wrong? How can we know when are making a mistake? We cannot, of course, because
being wrong feels exactly like being right. We are oblivious to our errors at the time that we commit them. There is
only the experience of realizing that we have been wrong. This idea of error-blindness, put forth by Kathryn Schulz,
is summarized by her as: "we can be wrong, or we can know it, but we can't do both at the same time."[1]
Naturally, erroneous thinking can be due to lack of information. However, this course focuses on cognitive errors -
mistakes rooted in faulty subconscious thought processes. They are distinct from knowledge gaps because the
thinker possesses adequate information and understanding of the subject matter to arrive at the correct conclusion.
Simply put, cognitive errors are mistakes that are made despite "knowing better."
Why are cognitive errors important?
In the early 1990s, medical errors were exposed for the enormous problem that they are. Few physicians need a
reminder that medical errors have been estimated to account for up to 98,000 deaths annually in the United States at
a cost to the US healthcare system of $24 billion per year.[2] According to Brennan et al[3], 1.5 jumbo jets would
need to crash every day for an equivalent death rate, making "medical errors" the fifth leading cause of death in the
United States (ahead of motor vehicle accidents, diabetes, kidney disease, breast cancer, and influenza).
While it is easy to agree that medical errors must be reduced, significant challenges remain regarding error
reporting, management, and prevention. Recent studies suggest that cognitive errors, a subset of medical errors
involving faulty thought processes and subconscious biases, are important contributors to missed diagnoses and
patient injury.[4] Indeed, according to Groopman, "technical errors account for only a small fraction of incorrect
diagnoses and treatments. Most errors are mistakes in thinking." He goes on to say that these thinking mistakes are
caused in part by subconscious processes, such as biases we may not even recognize, and certainly not admit.[5]In
the 1990s, early pioneers of the "crisis resource management" paradigms at Harvard and Stanford introduced this
topic by including fixation error, or "tunnel-vision", in their curricula. This is indeed a cognitive error, and likely a
very common one. Today, the psychology of decision-making is becoming ever more appreciated, as more vast
descriptions of a variety of cognitive errors have now been described in safety culture industries and many medical
specialties including anesthesiology[6]
"Be not ashamed of mistakes and thus make them crimes." ~Confucius
Historically, there has been a notion that making a mistake is shameful, diminishing a person's worth and
undermining their expertise. However, fallibility is not equivalent to stupidity.[1] In fact, Pulitzer winner Hallinan,
an expert on human perception pitfalls, asserts that the same qualities that make us efficient (rapid pattern
recognition in lieu of detail scrutiny, for example) also make us error prone; thus the mechanisms by which we
perceive, process, and remember actually set us up to make mistakes. As well, he asserts, humans have significant
435
Page 2
capacity for self-deception and/or delusion. We are prone to bias, and are poorly calibrated, meaning that our
perception of our performance rarely approximates our actual performance. We tend to hold fast to old strategies
that work poorly in new situations, and rely upon memories that are much less accurate than we realize.[7]
Any reader now thinking, "This subject may be interesting, but it doesn't actually apply to me," is in fact committing
a cognitive error right now! Study after study consistently shows that people, including doctors, tend to
overestimate their capabilities and remain very certain of decisions even in the face of irrefutable evidence to the
contrary.[8-10] We attribute favorable personal characteristics (talent, intelligence, dexterity) to our successes, yet
blame circumstances for our failures.[8] Whether or not we are personally prepared to be open to our own fallibility
factors prominently in our potential abilities to avoid and manage these kinds of thought process errors.
What exactly are cognitive errors?
Cognitive errors are thought process traps that are ubiquitous human experiences, usually linked to failed biases or
heuristics. It is worth repeated that they are distinct from knowledge gaps. It is noteworthy that heuristics and
biases are frequently useful in clinical medicine; they allow experts to arrive at decisions quickly and (usually)
accurately. However, cognitive error arises when these subconscious processes and mental shortcuts are relied upon
too heavily, or under the wrong circumstances.
Because cognitive errors are rooted in subconscious processes, we are often unaware of their influence. According
to Kida, humans believe strongly in anecdotes, demonstrating a powerful preference for stories over statistics and a
tendency to ignore the concepts of chance and coincidence. The human brain subconsciously reshapes and
enhances memories as time goes by, and then we rely on these faulty memories to shape future decisions. People
seek to confirm what they already believe and gloss over contradictory evidence. We tend to oversimplify or
misinterpret complex situations. While there is a plethora of science and documentation of evidence to these points,
we humans continue to repeat the same errors of thinking.[11]
"Experience is that marvelous thing that enables you to recognize a mistake when you make it again."
~ Franklin P. Jones
How do cognitive errors manifest in anesthesiology?
Experts rely heavily on cognitive shortcuts and intuitive processes, especially when making high-stakes decisions
under time pressure; this thinking environment may be particularly prone to cognitive error. [10, 12]In
anesthesiology, it is easy to describe examples of particular cognitive errors that may arise in routine practice and
during emergency situations.
The following is a brief introduction to just a few specific examples (which may be known by other synonymous
terms). By way of an acknowledgement, it is true that the mere provision of a vignette example may bias the
reader's interpretation of the error. Please consider these illustrations to be just that, and focus on the thought
process problem being described, rather than the medical situation in which it is depicted. Refrain from judging the
error as careless or stupid, and keep an open mind to the fallibility of human nature, even among experts.
Premature Closure
"No problem can withstand the assault of sustained thinking." ~Voltaire
Premature closure describes the cognitive error of accepting the first plausible diagnosis before it has been fully
verified. For example, if a patient is hypotensive after induction, the tendency may be to attribute this to the effect of
deep anesthesia without adequate stimulation, and not investigate further. (A different physician may select
anaphylaxis just as readily, or myocardial infarction, etc and not consider other key items on the differential
diagnosis). The error lies not in the nature of the preliminary diagnosis, but in the premature cessation of
investigation. Putting premature closure in the context of useful heuristics is important, for patients often do have a
decrease in blood pressure after induction, particularly in the period prior to surgical stimulation. This experience
shapes the expert mind to expect this result, and does not require an exhaustive differential diagnosis at every
435
Page 3
occurrence. Playing the odds, this premature conclusion will be correct a good percentage of the time. It becomes a
cognitive error on the more rare occasions when these shortcuts lead us astray.
Feedback Bias
"The greatest of faults is to be conscious of none" ~Thomas Carlyle
Feedback bias is another cognitive error that may be particularly pertinent to anesthesiology. This describes the
process that occurs when significant time elapses between actions and consequences, or outcome data is never
reported back to the practitioner. When important information does not return to the decision maker, it is impossible
to shape future decisions based upon that information. As such, the absence of feedback is subconsciously noted as
positive feedback.
Confirmation Bias
"I will look at any additional evidence to confirm the opinion to which I have already come"
--Lord Molson
Believing is seeing: confirmation bias is an error characterized by seeking confirming evidence to support a
diagnosis while discounting disconfirming evidence, despite the latter often being more definitive. Sometimes this
will manifest by "cherry-picking", or trying to force data to fit a desired or suspected diagnosis. A simple example in
anesthesiology might be the repeating of blood pressure measurements, changing cuff sizes and locations, in an
effort to get a reassuring reading, instead of recognizing the hypotension as real. The same could be said for nearly
any monitoring device or interpretation of labs or other studies.
Availability Bias
"Nothing fixes a thing so intensely in the memory as the wish to forget it." ~Michel de Montaigne
Availability bias is an error in diagnosis due to an emotionally memorable past experience. These are the
experiences by which physicians sometimes say they've "been burned", and these memories make the diagnosis
readily available at the forefront of the mind. When this error occurs, the physician may subconsciously ignore
important differences between the current presentation and that prior experience.
Omission Bias
"The man who makes no mistakes does not usually make anything." ~Edward Phelps
Omission Bias is the tendency toward inaction rather than action, out of fear of failure or being wrong. In the
operating room environment, "group think" can contribute heavily towards this, especially if others do not agree
with the proposed diagnosis or treatment. Consider the case of a suspected pneumothorax, yet the surgeons are
adamant that none could exist and they resist placing a chest tube. Psychologically, it may be difficult to override
this and perform needle decompression. This may be especially likely when a significant authority gradient is
perceived (as with a less experienced anesthesiologists and very senior surgeon) or is real (as may be the case with a
surgeon directly supervising a nurse anesthetist, without an anesthesiologist).
Other cognitive errors include:
Commission Bias
"You will do foolish things, but do them with enthusiasm." ~ Sidonie-Gabrielle Colette
This describes the tendency towards action rather than inaction, even when those actions are un-indicated or founded
on desperation.
435
Page 4
Sunk Costs
"Insanity is doing the same thing over and over again and expecting different results." ~ Albert Einstein
Sunk costs describes the phenomenon during which the more effort and commitment invested towards a plan, the
harder it may become psychologically to abandon or revise that plan, because it has been established as the "right"
plan. Continued unsuccessful perseveration may result in patient harm.
Fixation
"If you can see the light at the end of the tunnel, you are looking the wrong way. ~ Barry Commoner
"He who has a one-track mind, his train of thought often becomes derailed ~ Arthur Blank
Fixation is focusing on one feature or problem exclusively, at the expense of comprehensive situation awareness.
This may lead to misdiagnosis of a single problem by failing to understand all of its facets, or missing concurrent
diagnoses by focusing on just one.
Framing Effect/Unpacking Principle
"An error does not become truth by reason of multiplied propagation" ~ Gandhi
These describe the mistake of allowing early presenting features to unduly influence decisions. This may be related
to the way a patient history is presented by others, or to our own filters as we review information. Related to this
concept is that of the "Sticky Diagnosis," in which an erroneous diagnosis is recorded in the chart (Latex allergy, for
example) and is never removed despite its discovery by many subsequent caregivers.
Overconfidence/Denial
"Thinking you know when in fact you don't is a fatal mistake ~ Bertrand Russell
The labels "Overconfidence" and "Denial" need no explanation, but it may be puzzling as to why these are so
heavily represented in adverse outcome anecdotes, cases resulting is legal action or quality committee reviews, and
autopsy studies.[10]
What can be done to prevent cognitive errors?
Cognitive errors are considerably less tangible than procedural or factual errors. They are described as "low-
visibility", rarely witnessed or recorded, usually with low awareness on the part of the thinker, not conducive to
root-cause analysis, yet potentially highly preventable. [13]
Before we can do anything to prevent errors, we need to understand why we make them.
Reducing cognitive errors depends upon a few distinct but related factors: self-awareness, metacognition, and
cognitive de-biasing.
Increased self-awareness is imperative. Studies of unconscious mental influences demonstrate that increased self-
awareness leads to better management of these cognitive distortions.
7
How can we increase our self-awareness
about our own errors? Although error-blindness presents an inherent challenge, one strategy is the systematic and
deliberate reflection upon one's thoughts, forecasts, and predictions to reveal inherent biases. [1] A self-guided
"debriefing" at the conclusion of each case or each day is one way to accomplish this, though it requires routinely
challenging one's own decisions and rationale with a good deal of skepticism.
Second, because no single strategy of decision making is appropriate for every situation, selection of thought
strategy must be deliberate, and less automatic. Our brains are pluralist: we can carefully analyze and reason
through options, and we can make intuitive "gut instinct" decisions. A crucial step towards avoiding error is
figuring out which brain system is best for a given circumstance. Should we trust our intuitions or calculate the
probabilities? Have we considered the true base-rate, or are we allowing anecdotes to inflate or deflate the

435
Page 5
prevalence of a particular problem? We must be thinking about how we think, and considering the specific
environment in which we are thinking. [14]This process is called metacognition.

Third, we must employ counterbalancing strategies in our metacognitive practice, which have been shown to reduce
the impact of subconscious tendencies on decision making. Basic features of metacognitive practice include
recognition of limitations of memory, ability to mentally "step back" and appreciate a broader perspective, good
capacity for self-critique and harnessing overconfidence, and the ability to select specific strategies for best decision
making. Engage in deliberate self checks, asking: "Am I using the best decision-making strategy right now?" and
"Am I relying too heavily on pattern-recognition or bias?" Routinely force yourself to be less certain, and treat
predictions as provisional works-in-progress at all times. [1] Engage in the process of prospective hindsight (used
in military strategy) in which the physician imagines his decision ultimately found to be wrong, and then answers
the question What did I miss?[15]

Cognitive self-monitoring requires a trigger that helps clinicians rescue themselves from error[16]. One such
strategy in anesthesiology is the Rule of Three[17]. This strategy may be applied to both therapeutic as well as
diagnostic decisions, and requires that the anesthesiologist consider at least three alternative explanations before a
diagnosis may be accepted, and also requires a re-assessment of the diagnosis if the first three treatment maneuvers
do not have the response expected.

In conclusion, human nature and largely hardwired cognitive processes leave us prone to error by the same
mechanisms we make usually accurate decisions. Awareness of these tendencies, as well as regular use of
counterbalancing strategies, may prevent us from making mistakes, or at least allow us to recognize and recover
more quickly.

"An expert is a man who has made all the mistakes which can be made in a very narrow field."
~Niels Bohr

1. Schulz, K., Being Wrong: Adventures in the Margin of Error.2010, New York, NY: Harper Collins
Publishers.
2. Kohn, L.T., J. Corrigan, and M.S. Donaldson, To err is human : building a safer health system2000,
Washington, D.C.: National Academy Press. xxi, 287 p.
3. Brennan TA, L.L., Laird NM, Hebert L, Localio AR, Lawthers AG, et al. , Incidence of adverse events and
negligence in hospitalized patients. . N Engl J Med, 1991(324): p. 370-376.
4. Croskerry, P., Achieving quality in clinical decision making: cognitive strategies and detection of bias.
Acad Emerg Med, 2002. 9(11): p. 1184-204.
5. Groopman, J., How Doctors Think2007, New York, NY: Houghton Mifflin.
6. Stiegler, M.P., et al., Cognitive errors detected in anaesthesiology: a literature review and pilot study. Br J
Anaesth, 2012. 108(2): p. 229-35.
7. Hallinan, J., Why We Make Mistakes: How We Look Without Seeing, Forget Things in Seconds, and Are All
Pretty Sure We Are Way Above Average2009, New York, NY: Random House.
8. Fine, C., A mind of its own: how your brain distorts and deceives. . 1st ed ed2006, New York, NY: W.W.
Norton & Company.
9. Tavris C, A.E., Mistakes Were Made (But Not By Me): Why We Justify Foolish Beliefs, Bad Decisions, and
Hurtful Acts. 2007, Orlando, FL: Houghton Mifflin Harcourt.
10. Berner, E.S. and M.L. Graber, Overconfidence as a cause of diagnostic error in medicine. American
Journal of Medicine, 2008. 121(5): p. 2-23.
11. Kida, T., Don't Believe Everything You Think: The 6 Basic Mistakes We Make in Thinking2006, Amherst,
NY: Promethius Books.
12. Graber, M.L., N. Franklin, and R. Gordon, Diagnostic error in internal medicine. Arch Intern Med, 2005.
165(13): p. 1493-9.
13. Croskerry, P., Cognitive forcing strategies in clinical decisionmaking. Ann Emerg Med, 2003. 41(1): p.
110-20.
14. Lehrer, J., How We Decide2009, New York, NY: Houghton Mifflin Harcourt.

435
Page 6
15. Singh, H. and M. Graber, Reducing diagnostic error through medical home-based primary care reform.
JAMA, 2010. 304(4): p. 463-4.
16. Kassirer, J.P., Teaching clinical reasoning: case-based and coached. Acad Med, 2010. 85(7): p. 1118-24.
17. Stiegler, M.P. and K.J. Ruskin, Decision-making and safety in anesthesiology. Curr Opin Anaesthesiol,
2012. 25(6): p. 724-9.

Disclosure

101
Page 1
Cancer Pain Management in 2013
Oscar A. de Leon-Casasola, M.D. Buffalo, New York
Lecture Objectives:
1) Review the fundamental steps for evaluating cancer pain in patients.
2) Discuss the available therapies for managing cancer pain.
3) Develop a plan for evaluating and treating cancer pain patients.
Outline:
1. Incidence and prevalence of cancer related pain
2. Prevalence of untreated cancer related pain
3. Somatic, visceral and/or neuropathic pain in cancer
4. Selecting appropriate therapy for cancer pain
5. Choosing the appropriate long-acting and short-acting opioides for cancer related pain: an individualized
approach
6. Indications for adjuvant medications in cancer related pain
7. How to choose adjuvant medication in cancer related pain
8. Caveats in the use of opioids and adjuvant analgesics in cancer related pain
9. Is neurolysis of the sympathetic axis (celiac, splanchnic, and superior hypogastric neurolytic blocks) still
indicated?
10. Indications for epidural and intrathecal techniques in cancer related pain
11. How to optimize IT techniques for optimal pain control
12. Does spinal cord stimulation have a place in cancer related pain control?
13. What is the role of peripheral nerve stimulation in cancer related pain?
14. Should I still use vertebroplasty and/or kyphoplasty for vertebral metastatic fractures control of pain?
15. Conclusions.
111
Page 1
Complications in Pain Medicine Practice
Richard W. Rosenquist, M.D. Cleveland, Ohio
Introduction
Contemporary pain management is founded on appropriate diagnostic evaluation followed by multimodal treatment
incorporating medical, psychological, physical and interventional modalities. The use of interventional therapies in
this context has seen consistent growth in both type and volume of interventional procedures used to treat chronic
pain conditions. Incomplete or inadequate treatment responses to current treatment modalities have fostered
ongoing research and the introduction of many new treatment modalities. While new interventional techniques have
improved outcomes in some patients, they have also been associated with severe complications. These include
commonly reported complications such as pneumothorax, headache, back pain, bleeding, drug toxicity and infection
as well as reports of catheter, lead or device breakage, methylmethacrylate migration, granuloma development,
direct neural trauma, stroke and death. This refresher course addresses complications related to interventional pain
treatments and suggests methods for their avoidance when appropriate.
Scope of the Problem
The relative risks of interventional pain therapies have been steadily increasing in concert with the increase in
medical judgment and technical skill required to use them effectively. In a 2004 publication derived from data
maintained within the American Society of Anesthesiologists Closed Claims Project, Fitzgibbon et al.
1
identified and
described issues and trends in liability related to chronic pain management by anesthesiologists. The authors
reviewed the closed claims database between 1970 and 1999 to identify liability related to chronic pain
management. They excluded all claims related to acute pain management. They compared outcomes and liability
characteristics of 284 pain management claims to 5,125 surgical/obstetric claims. Claims related to chronic pain
management increased over time in concert with the growth in pain medicine. They accounted for 2% of the claims
in the 1970s, 3% in the 1980s and 10% of all claims in the 1990s. Payments for chronic pain management claims
were lower than surgical/obstetric claims from 1970-1989. During the 1990s, there was no difference in size of
payments between chronic pain management and surgical/obstetric claims. Almost one-third of chronic pain
management claims resulting in payment in the 1990s involved a permanent and disabling injury as compared to
only 17% from 1979-1989 although this difference was not considered statistically different. In 64% of chronic pain
management claims, the injury became apparent after discharge from the treatment facility. Of the 284 chronic pain
management claims in the database, 276 involved invasive procedures. Epidural steroid injections accounted for
83% of injections and 40% of all chronic pain management claims. Peripheral and autonomic blocks accounted for
36% of the block claims. The most common complication of blocks was pneumothorax. The most common
complications involving epidural steroids were nerve injury, infection and headache. Claims related to ablative
procedures involved unintentional nerve injury in 47% of the cases. Infection or retained catheter fragments were
the most common complications related to implantation or removal of devices, while the most common outcome of
claims related to maintenance of devices was death or brain damage. In 2010, Rathmell et al,
2
compared cervical
procedures to other chronic pain claims collected from 2005 through 2008 in the ASA Closed Claims Database. The
data in this manuscript is notable not only for the dramatic number of claims related to cervical procedures, but the
fact that more chronic pain claims were entered in a four year period than in the entire previous review of chronic
pain claims for a 30 year period. There were 64 cervical procedure claims (22%) among 294 chronic pain claims.
Cervical procedure claims occurred more often among women and in healthier individuals. The most common
diagnoses included cervical radicular pain (50%) and neck pain of musculoskeletal origin (28%), CRPS (11%) and
spinal stenosis (5%). Ninety-one percent of the cervical procedures were blocks with (67%) being epidurals, (11%)
stellate ganglion blocks, (9%) trigger point injections and (3%) intra-articular facet injections. In eighty percent of
the cases, the damaging event was directly related to the procedure; needle trauma to the cord (31%), cord
infarction/stroke after intra-arterial injection (14%), dural puncture (6%), compressive hematoma (5%), infection or
abscess (5%), high block/total spinal (5%), inadvertent intravascular injections of local anesthetic (3%) and

111
Page 2
pneumothorax (3%). General anesthesia or sedation was used in (67%) of cervical procedure claims with spinal
cord injuries, but only (19%) of cervical procedure claims without spinal cord injuries. In claims with information
regarding radiographic guidance, it was used in (76%) of cases with spinal cord injury. The authors found evidence
of contrast use with radiographic guidance in (57%) of claims with spinal cord injury compared with (17%) of
claims without spinal cord injury after a cervical procedure. Further study is needed to develop reliable approaches
to prevent catastrophic neurologic injuries occurring during pain procedures at the cervical level and to clarify the
role that general anesthesia and/or sedation may have in the occurrence and severity of injury. Although data in
these studies is limited to closed claims, the trends identified provide valuable insight into the significant
complications associated with interventional pain procedures and in particular cervical interventional pain
procedures that have limited evidence to support their use.

Injections (Trigger Point, Facets, Epidural Steroid Associated Agents, Other)

Injections are performed with the greatest frequency and have the greatest number of complications. Trigger point
injections have been associated with a variety of significant complications including, bleeding, local infection,
epidural abscess,
3
seizure, myotoxicity
4
and pneumothorax.
5
Facet injections are performed less commonly, but have
been associated with significant complications as well. Those reported in the medical literature include infection,
6,7

pneumothorax
1
, spinal cord injury and death.
8,.9,10
The medical literature is sparse concerning other complications
that may have occurred in association with facet injection, but hematoma and nerve injury would not be unexpected.
The largest and most devastating group of complications has been associated with performance of epidural steroid
injections. Although common, the occurrence of accidental dural puncture is less threatening than other reported
complications. Some practitioners have advocated the use of the transforaminal approach as a means of avoiding
dural puncture. A cases series of transforaminal injections published in 2000 using both fluoroscopy and contrast
confirmation identified 0/322 procedures with dural puncture, although the incidence of transient headache in the
same study was reported at 3.1%.
11
Another prospective series performed at two academic medical centers using an
interlaminar approach reported a 0.8% incidence of dural puncture with only 25% of cases being performed with
fluoroscopy and contrast confirmation.
12
Epidural hematoma has been reported at all levels of the spine following
epidural injections and has an estimated incidence of 1:150,000.
13
There have been numerous reports of epidural
hematoma occurring after epidural steroid injection.
14,15,16,17
In general, if anticoagulant agents are avoided as
described in the ASRA guideline for neuraxial anesthesia or limited to NSAIDs alone, the risk of epidural hematoma
is felt to be unchanged from the norm.
12,13
Infection involving the epidural space, discitis, meningitis and
osteomyelitis has been reported following epidural steroid injection.
18
Epidural abscesses occur spontaneously with
an incidence that has been reported as 0.33-1.96:10,000 admissions per year
19
.The incidence of epidural abscess
development related to performance of epidural steroid injections has not been reported. However, there are
numerous case reports identifying epidural abscess development.
20,21,22,23,24,25,26
This complication is more insidious
as it develops after the patient has left the treatment facility and may not be promptly discovered or reported by the
patient. Underlying medical illnesses and impaired immune function may increase the risk of this complication,
which is most commonly produced by Staphylococcus aureus species. In those with significant immune
compromise, prophylactic antibiotics at the time of the procedure may be warranted. In 2012, a multistate outbreak
of fungal meningitis and other infections was reported by the Centers for Disease Control and Prevention (CDC), in
collaboration with state and local health departments and the Food and Drug Administration (FDA). This outbreak
was ultimately tied to contaminated steroid injections using compounded steroids prepared by the New England
Compounding Center. As of June 3, 2013 the reported case count related to these injections was 745 in 20 states
with 58 fatalities.
27
Neuropathic pain may develop following epidural steroid injection and has been hypothesized
to be the result of nerve root irritation caused by the steroid solution or damage to the spinal cord or nerve roots
without dural puncture by minor compression of neural elements.
28
Direct trauma to the spinal cord in association
with performance of cervical, thoracic and lumbar epidural steroid injections has been reported in procedures
performed both with and without fluoroscopic imaging.
29
Those cases associated with demonstrable spinal cord
injury have been associated with permanent neurological injury. A variety of methods to avoid this type of
devastating complication have been proposed, including avoiding sedation, using imaging, contrast administration or
use of a local anesthetic test dose prior to injection. However, significant injury has occurred despite the use of all
currently recommended safety measures. Tripathi et al., reported a case of paraplegia after intracord injection
during attempted epidural steroid injection in an awake patient under fluoroscopic guidance.
30
In the case report,
they comment it seems fluoroscopy guidance may not prevent intrathecal perforation or spinal cord penetration.
In a letter to the editor regarding this article published in May 2006, Drs. Munir, Rastogi and Nedeljkovic comment
that the implications of this statement cannot be understated and reiterate the fact fluoroscopy does not protect

111
Page 3
patients from injection related complications.
31
This is corroborated in the Anesthesia Patient Safety Foundation
newsletter published in 2005 that analyzed 13 claims related to complications after cervical epidural steroid
injections.
32
Twelve of 13 cases had been performed with fluoroscopic guidance. In recent years, transforaminal
approaches to epidural steroid injections including both lumbar and cervical approaches have been associated with a
growing number of severe complications including blindness, stroke, spinal cord injury and death.
33,34,35,36,37,38
The
exact etiology of these devastating injuries is not clear, but has been variously theorized to be the result of radicular
artery spasm, vascular injury or intravascular injection of particulate steroid into medullary or vertebral arteries.
Although an outright recommendation to abandon this approach has not been advocated, modifications in needle
choice, needle location, imaging and drug choice have all been proposed. At the present time, needle placement in
a dorsal portion of the foramen where medullary vessels are less likely to be located is being proposed as one means
of reducing risk. In addition, the use of live fluoroscopy during injection of contrast along with digital subtraction
angiography (DSA) if it is available is recommended. The use of DSA improves the sensitivity of detecting
intravascular injection.
39
Some clinicians have advocated injecting local anesthetics prior to injecting a steroid
medication and the use of non-particulate steroids such as Dexamethasone as a means of avoiding these
complications. Initial outcome data examining the use of Dexamethasone is limited and although effective, it may
not work as well as traditional long lasting preparations.
40,41
A 2011 dose-response trial for Dexamethasone
demonstrated meaningful improvement in radicular pain at 12 weeks after injection with parallel improvements in
disability, impression of change and satisfaction measures. There was no difference in efficacy for Dexamethasone
4 mg compared to 8 or 12 mg.(Ahadian 2011 RAPM)
42
In addition, there have been some reports of flushing after
the use of Dexamethasone in this setting with the occurrence more common in females than males.
44
The frequency
of complications related to transforaminal steroid injections has garnered the attention of the FDA and there is an
ongoing effort on their part to understand the problem and collaborate with physicians to develop recommendations
to reduce the risk of complications. Finally, co-administration of opioids, local anesthetic or both occurred in 61%
of claims reported in the ASA closed claims epidural steroid injection cases and death or brain damage occurred
only in epidural steroid injection cases that involved local anesthetics with or without opioids in the injection.
1

Blocks (Peripheral, Axial, Neuraxial, Autonomic)

The most common complication following the performance of blocks is pneumothorax and accounted for 51% of all
block claims in the ASA closed claims database. Other complications include infection, nerve injury, dural puncture,
vascular injury, hematoma, seizure and death.
43,44,45,46,47

Diagnostic Procedures (Discography)

Diagnostic discography continues to be used as a diagnostic procedure. While the performance, interpretation and
utility of this diagnostic procedure remains controversial, the technical performance of the procedure has been
associated with complications. These include direct neural trauma, dural puncture, vascular injury, drug reaction,
disc herniation and infection.
48,49,50,51,52,53
Of these, infection is the most common complication. Meticulous
technique and the use of a two-needle technique are well accepted means of reducing infectious risk.
54
Both
intravenous or intradiscal antibiotics have been utilized as infection prophylaxis although the relative success of
using either approach individually or in a combined fashion has not been defined.

Ablative Procedures (Radiofrequency ablation, IDET, Coblation, Chemical)

The performance of neuroablative procedures has been associated with a variety of complications. The common
complications of infection, hematoma and direct nerve injury as reported with other nonablative procedures are
expected. However, complications reported with ablative techniques may also be produced by heat injury outside of
the desired area of effect in the case of radiofrequency ablation or IDET and unexpected spread of the neurolytic
agent in the case of chemical denervation.
55
The most commonly reported complications related to IDET include
disc herniation and nerve root injury.
56,
In addition, a case report of a broken IDET catheter migrating intradurally,
producing radiculopathy and requiring surgical removal has been published. There have also been reports of spinal
cord injury due to inappropriate lead placement. Major neurologic injury has been reported in relation to the
performance of neurolytic celiac plexus blocks with both alcohol and phenol and in one series had an incidence of
1:683.
60
The mechanism of injury may be related to vascular injury, vascular injection of the neurolytic agent or
direct neural trauma.
61,62,63,64

111
Page 4
Disc Decompression, Nucleoplasty and Laser Discectomy

There is growing interest in the use of devices to reduce disc volume as an alternative to microdiscectomy or open
discectomy in patients with contained disc herniation. A variety of techniques have been used including mechanical
devices that remove small amounts of disc material, lasers and plasma-mediated ablation. Complications following
the performance of these procedures have included mechanical failure of a Dekompressor unit resulting in four
inches of the probe remaining in the patient after removal of the probe and epidural fibrosis.
65,66
As with any
percutaneous procedure, complications such as localized pain, infection, bleeding and nerve injury have also been
reported.
67,68

Vertebroplasty and Kyphoplasty

Despite the controversies surrounding the use of vertebroplasty and kyphoplasty, these techniques are still in
widespread use and for well selected patients, the outcomes are excellent. These procedures have been associated
with a wide variety of devastating complications including; spread into the spinal canal, late collapse after
vertebroplasty,
69
migration of cement mass,
70
pulmonary migration of cement,
71
pericardial tamponade and right
ventricular cement embolus due to right ventricle perforation during kyphoplasty (reference Tran I, Gerckens U,
Remig J, Zintl G, Textor J. First report of a life-threatening cardiac complication after percutaneous balloon
kyphoplasty. Spine 2013;38:E316-8.
7270
and lumbar artery pseudoaneurysm.
72
These procedures require great care
in patient selection and technique to optimize outcomes.

Implantation, Maintenance or Removal of Devices (Intrathecal, Epidural, Spinal Cord Stimulation)

The use of devices to facilitate drug delivery into the epidural or subarachnoid spaces or provide analgesia via
electrical stimulation of the spinal cord has seen significant growth related to the treatment of both non-cancer and
cancer related pain. Complications have resulted from implantation, maintenance and removal of these devices.
Nerve injury, infections, retained catheter fragments or equipment failure are the most common complications
related to implantation and removal of devices.
73,74
A prospective study by Follett and Naumann identified frequent
procedure related complications and underscored the need for careful surgical technique and adherence to implant
guidelines.
75
Complications occurring with maintenance of devices were related to pump programming errors, drug
overdose, drug error, concomitant administration of other central nervous system depressants and toxicity or
granuloma formation related to chronic intrathecal drug administration.
1,76,77,78,79,80,81
The incidence of granuloma
formation has not been reported, but may be much higher than expected as a result of slow growth and lack of
immediate symptom development. In addition, a recent study has suggested that non-cancer pain patients receiving
intrathecal opioids have an increased risk of mortality.
81
Regular evaluation of equipment performance, patient
function and response to treatment to facilitate detection and treatment of complications at the earliest opportunity is
important.

Training in Pain Medicine and Interventional Procedures

The role of training in the incidence and severity of complications related to interventional pain procedures has not
been examined. The range of training received prior to the performance of interventional procedures is highly
variable and ranges from fellowship trained pain medicine physicians with board certification to physicians with
some exposure during residency to physicians from non-interventional specialties taking weekend courses to learn
interventional procedures to improve the revenue stream of their practice. In addition, there are non-physician
providers with no formal pain training or certification who are performing the entire range of interventional pain
procedures. In most cases, the public lacks sufficient sophistication to inquire about the extent of training or board
certification prior to undergoing procedures. In other cases, there may be active misrepresentation of credentials. In
the case of free standing offices, there is no formal requirement to examine the training or certification of individuals
providing pain care. In the hospital setting, the credentials committee may choose to establish a low or high
standard in granting privileges to perform interventional pain procedures. In addition, various states have
established certain criteria through the medical boards to regulate pain medicine or establish standards. The net
effect of these efforts to improve care and reduce complications remains to be seen.

111
Page 5
Avoiding Complications

The ability to avoid complications prospectively is a desirable and appropriate goal for pain medicine. This
includes the need to maintain high standards throughout our practices and participate in ongoing education. There
are fundamentals such as using appropriate sterile technique for the handling of medications and performance of
interventional procedures. We need to examine new procedures from multiple perspectives including anatomy,
physiology, pharmacology and predicted outcome prior to performing them on humans to determine what
complications may occur and how best to avoid them. We also need to develop consistent approaches that
represent best practices in order to reduce the risks to our patients. This may include the use of algorithms or
checklists to standardize approaches. However, even if these are developed and used, we must constantly question
each step along the way and look for ways to improve further. We must also improve our collection of outcome
data and report them into national databases. This will not only help to determine which procedures are effective,
but to identify disturbing trends in a more proactive fashion. In most cases, if an unusual circumstance is
encountered such as aspiration of blood or vascular runoff during injection of contrast, it is reasonable to consider
stopping the procedure and either performing it again later the same day or rescheduling for another day. There is
no substitute for good judgment and few chronic pain procedures are emergent.

Conclusions

Interventional therapies provide pain relief to a broad range of patients, but are associated with the potential for
disastrous consequences. It is critical that we continue to examine the complications associated with these
procedures and develop clear criteria for patient selection, training and technical performance to provide the greatest
potential to produce the desired outcomes. We must be acutely aware of unusual or unexpected symptoms or
images before, during or after procedures and aggressive in diagnosing and treating complications as they arise.
Furthermore, we must educate our patients about the potential complications that may develop following discharge
so that they may promptly seek appropriate medical care. Finally, we must systematically examine treatment
outcomes and complications in our own practices, through reports in the medical literature and through systems like
the Anesthesia Quality Institute (AQI) and the ASA closed claims database so that awareness may be raised,
disturbing patterns recognized and improvements in patient selection and technique promoted to the medical
community.

References:

1. Fitzgibbon DR, Posner KL, Domino KB, Caplan RA, Lee LA, Cheney FW. Chronic Pain Management:
American Society of Anesthesiologists Closed Claims Project. Anesthesiology 2004 Jan;100:98-105.
2. Rathmell JP, Michna E, Fitzgibbon DR, Stephens LS, Posner KL, Domino KB. Injury and liability associated
with cervical procedures for chronic pain. Anesthesiology 2010;114:918-26.
3. Elias M. Cervical epidural abscess following trigger point injection. J Pain Symptom Manage. 1994 Feb;9:71-
2.
4. Zink W, Graf BM. Local anesthetic myotoxicity. Reg Anesth Pain Med 2004 Jul-Aug;29:333-40.
5. Shafer N. Pneumothorax following trigger point injection. JAMA 1970 Aug;213:1193
6. Orpen NM, Birch NC. Delayed presentation of septic arthritis of a lumbar facet joint after diagnostic facet
joint injection. J Spinal Disord Tech 2003 Jun;16:285-7.
7. Cook NJ, Hanrahan P, Song S. Paraspinal abscess following facet joint injection. Clin Rheumatol
1999;18:52-3.
8. Kim SY, Han SH, Jung MW, Hong JH. Generalized infection following facet joint injection A case report.
Korean J Anesthesiol 2010;58:401-4.
9. Hoelzer BC, Weingarten TN, Hooten WM, Wright RS, Wilson WR, Wilson PR. Paraspinal abscess
complicated by endocarditis following a facet joint injection. Eur J Pain 2008;12:261-5

111
Page 6
10. Edlow BL, Wainger BJ, Frosch MP, Copen WA, Rathmell JP, Rost NS. Posterior circulation stroke after C1-
C2 intraarticular facet steroid injection: evidence for diffuse microvascular injury. Anesthesiology
2010;112:1532-5.
11. Botwin KP, Gruber RD, Bouchlas CG, Torres-Ramos FM, Freeman TL, Slaten WK. Complications of
fluoroscopically guided transforaminal lumbar epidural injections. Arch Phys Med Rehabil 2000
Aug;81:1045-50.
12. Horlocker TT, Bajwa ZH, Ashraf Z, Khan S, Wilson JL, Sami N, Peeters-Asdourian C, Powers CA,
Schroeder DR, Decker PA, Warfield CA. Risk assessment of hemorrhagic complications associated with
nonsteroidal anti-inflammatory medications in ambulatory pain clinic patients undergoing epidural steroid
injection. Anesth Analg 2002 Dec;95:1601-7.
13. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT, Brown DL, Heit JA, Mulroy
MF, Rosenquist RW, Tryba M, Yuan CS. Regional anesthesia in the patient receiving antithrombotic or
thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based
Guidelines (Third Edition). Reg Anesth Pain Med 2010;35:64-101.
14. Ain RJ, Vance MB. Epidural hematoma after epidural steroid injection in a patient withholding enoxaparin
per guidelines. Anesthesiology 2005 Mar;102:701-3.
15. Stoll A, Sanchez M. Epidural hematoma after epidural block: implications for its use in pain management.
Surg Neurol 2002 Apr;57:235-40.
16. Williams KN, Jackowski A, Evans PJ. Epidural hematoma requiring surgical decompression following
repeated cervical epidural steroid injections for chronic pain. Pain 1990 Aug;42:197-9.
17. Ghaly RF. Recovery after high-dose methylprednisolone and delayed evacuation: a case of spinal epidural
hematoma. J Neurosurg Anesthesiol 2001 Oct;13:323-8.
18. Hlavin ML, Kaminski HJ, Ross JS, Ganz E. Spinal epidural abscess: a ten-year perspective. Neurosurgery
1990;27:177-184.
19. Hooten, WM, Mizerak A, Carns PE, Huntoon MA. Discitis after lumbar epidural corticosteroid injection: A
case report and analysis of the case report literature. Pain Med 2006;7:46-51.
20. Hooten WM, Kinney MO, Huntoon MA. Epidural Abscess and meningitis after epidural corticosteroid
injection. Mayo Clin Proc. 2004 May;79:682-6.
21. Saigal G, Donovan Post MJ, Kozic D. Thoracic intradural abscess formation following epidural steroid
injection. AJNR Am J Neuroradiol. 2004 Apr;25:642-4.
22. Huang RC, Shapiro GS, Lim M, Sandhu HS, Lutz GE, Herzog RJ. Cervical epidural abscess after epidural
steroid injection. Spine 2004 Jan;29:E7-9.
23. Koka VK, Potti A. Spinal epidural abscess after corticosteroid injections. South Med J 2002 Jul;95:772-4.
24. Knight JW, Cordingley JJ, Palazzo MG. Epidural abscess following epidural steroid and local anesthetic
injection. Anaesthesia 1997 Jun;52:576-8.
25. Waldman SD. Complications of cervical epidural nerve blocks with steroids: a prospective study of 790
consecutive blocks. Reg Anesth 1989 May-Jun;14:149-51.
26. Chan ST, Leung S. Spinal epidural abscess following steroid injection for sciatica. Case report. Spine 1989
Jan;14:106-8.
27. Centers for Disease Control and Prevention Multistate Fungal Meningitis Outbreak Investigation
www.cdc.gov/hai/outbreaks/meningitis.html
28. Field J, Rathmell JP, Stephenson JH, Katz NP. Neuropathic pain following cervical epidural steroid injection.
Anesthesiology 2000 Sep;93:885-88.
29. Hodges SD, Castleberg RL, Miller T, Ward R, Thornburg C. Cervical epidural steroid injection with intrinsic
spinal cord damage. Two case reports. Spine 1998 Oct;23:2137-42.

111
Page 7
30. Tripathi M, Nath SS, Gupta RK. Paraplegia after intracord injection during attempted epidural steroid
injection in an awake patient. Anesth Analg 2005;101:1209-1211.
31. Munir MA, Rastogi R, Nedeljkovic S. Fluroscopy and safety of spinal interventional procdures. Anesth
Analg 2006;102:1585-1598.
32. Lofsky AS. Complications of cervical epidural blocks attract insurance company attention. APSF Newsletter
2005;20:45-48.
33. Rozin L, Rozin R, Koehler SA, Shakir A, Ladham S, Barmada M, Dominick J, Wecht CH. Death during
transforaminal epidural steroid nerve root block (C7) due to perforation of the left vertebral artery. Am J
Forensic Med Pathol 2003 Dec;24:351-5.
34. Furman MB, Giovanniello MT, OBrien EM. Incidence of intravascular penetration in transforaminal cervical
epidural steroid injections. Spine 2003 Jan;28:21-5.
35. Karasek M, Bogduk N. Temporary neurologic deficit after cervical transforaminal injection of local
anesthetic. Pain Med 2004;5:202-5.
36. Baker R, Dreyfuss P, Mercer S, Bogduk N. Cervical transforaminal injection of corticosteroids into a
radicular artery: a possible mechanism for spinal cord injury. Pain 2003;103:211-15.
37. McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal
injection for cervical radiculopathy. Anesthesiology 2003 Aug;99:509-11.
38. Huntoon MA, Martin DP. Paralysis after transforaminal epidural injection and previous spinal surgery. Reg
Anesth Pain Med 2004 Sep-Oct;29:494-5.
39. Lee MH, Yang KS, Kim YH, Jung HD, Lim SJ, Moon DE. Accuracy of live fluoroscopy to detect
intravascular injection during lumbar transforaminal epidural injections. Korean J Pain 2010;23:18-23.
40. Lee JW, Park KW, Chung SK, Yeom JS, Kim KJ, Kim HJ, Kang HS. Cervical transforaminal epidural
steroid injection for the management of cervical radiculopathy: A comparative study of particulate versus
non-particulate steroids. Skeletal Radiol 2009;38:1077-82.
41. Park CH, Lee SH, Kim BI Comparison of the effectiveness of lumbar transforaminal epidural injection with
particulate and nonparticulate corticosteroids in lumbar radiating pain. Pain Med 2010;11:1654-8.
42. Ahadian FM, McGreevy K, Schulteis G. Lumbar transforaminal epidural dexamethasone: a prospective,
randomized, double-blind, dose-response trial. Reg Anesth Pain Med 2011;36:572-8

43. Kim CH, Issa MA, Vaglienti RM. Flushing following interlaminar lumbar epidural steroid injections with
dexamethasone. Pain Physician 2010;13:481-4.
44. Maeda S, Murakawa K, Fu K, Kamihara M, Tashiro C. A case of pyogenic osteomyelitis of the cervical spine
following stellate ganglion block. Masui 2004 Jun;53:664-7.
45. Artuso JD, Stevens RA, Lineberry PJ. Post dural puncture headache after lumbar sympathetic block: a report
of two cases. Reg Anesth 1991 Sep-Oct;16:288-91.
46. Maier C, Gleim M, Weiss T, Stachetzki U, Nicolas V, Zenz M. Severe bleeding following lumbar
sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors.
Anesthesiology 2002 Sep;97:740-3.
47. Sett SS, Taylor DC. Aortic pseudoaneurysm secondary to celiac plexus block. Ann Vasc Surg 1991
Jan;51:88-91
48. Kashiwagi M, Ikeda N, Tsuji A, Kudo K. Sudden unexpected death following stellate ganglion block. Leg
Med (Tokyo) 1999 Dec;1:262-5.
49. Junila J, Niinimaki T, Tervonen O. Epidural abscess after lumbar discography. A case report. Spine 1997
Sep 15;22:2191-3.

111
Page 8
50. Zeidman SM, Thompson K, Ducker TB. Complications of cervical discography: analysis of 4400 diagnostic
disc injections. Neurosurgery 1995 Sep;37:414-7.
51. Smith MD, Kim SS. A herniated cervical disc resulting from discography: an unusual complication. J Spinal
Disord 1990 Dec;3:392-4.
52. Lownie SP, Ferguson GG. Spinal subdural empyema complicating cervical discography. Spine 1989
Dec;14:1415-7.
53. Fraser RD, Osti OL, Vernon-Roberts B. Discitis after discography. J Bone Joint Surg Br. 1987 Jan;69:26-35.
54. Laun A, Lorenz R, Agnoli AL. Complications of cervical discography. J Neurosurg Sci 1981 Jan-Mar;25:17-
20.
55. Willems PC, Jacobs W, Duinkerke ES, De Kleuver M. Lumbar discography: should we use prophylactic
antibiotics? A study of 435 consecutive discograms and a systematic review of the literature. J Spinal Disord
Tech 2004 Jun;17:243-7.
56. Abbott Z, Smuck M, Haig A, Sagher O. Irreversible spinal nerve injury form dorsal ramus radiofrequency
neurotomy: A case report. Arch Phys Med Rehabil 2007;88:1350-2.
57. Cohen SP, Larkin T, Abdi S, Chang A, Stojanovic M. Risk factors for failure and complications of intradiscal
electrothermal therapy: a pilot study. Spine 2003;28:1142-47.
58. Saal JA, Saal JS, Wetzel FT, et al. IDET related complications: a multi-center study of 1675 treated patients
with a review of the FDA MDR data base. Proceedings of the 16th Annual Meeting of the North American
Spine Society. Seattle, WA, Oct-Nov 2001:187.
59. Davies DD. Incidence of major complications of neurolytic coeliac plexus block. J R Soc Med 1993
May;86:264-6.
60. Kumar A, Tripathi SS, Dhar D, Bhattacharya A. A case of reversible paraparesis following celiac plexus
block. Reg Anesth Pain Med 2001 Jan-Feb;26:75-8.
61. De Conno F, Careceni A, Aldrighetti L, Magnani G, Ferla G, Comi G, Ventafridda V. Paraplegia following
coeliac plexus block. Pain 1993 Dec;55:383-5.
62. van Dongen RT, Crul BJ. Paraplegia following coeliac plexus block. Anaesthesia 1991 Oct;46:862-3.
63. Cherry DA, Lamberty J. Paraplegia following coeliac plexus block. Anaesth Intensive Care 1984 Feb;12:59-
61.
64. Domsky R, Goldberg ME, Hirsh RA, Scaringe D, Torjman MC. Critical failure of a percutaneous discectomy
probe requiring surgical removal during disc decompression. Reg Anesth Pain Med 2006;31:177-9.
65. Smuck M, Benny B, Han A, Levin J. Epidural fibrosis following percutaneous disc decompression with
coblation technology. Pain Physician 2007;10:691-6.
66. Bhagia S, Slipman C, Nirschl M, Isaac Z, El-Abd O, Sharps L, Garvin C. Side effects and complications after
percutaneous disc decompression using coblation technology. Am J Phys Med Rehabil 2006;85:6-13.
67. Takeno K, Kobayashi S, Yonezawa T, Hayakawa K, Hachiya Y, Uchida K, Negoro K, Timbihurira G, Baba
H. Salvage operation for persistent low back pain and sciatica induced by percutaneous laser disc
decompression performed at outside institution: correlation of magnetic resonance imaging and
intraoperative and pathological findings. Photomed Laser Surg 2006;24:414-23.
68. Miyagi R, Sakai T, Bhatia NN, Sairyo K, Katoh S, Chikawa T. J Med Investigation 2011;58:148-53.
69. Cho SM, Heo DH, Cho YJ. Spontaneuous migration of a polymethylmethacrylate mass after vertebroplasty in
osteoporotic lumbar compression fracture with avascular osteonecrosis: A case report. Joint Bone Spine
2011;78:98-9.
70. Radcliff KE, Reitman CA, Delasotta LA, Hong J, Dilorio T, Zaslavsky J, Vaccaro AR, Hipp JA. Pulmonary
cement embolization after kyphoplasty: A case report and review of the literature. Spine J 2010;10:e1-e5.71.
Puri AS, Colen RR, Reddy AS, Groff MW, DiNoble D, Killoran T, Nikolic B, Thomas AJ. Lumbar artery

111
Page 9
pseudoaneurysm after percutaneous vertebroplasty: A unique vascular complication. J Neurosurg Spine
2011;14:296-99.
72. Tran I, Gerckens U, Remig J, Zintl G, Textor J. First report of a life-threatening cardiac complication after
percutaneous balloon kyphoplasty. Spine 2013;38:E316-8.
73. Quigley DG, Arnold J, Eldridge PR, Cameron H, McIvor K, Miles JB, Varma TR. Longterm outcome of
spinal cord stimulation and hardware complications. Stereotact Funct Neurosurg 2003;81:50-6.
74. Follett KA, Boortz-Marx RL, Drake JM, DuPen S, Schneider SJ, Turner MS, Coffey RJ. Prevention and
management of intrathecal drug delivery and spinal cord stimulation system infections. Anesthesiology 2004
Jun;6:1582-94.
75. Follett KA, Naumann CP. A prospective study of catheter-related complications of intrathecal drug delivery
systems. J Pain Symptom Manage 2000 19;209-15.
76. Perren F, Buchser E, Chedel D, Hirt L, Maeder P, Vingerhoets F. Spinal cord lesion after long-term
intrathecal clonidine and bupivacaine treatment for the management of intractable pain. Pain 2004
May;109:189-94.
77. Blount JP, Remley KB, Yue SK, Erickson DL. Intrathecal granuloma complicating chronic spinal infusion of
morphine. Report of three cases. J Neurosurg 1996 Feb;84:272-6.
78. Nitescu P, Sjoberg M, Appelgren L, Curelaru I. Complications of intrathecal opioids and bupivacaine in the
treatment of refractory cancer pain. Clin J Pain 1995 Mar;11:45-62.
79. Peng P, Massicotte EM. Spinal cord compression from intrathecal catheter-tip inflammatory mass: case
report and a review of etiology. Reg Anesth Pain Med 2004 May-June;29:237-42.
80. Jones TF, Feler CA, Simmons BP, Melton K, Craig AS, Moore WL, Smith MD, Schaffner W. Neurologic
complications including paralysis after a medication error involving implanted intrathecal catheters. Am J
Med 2002 Jan;112:31-6.
81. Toombs JD, Follett KA, Rosenquist RW, Benton LM. Intrathecal catheter tip inflammatory mass: a failure of
clonidine to protect. Anesthesiology 2005 Mar;102:687-90.
82. Coffey RJ, Owens ML, Broste SK, Dubois MY, Ferrante FM, Schultz DM, Stearns LJ, Turner MS. Mortality
associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer
pain. Anesthesiology 2009;111:881-91.

Disclosure

203
Page 1
Epidural Steroids: Evidence Basis, Emerging Science and Safety Issues
Marc A. Huntoon, M.D. Nashville, Tennesee
Introduction
The Institute of Medicine report on chronic pain suggests that more patients suffer with chronic pain than
with heart disease, diabetes, and cancer combined. (1) The cost of this chronic pain is more than half a trillion
dollars per year, primarily due to lost productivity. Back pain is a significant proportion of the pain burden of
American society, driving the development, in some cases, of a chronic disease state. When pain becomes a
chronic disease, it requires a shift in treatment strategy from simple analgesics or isolated physical therapeutics,
to a multimodal/interdisciplinary model, wherein the focus is not necessarily on cure or complete amelioration
of the problem, but rather a disease management strategy. One of the problems with both those practitioners
that advocate primarily interventions or primarily pain medications such as opioids, is that other aspects of the
disease such as functionality or psychosocial health are neglected. Back pain is the leading cause of disability in
our most productive workers, aged 45 years or less. (2)
Pathophysiology
Radicular pain should be differentiated from radiculitis and radiculopathy, as the latter is associated with
neurological dysfunction and radiculitis connotes inflammation. Certainly the terms are not always mutually
exclusive, but may be. It is commonly thought that lumbar disc herniations, extrusions or protrusions may lead
to both mechanical compression on the spinal nerve and also cause inflammation of the spinal nerve(s). Studies
by Olmarker and colleagues and others have demonstrated that the inflammatory effects of cytokines and
prostaglandins produce pain in animal models. (3) This study demonstrated that Injections of disk homogenates
containing nucleus pulposus material onto cauda equina nerves in swine produced inflammatory effects. The
effects of thes disk homogenates can, in turn, be reproduced by known injections of cytokines. (4). Tumor-
necrosis factor-alpha (TNF-!), interleukin 1-beta (IL-1-") and IL-6 and IL-8 are notable inflammatory
cytokines. Studies in patients that have high levels of back pain demonstrate the expression of very high levels
of inflammatory cytokines, and the periradicular fat around patients with radiculitis also demonstrate high levels
of cytokines. (5), (6), (7)
Evidence
The evidence basis for epidural corticosteroids continues to evolve. Two recent large reviews have documented
that epidural corticosteroid injections are helpful for short -term treatment of leg pain and disability, consistent
with the preponderance of studies. (2), (8) The review by Pinto et al. (8) states that the findings of the review are
that there is a significant effect of the treatment ( epidural corticosteroids) compared to placebo for both leg pain
and disability, however the effects were in the range of 10-30 points on a 100 point scale. This effect size is
relatively small according to the authors, and below that which is often recommended in pain studies. (9, 10)The
review also found no effect on back pain. This review is unique compared to other reviews on this subject in the
past, as it was the first to attempt to quantify the effect size.
The more recent review by Cohen and colleagues is also unique in that they were able to characterize some
additional findings in terms of both the volume of the injectate and the effect of corticosteroids on need for
203
Page 2
surgical intervention. Notably, past reviews had not focused much on the volume of the injectate, as most
practitioners have not found this to be useful. Indeed, the 8 ml volume of interlaminar injection used in the
Carette et al. study (11) had often been criticized as excessive, and a reason for a loss of local selectivity. A
separate study by Rabinovitch et al. was noted by the Cohen review to indicate that larger volumes correlated
directly with effect size, i.e the larger the volume used the greater the analgesia noted. Rather than(12) The dose
of injection has been reviewed as well in the past. In one study, Ahadian et al. looked at doses of dexamethasone
from 4mg up to 12 mg in a total of 98 patients treated with transforaminal epidural injections for radicular pain.
Primary outcomes of visual analogue scales and Oswestry disability scores were not different between groups,
suggesting that the effect size foroptimal balance between relief of pain and lack of dose related side effects may
well be less than 4 mg. (13) In another study, doses of triamcinolone ranging from 5 mg to 40 mg were utilized
also via a transforaminal route for lumbar intervertebral disc herniation based on both clinical and magnetic
resonance imaging (MRI ) findings. The inclusion criteria required radicular leg pain and a concordant single
level disc herniation. Importantly, only the 5 mg group had different outcomes, suggesting that small doses are
effective. (14) Both of these studies are interesting as they suggest that the commonly used doses of
corticosteroids may be higher than necessary.
Infectious Complications
The latter part of 2012 was clouded by a fungal meningitis epidemic that few could have predicted.
Tennessee was hardest hit, and many patients were killed or injured when they were treated with predominately
interlaminar epidural injections for spinal radicular pain, using a contaminated lot of corticosteroids from a
compounding pharmaceutical supplier.(15, 16) Unfortunately, the procedure itself was maligned by many, who
had incomplete or erroneous information. Beyond the catastrophic type of pharmaceutical contamination, and
without the use of compounded agent in the first place, the risk for fungal abscess is negligible. Granted, the use
of depot steroids such as methylprednisolone or triamcinolone are off-label, but the procedures have been in
widespread use for decades. The best ways to mitigate risks for epidural infectious occurrences are self evident:
First, epidural corticosteroid injections should be avoided in individuals who are at high risk for infections
whenever possible. Thus, greater care than usual with patients who may be immunocompromised is
appropriate, e.g. hyperglycemic patients. The use of hand sanitation procedures ( proper handwashing; use of a
chlorhexidine/alcohol skin prep instead of povidone/iodine; wearing a face mask during the procedure;
swabbing the top of the sterile vials with alcohol prior to dispensing; sterile tray/gloves; and use of
pharmaceuticals approved by the FDA are some of the procedures.(17, 18)
The FDA Safe-Use Initiative
A working group of experts has been attempting to reach consensus on strategies to avoid catastrophic
complications related to posterior circulation strokes and spinal cord infarcts thought to be related to the use of
particulate corticosteroids in transforaminal epidural injections. (19, 20) The likely recommendations of the
group will be to recommend to the FDA that these injections be performed at upper lumbar and all thoracic and
cervical levels only with non-particulate corticosteroids, from which no cases of these catastrophic injuries have
been yet reported. It is important to realize that although these are devastating complications, they are rare.
Corticosteroid Alternatives?
There have now been several studies looking at the use of other drugs with anti-cytokine activity to target
inflammation of the spinal nerve. Cohen and colleagues examined the agent etanercept, a disease modifying
anti-rheumatic drug (DMARD) to test its effects on radicular pain in a small group of patients at various doses.
The trial of transforaminal epidural injection of etanercept was positive for intermediate pain relief. (21)
Another study looked at monoclonal antibodies to interleukin-6, with positive relief in comparison to
dexamethasone (22) Finally, the use of clonidine, an FDA approved agent for cancer-related neuropathic pain
via the epidural route, has recently been trialed in comparison to triamcinolone. (23) Although the corticosteroid
triamcinolone had slightly greater effects on function than clonidine, pain scores were similar in both groups.
Further study of these and similar agents is indicated. It is entirely plausible that in the future, administration of
a soup of different therapeutic agents will become normal and either replace or augment corticosteroid
epidurals.

203
Page 3
Conclusion
The fungal meningitis crisis underscores the benefit of a secure and safe drug supply. Nevertheless, therapeutic
corticosteroid epidurals remain a viable and effective treatment for patients with inflammatory radicular pain
due to herniated disc.

References
1. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Institute
of Medicine, National Academy of Science 2011
2. Cohen SP, Bicket MC, Jamison D, Wilkinson I, Rathmell JP. Epidural Steroids. A Comprehensive Evidence-
Based Review. Reg Anesth Pain Med 2013;38:175-200.
3. Olmarker K, Rydevik B, Nordborg C. Autologous nucleus pulposus induces neurophysiologic and histologic
changes in porcine cauda equina nerve roots. Spine 1993;18:142532
4. Olmarker K, Larsson K. Tumor necrosis factor alpha and nucleus-pulposusinduced nerve root injury. Spine
1998;23:253844.
5. Lee S, Moon CS, Sul D, et al. Comparison of growth factor and cytokine expression in patients with
degenerated disc disease and herniated nucleus pulposus. Clin Biochem 2009;42:150411.
6. Burke JG, Watson RW, McCormack D, et al. Intervertebral discs which cause low back pain secrete high levels
of proinflammatory mediators. J Bone Joint Surg Br 2002;84:196201.
7. Genevay S, Finckh A, Payer M, et al. Elevated levels of tumor necrosis factor-[alpha] in periradicular fat tissue
in patients with radiculopathy from herniated disc. Spine 2008;33:20416.
8. Pinto RZ, Maher CG, Ferreira ML, Hancock M, Oliveira V, McLachlan AJ, Koes B, Ferreira PH. Epidural
corticosteroid injections in the management of sciatica. A systematic review and meta-analysis. Ann Intern Med
2012;157:865-77.
9. Dworkin RH, Turk DC, Wyrwich KW, et al. Interpreting the clinical importance of treatment outcomes in
chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105-21.
10. Giraudeau B, Rozenberg S, Valat JP. Assessment of the clinically relevant change in pain for patients with
sciatica. Ann Rheum Dis 2004;63:1180-1.
11. Carette S, Leclaire R, Marcoux S, et al. Epidural corticosteroids injections for sciatica due to herniated nucleus
pulposus. NEJM 1197;336:1634-40.

203
Page 4
12. Rabinovitch DL, Peliowsky A, Furlan AD. Influence of lumbar epidural injection volume on pain relief for
radicular leg pain and/or low back pain. Spine Journal 2009;9:509-17.
13. Ahadian FM, McGreevy K, Schulteis G. Lumbar transforaminal epidural dexamethasone: a prospective,
randomized, double-blind, dose response trial. Reg Anesth Pain Med 2011;36:572-8.
14. Kang S-S, Hwang B-M, Son H-J, et al. The dosages of corticosteroid in transforaminal epidural steroid
injections for lumbar radicular pain due to a herniated disc. Pain Physician 2011;14:361-70.
15. Kainer MA, Reagan DR, Ngyuen DB, et al. Fungal infections associated with contaminated methylprednisolone
in Tennessee. NEJM 2012; 367:2194-2203.
16. Pettit AC, Kropski JA, Castilho JL, et al. The index case for the fungal meningitis outbreak in the United States.
NEJM 2012;367:2119-2125.
17. http://www.cdc.gov/HAI/settings/outpatient/basic-infection-control-prevention-plan-2011/standard-precautions-
d-f.html- Accessed November 12,2012
18. http://www.cdc.gov/injectionsafety/PDF/Clinical_Reminder_Spinal-Infection_Meningitis.pdf- Accessed
November 12,2012
19. Huntoon MA. Anatomy of the cervical intervertebral foramina: vulnerable arteries and ischemic neurologic
injuries after transforaminal epidural injections. Pain 2005;117:104-11
20. Huntoon MA, Burgher AH. Therapeutic Epidural Injections: Interlaminar and Transforaminal. In Deer TR,
Interventional and Neuromodulatory Techniques for Pain Management, Volume 4, Huntoon MA, Benzon HT,
Narouze S eds. Spinal Injections and Peripheral Nerve Blocks. Saunders/ Elsevier,Philadelphia.2012, pp.121-
128.
21. Cohen SP, Bogduk N, Dragovich A, et al. Randomized, double-blind, placebo-controlled, dose-response, and
preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology
2009;110:111626
22. Ohtori S, Miyagi M, Eguchi Y, Inoue G, Orita S, Ochiai N, Kishida S, Kuniyoshi K, Nakamura J, Aoki Y,
Ishikawa T, Arai G, Kamoda H, Suzuki M, Takaso M, Furuya T, Kubota G, Sakuma Y, Oikawa T, Toyone T,
Takahashi K. Efficacy of epidural administration of anti-interleukin-6 receptor antibody onto spinal nerve for
treatment of sciatica. Eur Spine J 2012;21:2079-84

203
Page 5
23. Burgher AH, Hoelzer BC, Schroeder DR, Wilson GA, Huntoon MA. Transforaminal Epidural Clonidine versus
Corticosteroid for Acute Lumbosacral Radiculopathy due to Intervertebral Disk Herniation. Spine (Phila Pa
1976). 2010 Dec 29. [Epub ahead of print]

Disclosure

207
Page 1
Update in the Management and Diagnosis of Complex Regional Pain Syndrome
Timothy Lubenow, M.D. Chicago, Illinois
215
Page 1
Neuropathic Pain: Past, Present, and Future
Robert Hurley, M.D., Ph.D Gainesville, Florida
305
Page 1
Psychiatric Co-Morbidities in the Chronic Pain Patient
Rafael Miguel, M.D. Tampa, Florida
As a result of completing this activity, the participant will be able to
Identify current problems with opioid use and misuse in pain
List potential specialty-specific and legislative actions
Describe monitoring and compliance, REMS, and other initiatives and discuss their implications for pain
physicians
Over the past 20 years, drug overdose deaths in United States have tripled.
1
More than 100 people die each day
secondary to prescription drug use, whether related to drug abuse, misuse, or adverse events.
2
In July 2012, the Drug
Abuse Warning Network (DAWN) reported that of 4.8 million drug-related visits to U.S. emergency departments in
2010, 46.8% were due to drug abuse or misuse. Prescription drugs had the highest representation of all abused drugs
at a frequency of 435 per 100,000 population.
3
Because Florida is the state with the greatest number of medications
dispensed and the highest drug mortality, the actions of that state have a far-reaching impact due to the enormous
volume of drugs diverted from Florida.
4
Recognizing the problem, the U.S. Food and Drug Administration (FDA)
started Risk Evaluation and Mitigation Strategies (REMS) as a source of education. REMS requires drug
manufacturers to educate physicians who, in turn, will educate their patients about the proper use of high-risk
medications, including opioids.
This chapter addresses the problem of clinics that appear to operate as pain clinics but really exist to
dispense prescriptions for medication, or pill mills, and their contribution to the national prescription drug
epidemic. A template for responsible controlled substance prescribing, which includes performing a complete
history and physical examination with particular attention to comorbidities (including psychiatric disorders), is
described. Finally, an overview of the available risk assessment and ongoing management tools is presented.
RISK EVALUATION AND MITIGATION STRATEGIES
In the FDA Amendment Act of 2007, the organization was authorized to require REMS from manufacturers to (1)
ensure that the biological benefits of a drug outweigh its side effects and (2) provide education about these drugs.
The goals of the REMS program are to educate physicians about the particular characteristics of the medications
prescribed, with emphasis on their adverse events profile, and to teach physicians how to share this information with
patients and their caregivers. A wide variety of medication classes are included in the REMS program. These
include agents such as retroviral medications, erythropoietin, testosterone, and opioid analgesics.
5
REMS can be for specific medications or shared among agents of a drug class. While there are numerous
individual REMS, there are currently four approved shared REMS two of which are for opioid analgesics (i.e., the
REMS for extended-release and long-acting opioid analgesics and for transmucosal immediate relief fentanyl
products); the others are for isotretinoin and mycophenolate (Table 1). REMS may consist of medication guides
given to physicians, communication plans that may be recommended from manufacturers to physicians and their
patients, or other elements to ensure an implementation system for and safe use of new drugs. The FDA decides
which of these educational tools is necessary depending upon the particular drug or drug class. Presently, in the
long-acting extended-release opioids REMS, the verbiage states that physicians are strongly encouraged to do all of
the following:
6
(1) train themselves using REMS-compliant training in order to educate themselves and counsel their
patients each time the medication is prescribed (with emphasis placed on assuring that the patient and caregiver
understand the medication guide); (2) consider using other publicly available tools to improve patient and
community safety when using extended-release or long-acting opioid analgesics; and (3) utilize patient-prescriber
agreements and risk assessment instruments.
305
Page 2
PILL MILLS AND THE PRESCRIPTION DRUG EPIDEMIC
Prescription drugs are presently the second most abused substances, after marijuana, in the United States according
to the 2008 Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug
Abuse. The United States has a disproportionate share of opioid use worldwide (Table 2). Unintentional overdoses
and overdose drug deaths with opioid analgesics have steadily risen since 1999, accompanied by a flattening or
decrease of deaths associated with cocaine and heroin.
8
Deaths due to unintentional prescription drug overdoses have
risen steadily, reaching 1 death every 19 minutes in 2007. There has been a linear relationship between sales of
opioid pain medications and the number of treatment admissions for adverse events including overdoses and deaths.
9

The overwhelming majority of patients are treated by one physician and receive prescriptions for relatively low
doses of opioids (less than 100 mg morphine equivalents daily); these medications account for 20% of deaths.
However, patients being treated by one physician and receiving higher doses of medication or patients receiving
prescriptions from multiple physicians account for 80% of deaths.
10

In Florida, an enormous number of clinics operate under the guise of being pain clinics, yet are really pill
mills and are the source of massive amounts of prescription drugs, primarily oxycodone and benzodiazepines (80%
of which is alprazolam). While OxyContin (Perdue Pharma, Stamford, CT) was an initial favorite, presumably due
to its higher milligram content and easily violated slow-release characteristic, it is expensive and has fallen out of
favor. The transition has led to a rise in the popularity of generic oxycodone and an escalation of death rates.
11
Additionally, the massive numbers of oxycodone units dispensed in Florida that are transported elsewhere constitute
a very large contribution to the national prescription drug crisis. There were approximately 42 million units of
oxycodone dispensed in one six-month period in Florida. Ohio is the next highest oxycodone dispensing state with
approximately 1.5 million units, followed by Georgia with approximately 1 million units. All remaining states had
well under 1 million units dispensed annually.
12
A technique commonly used by drug abusers and traffickers is the
criminal act of obtaining controlled substances by fraud, often called doctor shopping. This practice involves
requesting various prescribers to write prescriptions all within the same time period for medications already
provided. The absence of a prescription drug monitoring program (PDMP) in Florida is one of the factors that
contributed to the states popularity with drug abusers/diverters, as multiple physicians and pharmacies could be
targeted without difficulty. Prior to 2011, PDMPs existed in 36 states and Florida's became operational in October
2011. At the time of this report, New Hampshire became the 49th state to approve a PDMP, leaving Missouri as the
sole remaining state without active or pending legislative plans to create one
13
(Figure 1).
Still, Florida deaths continue to rise: the most recent Florida Medical Legal Examiners/Florida Department
of Law Enforcement Interim Report for January to June 2012 identified 4,126 drug-related deaths; prescription
drugs accounted for 85% of them. The most dangerous drug continued to be heroin, causing death 94% of the time it
was involved. However, there does appear to be light at the end of the tunnel. The same report also pointed out that
oxycodone- and hydrocodone-related deaths continued to decrease. They found a decrease in oxycodone and
hydrocodone deaths of 248 and 53, respectively, compared to the immediately preceding 6-month period (i.e., July-
December 2011) . There were 150 fewer deaths caused by oxycodone and 26 fewer by hydrocodone. Methadone
overdoses and deaths decreased by 18.3 and 21.7%, respectively, for the same period. While these decreases may
appear small, they are the first drop seen in 12 years and may be affected by the implementation of the PDMP in
October 2011.
RESPONSIBLE PRESCRIBING OF CONTROLLED SUBSTANCES
While pill mills are illegal operations that are little more than distribution outlets for opioids, there is no denying
that a striking swing in the pendulum in opioid prescribing has occurred. Physicians for Responsible Opioid
Prescribing (PROP), a highly respected group of medical, regulatory, and legal professionals, issued a letter to the
FDA on July 25, 2012, requesting that agency to revise its indications and recommendations for opioid use in
chronic noncancer pain.
14
Among the reasons cited in the letter were the dramatic increase in opioid prescribing, the
resultant increase in opioid addiction, the absence of studies proving the effectiveness of long-term opioid therapy,
the lack of patient improvement with long-term opioid use, and a significant increase in overdoses and opioid-
related deaths. Three basic changes in the indications for opioids in the treatment of chronic noncancer pain were
requested (Table 3).
In 2000, Passik and Wenreb proposed the four as in outcome assessment: analgesia, adverse events,
activities of daily living (ADLs), and aberrant drug taking.
15
The first concept necessary when faced with a patient
with pain is to recognize his or her realities. A comprehensive evaluation must be performed relating to the clinical
physical complaint and to the psychological pathologies that frequently accompany these complaints. Due to the
overwhelming predominance of low back pain (LBP) in our society, a detailed musculoskeletal examination is
305
Page 3
necessary. LBP is the most common cause of disability in patients under the age of 45 years and the third most
common etiology above that age.
16,17
LBP is increasing in frequency and has been found to have a lower incidence
in Asian-Americans than African-Americans and Caucasians.
18
While magnetic resonance imaging is extremely
valuable in establishing the etiology of LBP, it has limitations and often reveals routine findings associated with the
aging process that may not necessarily be the cause of pain and must be differentiated from true triggering
abnormalities.
19

PSYCHOLOGICAL ASSESSMENT OF THE CHRONIC PAIN PATIENT
The psychological evaluation of a patient is critical to assess mood, coping skills, family support structure,
expectations regarding pain management, and the impact of pain on quality and activities of daily life. Furthermore,
rates of chronic opioid treatment are higher in patients with mental health and substance abuse.
20,21
The prevalence
of psychiatric comorbidities in chronic pain patients has been well described and is estimated at a lifetime incidence
of 6080% by DSM-IV criteria.
2224
Depression is a frequent comorbid psychiatric condition in thehronic pain
patient. DSM-IV criteria for depression include the following:
1. Depressed most of the day nearly every day
2. Markedly diminished interest in activities
3. Significant weight change (5% in either direction)
4. Sleep abnormalities nearly every day
5. Psychomotor agitation or retardation
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive guilt
8. Diminished ability to think or concentrate
9. Recurrent thoughts of death/suicide (without plan)
For a diagnosis of depression to be made, at least 5 of these criteria must be met and must include daily depression
or diminished interest in activities.
25

The impact depression has on the treatment of chronic pain patients cannot be overstated. These patients
are more difficult to treat: the greater intensity of their pain is well documented and they have a greater affective
component.
26
Edit et al. compared consecutive inpatients with LBP to 199 age- and gender- matched patients
without back pain using the 36-Item Short-Form Health Survey Questionnaire, the Beck Depression Inventory, the
WHO-Five Well-being Index, and the Hospital Anxiety and Depression Scale. thats fine Approximately half of the
patients with LBP were found to have a depressed mood, ranging from mild to severe. There was a significant
correlation of depression to back surgery: 47% of patients with no surgery demonstrated depressive symptoms,
whereas 62.5% of those having more than one back surgery manifested depressive symptoms.
27

A differential diagnosis of depression is appropriate because there is heightened concern that some of the
prescribed medications (e.g., opioids, muscle relaxants, and anticonvulsants), by inducing fatigue and
hypersomnolence, may mimic the clinical signs and symptoms of depression. The effects of opioids on the
testosterone level can lead to fatigue, weakness, osteoporosis, and sexual dysfunction as well as depression.
Hypogonadism in both men and women consuming sustained oral opioids has been well described.
2830
Vestergaard
et al.,
31
in a large-scale Danish study, evaluated the risk of fracture associated with the use of morphine and other
opioids. They found an increased fall risk in patients taking opioid medication and reasonably concluded it could
lead to an increased fracture risk. More recently, Grey et al. published results from a bone densitometry study in
patients who received methadone for a median of 11 years. They found bone densitometry measurements were less
than normal in all males at all sites (e.g., lumbar spine, hips, and total body). All males evaluated also had
testosterone levels that were below normal.
32

The treatment of depression should include the use of oral antidepressants, which are most successful when
combined with cognitive behavioral therapies (CBTs). Electroconvulsive therapy has recently enjoyed renewed
interest as an antidepressant modality and there is some evidence that it may even help in chronic pain. Nutritional
supplement approaches and supplementing with omega-3 fatty acids as well as vitamin B complexes have also been
recommended as adjuncts to antidepressant therapy. While some studies have shown testosterone to be effective in
hypogonadal men with subthreshold depression,
33
testosterone should not be considered a first-line treatment for
depression. Amiaz and Seidman propose that its use is probably most indicated in men with hypogonadism,
resistance to antidepressants, early-onset depression, or HIV.
34

Anxiety disorders affect 30 to 60% of chronic pain patients, generalized anxiety disorder (GAD) being the
most common. DSM-IV criteria for anxiety include anxiety out of proportion to the likelihood of negative effects, on
more days than not, for at least six months, and worry associated with three or more of the following six symptoms
with some occurring on more days than not for the past six months:
305
Page 4
1. Restlessness
2. Easy fatigability
3. Difficulty concentrating or mind going blank
4. Irritability
5. Muscle tension
6. Sleep disturbance, which could be difficulty falling or staying asleep, or restless and unsatisfying sleep
Other associated symptoms are anxiety that interferes socially or with work, and is not exclusively associated with
medical disorder or substance factor.
The treatment of anxiety is based on CBTs, which include relaxation techniques, meditation, biofeedback,
and Mindfulness Meditation programs. Antidepressants are also useful, i.e., selective serotonin reuptake inhibitors
(SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs); however, higher doses of these agents are
required than when they are used for an antidepressant effect. While anxiolytics have a more rapid onset, they are
fraught with side effects. These include excessive sedation and forgetfulness, but most serious among them is
dependency, which may actually worsen anxiety with long-term use.
When prescribing antidepressants, whether for depression or anxiety, consider the following:
1. The specifics of the patients condition (e.g., does the patient need a more sedating [SSRI] or more
activating [SNRI] antidepressant?)
2. The patients prior experience, if any, with antidepressants (e.g., prior success with a particular
antidepressant may warrant use of the same one)
3. Properties of the drug: evaluate the cost, drug interactions, and side effects profile
4. Advise the patient about the onset and duration of action

RECOGNIZING ABERRANT BEHAVIOR
It is essential to differentiate physical dependence and tolerance from addiction. The first two are states of
adaptation, which every patient taking opioids for a period of time will experience, and are not associated with a
specific disease process. Addiction is a primary chronic neurobiological disease with genetic, psychosocial, and
environmental influencing factors.
35
Addiction behaviors include impaired control over drug use, and compulsive
and continued use despite harm and cravings.
Identifying aberrant behaviors has been discussed by Passik, Portenoy, and Ricketts, who divided them into
less predictive and more predictive types.
36
They proposed that among the less predictive aberrant behaviors are
aggressive complaining of a need to increase a dose of a drug, drug hoarding, requesting specific drugs, acquisition
from other physicians, unsanctioned dose escalation (one or two times), unapproved use of the drugs to treat another
symptom, and reporting unintended psychic effects. Among the more predictive behaviors associated with aberrant
drug use are selling prescription drugs, prescription forgery, stealing or borrowing another patients drugs, injecting
oral formulations, obtaining prescription drugs from nonmedical sources, concurrent abuse of related illicit drugs,
multiple unsanctioned dose escalations, and recurrent prescription losses.
These behaviors need to be considered when starting opioid therapy and with continued prescribing, and
should be looked for at every visit as well as between them. The patient's aberrant behavior may manifest itself with
increasing requests for early refills or repeated phone calls. There are a multitude of validated screening
questionnaires that can assist in identifying patients at risk for aberrant drug behavior. The CAGE (acronym for the
questions asked) questionnaire,
37
originally used for alcohol abuse, has been Adapted to Include Drug use (CAGE-
AID). It consists of four basic questions:
1. Have you ever thought you should Cut down on your drug use?
2. Have you ever felt Annoyed by criticism of your drug use?
3. Have you ever felt Guilty about your drug use?
4. Do you frequently having a morning Eye opener?
Brown et al. found that three positive answers on the CAGE/CAGE-AID questionnaire is equal to a 75% probability
of aberrant drug behavior, and 81% of the variance would lie within the first two questions.
38

Another validated tool is the Michigan Alcohol Screening Test, which also has been modified to identify
aberrant drug users (MAST and DAST). The Opioid Risk Tool (ORT) is validated, simple to use, takes 1 minute to
complete, and can be adjusted for gender. Other validated screening tests include the Addiction Behaviors Checklist
(ABC), which tracks prescription drug behaviors in pain patients; the National Institute on Alcohol Abuse and
Alcoholisms modified Alcohol, Smoking, Substance Involvement Screening Test (ASSIST), version 2.0, which is a
modification of the ASSIST developed and validated by the World Health Organization to include prescription drug
abuse; the Prescribed Opioids Difficulty Scale (PODS), which addresses problems encountered by the patient
305
Page 5
receiving opioids; and the Current Opioid Misuse Measure (COMM), which has a low cut-off score and purposely
overidentifies misusers in order not to miss potential abusers.
Because sole dependence on the clinical examination has proven to be unreliable when trying to identify
patient deceit,
39
an objective method for monitoring patients receiving controlled substances is urine drug screening
(UDS). UDS has a longer detection window than blood screening and is cheaper and less invasive. It does not
require a detailed drug history with respect to the timing of the medications taken, but it does have significant cross-
reaction with many over-the-counter drugs and herbal medications (Table 4). Communication with the testing center
is necessary if a questionable result appears, especially with office point-of-care testing. Pharmacological impurities,
which may produce confusing results, need to be taken into consideration prior to determining if a patient is abusing
a nonprescribed or illicit drug. Most notable among these is a relatively recent finding that hydromorphone is a
metabolite of morphine. Furthermore, codeine can be found with morphine testing, and vice versa.
40

Looking for point-of-care false negatives is very important when monitoring a patient in the office. Drugs
routinely not included in office point-of-care testing include oxycodone, fentanyl, butalbital, and carisoprodol. Drug
metabolites do not normally react in point-of-care testing. In these, very high thresholds are used so lower levels of
nonprescribed drugs may not be identified and will require mass spectrometry confirmation for identification.
Therefore, especially with initial evaluation, it is not unreasonable to withhold prescription medications until
negative confirmation is obtained, which usually takes 2 to 5 days.
Underlying patient factors can impact the UDS. These include nausea and vomiting, diseases that affect
organ function, drugdrug or drugfood interactions (e.g., grapefruit juice is a potent cytochrome P-450 3A4
inhibitor and 200 mL raises methadone levels 17%
41
), acute weight loss, heat application, dehydration/fluid status,
and timing of collection. A recently convened consensus panel has developed recommendations for UDS monitoring
in the chronic pain patient
42
(Table 5).

Chemically dependent patients may very well have chronic intractable pain and require treatment. The
management of these particular patients needs to be individualized and maximally structured. They require more
frequent office visits, a limited supply of medication, management primarily with long-acting opioids that have a
very low street value, routine urine toxicology, and mandatory participation in a recovery program and
psychotherapy. It is of utmost importance to follow these patients with an addictionologist and proceed with care,
assuring the safest and most appropriate manner of therapy including interventional analgesic and complementary
techniques (e.g., transcutaneous electrical nerve stimulation [TENS], acupuncture, chiropractic, physical therapy,
CBTs [for coping skills], etc). While these should also be considered in the nonabusing patient, the concept of
interdisciplinary care provides significant advantages when dealing with the abusing patient.

SUMMARY
The management of chronic pain requires an interdisciplinary approach. The exclusive use of opioids and other
controlled substances for the relief of chronic nonmalignant pain is rarely indicated. One should have a low
threshold for consulting other specialists such as the interventional pain physician, a neurologist, a neurosurgeon, a
physiatrist, psychiatrist, and others, as indicated by clinical condition. The primary care physician and other relevant
treating physicians should receive information about office and procedural visits so they may all be aware of
medication and interventional procedures that are contemplated. All treating physicians should participate in
complementary management of the complex chronic pain patient and only one should prescribe controlled
substances for pain relief. An individualized prescription for care is mandatory.

REFERENCES
1. National Vital Statistics System. Drug overdose death rates by state. 2008.
2. Centers for Disease Control. Vital Signs: Overdoses of Prescription Opioid Pain RelieversUnited States,
1999-2008. MMWR 2011; 60: 1-6
3. The DAWN Report, July 2, 2012. Available from URL:
http://www.samhsa.gov/data/2k12/DAWN096/SR096EDHighlights2010.htm
4. Valarie Honeycutt Spears. Ky. sees rise in overdose deaths from pills obtained in Fla. Lexington Herald-
Leader 2009 Apr 12. Available from URL: http://www.kentucky.com/2009/04/12/758845/ky-sees-rise-in-
overdose-deaths.html
5. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders;
Accessed Sept 22, 2012
6. PDR Drug Alert, July 24, 2012. Available from URL:
http://www.pdr.net/drugpages/productsafetyalert.aspx?ha=1000133. Accessed September 24, 2012
305
Page 6
7. SAHMSA 2008 National Survey on Drug Abuse and Health. Accessed at:
http://www.whitehousedrugpolicy.gov/drugfact/prescrptn_drgs/rx_ff.html
8. Center for Disease Control/Morbidity and Mortality Weekly Report (CDC/MMWR) January 13,
2012/61(01);10-13
9. CDC/MMWR November 4, 2011 / 60(43); 1487-1492
10. 2009 Florida Department of Law Enforcement/Florida Medical Legal Examiners Annual Report on
Dangerous Drugs in Decedents. Available at URL: http://www.fdle.state.fl.us/Content/getdoc/0f1f79c0-
d251-4904-97c0-2c6fd4cb3c9f/MEC-Publications-and-Forms.aspx
11. Automation of Reports and Consolidated Orders System (ARCOS). Available (by sign up and request)
from URL: http://www.deadiversion.usdoj.gov/arcos/index.html
12. General Accounting Office (GAO) Analysis of Medicare Part D claims data, 2008
13. 2012 Florida Department of Law Enforcement/Florida Medical Legal Examiners Interim Report on
Dangerous Drugs in Decedents. Available at URL: http://www.fdle.state.fl.us/Content/getdoc/9c4df7c2-
4b07-4f7a-acfb-6461719c0e44/2012-interim-drug-reportFINAL.aspx (accessed March 25, 2013)
14. Physicians for Responsible Opioid Prescribing, Letter to FDA, July 25, 2012
(www.citizen.org/documents/2048.pdf; accessed October 4, 2012)
15. Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids.
Adv Ther. 2000; 17:70-80.
16. Institute for Clinical Systems Improvement. Adult low back pain. Bloomington, Minn: Institute for Clinical
Systems Improvement; Sept 2005.
17. Freburger et. al., The rising prevalence of chronic low back pain. Arch Intern Med. 2009 Feb 9; 169(3):
251-8
18. Waterman et. al., Low back pain in the United States: incidence and risk factors for presentation in the
emergency setting. The Spine Journal 12:1: 63-70, 2012
19. Deyo and Weinstein, NEJM 344:363-370, 2001
20. Sullivan et. al. Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and
Medicaid insurance plans: the TROUP study. Pain 2008; 138:440-449
21. Weisner et. al. Trends in prescribed opioid therapy for non-cancer pain for individuals with prior substance
use disorders. Pain 2009:145:287-293
22. Am Psychiatric Assoc; Psy Clin NA 25(1): 71-88, 2002
23. Am J Psychiatry 142(10): 1156-1160, 1985
24. Pain 26:186-197, 1986
25. Diagnostic and Statistical Manual of Mental Disorders IV-TR. Washington, DC, American Psychiatric
Association, 2000.
26. Boscarino et. al. Anxiety and Depression Among Chronic Pain Patients on Opioids Associated with Poorer
Treatment Success and Health Status. Clin Med Res. 2012 Aug;10(3):183.
27. Edit et. al. Psychosocial, educational and somatic factors in chronic nonspecific low back pain. Rheumatol
Int; April 3, 2012 (Epub online)
28. Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. Pain 3(5), 377-384, 2002
29. Daniell HW. DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for
opioid-induced inhibition of adrenal androgen production. J Pain, 7(12), 901-907, 2006
30. Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained action opioids for control
of nonmalignant pain. J Pain, 9(1), 38-36, 2008
31. Vestergaard et. al. Fracture risk associated with the use of morphine and opiates. J Int Med 2006
Jul;260(1):76-87
32. Grey et. al. Decreased bone density in men on methadone maintenance therapy. Addiction 106(2) 249-
254, 2011
33. Shores et. al. A randomized, double-blind, placebo-controlled study of testosterone treatment in
hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psy [2009,
70(7): 1009-1016]
34. Amiaz and Seidman: Curr Op in Endocrinology, Diabetes & Obesity: June 2008;15(3): 278-283
35. 2001 "Definitions Related to the Use of Opioids for the Treatment of Pain,", the American Academy of
Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine. Available at
URL: www.painmed.org/pdf/definition
36. Passik, Portenoy and Ricketts. Oncology (Williston Park). 1998 Apr; 12(4):517-21, 524.
37. Bernadt et al, Lancet 6 (8267) 325-328, 1982
305
Page 7
38. Brown et. al., J Fam Pract 33:151-160, 1997
39. Jung B and Reidenberg MM. Physicians being deceived. Pain Med 2007, 8(5): 433-437
40. Haddox JD et al. Clinical considerations for interpretation of unexpected results from urine drug testing.
2010
41. Benmebarek et.al., Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone.
Clin Pharm Ther 2004, 76(1): 55-63
42. Peppin, Passik, Couto et.al., Recommendations for urine drug monitoring as a component of opioid therapy
in the treatment of chronic pain. Pain Medicine 2012, 13(7): 886-896

Figure 1. Status of Prescription Drug Monitoring Programs (PDMP) in the United States (June 13, 2012).
Alliance of State with Prescription Drug Monitoring Programs.
http://www.pmpalliance.org/pdf/pmp_status_map_2012.pdf (accessed March 25, 2013)

Disclosure

309
Page 1
Improving Safety Through Use of Diagnostic Imaging and
Image Guidance in Pain Medicine
James P. Rathmell, M.D. Boston, Massachusetts
Introduction
Until recent years, use of radiographic guidance in the pain clinic was reserved for major procedures like neurolytic
celiac plexus block. Two forces have been at work, which have led to the widespread use of imaging modalities in
the field of pain medicine. Patients and referring practitioners now expect pain physicians to be familiar with use of
imaging in diagnosing pain conditions. At the same time, pain practitioners have demonstrated the usefulness of
radiographic guidance for guiding precise anatomic placement of needles and catheters. The evidence to support
routine use of radiographic guidance is still evolving. The intuitive appeal of this precise approach has already
caught on to the point where the majority of practitioners now perform most of their injections using fluoroscopic
guidance. In patients with intractable pain associated with metastatic cancer, diagnostic imaging studies has proven
invaluable in the planning and implementation of therapy. The use of fluoroscopy, computed tomography (CT), and
most recently, ultrasound in the pain clinic have all advanced rapidly, yet there is scant evidence that this improves
the safety or efficacy of pain treatment. Herein, we will review the available evidence about the usefulness of
diagnostic imaging and image guidance in planning and delivering pain treatment.
Use of Diagnostic Imaging to Improve Safety when Planning Pain Treatment
Pain is among the most common presenting symptoms that lead patients to seek medical care. Diagnostic imaging is
used broadly to search for the anatomic basis for new onset of many symptoms, including pain. Indeed, diagnostic
imaging is the cornerstone of diagnosis in many cases, such as new onset of sciatica associated with disc herniation.
A broad discussion of the use of diagnostic imaging is beyond the scope of this article, but several examples where
diagnostic imaging can provide critical information for planning treatment will be reviewed.
There is moderate scientific evidence that epidural injection of steroids can speed the resolution of radicular
pain early after acute lumbar disc herniations
1,2,3
and this treatment is in widespread use. By extrapolation from the
evidence for lumbar disc herniation, the technique has also been used for pain associated with thoracic and cervical
disc herniations and spinal stenosis. Use of diagnostic imaging to establish the exact anatomic level of disc
herniation was unusual just ten years ago. At that time, most practitioners doing
epidural injections were doing so with no experience in interpreting imaging studies;
most often they were using the blind loss-of-resistance technique to identify the
epidural space.
4
Conventional wisdom at that time held that the injection should be
placed at the level of the disc herniation to produce maximal benefit. Most
practitioners simply placed epidural injections guided only by the radiologists report:
if there was a disc herniation at C6/7, then the injection was placed at that level.
Reports of spinal cord injury during these injections began to appear, and a connection
between spinal cord injury during injection and high-grade spinal stenosis was made.4
Indeed, in high grade stenosis of the central spinal canal from any cause, there is often
complete loss of the CSF and epidural fat surrounding the cord, often with direct
pressure on the spinal cord. This is the case in a few patients with large disc
herniations (Figure 1. Cervical MRI in a patient with a large C6/7 disc herniation that
causes significant stenosis of the central spinal canal. This patient developed
neuropathic pain suggestive of minor spinal cord injury during epidural steroid
injection conducted using a blind technique at the C6/7 level. Review of diagnostic
imaging studies before injection would have identified this high grade stenosis and use
of fluoroscopy to select a intervertebral level where the stenosis was less severe may
have prevented this injury. A: Axial T1-weighted magnetic resonance image at the

309
Page 2
C6/7 level. There is a large central herniated intervertebral disk that lateralizes to the left (arrow heads). The spinal
cord is displaced toward the rightposterior portion of the spinal canal (arrows). B:Sagittal T2-weighted image at the
midline of the cervicalspine. There is a large disk herniation at the C6/7 level, causing posterior displacement of the
spinal cord (arrow) and effacement of the cerebrospinal fluid signal anterior to the spinal cord. Reproduced with
permission from Reference 4.) . In such cases, it is
critical to recognize the lack of enough space in the
posterior epidural canal to allow for safe needle entry
and placement of the epidural steroid. The use of
diagnostic imaging and careful review of the actual
images prior to epidural injection is now routine. When
there is severe spinal canal stenosis, injection at the
stenotic levels is avoided by using fluoroscopy to guide
needle placement at an anatomic level where prior
diagnostic imaging has demonstrated room for needle
entry.
Neurolytic celiac plexus block is another
technique that has moderate scientific evidence from
controlled trials demonstrating reduced pain and
analgesic use in patients with painful intra-abdominal
malignancies, particularly pancreatic cancer. The
complications associated with this technique include
renal trauma, trauma to the large vessels of the
abdomen, and pneumothorax. Diagnostic imaging for
identification and staging of pancreatic cancer is
standard practice worldwide, thus imaging studies are
almost universally available at the time patients are
referred for celiac plexus neurolysis. Analysis of the diagnostic studies can assist in planning the spinal level of
needle entry, as well as the angle and depth of needle advancement. These planning measurements are made on the
diagnostic images and used to guide needle placement during celiac plexus block done subsequently using either CT
of fluoroscopy (Figure 2. Use of diagnostic computed tomography angiography study of the abdomen in a patient
referred for celiac plexus block to plan position and depth of needle placement. The diagnostic CT angiogram can be
used to determine the safest position to place needles and plan the final depth on needle insertion; these
measurements can then be used to carry ot the block with either fluoroscopy or CT guidance. Axial image one
centimeter inferior to the origin of the celiac artery from the anterior aorta, below the inferior reflections of the
pleura. The distance from the anterolateral surface of the aorta to the skin surface (124 mm) and from the spinous
process to the point of needle entry (41 mm); similar
measurements can be made for placement of the needle
on the right side. Performing the celiac plexus block
somewhat inferior to the celiac artery in this patient was
carried out successfully: the needles were well below
the pleura at this level. Adapted with permission from
Rathmell JP. Atlas of image guided intervention in
regional anesthesia and pain medicine. Lippincott
Williams and Wilkins, Philadelphia, 2012.) . Existing
diagnostic studies can be help to avoid adjacent
structures thus improving safety.

Use of Image-Guidance to Improve the Precision of
Image-Guided Intervention
Early work suggests that image guidance can increase
the precision of epidural placement. One of the most
quoted studies demonstrated that using a blind loss-of-
resistance technique correctly identified the epidural
space in only 30% of cases.
5
This study has been
criticized, as the investigators were not frequent users
of the loss of resistance technique. When experienced

309
Page 3
physicians placed epidurals in the setting of labor and delivery, the success rose to 61.7% in comparison to a success
rate of 47.7% in those who had performed few injections previously.
6
Subsequent investigators reported successful
caudal epidural injection in 97.5% of cases performed using fluoroscopic guidance.
7
Radiographic guidance can be
used to display images in multiple planes at all spinal levels, and the epidural space can be identified the vast
majority of the time (Figure 3. Radiographic identification of the lumbar epdiural space. Lateral radiograph of the
lumbar spine during interlaminar lumbar epidural injection. A Tuohy needle is in place in the L5/S1 interspace
extending to the posterior epidural space. Clarity of lateral radiographs of the lumbar spine is often hindered by the
overlying iliac crests. During lumbar interlaminar epidural injection, the needle can be safely advanced using the
lateral radiograph to guide depth. The posterior-most extent of the ligamentum flavum lies just anterior to the
junction of the spinous process with the laminae (red arrows). The needle can be safely advanced to this depth
before starting the LOR technique during the last few millimeters of advancement through the ligamentum flavum to
precisely identify the epidural space. The junction of the spinous process with the lamina can be easily identified in
the lateral radiograph by following the inferior margin of the spinous processes anteriorly until the junction with the
lamina is seen as a line that extends in an inferior and anterior direction (dashed line). The approximate location of
the thecal sac is shown (gray lines indicate the approximate location of the anterior and posterior aspects of the dura
mater). Adapted with permission from Rathmell JP. Atlas of image guided intervention in regional anesthesia and
pain medicine. Lippincott Williams and Wilkins, Philadelphia, 2012.).
Use of radiographic guidance employing a co-axial technique can also improve the precision of needle
placement, reduce or eliminating the need for redirection of the needle to reach the epidural space.
8
By aligning the
axis of the x-ray beam with the final radiographic target, the skin directly overlying the target can be anesthetized,
and a needle passed directly from the skins surface to the target at a depth in a single pass. Antero-posterior
radiographs demonstrate the needle position from lateral to medial and cephalad to caudad; lateral radiographs
demonstrate the needles depth from the skins surface. While radiographic guidance can bring the needle in to close
proximity to the epidural space, only bony structures can be identified using fluoroscopy, thus final needle
advancement into the epidural space requires use of the loss-of-resistance technique. Once the needle is in final
position, epidural location can be confirmed by injecting radiographic contrast. If the contrast spreads in a
characteristic pattern without evidence of vascular flow, then epidural location is confirmed.
Identification of intravascular needle location using fluoroscopy requires special attention. Use of a live or
real-time technique rather than static images is essential. Any contrast placed within a blood vessel will be rapidly
carried away in the blood stream and will no longer be visible on static images taken subsequently. Another
difficulty with use of radiographic guidance is the appearance of confusing patterns of contrast spread, particularly
in patients who have had prior surgery, including fusion masses along the bony spine or scarring in the epidural
space. Use of radiographic guidance does not assure the safety of image-guided injections, but the use of these
techniques has strong face validity as a means to improve safety: if you can directly visualize or more precisely infer
the position of critical structures like blood vessels and the spinal cord, then it stands to reason that these structures
can be avoided with the use of image guidance. Caution is in order: images are often confusing, the skill of
practitioners is variable, and despite there is still little evidence for improved safety with image guidance. A recent
study published by the American Society of Anesthesiologists (ASA) examined closed malpractice claims, in a
subgroup of patients who sustained spinal cord injuries during the course of cervical spinal injections.
9
Radiographic
guidance was more common in those who sustained spinal cord injuries than in those who had cervical procedures
performed without radiographic guidance. Did use of radiographic guidance make spinal cord injury more likely?
Perhaps, but it is equally plausible that injections that led to spinal cord injury, e.g. cervical epidural steroid injection
using an interlaminar technique, were done more often with radiographic guidance. Without knowledge about how
many total injections were done with and without radiographic guidance, there is no means to know the actual
incidence of injury with each method. Nonetheless, the ASA Closed Claims report does demonstrate that direct
trauma to the spinal cord can occur during transforaminal injection, interlaminar epidural injection, and trigger point
injection at the level of the cervical spine, even when image guidance is used.
Intravascular injection can lead to local anesthetic toxicity or catastrophic neural injuries to the brain or
spinal cord. With disciplined use of radiographic guidance, intravascular needle location can be detected before local
anesthetic or steroid is injected. In this way, use of radiographic guidance can improve safety. Intravascular needle
location exceeds 20% during cervical transforaminal injection,
10,11
and it is unclear what proportion are intravenous
versus intra-arterial.
12
Use of digital subtraction appears to further increase the likelihood of detection of
intravascular injection.
13
Intravascular injection is common during cervical transforaminal injection, but the
incidence during other techniques is unclear. The proximity of the vertebral artery during stellate ganglion block and
the proximity of the aorta during celiac plexus block make intra-arterial injection distinctly possibility. Means to
detect intra-arterial needle location before injection must be a routine part of performing these techniques.

309
Page 4
Without any direct reporting mechanism, any real estimate of the incidence of injuries occurring during the
course of pain treatment is impossible. The ASA Closed Claims study gives us a glimpse of injuries that can occur.
The incidence of these injuries appears to be low, likely less than 1 in 10,000 injections and perhaps even lower;
while it is difficult to estimate this risk with accuracy, in 2006, nearly 800,000 Medicare patients in the United
States
14
underwent epidural injections. Catastrophic neural injuries on record number less than 100. From published
studies, it is clear that the use of common injections for pain treatment has risen exponentially in the United States
during the last decade
14
and use of fluoroscopy to guide needle placement during these treatments is now the rule
rather than the exception. We need large-scale, prospective studies that examine the frequency of use of these
treatments and their safety and effectiveness to guide practitioners in making rational treatment decisions.

Mechanism of Injury during Image-Guided Pain Treament
Injuries associated with image-guided pain treatment fall into several broad categories. Bleeding and infectious
complications, while devastating, are rare: epidural hematoma and epidural abscess. Use of image-guidance is
unlikely to impact either of these complications, but diagnostic imaging is plays a major role in prompt diagnosis
and treatment. Image guidance does play a critical role in avoiding direct trauma to neural structures and preventing
intravascular or intrathecal injection.

Direct Trauma to Neural Structures
Trauma to neural structures, including spinal nerves, the cauda equina, or the spinal cord itself, have all been
associated with injections used in pain treatment. Specifically, direct needle contact with spinal nerves during
transforaminal injection is common. This may cause a transient paresthesia, which resolves with redirection of the
needle or can lead persistent pain. Transforaminal injection is often carried out to treat radicular pain associated with
foraminal stenosis or nerve compression associated with disc herniation. With these conditions, there is little space
around the spinal nerve to accommodate the injected fluid and the injected fluid may lead to worsened nerve
compression. The spinal cord lies in front of the advancing needle during both transforaminal and interlaminar
epidural injections at the cervical level, and direct needle trauma to the cord can occur.9 Patients with severe central
spinal stenosis may be at particular risk for spinal cord injury, especially when using an interlaminar technique.4

Vascular Compromise
Evidence for vascular compromise has arisen in two areas: paraplegia following neurolytic celiac plexus block
15,16

and catastrophic neural injuries associated with injection of particulate steroid during cervical transforaminal
injection.
17
celiac plexus block is commonly carried out at the T12/L1 vertebral level. Injectate is placed over the
anterolateral vertebral bodies or around the anterolateral aspect of the aorta. The artery of Adamkiewicz arises from
the posterolateral aspect of the aorta, most often on the left between the T10 and L2 vertebral levels, in close
proximity to where the injectate is placed for celiac plexus block. This artery often provides critical blood supply to
the anterolateral spinal cord at the low thoracic level and compromise can lead to spinal cord ischemia or infarction.
The injection of neurolytic solution in this region has been hypothesized to lead to vasospasm of this critical
reinforcing artery, and there is at least one case of transient paraplegia.
15
The neurologic insult is more often
permanent. While the mechanism may by arterial spasm and resultant ischemia, it seems more plausible that spinal
cord injury is the result of intra-arterial injection of the neurolytic solution.
Catastrophic neural injury following intra-arterial injection of particulate steroid has been well-described
with transforaminal injections,
17
stellate ganglion block,9 and cervical facet injections
18
. Several mechanisms of
injury have been postulated, including arterial spasm or dissection, but no evidence to support these alternate
mechanisms has appeared. The most likely mechanism is direct intra-arterial injection of steroid particles that
occlude the end-arteriolar circulation, leading to ischemia and infarction. During transformaminal injection,
injection into the spinal medullary arteries can lead to spinal cord infarction, and injection in to the vertebral artery
can lead to stroke involving the posterior cerebral, resulting in cortical blindness, cerebellar infarction and death
from intracranial hypertension. Direct injection in to the vertebral artery can also occur with stellate ganglion block
or high cervical facet injections. Studies in experimental animals strongly support this mechanism of injury
19,20
as do
case reports.
18
In anesthetized swine, injection of particulate steroid into the vertebral artery resulted in massive
posterior circulation stokes on MRI and persistent coma without return of spontaneous respiratory;
19
in contrast,
intra-arterial injection of the non-particulate steroid dexamethasone caused no apparent injury. In a report of a man
receiving a C1/C2 intra-articular facet injection with particulate steroid, intra-arterial injection into the vertebral
artery resulted in a fatal posterior circulation stroke
18
. These publications strongly support the mechanism of injury
of particulate steroid causing end-arteriolar occlusion.

309
Page 5
Prevention of Direct Trauma to Neural Structures
Neural structures cannot be directly visualized using fluoroscopy. Their position must be inferred from their typical
proximity to bony structures that can be seen. Prevention of trauma starts with review of available diagnostic studies
and careful planning of needle placement for the injection. Severe spinal stenosis caused by cervical
spondyloarthropathy or disc herniation can lead to complete effacement of the epidural fat and spinal fluid
surrounding the spinal cord. Needle entry into the spinal canal at such a severely stenotic level can lead to direct
cord trauma, even without dural puncture.
4
Interlaminar epidural injection at severely stenotic levels should be
avoided. In a similar fashion, severe spinal foraminal stenosis can lead to neural compression when even small
volumes of injectate are placed within the foramina. The only means to avoid neural injury is to monitor any
symptoms reported during injection, and to slow or halt the injection if symptoms appear.
The use of deep sedation or general anesthesia during the conduct of pain treatment techniques has been the
subject of much debate.
21
Proponents hold that sedation improves safety by assuring that the patient will remain
relatively immobile when the needle is in close proximity to critical structures; opponents point out that deep
sedation eliminates the ability of the patient to report contact with neural structures, eliminating any possibility of
using the patients early report of symptoms as an early warning sign of impending neural injury. In the ASA Closed
Claims study, use of deep sedation unresponsiveness was associated with an increase in the probability of permanent
spinal cord injury during pain treatment at the cervical spinal level.9 When the patient does report a paresthesia, the
practitioner should suspect contact with a spinal nerve if the pain is localized to an extremity or the spinal cord if the
patient reports both upper and lower extremity pain. If this occurs, the needle should be withdrawn and redirected.
The spinal cord can be entered without producing neural injury; however, if the spinal cord is penetrated and any
substance is injected, it is likely that neurologic injury will occur. The neuronal disruption caused by placing
injectate into the substance of the cord appears to be what causes the most severe injury, rather than direct trauma
caused by needle entry alone. However, if an arterial structure within the cord is disrupted, bleeding into the cord
can also produce significant injury.
Once the needle is in final position, it is critical to use images obtained in multiple planes to establish the
final needle position. An AP image tells little about the needles depth, while a lateral image tells little about the
medial to lateral deviation of the needle. Combining the two images, an accurate measure of the needles position in
three dimensions can be reconstructed.
Use of ultrasound has gained rapid acceptance for performing peripheral nerve blocks for surgical
anesthesia.
22
Ultrasound can be used to directly visualize superficial neural structures, like the brachial plexus. The
success rate of many peripheral nerve blocks has improved with use of ultrasound. It is less clear if ultrasound will
improve the safety of these techniques.
23
Direct intraneural injection and intravascular injection can still occur with
the use of ultrasound. In pain treatment, use of ultrasound has not advanced as rapidly. Pain practitioners have been
using fluoroscopy for years and fluoroscopy allows direct and precise visualization of the bony elements of the
neuraxis. Use of ultrasound to image neuraxial stuctures is limited by the echogenicity of the bony elements of the
spine, preventing direct visualization of many
structures. Nonetheless, the safety of several pain
treatment techniques may be improved by the use of
ultrasound. Stellate ganglion block is foremost among
these. The position of the great vessels of the neck,
the thyroid gland, the esophagus, and the vertebral
artery can only be inferred from the position of the
bony elements of the spine using fluoroscopy (Figure
4. Stellate ganglion block. Anatomy relevant to
stellate ganglion block as seen on ultrasound.
Transverse (short-axis) ultrasound view at the level of
the transverse process of C7. Note that the vertebral
artery can be seen anterior to the echogenic transverse
process at the level of C7. The vertebral artery cannot
be seen clearly at the C6 level on ultrasound, as it lies
posterior to the echogenic transverse process within
the foramen transversarium. At the level of C7, the
superior margin of the thyroid is seen just lateral to
the trachea. The dashed arrow indicates the optimal
trajectory for placing a needle using an in-plane
approach, for example, placing the needle in a lateral

309
Page 6
to medial direction with the shaft in the transverse plane of the ultrasound image. Ultrasound image courtesy of Urs
Eichenberger MD, PhD, University Department of Anesthesiology and Pain Therapy, University Hospital of Bern,
Bern, Switzerland, 2011.) These structures can be directly visualized using ultrasound. Techniques for using
ultrasound to safely perform this block have been described.
24
The use of ultrasound is likely to quickly replace the
use of fluoroscopy based for stellate ganglion block. The position of the pleura during intercostal block can only be
inferred from the position of the inferior margin of the rib during intercostal nerve block when using fluoroscopy.
The pleura and the neurovascular bundle can both be seen directly using ultrasound, facilitating precise placement of
the injectate adjacent to the intercostal nerve while avoiding penetration of the pleura. If a pneumothorax is
suspected following injection, M-mode ultrasound provides a simple bedside means to detect even the smallest air
collections.
25

Prevention of Intra-Arterial Injection
Prevention of intravascular injection relies on the ability to identify when the tip of a needle or catheter lies within a
vascular structure before local anesthetic or particulate steroid is administered. The consequences of intravascular
injection depend on the vascular structure into which the injectate is placed and the nature of the injectate. Local
anesthetic and neurolytic solutions are often administered in relatively large doses for specific procedures in pain
treatment, doses of local anesthetic large enough to produce systemic toxicity are employed only during less
common procedures, like celiac plexus block. Conventional means for detecting intravascular injection rely on
visual evidence of blood on aspiration or detection of signs and symptoms associated with intravascular injection.
Local aesthetics can produce unique symptoms when injected into the blood stream, including tinnitus, circumoral
paresthesias, and metallic taste but these symptoms do not occur reliably, particularly with more potent agents like
bupivacaine. The addition of epinephrine to the injectate in small concentrations, e.g. 1:200,000, can lead to an
increase in heart rate following intravascular injection, but this also can be unreliable, particularly in those with
cardiac disease receiving beta-blockers. Local anesthetic toxicity can occur after either intravenous or intra-arterial
injection; recognition and treatment have been discussed in detail in previous reviews.
26

Intra-arterial injection of particulate steroid can lead to devastating neurologic injury. Radiographic
guidance lends a unique and sensitive means to detect intravascular needle or catheter location, and this approach
can be used to prevent inadvertent injection of local anesthetic or steroid into a vascular structure. Injection of
radiographic contrast into a vascular structure can only be detected reliably by using a live technique. If contrast is
injected followed by obtaining a single, static image thereafter, any contrast that was injected intravascularly will
have been carried away from the site of injection by the passing blood flow. The contrast must be injected under
continuous x-ray exposure. The use of digital subtraction improves visualization of vascular structures by
subtracting the baseline image and leaving only those structures that are in motion as the image sequence is taken
(Figure 5. Posterior-Anterior view of the cervical spine during C7/T1 transforaminal injection, including a digital
subtraction sequence after
contrast injection. An
anteroposterior view of
an angiogram obtained
after injection of contrast
medium, prior to planned
transforaminal injection
of corticosteroids. A:
Image as seen on
fluoroscopy. The needle
lies in the left C7/T1
intervertebral foramen.
Contrast medium outlines
the spinal nerve (large
arrow). The radicular
artery appears as a thin
tortuous line of contrast
passing medially from the
site of injection (small
arrow). B: Digital
subtraction angiogram
reveals that the radicular

309
Page 7
artery (small arrow) extends to the midline to join the anterior spinal artery and much of the contrast is located in the
correct location surrounding the spinal nerve (large arrow). Reprinted from Rathmell JP, Aprill C, Bogduk N.
Cervical transforaminal injection of steroids. Anesthesiology 2004;100:1,597, with permission.) Live fluoroscopy,
with or without digital subtraction, increases the sensitivity of detecting intravascular needle location. In one series,
20% of cervical transforaminal injections were identified with live fluoroscopy,
10
while only 20% had evidence of
blood return on aspiration.
11
The addition of digital subtraction increases the sensitivity for detection of intravascular
location.
13
After intravascular needle position has been ruled out using contrast injection and a live x-ray technique,
it is critical to assure that the needle position does not move. Attaching a short, flexible extension tubing to the
needle at the start of the procedure allows the practitioner performing the injection to attach and detach syringes to
the catheter without touching the needle, thus reducing the chance of any change in needle position before the
particulate steroid is administered. Using this combination of live x-ray and radiographic contrast, there have been
no reports of neural injury attributed to particulate steroid. It is important to remain vigilant, as patient movement
and confusing patterns of contrast spread can easily be missed and intravascular needle position could be
overlooked.

Prevention of Intrathecal Injection
Use of radiographic guidance and injection of small volumes of radiographic contrast can also be used to identify
when a needle has penetrated the dura. Injection of subarachnoid local anesthetic will lead to a sensory and motor
block when administered at the lumbar level and total spinal anesthesia accompanied by respiratory arrest when
injected at the cervical level. While the topic of ongoing debate, intrathecal injection of particulate steroid
preparations may lead to neurotoxicity. Practitioners must learn to recognize the characteristic patterns of epidural
and intrathecal contrast spread. It is also important to recognize unusual patterns like the loculated posterior contrast
collections that signal subdural injection.
27
During epidural steroid injection, it is wise to abort the procedure before
placing steroid when either subdural or intrathecal needle position is suspected.

Treatment and When to Seek Consultation
Prevention of injury is the only reliable means to assure the safety of image-guided pain interventions. Once either
direct trauma to neural structures or intra-arterial injection of particulate steroid has occurred, there is no effective
means to improve the outcome. Immediate, supportive care should be given, including airway management,
hemodynamic resuscitation, and treatment of seizures. Diagnostic imaging should be obtained when feasible to
establish the location, nature and magnitude of the injury. Thereafter, transfer to the care of a neurologist or
neurosurgeon for supportive care is likely the best route. In the case of spinal cord injury, there is some evidence
that use of high dose intravenous steroids following traumatic spinal cord transection can improve neurologic
outcome
28,29
and on this basis some experts advocate treatment of spinal cord injury secondary to needle trauma or
ischemia in the same way. Permanent, disabling spinal cord injury is more the most likely long-term outcome.9
After acute stabilization, most patients will need rehabilitation aimed at regaining functional capacity.

Summary
The use of image guidance has become a routine and integral component of pain treatment, however, there is
insufficient scientific evidence to judge whether this has improved safety. The logical appeal is overwhelming, to
the point that it is now unlikely that scientific comparisons of most techniques with and without radiographic
guidance will ever be conducted. This manuscript is meant to be a pragmatic discussion of what we know about the
utility of imaging in improving the safety of interventional pain treatments. This analysis can also serve to guide
future investigators who set out to understand how to apply new imaging techniques, and in the process how to
rigorously evaluate their usefulness.

References
1
Chou R, Atlas SJ, Stanos SP, Rosenquist RW. Nonsurgical interventional therapies for low back pain: a review of
the evidence for an American Pain Society clinical practice guideline. Spine (Phila Pa 1976) 2009; 34:1078-93.
2
Sethee J, Rathmell JP. Epidural steroid injections are useful for the treatment of low back pain and radicular
symptoms: pro. Curr Pain Headache Rep 2009;13:31-4.
3
Armon C, Argoff CE, Samuels J, Backonja MM; Therapeutics and Technology Assessment Subcommittee of the
American Academy of Neurology. Assessment: use of epidural steroid injections to treat radicular lumbosacral pain:
report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
Neurology 2007;68:723-9.

309
Page 8

4
Field J, Rathmell JP, Stephenson JH, Katz NP. Neuropathic pain following cervical epidural steroid injection.
5
White AH, Derby R, Wynne G. Epidural injections for the diagnosis and treatment of low back pain. Spine
1980;5:7886.
6
Renfrew DL, Moore TE, Kathol MH, et al. Correct placement of epidural steroid injections: Fluoroscopic guidance
and contrast administration. AJNR Am J Neuroradiol 1991;12:10037.
7
El-Khoury G, Ehara S, Weinstein JN, et al. Epidural steroid injection: a procedure ideally performed with
fluoroscopic control. Radiology 1988;168:554 7.
8
Stevens DS, Balatbat GR, Lee FM. Coaxial imaging technique for superior hypogastric plexus block. Reg Anesth
Pain Med 2000;25(6):643-7.
9
Rathmell JP, Michna E, Fitzgibbon DR, Stephens LS, Posner KL, Domino KB. Injury and liability associated with
cervical procedures for chronic pain. Anesthesiology 2011;114:918-26.
10
Nahm FS, Lee CJ, Lee SH, Kim TH, Sim WS, Cho HS, Park SY, Kim YC, Lee SC. Risk of intravascular injection
in transforaminal epidural injections. Anaesthesia 2010;65:917-21.
11
Kim do W, Han KR, Kim C, Chae YJ. Intravascular flow patterns in transforaminal epidural injections: a
comparative study of the cervical and lumbar vertebral segments. Anesth Analg 2009;109:233-9.
12
Rathmell JP. Toward improving the safety of transforaminal injection. Anesth Analg 2009;109:8-10.
13
McLean JP, Sigler JD, Plastaras CT, Garvan CW, Rittenberg JD. The rate of detection of intravascular injection in
cervical transforaminal epidural steroid injections with and without digital subtraction angiography. PM R
2009;1:636-42.
14
Manchikanti L, Pampati V, Boswell MV, Smith HS, Hirsch JA. Analysis of the growth of epidural injections and
costs in the Medicare population: a comparative evaluation of 1997, 2002, and 2006 data. Pain Physician
2010;13:199-212.
15
Wong GY, Brown DL. Transient paraplegia following alcohol celiac plexus block. Reg Anesth 1995;20:352-5.
16
Abdalla EK, Schell SR. Paraplegia following intraoperative celiac plexus injection. J Gastrointest Surg
1999;3:668-71.
17
Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004;100:1595-
600.
18
Edlow BL, Wainger BJ, Frosch MP, Copen WA, Rathmell JP, Rost NS. Posterior circulation stroke after C1-C2
intraarticular facet steroid injection: evidence for diffuse microvascular injury. Anesthesiology 2010;112:1532-5.
19
Okubadejo GO, Talcott MR, Schmidt RE, Sharma A, Patel AA, Mackey RB, Guarino AH, Moran CJ, Riew KD.
Perils of intravascular methylprednisolone injection into the vertebral artery. An animal study. J Bone Joint Surg
Am 2008;90:1932-8.
20
Dawley JD, Moeller-Bertram T, Wallace MS, Patel PM. Intra-arterial injection in the rat brain: evaluation of
steroids used for transforaminal epidurals. Spine (Phila Pa 1976) 2009;34:1638-43.
21
Bernards CM, Hadzic A, Suresh S, Neal JM. Regional anesthesia in anesthetized or heavily sedated patients. Reg
Anesth Pain Med 2008;33:449-60.
22
Sites BD, Chan VW, Neal JM, Weller R, Grau T, Koscielniak-Nielsen ZJ, Ivani G. The American Society of
Regional Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and Pain Therapy joint
committee recommendations for education and training in ultrasound-guided regional anesthesia. Reg Anesth Pain
Med 2010;35(2 Suppl):S74-80.
23
Neal JM. Ultrasound-guided regional anesthesia and patient safety: An evidence-based analysis. Reg Anesth Pain
Med 2010;35(2 Suppl):S59-67.
24
Gofeld M, Bhatia A, Abbas S, Ganapathy S, Johnson M. Development and validation of a new technique for
ultrasound-guided stellate ganglion block. Reg Anesth Pain Med 2009;34:475-9.
25
Ueda K, Ahmed W, Ross AF. Intraoperative pneumothorax identified with transthoracic ultrasound.
26
Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist
RW, Weinberg GL. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med
2010;35:152-61.
27
Ajar AH, Rathmell JP, Mukherji SK. The subdural compartment. Reg Anesth Pain Med 2002;27:72-6.
28
Delamarter RB, Coyle J. Acute management of spinal cord injury. J Am Acad Orthop Surg 1999;7:166-75.
29
Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR. Pathophysiology and pharmacologic treatment of acute
spinal cord injury. Spine J 2004;4:451-64. Anesthesiology 2011;115:653-5.
29
Delamarter RB, Coyle J. Acute management of spinal cord injury. J Am Acad Orthop Surg 1999;7:166-75.

309
Page 9

29
Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR. Pathophysiology and pharmacologic treatment of acute
spinal cord injury. Spine J 2004;4:451-64.

Disclosure

314
Page 1
Algorithmic Approach to Back Pain
Nagy Mekhail, M.D., Ph.D Cleveland, Ohio
ANATOMIC CONSIDERATIONS:
The lumbar spine plays an instrumental role in locomotion and posture. The intricate anatomy of the lumbar spine is
a remarkable combination of five strong vertebrae, multiple bony elements linked by joints, ligaments, and tendons,
large muscles, complex innervations and vascular supply.
A typical vertebra consists of a vertebral body joined by pedicles to the posterior elements, namely the laminae,
superior and inferior articular processes, transverse processes, and the spinous process. The top and bottom of each
vertebral body is coated with an endplate. The endplates of the vertebral bodies are joined to one another by an
intervertebral disc and help support the disc.
Intervertebral discs consist of a central gelatinous nucleus pulposus composed of water and proteoglycans. The
nucleus pulposus is surrounded by the annulus fibrosus. The inner portion of the annulus is composed of
fibrocartilage, whereas the outer fibers are made of concentrically oriented lamellae of collagen fibers. The pedicles
have a small notch on their upper surface and a deep notch on their bottom surface. These superior and inferior
vertebral notches that are located above and below the pedicles form the intervertebral foramen, where the nerve
roots exit the spinal canal.The spinous process extends posteriorly from the point where the two laminae join, and
acts as a lever to effect motion of the vertebra. The 4 articular processes link with the articular processes of adjacent
vertebrae to form facet joints. The lumbar facet joints form the posterolateral articulations connecting the vertebral
arch of one vertebra to the arch of the adjacent vertebra. Each facet joint receives dual innervation from medial
branches arising from the dorsal ramus at the same level and the medial branch of the nerve one level above the
facet joint.The lateral recess is the space within the spinal canal located toward the sides. Anatomically, the lateral
recess is bordered laterally by the pedicle, posteriorly by the superior articular process, and anteriorly by the
posterior lateral surface of the vertebral body and adjacent intervertebral disc. The thecal sac forms the medial
border of the lateral recess. Age-related changes in bones, facet joints, ligaments etc. may cause these structures to
encroach on the lateral recess, creating a condition known as lateral spinal stenosis.
For the sake of providing a comprehensive yet simplified approach to the most common low back pain problems,
will divide the lumbar spine into three compartments and address the pain generators in each compartment.
The anterior column is composed of:
Anterior longitudinal ligament
The vertebral body and intervertebral disc
The middle column is composed of:
Posterior longitudinal ligament
The spinal canal with all its contents
The posterior column is composed of:
Spinous process
Pedicle
Lamina
Faceted joints
Interspinous ligament
Supraspinous ligament
Ligamentum flavum

314
Page 2
THE ANTERIOR COMPARTMENT
The anterior compartment is both the largest and strongest of the three spinal compartments, and is comprised of the
bony vertebral bodies and intervertebral discs. These elements are bounded ventrally by the anterior longitudinal
ligament and dorsally by the posterior longitudinal ligament. The center of gravity passes through the center of the
anterior compartment supporting a majority of the weight of the head, upper body and trunk. Despite its large
volume, the anterior compartment contains few structures, and pain complaints originate primarily from pathology
within either the bony vertebral body or the intervertebral disc.

DISCOGENIC PAIN
Discogenic pain can be defined as pain that results from internal disc derangement (IDD). Pain arising from IDD in
the lower lumbar segments can be mistaken for radicular pain since both etiologies have symptoms which can
radiate to one or more lower extremity dermatomes.

Diagnosis
There are no widely accepted diagnostic criteria for low back discogenic pain. Typical characteristics include pain
lasting in spite of conservative treatment, for six months or longer that is localized to the medial aspect of the spine.
Discogenic pain worsens with sitting or loading maneuvers, and is improved with recumbency. Although
discogenic pain might radiate to the buttock, thigh or leg, but such radiation does not follow the typical radicular
distribution as the in radiculopathy secondary to HNP. The neurologic exam is usually normal and provocative
straight-leg raising maneuvers are negative differentiating this condition from lumbar radicular pain syndrome.
Physical exam maneuvers aimed specifically at provoking discogenic pain are non-specific.
Imaging modalities can suggest IDD when an annular tear is present, and may be supported by the presence of a
high intensity zone (HIZ) on MRI. Nerve root compression is usually abscent. Despite the ability of MRI to
visualize disc degeneration and quantify disc height, degenerative MRI findings are frequently seen in asymptomatic
people.
Although discography remains a controversial test yet, if properly administered, it yields very valuable diagnostic
information. Contrast is introduced into the nucleus pulopsus under pressure to describe the disc morphology,
visualize annular fissures that might be contained or communicating with the epidural space and elicit pain that is
concordant to the patients discogenic pain. The procedure is performed in the lightly sedated patient at a minimum
of two contiguous levels with the second level serving as a control. Manometry performed during the procedure
provides the basis for interpretation. A chemically sensitive disc will generate concordant pain at <15psi above
opening pressure following injection of <1mL of contrast. A mechanically sensitive disc will generate pain between
15-50psi above opening pressure, while pain generated between 51-90psi represents an intermediate response. Lack
of a pain response at pressures greater than 90psi is considered normal. It is important to note that a positive result
reproduces pain, which is similar in character, and location to the patients typical pain and that adjacent disc are
pain free.
The diagnostic discogram can be followed with a functional assessment post-procedurally by injecting 0.5mL of
local anesthetic into the painful disc through a tiny plastic catheter left within the nucleus pulposus. Following
recovery from sedation, the patient is instructed to perform those activities, which provoke their typical pain, and if
both patient-reported and functional assessments shows improvement of pain and function after injecting a very
small volume of local anesthetic into the nucleus pulposus, the diagnosis of discogenic pain is confirmed. Despite
the promising initial results of identifying as high as 38% false positive provocative discogram, functional anesthetic
discography has not been adopted in clinical practice.

Treatment
Conservative options for discogenic pain are limited and lack a large quantity of supporting evidence. NSAIDs and
acetaminophen/opiate combinations are often employed as first line agents for symptomatic relief. Physical therapy,
bed rest and spinal manipulation were shown to be ineffective modalities in a systematic review.
A number of non-surgical interventional procedures have been either adapted or developed for the treatment of
discogenic pain including, intradiscal radiofrequency ablation, intradiscal electrothermal therapy (IDET) and
biaculoplasty. Injection of intradiscal corticosteroid following positive discography does not consistently improve
pain outcomes. Similarly, radiofrequency ablation of the nucleus pulposus using equipment adapted from
radiofrequency neurotomy procedures or with the discTRODE system has not consistently resulted in significant
improvements in pain scores or functional improvements.
IDET requires placement of an electric thermocoil along the posterior border of the junction between the nucleus
pulposus and the annulus fibrosis. The intradiscal portion of the catheter is heated with the likely mechanism

314
Page 3
resulting in ablation of the aberrant nerves thought to be responsible for generating discogenic pain. Although there
were good amount of supportive trials, IDET is no longer part of clinical practice due to the initial over utilization
which led to lack of reimbursement by health care payers.
Intradiscal Biaculoplasty was developed to address the technical challenges of IDET and offers several advantages.
The procedure entails placing bilateral intradiscal electrodes within the posterior aspect of the disc. The bilateral
probes create a uniform band lesion along the posterior wall of the disc at lower temperatures and for shorter
duration than IDET. A randomized sham controlled study showed a sustained pain relief and improvements
disability.

DISCITIS AND VERTEBRAL OSTEOMYELITIS:
Discitis and vertebral osteomyelitis are additional etiologies of anterior compartment spine pain, and are considered
collectively since the pathophysiology and treatment are complimentary. Rates of both discitis and vertebral
osteomyeltis are increasing likely due to a combination of the increased use of injectable drugs, increasing age of the
population and increasing incidence of nosocomial infections. Because the intervertebral disc has no blood supply,
discs become infected due to spread from the adjacent vertebral bodies and also it is difficult to treat with IV
antibiotics.

Diagnosis
Discitis and vertebral osteomyelitis present as axial back pain that worsens at night. Fever is not a universal finding
and its absence should not exclude the possibility of an infectious etiology. Tenderness to palpation over the effected
segments is a sensitive, but not specific, clinical indicator. Acute phase reactants including erythrocyte
sedimentation rate (ESR) and c-reactive protein (cRP) are of great value as prognostic indicators. Blood cultures are
positive in a small majority of patients and should be obtained since positive cultures can guide therapy and can
limit the need for further diagnostic workup.
Plain radiographs are initially normal within the first two weeks of presentation, but destructive changes in two
contiguous endplates and collapse of the intervertebral body can occur with progression. Rarely are two adjacent
vertebrae involved with the presence of a normal intervertebral disc, and if observed, should prompt investigation
into another diagnosis such as malignancy or fracture.
Magnetic resonance imaging (MRI) is the most sensitive imaging modality to detect osteomyelitis. T1 weighted
MRI findings consistent with osteomyelitis include signal loss in the vertebral endplate and decreased signal
intensity in the vertebral body. Discitis is seen on T2 imaging as increased signal intensity within the disc. Triple
phase bone scan is an alternative radiographic modality that has high sensitivity, but is indistinguishable from
vertebral fractures. Surgical biopsy can be performed when blood cultures do not implicate a causative organism
and the response to standard antimicrobial treatments has failed.

Treatment
The primary goal of therapy is to eradicate the offending organism and limiting the spread of the infection.
Staphlococcal, streptococcal and gram-negative bacilli are the most often causative agents and empiric antimicrobial
therapy against these organisms are often employed while awaiting microbial cultures. Morbidity and mortality are
reduced when antimicrobial therapy is introduced shortly after initial presentation. Duration of therapy tends to be
long, and may necessitate the use of parenteral antimicrobials if an agent is isolated which is not sensitive to oral
therapy. An analgesic regimen is often required with the goal of improving mobility and restoring functional status.
Surgery may be required in those patients with progressive disease unresponsive to antimicrobials, those with cord
compression or with the presence of coexisting abscess.

VERTEBRAL COMPRESSION FRACTURES:
Vertebral compression fractures (VCF) are a common cause of back pain in the elderly population with a 25%
lifetime incidence in postmenopausal women and an estimated 40% incidence in those over the age of eighty years.
700,000 VCFs /year occur as consequence of advanced osteoporosis, though neoplastic and traumatic etiologies are
also, to a much lesser extent, implicated. Often as important as the fracture and associated pain, is the disability and
social withdrawal which develops as a consequence of the VCF. Sequelae of VCFs include venous thromboembolic
disease, progressive muscle weakness, restrictive lung disease and increased likelihood of nursing home admission.
Long-term bed rest after VCFs result in accelerated bone loss and increases in both morbidity and mortality.

314
Page 4
Diagnosis
A history supporting VCF can vary widely, but often includes discrete onset of acute back pain after lifting or
bending. It is estimated that two-thirds of VCFs pass undiagnosed, hampering early interventions to interrupt the
sequelae of immobility which rapidly develop. A vague history in those patients who seek medical intervention for
back pain complaints can be inadequately assessed and incorrectly attributed to worsening of chronic arthritic spine
pain complaints precluding early intervention.
VCFs occur most often at the T12 or L1 levels due to the transition of the rigid thoracic zygophyseal architecture to
the more mobile lumbar spine. Subtle height loss and kyphosis can develop in those patients affected with VCF.
Typically VCF results in at least 1cm of height loss, but height loss of >6cm was 94% specific to diagnose VCF by
measurement alone. Because 19% of patients with a VCF will suffer a subsequent VCF within one year, recognition
and early intervention is important. The risk of developing subsequent VCFs increases exponentially with a five-fold
increased incidence after a single VCF, twelve-fold increase after two VCFs and a 75-fold increase after three or
more VCFs in patients with persistent low bone density.
Lateral spine radiograph of the thoracolumbar spine is recommended as the initial diagnostic imaging modality
when considering the diagnosis of VCF. Anterior wedge shaped deformities are most characteristic, and can be
associated with vertebral end plate changes. MRI is the definite advanced diagnostic imaging modality of choice.
MRI helps identify the age of the VCF with acute fractures demonstrating characteristic bone marrow edema. MRI
adds the additional benefit of determining the integrity of the posterior wall of the vertebral body if an interventional
approach is planned. CT scan provides a good assessment of the bony architecture and can be substituted in those
patients with contraindications to MRI.
A musculoskeletal and neurologically focused physical exam should be performed to exclude cord compression,
infection or other etiologies that may necessitate an urgent surgical consultation. Laboratory analysis is typically
obtained by the primary care provider upon diagnosis and may include assessment of serum calcium, phosphate, 25-
hydroxy Vitamin D levels and advanced tests to evaluate bone density include dual energy X-ray bone densitometry
(Dexa Scan) or quantitative computed tomography. Laboratory analysis is also useful if malignancy is suspected by
clinical history, and may include complete blood cell count, erythrocyte sedimentation rate or protein
electrophoresis.

Treatment
Initial management should be directed toward providing analgesia and resuming function to decrease the sequelae of
immobility including venous thromboembolic disease, restrictive lung disease and mood impairments. No
randomized controlled trial has demonstrated the superiority of one class of analgesic agents over another in the
treatment of VCF, and selection of an agent is dependent upon the patients comorbidities. The use of non-steroidal
anti-inflammatory agents (NSAIDs) is somewhat controversial due to the uncertain effects of these agents on bone
healing when studied in long-bone fractures. Many will chose to use a combination of opiate and acetaminophen to
assist with the acute pain of a VCF, and avoid any potential increased risk of non-union. If osteoporosis is the
etiology of the VCF, specific assessment and treatment of bone density should commence shortly after diagnosis.
Optimization of calcium supplementation and antiresorptive therapies remains an important aspect of the VCF
treatment strategy.

Although the effectiveness of back bracing has been studied prospectively in traumatic vertebral fractures and
decreases in both pain and disability scores was demonstrated, caution should be exercised if a brace is provided to
ensure that the device is to be used only temporarily for symptomatic relief and should not be used to foster
immobility. It is worthwhile to note that with each week of bed rest, the osteoporotic patient can lose up to 2% of
their bone mass.

Deciding upon proceeding toward interventional treatments should be individualized based upon patient
comorbidity and level of disability. When assessing the natural history of patients with osteoporotic VCFs, the
majority achieved pain relief after three months with conservative treatment alone, though no predictors of those
who would fail conservative treatment were identified.
VCF can be treated percutaneously on an outpatient basis with both kyphoplasty and vertebroplasty. Large-scale
retrospective studies have associated percutaneous vertebral augmentation with a 37% decrease in mortality when
compared to those in the conservative treatment arm. Vertebral augmentation has been shown to offer short-term
pain relief, limit or reverse the local kyphotic deformity and increase functional capacity. Kyphoplasty offers
advantages including restoration of vertebral height and a decrease in the local kyphotic angle, but is more costly
than vertebroplasty and the importance of restoring vertebral height has not been quantified. The effectiveness of

314
Page 5
kyphoplasty is most pronounced at one-month follow-up, but improvements in treated populations have also been
sustained at two-year follow-up. The most notable potential risks with vertebral augmentation include local cement
extravasation and cement embolism, which are claimed to be less with kyphoplasty versus vertebroplasty.

The Middle Compartment
Lumbar spinal stenosis
Lumbar spinal stenosis (LSS) functionally impacts significant numbers of Americans per year. Current estimates
place the number of Americans suffering from elderly lumbar spinal stenosis at 400,000. 47% of patients ranging
from 60 to 69 years of age have mild to moderate stenosis and 19.7% have severe stenosis. LSS is becoming major
health-care issue as the population ages. Although LSS is not life threatening, it can cause substantial disability with
limitations to performing daily activities, and thus, the associated negative impact on quality of life (QOL).
The pathophysiological changes of Lumbar spinal stenosis (LSS) are caused by degenerative changes of the lumbar
spine including thickened and buckled ligamentum flavum (LF), osteophyte formation, facet hypertrophy, and
bulging of the intervertebral disk. This usually leads to narrowing of the central spinal canal with compression
ischemia of the cauda equine. In a study of 191 symptomatic patients; LF hypertrophy was found to be the key
contributor to their LSS.

Schonstrom et al, 1989 studies the changes in the dimensions of the lumbar spinal canal under both flexion-
extension and axial compression-distraction using computerized tomography (CT) scans in human cadaver lumbar
spine specimens. The cross-sectional area of the spinal canal was reduced by 16% (around 40 mm) when the lumbar
spines were moved both from flexion to extension and from distraction to compression. An analogous decrease in
the midsagittal diameter of the canal of 2 mm was found. During these motions, LF did not appear to be a significant
factor for the dynamic changes affecting the dimensions of the canal.

Diagnosis
Patients classically present with low back pain that may be associated with neurogenic claudication; described as
pain radiating to the lower extremities that begins and worsens as the patient ambulates or stands and is relieved
with flexion of the spine and sitting down. Neurogenic claudication is believed to result from structural narrowing of
the vertebral canal that impedes venous return causing venous hypertension resulting in arterial ischemia of the
cauda equina.

Imaging studies include standing AP, lateral, and flexion-extension lumbar spine radiographs to rule out
spondylolisthesis. Plain films can show degenerative processes including disc degeneration, osteophytes and facet
hypertrophy. While CT can directly view the effects of disc pathology, facet hypertrophy and buckled LF on the
cross sectional area of the canal, the poor soft tissue contrast of the CT may impose difficulties in delineating the
disc/thecal sac/LF interfaces. The addition of intrathecal myelography contrast resolves this problem and provides
excellent spatial and soft tissue resolution. Furthermore, it allows a dynamic imaging component. Standing views in
flexion/extension can demonstrate the reduction of the cross sectional area of the dural sac. . The gold standard
imaging modality is MRI. T2 weighted MR scans allows noninvasive evaluation of central canal stenosis. Earlier
studies used AP diameters of the dural sac to determine the degree of stenosis 10 mm was considered absolute
stenosis and 12 mm was suggestive of severe stenosis (10). MR scans also allows accurate measurement of the
thickness of LF.

It is important to differentiate neurogenic claudication due to LSS from radicular pain due to lumbar disc herniation
or from intermittent claudication due to vascular ischemia. The latter may be mistaken for lumbar spinal stenosis
because both conditions are associated pain that is exacerbated with exercise.
While vascular claudication diminishes with rest whether standing or sitting, neurogenic claudication often persists
with standing still in an erect posture, but can only be relieved by assumption of stooped, flexed posture, or with
sitting. Lumbar disc herniation may be associated with radicular pain similar to the neurogenic claudication that is
worse with walking and standing. However, the pain is usually unilateral, rarely bilateral, but localized to the
distribution of the affected nerve root(s) and will not be diminished with flexion of the spine nor will it be
intensified with extension of the spine.

314
Page 6
Teatment
Current therapeutic options range from conservative management to invasive spinal surgical decompression with
lumbar fusion and with or without instrumentation. In between there are multiple minimally invasive and
microsurgical options.

Conservative therapy versus surgery
Conservative methods of therapy may be of use in early to moderate cases, once patients progress to the point of
moderate symptom severity, conservative methods may become ineffective or unrealistic.
Surgical decompression is shown to be helpful in about two thirds (2/3) of patients, but is associated with
considerable morbidities. Patients who delay surgery have similar outcomes to patients who proceed immediately
with surgery. Thus, the consideration of proceeding with surgery may await evaluation of comorbidities as well as
assessing the patient's response to conservative therapy.
In a systematic review of the randomized controlled study comparing conservative and surgical approaches, the
advantage of surgery was evident at 3 to 6 months and was maintained for up to 2 to 4 years. Nevertheless, the
differences tended to be smaller beyond the four years.

Conservative therapy
Current recommendations for conservative treatment are based on empiric evidence and expert opinion.
Additionally, there are no comparative trials of conservative therapies versus the natural history of spinal stenosis.
Many studies do not specify the type of conservative therapy that is prescribed to the patients. Multidisciplinary
treatment programs including physiotherapy, behavioral therapy, epidural steroid injections and a back exercises
program have been recommended but not specifically validated.

Physical Therapy
Physical therapy is a recommended treatment of neurogenic claudication; but its role has not been established with
current evidence. It is uncertain which exercises constitute an effective exercise program are. Flexion-based
exercises (e.g., stationary bicycle and inclined treadmill) increase the cross sectional area of the spinal canal and
improve the microcirculation of the neural elements. These allow patients to tolerate the exercise program better and
help improve weight loss and cardiovascular fitness. Aquatic therapy is also useful; it stretches the hip flexors and
hamstrings and strengthens the abdominal and trunk muscles.

Interventional pain management options
Caudal epidural steroid injections produced significant reduction in reported pain and disability scores in 60% of
patients trialed. Similarly, other studies have shown that both caudal and interlaminar lumbar epidural steroid
injections were associated with improved function and decreased opioid intake. However, the benefits are usually,
short term and the efficacy decreases with time.

Surgical Options
While early and milder cases respond to conservative measures, moderate and severe LSS may fail to sustain an
adequate long-term relief and, thus progression to the next option, which conventionally used to be open surgery,
was inevitable in some patients.

Open Surgical Decompression
The wide variety of open surgical procedures developed to treat lumbar spinal stenosis has in some ways
complicated the ability to clearly analyze outcomes as well as complication rates, and it is partly for this reason that
such wide ranges of outcomes have been reported in the literature. Historically lumbar laminectomy, either hemi or
bilateral laminectomy, or more extensive decompression with fusion has been the standard of care for surgical
management of lumbar spinal stenosis. Obviously these surgical options were associated with extensive degrees of
tissue trauma, hospital stay, longer recovery times and a long list of other potential complications.

Outcomes and Complications of Surgery
In a meta-analysis of surgical lumbar decompression literature by Turner et al, the average improvement in pain and
mobility was reported as 64%, while others showed deterioration in the results over time. Late deterioration was
thought to be due to compromising the stability of lumbar spine structures by wide open-surgical laminectomy
resulting in instability and allowing for possible recurrence or worsening of the symptoms. The Maine and SPORT
studies reported that surgical decompression outcomes were superior to those of nonsurgical measures.

314
Page 7
Randomization bias was the most significant flaw in both studies. It was clear in the 10-year outcome of the Maine
study, that the benefit of decompressive surgery diminished over time and there was no significant differences in
lower back pain and patient satisfaction. Furthermore, those who underwent subsequent surgical procedures had less
improvement in outcomes over time compared with patients who did not.
A landmark study regarding the complications of open surgical treatment that the complication rate was 7% in spite
of the highly skilled surgeons involved and the chance of death was one in one thousand. The rate of dural tear or
spinal fluid leak in the surgical series was ranging from 2.0% to 20.0% in open surgery, and 1.1% to 12.5% in
minimally invasive surgery. Castro-Menendez et al reported that despite those endoscopic surgeries were less
invasive than open surgeries; they had an average procedure-related complication of 16%; with the most frequent
being; incidental dural tear at a rate of 10%. Such complications usually require longer hospital stay, and possible
additional surgery; all adding to health-care cost. Other serious complications like epidural hematoma and required
blood transfusion were also reported after open and minimally invasive decompression surgeries.
Minimally Invasive Lumbar Decompression mild procedure:
The mild procedure attenuates the effect of a hypertrophic ligamentum flavum by thinning, partially detaching, and
remodeling the ligament.

The complications rate of mild procedure is definitely lower than the complication rates reported for both open and
minimally invasive lumbar spinal stenosis surgeries. Several studies documented the safety profile of the mild
procedure.

Effectiveness and cost effectiveness
Several studies have demonstrated that mild procedure is effective in reliving pain, decrease disability and improve
the walking distance and standing time in patients with moderate to severe lumbar spinal stenosis. Also recent Study
from The Cleveland Clinic showed that mild procedure is the cost effective strategy as far quality adjusted life year
(QALY) is concerned in patients with LSS.

THE POSTERIOR COMPARTMENT
Lumbar Facets Joints Pain
Pain originating from the lumbar facets joints is a common cause of chronic low back pain. The common
mechanism is inflammation of those joints due to repetitive stress and accumulating low-level trauma. The joint
capsule is filled and stretched out with inflammatory fluid, thus generating pain. Predisposing factors include;
spondylolistheis, degenerative disc disease, over weight and advanced age.

Diagnosis
Patients usually present with chronic axial low back pain, which is not uncommonly associated with referred pain
too. Pain from the upper lumbar facets might be referred to the flank, hip and upper lateral thigh where as lower
lumbar facets mediated pain is more likely to be referred to the thigh along the posterior and lateral aspect.
However, such referred pain is always above the knees and do not follow a specific nerve root distribution as in
lumbar radiculopthy.

Although there are no characteristics findings in the physical examination, however, it is widely accepted that
lumbar paravertebral tenderness may indicate facetogenic pain. Pain is usually reproduced with facet loading, and
extension and rotation maneuvers.

The lack of correlation between history and physical examination and the facet mediated pain resulted in the
prevalent acceptance of the diagnostic blocks as a useful tool to establish the diagnosis. Intra-articular (IA) facet
joint injections and medial branch block (MBB) have been found to be equally beneficial diagnostic tools.
Several studies have showed a false-positive rate for lumbar facet blocks, ranging from 25% to 40% using
comparative blocks or saline controls. This was regardless of the technique used whether IA or MBB. The reasons
for false-positive facet blocks are multifactorial and include placebo response (1832%), use of sedation, the
copious use of superficial LA, and the spread of injectate to other pain generators.
On the other hand false negative results occur in 11% of the time. This was probably because LA never fully
immersed the targeted nerves, or may due to aberrant or additional innervations to facet joints aside from medial
branches.

314
Page 8
For these reasons, it has been recommended to do double blocks, using either saline controls or two different LA,
before proceeding to definitive therapy.

Treatment
Facet Joints Blocks
The use of intraarticular steroid injections to treat facet joint pain is controversial. In uncontrolled studies the
response varied from intermediate pain to long-term relief. Long-term relief ranged from 18% to 63%. Most of the
patients involved in those studies did not undergo diagnostic facet joint blocks. Intermediate pain relief has been
reported after intraarticular LA alone.
No significant difference in outcomes between local anesthetic, steroid or saline injections. Another randomized,
controlled study demonstrated a statistically significant benefit that favors steroid over saline at 6 months after the
procedure. Based on the existing evidence 128,181,212214, and the presence of inflammatory mediators in and
around degenerated facet joints, a small subset of patients with lumbar facet joint pain may benefit from
intraarticular steroid injections if accompanied by an active inflammatory process.

Radiofrequency Ablation:
Several uncontrolled trials have shown that radiofrequency denervation of lumbar facet joint pain, may provide
sustained relief in 5080% of subjects without previous back surgery and 3550% of patients with failed back
surgery syndrome.

Seven placebo-controlled studies have been conducted to evaluate the role of radiofrequency denervation in
treatment of lumbar facet join pain. Six studies were positive and a non-interventional pain physician conducted the
only negative study where patients selection was not strict.

Complications:
Patient may complain of temporary paresthesia in the legs and temporary loss of motor functions, if large volume of
LA was injected and spread to the segmental nerves.
Transient localized burning pain is one of the most common complications. The incidence of worsening back pain
was 2.5 %, however, it was self-limiting lasting up to 2 weeks. Although they are uncommon but serious sequlae
may follow facet joints steroids injections may cause suppression of the hypothalamicpituitaryadrenal axis for a
duration lasting up to 4 weeks, and impaired insulin sensitivity thus increasing the glucose levels for less than a
week. Septic arthritis, epidural abscess, and meningitis; have been reported after intraarticular injections.

As for RF, transient and self-limiting numbness and/or dysesthesias have been reported after radiofrequency
denervation. Although rare, burns may occur with RF due to electrical faults, insulation breaks in the electrodes, and
generator malfunction. The most prevalent complication after RF is neuritis, with incidence less than 5%. The
administration of corticosteroid was found to decrease the incidence of post procedure pain after radiofrequency
denervation. There is also a potential risk of thermal injury to the ventral rami if an electrode is advanced ventrally
over the transverse process.

Sacroiliac Joint Pain
Sacroiliac joint (SIJ) pain is a common cause of low back pain. The current literature estimates that in 10-30% of
patients presenting with low back pain, the SIJ has been found to be the pain generator. Several risk factors leading
to SIJ pain are identified. Pregnancy induced ligamentous laxity, trauma from motor vehicle accidents, athletic
events requiring unilateral loading (cross-country skiing, in-line skating) and the spondylarthropathies have all been
implicated as underlying causes of SIJ mediated pain. Tumor, infection and occult fractures are other less common
sources of SIJ dysfunction.

Additionally, patients will often develop SIJ mediated pain following lumbar fusion
surgeries as the biomechanics of the lumbar spine and the stresses transmitted to the SIJ are altered. The prevalence
of SIJ dysfunction following lumbar fusion to ranges from 32-61%.

Despite numerous studies there remains no consensus regarding the innervation of the SI joint. The anterior SI joint
has been found to have direct input ranging from the ventral Rami of L2-S2, whereas the posterior SIJ innervation
travels through the dorsal Rami of L4-S3.

Diagnosis
The diagnosis of SI joint (SIJ) dysfunction or SI mediated pain is initially suspected based on the combination of
history and physical examination. Several studies have been conducted to determine the pain referral pattern most

314
Page 9
associated with SIJ mediated pain. Fortin et al injected asymptomatic volunteers with contrast and lidocaine in
order to determine a pain referral pattern upon distension of the SIJ. SIJ mediated pain correlates to an area in the
buttocks and radiating to the posterolateral thigh. There are single provocative or alignment tests that have been
proven to accurately determine the SIJ as the primary pain generator in patients presenting with low back pain.
However, there has been research suggesting that a combination of 3 positive provocative tests has led to a
specificity of 78-79% and sensitivity of 85-94%. To add to the diagnostic dilemma there are very few radiographic
signs to suggest SIJ involvement.

Treatment
The treatment of SIJ dysfunction usually includes conservative treatment with a multidisciplinary approach
including medication management, physical therapy. Interventional procedures such as SIJ injections is
recommended if conservative treatment fails there is a need to maximize participation and benefits from physical
therapy.

If the diagnosis of SIJ pain is confirmed with a diagnostic injection with local anesthetic alone the injection may be
repeated with local anesthetic and corticosteroids to improve the duration of pain relief. If there is greater than 50%
improvement in pain with transient results then the current literature supports the use of radiofrequency ablation.
Conventional radiofrequency ablation (RFA) has been commonly used in the past with acceptable result but recent
literature suggests that cooled radiofrequency ablation may produce improved results due to the larger lesions. When
performing radiofrequency ablation of the SIJ innervation, it is common to create a strip lesion at the dorsal rami of
L5 and the lateral branches of S1-S2 or 3 whose anatomic course can be quite variable. The theoretical advantage of
cooled RFA is that a larger lesion can be reliably created to cover the variable path of the lateral branches of S1-3.
Randomized placebo-controlled study using Cooled RFA on L5 primary dorsal Rami and S1-3 Lateral branches on
14 patients showed significant improvement at 1, 3 and 6 months follow up. Additionally, 11 of the patients in the
placebo group were allowed to crossover and undergo conventional RFA. Again significant relief was shown in the
crossover group.

If patients fail conservative and interventional treatment, surgical intervention may be the patients last option for a
meaningful recovery. A recent prospective study showed promising results in those who failed all other modalities.

Selected References
1. Alamin, T. International Society for the Study of the Lumbar Spine. Abstracts. Bergen, Norway; June 13-
17, 2006:52-53
2. An HS, Seldomridge JA. Spinal infections: diagnostic tests and imaging studies. Clin Orthop Relat Res.
2006 Mar;444:27-33.
3. Anderson PA, Froyshteter AB, Tontz WL Jr. Meta-analysis of vertebral augmentation compared with
conservative treatment for osteoporotic spinal fractures. J Bone Miner Res. 2013 Feb;28(2):372-82.
4. Appleby D, Andersson G, Totta M. Meta-analysis of the efficacy and safety of intradiscal electrothermal
therapy (IDET). Pain Med. 2006 Jul-Aug;7(4):308-16.
5. Boonen S, Van Meirhaeghe J, Bastian L, Cummings SR, Ranstam J, Tillman JB, Eastell R, Talmadge K,
Wardlaw D. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results
from a randomized trial. J Bone Miner Res. 2011 Jul; 26(7):1627-37.
6. Melton LJ 3d. Epidemiology of spinal osteoporosis. Spine. 1997;22(24 Suppl):2S11S.
7. Pauza KJ, Howell S, Dreyfuss P, Peloza JH, Dawson K, Bogduk N. A randomized, placebo-controlled trial
of intradiscal electrothermal therapy for the treatment of discogenic low back pain. Spine J. 2004 Jan-
Feb;4(1):27-35.
8. Ross PD, Davis JW, Epstein RS, Wasnich RD. Pre-existing fractures and bone mass predict vertebral
fracture incidence in women. Ann Intern Med. 1991 Jun 1; 114(11): 919-23.
9. Kalichman L, Cole R, Kim DH, Ling. L. Spinal stenosis prevalence and association with symptoms: The
Framingham study. Spine J 2009; 9 :545-550
10. Mekhail N, Benyamin R, et al. Long term results of percutaneous Lumbar decompression. Pain Practice
2011; 11: 1530-7085
11. Schonstrom N, Lindhl S, Willen J, et al. dynamic changes in the dimensions of the lumbar spinal canal: an
experimental study in vitro. J Ortho Res. 1989;7 :115-121

314
Page 10
12. Inufsa A, An HS, Lim TH, et al. Anatomic changes in the spinal canal and intervertebral foramen associated
with flexion-extension movement. Spine 1996;21:2412-2420
13. Sairyo K, Biyani A, Goel V, et al. Pathomechanism of ligamentum flavum hypertrophy: a multidisciplinary,
investigation based on clinical, biochemical, histologic, and biologic assessments. Spine 2005; 30:2649-
2656.
14. Amundsen T, et al. Lumbar spinal stenosis. Conservative or surgical management: A 10 year prospective
trial. Spine, 2000; 25(11):1424-1436.
15. Fu K-M, Smith J, Polly Jr. D, et al. Morbidity and mortality in the surgical treatment of 10,329 adults with
degenerative lumbar stenosis. J Neurosurg Spine 12:443-446, 2010.
16. Castro-Menendez M, Bravo-Ricoy JA, Casal-Moro R, Hernandez-Bianco M, Jorge-Barreiro FJ. Midterm
outcome after microendoscopic decompressive laminotomy for lumbar spinal stenosis: 4 year prospective
Study. Neurosurgery 2009; 65:100-110.
17. Katz JN, Lipson SJ, Chang LC, Levine SA, Fossel AH, Liang MH. Seven to ten years outcome of
decompressive surgery for degenerative lumbar spinal stenosis. Spine 1996; 21:92-97.
18. Atlas SJ, Deyo RA, Keller RB, Chapin AM, Patrick DL, Long JM, Singer DE. The MAINE lumbar spine
study, part III: One year outcome of surgical and nonsurgical management of lumbar spinal stenosis.
19. Weinstein JN, Tosteson TD, Lurie JD, Tosteson AN, Blood E, Hanscom B, Herkowitz H, Cammisa F,
Albert T, Boden SD, Hilibrand A, Goldberg H, Berven S, An H; SPORT Investigators. Surgical versus non
surgical therapy for lumbar spinal stenosis. N Engl J Med 200; 358:794-810.
20. Ng LCL, Tafazal S, Sell P. The effect of duration of symptoms on standard surgical outcomes in the surgical
treatment of spinal stenosis. Eur Spine J 2007; 32:1-1-8.
21. Epstien NE. The frequency and etiology of intraoperative dural tears in 110 predominantly geriatric patients
undergoing multi-level laminectomy with non-instrumented fusions. J Spinal Disord Tech 2007; 20:380-
386.
22. Mekhail N, Costandi S, Samuel S: Functional and patient reported outcomes in symptomatic lumbar spinal
stenosis following percutaneous decompression. Pain Pract.2012 Jul;12(6);417-25
Disclosure
323
Page 1
Spinal Cord Stimulation for the Treatment of Pain. An Update of New Technology
Timothy R. Deer, M.D., DABPM, FIPP Charleston, West Virginia
INTRODUCTION: Spinal Cord Stimulation (SCS) is an important and evolving therapy that can change lives,
improve function and positively impact society concerning those who suffer from chronic pain. The use of SCS is
an important part of the pain treatment algorithm and should be applied judiciously based on the SAFE principles.
SAFE: The use of any interventional therapy should be based on careful selection and logical thought progression.
The introduction of the SAFE algorithm should be applied to these techniques. This is an acronym for the
requirements that should be applied to interventional treatments: they should be relatively safe, appropriate, fiscally
neutral and efficacious. (Krames). SCS meets these criteria in many conditions to which physicians are asked to
treat.
TOPICS OF DISCUSSION: The goals of this presentation will be to advance the knowledge of members
regarding current, evolving and future uses of spinal cord stimulation. We will focus on exciting new technology
such as dorsal root ganglion stimulation, high frequency stimulation, and burst stimulation.
CONVENTIONAL SPINAL CORD STIMULATION (SCS):
SCIENTIFIC PRINCIPLE-
The use of SCS to treat chronic pain involves the strategic placement of a stimulating combination of electrodes
over a neural target in the epidural space. This is achieved by placing the electrodes on a lead attached to an
implanted programmable computer and power source. By using a programmable generator the amplitude, rate,
frequency and shape of the electrical field can be manipulated to create pain relief. The mechanism of neural effect
has been theorized to change the balance of inhibitory to excitatory fiber activity by the gate control process, by
manipulating the number and position of cathodes and anodes on the lead.
LOGICAL PROGRESSION OF PAIN TREATMENT
The algorithmic treatment of pain is currently the standard of care for improving patients pain levels, function, and
quality of life. In recent years, many experts have recommended the use of SCS much earlier in the algorithm:
namely before a second spine surgery in neurologically stable patients, before chronic high dose opioids in patients
with mixed or neuropathic pain, and in some cases prior to the first back surgery in patients with multi-level disease
or uncertain surgical outcomes. The change in the algorithm is due to several factors including the simplification of
stimulation trialing, improvement of programming, and diversity of arrays. Evidence based medicine also is
favoring SCS over other strategies, shown nicely in two randomized studies by Kumar and North. Kumars study
showed that stimulation was superior to conventional medical treatment alone in patients with a history of failed
back surgery with leg pain. Norths study showed that spinal cord stimulation is superior to a second back surgery
in regard to pain relief, satisfaction, and need to have the other therapy.
In addition to improved evidence the desire to avoid opioids and addiction is leading to an interest in these methods.
INDICATIONS AND PATIENT SELECTION:
In the United States, the Food and Drug Administration have approved this therapy for the treatment of moderate to
severe pain in the trunk or limbs. The specific indications for which these devices are most commonly used have
been well defined. The most common indication for spinal cord stimulation is failed back surgery syndrome. Other

323
Page 2
common reasons patients undergo these surgeries include cervical and lumbar radiculitis, complex regional pain
syndrome, peripheral neuropathies, post herpetic neuralgia, ischemic limb pain, angina, pelvic pain and other
neuropathic and visceral pain syndromes. New treatment options may change this broaden the patients appropriate
for this therapy.

Patients are selected for SCS based on pain location, pain quality, and pain intensity. The patients have often failed,
or are not appropriate for, other more conservative methods. The patient should have no untreated coagulation
disorders, have no active infection, have no unstable depression or anxiety, are not actively psychotic, and have an
appropriate response to a SCS trial.

SPINAL CORD STIMULATION: THE PROCEDURE

GENERAL PRINCIPLES:
After appropriate patient selection and education the patient should undergo preoperative evaluation for
perioperative risks. Once cleared for trialing, the patient should be interviewed by the anesthesiologists and
stabilized. Preoperative antibiotics are based on local pathogens and susceptibilities. Most common antibiotics
include intravenous vancomycin or a third generation cephalosporin preoperatively, bacitracin or kantrex
intraoperatively. Intraoperative prepping and draping is should be broad and extend well beyond the surgical field.
Positioning should facilitate surgical technique and patient safety and comfort.

IMPLANT METHOD:
The use of a percutaneous lead or surgical paddle lead is at the discretion of the implanting physician. Percutaneous
leads are introduced in a less invasive and less dangerous method so are usually preferable, but in some cases such
as those with complex spinal disease, extensive scar tissue, or primary axial back pain a paddle lead may be a better
choice. In those who obtain a percutaneous lead, whether using a cylindrical lead or new paddle constructs, a needle
must be placed appropriately prior to delivering the device.

NEEDLE PLACEMENT: Prior to implanting a device physicians should consider planning the needle placement
including the level of entry, the side of entry and the angle. In the lumbar spine needles are usually placed into the
epidural space at 30 to 45 degrees. A paramedian approach is preferred, with a skin entry site one and half to two
levels below the desired entry space. The needle entry into the epidural space should be two to three levels below
the final lead target. In the cervical spine the needle entry should be below the C7-T1 interspace. Usually at T2-3 or
T3-4. In some cases, implanters place the needle in the epidural space at a lumbar level and deliver the leads to the
cervical spine.

LEAD PLACEMENT: Lead placement has evolved in recent years. Classically the lead is placed into the
posterior epidural space and confirmed on AP and Lateral fluoroscopy. The targets are noted below. New clinical
practice has shown the addition of leads in the paravertebral adipose tissues in the areas of pain to the epidural leads
may lead to improved coverage through a process referred to as triangulation.

EPIDURAL LEAD TARGET: The physician should understand the target for the led to achieve proper
stimulation. Table one provides general targets for spinal cord stimulation.

323
Page 3
Table 1. Lead Placement for Anatomical Stimulation

LEAD PROGRAMMING: The field of stimulation or the array is influenced by the number of the cathode
(negative) and anode (positive) electrodes and the orientation of each contact. Current is driven into the neural
tissue based on the presence of a cathode. The optimal current delivery occurs when a cathode is surrounded or
guarded by an anode on each side. New lead arrays have been developed using percutaneous, percutaneous
paddle and paddle leads. Cross talk between leads, stim cycling and rapid settings to move the active electrodes
may impact the outcome.

LEAD ANCHORING: In analysis of complications of SCS, the possibility of lead movement is always a major
concern. The advent of new mechanical or locking anchors has reduced this problem. Other factors appear to be
moving the anchor into the ligament, angle of needle entry, and suture methods.

POCKET FORMATION: The position of the pocket is based on patient preference and body habitus. Options
include the buttock, abdominal wall, flank, and chest wall. The depth of the pocket should be appropriate to avoid
skin erosion, but should also assure good communication with telemetry. The implanter should consider sleeping
patterns, shoulder mobility and patient clothing preferences when planning the pocket. Hemostasis and antibiotic
irrigation is important prior to closing the wound. Thrombin and gel foam may improve hemostasis prior to closing.

COMPLICATIONS OF SCS: The most common complications of spinal cord stimulation include lead migration,
superficial infection, impedance abnormalities, wet tap, and nerve irritation. More serious problems include
epidural hematoma, epidural abscess, paraplegia, and death. The number of complications can be reduced by sterile
technique, preoperative assessment, and proper selection.

Region Position Target
Cervical C2 Lateral Mandible, Neck, Shoulder
C2-3 Shoulder, Arm
C4-6 Arm, Hand
C7-T2 Anterior Shoulder, Chest
Thoracic T3-T6

Abdominal, Thoracic, Visceral Organs
Thoracic T1-3 Angina, Chest
T4-6 Visceral Abdomen
T7-9 Axial Back
T10 Knee, Hip
T11-12 Leg, Foot

Lumbar L1 Foot, Possible Pelvic Organs
L5-S1
Nerve Root
Foot

Sacral S2-4 Pelvis, Rectum, Perineum

323
Page 4
ADVANCES IN STIMULATION OF THE SPINE

STIMULATION OF THE DORSAL ROOT GANGLION: The anatomy of the DRG makes it an attractive
target for neuromodulation. The structure is a sensory neural body that contains the soma from primary sensory
neurons. The ganglion is located within the bony structure of the spine just below the pedicle where it reliably lies in
all patients, and both transmits and influences sensory neural impulses traveling from the periphery. The ganglion
contains multiple cell types including neurons and glial cells that change and become hyperexcitable in chronic pain
conditions. (figure 1, with permission of Jeff Kramer, PhD) The DRG has been a target for injection, surgical
interventions and radiofrequency in the past, but with no long standing efficacy. The development of new novel
leads, delivery tools and multi-channel generators has led to the use of DRG stimulation as a major advance in the
treatment of intractable pain syndromes. The lead shape allows for selective stimulation of the DRG without
encompassing the surrounding structures. (figure 2, with approval of Jeff Kramer, PhD) Approval of this therapy
has now been given in the European Union, and a multi-center randomized prospective study in being initiated this
summer in the United States. Based on the European study data, DRG-SCS has expanded the field of stimulation
for patients traditionally not good candidates for SCS. These patients include patients suffering from phantom limb
pain, foot pain, chest wall pain and groin pain.

The presence of hyperexcitable fibers in the DRG appears to lead to selective stimulation of the abnormal areas of
the pain transmission and avoids the over stimulation of fibers that may lead to motor stimulation. (figure 1)

Figure 2.

323
Page 5
HIGH FREQUENCY METHODS OF SCS: In the past the variables of SCS included amplitude, pulse width, and
rate. Frequency was felt to be a minor variable and that most patients responded to low frequency stimulation. This
concept has recently been challenged. Work done in the United States, Europe and Australia has suggested that the
use of High Frequency Stimulation (HFS) may give significant relief in those who have primary axial back pain or
those with inability to tolerate the feeling of parasthesia with conventional stimulation. HFS involves the use of
leads, similar to conventional systems, placed based on anatomical strategies noted above. In these implants there
are no parathesias created. The frequency used in these devices approach 10, 000 Hz, but may also be used to deliver
more standard frequencies. Recent work on using 5,000 Hz did not show efficacy suggesting that the higher
frequency may be more efficacious.

BURST STIMULATION; The use of tonic stimulation in both high and low frequency ranges have shown good
outcomes in thousands of patients. Recent work by DeRidder and colleagues have suggested using rapid non-tonic
bursts of high frequency signal rotated with periods of electrical silence to produce pain relief without parasthesia.
This concept has great potential to salvage those failing traditional low frequency tonic stimulation and is attractive
that using the same generator you could use both tonic and burst stimulation to optimize outcomes.

PERCUTANEOUS PADDLE DELIVERY: The choice of delivering a cyndrilical lead via a needle approach or a
paddle lead via a laminotomy open approach has been complicated based on the risk to benefit ratio. In many
cases, a paddle lead has been placed although only a small capacity of the lead has been needed. A need to deliver a
more efficient lead via a percutaneous approach has been present for some time. In the past several months the
approval of a percutaneous sheath to delivery a small streamlined efficient unidirectional lead has changed this
equation. Now the ability to place one or two paddles without a laminectomy is available to the nonsurgical
implanter. The use of hybrid systems with both paddle and percutaneous leads has recently been presented as an
option for patients who suffer from both limb and axial pain.
The availability of percutaneous paddle leads does not totally alleviate the need for surgically placed paddle leads.
The complex paddles with multiple columns are needed in some patients who have failed percutaneous attempts at
stimulation, or require a complicated revision, or who have anatomical spinal challenges. When placing a paddle
lead via a percutaneous approach the needle angle and useo of a paramedian approach are important. (figure 3,4).
These techniques allow for proper placement of the guidewire to direct the sheath which is placed via the Seldinger
technique. (figure 5 and 6). The sheath is used to pass the paddle lead to the target. Recent publications have
suggested both favorable safety data, and good initial efficacy data.

figure 3. figure 4.

323
Page 6

Figure 5.

Figure 6.

MOTION SENSING AND ADAPTATION: When a lead is placed in the epidural space, it is used to delivery
current to the spinal cord and neural structures. The spinal cord moves in the cerebral spinal fluid as the patient
changes positions. In a small number of patients this movement of the cord causes difficulty in achieving reliable
stimulation. There have been some methods to achieve a reduction in this variability. Options include hardware to
further occupy the space such as paddle leads, or complex arrays, or new technology. A new method of adapting the
device to motion has FDA approval and involves an implanted motion sensor that changes stimulation with
variances in the patients body position. This implant is a part of the normal programmable device, and does not
change the technique or size. The role in satisfaction with this device appears quite good, but we have not seen
improvements in efficacy or function in any current studies.

FUTURE ADVANCES: New advances in the field have led to promise for many patients who suffer from
intractable pain. In the future we will see an evolution of therapies including microwave technology, blue tooth
energy transfer, and new methods of programming, and lead placement. The possibility of advanced expandable
percutaneous paddle leads could be the next disruptive technology in our field.
Recently, conditional MRI has been approved for some devices. This is a tremendous advance, and the field is in
need of eventual approval for all devices for non-restricted MRI.

SELECTED READING:

Deer T., Bowman R., Schocket S.M., et. al. The Prospective Evaluation of Safety and Success of a New Method of
Introducing Percutaneous Paddle Leads and Complex Arrays With an Epidural Access System Neuromodulation:
Technology at the Neural Interface Volume 15, Issue 1, pages 2130, January/February 2012.

!"#$%"
'$()*"$
#
+("*,-
.+/
0/'%
-"
)1(,
%
+(-%
323
Page 7
Krames E., Poree L., Deer T., Levy R. Implementing the SAFE Principles for the Development of Pain Medicine
Therapeutic Algorithms That Include Neuromodulation Techniques Neuromodulation: Technology at the Neural
Interface Volume 12, Issue 2, pages 104113, April 2009
Deer T. Atlas of Implantable Therapies for Pain Management Springer; 2011 edition (December 3, 2010)
Deer T. (Editor), Leong M. (Editor), Buvanendran A. (Editor), et. al. Comprehensive Treatment of Chronic Pain by
Medical, Interventional, and Integrative Approaches: The American Academy of Pain Medicine textbook on Patient
Management. Springer; 2013 edition (October 24, 2012)
Fielus, R. B. (2uu9). "New culpiits in chionic pain." Sci Am !"#(S): Su-S7.
Bogan, Q. B. (2u1u). "Labat lectuie: the piimaiy sensoiy neuion: wheie it is, what it uoes, anu why it
matteis." Reg Anesth Pain Neu !$(S): Su6-S11.
Deer T, Masone R. Selection of Spinal Cord Stimulation Candidates for the Treatment of Chronic Pain. Pain
Medicine, Volume 9 Issue S1, Pages S82-S92
North R, Kidd D, Farraokhi F, Piantadosi S. Spinal cord stimulation versus repeated lumbosacral spine surgery for
chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98-106.
Mekhail N, Aeshbach A, Stanton-Hicks M. Cost Benefit analysis of neurostimulation for chronic pain. Clin J Pain.
2004 Nov-Dec:20(6): 462-8.
Kumar. K, Taylor RS, Jacques L, et.al., Spinal Cord Stimulation versus conventional medical management for
neuropathic pain: A Multicenter randomized controlled trial in patients with failed back surgery syndrome. Pain
(2007); doi:10.1016/j.pain.2007.07.028
Taylor R, Van Buyten J, Buscher E. Spinal cord stimulation for complex regional pain syndrome: a systematic
review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006
Feb;10(2):91-101
Deer T. Current and future trends in spinal cord stimulation for chronic pain. Current pain and headache reports
2001, (5): 503-509.
Deer T. A Critical Time for Practice Change in the Pain Treatment Continuum: We need to reconsider the role of
pumps in the patient care algorithm. Pain Medicine. June 2010.
Disclsoure
St. Jude Medical, Funded Research, ConsultingFees; Spinal Modulation, Funded Research, Consulting Fees;
Medtronic Inc., Consulting Fees ; Nevro Inc.,Consulting Fees ; Bioness Inc., Funded Research, Consulting Fees
329
Page 1
Neuroimaging of Pain
Sean Mackey M.D., Ph.D Stanford, California
Introduction
Pain has an astounding impact on the individual patient, the family, and society as a whole. According to the recent
Institute of Medicine report on pain, pain affects 100 million Americans and costs over half a trillion dollars per
year. It is a highly personal and subjective experience modulated by cognitive, emotional, and environmental
factors. During the 1990s, designated the Decade of the Brain, investigators significantly advanced our
understanding of the function and structure of the brain through imaging techniques such as functional magnetic
resonance imaging (fMRI), voxel-based morphometry (VBM), magnetoencephelography (MEG), single-photon
computed tomography (SPECT), and positron-emission tomography (PET). Investigations conducted with these
techniques revealed a complex neural matrix involved in pain processing and perception and laid to rest a previously
controversial concept: the involvement of the cerebral cortex in pain processing. Recently, functional neuroimaging
has provided us with useful information regarding: 1) brain regions involved in cognitive, affective, and
physiological manipulation of pain; 2) neural plasticity associated with neuropathic pain conditions as well as other
chronic pain disorders; and 3) the effects of therapeutic agents on central neural systems.
Nociception vs. Pain
Pain has been defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory or
emotional experience associated with actual or potential tissue damage, or described in terms of such damage.2
This definition classifies pain as a subjective experience; therefore, unlike the experience of many diseases such as
hypertension or diabetes, there is no objective measurement for a patients pain. We must do our best to correlate
objective data (physical exam findings, imaging results, lab tests) with the patients subjective reporting. Further
complicating the problem is the fact that pain is often confused with the nociception the neural signals generated
and transmitted to the spinal cord and brain in the face of stimuli that are potentially or actually tissue-damaging.
Pain, in contrast, requires a functioning brain to process these nociceptive signals and translate them into a
subjective experience.
This contrast between nociception and pain is particularly important in chronic pain conditions where there is a lack
of objective tissue damage but pain is still present. These neuropathic or non-nociceptive conditions are often the
result of dysfunction or damage within the spinal cord, brainstem, or brain. It is this damage to the peripheral and
central nervous system that warns us of actual or potential tissue damage. However, with neuropathic pain, these
signals have become maladaptive in that they impart no beneficial survival value. Chronic neuropathic pain becomes
insidious in that it is often associated with depression, anxiety, decreased libido, altered appetite, and sleep
disturbances.3
Functional Neuroimaging and the Brain Regions Involved in Pain
Until recently, the basis of our understanding of the mechanisms of pain generation and transmission from the spinal
cord to the brain has been primarily animal studies. The recent introduction of noninvasive imaging technologies has
made the human CNS available for direct examination and comparison between healthy subjects and chronic pain
patients. This permits us to confirm and extend the wealth of knowledge about basic nociceptive processing and
plasticity, learned from animal research, and translate it more confidently to humans.
Neuroimaging studies have helped identify and characterize brain structures involved in the processing and
perception of pain 2, 3. These structures encompass at least two, main systems working in parallel: the lateral and
the medial pain systems 3. The lateral system, primarily composed of the primary and secondary somatosensory

329
Page 2
cortices (S1, S2), is responsible for the sensory-discriminative components of pain. In contrast, the medial system,
consisting of brain regions including the anterior cingulate cortex (ACC), insular cortex (IC), prefrontal cortex
(PFC), basal ganglia, and periaqueductal gray (PAG), is primarily responsible for the affective, motivational,
attentional, and evaluative components of pain. The lateral and medial pain systems overlap significantly with each
other and other pain matrix areas supplementary motor area, premotor cortex, parietal cortex, and hypothalamus.
These areas are potential targets for therapeutic interventions and a better understanding of the mechanisms linking
cognition, emotion, and pain.

In addition to identifying brain regions classically thought of as being involved in the processing and perception of
pain, neuroimaging techniques have discovered numerous brain regions and subregions not previously implicateda
For example, we now appreciate the more essential role played in pain by such traditional reward areas as the
ventral tegmental area and the nucleus accumbens (Scott, 2006). Further, Schweinhardt et al (2006) used fMRI to
characterize different functional regions of the insular cortex (posterior insular, caudal anterior insular, and rostral
anterior insular) in allodynic pain. Whereas the pain matrix suggests each region contributes uniquely to the
experience of pain, neuroimaging elucidates the reality that the regions are complex and overlapping in their
functions with other cognitive and emotional experiences.

Emotional and Cognitive Influences on Pain
Pains intensity and unpleasantness correlate well with levels of noxious stimulation. We know, however, that the
pain experience can be significantly modulated by our own thoughts and feelings. Neuroimaging has helped
elucidate many of the neural correlates regarding factors well known to modulate the experience of pain, including
attention 4, anticipation 5, placebo 6, empathy 7, 8, and fear/anxiety 9. Each factor impacts how we perceive pain,
and an increasing number of functional neuroimaging studies are investigating how these factors affect pain
perception and activity in the brain.

Effects of Attention on Pain
There have been anecdotal reports for centuries of people who suffer traumatic injuries and yet experience little or
no pain. Furthermore, it is well-established that distraction from a noxious stimulus results in a decreased perception
of pain10. Many chronic pain patients use distraction in its many forms to manage their pain: walking the dog,
listening to music, reading a book, and working are just some examples. Attention to a different task or cognitive
distraction attenuates activity in the ACC, insular cortex, thalamus, somatosensory regions, and the PAG11.

Attention to pain, however, has produced varied results, sometimes enhancing pain perception and sometimes
reducing it. The variability may be gender-related and potentially due to differences between normal subject
populations and pain patients.

The neural correlates responsible for attentional modulation of pain are not known. Data suggest multiple levels of
the central nervous system are involved. One such system is the opiate-sensitive descending and ascending
pathways: a pathway from the frontal cortex to the amygdala, PAG matter, rostral ventral medulla, and finally the
dorsal horn of the spinal cord, as well as ascending pathways through the medial thalamus to the ACC12.

Although data is limited, studies have demonstrated that patients with chronic pain have impaired ability to distract
themselves from their chronic pain, independent of their pain intensity. These studies strongly suggest cortical
and/or subcortical dysfunction as a cause for this impairment. Probable areas involved in this dysfunction include
the orbitofrontal cortex and ACC. Apkarian used another method of neuroimaging volumetric brain morphometry
to characterize changes in anatomical gray and white matter in patients with chronic back pain. He found that
these patients showed 5-11% less gray matter, particularly in the prefrontal cortical regions, an area strongly
associated with attentional modulation. This loss was equivalent to 10-20 years of normal aging.

Effects of Anticipation, Fear, and Anxiety on Pain
Expectation and anticipation of pain are known to influence the immediate unpleasantness of pain. Uncertain pain
has been demonstrated to increase unpleasantness and to result in less pain tolerance compared with certain pain.
There is also evidence in humans that acute stress can activate the pain-modulating circuit that contributes to
analgesia. This analgesia may be achieved by the stress-regulatory systems including endocrine, autonomic,
immune, and opioid systems. A small number of studies have examined the neural mechanism underlying the
anticipation of pain. Expectation of pain activated the neighbor medial frontal lobe, insular cortex, and cerebellum,

329
Page 3
but expectation did not activate locations mediating pain experience itself15. More recently, investigators found that
most brain systems associated with pain processing can be activated by anticipation of a painful stimulus; however,
the anticipatory responses are smaller than the pain intensity-related responses16.

Effects of Mood on Pain
Mood and emotion have also been shown to alter pain perception, although the difficulty in dissociating mood and
attention may have confounded previous reports. Manipulations positively affecting mood or emotion such as
soothing music, pleasant pictures, and humorous films, generally reduce pain perception. However, manipulations
negatively affecting mood or emotion have not always been consistent.

Recent research indicates that people who fear pain tend to report more negative pain experiences. Those with a high
fear exhibited a selective attentional bias towards pain-related information, compared to those classified as low in
their fear of pain. We investigated the effects of fear and anxiety related to painful sensations as a means of
explaining individual differences in pain perception. We identified that fear of pain correlated strongly with lateral
orbitofrontal brain activation a region associated with response regulation. Anxiety related to pain correlated with
medial prefrontal activation a region associated with self-focused attention17. We believe that these psychological
factors may play a significant role in explaining the differences in pain perception related to emotion.

Results from studies on the attentional, anticipatory, and other cognitive modulations of pain, combined with
biochemical and anatomical understandings of analgesia, provide us with insights into the top-down and bottom-up
plastic changes that occur in the central nervous system. Functional neuroimaging research in this area has just
begun, concentrating on the interplay between affect and pain perception. Future research using functional
neuroimaging is likely to have a significant impact on cognitive and other therapeutic interventions.

Neuroimaging Chronic Pain States
In contrast to what is known about acute pain, evidence about the generation and maintenance of chronic pain
suggests that changes in central pain processing are mediated through mechanisms of neural plasticity, ultimately
leading to hyper-excitability of central structures17. It has been thought for many years that the processes of acute
and chronic pain are very distinct, involving different pain systems (i.e., the medial system with chronic pain and
lateral system with acute pain). So far, functional neuroimaging studies provide little evidence that acute pain and
chronic pain are processed within different parts of the pain matrix. Neuroimaging studies in patients with peripheral
or central nerve lesions have also implicated similar brain structures activated during experimental acute pain.
Peripheral nerve lesions (compression, nerve section, or amputation) often lead to spontaneous neuropathic pain in
the involved area. Imaging studies have demonstrated a decrease in regional cerebral blood flow in the contralateral
thalamus in patients with neuropathic pain. Interestingly, deep-brain stimulation of the contralateral thalamus in
patients with neuropathic pain has been shown to provide symptomatic relief with accompanying increase in rCBF
in this area as well as in SI and insular cortex. Additionally, changes in the somatotopy of the primary sensory
cortex have been shown to occur in amputees and have correlated with their experience of phantom pain; similar
findings have been found in low-back pain (LBP) patients18.

Recent neuroimaging studies have identified abnormalities within brain systems in patients with fibromyalgia (FM)
10. A consistent finding in the literature is that FM patients show greater activity in pain-processing structures when
intensity of mechanical pressure stimulus is controlled. Areas of greater activation in response to a low-stimulus
pressure in FM patients include contralateral SI, inferior parietal lobule, IC, ACC, posterior cingulate cortex (PCC),
ipsilateral S2, bilateral superior temporal gyrus, and cerebellum. The findings suggest that individuals with FM
experience centrally-augmented pain processing 10. Similar findings were obtained when a thermal stimulus was
used 11.

While fMRI provides important functional activation information, structural imaging techniques also provide
unique, mechanistic information about healthy and diseased CNS processes. Voxel-based morphometry (VBM), a
structural MRI technique that involves morphometric analysis on a voxel-by-voxel basis, is used to quantify the
density of gray and white brain matter. VBM has been widely used in psychology and psychiatry to yield novel
insights into the mechanisms of Alzheimers disease 12, panic disorder 13, schizophrenia, and bipolar disorder 14.
VBM has recently been used to detect changes within patients with low-back pain 15, cluster headache 16 and most
recently FM. A small, preliminary study found that the FM patients had decreased gray matter in the ACC, IC,
medial frontal cortices and parahippocampal gyri 17. Notably, these areas overlap heavily with abnormal functional

329
Page 4
activity identified in other studies and in other pain conditions 18, 19. We have also recently identified abnormalities
in trigeminal and cortical gray matter distributions in patients with temporomandibular disorder 20.

Magnetic resonance spectroscopy (MRS) makes it possible to directly investigate tissue metabolism and
biochemistry. Recently, investigators demonstrated differences in N-Acetyl aspartate concentration in patients with
chronic lower-back pain compared with controls, anxiety levels (high vs. low) and brain regions (dorsolateral PFC,
orbitofrontal cortex, thalamus, cingulate), resulting in an 3-way interaction19. They found a precise relationship
between perception and brain chemistry in that sensory vs. affective pain was represented best in the DLPFC and
OFC in chronic LBP patients, high vs. low anxiety in OFC in normals, and all four regions in chronic LBP patients,
and the affective component of pain in the cingulate. It is expected that as the spatial and temporal resolution and the
number of substances increase, this technique will become more prevalent on its own or in combination with other
neuroimaging techniques with better spatial and temporal resolution.

The neuroimaging of the brain in patients with chronic pain is still in its infancy. The preliminary data support the
notion that persistent chronic pain states involve functional abnormalities in the cortical and subcortical areas
activated by noxious experimental stimuli in normal subjects.

Future Functional Neuroimaging Studies of Pain in Humans
Advances in functional neuroimaging promise unprecedented explorations of the neural mechanisms underlying
pain, including being able to link decades of research in animal models to clinical practice. While the field of
functional neuroimaging is coming of age, there are still many obstacles to overcome. For instance, many key brain
regions involved with pain, or they lie at the spinal cord level. These regions may involve small volumes difficult to
investigate with current functional neuroimaging technology because of what is being measured (e.g., fMRI
measures blood oxygenation and flow, EEG measures extracellular, and MEG measures intracellular current).
Furthermore, there are significant limitations in spatial resolution (e.g., PET, MRS) and in source localization (e.g.
EEG, MEG). Studies using multi-modal imaging may help overcome these obstacles. Studies of anatomical and
functional connectivity the neural circuitry involved in pain perception and the cognitive and affective factors
modulate pain may provide converging evidence. For example, diffusion tensor imaging (DTI) noninvasively
provides microscopic structural information of oriented tissue in vivo . White matter tract structure measured by
water proton, anisotropic diffusion is highly sensitive to subtle changes and is being used in studies of cognition,
mood, other various disorders, and most recently pain 21, 22.

While functional connectivity can be studied using fMRI, EEG, and MEG, issues related to signal detection and
statistical inference remain. In addition, imaging techniques such as MEG are a valuable tool to measure the
temporal relationship between brain regions. PET and MRS are also valuable in identifying the metabolism and
specific neurotransmitters involved in pain processing. The advent of real-time fMRI is another exciting tool that
may be useful in the studies of pain. We have studied chronic pain patients and healthy individuals by externally
applying pain to elucidate whether one can learn to modulate the perception of pain using feedback of fMRI BOLD
signals of brain regions related to pain in real time20. This technique not only provides causal evidence between
certain brain regions and the perception of pain but it also may have therapeutic potential. These directions will
further shape our understanding of pain perception, and they may be useful in assessing or developing new or
existing treatments.

Conclusion
Pain remains a serious health care problem, affecting millions of individuals, costing billions of dollars, and causing
an immeasurable amount of human suffering. In designing improved therapies, there is still much to learn about
peripheral nociceptors, nerves, spinal cord, and brainstem modulatory systems. However, it is the brain that presents
us with an incredible opportunity to finally understand the experience we call pain. Functional neuroimaging is
helping unlock the secrets of the sensory and emotional components of pain and its autonomic responses. These
techniques are helping us to understand that pain is not a static disease with the pathology localized to the periphery,
but instead a highly plastic condition affecting multiple central neural systems. Functional neuroimaging is
transforming our understanding of the neurobiology of pain, and it will be instrumental in helping us design more
rational treatments ultimately aimed at reducing pains impact on our patients.

329
Page 5
REFERENCES
1. Melzack, R. Phantom limbs and the concept of a neuromatrix. Trends Neurosci 1990;13(3):88-92.

2. Melzack, R. From the gate to the neuromatrix. Pain 1999;Suppl 6:S121-6.

3. Jones, A.K., B. Kulkarni, and S.W. Derbyshire. Pain mechanisms and their disorders. Br Med Bull
2003;65:83-93.

4. Petrovic, P., et al. Pain-related cerebral activation is altered by a distracting cognitive task. Pain 2000;85(1-
2):19-30.

5. Koyama, T., et al. The subjective experience of pain: where expectations become reality. Proc Natl Acad
Sci U S A 2005;102(36):12950-5.

6. Wager, T.D., et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science
2004;303(5661):1162-7.

7. Singer, T., et al. Empathy for pain involves the affective but not sensory components of pain. Science
2004;303(5661):1157-62.

8. Zaki, J., et al. Different circuits for different pain: Patterns of functional connectivity reveal distinct
networks for processing pain in self and others. . Social Neuroscience 2007;2(3 & 4):276-291.

9. Ochsner, K.N., et al. Neural correlates of individual differences in pain-related fear and anxiety. Pain
2006;120(1-2):69-77.

10. Williams, D.A. and R.H. Gracely. Biology and therapy of fibromyalgia. Functional magnetic resonance
imaging findings in fibromyalgia. Arthritis Res Ther 2006;8(6):224.

11. Cook, D.B., et al. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol
2004;31(2):364-78.

12. Teipel, S.J., et al. Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain
2005;128(Pt 11):2626-44.

13. Protopopescu, X., et al. Increased brainstem volume in panic disorder: a voxel-based morphometric study.
Neuroreport 2006;17(4):361-3.

14. McIntosh, A.M., et al. Genetic liability to schizophrenia or bipolar disorder and its relationship to brain
structure. Am J Med Genet B Neuropsychiatr Genet 2006;141(1):76-83.

15. Apkarian, A.V., et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter
density. J Neurosci 2004;24(46):10410-5.

16. May, A., et al. Correlation between structural and functional changes in brain in an idiopathic headache
syndrome. Nat Med 1999;5(7):836-8.

17. Kuchinad, A., et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the
brain? J Neurosci 2007;27(15):4004-7.

18. Apkarian, A.V., et al. Imaging the pain of low back pain: functional magnetic resonance imaging in
combination with monitoring subjective pain perception allows the study of clinical pain states. Neurosci Lett
2001;299(1-2):57-60.

19. Apkarian, A.V., et al. Prefrontal cortical hyperactivity in patients with sympathetically mediated chronic
pain. Neurosci Lett 2001;311(3):193-7.

329
Page 6

20. Younger, J.W., et al. Chronic myofascial temporomandibular pain is associated with neural abnormalities
in the trigeminal and limbic systems. Pain 2010;149(2):222-8.

21. Moseley, M., R. Bammer, and J. Illes. Diffusion-tensor imaging of cognitive performance. Brain Cogn
2002;50(3):396-413.

22. Geha, P.Y., et al. The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional
and autonomic regions. Neuron 2008;60(4):570-81.

Disclosure

409
Page 1
Botulinum Toxin Therapy for Pain Medicine and Headache
F. Micahel Ferrante, M.D. Santa Monica, California
There are many published reports utilizing botulinum serotypes A and B in a diverse group of pain disorders:
spasmodic torticollis, chronic migraine headache, neck and low back pain, neurogenic thoracic outlet syndrome,
regional muscle pain (myofascial) syndromes, chronic muscular pain (dystonia, spasticity and cerebral palsy), joint
pain (RA, osteoarthritis), and chronic pelvic pain. (1,2) Anesthesiology-based pain practitioners mistakenly view
the use of Botulinum toxins as solely the purview of the neurologist and physiatrist. Because of the burgeoning use
of Botulinum toxins for pain, it is incumbent upon the anesthesiology-based pain practitioner to become conversant
with the potential applications of Botulinum toxins for pain. This refresher course will review several of those
therapeutic domains.
Clinical Pharmacology of Botulinum Neurotoxin
Botulinum neurotoxin is a potent toxin produced by Clostridium botulinum. It relaxes muscles by blocking
acetylcholine release at the neuromuscular junction. It is currently approved in the United States for treating
cervical dystonia, strabismus, blepharospasm and hemifacial spasm, glabellar lines and primary axillary
hyperhidrosis, cosmesis, and treatment of chronic daily headache.
There are seven distinct serotypes of botulinum toxin (A, B, C1, D, E, F, G). Serotype A is the most potent. Two
formulations are currently available in the United States for clinical use: botulinum toxin type A (BoNT-A) and
type B (BoNT-B). Botulinum toxin is composed of a dichain polypeptide with a molecular weight of approximately
150,000 Daltons. The 100,000 Dalton heavy chain is linked by a disulfide bond to a 50,000 Dalton light chain.
The heavy chain allows internalization of the light chain within the presynaptic nerve terminus by endocytosis.
A number of SNARE proteins (Synaptobrevin, SNAP-25, and Syntaxin) allow synaptic vesicles containing
acetylcholine to bind to the presynaptic membrane and fuse, releasing neurotransmitter into the synaptic cleft. The light
chain of botulinum toxin serotype A binds to SNAP-25. The light chain of botulinum serotype B binds to
Synaptobrevin. The end result is the same: inability of the synaptic vesicles containing acetylcholine to bind to the
presynaptic membrane and to release neurotransmitter. Each neurotoxin serotype has an individual and unique
cleavage sight. Botulinum toxin serotype A and E cleave the C-terminus of SNAP-25. Serotype E removes three less
amino acid residues. This difference in cleavage of amino acids may have clinical significance with respect to the
duration of action. The clinical effect of serotype A can last approximately three months. The clinical effects of
serotype E fade within a matter of a few weeks. Botulinum toxin serotype A has been shown to inhibit the release
of a number of peripheral peptides via an identical mechanism involving SNAP-25. These nociceptive
neurotransmitters include glutamate, substance P, and CGRP. Thus, the potential mechanisms for botulinum toxin
efficacy include a chemodenervation effect from inhibition of release of acetylcholine producing a focal relaxation of
muscle but also a direct antinociceptive effect due to inhibition of peripheral and central sensitization. (3)
Piriformis Syndrome
Classical piriformis syndrome is characterized by sciatica-like radicular pain with a normal neurologic exam and
lumbar MRI. Abnormal findings include limitation of straight leg raising, sciatic notch tenderness and painful
palpation of muscle via external hip rotation, but preferably muscle palpation via vaginal or rectal exam. As pain in
the area of the hip and buttocks can be derived from many sources: referred pain from the low back (discogenic,
facet, sacroiliac joint), pelvic etiologies, hip arthridites, and myofascial etiologies, confirmation of the diagnosis via
diagnostic piriformis injection with local anesthetic is mandatory. If the diagnosis is confirmed, a trial of


409
Page 2
conservative therapy with physical therapy should be undertaken. If conservative therapy fails, injection of the
piriformis muscle with Botulinum toxin coupled with physical therapy can give long-term relief. (4)
Myofascial Pain Syndrome: Pathophysiology
Myofascial pain syndrome is directly and causally related to soft tissue injury or secondarily related to
biomechanical adaptation to injury. There have been several proposed mechanisms for the development of
myofascial pain. These include: (1) fatigue, local ischemia, and release of peptides after sustained muscle overload
or repetitive strain injury, (2) deconditioning, atrophic changes, dysfunctional biomechanical habitus, and functional
loss, (3) an abnormal neuromuscular junction possessing a lower activation threshold due to an energy deficit for
recovery of calcium, and (4) nociceptor sensitization, either peripheral or central. All mechanisms attempt to define
myofascial pain as either a primary muscle pathologic process (mechanisms 1 through 3) or merely a secondary
muscular manifestation of a pathologic process occurring elsewhere (mechanism 4). The first three potential
mechanisms may be interrelated. Either chronic sustained overuse of muscles (such as may occur with protracted
heavy lifting) or repeated minor trauma (which may occur from repetitive typing) can lead to local ischemia, release
of excitatory neurotransmitters and development of biomechanical postural deficits. At the same time or
subsequently, it is hypothesized that an abnormal neuromuscular junction may develop.
Biomechanical Abnormality
The evaluation and treatment of myofascial pain syndrome should not merely address trigger points and their
location but focus upon normalization of posture and biomechanics. (3) The patients spine from neck to
coccyx should be aligned in a neutral position. An anatomic plumb line extends from the tragus of the ear to the
coracoid process of the shoulder to the greater trochanter of the femur to the lateral malleolus of the knee. Any
deviation from this line can potentially generate a myofascial pain syndrome. When patients present with myofascial
pain syndrome of the shoulders and the neck, the first physical measurement of the musculoskeletal exam should be
measurement of the coracoid-to-tragus line. Many patients with myofascial pain syndrome, particularly in the head
and shoulders, have developed a forward head posture (forward head syndrome). There is cervical protraction and
capital extension. Cervical paraspinal muscles are shortened. The upper trapezius muscles and levator scapulae
muscles are elevated and shortened. There is scapular protraction and an eccentric lengthening of the scapular
stabilizer muscles: rhomboids, lower trapezius, infraspinatus, and supraspinatus muscles. The pectoral muscles are
shortened and painful. The weakening of the scapular stabilizer muscles with shortening of the pectoral muscles causes
internal rotation of the shoulder girdles. This syndrome is referred to as propulsion or forward head syndrome or
cervicobrachial syndrome. It is quite common in patients with myofascial pain, particularly of the shoulders and
the neck.
Injection of trigger points with Botulinum toxin using a trigger point injection paradigm with local anesthetic will
not result in therapeutic benefit. However, Botulinum toxin is most effective in patients with a postural abnormality
such as forward head syndrome. Injection technique employs a pattern injection technique (such as in migraine)
adapted for individual patient complaint of severity of muscle pain. (5, 6)

Neurogenic Thoracic Outlet Syndrome

Neurogenic thoracic outlet syndrome involves compression of the brachial plexus (usually the lower trunk).
Compression occurs as neural structures pass over, or are adjacent to, the first rib. The thoracic outlet is bounded by
the anterior and middle scalene muscles, the first rib and the tendon of the pectoralis minor muscle. The presence of
a cervical rib and /or a fibrous band, and/or increased tension in the scalenes can cause compression of nerves
(scalenus anticus syndrome). Thoracic outlet syndrome will present as a painful sensation in the shoulder and ulnar
nerve distribution of the hand (lower trunk). Injection on Botulinum toxin into the anterior and middle scalene
muscles can be used to successfully treat neurogenic thoracic outlet syndrome (7)

Headache

Botulinum toxin injection is indicated for the prophylaxis of chronic migraine headache in patients who have
migraine for > 15 days per month with headache lasting 4 hours a day or longer. A fixed-pattern injection is used.


409
Page 3
References
1. Botulinum Toxin in Painful Diseases, Jost, WH, ed., Karger, Basel, 2003
2. Botulinum Toxin Type A in Pain Management, Childers, MK, ed., Academic Information Systems,
Columbia, MO, 2002
3. Cui M, Khanijou S, Rubino J, Aoki KR: Subcutaneous administration of botulinum toxin A reduces
formalin-induced pain. Pain 2004; 107: 125-133
4. Lang AM: Botulinum toxin type B in piriformis syndrome. Am J Phys Med Rehabil. 2004
Mar;83(3):198-202.
5. Ferrante FM, Bearn L, Rothrock R, King L: Evidence against trigger point injection technique for the
treatment of cervicothoracic myofascial pain with botulinum toxin type A. Anesthesiology 2005: 103: 377-
83.
6. Benecke R, Heinze A, Reichel G, et al: Botulinum type A toxin complex for the relief of upper back
myofascial pain syndrome: how do fixed-location injections compare with trigger point-focused injections?
2011;12(11):1607-14.
7. Jordan SE, Ahn SS, Freischlag JA, Gelabert HA, Machleder HI. Selective botulinum chemodenervation of
the scalene muscles for treatment of neurogenic thoracic outlet syndrome. Ann Vasc Surg. 2000;14:365-9.
Disclosure
506
Page 1
Practical Approach to Head and Neck Pain
Samer Narouze, M.D., Ph.D Cuyahoga Falls, Ohio
Head pain stemming from the neck or neck pain radiating up to the head is usually referred to as
cervicogenic headache. Cervicogenic headache was initially defined as unilateral headache that is provoked by
neck movement or pressure over tender points in the neck with associated reduced range of movement of the
cervical spine. The headache occurs in non-clustering episodes and is usually non-throbbing in nature, originating
from the neck, and spreading over the occipital, temporal, and frontal regions.
1-3
These clinical criteria are not
enough to make a definite diagnosis of cervicogenic headache, as it is sometimes difficult to differentiate clinically
between cervicogenic headache, migraine, and tension-type headache.
4-6
Response to diagnostic block of the nerve
supply of these cervical structures or intraarticular injection of local anesthetic into the affected joint is now
considered the major criterion in the diagnosis of cervicogenic headache.
7
Also, cervicogenic headache can be
unilateral or bilateral.
7
These clinical findings prompted the development of new diagnostic criteria for the
diagnosis of cervicogenic headache by the International Headache Society (IHS) in 2004 (ICHD-2
nd
edition).
8

Currently, the third edition is underway.
Cervicogenic headache diagnostic criteria by the International Classification of Headache Disorders (ICHD,
2
nd
edition):
A. Pain, referred from a source in the neck and perceived in one or more regions of the head and/or face, fulfilling
criteria C and D
B. Clinical, laboratory, and/or imaging evidence of a disorder or lesion within the cervical spine or soft tissues of the
neck known to be, or generally accepted as, a valid cause of headache.
C. Evidence that the pain can be attributed to the neck disorder or lesion based on at least one of the following:
1. Demonstration of clinical signs that implicate a source of pain in the neck
2. Abolition of headache following diagnostic block of a cervical structure or its nerve supply using placebo or other
adequate controls. Abolition of headache means complete relief of headache, indicated by a score of zero on a visual
analogue scale
D. Pain resolves within 3 months after successful treatment of the causative disorder or lesion
Tumors, fractures, infections and rheumatoid arthritis of the upper cervical spine have not been validated formally as
causes of headache, but are nevertheless accepted as valid causes in individual cases.
It is worth mentioning that cervical spondylosis and osteochondritis are not accepted as valid causes fulfilling
criterion B and when myofascial tender spots are the cause, the headache should be coded under tension-type
headache.
Clinical signs acceptable for criterion C1 must have demonstrated reliability and validity. Clinical features such as
neck pain, focal neck tenderness, history of neck trauma, mechanical exacerbation of pain, unilaterality, coexisting
shoulder pain, reduced range of motion in the neck, nuchal onset, nausea, vomiting, photophobia etc are not unique
to cervicogenic headache. These may be features of cervicogenic headache, but they do not define the relationship
between the disorder and the source of the headache.
Etiology:
Cervicogenic headache is referred pain from cervical structures innervated by the upper three cervical
spinal nerves. Thus possible sources of cervicogenic headache are: atlanto-occipital joint, median and lateral atlanto-
axial joints, C2-3 intervertebral disc, C2-3 zygapophysial joint, upper posterior neck, and paravertebral muscles.
Other sources include the trapezius and the sternocleidomastoid muscles, spinal and posterior cranial fossa dura
matter, cervical spinal nerves, and roots and the vertebral artery.
9

506
Page 2
Neuroanatomy and Neurophysiology:
The spinal nucleus of the trigeminal nerve extends caudally to the outer lamina of the dorsal horn of the
upper three to four cervical spinal segments. This is known as the trigeminocervical nucleus, which receives
afferents from the trigeminal nerve as well as the upper three cervical spinal nerves. Convergence between these
afferents accounts for the cervical-trigeminal pain referral. Therefore, pain originating from cervical structures
supplied by the upper cervical spinal nerves could be perceived in areas innervated by the trigeminal nerves such as
the orbit and the frontotemporoparietal region (Figure 1).
Bartsch and Goadsby
10
showed that noxious stimulation of the greater occipital nerve induces increased central
excitability of supratentorial afferents and vice versa, stimulation of the dura mater increases trigeminocervical
neurons responsiveness to cervical input.
11

Figure 1: The trigemino-cervical complex
Differential Diagnosis of Cervicogenic Headache
Atlanto-occipital joint
Atlanto-axial (C1-2) joints
C2-3 zygapophysial joint
C2-3 intervertebral disc
Occipital, suboccipital, and upper cervical paravertebral muscles
Posterior cranial fossa lesions
Cervical spinal nerves lesions
Vertebral artery disorders
Common Sources of Cervicogenic Headache:
We will discuss here the clinical presentations of the common causes of cervicogenic headache and how to come up
with an accurate diagnosis, and a plan of care.
Atlanto-axial Joint
The lateral atlanto-axial joint, which is innervated by the C2 ventral ramus, is not an uncommon cause of
cervicogenic headache. It may account for 16% of patients with occipital headache.
12
In human volunteers,
distending the lateral atlanto-axial joint with a contrast agent produces occipital pain and injection of local anesthetic
into the joint relieves the headache.
12, 13
Clinical presentations suggestive of pain originating from the lateral atlanto-
axial joint include occipital or suboccipital pain, focal tenderness over the suboccipital area or over the transverse
process of C1, restricted painful rotation of C1 on C2, and pain provocation by passive rotation of C1. These clinical

506
Page 3
presentations merely indicate that the lateral atlanto-axial joint could be a possible source of occipital headache,
however they are not specific and therefore cannot be used alone to establish the diagnosis.
9

The pathology of lateral atlantoaxial joint pain is usually osteoarthritis or post-traumatic in nature.
14,15

However, the presence of osteoarthritic changes on imaging studies doesnt mean than the joint is necessary painful,
also the absence of abnormal findings doesnt preclude the joint from being painful. The only means of establishing
a likely diagnosis is a diagnostic block with intra-articular injection of local anesthetic.
12

There is no conservative treatment for lateral atlanto-axial joint pain. However intra-articular steroids are effective
in short-term relief of pain originating from the lateral atlanto-axial joint.
16,17
Long-lasting pain relief may require
arthrodesis of the lateral atlanto-axial joint.
18, 19

Atlanto-axial joint intra-articular injection has the potential for serious complications, so it is imperative
that the interventional pain physician is familiar with the anatomy of the joint in relation to the surrounding vascular
and neural structures (Fig 2). The vertebral artery lies lateral to the atlanto-axial joint as it courses through the C2
and C1 foramina. Then it curves medially to go through the foramen magnum crossing the medial posterior aspect of
the atlanto-occipital joint (Fig 2). The C2 dorsal root ganglion and nerve root with its surrounding dural sleeve
crosses the posterior aspect of the middle of the joint. Therefore, during atlanto-axial joint injection, the needle
should be directed toward the posterolateral aspect of the joint. This will avoid injury to the C2 nerve root medially
or the vertebral artery laterally (Fig 3-4).
12, 17
Meticulous attention should be paid to avoid intravascular injection as
the anatomy may be variable. Injection of a contrast agent should be performed under real-time fluoroscopy,
preferably with digital subtraction, prior to the injection of the local anesthetic, as negative aspiration is of low
sensitivity. Inadvertent puncture of the C2 dural sleeve with CSF leak or high spinal spread of the local anesthetic
may occur with atlanto-axial joint injection if the needle is directed a few millimeters medially. Spinal cord injury
and syringomyelia are potential serious complications if the needle is directed further medially.

Figure 2: Illustration showing the relationship of the atlantoaxial and atlantoccipital joints to the vertebral artery

506
Page 4

Figure 3: A. The lateral atlanto-axial joint, B. The tip of the needle and the contrast agent within the lateral
AA joint

Figure 4: Lateral view showing the tip of the needle and the contrast agent within the lateral AA joint

C2-3 zygapophysial joint and third occipital headache
The C2-3 zygapophyseal joint is innervated by the third occipital nerve, which is the superficial medial
branch of the dorsal ramus of C3.
20
Pain stemming from this joint (named third occipital headache) is seen in 27%
of patients presenting with cervicogenic headache after whiplash injury.
21
Tenderness over the C2-3 joint is the only
suggestive physical examination finding and a diagnostic third occipital nerve block is mandatory to confirm the
diagnosis. Earlier reports showed that radiofrequency neurotomy of the third occipital nerve were not effective.
22

With improved radiofrequency technique, complete relief was obtained in 88% of patients with third occipital
headache (Fig 5).
23

C2-3 zygapophyseal joint intra-articular steroid injection was effective in one study.
24
On the other hand; Barnsley
et al
25
reported the lack of efficacy of intra-articular steroids for chronic pain stemming from the cervical
zygapophyseal joints.

506
Page 5
Third occipital nerve neurolysis:

The third occipital nerve is the superficial medial branch of C3 dorsal ramus. It supplies the C2-3
zygapophysial joint while crossing the joint laterally. Also it supplies part of the semispinalis capitis muscle and its
cutaneous branch supplies a small area of skin below the occiput.
20
Third occipital radiofrequency neurolysis was
shown to be effective in the treatment of headache stemming from the C2-3 joint. There is usually incomplete
lesioning of the third occipital nerve because of its variable anatomy.
22
The use of the three needles technique to
accommodate all variations in the anatomy of the third occipital nerve from just lateral to the joint line to above or
below the joint, and creating consecutive lesions no more than one electrode width from adjacent lesion markedly
improves the results.
23
(Fig 5)

Figure 5: Lateral view showing three radiofrequency needles appropriately placed just lateral to the C2-3
joint, above and below the joint line

Anesthesia dolorosa has not been reported with neurolysis of the third occipital nerve. However numbness
in the cutaneous distribution of the nerve is very common, whereas dysesthesia and hypersensitivity typically at the
border of the area of numbness occur in up to 50% of cases. These are temporary complications that usually persist
for only a few days to weeks.
22, 23
Temporary ataxia has been reported in most patients as third occipital neurotomy
partially denervates the semispinalis capitis muscles with the resultant interference of the tonic neck reflexes. Most
patients can overcome this sensation by relying on visual cues.
22, 23

Occipital neuralgia
According to the 2
nd
edition of the International Classification of Headache Disorders (ICHD), occipital
neuralgia is coded separately under cranial neuralgias.
8
It is discussed because of its relevance to cervicogenic
headaches. The diagnostic criteria include the following:
A. Paroxysmal stabbing pain, with or without persistent aching between paroxysms, in the distribution(s) of the
greater, lesser and/or third occipital nerves
B. Tenderness over the affected nerve
C. Pain is eased temporarily by local anaesthetic block of the nerve

Occipital neuralgia was long thought to be the result of entrapment of the greater occipital nerve as it
emerges from the trapezius muscle. However, surgical nerve release gives only short-term relief in about 80% of
cases, while nerve excision provides short-term relief in about 70% of patients.
26, 27
Occipital neuralgia must be

506
Page 6
distinguished from occipital referral of pain from the atlantoaxial or upper zygapophyseal joints or from tender
trigger points in neck muscles or their insertions.
8

The greater occipital nerve is the terminal branch of the dorsal ramus of C2 with contribution from C3
while the lesser occipital nerve is a branch of the dorsal ramus of C3 with contributions from C2. Segmental nerve
blocks at C2 and C3 may be necessary to make the diagnosis in some cases.
28
Cryoneurolysis, radiofrequency
ablation, and more permanent neuroablative approaches as dorsal rhizotomy at C1-3 and partial posterior rhizotomy
at C1-3 showed variable responses.
29-32

Occipital neurostimulation

Percutaneous occipital nerve stimulation, unlike neuroablative techniques, offer the potential for a
minimally invasive, low risk, and reversible approach to managing occipital neuralgia, chronic migraine, cluster
headaches, and other types of intractable primary headaches.
33-35
PET scan studies showed increased regional
cerebral blood flow in areas involved in central neuromodulation in chronic migraine patients treated with occipital
nerve electrical stimulation.
36
A percutaneous trial of peripheral nerve stimulation is performed using subcutaneous
electrodes placed superficial to the cervical muscular fascia at the level of the C1 or the nuchal line. If effective, a
permanent implant may be carried out using the same electrode lead type or paddle-type surgical lead and attached
to a pulse generator implanted in the infraclavicular area, abdomen, flank, or upper buttock (Fig 6,7).

The ONSTIM (occipital nerve stimulation for the treatment of intractable migraine) trial, examined the safety and
efficacy of ONS.
37
It is a multi-center prospective randomized single-blind controlled feasibility study. Patients who
responded favorably to occipital nerve block (ONB) were randomized (2:1:1) into 3 groups: adjustable stimulation
(AS), preset stimulation (PS), or medical management (MM). Those who did not respond to ONB formed an
ancillary group (AG). One hundred and ten patients were enrolled from 9 centers. Sixty sex subjects completed diary
data during 3-month follow-up. At 3 months, percent reduction in headache days/month was 27.0% (AS), 8.8% (PS)
(p = 0.132), 4.4% (MM) (p = 0.058), 39.9% (AG) (p = 0.566). Responder rate was 39% (AS), 6% (PS) (p =0.032),
0% (MM) (p = 0.003), and 40% (AG) (p = 1.000).

More recently, another prospective, multi-center, double-blind, controlled study of ONS in patients with CM.
38
One
hundred and fifty-seven patients from 15 centers were enrolled and randomized (2:1) to either a stimulation trial
followed by device implantation and active stimulation for 12 weeks (n = 105) or a stimulation trial followed by
device implantation but sham stimulation for 12 weeks (n = 52). After 12 weeks, subjects were un-blinded but
patients were followed for one year. There was a significant difference in the percentage of patients that achieved a
30% reduction in daily visual analog scale scores (p = 0.01). There were significant group differences for all
assessments at 12 weeks (p< 0.01).
The most frequent complication of the ONS is lead migration. Various anchoring techniques were described to
improve lead stability, however the problem persists.
35

In one review, lead migration was found to be 33% and 60% 6 months and one year post-implant respectively.
39

The ONSTIM study reported lead migration in 24% of subjects.
37
The use of self-anchoring leads (e.g. tined leads)
looks promising. 37 In a series of 12 patients, only one patient had a few mm lead migration with little change in the
stimulation pattern, there was no loss of efficacy.
40
None of 12 patients required a surgical revision for lead
migration during a mean follow up period of 13 months (Fig 9). Unlike spinal cord stimulation, wound dehiscence
and infection carry a lower morbidity risk although this usually requires total system explant.

506
Page 7

Figure 6: AP view showing bilateral occipital surgical leads

Figure 7: AP view showing right occipital percutaneous lead

Figure 8: AP view showing bilateral occipital self anchoring leads.

506
Page 8

C2 Neuralgia

C2 neuralgia is a distinctive type of occipital neuralgia and it is caused by lesions affecting the C2 nerve
root or dorsal ganglion such as neuroma, meningioma, or anomalous vessels.
41,42
The C2 root lies posterior to the
lateral atlanto-axial joint, thus disorders or inflammation of this joint may lead to irritation or entrapment of the
nerve root.
43
C2 neuralgia manifests as intermittent lancinating occipital pain that is associated with lacrimation,
ciliary injection, and rhinorrhea. Abolition of pain by selective C2 nerve root block is essential to make the
diagnosis. C2 neuralgia that responds poorly to pharmacotherapy and thermocoagulation, decompression, or C2
ganglionectomy may be indicated.
9

Cervical Myofascial Pain
Trigger points in the posterior neck muscles specially the trapezius, sternocleidomastoid, and the splenius
capitis have been proposed as a cause of headache.
44,45
According to the 2
nd
edition of the International
Classification of Headache Disorders (ICHD), Headache causally associated with cervical myofascial tender spots is
coded as episodic or chronic tension-type headache associated with pericranial tenderness.
8

Moreover these tender points usually overlie the zygapophyseal joints, so it is difficult to be distinguished from
underlying painful joints.
9
Needling therapies in the management of myofascial pain showed no efficacy beyond
that of placebo.
46
The use of botulinum toxin is controversial. It might be effective in the management of migraine
and chronic daily headaches, however its efficacy in myofascial pain and cervicogenic headaches still debatable.
47-
49

Cervical discogenic pain

C2-C3 provocative discography, but not at the lower levels, can reproduce cervicogenic headache.
50
Radiofrequency lesioning was shown to be effective in obtaining some pain relief for a few months in one study.
51

However, cervical disc interventions are not commonly performed because of the potential for serious
complications.

In summary, cervicogenic headache is one of the most debatable and challenging area in headache
medicine. Patients usually benefit the most from a multidisciplinary approach incorporating physical therapy,
pharmacotherapy, psychotherapy (biofeedback and relaxation therapy), alternative medicine (acupuncture), and the
judicious utilization of interventional pain management modalities.

References

1- Sjaastad O, Saunte C, Hovdahl H. et al. Cervicogenic headache. A hypothesis. Cephalalgia 1983; 3: 249-256.
2- Fredriksen TA, Hovdal H, Sjaastad O. Cervicogenic headache: clinical manifestation. Cephalalgia 1987; 7: 147-
160.
3- Sjaastad O. Fredriksen TA, Pfaffenrath V. Cervicogenic headache: diagnostic criteria. Headache 1990; 30: 725-
726.
4- Leone M, DAmico D, Moschiano F, et al. Possible identification of cervicogenic headache among patients
with migraine: an analysis of 374 headaches. Headache 1995; 35: 461-464.
5- Leone M, DAmico D, Grazzi L, et al. Cervicogenic headache: a critical review of the current diagnostic
criteria. Pain 1998; 78: 1-5.
6- Suijlekom JA, de Vet HCW, van den Berg SGM, Weber WEJ. Interobserver reliability of diagnostic criteria for
cervicogenic headache. Cephalgia 1999; 19: 817-823.
7- Sjaastad O. Fredriksen TA, Pfaffenrath V. Cervicogenic headache: diagnostic criteria. Headache 1998; 38: 442-
445
8- Headache Classification Subcommittee of the International Headache Society. The international classification
of headache disorders (2
nd
edn.). Cephalalgia 2004; 24 (Suppl 1): 1-160.
9- Bogduk N. The neck and headache. Neurologic clinics 2004;22(1): 151-171
10- Bartsch T, Goadsby PJ. Stimulation of the greater occipital nerve induces increased central excitability of dural
afferent input. Brain 2002; 125:1496-1509

506
Page 9
11- Bartsch T, Goadsby PJ. Increased responses in trigeminocervical nociceptive neurons to cervical input after
stimulation of the dura mater. Brain 2003; 126:1801-1813
12- Aprill C, Axinn MJ, Bogduk N. Occipital headaches stemming from the lateral atlanto-axial (C1-2) joint.
Cephalalgia 2002; 22(1):15-22.
13- Busch E, Wilson PR. Atlanto-occipital and atlanto-axial injections in the treatment of headache and neck pain.
Reg Anesth 1989; 14(Suppl 2):45.
14- Ehni G, Benner B. occipital neuralgia and the C1-2 arthrosis syndrome. J Neurosurg 1984; 61: 961-965.
15- Schonstorm N, Twomey L, taylor J. The lateral atlanto-axial joints and their synovial folds: an in vitro study of
soft tissue injury and fractures. J Trauma 1993; 35: 886-892.
16- Narouze SN, Casanova J. The efficacy of lateral atlanto-axial intra-articular steroid injection in the management
of cervicogenic headache. Anesthesiology 2004; 101: A1005.
17- Narouze SN, Casanova J, Mekhail N. The longitudinal effectiveness of lateral atlanto-axial intra-articular
steroid injection in the management of cervicogenic headache. Pain Med 2007;8:184-188
18- Joseph B, Kumar B. Gallies fusion for atlantoaxial arthrosis with occipital neuralgia. Spine 1994; 19: 454-455.
19- Ghanayem AJ, Leventhal M, Bohlman HH. Osteoarthrosis of the atlantoaxial joints- long term follow up after
treatment with arthrodesis. J Bone Joint Surg (Am) 1996; 78: 1300-1307.
20- Bogduk N. The clinical anatomy of cervical dorsal rami. Spine 1982; 7: 319-30.
21- Lord S, Barnsley L, Wallis B, Bogduk N. Third occipital headache: a prevalence study. J Neurol Neurosurg
Psychiatr 1994; 57: 1187-90.
22- Lord SM, Barnsley L, Bogduk N. Percutaneous radiofrequency neurotomy in the treatment of cervical
zygapophyseal joint pain: a caution. Neurosurgery 1995; 36: 732-39.
23- Govind J, King W, Baily B. Bogduk N. Radiofrequency neurotomy for the treatment of third occipital
headache. J Neurol Neurosurg Psychiatr 2003; 74: 88-93.
24- Slipman CW, Lipetz JS, Plastara CT, et al. Therapeutic zygapophyseal joint injections for headache emanating
from the C2-3 joint. Am J Phys Med Rehabil 2001; 80: 182-88.
25- Barnsley L, Lord SM, Wallis BJ et al. Lack of effect of intraarticular corticosteroids for chronic pain in the
cervical zygapophyseal joints. N Engl J Med 1994; 330:1047-1050.
26- Bovim G, Fredriksen TA, Stolt-Nielsen A, Sjaastad O. Neurolysis of the greater occipital nerve in cervicogenic
headache. A follow up study. Headache 1992; 32: 175-9.
27- Anthony M. Headache and the greater occipital nerve. Clin Neurol Neurosurg 1992; 94: 297-301.
28- van Suijlekom JA, Weber WE, van KM. Cervicogenic headache: techniques of diagnostic nerve blocks. Clin
Exp Rheumatol 2000; 18:S39-S44.
29- Silverman SB. Cervicogenic headache: interventional, anesthetic, and ablative treatment. Curr Pain Headache
Rep 2002; 6: 308-314.
30- Sjaastad O, Stolt-Nielsen A, Blume H et al. Cervicogenic headache. Long-term results of radiofrequency
treatment of the planum nuchale. Funct Neurol 1995; 10: 265-271.
31- Horowitz MB, Yonas H. Occipital neuralgia treated by intradural dorsal nerve root sectioning. Cephalalgia
1993; 13: 354-60.
32- Dubuisson D. Treatment of occipital neuralgia by partial posterior rhizotomy at C1-3. J Neurosurg 1995; 82:
591-6.
33- Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia.
Neuromodulation 1999; 2: 217-221.
34- Kapural L, Mekhail N, Hayek SM, et al. Occipital nerve electrical stimulation via the midline approach and
subcutaneous surgical leads for treatment of severe occipital neuralgia: a pilot study. Anesth Analg 2005;
101:171-174.
35- Weiner RL. Occipital neurostimulation (ONS) for treatment of intractable headache disorders. Pain Med
2006;7:S137-S139
36- Matharu MS, Bartsch T, Ward N, et al. Central neuromodulation in chronic migraine patients with suboccipital
stimulation: A PET study. Brain 2004; 127:120-130
37- Saper JR, Dodick DW, Silberstein SD, McCarville S, Sun M, Goadsby PJ. Occipital nerve stimulation for the
treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia. 2011;31(3):271-
285.
38- Silberstein SD, Dodick DW, Saper J, et al. Safety and efficacy of peripheral nerve stimulation of the occipital
nerves for the management of chronic migraine: results from a randomized, multicenter, double blinded,
controlled study. Cephalalgia. 2012;32:1165-1179.

506
Page 10
39- Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic
headache- Long term safety and efficacy: Cephalalgia 2007;27:153-157.
40- Narouze SN, Saad R, Nagem H, Kapural L. Occipital Nerve Stimulation with self-anchoring leads for the
management of refractory chronic migraine headache (abstract). Pain Med 2009;10:221
41- Kuritzky A. Cluster headache-like pain caused by an upper cervical meningioma. Cephalalgia 1984; 4: 185-6.
42- Sharma RR, Parekh HC, Prabhu S, et al. Compression of the C2 root by a rare anomalous ectatic vertebral
artery. J Neurosurg 1993; 78: 669-72.
43- Poletti CE, Sweet WH. Entrapment of the C2 root and ganglion by the atlantoepistrophic ligament: clinical
syndrome and surgical anatomy. Neurosurgery 1990; 27: 288-91.
44- Travell J, Rinzler SH. The myofascial genesis of pain. Postgrad Med 1952; 11: 425-34.
45- Freund B, Schwartz M. Post-traumatic myofascial pain of the head and neck. Curr Pain Headache Rep 2002; 6:
361-369.
46- Cummings TM, White AR. Needling therapy in the management of myofascial trigger point pain: a systemic
review. Arch Phys Med Rehabil 2001; 82: 986-92.
47- Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain
1994; 59: 65-69.
48- Freund BJ, Schwartz M. Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot
study. J Rheumatol. 2000; 27: 481-484.
49- Wheeler AH, Goolkasian P, Gretz SS. A randomized, double-blind, prospective pilot study of botulinum toxin
injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine 1998; 23:
1662-1666.
50- Grubb SA, Kelly CK. Cervical discography: clinical implications from 12 years of experience. Spine 2000; 25:
1382-1389.
51- Blume HG. Cervicogenic headaches: radiofrequency neurotomy and the cervical disc and fusion. Clin Exp
Rheumatol. 2000; 18: S53-S58.
Disclosure
Philips, Self, Honoraria
"##
Page 1
Radiofrequency Ablation for the Treatment of Spine Pain:
Understanding the Basic Principles and Clinical Application
David A. Provenzano, M.D. Pittsburgh, Pennsylvania
Introduction
Radiofrequency (RF) treatment is a frequently employed interventional technique used for the treatment of specific
pain conditions originating from the axial spine including lumbar and cervical facet syndrome and sacroiliac joint
dysfunction. Facet joint mediated pain and sacroiliac joint dysfunction are common conditions associated with
significant treatment costs. Facet joint (zygapophysial) mediated pain has been identified as a source of chronic axial
spine pain. The prevalence of facetogenic pain in the cervical spine ranges from 45% to 55%.
#
The lumbar facet
joints are the etiology of low back pain in 15% to 45% of cases depending on the age of the studied population.
$%&

The prevalence of low back pain secondary to sacroiliac joint dysfunction ranges between 10% and 25%.
'

In order to effectively utilize this technology, it is important for practitioners to understand the electrophysiological
principles and technical aspects of RF lesions to successfully treat the targeted structure and limit the risk of
complications. In addition, it is important for practitioners to have an in-depth understanding of relevant anatomy
and appropriate patient selection, both of which are required for improving procedural outcomes. Herein and in the
refresher course lecture, we will provide an overview of the utilization of radiofrequency for the treatment of spine
conditions. Particular areas that will be discussed will include the current level of efficacy and safety data, patient
selection and electrophysiological principles of thermal, pulsed, and cooled probe radiofrequency. Furthermore, the
technical limitations of radiofrequency and methods to optimize and modulate lesion size will also be described.
Electrophysiological Principles and Technical Aspects of Radiofrequency Lesioning
General Principles
The electrophysiologic principles of RF define the size of a lesion. The ability to lesion specific tissues, while
limiting destruction to non-targeted tissues in selected environments, is dependent on factors that influence energy
delivery and local physiologic tissue characteristics.
Coagulation necrosis can be described by the Bioheat equation.
"

Coagulation necrosis = (heat generated x local tissue interactions) heat lost
In a simplified thermal RF system, 3 primary factors determine heat generation and the size of the lesion: 1) distance
from the active tip, 2) RF current density, and 3) duration of application of the RF current (Table 1).
(

Table 1. Factors Involved in Radiofrequency Lesion Generation.
Radiofrequency Element Electrophysiologic Principle
Distance from active tip Heat generation = 1/radius from active tip
4
Tissue heating decreases rapidly with increasing
distance from the active tip.
RF current intensity Heat generation = current density
2
Heat generated from RF is directly proportional to the
current density
Current intensity has a strong influence on tissue
heating.
Duration of RF application The duration of heating influences lesion size.
Heat losses that influence RF lesioning include: 1) conduction (heat diffusion), 2) convection (circulation), and 3)
low-resistance shunting.

")(
Page 2
Thermal Radiofrequency Monopolar and Bipolar
Thermal RF involves the use of low-energy, high-frequency alternating current (300,000 to 500,000 Hz). Thermal
RF results in irreversible cellular energy from focal high temperature tissue heating.
*
For a monopolar system, the
equipment includes an RF electrode and a grounding pad. The RF electrode is placed in an RF cannula, which has
an electrically insulated shaft and an uninsulated active tip. The high-frequency alternating current flows from the
uninsulated active tip into the tissue. The ions in the tissue serve as the carriers of the electrical current. The
alternating current produces frictional heating in the tissue surrounding the electrode.
(
In RF, heat flows from the
tissue to the cannula. The primary source of heat for RF is the tissue surrounding the electrode. The grounding pad
serves as a return path for the RF current. Lesioning does not occur at the grounding pad because of its large surface
area. Temperature-controlled RF lesion systems are primarily employed in interventional pain medicine.
For conventional RF, the time of lesioning, tip size, and set temperature all influence the final lesion size. With
Monopolar RF lesions are in the shape of a prolate spheroid with coagulation occurring primarily in the radial
direction perpendicular to the long axis of the electrode. Minimal lesioning occurs distal to the tip. Therefore, for
monopolar RF the cannula should be placed with the shaft of the cannula parallel to the target nerve.
+%,
When
performing monopolar thermal RF it is important to understand the maximum tolerable margin of error for
placement that is allowed with a specific cannula and radiofrequency settings that will still allow for a lesion to
incorporate the full diameter of the targeted nerve (Fig 1). The current interventional pain medicine monopolar
lesion size is small, and the radius of the lesion is approximately 1 to 2 times the width of the electrode.
+%#)

Figure 1. Schematic diagram demonstrating monopolar radiofrequency lesioning of a nerve (yellow structure) with
an 18 gauge cannula. The cannulas active tip is white. The red circle highlights the zone of lesioning. d: diameter of
the nerve, e: maximum tolerable margin of error, r: effective radius of lesioning, L: length of nerve lesioned. For an
18 gauge cannula with a 10 mm curved active tip the mean effective radius is 1.6 mm 0.5 mm.
11,12
If the
theoretical nerve lesioned had a diameter of 1 mm then maximal tolerable margin of error would be 0.6 mm. The
mean diameter of the cervical medial branches from C3 to C7 is less than 1 mm.
#)
Figure adapted.
#)

In bipolar RF, a passive electrode replaces the grounding pad. Bipolar RF is employed when a larger lesion is
required and it has been used for such conditions such as sacroiliac joint dysfunction, lumbosacral junction
pseudoarticulation, and Raynauds phenomenon in the upper and lower extremities.
#&-#+
When performing bipolar
RF, it is important to understand specific configuration parameters that will influence lesion development (Table
2).
#*
One parameter that is of crucial importance is the set interelectrode distance (IED). The goal should be to
choose an IED that will allow for the ablation of the desired area and limit destruction to non-targeted structures. In
addition, the IED should be set to limit hourglass lesioning which may result in missing the targeted structure. The
maximum IED will depend on multiple configuration parameters including the size of the active tip, lesioning time,
and composition of the pre-injected fluid.
#&%#*%#,

")(
Page 3
Table 2. Bipolar Configuration Parameters Involved in Lesion Development
Technical Parameter
Active tip dimensions size and length
Interelectrode distance
Lesion time
Tip configurations offset, angle, skew
Tip temperature

Recently, cooled probe radiofrequency ablation (RFA) has been used for the treatment of sacroiliac joint
dysfunction.
$)-$$
Compared to traditional thermal RFA, cooled RFA results in significant lesion development distal
to the tip of the radiofrequency cannula. Lesioning distal to the tip is advantageous in certain anatomical areas, such
as the sacroiliac joint, where perpendicular placement of the RF cannula is often required. In cooled RFA, an
internally cooled electrode is utilized which allows for continuous internal cooling of the tip with a perfusate.
$&
The
internal perfusate serves as a heat sink and removes heat closest to the electrode. Therefore, the heating of the tissue
nearest to the electrode is reduced and greater current deposition is allowed with results in larger lesions.
Methods to Modulate the Local Tissue Environment to Increase Lesion Size
In the quest for the enlargement of the coagulation zone, methods to modulate the local tissue environment
surrounding the RF cannula to allow for greater energy deposition have been investigated.
##%#$%#,%$&%$'
The nerves
innervating the facet joints have a diameter of less than 2 mm and are associated with anatomical variability.
#)%$"%$(

Therefore, the development of controlled and defined larger lesions may assist with lesioning structures that are
small and have variable courses with the goal of limiting technical failures The chemical composition of the pre-
injected fluid has been shown to alter lesion size and development in both monopolar and bipolar RFA setups.
Increasing the sodium chloride (NaCl) concentration of the pre-injected fluid has been shown to significantly
increase power output and lesion size.
##%$'
Studies to date have been in ex vivo models and further research is
warranted.
Pulsed Radiofrequency
Pulsed RF uses brief bursts of RF energy separated by longer time periods where RF energy is not applied. The
pauses between bursts allow for heat to dissipate within the surrounding tissue. Since the tip temperature does not
rise above 42C, neurodestructive temperatures are not achieved.
$*-&#
Although the exact mechanism of pulsed RF is
unknown, changes in gene expression have been demonstrated in the neurons within the dorsal horn of the spinal
cord.
$*
The theoretical appeal of pulsed RF is the ability to modulate pain without causing extensive tissue injury as
seen with thermal RFA.
&$
For the treatment of lumbar facet pain, thermal RFA has been shown to be superior to
pulsed RF.
&&%&'
Further research is warranted on the mechanism of action of pulsed RF and its clinical efficacy
before its widespread adoption for the treatment of axial spine pain.
Lumbar Medial Branch Radiofrequency for Facet Joint Mediated Pain
The therapeutic efficacy of lumbar medial branch RF has been evaluated in observational and randomized controlled
trials (RCTs). Of the six RCTs, three had technical flaws in both patient selection and surgical technique which
hinder the interpretation of the results.
&"-&*
When performing RF, it is important to understand the anatomy of the
lumbar medial branch and the technical specifications of a RF lesion.
,%&+
The medial branches targeted are small,
often less than 2 mm in diameter.
&,
Therefore, incorrect needle technique will result in the inability to lesion the
targeted nerve. Electrodes should be placed parallel to the target nerve.
+
Additionally, the influence of the
composition of the preinjection fluid should be considered when performing monopolar RF ablation.
##%#$

Three RCTs studies had definitively positive results for RF.
&&%')%'#
The Nath et al.
'#
study demonstrated that the
active treatment groups had statistically significant improvement in back/leg pain and back/hip movement at six
months. Improvement was also seen in quality-of-life scores and in the reduction in the use of analgesics. No
significant complications were reported. Two observational studies also demonstrated that RF is effective.
'$%'&

Dreyfuss et al.
'&
demonstrated in a study of 15 patients with a diagnosis of lumbar facet syndrome made with

")(
Page 4
diagnostic controlled medial branch blocks, 90% pain relief in 60% of treated individuals at 12 months. At least
60% pain reduction was seen in 87% of the patients at 12 months. Gofeld et al.
'$
in a large clinical audit of 209
patients (179 completed the study, 35 patients lost to follow-up), showed 68.4% of patients had good (> 50% pain
relief) to excellent (>80% pain relief) results lasting from 6-24 months.
Cervical Medial Branch Radiofrequency for Facet Joint Mediated Pain
A systematic review evaluating a randomized controlled trial and four observational studies provide
strong evidence that cervical medial branch radiofrequency is a successful treatment for chronic neck
pain.
''
Lord et al.
'"
, in a randomized double-blind trial, compared RF to sham denervation in patients with
cervical facet pain confirmed with double-blind placebo-controlled local anesthetic blocks. The RF
denervation was found to be superior to sham and the median time that elapsed before pain returned to at
least 50% of the preoperative level in the RF group was 263 days.
45

Sacroiliac Joint Radiofrequency
Several RF techniques, which target the posterior innervation of the joint, have been developed to treat SI joint pain.
One of the associated challenges with SI joint RF includes an incomplete understanding of the innervation of the
joint. Techniques developed include bipolar intra-articular RF, bipolar lateral branch RF, cooled RF ablation of the
lateral branches, and sensory stimulation-guided SI joint RF.
#'%#*%$)%$#%'(%'*
Ferrante et al.
#'
utilized an intra-articular
bipolar leapfrog technique. Only 36.4% of individuals who underwent this procedure obtained at least a 50%
decrease in VAS for a minimum of 6 months.
#'
In an attempt to improve results, a sensory stimulation guided
approach was developed which targeted the L5 dorsal ramus sensory branch and the SI joint lateral branches.
46
The
data from retrospective review indicated that 64% of individuals obtained a successful outcome, defined as greater
than 60% consistent subjective relief and greater than 50% consistent decrease in the pain score for a minimum of 6
months.
46
Bipolar RF strip lesions have also been used to target the lateral branches. Burnham and Yasui
47
treated
the L5 dorsal ramus and then performed 3 bipolar strip lesions at S1-S3 in 9 patients. The procedure was associated
with reductions in back/leg pain frequency and severity, analgesic usage, and high satisfaction scores. In a
randomized placebo-controlled study examining lateral branch RF denervation with cooled RF probes, 57% of
patients obtained pain relief of 50% or greater at 6 months.
$#
Cooled probe RF creates wide diameter lesions that
may increase the ability to target areas of nociceptive input. Similar to Burnham and Yasui
47
, this study also
demonstrated functional improvements. In individuals with successful pain relief, the median duration of pain relief
was 7.9 4.7 months. Patel et al.
$)
also studied the efficacy of lateral branch cooled probe RF in the randomized
placebo-controlled study. Significant improvements were demonstrated with cooled probe RF in comparison to
placebo for pain, disability, physical function and quality of life at 3 month follow-up.
Complications
Although radiofrequency treatment can be associated with both minor and major complications, there is limited data
documenting the occurrence of these complications.
48,49
Following radiofrequency, a temporary exacerbation of pain
secondary to an inflammatory response will often occur, lasting several days to two weeks. Lord et al.
#)
audited 83
cervical medial branch RF procedures and recorded procedural side effects and complications. Following cervical
medial branch RF, increasing temporary postoperative pain occurred in 97% of cases with a median duration of 10
days. The three-day administration of diclofenac sodium has been shown to improve analgesia and patient
satisfaction scores after conventional monopolar lumbar facet RF denervation.
50
In addition, the injection of
corticosteroids through the RF cannulae at the conclusion of the procedure has been shown to reduce post procedure
lumbar paraspinal tenderness.
51
Some patients may also experience transient dysesthesias of the skin over the
operative area, arising from partial denervation of the lateral branch of the posterior primary ramus. These transient
dysesthesias occur more frequently with cervical medial branch RF.

Other complications that may occur following cervical medial branch and third occipital nerve (TON) RF include
ataxia and spatial disorientation.
#)%"$
Ataxia and spatial disorientation is more common with cervical medial branch
RF of the upper cervical levels, especially the TON, and is usually mild and self-limiting.

One of the most feared complications is damage to surrounding non-targeted spinal nerves. Methods to prevent this
complication include precise anatomic placement of the RF cannula through fluoroscopic guidance, physiological

")(
Page 5
testing, and a detailed understanding of lesion dimensions. This is
especially relevant when methods are used to enhance lesion size
including cooled probe RF and fluid preinjection. Retrograde lesioning
has been shown to occur with fluid preinjection prior to RF
treatment.
##%#$%#,%$#
In addition, the risk of toxicity to non-targeted tissues,
including central and peripheral nervous system structures, should also be
considered prior to injecting specific fluids (i.e. high NaCl
concentrations).
##
Injected volumes of 0.5 mL for medial branch blocks
have been shown to spread to adjacent non-targeted tissues including the
neuroforamen.
"&%"'
Figure 2 is a corresponding lateral radiograph
demonstrating the placement of the radiofrequency cannulae for the left
L3 and L4 medial branches and L5 dorsal primary ramus. The active tips
are positioned safely away from the neuroforamen to avoid thermal
lesioning of the spinal nerves.

Conclusion
Radiofrequency is an effective therapeutic treatment for spinal pain originating from cervical and lumbar facet joints
and sacroiliac joints. Additional work is needed on improving patient selection, extending the duration of relief, and
limiting technical failures. Methods to enlarge lesion size in a controlled manner to assist with the inclusion of the
targeted nerve in the coagulation zone should be further studied.
Disclosures
Dr. Provenzano has served as a consultant for Kimberly-Clark.

All figures and videos were reprinted with permission from Pain Diagnostics and Interventional Care.
References
1. van Eerd M, Patijn J, Lataster A, Rosenquist RW, van Kleef M, Mekhail N, Van Zundert J. 5. Cervical facet pain.
Pain Pract 2010;10(2):113-23.
2. Schwarzer AC, Wang SC, Bogduk N, McNaught PJ, Laurent R. Prevalence and clinical features of lumbar
zygapophysial joint pain: a study in an Australian population with chronic low back pain. Ann Rheum Dis
1995;54(2):100-6.
3. Schwarzer AC, Aprill CN, Derby R, Fortin J, Kine G, Bogduk N. Clinical features of patients with pain stemming
from the lumbar zygapophysial joints. Is the lumbar facet syndrome a clinical entity? Spine 1994;19(10):1132-7.
4. Hansen H, Manchikanti L, Simopoulos TT, Christo PJ, Gupta S, Smith HS, Hameed H, Cohen SP. A systematic
evaluation of the therapeutic effectiveness of sacroiliac joint interventions. Pain Physician 2012;15(3):E247-78.
5. Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation therapy for focal malignancy: a unified approach to
underlying principles, techniques, and diagnostic imaging guidance. AJR Am J Roentgenol 2000;174(2):323-31.
6. Organ LW. Electrophysiologic principles of radiofrequency lesion making. Appl Neurophysiol 1976;39(2):69-76.
7. Haemmerich D. Biophysics of radiofrequency ablation. Crit Rev Biomed Eng 2010;38(1):53-63.
8. Bogduk N. Practice Guidelines for Spinal Diagnostic and Treatment Procedures. First Edition ed. San Francisco,
California: International Spine Intervention Society; 2004.
Figure 2

")(
Page 6
9. Lau P, Mercer S, Govind J, Bogduk N. The surgical anatomy of lumbar medial branch neurotomy (facet
denervation). Pain Med 2004;5(3):289-98.
10. Lord SM, McDonald GJ, Bogduk N. Percutaneous radiofrequency neurotomy of the cervical medial branches: a
validated treatment for cervical zygapophysial joint pain. Neurosurgery Quarterly 1998;8(4):288-304.
11. Provenzano DA, Liebert MA, Somers DL. Increasing the NaCl concentration of the preinjected solution
enhances monopolar radiofrequency lesion size. Reg Anesth Pain Med 2013;38(2):112-23.
12. Provenzano DA, Lassila HC, Somers D. The effect of fluid injection on lesion size during radiofrequency
treatment. Reg Anesth Pain Med 2010;35(4):338-42.
13. Pino CA, Hoeft MA, Hofsess C, Rathmell JP. Morphologic analysis of bipolar radiofrequency lesions:
implications for treatment of the sacroiliac joint. Reg Anesth Pain Med 2005;30(4):335-8.
14. Ferrante FM, King LF, Roche EA, Kim PS, Aranda M, Delaney LR, Mardini IA, Mannes AJ. Radiofrequency
sacroiliac joint denervation for sacroiliac syndrome. Reg Anesth Pain Med 2001;26(2):137-42.
15. Burnham R. Radiofrequency sensory ablation as a treatment for symptomatic unilateral lumbosacral junction
pseudarticulation (Bertolotti's syndrome): a case report. Pain Med 2010;11(6):853-5.
16. Kang SS, Shin KM, Jung SM, Park JH, Hong SJ. Sequential bipolar radiofrequency lumbar sympathectomy in
Raynaud's disease: a case report. Korean J Anesthesiol 2010;59(4):286-9.
17. Cosman ER,Jr, Gonzalez CD. Bipolar radiofrequency lesion geometry: implications for palisade treatment of
sacroiliac joint pain. Pain Pract 2011;11(1):3-22.
18. Kang SS, Park JC, Hong SJ, Yoon YJ, Shin KM. Percutaneous bipolar radiofrequency T3 sympathicotomy in
Raynaud's disease: a case report. Korean J Anesthesiol 2012;63(5):461-4.
19. Provenzano DA, Lutton EM, Somers DL. The effects of fluid injection on lesion size during bipolar
radiofrequency treatment. Reg Anesth Pain Med 2012;37(3):267-76.
20. Patel N, Gross A, Brown L, Gekht G. A randomized, placebo-controlled study to assess the efficacy of lateral
branch neurotomy for chronic sacroiliac joint pain. Pain Med 2012;13(3):383-98.
21. Cohen SP, Hurley RW, Buckenmaier CC,3rd, Kurihara C, Morlando B, Dragovich A. Randomized placebo-
controlled study evaluating lateral branch radiofrequency denervation for sacroiliac joint pain. Anesthesiology
2008;109(2):279-88.
22. Stelzer W, Aiglesberger M, Stelzer D, Stelzer V. Use of cooled radiofrequency lateral branch neurotomy for the
treatment of sacroiliac joint-mediated low back pain: a large case series. Pain Med 2013;14(1):29-35.
23. Goldberg SN. Radiofrequency tumor ablation: principles and techniques. Eur J Ultrasound 2001;13(2):129-47.
24. Goldberg SN, Ahmed M, Gazelle GS, Kruskal JB, Huertas JC, Halpern EF, Oliver BS, Lenkinski RE. Radio-
frequency thermal ablation with NaCl solution injection: effect of electrical conductivity on tissue heating and
coagulation-phantom and porcine liver study. Radiology 2001;219(1):157-65.
25. Bogduk N, Wilson AS, Tynan W. The human lumbar dorsal rami. J Anat 1982;134(Pt 2):383-97.
26. Cohen SP, Rathmell JP. Tackling the technical challenges that hinder the success of facet joint radiofrequency
treatment for spinal pain. Reg Anesth Pain Med 2010;35(4):327-8.

")(
Page 7
27. Van Zundert J, de Louw AJ, Joosten EA, Kessels AG, Honig W, Dederen PJ, Veening JG, Vles JS, van Kleef M.
Pulsed and continuous radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late
cellular activity in the dorsal horn. Anesthesiology 2005;102(1):125-31.
28. Chua NH, Vissers KC, Sluijter ME. Pulsed radiofrequency treatment in interventional pain management:
mechanisms and potential indications-a review. Acta Neurochir (Wien) 2011;153(4):763-71.
29. Byrd D, Mackey S. Pulsed radiofrequency for chronic pain. Curr Pain Headache Rep 2008;12(1):37-41.
30. Bogduk N. Pulsed radiofrequency. Pain Med 2006;7(5):396-407.
31. Cahana A, Van Zundert J, Macrea L, van Kleef M, Sluijter M. Pulsed radiofrequency: current clinical and
biological literature available. Pain Med 2006;7(5):411-23.
32. Podhajsky RJ, Sekiguchi Y, Kikuchi S, Myers RR. The histologic effects of pulsed and continuous
radiofrequency lesions at 42 degrees C to rat dorsal root ganglion and sciatic nerve. Spine (Phila Pa 1976)
2005;30(9):1008-13.
33. Tekin I, Mirzai H, Ok G, Erbuyun K, Vatansever D. A comparison of conventional and pulsed radiofrequency
denervation in the treatment of chronic facet joint pain. Clin J Pain 2007;23(6):524-9.
34. Kroll HR, Kim D, Danic MJ, Sankey SS, Gariwala M, Brown M. A randomized, double-blind, prospective study
comparing the efficacy of continuous versus pulsed radiofrequency in the treatment of lumbar facet syndrome. J
Clin Anesth 2008;20(7):534-7.
35. Gallagher J, Petriccione dVP, Wedley J, Hamman W, Ryan P, Chikanza I, Kirkman B, Price R, Watson M,
Grahame R, Wood S. Radiofrequency facet joint denervation in the treatment of low back pain: A prospective-
controlled double-blind study to assess its efficacy. Pain Clinic 1994;7:193.
36. Leclaire R, Fortin L, Lambert R, Bergeron YM, Rossignol M. Radiofrequency facet joint denervation in the
treatment of low back pain: a placebo-controlled clinical trial to assess efficacy. Spine 2001;26(13):1411,6;
discussion 1417.
37. van Wijk RM, Geurts JW, Wynne HJ, Hammink E, Buskens E, Lousberg R, Knape JT, Groen GJ.
Radiofrequency denervation of lumbar facet joints in the treatment of chronic low back pain: a randomized, double-
blind, sham lesion-controlled trial. Clin J Pain 2005;21(4):335-44.
38. Bogduk N, Macintosh J, Marsland A. Technical limitations to the efficacy of radiofrequency neurotomy for
spinal pain. Neurosurgery 1987;20(4):529-35.
39. Giles LG, Taylor JR. Human zygapophyseal joint capsule and synovial fold innervation. Br J Rheumatol
1987;26(2):93-8.
40. van Kleef M, Barendse GA, Kessels A, Voets HM, Weber WE, de Lange S. Randomized trial of radiofrequency
lumbar facet denervation for chronic low back pain. Spine (Phila Pa 1976) 1999;24(18):1937-42.
41. Nath S, Nath CA, Pettersson K. Percutaneous lumbar zygapophysial (Facet) joint neurotomy using
radiofrequency current, in the management of chronic low back pain: a randomized double-blind trial. Spine
2008;33(12):1291,7; discussion 1298.
42. Gofeld M, Jitendra J, Faclier G. Radiofrequency denervation of the lumbar zygapophysial joints: 10-year
prospective clinical audit. Pain Physician 2007;10(2):291-300.

")(
Page 8
43. Dreyfuss P, Halbrook B, Pauza K, Joshi A, McLarty J, Bogduk N. Efficacy and validity of radiofrequency
neurotomy for chronic lumbar zygapophysial joint pain. Spine (Phila Pa 1976) 2000;25(10):1270-7.
44. Falco FJ, Manchikanti L, Datta S, Wargo BW, Geffert S, Bryce DA, Atluri S, Singh V, Benyamin RM, Sehgal
N, Ward SP, Helm S,2nd, Gupta S, Boswell MV. Systematic review of the therapeutic effectiveness of cervical facet
joint interventions: an update. Pain Physician 2012;15(6):E839-68.
45. Lord SM, Barnsley L, Wallis BJ, McDonald GJ, Bogduk N. Percutaneous radio-frequency neurotomy for
chronic cervical zygapophyseal-joint pain. N Engl J Med 1996;335(23):1721-6.
46. Yin W, Willard F, Carreiro J, Dreyfuss P. Sensory stimulation-guided sacroiliac joint radiofrequency neurotomy:
technique based on neuroanatomy of the dorsal sacral plexus. Spine (Phila Pa 1976) 2003;28(20):2419-25.
47. Burnham RS, Yasui Y. An alternate method of radiofrequency neurotomy of the sacroiliac joint: a pilot study of
the effect on pain, function, and satisfaction. Reg Anesth Pain Med 2007;32(1):12-9.
48. Kornick C, Kramarich SS, Lamer TJ, Todd Sitzman B. Complications of lumbar facet radiofrequency
denervation. Spine (Phila Pa 1976) 2004;29(12):1352-4.
49. Neal JM, Rathmell JP. Complications in Regional Anesthesia & Pain Medicine. Philadelphia,PA: Saunders
Elsevier; 2007.
50. Ma K, Yiqun M, Wu T, Wang W, Liu X, Huang X, Wang Y. Efficacy of diclofenac sodium in pain relief after
conventional radiofrequency denervation for chronic facet joint pain: a double-blind randomized controlled trial.
Pain Med 2011;12(1):27-35.
51. Dobrogowski J, Wrzosek A, Wordliczek J. Radiofrequency denervation with or without addition of
pentoxifylline or methylprednisolone for chronic lumbar zygapophysial joint pain. Pharmacol Rep 2005;57(4):475-
80.
52. Lord SM, Bogduk N. Radiofrequency procedures in chronic pain. Best Pract Res Clin Anaesthesiol
2002;16(4):597-617.
53. Dreyfuss P, Schwarzer AC, Lau P, Bogduk N. Specificity of lumbar medial branch and L5 dorsal ramus blocks.
A computed tomography study. Spine (Phila Pa 1976) 1997;22(8):895-902.
54. Cohen SP, Strassels SA, Kurihara C, Forsythe A, Buckenmaier CC,3rd, McLean B, Riedy G, Seltzer S.
Randomized study assessing the accuracy of cervical facet joint nerve (medial branch) blocks using different
injectate volumes. Anesthesiology 2010;112(1):144-52.
Disclosure
Medtronic, Self, Consulting Fees; Janssen Pharmaceuticals, Self, Consulting Fees

515
Page 1
The Spinal Cord as a Key Site for Pain and Analgesia
James C. Eisenach, M.D. Winston-Salem, North Carolina
105
Page 1
Current Concepts and Controversies in Acute Pain Management
Eugene Viscusi, M.D. Philadelphia, Pennsylvania
Acute pain management continues to be challenging. Studies have demonstrated continued unmet needs with the
majority of patients experiencing significant pain at some point following surgery.
1
Analgesic gaps (periods of
breakthrough pain) continue to be a problem for most patients. There is increasing awareness to opioid related side
effects and the need to minimize opioids generally through the use of multimodal analgesic techniques. Opioid
related respiratory depression and sleep apnea are now major considerations in the postoperative period. The recent
Joint Commission Sentinel Event Alert of August 2012 highlights the need for greater caution when prescribing
opioids including patient risk stratification, heightened monitoring and les reliance on opioids. At the other end of
the opioid spectrum, we have the challenge of managing postoperative pain in the presence of opioid tolerance and
chronic opioid use. There is also an emerging theme of chronic pain following surgery.
Multimodal Analgesia
Historically, we have relied heavily on opioids as single agents for postoperative pain. While opioids are potent and
effective analgesics, this comes at the price of opioid related side effects. Patients typically balance side effects with
pain relief often requesting less pain relief rather than suffer opioid related nausea and vomiting.
2
These
gastrointestinal side effects are distressing to patients and the most common reasons for refusing treatment. Further,
opioids have limited efficacy for some types of pain, particularly visceral and neuropathic pain. Acute postoperative
pain is often a mixed pain syndrome with multiple components and hence may not be relieved well with opioids
alone.
The concept of multimodal analgesia entered the acute pain literature in the early 1990s when Kehlet described the
benefits of balanced analgesia.
3
Today, multimodal analgesia, the application of two or more analgesics acting at
different pain pathways and by different mechanisms, is considered standard practice to enhance analgesia and
minimize reliance on opioids. The ASA Guidelines on Acute Pain Management support the use of nonopioids as
around the clock agents with opioids as supplemental agent. The most commonly employed agents are local
anesthetics, acetaminophen, NSAIDs, COX-2 selective inhibitors, gabapentin and pregabalin, and ketamine. While
these agents may be viewed as less potent than opioids, emerging information suggests they may be able to play a
more significant role than previously thought.
4
Opioid reduction or sparing is at the heart of many of the
challenges and controversies in acute pain management. Future acute pain management strategies are likely to rely
much less on opioids.
Opioid Related Respiratory Depression and Sleep Apnea
The effects of opioids on respiration are well known. In recent years there has been increasing awareness to critical
respiratory events.
5,6
The emphasis place on pain the 5
th
vital sign by the Joint Commission several years back
may have increased the use of opioids in the hospital setting in an attempt to improve pain assessments. The
increasing incident of sleep apnea, often blamed on the increasing obesity in our society, is also considered a risk
factor for opioid use.
Obstructive sleep apnea (OSA) is usually associated with obesity, snoring or other signs of airway obstruction. Yet,
the majority of patients with OSA are undiagnosed and many are not obese.
7
Further, OSA may coexist with central
sleep apnea (CSA).
8
Further, it has been demonstrated that patients with OSA may develop respiratory depression
from opioids but that it is in fact on a central basis and not obstructive.
9
Up to 5% of long term opioid dependent
patients will exhibit CSA.
10
(Chronic opioid use also suppresses REM sleep which may share a similar mechanism.)

105
Page 2
Opioids are potent analgesics and remain the most widely used analgesics for postoperative pain at this time.
Hence, we will be dealing with these challenges for the foreseeable future.

While respiratory depression (RD) is a serious problem, definitions of RD vary widely. Reported incidences range
from 1% to approximately 40%.
11
However, these definitions include transient oxygen desaturation or transient
respiratory rates below 10 breaths per minute. While these events should not be taken lightly, it is difficult to
predict which or how many of these events will progress to critical situations requiring intervention. In one series of
over 2000 patients with standard patient controlled analgesia settings, the incident of critical respiratory depression
was 0.1-0.3%.
12
The controversy here is determining if and what type of monitoring is appropriate for patients
receiving opioids and how to minimize opioid use.

An ASA task force provided guidance on managing patients with OSA.
13
There are no specific analgesic
recommendations but rather favor minimal opioids use and multimodal analgesia. Local anesthetic techniques are
encouraged. One specific recommendation is to avoid discharge to an unmonitored setting until there is no further
risk of respiratory depression. Can we reliably make such a prediction?

There are various monitoring techniques recommended for the OSA patient but no definitive approach. Pulse
oximetry is generally recommended although capnometry may be a more sensitive indicator. Observational
monitoring in the PACU with an OSA prescreening tool may have a role in risk stratifying patients who would
benefit from the most aggressive monitoring.
14
The STOP-Bang scoring system has also shown merit in identifying
at-risk patients.
15

Using the STOP-Bang questionnaire, one team of investigators found 41.5% of a standard preoperative elective
population had OSA. These investigators also identified a ten-fold increase in pulmonary and cardiac complications
in patients with OSA.
16
Clearly, patients with OSA may benefit from advance planning. Early identification is key.
This allows planning an anesthetic to minimize reliance on opioids both intra- and postoperatively as well as
designing an appropriate multimodal approach with appropriate monitoring.

Emerging Views on Opioids
Mu-opioid receptors are ubiquitous within the CNS and at peripheral sites. The analgesic action of opioids within
the CNS is well known. Opioid adverse events are related to both central and peripheral receptors. Peripheral
opioid receptors have a role in ileus, constipation, hormonal regulation, tumor growth, angiogenesis and
immunological function. While long term opioid use has clear risks, there is emerging evidence that the short term
use of opioids may have significant consequences. Use of opioids for as little as one month may produce lasting
changes in the brain.
17
Elderly patients given opioids for postoperative pain are at risk for long term opioid use.
18

Opioids may reduce survival after cancer surgery.
19
Perioperative plans that reduce opioids have been shown to
increased cancer survival following surgery for breast cancer, prostate cancer and possibly bowel cancer. These
typically involve regional anesthetic techniques (paravertebral blocks, epidurals). Opioids are known to enhance
angiogenesis leading to tumor growth and to inhibit the immunological response which may alter survival. Recent
work in rodents with peripheral opioid antagonism demonstrated an inhibition of tumor growth.
20

Opioid Tolerance and Hyperalgesia
Long term use of opioids is known to produce tolerance or decreased efficacy requiring dose escalation. Some
patients on chronic opioids also exhibit hyperalgesia or altered pain sensitivity.
21
As a group, patients on chronic
opioid therapy for pain or methadone maintenance are well known to present significant postoperative pain
challenges.
For these patients in the postoperative period, increased opioid requirements are expected but often pain is
unrelieved with opioids alone.
22
Opioid tolerant patients benefit from aggressive multimodal analgesia with regional
anesthetic techniques. Recently, ketamine has shown efficacy in this setting. In opioid tolerant spine surgery
patients, Loftus and colleagues demonstrated that pre- and intra-operative ketamine reduced pain and opioid
requirements in the immediate postoperative period and up to six weeks following surgery.
23,24,25
Low dose
ketamine is now commonly employed in opioid tolerant patients. There is some controversy as to when and where

105
Page 3
ketamine should be administered. Loftus and colleagues demonstrated benefit from pre and intraop administration.
Postoperative ketamine infusion is a useful adjunct in multimodal analgesia for these patients but further studies are
warranted to evaluate dosing and duration of treatment.
Chronic Pain Following Surgery
Chronic pain may be a consequence of surgery. Until recently, normal resolution of acute pain was expected to be a
routine occurrence. There is a significant burden of long-term pain following surgery. The incidence following
thoracotomy and radical mastectomy may exceed 50%. The incidence following inguinal hernia repair is 19-40%.
There is now an understanding that healing with neuronal plasticity may occur resulting in chronic postsurgical pain
(CPSP). CPSP has been linked to severity of acute pain.
26
Following thoracotomy, patients who experience pain of
greater intensity and for a longer duration had a higher risk of persistent pain. Kehlet has identified not only intense
acute pain but also, nerve injury and intense inflammatory response as associated factors.
27

Surgery often results in an intense peripheral inflammatory response (peripheral sensitization) as a consequence of
the release of local inflammatory mediators. This inflammatory soup causes peripheral sensitization leading to
central sensitization (the release of central inflammatory mediators) which in turn results in further pain
sensitization.
28
Even in the presence of total neuronal blockade (spinal anesthesia), there is still a central humoral
response to peripheral inflammation. Hence, local anesthetic techniques alone cannot inhibit this process of central
sensitization.
Total knee arthroplasty has a reported incidence of CPSP approaching 9%. A recent study utilizing a complex
multimodal regimen with pregabalin for total knee arthroplasty showed a marked reduction in chronic neuropathic
pain.
29
While this is one study, it provides a basis for the potential use of multimodal analgesia as an approach to
reducing the prevalence of CPSP. Still, another study with chronic pain following total joint arthroplasty supports
that patients may have underlying vulnerabilities such as major depression or chronic pain elsewhere.
30
There is
some evidence correlating CPSP to individual pain response with experimental pain models.
31

In a number of surgical models, perioperative pregabalin either alone or within a complex multimodal regimen has
been shown to reduce pain in the immediate postoperative period and in some studies in the months following
surgery.
32-37
Recently, intraoperative lidocaine infusion was shown to reduce chronic pain following breast
surgery.
38

Ultimately chronic post-surgical pain is likely to be multifactorial in origin. Current best evidence suggests that a
multimodal analgesic approach may offer the best current approach for reducing long-term pain after surgery. If
specific at-risk individuals can be identified in the future, targeted approaches might be possible.

Conclusions

Acute pain management continues to be challenging. While significant strides have been made in many areas,
specific patient populations and surgical pain models remain underserved. Opioid related adverse events,
particularly respiratory depression are now identified for their significant impact on poor outcome. Patient
satisfaction, largely driven by experience with pain and treatment side effects, is now an important component for
reimbursement within the Affordable Healthcare Act of 2010. Multimodal analgesia is now recognized as a
standard of care and is familiar to our surgical colleagues. The most current literature supports opioid reduction
techniques and multimodal analgesia from the preoperative period and through the recovery period. Integration of
multimodal analgesia into our anesthetic plan will promote early utilization both pre- and intra-operative to
maximize the benefits. The emerging information on opioids suggests that these agents will likely play a lesser role
in our future approaches to acute pain management.

105
Page 4
References

1. ApfelbaumJL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest
postoperative pain continues to be undermanaged. Anesth Analg 2003;97:534-40
2. Gan TJ, Lubarsky DA, Flood EM, et al. Patient preferences for acute pain treatment. Brit J Anaesth
2004;92:681-8
3. Kehlet H, Dahl JB. The value of multimodal or balanced analgesia in postoperative pain treatment.
Anesth Analg1993;77:1048-56
4. Moore RA, Derry S, McQuay HJ, et al. Single dose oral analgesics for acute postoperative pain in adults.
Cochrane Database of Systematic Reviews2011, Issue 9
5. WeingerMB. Dangers of postoperative opioids: APSF workshop and white paper addresses prevention of
postoperative respiratory complications. APSF Newsletter 2006-07;21:61, 63-7
6. Overdyk FJ. Letter to the editor: Postoperative opioids need system-wide overhaul. APSF Newsletter 2009-
10;244, 61
7. Young T, Evans L, Finn L, et al. Estimation of clinically diagnosed proportion of sleep apnea syndrome in
middle-aged men and women. Sleep 1997;20:705-6
8. Badr MS, Toiber F, Skatrud JB, et al. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl
Physiol 1995;78:1806-15
9. Bernards CM, Knowlton SL, Schmidt DF, et al. Respiratory and sleep effects of remifentanil in volunteers
with moderate obstructive sleep apnea. Anesthesiology 2009;110:41-49
10. Ecker DJ, Jordan AS, Merchia P, et al. Central sleep apnea: pathophysiology and treatment. Chest
2007;131:595-607
11. Overdyk FJ, Carter R, Maddox RR, et al. Continuous oximetry/capnometry monitoring reveals frequent
desaturation and bradypnea during patient-controlled analgesia. Anesth Analg 2007;105:412-8
12. Viscusi ER, Sicardi M, Damaraju CV, et al.The safety and efficacy of fentanyl iontophoretic transdermal
system compared with moprhine intravenous patient-controlled analgesia for postoperative pain management:
an analysis of pooled data from three randomized, active-controlled clinical studies. Anesth Analg
2007;105:1428-36
13. ASA Task Force on Perioperative Management of Patients with OSAAnesthesiology 2006;104:1081-1952
14. Gali B, Whalen FX, Schroeder DR, et al. Identification of patients at risk for postoperative respiratory
complications using a preoperative obstructive sleep apnea screening tool and postanesthesia care assessment.
Anesthesiology 2009;110:869-77
15. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep
apnea. Anesthesiology 2008;108:812-21
16. Vasu T, Doghramji K, Cavallazzi R, et al. Obstructive sleep apnea syndrome and postoperative
complications. Arch Otolaryngo Head Neck Surg 2010;136:1020-4
17. Younger JW, Chu LF, DArcy NT, et al. Prescription opioid analgesics rapidly change the human brain. Pain
2011;152(8):1803-10
18. Alam A, Gomes T, Zheng H, et al. Long-term analgesia use after low-risk surgery: a retrospective cohort
study. Arch Intern Med 2012;172(5):425-30
19. Lennon FE, Moss J, Singleton PA. The u-opioid receptor in cancer progression: is there a direct effect?
Anesthesiology 2012;116(4):1-6
20. Mathew B, Lennon F, Siegler J, et al. The novel role of the mu opioid receptor in lung cancer progression: a
laboratory investigation. Anesth Analg 2011;112(3):558-67
21. Angst M, Clark D. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology
2010;113:514-5
22. Viscusi ER, Pappgallo M. A review of opioids for in-hospital pain management. Hospital Practice
2012;40(1):149-59
23. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in
opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010;113:639-46
24. Angst MS, Clark JD. Ketamine for managing perioperative pain in opioid-dependent patients with chronic
pain: a unique indication? Anesthesiology 2010,113:514-5
25. Domino EF. Taming the ketamine tiger. Anesthesiology 2010;113:678-86
26. Pluijms WA, Steegers MA, Verhagen AF, et al. Chronic post-thoracotomy pain: a etrospective study. Acta
Anaesthesiol Scand 2006;50:804-8

105
Page 5
27. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet
2006;367:1618-25
28. Woolf CJ, Salter MW. Neuronal plasticity: increasing he gain in pain. Science 2000;288:1765-8
29. Buvanendran A, Kroin JS, Della Valle CJ, et al. Perioperative oral pregabalin reduces chronic pain after total
knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg 2010;110:199207
30. Wylde V, Hewlett S, Learmouth ID, et al. Persistent pain after joint replacement: prevalence, sensory
qualities, and postoperative determinants. Pain 2011;152:566-73
31. Werner MU, Mjobo HN, Nielsen PR, et al. Prediction of postoperative pain: a systemic review of predictive
experimental pain studies. Anesthesiology 2010:112:1494-502
32. Kim JC, Choi YS, Kim KN, et al. Effective dose of peri-operative oral pregabalin as an adjunct to multimodl
analgesic regimen in lumbar spinal fusion surgery. Spine 2011;36:42833
33. Burke SM, Shorten GD. Perioperative pregabalin improves pain and functional outcomes 3 months after
lumbar discectomy. Anesth Analg 2010;110:1180-5
34. Gianesello L, Pavoni V, Barboni E, et al. Perioperative prebagalin for postoperative pain control and quality
of life after major spinal surgery. J NeurosurgAnesthesiol 2012;24(2):121-6
35. Trabulsi EJ, Patel J, Viscusi ER, et al. Preemptive multimodal pain regimen reduces opioid analgesia for
patients undergoing robotic-assisted laparoscopic radical prostatectomy. J Urology 2010;76(5):122-4
36. Balaban F, Yagar S, Ozgok A, et al. A randomized, placebo-controlled study of pregabalin for postoperative
pain intensity after laparoscopic cholecystectomy. J Clin Anesth 2012;24:175-8
37. Bornemann-Cimenti H, Lederer AJ, Wejbora M, et al. Preoperative prebagalin administration significantly
reduces postoperative opioid consumption and mechanical hyperalgesia after transperitoneal nephrectomy. Br
J Anaesth 2012;108:845-9
38. Grigoras A, Lee P, Sattar F. Perioperative intravenous lidocaine decreases the incidence of persistent pain
after breast surgery. Clin J Pain 1012;28(7):567-72.

Disclosure
Cubist, Self, ConsultingFees; Incline, Self, Consulting Fees; Cadence, Self, Consulting Fees; AcelRx, Self,
Consulting Fees; Pacira, Self, Funded Research, Consulting Fees; Cumberland, Funded Research; Adolor, Funded
Research

110
Page 1
Local Anesthetic Toxicity: Optimal Management to
Avoid Neurotoxic Injury and Treat Cardiac Arrest
Kenneth Drasner, M.D. San Francisco, California
Continued reports of major and minor neurologic sequelae following central neuraxial blockade have
renewed concern regarding the potential toxicity of currently available local anesthetic agents. These reports, along
with the experimental literature, have led to modifications in clinical practice. This lecture will summarize some of
this clinical experience and the experimental findings that form the basis of these modifications, with particular
emphasis on the rational selection of a local anesthetic for short-duration outpatient spinal anesthesia. In addition,
the lecture will review the issue of local anesthetic systemic toxicity, focusing on the recent development of lipid
rescue for bupivacaine cardiotoxicity, and the extension of lipid resuscitation beyond cardiotoxicity, and beyond
treatment of the local anesthetics.
ANESTHETIC NEUROTOXICTY
Cauda equina syndrome and continuous spinal anesthesia (CSA).
In 1991, reports of cases of cauda equina syndrome following continuous spinal anesthesia (CSA) created
concern regarding the potential neurotoxicity of local anesthetics (1). Most involved lidocaine administered through
microcatheters, though some occurred with other anesthetics and/or macro (epidural) catheters. In all of these cases,
there was evidence of a restricted sacral block that required repetitive doses of local anesthetic to achieve an
adequate level of anesthesia. It was hypothesized that the combination of maldistribution and the high dose of
anesthetic led to neurotoxic concentrations in the subarachnoid space. Studies performed with models of the
subarachnoid space (2), and other in vitro (3-6) and in vivo (7,8) investigations provided support for this mechanism
of injury. Most critically, administration of anesthetic in a restricted sacral pattern could induce functional loss that
closely paralleled clinical injury and caused histologic damage consistent with impairment.
In response to these reported injuries, spinal microcatheters were removed from the U.S. market. However,
they remain available in some countries, while CSA is still practiced in the U.S. using epidural equipment, and this
technique is commonly used when dural puncture accidentally occurs during epidural placement. It is therefore
essential that the practitioner appreciate the factors that may contribute to neurotoxicity, and how they impact
clinical management of an intrathecal catheter. Most critically, the clinician should limit the combined anesthetic
dosage used to achieve surgical anesthesia to the maximum amount reasonable to administer as a single
intrathecal injection.
Continuous Spinal Anesthesia: Guidelines for Anesthetic Administration
Insert the catheter just far enough to confirm and maintain placement.
Use the lowest effective local anesthetic concentration.
Place a limit on the dose of local anesthetic to be used.
Administer a test dose and assess the extent of any sensory and motor block.
If maldistribution is suspected, use maneuvers to increase the spread of local anesthetic (change the
patients position, alter the lumbosacral curvature, switch to a solution with a different baricity).
If well-distributed sensory anesthesia is not achieved before the dose limit is reached, abandon the
technique.

110
Page 2
Risk associated with repetitive injection after failed spinal.
As with CSA, inadequate sensory block with single-injection spinal anesthesia is often the result of
maldistribution. Under such circumstances, there is also the potential for repeat injections to distribute in the same
pattern resulting in neurotoxic concentrations of anesthetic within a restricted area of the subarachnoid space.
Review of the closed claims database (9) and subsequent case reports (10) have confirmed these concerns.
Based on these considerations, there have been suggestions for management of a failed spinal that include
assessment of the likelihood of technical error and adjustment of dosage for the second injection (9). However,
adherence to these recommendations imparts significant delay, as one must allow sufficient time for achievement of
near-maximal block prior to assessment of sensory anesthesia. A more efficient and safer alternative strategy is to
assume that the injected anesthetic has been administered intrathecally. Accordingly, similar to the strategy used for
CSA, the practitioner should simply limit the combined anesthetic dosage to the maximum amount reasonable to
administer as a single intrathecal injection.

Injury associated with inadvertent subarachnoid injection of an epidural dose.
There is a third circumstance under which excessive doses of anesthetic might be delivered into the
subarachnoid spaceaccidental injection of a dose intended for epidural administration. In the 1980s, reports of
deficits associated with apparent subarachnoid administration of chloroprocaine solutions containing bisulfite
generated concern that injury might occur if epidural doses of this anesthetic solution are administered intrathecally.
Beginning in 1992, similar cases have been reported with lidocaine (11), expanding this concern to include an
anesthetic once considered the gold standard of safety. These cases serve to reinforce the critical importance of the
test dose and fractional administration of anesthetic during performance of epidural anesthesia. Additionally,
should high doses of an anesthetic be administered through a misplaced catheter, repetitive withdrawal of small
volumes (4-5 ml) of CSF and replacement with saline should be considered, regardless of the anesthetic.

Injury following single-injection lidocaine spinal anesthesia.
The aforementioned volley of clinical reports provides compelling evidence that injury can result if high
doses of any anesthetic are administered intrathecally. More surprising, two subsequent reports raised suspicion that
neurologic deficits might occur with administration of lidocaine at doses recommended for single-injection spinal
anesthesia (12,13). One was a case report of cauda equina syndrome following intrathecal injection of 100 mg of
lidocaine with epinephrine (13). The second was a prospective study of regional anesthesia from France (12). In a
database that included roughly 10,000 lidocaine spinals, there were eight cases of persistent deficits following
single-injection spinal anesthesia that could not be explained on any other basis. All of these injuries occurred with
relatively high doses (!75mg); two of these cases were permanent, both of which followed injection of the
maximum recommended clinical dose (100 mg). The lack of an alternative etiology and the occurrence of injury at
the high end of the dose range make toxicity the most likely explanation (14), and argue that the potential benefit of
using a dose higher than 75 mg of intrathecal lidocaine would seem inadequate to override the added risk.

Transient neurologic symptoms (TNS) following single-injection lidocaine spinal anesthesia.
In 1993, Schneider and colleagues reported four cases in which transient pain/dysesthesia followed routine
administration of conservative doses of intrathecal lidocaine (15). These symptoms were initially called transient
radicular irritation, but this term was later abandoned in favor of transient neurologic symptoms or TNS,
owing to the lack of certainty regarding their etiology. In this initial report, all four patients were in lithotomy
position, which led the authors to postulate that this position put stretch on the nerve roots of the cauda equina,
reducing blood flow, and potentiating toxicity (15). A follow-up study documented a 37% incidence of TNS with
spinal lidocaine, but a near-zero incidence with bupivacaine (16). Abundant data from numerous studies have
subsequently confirmed these findings, and have established the co-factors that contribute to the occurrence of
symptoms. In addition to lithotomy, positioning for knee arthroscopy and outpatient status markedly enhance risk
(17,18). While self-limited, the pain can be quite severe, often exceeding that induced by the surgical procedure.
Importantly, TNS is not associated with sensory loss, motor weakness, or bowel or bladder dysfunction. The
etiology and significance of these symptoms remains to be established, but discrepancies between factors affecting
TNS and experimental animal toxicity cast doubt that TNS and persistent neurologic deficits represent opposite
extremes on a single spectrum of toxicity. While these recent issues have led to restricted use for spinal anesthesia,
lidocaine remains a popular agent for all other applications, including epidural anesthesia.

110
Page 3
Chloroprocaine spinal anesthesia: back to the future?
The problems associated with lidocaine spinal anesthesia, particularly the high incidence of TNS have led
many clinicians to abandon the use of this anesthetic for spinal anesthesia. While there are reports describing the use
of low-dose bupivacaine combined with fentanyl (19), many practitioners report a high failure rate with this
technique, and complete recovery may still be delayed. Of other available options, neither procaine (20) nor
mepivacaine (21) appear to offer sufficient advantage with respect to TNS.
Despite a rather blemished past, considerable attention has been focused on the possibility of using
chloroprocaine to fill this anesthetic void. Introduced into clinical practice over 50 years ago, chloroprocaine never
evolved as a spinal anesthetic agent, perhaps related to the development and marketing of the amide, lidocaine. In
any case, reports of neurologic deficits associated with possible intrathecal injection of epidural chloroprocaine in
the early 80s raised concern regarding the potential neurotoxicity of this anesthetic, which, until recently, would
have subdued any enthusiasm for deliberate intrathecal administration.
The dissatisfaction with spinal lidocaine encouraged Kopacz and colleagues to re-investigate the use of
spinal chloroprocaine. Their rigorous systematic volunteer studies documented effective spinal anesthesia with
little, if any, risk of TNS (22-26). Duration of effect was shorter with chloroprocaine than with an equal dose of
lidocaine (23), and institutional discharge criteria were achieved more rapidly than with lidocaine (23), procaine
(22), or low-dose bupivacaine (26). As expected, anesthesia could be prolonged or enhanced by co-administration of
fentanyl (25) or epinephrine (24). However, an unexpected and worrisome finding was the occurrence of flu-like
symptoms in volunteers receiving chloroprocaine containing epinephrine (24), the etiology of which remains
obscure.
A recently published summary of the clinical literature concerning spinal chloroprocaine identified five
prospective trials and two retrospective reviews, containing a total of 172 and 600 patients, respectively (27). These
reports confirm the suitability of chloroprocaine for outpatient spinal anesthesia with respect to block characteristics
and a low incidence of TNS, with only five patients reporting such symptoms. However, of considerable concern
was the occurrence of a case of resolving cauda equina syndrome (28). These limited published data regarding
chloroprocaine as a spinal anesthetic are obviously insufficient to establish safety, particularly with the reported
complication, albeit a single case. However, the off-label clinical experience with this drug is fairly substantial,
and there is now a formulation of chloroprocaine approved for use in Europe. Whether this unpublished experience
provides adequate evidence of safety is a judgment that needs to be made by the individual anesthetist. However,
should chloroprocaine be used for spinal anesthesia, the available data and clinical experience would suggest
that the solution should be bisulfite-free, the dose limited to 60 mg, and the use of epinephrine be avoided.

ANESTHETIC CARDIOTOXITY AND LIPID RESCUE

Historical context
The most feared complication associated with administration of local anesthetics is the profound effect that
these agents can have on cardiac conduction and function. In the past, it was generally accepted that the
cardiovascular system was more resistant than the central nervous system to toxic effects of modern local
anesthetics. It was also well accepted that prompt treatment of CNS toxicity, particularly maintenance of ventilation
and oxygenation, could avert catastrophe. This conventional wisdom was called into question by a sentinel case
reported by Prentiss, in which administration of etidocaine for caudal anesthesia in a healthy 31-yr-old male was
associated with near simultaneous convulsions and cardiac arrest. Shortly thereafter, a seminal editorial by Albright
incorporated Prentiss case, along with five others, to support the concept that these long acting lipid-soluble
anesthetic agents (etidocaine and bupivacaine) could induce profound cardiac toxicity preceding or concurrently
with CNS toxicity, and independent of hypoxia (29). Although this suggestion met with considerable resistance,
cases of bupivacaine-induced cardiac collapse continued to occur. By early 1983, the FDA had received reports
from the pharmaceutical industry of twelve cases of cardiac arrest, ten fatal, associated with the use of bupivacaine
in obstetrics, most associated with the use of the 0.75% solution. In response, the package labeling was modified,
and a Dear Doctor letter was sent stating that the 0.75% solution of bupivacaine was no longer to be used for
obstetrical anesthesia, nor any concentration to be used for intravenous regional anesthesia or paracervical block.
This communication also stressed the importance of an adequate test dose, and injection of anesthetic in incremental
doses. In addition to putting into play these changes in clinical practice, the occurrence of these cases stimulated
research generating an enormous literature, which has provided evidence for the distinctive cardiotoxicity of these
agents. The most likely mechanism seems to relate to the nature of bupivacaines interaction with cardiac sodium
channels (30). Simply put, recovery from bupivacaine blockade during diastole is relatively prolonged, making it far
more potent with respect to depressing the maximum upstroke velocity of the cardiac action potential (Vmax) in

110
Page 4
ventricular cardiac muscle. As a result, bupivacaine has been labeled a fast-in, slow-out local anesthetic, which
likely creates conditions favorable for unidirectional block and reentry. Other mechanisms may contribute to
bupivacaines cardiotoxicity, including disruption of atrioventricular nodal conduction, depression of myocardial
contractility, and indirect effects mediated by the central nervous system (31). This cardiotoxicity has obviously
been the driving force for development of the single enantiomer anesthetics, ropivacaine and levo-bupivacaine.
Unfortunately, despite these pharmaceutical advancements and the aforementioned modifications in clinical
practice, cardiotoxicity has remained a concern, and with the exception of cardiopulmonary bypass, treatment
options have been largely ineffective.

Lipid Rescue
Recently, a series of clinical events, insightful observations, systematic experimentation, and astute clinical
decisions have identified a practical and apparently effective therapy for bupivacaine cardiotoxicity. Additionally,
this therapy appears to have applications that go well beyond the initial problem of bupivacaine cardiotoxicity,
finding application in the treatment of other manifestations of local anesthetic systemic toxicity, as well as
resuscitation from cardiotoxicity secondary to a wide variety of toxicological challenges.
After learning of a case of apparent cardiotoxicity from only 22 mg of bupivacaine in a patient with
carnitine deficiency (32), Weinberg postulated that this metabolic derangement led to enhanced toxicity due to the
accumulation of fatty acids within the mitochondria. He then hypothesized that administration of lipid would
potentiate cardiotoxicity. However, experiments he conducted to test this hypothesis demonstrated protection rather
than enhancement of bupivacaines cardiotoxicity by lipid. Encouraged by this serendipitous finding, he instituted a
series of deliberate systematic investigations in rats (33) and dogs (34), which clearly demonstrated the potential
efficacy of intravenous lipid for treating the highly-resistant cardiotoxicity of bupivacaine.
Clinical confirmation came eight years after Weinbergs initial studies. Faced with a patient who developed
cardiotoxicity refractory to standard ACLS after receiving 20 mL 0.5% bupivacaine and 20 mL 1.5% mepivacaine
for an interscalene block, Rosenblatt administered a 100 mL bolus of 20% Intralipid (35). The patient
subsequently responded to defibrillation, ultimately making a complete recovery. A subsequent report by Litz
provided additional confirmation, while extending the potential utility of this treatment to cardiotoxicity induced by
ropivacaine (36). Several reports soon followed, including a report by Spence suggesting that lipid may have utility
in treating local anesthetic CNS toxicity (37), as well as others suggesting efficacy in treating toxicity induced by
other classes of compounds. With respect to the latter, laboratory investigations have demonstrated utility for
resuscitation from cardiotoxicity secondary to various compounds including verapamil (38) and clomipramine (39),
and there are anecdotal clinical reports of successful resuscitations from bupropion-induced cardiovascular collapse
(40) and multiform ventricular tachycardia provoked by haloperidol (41).
The mechanism by which lipid is effective is incompletely understood, but almost certainly some of its
effect is related to its ability to extract bupivacaine (or other lipophilic drugs) from aqueous plasma or tissue targets,
thus reducing their effective concentration (lipid sink). Accordingly, its potential utility may be predictable based
on physiochemical properties of the toxic compound (42). However, the extent of this extraction may not be
adequate to account for the magnitude of clinical effect, suggesting that other mechanisms at least contribute to the
efficacy of lipid rescue (43,44). For example, bupivacaine has been shown to inhibit fatty acid transport at the inner
mitochondrial membrane, and lipid might act by overcoming this inhibition serving to restore energy to the
myocardium, or derive benefit via elevation of intramyocyte calcium concentration.
Although the mechanism is uncertain, and numerous questions remain, the evidence is more than sufficient
to warrant administration of lipid in cases of systemic anesthetic toxicity. The timing of lipid is somewhat
controversial, though the trend over time has been toward earlier use. While it is has been argued that infusing lipid
at the earliest signs of systemic toxicity could result in unnecessary treatment of some patients, it seems imprudent
to wait until severe cardiovascular dysfunction is evident. With respect to treatment of severe cardiac toxicity, there
is evidence to suggest that vasopressin is best avoided (42). The literature is inconsistent with respect to
epinephrine, the data demonstrating both benefit and potential deleterious effects (45-50). Nonetheless, it is
reasonable to conclude that epinephrine might be useful in augmenting the return of spontaneous circulation, but
high doses are probably to be avoided, the drug preferably administered in the 10-100 mcg bolus range, at least
initially. Most critically, it should be evident that solutions of 20% lipid should be stocked and readily accessible
in any area where local anesthetics are administered, as well as locations where overdoses from any lipophilic
drug might be treated. And critically, propofol should not be administered for this purpose, as the relatively
enormous volume of this solution required for lipid therapy (~200 ml) would deliver potentially lethal quantities of
propofol. However, small does of propofol might be appropriate for seizure control, particularly in the case where
there would be a delay in administering a benzodiazepine.

110
Page 5
Many important issues have yet to be adequately addressed in this rapidly developing area, including
identification of the most effective lipid emulsion (51-53) and optimal dosage parameters. Timely information on
this topic, as well as downloadable treatment protocols, can be found at lipidrescue.org, a website established and
maintained by Guy Weinberg. Additionally, the March-April 2010 issue of Regional Anesthesia and Pain Medicine
contains a collection of articles developed by an ASRA Practice Advisory Panel (54-59). The summary
recommendations from this group (58) are available for download without subscription at journals.lww.com/rapm.
The recommendations from this manuscript for treatment of systemic toxicity and the level of evidence for each
intervention are presented in the following table.

Recommendations for Treatment of Local Anesthetic Systemic Toxicity (LAST)
If signs and symptoms of LAST occur, prompt and effective airway management is crucial to preventing hypoxia
and acidosis, which are known to aggravate LAST (I; B).
If seizures occur, they should be rapidly halted with benzodiazepines. If benzodiazepines are not readily
available, small doses of propofol or thiopental are acceptable. Future data may support the early use of lipid
emulsion to treat seizures (I; B).
Although propofol can stop seizures, large doses further depress cardiac function; propofol should be avoided
when there are signs of cardiovascular compromise. (III; B). If seizures persist despite benzodiazepines, small
doses of succinylcholine or similar neuromuscular blocker should be considered to minimize acidosis and
hypoxia (I; C).
If cardiac arrest occurs, we recommend standard Advanced Cardiac Life Support, with the following
modifications:
o If epinephrine is used, small doses (10 to 100 mcg boluses in the adult) are preferred (IIa; C)
o Vasopressin is not recommended (III; B)
o Avoid calcium channel blockers and beta-adrenergic receptor blockers (III; C)
o If ventricular arrhythmias develop, amiodarone is preferred (IIa; B); treatment with local anesthetics
(lidocaine or procainamide) is not recommended (III; C)
Lipid emulsion therapy (IIa; B):
o Consider administering at the first signs of LAST, after airway management
o Dosing:
! 1.5 mL/kg 20% lipid emulsion bolus
! 0.25 mL/kg/min infusion, continued for at least 10 minutes after circulatory stability is
attained.
! If circulatory stability is not attained, consider re-bolus and increasing infusion to 0.5
mL/kg/min
! Approximately 10 ml/kg lipid emulsion for 30 minutes is recommended as the upper limit
for initial dosing.
Propofol is not a substitute for lipid emulsion (III; C)
Failure to respond to lipid emulsion and vasopressor therapy should prompt institution of cardiopulmonary
bypass (CPB) (IIa; C). Because there can be considerable lag in beginning CPB, it is reasonable to notify the
closest facility capable of providing it when cardiovascular compromise is first identified during an episode of
LAST.

110
Page 6
References

1. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, Bohner D. Cauda equina syndrome
after continuous spinal anesthesia. Anesth Analg 1991;72:275-81.
2. Rigler ML, Drasner K. Distribution of catheter-injected local anesthetic in a model of the subarachnoid space.
3. Gold MS, Reichling DB, Hampl KF, Drasner K, Levine JD. Lidocaine toxicity in primary afferent neurons
from the rat. J Pharmacol Exp Ther 1998;285:413-21.
4. Johnson ME, Saenz JA, DaSilva AD, Uhl CB, Gores GJ. Effect of local anesthetic on neuronal cytoplasmic
calcium and plasma membrane lysis (necrosis) in a cell culture model. Anesthesiology 2002;97:1466-76.
5. Kanai Y, Katsuki H, Takasaki M. Graded, irreversible changes in crayfish giant axon as manifestations of
lidocaine neurotoxicity in vitro. Anesth Analg 1998;86:569-73.
6. Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high
concentrations of local anesthetics. Anesthesiology 1994;80:1082-93.
7. Drasner K, Sakura S, Chan VW, Bollen AW, Ciriales R. Persistent sacral sensory deficit induced by
intrathecal local anesthetic infusion in the rat. Anesthesiology 1994;80:847-52.
8. Hashimoto K, Sakura S, Bollen AW, Ciriales R, Drasner K. Comparative toxicity of glucose and lidocaine
administered intrathecally in the rat. Reg Anesth Pain Med 1998;23:444-50.
9. Drasner K, Rigler M. Repeat injection after a "failed spinal"At times, a potentially unsafe practice.
10. Loo CC, Irestedt L. Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: a review
of six cases of cauda equina syndrome reported to the Swedish Pharmaceutical Insurance 1993-1997. Acta
Anaesthesiol Scand 1999;43:371-9.
11. Drasner K, Rigler ML, Sessler DI, Stoller ML. Cauda equina syndrome following intended epidural
anesthesia. Anesthesiology 1992;77:582-5.
12. Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional
anesthesia: results of a prospective survey in France. Anesthesiology 1997;87:479-86.
13. Gerancher J. Cauda equina syndrome following a single spinal administration of 5% hyperbaric lidocaine
through a 25-gauge Whitacre needle. Anesthesiology 1997;87:687-9.
14. Drasner K. Lidocaine spinal anesthesia: a vanishing therapeutic index? Anesthesiology 1997;87:469-72.
15. Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A, Hampl K, von Hochstetter A. Transient
neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth
Analg 1993;76:1154-7.
16. Hampl KF, Schneider MC, Ummenhofer W, Drewe J. Transient neurologic symptoms after spinal anesthesia.
Anesth Analg 1995;81:1148-53.
17. Pollock JE, Neal JM, Stephenson CA, Wiley CE. Prospective study of the incidence of transient radicular
irritation in patients undergoing spinal anesthesia. Anesthesiology 1996;84:1361-7.
18. Freedman JM, Li DK, Drasner K, Jaskela MC, Larsen B, Wi S. Transient neurologic symptoms after spinal
anesthesia: an epidemiologic study of 1,863 patients. Anesthesiology 1998;89:633-41.
19. Ben-David B, Solomon E, Levin H, Admoni H, Goldik Z. Intrathecal fentanyl with small-dose dilute
bupivacaine: better anesthesia without prolonging recovery [see comments]. Anesth Analg 1997;85:560-5.
20. Hodgson PS, Liu SS, Batra MS, Gras TW, Pollock JE, Neal JM. Procaine compared with lidocaine for
incidence of transient neurologic symptoms. Reg Anesth Pain Med 2000;25:218-22.
21. Liguori GA, Zayas VM, Chisholm MF. Transient neurologic symptoms after spinal anesthesia with
mepivacaine and lidocaine. Anesthesiology 1998;88:619-23.
22. Gonter AF, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with procaine in volunteers. Anesth Analg
2005;100:573-9.
23. Kouri ME, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers. Anesth Analg
2004;98:75-80.
24. Smith KN, Kopacz DJ, McDonald SB. Spinal 2-chloroprocaine: a dose-ranging study and the effect of added
epinephrine. Anesth Analg 2004;98:81-8.
25. Vath JS, Kopacz DJ. Spinal 2-chloroprocaine: the effect of added fentanyl. Anesth Analg 2004;98:89-94.
26. Yoos JR, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with small-dose bupivacaine in volunteers.
Anesth Analg 2005;100:566-72.

110
Page 7
27. Goldblum E, Atchabahian A. The use of 2-chloroprocaine for spinal anaesthesia. Acta Anaesthesiol Scand
2013; 57: 545552.
28. Vaghadia H, Neilson G, Lennox PH. Selective spinal anesthesia for outpatient transurethral prostatectomy
(TURP): randomized controlled comparison of chloroprocaine with lidocaine. Acta Anaesthesiol Scand
2012; 56: 21723.
29. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology
1979;51:285-7.
30. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast block of
sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology
1985;62:396-405.
31. Bernards CM, Artu AA. Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by
intracerebroventricular bupivacaine in rabbits. Anesthesiology 1991;74:89-96.
32. Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK. Malignant ventricular dysrhythmias in a
patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth
1997;9:668-70.
33. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation
with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology
1998;88:1071-5.
34. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-
induced cardiac toxicity. Reg Anesth Pain Med 2003;28:198-202.
35. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to
resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006;105:217-8.
36. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole
after axillary plexus block using lipid infusion. Anaesthesia 2006;61:800-1.
37. Spence AG. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anesthesiology
2007;107:516-7.
38. Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity.
Acad Emerg Med 2006;13:134-9.
39. Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity.
Ann Emerg Med 2007;49:178-85, 85 e1-4.
40. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL, Henretig
FM. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after
overdose of bupropion and lamotrigine. Ann Emerg Med 2008;51:412-5, 5 e1.
41. Weinberg G, Di Gregorio G, Hiller D, Hewett A, Sirianni A. Reversal of haloperidol-induced cardiac arrest
by using lipid emulsion. Ann Intern Med 2009;150:737-8.
42. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu, AH. Partition constant and volume of distribution as
predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clinical Toxicol 2011;49:801-9
43. Weinberg GL. Lipid resuscitation: More than a sink. Crit Care Med 2012;40:2521-2523.Di Gregorio G,
Schwartz D, Ripper R, Kelly K, Feinstein DL, Minshall RD, Massad M, Ori C,
44. Kuo I, Akpa BS.Validity of the Lipid Sink as a Mechanism for the Reversal of Local Anesthetic Systemic
Toxicity: A Physiologically Based Pharmacokinetic Model Study. Anesthesiology 2013; 118:1350-61.
45. Weinberg GL. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-
induced cardiac arrest. Crit Care Med 2009;37:993-9.
46. Weinberg GL, Di Gregorio G, Ripper R, Kelly K, Massad M, Edelman L, Schwartz D, Shah N, Zheng S,
Feinstein DL. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose.
47. Mayr VD, Mitterschiffthaler L, Neurauter A, Gritsch C, Wenzel V, Muller T, Luckner G, Lindner KH,
Strohmenger HU. A comparison of the combination of epinephrine and vasopressin with lipid emulsion in a
porcine model of asphyxial cardiac arrest after intravenous injection of bupivacaine. Anesth Analg
2008;106:1566-71.
48. Hicks SD, Salcido DD, Logue ES, Suffoletto BP, Empey PE, Poloyac SM, Miller DR, Callaway CW,
Menegazzi JJ. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a
swine model of bupivacaine-induced cardiac arrest. Anesthesiology 2009;111:138-46.

110
Page 8
49. Hiller DB, Gregorio GD, Ripper R, Kelly K, Massad M, Edelman L, Edelman G, Feinstein DL, Weinberg
GL. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology
2009;111:498-505.
50. Harvey M, Cave G, Prince G, Lahner D. Epinephrine injection in lipid-based resuscitation from bupivacaine-
induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 2010;111:791-6.
51. Mazoit JX, Le Guen R, Beloeil H, Benhamou D: Binding of long-lasting local anesthetics to lipid emulsions.
52. Li Z, Xia Y, Dong X, Chen H, Xia F, Wang X, Dong H, Jin Z, Ding X, Papadimos TJ, Xu X: Lipid
resuscitation of bupivacaine toxicity: Long-chain triglyceride emulsion provides benefits over long- and
medium-chain triglyceride emulsion. Anesthesiology 2011; 115:121928.2.
53. Ruan W, French D, Wong A, Drasner K, Wu, AHB. A mixed (long- and medium-chain) triglyceride lipid
emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion.
Anesthesiology 2012;116:334-9
54. Butterworth JFt. Models and mechanisms of local anesthetic cardiac toxicity: a review. Reg Anesth Pain
Med;35:167-76.
55. Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic
toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med;35:181-7.
56. Drasner K. Local anesthetic systemic toxicity: a historical perspective. Reg Anesth Pain Med 2010;35:162-6.
57. Mulroy MF, Hejtmanek MR. Prevention of local anesthetic systemic toxicity. Reg Anesth Pain Med
2010;35:177-80.
58. Neal JM, Bernards CM, Butterworth JFt, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist
210;35:152-61.
59. Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med 2010;35:188-
93.

Disclosure

227
Page 1
Clinical Pathways for Total Joint Arthroplasty: Essential Components for Success
James R. Hebl, M.D.
Rochester, Minnesota
Clinical Pathways: An Overview
The term clinical pathway refers to a multidisciplinary process of mutual decision-making that results in the
organized care of a well-defined group of patients during a well-defined period of time.[1, 2] Clinical pathways
were first introduced in the 1980s when escalating medical costs pressured physicians to decrease resource
utilization without jeopardizing patient safety or clinical outcomes. At that time, pathways were typically
procedure-specific (e.g., coronary artery bypass grafting, total knee arthroplasty) and tailored to a specific
institution.[3, 4] As a result, tremendous variability often existed from one institutional clinical pathway to another,
making clinical comparisons between pathways and formal scientific study exceedingly difficult.
Despite this variability, it is generally agreed upon that clinical pathways provide several distinct advantages. These
include the ability to (1) provide coordinated care between departments and across patient care units; (2) standardize
patient care and reduce hospital length-of-stay; (3) convert typical inpatient (i.e., same-day admission) procedures to
outpatient (i.e., same-day discharge) procedures; (4) prompt change in the care process to better emphasize patient
outcomes and cost containment; (5) control hospital costs; and (6) serve as a marketing tool with the public or with
third-party payers.[5]
Despite these challenges, this review will summarize the important components of a successful clinical pathway and
attempt to evaluate the impact of differing clinical pathways on major perioperative outcomes after total joint
arthroplasty. Perioperative outcomes that will be evaluated include postoperative complications, hospital length-of
stay, clinical outcomes, and medical costs.
Clinical Pathway Components
Effective clinical pathways for major orthopedic surgery include the coordination and standardization of several
patient care activities during the pre-, intra-, and postoperative period. Essential components of some of the most
effective orthopedic clinical pathways are listed in Table 1.
Preoperative Patient Education
Major orthopedic surgery can be a stressful and anxiety-provoking experience for most patients. Bondy and
colleagues [6] examined the effect of anesthesia patient education on preoperative anxiety and found that a detailed
patient education program may have several beneficial effects. Preoperative patient education may significantly
relieve patient anxiety and emotional stress by providing a better understanding of the perioperative process (e.g.,
preoperative evaluation, hospital admission process, anesthetic options, expected clinical course) and establishing
clear expectations with regard to hospital length-of-stay and the discharge process (e.g., dismissal to home vs.
rehabilitation swing-bed vs. nursing home). Because patients have a better understanding of the perioperative
process, they will often present for surgery with increased confidence in the therapeutic plan and a willingness to
more actively participate in their care. Increased participation often results in greater patient satisfaction and
potentially improved perioperative outcomes. However, the extent to which patient education influences
postoperative outcomes is somewhat unclear.[7-9] McDonald and colleagues [8] demonstrated that preoperative
patient education may result in a modest benefit in preoperative anxiety. However, this benefit failed to persist on
Postoperative Day (POD) 2 or at the time of hospital discharge. A review of the Cochrane Database on this topic
fails to demonstrate that preoperative patient education has a significant impact on postoperative clinical outcomes
(e.g., postoperative pain, functional outcomes, hospital length-of-stay) in patients undergoing total hip or total knee
arthroplasty.

227
Page 2
Multimodal Analgesia
Patients undergoing total knee and total hip arthroplasty experience significant postoperative pain.[10] Severe pain
occurs in 60% of patients and moderate pain in up to 30% of patients undergoing total knee arthroplasty. Failure to
provide adequate analgesia may impede early physical therapy and rapid rehabilitation,[11] which are both
important factors for maintaining joint range of motion and facilitating hospital discharge.[12] In an effort to avoid
many of the side effects commonly associated with opioid-induced analgesia, clinicians have begun adopting
multimodal therapeutic regimens. Multimodal analgesia has become an important concept in the field of modern
pain management.[12-17] The concept is designed to combat pain perception along several pathways of signal
transmission, including the surgical site and surrounding tissues, local sensory nerves, and central nervous system.
Advantages include superior analgesia secondary to the synergistic effects of multiple agents acting via different
pathways, the ability to limit parenteral opioid administration, and minimizing opioid-related side effects. Several
investigations have demonstrated the beneficial effects of multimodal analgesia,[14-16] including its value in
patients undergoing major orthopedic joint replacement surgery.[17-24]

Table 1. Essential Clinical Pathway Components

Preoperative
Preoperative patient education program
Appropriate management of preoperative pain and psychological symptoms (fear, anxiety, depression)
Intraoperative
Development of a comprehensive multimodal analgesic regimen
The use of peripheral nerve blockade and continuous perineural catheters
Postanesthesia Care Unit (PACU) algorithms for the management of acute postoperative pain
Postoperative
Standardized method of pain assessment on the nursing floors and pain score documentation within the medical
record
Early and accelerated rehabilitation regimen
Development of an integrated and multidisciplinary Acute Pain Service
Staff education regarding the importance of pain management
Written protocols for acute postoperative pain management

Several medications may be used as part of a multimodal analgesic pathway. Specifically, the use of
acetaminophen,[25] non-steroidal anti-inflammatory agents,[26] selective cyclooxygenase-2 inhibitors,[18]
pregabalin,[21] and ketamine,[22] have all been shown to have analgesic benefits in patients undergoing joint
replacement surgery. Most experts recommend using multiple agents during the pre- and postoperative period in
small quantitative doses to maximize the analgesic effect while minimizing associated side effects. Documented
benefits include superior postoperative analgesia,[18, 22, 25, 26] reduced supplemental opioid requirements, [18, 21,
22, 25, 26] fewer opioid-related side effects,[13, 18] improved joint range-of-motion,[18, 21] fewer postoperative
sleep disturbances,[18] shorter time to achieve hospital discharge criteria,[21] improved functional mobility,[22] and
a lower incidence of chronic neuropathic pain.[21]

Finally, poorly controlled acute postoperative (i.e., nociceptive) pain may contribute to the development of chronic
neuropathic pain or complex regional pain syndrome after total joint arthroplasty.[27] Nikolajsen and colleagues
examined the Danish Hip Arthroplasty Registry and found that 12% of patients continue to experience moderate-to-
severe pain 12-18 months after surgery.[28] Similarly, up to 13% of total knee arthroplasty patients may experience
moderate-to-severe pain 12-months after surgery.[29] Additional risk factors for the development of chronic
postoperative pain include preoperative pain for greater than 1-month, an increased intensity of preoperative pain,
and a patient history of preoperative fear, anxiety or depression.[29, 30] Poorly controlled postoperative pain has
also been shown to impede global recovery and lower the reported quality of life 6-months after surgery.[31]
Therefore, clinical pathways that integrate (1) a comprehensive multimodal analgesic regimen to adequately manage
pre- and postoperative pain; and (2) a comprehensive psychiatric program to manage preoperative psychological
symptoms may have a significant benefit in improving long-term clinical and psychiatric outcomes.

227
Page 3
Peripheral Nerve Blockade and Continuous Perineural Catheters
Many treatment regimens for managing severe postoperative orthopedic pain include significant doses of parenteral
opioids. These treatment regimens are commonly associated with significant opioid-related side effects such as
sedation, nausea, vomiting, ileus, and urinary retention that can adversely effect patient outcomes and prolong
hospital length-of-stay.[19] Therefore, clinical pathways that minimize (or eliminate) opioid administration may
significantly reduce opioid-related side effects and improve postoperative patient outcomes.

The integration of regional anesthesia and peripheral nerve blockade into clinical pathways for orthopedic surgery is
an essential step to minimize opioid use and improve perioperative outcomes. Both single-injection [32-35] and
continuous [36-40] peripheral nerve block techniques have been shown to provide superior analgesia, reduce
supplemental opioid requirements, decrease opioid-related side effects, and improve functional outcomes after total
joint arthroplasty. In a recent meta-analysis of 19 articles and 603 patients, Richman and colleagues [41] also
demonstrated that patients receiving continuous peripheral nerve blockade have superior analgesia, fewer opioid-
related side effects (nausea, vomiting, pruritus, sedation), and improved patient satisfaction when compared to
traditional intravenous opioids alone. Although single-injection techniques have been shown to be superior to
placebo or systemic analgesia [32-35], comparison studies have shown that single-injection blocks fail to provide
the extended benefits of continuous perineural catheters.[37, 42, 43] Continuous peripheral nerve block techniques
have also been shown to have similar analgesia but a more desirable side effect profile when compared to
epidural analgesia.[44] A recent review by Fowler and colleagues [44] demonstrated that patients receiving
peripheral nerve blocks had less urinary retention and fewer episodes of postoperative hypotension when compared
to patients receiving neuraxial techniques.

A primary concern regarding the use of peripheral nerve blockade is the risk of neurologic complications.
Barrington and colleagues [45] recently performed a prospective audit of more than 7,000 peripheral nerve blocks
performed at 9 Australian hospitals. Overall, they identified a neurologic injury rate of 0.5%. However, only 10%
of these injuries were attributed to peripheral nerve blockade suggesting that the vast majority of perioperative nerve
injuries have a non-anesthesia related etiology. The nerve injury rate attributed to peripheral nerve blockade was
found to be 0.04% ! a rate similar to other large-scale investigations.[46, 47] Jacob and colleagues [48] have also
demonstrated that neither the type of intraoperative anesthesia (general versus neuraxial) nor the use of peripheral
nerve blockade was associated with an increased risk of perioperative nerve injury in 12,329 patients undergoing
total knee arthroplasty. Rather, bilateral surgical procedures and total tourniquet time were found to be associated
with an increased risk of nerve injury.[48]

Standardized Pain Assessment and Documentation, Pain Management Protocols and Staff Education
In 2001, the Joint Commission declared pain as the Fifth Vital Sign and instituted Pain Management Standards for
accredited ambulatory care facilities, behavioral health care organizations, critical access hospitals, home care
providers, hospitals, office-based surgery practices, and long-term care providers.[49] The standard requires health
care providers to (1) Appropriately assess and manage pain; (2) Document pain management interventions and
subsequent reassessments; (3) Perform pain screenings during initial patient assessments; and (4) Educate patients
and their families about pain management. Benhamou [50] and Fletcher [51] report that similar guidelines and
recommendations have been put forward by the Royal College of Surgeons, the French Ministry of Health, the
French Society of Anesthesia and Intensive Care, the European Task Force on Pain Management, and the
International Association for the Study of Pain. The overwhelming consensus is that each of these interventions
should be considered essential components to any clinical pathway designed to optimize pain management and
patient care. Despite these recommendations, the literature suggests that pain remains under-treated in both U.S.
[52] and European [53] health care facilities in part, because of a lack of adherence to previously published
standards and guidelines.

Early and Accelerated Rehabilitation
An early and accelerated rehabilitation program should also be integrated into clinical pathways designed for total
hip and total knee arthroplasty patients. A review of the literature suggests that early and accelerated rehabilitation
may have a major impact on improved perioperative outcomes in orthopedic patients.[9, 55] Munin and colleagues
[55] demonstrated that early inpatient rehabilitation resulted in a shorter hospital length-of-stay and a more rapid
attainment of short-term functional outcomes after joint replacement surgery when compared to a delayed
rehabilitation program. Pour and colleagues [9] also examined the impact of an accelerated pre- and postoperative
rehabilitation program versus a standard regimen on functional outcomes after total hip arthroplasty. Patients

227
Page 4
randomized to the accelerated pathway were seen earlier on the day of surgery and more frequently on subsequent
postoperative days (twice daily versus once daily). There was also a greater emphasis on oral analgesics (versus
intravenous patient-controlled analgesia) in patients receiving accelerated rehabilitation. In addition to a shorter
hospital length-of-stay, accelerated pathway patients were able to walk for longer distances, had improved pain
control, and reported higher patient satisfaction at the time of hospital discharge.[9]

Finally, Mahomed and colleagues [56] have demonstrated that rehabilitation after total hip or total knee arthroplasty
does not need to be restricted to the inpatient setting. Home-based rehabilitation programs may provide similar
degrees of postoperative analgesia, functional outcomes, and patient satisfaction at a significantly lower cost when
compared to hospital-based regimens.[56]

Clinical Pathways and Perioperative Outcomes
The goal of most clinical pathways is to provide standardized, evidence-based care to patients in such a way as to
minimize the variability of care provided by individual providers. This process has the potential to significantly
enhance the quality, improve the safety, and reduce the cost associated with surgical procedures. Several clinical
pathways have been reported in the literature for patients undergoing total joint arthroplasty [1, 4, 19, 20, 57-59];
with no two pathways being identical. As a result, comparison of clinical pathways is exceedingly difficult
forcing systematic reviews or meta-analyses that examine the topic to comment on the concept of clinical
pathways versus their individual component parts. Barbieri and colleagues [1] recently performed a systematic
review of clinical pathways used for joint replacement surgery. The review examined 22 studies and included 6,316
patients. The aggregate results demonstrated a significant reduction in postoperative complications (deep venous
thrombosis, pulmonary embolism, manipulation, superficial infection, deep infection, heel decubitus ulcers), a
shorter hospital length-of-stay, and lower hospital costs in patients undergoing clinical pathways versus standard
care.[1] Publications from the University of California Irvine, the University of Utah, and the Mayo Clinic are
described below; and represent typical examples of clinical pathways developed for orthopedic surgical patients.

Clinical Pathways for Total Joint Arthroplasty
Skinner and colleagues [57] performed a retrospective, case-controlled investigation of 102 patients undergoing total
hip or total knee arthroplasty at the University of California Irvine. They compared a multimodal clinical pathway
that incorporated COX-II inhibitors, tramadol, dexamethasone, acetaminophen, and intra-articular bupivacaine to
patients receiving standard management with patient-controlled analgesia and intravenous opioids. Importantly,
the authors did not incorporate regional anesthesia or peripheral nerve blockade as a component of the clinical
pathway. Clinical endpoints were evaluated during POD 1 through 4. For patients receiving the clinical pathway,
opioid requirements were reduced 66% for total hip arthroplasty (POD 2 only) and 68% for total knee arthroplasty
(POD 3 only). Although VAS pain scores were no different among total hip arthroplasty patients, patients
undergoing total knee arthroplasty reported lower VAS pain scores on POD 2 and at the time of hospital discharge.
Implementation of the clinical pathway resulted in no differences in perioperative complications. Hospital length-
of-stay was reduced in only total knee arthroplasty patients undergoing the clinical pathway (4.0 vs. 4.9 days;
P<0.02). [57]

In contrast to clinical pathways not incorporating regional anesthesia [57] multimodal regimens utilizing
peripheral nerve blockade have been shown to consistently reduce hospital length-of-stay, improve perioperative
analgesia with fewer opioid medications, facilitate postoperative rehabilitation, and reduce opioid-related side
effects.[19, 20, 58] Peters and colleagues [58] performed a retrospective analysis of 100 patients undergoing total
hip and total knee arthroplasty at the University of Utah.[58] The clinical pathway included a multimodal analgesic
regimen (sustained-release oxycodone, COX-II inhibitors, and acetaminophen), intraoperative regional anesthesia
with intrathecal opioids, and an ultrasound-guided femoral nerve catheter (total knee arthroplasty patients only) for
extended postoperative analgesia. Prior to wound closure, patients undergoing both total hip and total knee
arthroplasty received <1 mg/kg of 0.25% bupivacaine injected into the deep and subcutaneous tissues by the
orthopedic surgeon. A multimodal oral analgesic regimen was then continued into the postoperative period.
Control patients were managed with intraoperative general or spinal anesthesia (within intrathecal morphine),
continuous femoral nerve blockade (total knee arthroplasty patients only), and postoperative patient-controlled
analgesia with intravenous opioids. Patients receiving the clinical pathway had significantly lower pain scores at
rest on POD 1 and 2, lower opioid requirements, improved ambulation during rehabilitation sessions, and reduced
hospital length-of-stay. There were no differences in perioperative complications when comparing clinical pathway
to control patients. Overall, the investigators concluded that the development and implementation of a

227
Page 5
comprehensive clinical pathway combined with early and aggressive physical therapy improves perioperative
outcomes, shortens hospital length-of-stay, and allows patients to achieved physical therapy goals earlier when
compared to non-clinical pathway patients.[58]

Finally, Hebl and colleagues have described the development and implementation of the Mayo Clinic Total Joint
Regional Anesthesia (TJRA) Clinical Pathway in patients undergoing both minimally-invasive [19] and traditional
[20] total hip and total knee arthroplasty. The TJRA Clinical Pathway incorporates preoperative patient education, a
multimodal analgesic regimen emphasizing peripheral nerve blockade, standardized PACU algorithms, pain
assessments, and medical record documentation, pain management protocols, and a standardized postoperative
physical therapy regimen for patients undergoing total joint arthroplasty. Similar to most clinical pathways, the
TJRA Clinical Pathway was developed by a multidisciplinary group of Mayo Clinic surgeons, anesthesiologists,
pharmacists, nurses, and physical therapy staff based upon their collective experience and exposure to physicians
and practice models outside the institution. Although the basic principles of the pathway have remained unchanged
(e.g., preoperative patient education, multimodal analgesia, peripheral nerve blockade, pain management protocols),
its individual components are continually being evaluated and modified as necessary based upon changes in clinical
practice.

Limitations of Clinical Pathways
Effective perioperative pain management is not without potential consequences. In 2001, the Joint Commission on
Accreditation of Healthcare Organizations (JCAHO) declared pain as the 5
th
vital sign and mandated that pain
management become an integral component of all patient care activities as a condition of hospital accreditation. As
a result, many institutions implemented aggressive pain management protocols that were guided by patient reports
of pain intensity as quantified by a numeric pain scale. Although numeric pains scales may be useful to monitor
pain trends within a given patient, these subjective methods of pain assessment are an extremely poor guide for
directed analgesic management. In fact, because these subjective and often non-reproducible pain scales do not take
into consideration patient comorbidities or associated medication risks, adverse outcomes such as oversedation and
respiratory depression may lead to catastrophic outcomes including death.[70, 76, 77]

Vila and colleagues [78] demonstrated the potential negative impact of implementing a hospital-wide pain
management protocol that treats pain based upon patient self-reports. After implementation of a numeric pain
treatment algorithm, the number of adverse drug reactions secondary to opioid oversedation more than doubled
when compared to pre-implementation values (24.5 vs. 11 adverse events per 100,000 inpatient hospital days;
P<0.001). A decreased level of consciousness preceded 94% of events, emphasizing the importance of careful
clinical assessment and ongoing patient monitoring while managing pain.[78] Overmedication in preparation for an
imaging study,[70] overmedication after discharge from the ICU ,[70] and the first 24 hours after surgery [77]
appear to be the clinical scenarios or time periods in which patients are at greatest risk for respiratory depression and
oversedation.

Finally, clinical pathways that incorporate regional anesthesia and peripheral nerve blockade may increase the
likelihood of residual motor blockade which may impede early mobilization, increase the risk of patient falls, and
prolong hospital length-of-stay.[43, 79-82] Kandasami and colleagues [80] recently reported a fall rate of 2% in
patients undergoing total knee arthroplasty with the use of femoral nerve blockade. Fall-related injuries included
wound dehiscence (n=4) and periprosthetic fracture (n=1). Hospital length-of-stays were extended 10 to 42 days
secondary to complications from the fall. However, it has been argued that residual motor blockade is a
multifactorial phenomenon and cannot be entirely attributed to regional anesthesia. In addition to local anesthetic-
induced quadriceps weakness, it is believed that motor block can occur secondary to surgical pain, muscle spasm,
joint stiffness, swelling, dysesthesias, or other surgical factors.[83] Regardless of the cause, anesthesia providers
need to play their role in minimizing the risk of residual motor blockade in patients undergoing total hip and total
knee arthroplasty. Clinical pathways that incorporate peripheral nerve blockade need to do so in such a way that the
benefits of regional anesthesia are achieved (i.e., identifying the optimal local anesthetic, dose, and concentration);
while the contemporary concerns of delayed rehabilitation, prolonged hospital length-of-stay, and increased hospital
costs are avoided.

227
Page 6
Summary
Total hip and total knee arthroplasty are two of the most commonly performed surgical procedures in the United
States with increased volumes expected over the next several decades. Clinical pathways represent a standardized,
evidence-based approach to patient care designed to enhance the quality, improve the safety, and reduce the cost
associated with surgical procedures. Clinical pathways for total joint arthroplasty have been shown to significantly
improve the perioperative outcomes of patients undergoing joint replacement surgery. Effective clinical pathways
include preoperative patient education, a multimodal analgesic regimen, peripheral nerve blockade, standardized
pain assessment and medical record documentation, pain management protocols, staff education, and early and
accelerated rehabilitation. Potential clinical benefits include superior postoperative analgesia, fewer opioid-related
side effects, earlier ambulation, improved joint range-of-motion, fewer postoperative complications, and reduced
hospital length-of-stays. The financial benefits of clinical pathways include a reduction in both total hospital and
direct medical costs. However, further study is needed to determine precisely which component(s) of a
comprehensive clinical pathway are most active in contributing to these clinical and financial benefits.

References

1. Barbieri A, Vanhaecht K, Van Herck P, et al. Effects of clinical pathways in the joint replacement: a meta-
analysis. BMC Med 2009;7:32.
2. Panella M, Marchisio S, Di Stanislao F. Reducing clinical variations with clinical pathways: do pathways
work? Int J Qual Health Care 2003;15(6):509-521.
3. Kim S, Losina E, Solomon DH, et al. Effectiveness of clinical pathways for total knee and total hip
arthroplasty: literature review. J Arthroplasty 2003;18(1):69-74.
4. Macario A, Horne M, Goodman S, et al. The effect of a perioperative clinical pathway for knee
replacement surgery on hospital costs. Anesth Analg 1998;86(5):978-984.
5. B.A. W, M.L. K. Clinical pathways and the anesthesiologist. Current Anesthesiology Reports 2000;2:418-
424.
6. Bondy LR, Sims N, Schroeder DR, et al. The effect of anesthetic patient education on preoperative patient
anxiety. Regional anesthesia and pain medicine 1999;24(2):158-164.
7. Lin YK, Su JY, Lin GT, et al. Impact of a clinical pathway for total knee arthroplasty. Kaohsiung J Med
Sci 2002;18(3):134-140.
8. McDonald S, Hetrick S, Green S. Pre-operative education for hip or knee replacement. Cochrane Database
Syst Rev 2004(1):CD003526.
9. Pour AE, Parvizi J, Sharkey PF, et al. Minimally invasive hip arthroplasty: what role does patient
preconditioning play? J Bone Joint Surg Am 2007;89(9):1920-1927.
10. Capdevila X, Macaire P, Dadure C, et al. Continuous psoas compartment block for postoperative analgesia
after total hip arthroplasty: new landmarks, technical guidelines, and clinical evaluation. Anesth Analg
2002;94(6):1606-1613, table of contents.
11. Tali M, Maaroos J. Lower limbs function and pain relationships after unilateral total knee arthroplasty. Int J
Rehabil Res 2010;33(3):264-267.
12. Horlocker TT, Kopp SL, Pagnano MW, et al. Analgesia for total hip and knee arthroplasty: a multimodal
pathway featuring peripheral nerve block. J Am Acad Orthop Surg 2006;14(3):126-135.
13. Elia N, Lysakowski C, Tramer MR. Does multimodal analgesia with acetaminophen, nonsteroidal
antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine
offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology
2005;103(6):1296-1304.
14. Fassoulaki A, Triga A, Melemeni A, et al. Multimodal analgesia with gabapentin and local anesthetics
prevents acute and chronic pain after breast surgery for cancer. Anesth Analg 2005;101(5):1427-1432.
15. Jin F, Chung F. Multimodal analgesia for postoperative pain control. J Clin Anesth 2001;13(7):524-539.
16. Straube S, Derry S, McQuay HJ, et al. Effect of preoperative Cox-II-selective NSAIDs (coxibs) on
postoperative outcomes: a systematic review of randomized studies. Acta Anaesthesiol Scand
2005;49(5):601-613.
17. Maheshwari AV, Boutary M, Yun AG, et al. Multimodal analgesia without routine parenteral narcotics for
total hip arthroplasty. Clin Orthop Relat Res 2006;453:231-238.

227
Page 7
18. Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioperative administration of a selective
cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a
randomized controlled trial. Jama 2003;290(18):2411-2418.
19. Hebl JR, Kopp SL, Ali MH, et al. A comprehensive anesthesia protocol that emphasizes peripheral nerve
blockade for total knee and total hip arthroplasty. J Bone Joint Surg Am 2005;87 Suppl 2:63-70.
20. Hebl JR, Dilger JA, Byer DE, et al. A pre-emptive multimodal pathway featuring peripheral nerve block
improves perioperative outcomes after major orthopedic surgery. Regional anesthesia and pain medicine
2008;33(6):510-517.
21. Buvanendran A, Kroin JS, Della Valle CJ, et al. Perioperative oral pregabalin reduces chronic pain after
total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg 2010;110(1):199-207.
22. Remerand F, Le Tendre C, Baud A, et al. The early and delayed analgesic effects of ketamine after total hip
arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg 2009;109(6):1963-
1971.
23. Fischer HB, Simanski CJ, Sharp C, et al. A procedure-specific systematic review and consensus
recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia
2008;63(10):1105-1123.
24. Parvizi J, Miller AG, Gandhi K. Multimodal pain management after total joint arthroplasty. J Bone Joint
Surg Am 2011;93(11):1075-1084.
25. Sinatra RS, Jahr JS, Reynolds LW, et al. Efficacy and safety of single and repeated administration of 1
gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic
surgery. Anesthesiology 2005;102(4):822-831.
26. Silvanto M, Lappi M, Rosenberg PH. Comparison of the opioid-sparing efficacy of diclofenac and
ketoprofen for 3 days after knee arthroplasty. Acta Anaesthesiol Scand 2002;46(3):322-328.
27. Cousins MJ, Power I, Smith G. 1996 Labat lecture: pain--a persistent problem. Regional anesthesia and
pain medicine 2000;25(1):6-21.
28. Nikolajsen L, Brandsborg B, Lucht U, et al. Chronic pain following total hip arthroplasty: a nationwide
questionnaire study. Acta Anaesthesiol Scand 2006;50(4):495-500.
29. Brander VA, Stulberg SD, Adams AD, et al. Predicting total knee replacement pain: a prospective,
observational study. Clin Orthop Relat Res 2003(416):27-36.
30. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors.
Anesthesiology 2000;93(4):1123-1133.
31. Peters ML, Sommer M, de Rijke JM, et al. Somatic and psychologic predictors of long-term unfavorable
outcome after surgical intervention. Ann Surg 2007;245(3):487-494.
32. Allen HW, Liu SS, Ware PD, et al. Peripheral nerve blocks improve analgesia after total knee replacement
surgery. Anesth Analg 1998;87(1):93-97.
33. Wang H, Boctor B, Verner J. The effect of single-injection femoral nerve block on rehabilitation and length
of hospital stay after total knee replacement. Regional anesthesia and pain medicine 2002;27(2):139-144.
34. Szczukowski MJ, Jr., Hines JA, Snell JA, et al. Femoral nerve block for total knee arthroplasty patients: a
method to control postoperative pain. J Arthroplasty 2004;19(6):720-725.
35. YaDeau JT, Cahill JB, Zawadsky MW, et al. The effects of femoral nerve blockade in conjunction with
epidural analgesia after total knee arthroplasty. Anesth Analg 2005;101(3):891-895, table of contents.
36. Edwards ND, Wright EM. Continuous low-dose 3-in-1 nerve blockade for postoperative pain relief after
total knee replacement. Anesth Analg 1992;75(2):265-267.
37. Singelyn FJ, Deyaert M, Joris D, et al. Effects of intravenous patient-controlled analgesia with morphine,
continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee
rehabilitation after unilateral total knee arthroplasty. Anesth Analg 1998;87(1):88-92.
38. Ganapathy S, Wasserman RA, Watson JT, et al. Modified continuous femoral three-in-one block for
postoperative pain after total knee arthroplasty. Anesth Analg 1999;89(5):1197-1202.
39. Kaloul I, Guay J, Cote C, et al. The posterior lumbar plexus (psoas compartment) block and the three-in-
one femoral nerve block provide similar postoperative analgesia after total knee replacement. Can J
Anaesth 2004;51(1):45-51.
40. Siddiqui ZI, Cepeda MS, Denman W, et al. Continuous lumbar plexus block provides improved analgesia
with fewer side effects compared with systemic opioids after hip arthroplasty: a randomized controlled
trial. Regional anesthesia and pain medicine 2007;32(5):393-398.
41. Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain
control to opioids? A meta-analysis. Anesth Analg 2006;102(1):248-257.

227
Page 8
42. Biboulet P, Morau D, Aubas P, et al. Postoperative analgesia after total-hip arthroplasty: Comparison of
intravenous patient-controlled analgesia with morphine and single injection of femoral nerve or psoas
compartment block. a prospective, randomized, double-blind study. Regional anesthesia and pain medicine
2004;29(2):102-109.
43. Ilfeld BM, Ball ST, Gearen PF, et al. Ambulatory continuous posterior lumbar plexus nerve blocks after hip
arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology
2008;109(3):491-501.
44. Fowler SJ, Symons J, Sabato S, et al. Epidural analgesia compared with peripheral nerve blockade after
major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth
2008;100(2):154-164.
45. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary results of the Australasian Regional Anaesthesia
Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and
other complications. Regional anesthesia and pain medicine 2009;34(6):534-541.
46. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia: results of a
prospective survey in France. Anesthesiology 1997;87(3):479-486.
47. Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: The SOS
Regional Anesthesia Hotline Service. Anesthesiology 2002;97(5):1274-1280.
48. Jacob AK, Mantilla CB, Sviggum HP, et al. Perioperative nerve injury after total knee arthroplasty:
regional anesthesia risk during a 20-year cohort study. Anesthesiology 2011;114(2):311-317.
49. Commission J. Pain Management Standards. 2001; Available at:
http://www.jointcommission.org/pain_management/. Accessed July 1, 2011.
50. Benhamou D, Berti M, Brodner G, et al. Postoperative Analgesic THerapy Observational Survey
(PATHOS): a practice pattern study in 7 central/southern European countries. Pain 2008;136(1-2):134-141.
51. Fletcher D, Fermanian C, Mardaye A, et al. A patient-based national survey on postoperative pain
management in France reveals significant achievements and persistent challenges. Pain 2008;137(2):441-
451.
52. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey
suggest postoperative pain continues to be undermanaged. Anesth Analg 2003;97(2):534-540, table of
contents.
53. Strohbuecker B, Mayer H, Evers GC, et al. Pain prevalence in hospitalized patients in a German university
teaching hospital. J Pain Symptom Manage 2005;29(5):498-506.
54. Harmer M, Davies KA. The effect of education, assessment and a standardised prescription on
postoperative pain management. The value of clinical audit in the establishment of acute pain services.
Anaesthesia 1998;53(5):424-430.
55. Munin MC, Rudy TE, Glynn NW, et al. Early inpatient rehabilitation after elective hip and knee
arthroplasty. Jama 1998;279(11):847-852.
56. Mahomed NN, Davis AM, Hawker G, et al. Inpatient compared with home-based rehabilitation following
primary unilateral total hip or knee replacement: a randomized controlled trial. J Bone Joint Surg Am
2008;90(8):1673-1680.
57. Skinner HB, Shintani EY. Results of a multimodal analgesic trial involving patients with total hip or total
knee arthroplasty. Am J Orthop (Belle Mead NJ) 2004;33(2):85-92; discussion 92.
58. Peters CL, Shirley B, Erickson J. The effect of a new multimodal perioperative anesthetic regimen on
postoperative pain, side effects, rehabilitation, and length of hospital stay after total joint arthroplasty. J
Arthroplasty 2006;21(6 Suppl 2):132-138.
59. Salinas FV, Liu SS, Mulroy MF. The effect of single-injection femoral nerve block versus continuous
femoral nerve block after total knee arthroplasty on hospital length of stay and long-term functional
recovery within an established clinical pathway. Anesth Analg 2006;102(4):1234-1239.
70. Lucas CE, Vlahos AL, Ledgerwood AM. Kindness kills: the negative impact of pain as the fifth vital sign.
Journal of the American College of Surgeons 2007;205(1):101-107.
76. Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J
Surg 2003;186(5):472-475.
77. Taylor S, Kirton OC, Staff I, et al. Postoperative day one: a high risk period for respiratory events.
American journal of surgery 2005;190(5):752-756.
78. Vila H, Jr., Smith RA, Augustyniak MJ, et al. The efficacy and safety of pain management before and after
implementation of hospital-wide pain management standards: is patient safety compromised by treatment
based solely on numerical pain ratings? Anesth Analg 2005;101(2):474-480, table of contents.

227
Page 9
79. Ilfeld BM, Le LT, Meyer RS, et al. Ambulatory continuous femoral nerve blocks decrease time to
discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked, placebo-
controlled study. Anesthesiology 2008;108(4):703-713.
80. Kandasami M, Kinninmonth AW, Sarungi M, et al. Femoral nerve block for total knee replacement - a
word of caution. Knee 2009;16(2):98-100.
81. Klein SM, Nielsen KC, Greengrass RA, et al. Ambulatory discharge after long-acting peripheral nerve
blockade: 2382 blocks with ropivacaine. Anesth Analg 2002;94(1):65-70, table of contents.
82. Williams BA, Kentor ML, Bottegal MT. The incidence of falls at home in patients with perineural femoral
catheters: a retrospective summary of a randomized clinical trial. Anesth Analg 2007;104(4):1002.
83. Barrington MJ, Olive D, Low K, et al. Continuous femoral nerve blockade or epidural analgesia after total
knee replacement: a prospective randomized controlled trial. Anesth Analg 2005;101(6):1824-1829.

Disclosure

233
Page 1
Multimodal Analgesia for Perioperative Pain Management
May L. Chin, M.D. Washington, D.C.
Introduction
A satisfying and potentially cost efficient perioperative experience includes optimal perioperative pain control and
minimal side effects from anesthetic and analgesic drugs.
1
We have the skills, as perioperative physicians, to
facilitate the recovery and discharge of both inpatients and outpatients after surgery. Although opioids have
traditionally been the analgesic of choice for postoperative pain control, monotherapy using opioid analgesics alone
is often inadequate and may be associated with significant side effects.
2
Multimodal analgesia was coined 15 to
20 years ago and describes the combination of pharmacologically different analgesics for additive or synergistic
effects in the control of postoperative pain.
3
This lecture will review the evidence on 1) the current understanding of the pathophysiology of surgical pain, 2)
adjuvant analgesics that can be used to optimize postoperative pain control and 3) clinical outcomes using
multimodal techniques.
Nociception, Sensitization and Neuronal Plasticity
Tissue injury and inflammation result in the release of chemical mediators which activate high threshold
nociceptors, A delta and C fibers. With peripheral sensitization the threshold for nociceptor firing is diminished
resulting in amplication of signaling from the periphery. Non noxious stimuli now elicit pain (allodynia) and a
painful stimulus produces an exaggerated pain response (hyperalgesia). The signals from the periphery enter the
central nervous system in dorsal horn of the spinal cord where complex processing of the signals occur. The
nociceptive signals from the periphery are modulated within the spinal cord and by descending excitatory and
inhibitory mechanisms. The result of this complex interplay is ultimately transmitted to areas in the brain involved
with sensory, motor, autonomic and emotional processing, resulting in the perception of pain. With surgical trauma
and continuous nociceptive input from the periphery, the dorsal horn neurons become more excitable. The receptive
field properties of these neurons expand such that low threshold A beta mechanoreceptors which normally do not
produce painful sensations now do so. These changes ultimately result in a state of hypersensitivity called central
sensitization, in which the nervous system demonstrates an enhanced response to noxious stimulation.
4

Tolerance and hyperalgesia
Repeated C fiber stimulation leads to central sensitization and hyperalgesia. The development of hyperalgesia
involves activation of excitatory amino acids which lead to intracellular events and nitric oxide production.
Activation of the mu receptor by opioids ironically also enhances NMDA receptor activation through similar
intracellular events, resulting in reduced potency of the opioid.
5
These events are thought to play a role in the
development of tolerance to morphine suggesting that neural mechanisms leading to hyperalgesia and tolerance both
involve NMDA receptor activation.
5, 6

Targets for adjuvant analgesics
The main contributors to sensitization and pain include the NMDA receptors, sodium channels, calcium channels,
descending modulation via serotonergic pathways, noradrenergic systems that activate alpha 2 adrenergic receptors,
prostaglandins, cytokines and inflammatory mediators.
N-Methyl-D-aspartate (NMDA) receptor antagonists
NMDA receptors are activated by the excitatory neurotransmitter glutamate in the presence of tissue injury.
Consequently, the NMDA receptor plays a major role in pain processing in the spinal cord whereby receptor
activation results in a hyperexcitable state of the nervous system and increased pain. NMDA antagonists may
alleviate pain by the inhibition of central sensitization.
7
The NMDA receptor is a ligand gated ion channel permeable

233
Page 2
to calcium, potassium and sodium. At resting membrane potential, the NMDA receptor is blocked by a magnesium
ion which is removed on depolarization allowing glutamate to activate the receptor.
8
The NMDA receptor is
composed of several subunits. Some of these subunits are involved with CNS function; therefore an NMDA
antagonist may produce undesirable psychotomimetic effects, memory impairment, ataxia and uncoordinated motor
function.
7

Ketamine is an anesthetic agent that has been in clinical use for almost five decades. The risk of unpleasant CNS
side effects such as hallucinations has discouraged widespread use of ketamine in anesthesia. However there is
renewed interest in ketamine as an NMDA antagonist in the treatment of pain, especially with the understanding of
the role of the NMDA receptor in neuronal hyperexcitability. Ketamine is a non-competitive antagonist that binds
to the phencyclidine binding site of the NMDA receptor. It is available in as racemic ketamine which contains
equimolar amounts of S (+) and R (-) and as the S (+) stereoisomer which is twice as potent. The S (+) ketamine has
four times greater affinity for the NMDA receptor than the R (-) ketamine (5Mao). Ketamine has an elimination
half-life of 80 to 180 minutes. The metabolite nor-ketamine is one third as potent and has a longer halflife and may
contribute to the prolonged analgesic action of ketamine.
8

Providing adequate analgesia for chronic pain patients who are opioid dependent has always been challenging. The
perioperative use of ketamine has been reported to be helpful in these circumstances despite the lack of well
conducted studies. There are several systematic qualitative and quantitative reviews of randomized trials on the use
of ketamine in perioperative pain management.
6, 9, 10,11,12,13
The reviews collectively reported on large numbers of
patients worldwide but several criticisms were noted. In particular, there were large variations in clinical settings,
the trials were relatively small, and different ketamine regimens and various routes of administration were utilized.
Most of the studies reported reduced pain and analgesic consumption immediately and beyond the duration of action
of ketamine when administered in the perioperative period. A small (sub anesthetic) dose of ketamine was noted to
be safe and afforded opioid sparing but the reviews differed on whether opioid related side effects were decreased.
The optimal timing for perioperative administration of ketamine is not clearly defined. Various dosing regimens
have reported effective analgesia with ketamine given in various combinations of dosing such as preincision,
intraoperative, at wound closure and continuing for 48 to 72 hours postoperatively.
14, 15,16,17,18

Recent efforts looking at the perioperative use of ketamine include prospective, randomized, double blinded trials in
patients undergoing total hip arthroplasty in one
19
and major spine surgery in the other.
20
Both demonstrated
reduction in opioid use and decreased opioid consumption in opioid dependent patients with chronic pain. Pain was
decreased at six months in those who received ketamine undergoing major spine surgery. The opioid dependent
patients who underwent spine surgery received an initial dose of ketamine 0.5 mg/kg at induction followed by 10
mcg/kg/min infusion prior to incision and terminated upon closure. The patients for hip arthroplasty did not have a
history of high opioid use. They also received ketamine 0.5 mg/kg at induction followed by an infusion for 24 hours
at 2 mcg/kg/min.

An opioid administered by intravenous patient controlled analgesia (IV PCA) may be prescribed in the postoperative
period in addition to ketamine. Although reports on the effectiveness were conflicting
6,12
a large prospective study
of over one thousand patients found the combination of ketamine and morphine in IV PCA to be safe on the general
nursing floor.
21
The same study also reported low pain scores and high patient satisfaction. In a randomized double
blinded study, the administration of a small dose of ketamine at 250 mcg/kg (in addition to morphine), produced
immediate and sustained analgesia in those patients resistant to morphine in the post-anesthesia care unit (PACU).
22

Patients who received ketamine reported better pain scores, a better feeling of well being and wakefulness, higher
oxygen saturation. They had minimal nausea and vomiting or ketamine related side effects.

Memantine is a long acting oral NMDA antagonist which is FDA approved for use in patients with Alzheimers
disease. Case reports describe use for chronic pain as in phantom limb pain and opioid tolerant cancer patients.
23, 24,
25

Amantadine, another NMDA antagonist is available for both oral and parenteral delivery. It is primarily prescribed
for Parkinsons disease, dementia and spasticity. Perioperative use has had mixed results; one study showed
parenteral amantadine to be ineffective in postoperative analgesia
26
another reported decreased postoperative opioid
use.
27

233
Page 3
Dextromethorphan exhibits NMDA receptor antagonist property and a weak affinity for the mu opioid receptor. It
is commonly prescribed as an antitussive agent is associated with few side effects. Clinical studies indicated that the
administration of preoperative oral dextromethorphan resulted in an attenuated response to tourniquet pain
28
and that
pre incisional dextromethorphan reduced postoperative morphine requirements.
29
However, a systematic review of
the use of dextromethorphan in postoperative pain control did not report consistent analgesic or opioid sparing
effects of the drug.
30
The authors were unable to recommend a dosing regimen for the drug nor could they
recommend routine clinical use of dextromethorphan for postoperative pain control.

Voltage Gated Calcium Channel Blockers
In the postoperative patient, surgical trauma may lead to peripheral and central sensitization resulting in
hyperalgesia and allodynia seen as movement evoked pain. Several recent reviews on the use of anticonvulsants in
the postoperative period report opioid sparing effects, improvement in function and anxiolysis.
31,32,33,34,35,36

Gabapentin and Pregabalin are structural analogs of the inhibitory neurotransmitter gamma-amino butyric acid
(GABA), and both bind to alpha 2 delta subunits of voltage dependent calcium ion channels to produce
antihyperalgesic effects.
37,38
A randomized placebo controlled double blinded study in healthy volunteers showed
that gabapentin enhanced the analgesic effect of morphine.
39
Others have demonstrated that a single dose of 1200
mg oral gabapentin given preoperatively decreased opioid requirements and improved pain scores both at rest and
with movement.
40,41,42
Perioperative administration of pregabalin has been shown to decrease opioid consumption
and reduce side effects related to opioids.
43
Further studies however are needed to identify the anticonvulsant with
the best therapeutic profile, the optimal dose and duration of use, the prevention of persistent surgical pain, and the
patient population that would benefit most from this adjuvant analgesic.

Serotonin and Norepinephrine
Descending inhibitory pathways in the central nervous system modulate the perception of pain through actions of
serotonin and norepinephrine. Serotonin (5-hydroxytryptamine) is a monoamine neurotransmitter involved in pain
processing. There are several different 5-HT receptor types such that serotonin can inhibit or facilitate nociceptive
transmission. Serotonin and norepinephrine reuptake inhibitor drugs (SNRI) produce anti nociception and have been
used in the treatment of certain chronic pain states.
44
In an acute pain study, patients undergoing knee replacement
surgery were given Duloxetine before and after surgery. These patients required less morphine in the 48 hours after
knee surgery.
36

Voltage Gated Sodium Channel Blockers
Local anesthetics disrupt nerve conduction by blocking voltage gated sodium channels. Several subtypes of sodium
channels (Nav1.7, Nav1.8, Nav1.9) are highly expressed in nociceptors.
45
The TRPV1 (transient receptor potential
vanilloid 1) also found in nociceptors, and is activated by capsaicin followed by influx of sodium and calcium ions.
Lidocaine analogues acting on TRPV1 channels block sodium channels and may be a future solution to a pain fiber
specific block.
46
Currently local anesthetics provide postoperative relief predominantly with peripheral and
neuraxial analgesia.

Lidocaine is a local anesthetic that may be given intravenously. In the perioperative period administration of
intravenous lidocaine in patients undergoing abdominal surgery has been beneficial, showing faster bowel recovery,
improved analgesia and decreased hospital stay.
47,48,49,50
No beneficial effects were seen in other types of surgery
such as hip arthroplasty, tonsillectomy or coronary bypass surgery.
51.52

Non-Steroidal Anti Inflammatory Drugs (NSAIDS)
Prostaglandins, produced in the periphery in the presence of inflammation and tissue injury, activate peripheral
nociceptors. Spinal neurons may also produce prostaglandins in response to peripheral injury. COX inhibitors
provide analgesia by inhibiting COX mediated production of inflammatory prostaglandins. Centrally, COX
inhibition prevents NMDA and AMPA (alpha amino 3 hydroxy 5 methyl isoxazolpropionic acid) receptor activation
and the development of central sensitization.
53

NSAIDS are commonly prescribed in the perioperative period as part of a multimodal approach to optimize pain
control. Ketorolac is the only parenteral NSAID available in the US and is useful in the immediate postoperative
period. A recent meta analysis
54
reported better pain control and less nausea and vomiting with a single dose of
ketorolac as an adjunct analgesic. However there is no uniform consensus on the optimal dose of ketorolac.
54, 55, and 56

233
Page 4
Non selective NSAID inhibition of prostaglandins can be associated with serious side effects which include gastric
ulceration, renal dysfunction, and bleeding diathesis. Selective COX 2 inhibitors have been associated with fewer
gastrointestinal side effects compared to the non-selective NSAIDS. Although there appears to be little difference in
analgesic efficacy between the two groups
57
others have reported improved postoperative analgesia, decreased
opioid use and opioid related side effects with perioperative use of celecoxib.
58

Nonetheless concern for potential risks of surgical bleeding and impaired bone healing generate controversy
regarding the use of both selective and non-selective NSAIDS in the perioperative period.
59
A meta-analysis of
several randomized controlled trials showed a higher risk for postoperative bleeding after tonsillectomy with
postoperative use of NSAIDS.
60
However, others have disagreed with this analysis, citing differences in the dosing
of the drug, the duration of treatment, poor surgical technique, and that in some patients, the bleeding occurred at a
time when the drug had been eliminated from the body.
61
Spine surgeons are often reluctant to prescribe NSAIDS
in the perioperative period because of concern with impairment in bone healing. Animal and clinical studies suggest
that NSAIDS can potentially inhibit bone formation, healing, and fusion.
59
It is thought that COX 2 inhibitors may
have an advantage since this effect has not been substantiated in humans even though evidence from animal studies
suggest impaired bone healing with COX 2 inhibitors.
62

Acetaminophen
Acetaminophen, also known as paracetamol, has analgesic and antipyretic properties. Even though the mechanism
of action is largely unknown, it has a known safety profile and is used extensively in pediatric population. As an
adjunct analgesic, intravenous acetaminophen 1g given over 24 hours postoperatively was effective for moderate to
severe pain after orthopedic surgery.
63
A meta-analysis of paracetamol, non-steroidal anti-inflammatory drugs and
cyclooxygenase-2 inhibitors show a morphine sparing effect with each group. However, paracetamol may be less
efficacious in decreasing morphine requirements but nsaids are associated with an increased risk of bleeding.
64

Alpha 2 agonists
Alpha 2 agonists produce sedation and analgesia with minimal respiratory depression. There are 3 subtypes of alpha
2 adrenoreceptors that mediate the physiologic functions which produce sedation, analgesia, bradycardia and
sympatholysis. The locus ceruleus is the predominant site for sedation and the spinal cord the main site for
analgesia although peripheral and supra spinal sites are described.
65

Dexmedetomidine, Clonidine
Clonidine is a less selective alpha 2 agonist compared to dexmedetomidine. It has been prescribed for analgesia and
can be administered in several ways, namely: oral, parenteral, transdermal, neuraxial, by intra-articular injection or
injection around peripheral nerves. Dexmedetomidine, a highly selective alpha 2, has a significantly shorter half life
and therefore easily titratable is administered for sedation and analgesia. Dexmedetomidine infusions using small
doses (0.2 or 0.6 mcg/kg/hr) has been shown to produce easily reversible sedation and analgesia, associated with
stable cardio-respiratory function and therefore potentially useful in the intensive care unit and in the immediate
postoperative period.
66

A systematic review and meta-analysis looked at the effectiveness of perioperative use of alpha 2 agonists in almost
1000 out of 1800 patients.
67
Patients receiving clonidine or dexmedetomidine reported decreased postoperative
morphine requirement and pain intensity and had less nausea. However long term effects, i.e. decrease in chronic
postoperative pain is unknown.

Corticosteroids
Surgical trauma leads to inflammatory and stress responses and the production of cytokines which include the
interleukins, tumor necrosis factor (TNF) and chemokines all of which contribute to pain. Corticosteroids inhibit
phospholipase as well as cytokines, TNF and other inflammatory mediators and may be useful in reducing
postoperative pain. A meta-analysis reviewed 2500 patients receiving three different dose range of dexamethasone
with respect to opioid requirements and pain control.
68
Dexamethasone greater than 0.1 mg/kg IV decreased
postoperative pain and opioid requirement. However the resultant hyperglycemia from steroid administration and
risk of wound infection were not studied and the implications of these risks remain unclear.
69

233
Page 5
Outcomes
A Cochrane review on single dose analgesic studies show limitations in providing good pain relief
70
and a
systematic review on the combination of two analgesics shows improved analgesic efficacy compared to either drug
alone.
71
Using adjuvant analgesics in a multimodal approach has been shown to be beneficial in the perioperative
period by reducing opioid requirement, side effects of nausea and vomiting, early recovery of bowel function and
decrease in pain intensity.
57
Some studies have shown pain relief and facilitation of physical rehabilitation one
month out from surgery
19
and some show improved pain three to six months beyond surgery.
20,42
The role of
ketamine in multimodal analgesia continues to be better defined with higher quality studies. More information is
needed from long-term outcome studies, on the minimum effective dose, and the side effect profile of the drug. At
the present time, there is data to support that ketamine may be useful as an adjuvant analgesic in the opioid tolerant
patient with a history of chronic pain although this deserves further studies particularly in the long term benefits and
reduction of chronic postoperative pain.
72

In a recent prospective study, the implementation of a quality management system (QMS) for the treatment of
postoperative pain demonstrated clear benefits. Multimodal analgesia was individualized and the staff educated,
resulting in better pain control, less analgesia related side effects and increased patient satisfaction.
1

Even so, despite knowledge of pain mechanisms and reported benefits of non-opioid analgesics, pain control after
surgery is often reported to be suboptimal.
73
There may be several reasons for this observation: (a) pain control not
targeted to specific surgical procedures.
74
For instance outpatient surgeries such as hemorroidectomy and
tonsillectomy are painful but because patients are discharged home they are usually prescribed less analgesics; (b)
the lack of consistent use of multimodal analgesia techniques;
75,76
and (c) inconsistent assessment of movement
associated pain in postoperative patients.
77,78

Future directions toward improving postoperative pain control include (a) further investigation of the effect of acute
pain and the use of opioid analgesics on the immune system. Acute pain and surgical stress may compromise
immune function including suppression of natural killer (NK) cell activity. Retrospective analyses by some have
reported reduction in cancer recurrence using regional analgesia
79, 80
but others only found an association of less
cancer in patients older than 64 years citing the benefit may depend on the type of tumor;
81
(b) further investigation
into role of preventive analgesia;
82
(c) identifying patients who may be at risk for developing significant pain after
surgery
83, 76, 84
and (d) the use of pharmacogenomics in tailoring effective analgesic therapy.
76

References
1. Usichenko et al. BJA 2013; 110:87-95
2. Stoelting. APSF 2009. Vol 24,No.2:25-26
3. Kehlet et al. Anesth Analg 1993;77:1048-56
4. Woolf. Pain 2011;152:S2-S15
5. Mao et al. Pain 1995;62:259-274
6. Himmelseher et al. Anesthesiology 2005; 102:211-20
7. Petrenko et al. Anesth Analg 2003; 97:1108-16
8. Kohrs et al. Anesth Analg 1998; 87:1186-93
9. Schmid et al. Pain 82 (1999) 111-125
10. McCartney et al. Anesth Analg 2004; 98:1385-400
11. Subramaniam et al. Anesth Analg 2004;99:482-95
12. Elia et al. Pain 2005;113:61-70
13. Bell et al. Acta Anaesthesiol Scand 2005;49:1405-28
14. Zakine et al. Anesth Analg 2008;106:1856-61)
15. Bilgin. J Clin Anesthesia 2005,17:592-97
16. Webb et al. Anesth Analg 2007,104(4):912-917
17. Suzuki et al. Anesthesiology 2006;105(1):111-9
18. Lavand'homme et al. Anesthesiology, 2005;103(4):813-820
19. Remerand. Anesth Analg 2009;109:1963-71
20. Loftus. Anesthesiology 2010;113:639-46
21. Svetick et al. Acta Anesthesiol Scand 2005;49:870-875
22. Weinbroum et al. Anesth Analg 2003; 96:789-95
23. Hackworth et al. Anesth Analg 2008;107:1377

233
Page 6
24. Wiech et al. Anesth Analg 2004;98:408-13
25. Grande et al. Anesth Analg 2008;107:1380
26. Gottschalk et al. Anesth Analg 2001;93:192-6
27. Snijdelaar et al. Anesthesiology 2004;100:134-41
28. Yamashita et al. Anesth Analg 2004; 98:994-8
29. Helmy et al. Anesth Analg 2001; 92:739-44
30. Duedahl et al. Acta Anaesthsiol Scand 2006; 50:1-13
31. Kong et al. BJA 2007;99:775-86
32. Tippana et al. Anesth Analg 2007;104:1545-56
33. Gilron. Can J Anesth 2006;53:562-71
34. Hurley et al. Reg Anesth and Pain Med 2006; Vol. 31, No.3:237-47
35. Dahl et al. Acta Anaesthsiol Scand 2004;48:1130-36
36. Ho et al. Pain 2006; 126:91-101
37. Mao et al. Anesth Analg 2000;91:680-7
38. Gajraj et al. Anesth Analg 2007;105:1805-15
39. Eckhardt et al. Anesth Analg 2000; 91:185-91
40. Turan et al. Anesth Analg 2004; 98:1370-3
41. Dirks et al. Anesthesiology 2002; 97:560-4
42. Fassoulaki et al. Anesth Analg 2002; 95:985-91
43. Jokela et al. Pain 2008;134:106-112
44. Arnold et al. Pain 2005;116:109-18
45. Porrecca. IASP 2012;3-14
46. Ilfield et al. RAPM 2009;34:85-87
47. Kaba et al. Anesthesiology 2007;106:11-8
48. Koppert et al. Anesth Analg 2004;98:1050-5
49. Groudine et al. Anesth Analg 1998;86:253-9
50. Rimback et al. Anesth Analg 1990;70:414-9
51. Martin et al. Anesthesiology 2008;109:118-23
52. McCarthy et al. Drugs 2010;70:1149-63
53. McCrory et al. Anesth Analg 2002; 95:169-76
54. Oliveira et al. Anesth Analg 2012;114:424-33
55. Cepeda et al. Anesthesiology 2005;103:1225-32
56. White et al. Anesth Analg 2012;114:250-54
57. White et al. Anesth Analg 2011;112:323-29
58. Sun et al. Anesth Analg 2008;106:950-58
59. Gilron et al. Anesthesiology 2003; 99: 1198-1208
60. Marret et al. Anesthesiology 2003; 98: 1497-502
61. Dsida et al Anesthesiology 2004; 100:749-51
62. Gajraj. Reg Anesth and Pain Medicine, Vol 28, No.5, 2003:456-65
63. Sinatra et al. Anesthesiology 2005;102:822-31
64. Maund et al. BJA 2011;106:292-7
65. Kamibayashi et al. Anesthesiology 2000;93:1345-9
66. Hall et al. Anesth Analg 2000; 90:699-705
67. Blaudzun et al. Anesthesiology 2012;116:1312-22
68. Oliveira et al. Anesthesiology 2011;115:575-88
69. Turan et al. Anesthesiology 2011;115:457-9
70. McQuay et al. Pain 2012;153:1364-67
71. Ong et al. Anesth Analg 2010;1170-79
72. Angst et al. Anesthesiology 2010;113:514-5
73. Sommer et al. Eur J Anaesth 2008;25:267-74
74. Gerbershagen et al. Anesthesiology 2013;118:934-44
75. Benhamou et al. Pain 2008;136:134-41
76. White et al. Anesthesiology 2010;112:220-5
77. Srikandarajah et al. Pain 2011;152:1734-39
78. Kehlet et al. Pain 2011;152:1699-700
79. Exadakylos et al. Anesthesiology 2006;105:660-4

233
Page 7
80. Biki et al. Anesthesiology 2008;109:180-7
81. Gottschalk. Et al. Anesthesiology 2010;113:27-34
82. Katz et al. Anesth Analg 2011;113:1242-53
83. Werner et al. Anesthesiology 2010;112:1494-1502
84. Caumo et al. Acta Anaesthesiol Scand 2002;46:1265-71

Disclosure

Ultrasound-Guided Regional Anesthesia
Brian D. Sites, M.D. Lebanon, New H ampshire
Ultrasound Objectives:
There are essentially 4 primary objectives of the anesthesiologist conducting an ultrasound-guided nerve block.
1. Unequivocally image the nerve or plexus.
2. Identify collateral structures such as arteries or pleura.
3. Visualize the needle tip as it approaches the target and avoid collateral structures.
4. Confirm effective perineural spread of local anesthetic.
The ability to accomplish these tasks depends significantly upon the operators understanding and interaction with
the ultrasound machine.
Background Terminology:
Ultrasound is defined as sound waves that are at a frequency of 20,000 cycles per second or Hertz (Hz) or higher.
Most transducers used for UGRA are between 4 and 13 million Hz or 4 to 13 megahertz (MHz).
An ultrasound wave is produced when an electrical signal is placed across piezoelectric crystals that force the
crystals to vibrate. This vibration is then conducted through the body. All ultrasound waves are characterized by a
specific wavelength and frequency. The relationship between these variables is c is proportional to

(!)*(f), where c
= the propagation velocity and is presumed to be 1540 m/sec in the human body. Therefore, if c is held constant,
then to increase the frequency of an ultrasound wave, the wavelength would have to proportionately decrease. This
concept is at the core of UGRA since different frequency probes are used for different blocks.
Two additional and important concepts are ultrasound resolution and attenuation. Attenuation is the loss of
ultrasound wave energy as it travels through tissue. Generally, a lower frequency wave will attenuate less at a given
distance in comparison to a higher frequency wave. Thus, the lower frequency ultrasound wave will penetrate
deeper into the patient. Axial resolution, or the ability to identify two or more points in space (one lying in front of
the other), is between one to two wavelengths. This means that the lower frequency (larger wavelength) ultrasound
beam will penetrate deeper but will lack the resolution of the higher frequency and smaller wavelength beam.
Imagine (not image) if all structures reflected ultrasound to the same degree!
This is very interesting theoretical discussion. When ultrasound travels into the body and reflects off of an object,
some of the energy will return to the transducer. When this mechanical energy strikes the transducer, the
piezoelectric crystals vibrate again. This time, however, they convert mechanical energy back into electrical energy.
By convention, the more of this mechanical energy converted, the whiter or more echogenic the structure will
appear. Therefore, the physician identifies structures and pathological conditions by identifying various sine quo
non-shades of grey! If all structures reflected ultrasound to the same degree, all structures would appear the same
shade of grey and we would not have any useful clinical information. It would be like going to the opera and
hearing only one tone for 2 hours. No fun.
239
Page 1
239
Page 2
To be more scientific, targets for UGRA are generated based on the concepts of reflection and impedance.
Impedance can be referred to as the tendency of a medium to conduct ultrasound. When a sound wave travels
through an object and contacts an adjacent object with a different acoustic impedance, a demarcation is formed. An
example would be nerve tissue surrounded by adipose tissue. At these interfaces between objects with different
acoustic impedances, reflection occurs. This is known as Snells law. The larger the difference in acoustic
impedances between structures, the greater the reflection. Interfaces that are highly reflective are displayed as white
or hyperechoic. Examples include fascial planes, bones, and some nerves. Interfaces that weakly reflect ultrasound
waves are darker or hypoechoic. Examples of hypoechoic structures include muscle, fat, and some nerves. Blood
vessels are anechoic and appear black. The fundamental clinical challenge in UGRA is that many of the neural
structures lie in close proximity to other structures that have similar acoustic impedances. Thus, it can be
challenging to make a positive identification because these structures will appear similar and lack a clear acoustic
interface (black on white). The great example of this is the challenge of distinguishing tendon from nerve in the
distal arm or leg. Cardiac imaging is much easier secondary to the clear demarcation between blood filled
chambers (black) on myocardium (whiter).
Basic Imaging Techniques:
Structures of interest can be imaged either in the short-axis (cross-section) or the long-axis. A short-axis view
becomes a long-axis view when the transducer is turned 90 degrees in either direction. In general, regional
anesthesiologists prefer to image nerves and blood vessels in short axis. This is because the operator has a
simultaneous anterior-posterior and lateral-medial perspective. In the long axis view, the lateral-medial perspective
is lost.
Two techniques have emerged in the literature with respect to needle insertion. The needle can be inserted utilizing
the in-plane approach. Here, the needle is inserted parallel to the footprint of the transducer such that it is visualized
in long-axis, allowing full needle visualization. Alternatively, the needle can be inserted perpendicular to the
transducer footprint, generating a short-axis view of the needle. The major drawback to this out-of-plane approach
is that a short-axis view of a block needle appears as a small dot that can be very difficult to see. In addition, the
operator is often unable to confirm the exact location of the needle tip. There are two drawbacks to the in-plane
approach. First, it is likely that the needle will need to travel through more tissue, thus possibly increasing patient
discomfort. Second, given the very thin nature of the ultrasound beam, it can be very challenging to maintain
constant needle imaging throughout the entire procedure.
The ten steps of peripheral UGRA are to (Adopted from ASRA Guidelines
1
):
1. Visualize key landmark structures including muscles, fascia, blood vessels, and bone
2. Identify the nerves or plexus on short axis imaging
3. Confirm normal anatomy or recognize anatomical variation(s)
4. Plan for the safest and most effective needle approach
5. Use the aseptic needle insertion technique
6. Follow the needle under real-time visualization as it is advanced toward the target
7. Consider a secondary confirmation technique, such as nerve stimulation
8. When the needle tip is presumed to be in the correct position, inject a small volume of a test solution
9, Make necessary needle adjustments to obtain optimal perineural spread of local anesthesia
10. Maintain traditional safety guidelines of frequent aspiration, monitoring, patient response, and
assessment of resistance to injection
Systematic and methodical scanning can improve target image quality and needle image quality:
ASRA recommended scanning techniques:
1. Find landmark vascular structure (possibly assisted by color Doppler), bone, or muscle
2. Find nerve or plexus on short-axis imaging (transverse scan)
3. Place machine focus on target structures

239
Page 3
4. Place depth setting at 1 cm deep to target structures
5. Adjust gain, time gain compensation (TGC), and frequency as necessary
6. Initiate the P.A.R.T. maneuvers to optimize image quality

a. PRESSURE: varying degrees of transducer pressure on skin
b. ALIGNMENT: sliding movement of the transducer to define the
lengthwise course of the nerve
c. ROTATION: the transducer is turned in either a clockwise or
counterclockwise direction to optimize the image
d. TILTING: the transducer is tilted in both directions in order to
maximize the angle of incidence of the ultrasound beam with the target nerve

7. Scan anticipated needle trajectory with color Doppler to identify unsuspected vascularity.

Focus

Most ultrasound machines have a focus button. The focus is usually indicated by an icon on the screen that can be
moved up or down by button control. The idea is that when you place the focus of the ultrasound beam over the
target, then the beam is at its narrowest point at this location. The narrow beam results in the best axial and lateral
resolution for a given ultrasound frequency. In practical terms, this means that image will be the sharpest at this
location.

Depth

The scanning depth is set to just 1 cm below the target because this will result in the largest image on the screen as
well optimization of the frame rate. Slower frame rates can blur the image when there is needle, tissue, or
transducer motion. The reason why frame rates improve with depth setting minimization is that the ultrasound
waves are forced to travel less distance, meaning that they will return to the transducer in a shorter period of time.
Given that the definition of frame rate is the frequency (rate) at which an imaging device produces unique
consecutive images, then if you increase the number of images per second (by decreasing depth), the temporal
resolution must improve. This translates into less blurriness with movement, which is a nice added feature to an
ultrasound-guided block.

Gain and Frequency

As mentioned earlier, attenuation refers to the loss of ultrasound energy as it travels into the body. This loss of
energy mostly results from tissue absorption that generates heat. This is why the ultrasound appearance of deeper
structures appears degraded and more hypoechoic. The gain controls on the ultrasound machine try to compensate
for this degradation in the ultrasound image. There is usually an overall gain button that will make the entire image
brighter or darker as well as a set of dials called time gain compensation (TGC). These dials control the gain at
specified depths. The typical settings are to increase the TGC for the deeper aspect of the image and decrease the
TGC for the more superficial component. The frequency of the transducer is also directly related to the degree of
attenuation. The higher the frequency of the ultrasound system, the more attenuation. The general rule is to use the
highest frequency linear transducers for the superficial blocks such as the interscalene and supraclavicular.
Transducers that penetrate deeply tend to be the curved transducers that are made for abdominal and obstetrical
applications. These transducers are great for neuraxial and proximal sciatic blocks. Most transducers can be toggled
between a range of settings for various degrees of penetration. Trial and error is the best recommendation. That is,
when your target is identified, change the scanning frequency (penetration) using the machine interface and see what
generates the best image.

P.A.R.T.

The above ASRA suggestions build on the aforementioned primary opening objectives. The P.A.R.T. maneuvers are
very important for both optimizing the quality of the image for both the needle and target structures. There are no

239
Page 4
simple rules that mandate which one of the maneuvers will work best. Each patient is different and the operator is
encouraged to systematically go through the maneuvers for every procedure.

Color Doppler

This is an amazing technology that helps to distinguish artery from vein as well as unseen vascular structures within
the trajectory of the needle. It is very important to understand a central limitation of Doppler technology. The
Doppler equation accounts for the velocity and directionality of blood. For velocity measurements to be accurate,
the blood flow must be parallel to the ultrasound beam. It turns out that it is a good thing that we are not interested
in velocity measurements, since most of the relationships between our ultrasound beams and blood flows are
perpendicular. Take, for example, the interscalene block. Here we are imaging the carotid and IJ in short axis, so
there is in essence a 90-degree relationship. If you analyze these vascular structures with color Doppler, it may
appear that there is no flow (no color). Given that the patient is unlikely to be dead, this is an artifact error based on
the beam and flow generating a 90-degree relationship. Obviously, we do not need color flow to identify the
carotid. However, many of the branches that could be punctured such as the transverse cervical or lateral circumflex
arteries may be picked up much easier with color Doppler compared to the naked eye. The simple solution to deal
with the above problem is to tilt the transducer through various angles to establish a different angle relationship
between an area of interrogation and the ultrasound beam. Even though the exact velocity measurements will be
inaccurate, all we really care about is establishing that something either is or is not a blood vessel.

Quality Issues:

Although there are many novice behaviors and quality issues associated with UGRA, I would like to emphasize the
need to confirm screen orientation. One of the significant quality compromising behaviors that we have identified at
Dartmouth-Hitchcock Medical Center is confusion over screen orientation with respect to patient anatomy. To
address this, the ASRA initiative on ultrasound-guided regional anesthesia has made these suggestions:

Before needle insertion, each neural structure should be referenced to key landmark structures in the anterior-
posterior and lateral-medial planes. However, because of the bilateral nature of the peripheral nervous system,
variations in patient positioning, differing presets of various ultrasound systems, and the nuances of individual
techniques, it would be difficult to standardize the correlation of sidedness of the screen with an anatomical location.
This is in contrast to transesophageal echocardiography, where, in the transgastric short-axis view of the left
ventricle (for example), the anterior aspect of the left ventricle can be standardized to be on the bottom of the screen.
Therefore, the Joint Committee recommends this simple procedure for correlation of the ultrasound screen with
patient sidedness in any patient position.

1. After the application of the transducer onto the patients skin, the landmark structure or peripheral
nerve is identified. The primary operator states that the top of the ultrasound screen correlates with the
patients skin. To confirm this, pressure is applied with a finger onto the skin. This area should be
visualized being compressed on the ultrasound screen.

2. For patients in any position, the operator states that screen left represents a defined anatomical aspect
of the patient (e.g., cephalad). To confirm this, the primary operator again applies pressure with a
finger at this defined site. A corresponding indentation should be visualized on the left aspect of the
ultrasound screen. If indentation occurs on screen right the operator must turn the transducer 180
degrees. After such a correction, the operator should return to step 1 until correct imaging has been
obtained and confirmed.

I hope this handout helps. If you have any comments or questions, please feel free to email me at
[email protected].

239
Page 5
Reference:
1. Sites BD, Chan, VW, Neal JM, Weller R, Grau T, Koscielniak-Nielsen, ZJ, Ivani, G. The American Society
of Regional Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and Pain
Therapy Joint Committee Recommendations for Education and Training in Ultrasound-Guided Regional
Anesthesia. 2009;34:40-46.

Disclosure

306
Page 1
Upper Extremity Regional Anesthesia: Essentials for Your Practice
Joseph M. Neal, M.D. Seattle, Washington
Upon completion, participants will be able to:
1. Distinguish those techniques that can improve block success
2. Recognize the nuances of local anesthetics and additives used for upper extremity blocks
3. Identify the prevention and treatment of block-related complications
Contemporary data suggest that regional anesthesia for shoulder and arm/hand ambulatory surgery improves early
outcome measures such as analgesia, decreased opioid-related side effects, earlier readiness for discharge, and
reduced frequency of unplanned hospital admission. Continuous perineural catheters consistently improve analgesia,
and may facilitate earlier hospital discharge and rehabilitation after major shoulder surgery. Furthermore, plexus-
based regional anesthetic techniques generally result in superior analgesia as compared to surgeon-placed
subacromial infusion or wound infiltration while avoiding concerns over local anesthetic-induced chondrolysis. This
information is important, because it provides objective data that brachial plexus regional anesthesia can positively
affect outcome in patients undergoing upper extremity surgery.
This refresher course lecture focuses on the selection of approaches to the brachial plexus, techniques to improve
block quality, important pharmacologic considerations, and complications associated with upper extremity neural
blockade. Because of time and space constraints, actual techniques of performing upper extremity blocks will not be
discussed. Participants are referred to classic textbooks and atlases for this information.
APPROACHES TO THE BRACHIAL PLEXUS
Knowledge of surgical site and brachial plexus anatomy combine to determine ones approach to the brachial
plexus. The interscalene and posterior paravertebral approaches are ideally suited for shoulder surgery, but less
appropriate for surgery distal to the elbow because of their propensity to spare the lower trunk (ulnar distribution).
The supraclavicular approach is appropriate for most upper extremity surgery, although shoulder surgery may
require supplemental supraclavicular nerve block. The infraclavicular approach provides anesthesia distal to the
shoulder and is consistently superior to the axillary approach for hand and arm surgery, in part because of its better
propensity for anesthetizing the axillary and musculocutaneous nerves. The axillary approach provides anesthesia
for surgeries of and distal to the elbow, but supplementation of the musculocutaneous nerve is advised if the surgical
field involves the volar radial forearm.
TECHNIQUES THAT IMPROVE BLOCK SUCCESS
Nerve Localization
Despite over a century experience with brachial plexus blockade, studies have failed to identify a superior method to
localize nerves. Indeed, block success (a term that unfortunately encompasses multiple definitions) plateaus at 90-
98% regardless of whether nerves are localized using peripheral nerve stimulation, paresthesia, or in the case of
axillary block, perivascular techniques. When compared to peripheral nerve stimulation, randomized clinical trials
variably show that the use of ultrasound-guided regional anesthesia (UGRA) improves block onset, reduces block
performance time and the number of needle passes, and results in more reliable blockade of the lower trunk via the
interscalene approach. However, rates for surgical readiness and block success are similar. Studies of UGRA have
yet to prove increased safety as compared with other localization techniques.

306
Page 2
Ideal Number of Injections
Regardless of how a nerve is located, the ideal number of injections to optimize block quality is block- and
localization technique-specific. Ultrasound-guided blocks are typically multiple injection techniques that strive to
surround the nerves with local anesthetic. Nerve stimulator-guided proximal approaches to the brachial plexus
interscalene, posterior paravertebral, and supraclavicularachieve reliable blockade after a single injection. As the
brachial plexus architecture begins to diverge into more widely spaced components, the value of increasing the

number of local anesthetic injections becomes evident. Double ultrasound-guided injection leads to faster
supraclavicular block onset. Infraclavicular brachial plexus block is improved with double rather than single
injection, particularly when one of the stimulations involves the posterior cord. A single posterior injection appears
adequate for UGRA techniques. Axillary blocks are improved by using three, but not four, injections. Injecting near
the radial nerve is most important for attaining optimal anesthesia using the axillary approach, while injecting near
the ulnar nerve is least important. Recent studies suggest that a two-injection ultrasound-guided technique (injecting
at the musculocutaneous nerve and at the 6 oclock position below the axillary artery) may be equally efficacious to
a triple-injection nerve stimulation technique.

Continuous Perineural Catheters
Extended analgesia can be accomplished with continuous perineural catheters, but whether the ability of stimulating,
rather than non-stimulating, catheters to ensure perineural proximity translates into actual clinical advantage is
controversial and incompletely studied for upper extremity block. Particularly for painful shoulder surgeries,
continuous perineural catheters provide superior analgesia, limit opioid-related side effects, and improve patient
satisfaction and sleep. This technology has proven useful and safe for outpatients. There is less evidence that
perineural catheters improve economically-sensitive parameters such as earlier return to work, long-term
rehabilitation, or other health-related quality of life measures.

PHARMACOLOGIC CONSIDERATIONS

Local Anesthetics
Local anesthetic selection for upper extremity regional anesthesia is determined primarily by the desired anesthetic
and analgesic duration. There is no inherent advantage of one local anesthetic over another with regard to block
quality, although limited data suggest that ropivacaine infusion preserves motor function better than bupivacaine.
For single-injection brachial plexus blockade, bupivacaine 0.5% is equipotent to ropivacaine 0.75%, which implies
that the advantage of reduced cardiotoxicity with ropivacaine may be offset if an increased mass (concentration x
volume) of ropivacaine is used to overcome its reduced potency. There is no advantage to mixing a long-acting and
an intermediate-acting local anestheticblock onset is similar, but duration is shorter.

While it is intuitive to increase local anesthetic mass to optimize block characteristics, existing evidence suggests
that doing so does not provide clinically relevant improvements when using traditional volume techniques, i.e., 20
mL or greater. Indeed, increasing local anesthetic concentration, volume, or total dose does not hasten block onset,
improve quality, or prolong analgesia. Instead, increased concentration correlates with neurotoxic injury, while
increased mass worsens systemic toxicity in the setting of unintentional intravascular injection. Thus, modifying
local anesthetic characteristics to facilitate neural blockade is ineffective, but conceivably places the patient at
increased risk should nerve injury or intravascular injection occur. Ultrasound-guidance further supports this
concept, as excellent block characteristics are attainable using lower volumes of local anesthetic. However, there is
emerging evidence that block duration may be reduced when extremely low volumes (less than 10 mL) are used.
Particularly in the setting of continuous perineural analgesic techniques, evidence suggests that initial bolus dosing
can be accomplished with relatively low volumes and concentrations of local anesthetic, e.g., 20 mL of 0.375%
ropivacaine for interscalene block, followed by 0.2-0.3% ropivacaine infusion.

Additives
In the absence of continuous perineural techniques, limited prolongation of analgesia is achievable with local
anesthetic additives. Yet despite a myriad of choices, only epinephrine, clonidine, and buprenorphene reliably
prolong blockade from intermediate-acting local anesthetics; they do not significantly affect long-acting local
anesthetics. Epinephrine prolongs peripheral nerve blockade by reducing clearance of the local anesthetic, in
addition to serving as a marker of intravascular injection. Epinephrine 2.5 mcg/mL (1:400,000) achieves nearly the
same block prolongation as 5 mcg/mL (1:200,000), but with less tachycardia and less reduction in peripheral nerve

306
Page 3
blood flow. Clonidine 0.5 mcg/kg prolongs anesthesia and analgesia by 50% for intermediate-acting local
anesthetics, but <20% for long-acting agents (~2 hr prolongation for each). However, clonidine can cause sedation
(NNH 5) or hypotension (NNH 10) and lacks epinephrines ability to signal intravascular injection. Clonidine is
significantly more expensive than epinephrine; it is unclear if one is superior to the other or if indeed their actions
are synergistic. Neither epinephrine nor clonidine improves sensory block quality when used during continuous
infusion. Buprenorphene 0.3 mg prolongs duration of analgesia after axillary block. Dexamethasone has been shown

in limited studies to prolong the duration of mepivacaine analgesia to a degree similar to epinephrine or clonidine
(~50%), but may theoretically increase the risk for nerve injury in diabetic patients. Preliminary data are promising
for block prolongation from dexmedetomidine, but well-controlled human studies are lacking. Other additives
opioids, neostigmine, hyaluronidase, tramadol, and calcium channel blockersserve no useful purpose in brachial
plexus blockade, are reported without comparison to a systemic control group, or are incompletely studied with
regards to neurotoxicity. Alkalinization of intermediate-acting local anesthetics does not accelerate brachial plexus
block onset, despite its usefulness in hastening the onset of epidural block. Moreover, alkalinization has been shown
in animals to actually reduce block duration and intensity.

COMPLICATIONS OF BRACHIAL PLEXUS BLOCKS

Local Anesthetic Systemic Toxicity
Two unique circumstances related to brachial plexus blockade affect local anesthetic systemic toxicity. First,
seizures associated with local anesthetic injection are five times more likely to occur with peripheral nerve block
than with epidural block. Second, brachial plexus approaches are particularly prone to systemic toxicity because
they are often placed near arteries that directly supply the brain, thus seizures can occur after remarkably small doses
of local anesthetic, e.g., 2.5 mg bupivacaine injected into the vertebral artery during the interscalene approach. Case
reports document episodes of local anesthetic systemic toxicity (LAST) despite the use of UGRA, although recent
studies report an overall decrease in the incidence of LAST when ultrasound-guidance is used rather than peripheral
nerve stimulation. In accordance with the ASRA Practice Advisory on Local Anesthetic Systemic Toxicity, lipid
emulsion should be readily available to treat local anesthetic toxicity wherever upper extremity blocks are
performed.

Unintended Destinations of Local Anesthetics

Unintended destinations of local anesthetics can also result in nuisance symptoms such as Horners syndrome from
blockade of the cervicothoracic sympathetic trunk, or hoarseness from blockade of the vagus and/or recurrent
laryngeal nerves. These symptoms dissipate with resolution of local anesthetic blockade.

Needles can be placed unintentionally near the
neuraxis during interscalene block by advancing too
far medial into the epidural, subdural, or subarachnoid
space. The distance from the skin overlying the
interscalene groove to the neuraxis is as little as 23-
35mm. Local anesthetic can also enter the
subarachnoid space if a needle, seemingly placed at
the proper depth, enters a particularly long dural root
sleeve. (Figure 1) When local anesthetic reaches the
neuraxis, high spinal anesthesia or massive epidural
anesthesia develops. If this happens, patients may
present with unexpectedly high and bilateral sensory
and motor block, bradycardia, hypotension, or
asystole. Treatment is the same as for hypotension /
bradycardia following spinal anesthesia, and includes
early epinephrine to increase heart rate, contractility,
and coronary perfusion pressure.

Figure 1. Neal & Rathmell, 2013

306
Page 4

Hypotension / Bradycardia

Inadequate Cerebral Perfusion

Pneumothorax
Pneumothorax can occur with the supraclavicular approach; less so with the interscalene and infraclavicular
approaches. Importantly, symptoms may not become noticeable for 8-12 hours following the block, particularly in
the absence of positive pressure ventilation. Pleuritic chest pain is the most common presenting symptom, not
dyspnea. Development of techniques designed in part to avoid the pleura, such as the plumb bob or subclavian
perivascular approaches, or UGRA, have likely reduced the incidence of pneumothorax significantly, although no
large studies confirm this impression.

Vascular and Muscle Injury
Minor bruising occurs in up to a quarter of patients after axillary block. Serious vascular conditionscompressing
hematoma, vasospasm, or arterial dissectionare rare, but should be considered in patients with postoperative
neurologic impairment. The ASRA Consensus Conference on Anticoagulation and Regional Anesthesia suggests
that deep brachial plexus blocks, e.g., cervical paravertebral or infraclavicular, not be undertaken in anticoagulated
patients. Temporary myotoxicity can happen when local anesthetic, particularly bupivacaine, is infused into muscle.
Awake or sedated patients who undergo interscalene
brachial plexus block and are placed in the beach-
chair position are reported to develop sudden
hypotension and bradycardia in 13-24% of cases.
These hemodynamic changes typically occur about an
hour after block placement. The etiology of this
condition is unclear, but is believed to involve relative
preload deficit (from the sitting position) plus
increased ventricular contractility (from exogenous
and endogenous epinephrine), both combining to
(arguably) activate the Bezold-Jarisch reflex. (Figure
2) Incidence can be reduced with metoprolol pre-
treatment, but not glycopyrrolate.

Rare cases of cerebrovascular accident have
been reported in patients undergoing shoulder
surgery in the beach chair or upright position.
Although not specifically a complication of
upper extremity regional anesthesia,
practitioners should be aware of this
complication, the etiology of which is not
entirely certain, especially its association with
hypotension. Nevertheless, issues of particular
concern include measuring blood pressure at the
appropriate site or performing hydrostatic
calculations to accurately reflect pressure at the
level of the brain (1.33cm from cuff to brain =
1mmHg reduced pressure at the brain). (Figure
3) Care should be taken when inducing
hypotension, especially in patients at risk for
compromised cerebral perfusion.


306
Page 5
Hemidiaphragmatic Paresis

All interscalene blocks and ~50% of supraclavicular blocks result in temporary hemidiaphragmatic paresis (HDP)
secondary to anesthesia of the phrenic nerve. During interscalene anesthesia, a small subset of patients experience
25-32% reduction in pulmonary spirometric values. Pulmonary function is unaffected in healthy volunteers whose
hemidiaphragm is paretic following supraclavicular block, but this may not be the case in patients with
compromised pulmonary function. The incidence and severity of HDP can be reduced, but not completely and
predictably eliminated, when local anesthetic volumes are decreased to 5-10 mL using UGRA. The ultrasound-
guided approach probably blocks the phrenic nerve because of its proximity to the C5 nerve root. (Figure 4) In
general, above the clavicle blocks are relatively contraindicated in patients unable to withstand a ~30% reduction in
pulmonary function. Hemidiaphragmatic paresis following infraclavicular block is rare with the coracoid approach,
but ~25% of patients who undergo the (more medial) vertical infraclavicular approach develop HDP with an
accompanying 30% reduction in spirometric values.

Figure 4 Neal & Rathmell, 2013

306
Page 6
Peripheral Nerve Injury
Permanent peripheral neuropathy associated with brachial plexus block is a decidedly rare event (95% confidence
interval, 016 / 10,000 patients). Depending on how it is defined, temporary nerve dysfunction in the early
postoperative period may occur in up to 19% of patients and typically presents within the first 48 hours. Most
symptoms resolve by 6 weeks; well less than 0.1% remain after a year. When a patient sustains a peripheral nerve
injury after brachial plexus block, it is crucial the anesthesiologist recognize that the vast majority of these incidents
are related to surgical factorsdirect nerve trauma, positioning injury, stretch injury, or compressive etiologies from
hematoma, edema, or the application of constrictive tourniquets, casts, or dressings. When motor function is
impaired, the injury appears to be progressive, or improvement is not obvious after a few postoperative days, early
neurological consultation is advised. Although abnormalities on neurophysiologic studies (EMG, nerve conduction
studies) are most apparent 2 to 3 weeks after injury, earlier evaluation may be beneficial when injuries meet the
above noted criteria. Early, bilateral neurologic evaluation may establish baseline, document pre-existing conditions,
or identify reversible lesions.

Factors associated with anesthesia-related peripheral nerve injury are poorly understood. No human data exist to
guide our choice of short- vs. long-beveled needles in preventing injury. The relationship of paresthesia elicitation to
peripheral nerve injury is equally unclear. Pain on injection of local anesthetic is generally regarded as a sign of
potential nerve damage, but case reports suggest that this is an inconsistent warning sign. Not all pain on injection is
associated with clinical injury. In contrast, there are reports of injury occurring when pain on injection was
immediately followed by discontinuation of injection, implying that even if a warning occurs, the damage may
already be done. There is no evidence that using UGRA reduces the incidence or severity of nerve injury, but there
are case reports of injury despite the use of ultrasound. Two risks specific to brachial plexus regional anesthesia
deserve comment. Reports of intramedullary spinal cord injection during interscalene block in patients under general
anesthesia suggest that this practice may be dangerous. Furthermore, reports of peripheral nerve injury after
supplemental selective nerve block performed at the elbow or wrist in patients with incomplete proximal brachial
plexus blockade suggest that this practice too may be risky. There are no data to confirm or refute the contention that
UGRA can reduce these risks.

F
i
g
u
r
e

5

N
e
a
l

&

R
a
t
h
m
e
l
l
,

2
0
1
3

In the absence of those rare instances when a
needle fully or partially transects a nerve,
anesthesia-related nerve injury is believed to result
from a combination of factors. First, harmful
needle contact or intrafascicular (subperineurium)
injection damages the nerve-blood barrier. Once
this protective barrier is breached, normally
innocuous local anesthetics can cause
neurotoxicity, which in turn can be worsened if
epinephrine impairs clearance of local anesthetic
from the perineural area and/or causes ischemia to
the injured nerve. (Figure 5) Peripheral nerve
injury may also occur in the setting of a double
crush phenomenon. This theory suggests that
when nerves already compromised by an existing
subclinical injury, e.g., disc disease, diabetes
mellitus, or chemotherapy, are then exposed to a
second relatively minor injury, e.g., surgical
positioning or a minor needle injury, significant
clinical injury becomes manifest. There is clinical
evidence to both confirm and refute the role of
double crush in peripheral nerve injury.
Unfortunately we inadequately understand these
rare and usually temporary, but occasionally
devastating, peripheral nerve injuries associated
with brachial plexus regional anesthesia.

306
Page 7
Complications of Continuous Perineural Blocks
Continuous perineural catheters do not appear to consistently increase complication rates as compared to single-
injection techniques. Within the limitations of relatively few published studies, nerve injury does not appear to be
increased. Similar to single-injection interscalene block, nerve injury has been associated with catheter placement in
anesthetized patients. While the incidence of bacterial colonization is high (~39%), actual abscess formation is low
(0.07%).

SELECTED READINGS

1. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier F, Bouaziz H, Samii K: Major
complications of regional anesthesia in France. The SOS regional anesthesia hotline service. Anesthesiology
2002; 97: 1274-1280
2. Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following
peripheral nerve block. Reg Anesth Pain Med 2013;38:in press
3. Benumof JL: Permanent loss of cervical spinal cord function associated with interscalene block performed
under general anesthesia. Anesthesiology 2000; 93: 1541-1544
4. Bernards CM, Hadzic A, Suresh S, Neal JM: Regional anesthesia in anesthetized or heavily sedated patients.
5. Bernucci F, Gonzalez AP, Finlayson RJ, Tran DQH. A prospective, randomized comparison between
perivascular and perineural ultrasound-guided axillary brachial plexus block. Reg Anesth Pain Med
2012;37:473-477
6. Borgeat A, Ekatodramis G, Kalberer F, Benz C: Acute and nonacute complications associated with interscalene
block and shoulder surgery. A prospective study. Anesth Analg 2001; 95: 875-880
7. Capdevila X, Dadure C, Bringuier S, Bernard N, Gaertner E, Macaire P: Effect of patient-controlled perineural
analgesia on rehabilitation and pain after ambulatory orthopedic surgery. A multicenter randomized trial.
8. Cullen DJ, Kirby RR. Beach chair position may decrease cerebral perfusion; catastrophic outcomes have
occurred. APSF Newsletter 2007;22: 25-27
9. Gadsen J, Hadzic A, Gandhi K, Shariat A, Xu D, Maliakal T, Patel V. The effect of mixing 1.5% mepivacaine
and 0.5% bupivacaine on duration of analgesia and latency of block onset in ultrasound-guided interscalene
block. Anesth Analg 2011;112:471-476
10. Hadzic A, Karaca PE, Hobeika P, Unis G, Dermksian J, Yufa M, Claudio R, Vloka JD, Santos AC, Thys DM:
Peripheral nerve blocks result in superior recovery profile compared with general anesthesia in outpatient knee
arthroscopy. Anesth Analg 2005; 100: 976-981
11. Handoll HHG, Koscielniak-Nielsen ZJ. Single, double or multiple techniques for axillary brachial plexus block
for hand, wrist or forearm surgery. The Cochrane Database of Systematic Reviews 2006, issue 1. Art No.:
CD003842.
12. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK. Executive summary: Regional anesthesia in the patient
receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine
evidence-based guidelines (third edition). Reg Anesth Pain Med 2010;35:102-105
13. Ilfeld BM. Continuous peripheral nerve blocks: A review of the published evidence. Anesth Analg 2011; 113:
904-925
14. McCartney CJ, Brull R, Chan VW, Katz J, Abbas S, Graham B, Nova H, Rawson R, Anastakis DJ, von
Schroeder H: Early but no long-term benefit of regional compared with general anesthesia for ambulatory hand
surgery. Anesthesiology 2004; 101: 461-467
15. Neal JM. The upper extremity: Somatic block. In: Cousins MJ, Carr DB, Horlocker TT, Bridenbaugh PO.
Cousins and Bridenbaughs Neural Blockade In Clinical Anesthesia and Pain Medicine, 4
th
ed. Lippincott
Williams & Wilkins, Philadelphia, pp.316-342, 2009.

306
Page 8
16. Neal JM, Bernards CM, Butterworth JF, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist
2010;35:152-161
17. Neal JM, Bernards CM, Hadzic A, Hebl JR, Hogan QH, Horlocker TT, Lee LA, Rathmell JP, Sorenson EJ,
Suresh S, Wedel DJ: ASRA Practice Advisory on neurologic complications in regional anesthesia and pain
medicine. Reg Anesth Pain Med 2008; 33: 404-415
18. Neal JM, Brull R, Chan VWS, Grant SA, Horn J-L, Liu SS, McCartney CJL, Narouze S, Perlas A, Salinas FV,
Sites BD, Tsui BCH. The ASRA evidence-based medicine assessment of ultrasound-guided regional anesthesia
and pain medicine: Executive summary. Reg Anesth Pain Med 2010;35:S1-S9
19. Neal JM, Gerancher JC, Ilfeld BM, Hebl JR, McCartney CJL, Franco CD, Hogan QH: Upper extremity regional
anesthesia: Essentials of our current understanding, 2008. Reg Anesth Pain Med 2009; 34: 134-170
20. Neal JM, Rathmell JP: Complications in Regional Anesthesia and Pain Medicine, 2
nd
ed. Philadelphia,
Lippincott Williams & Wilkins, 2013
21. Parrington SJ, ODonnell D, Chan VWS, Brown-Shreves D, Subramanyam R, Qu M, Brull R. Dexamethasone
added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus block. Reg
Anesth Pain Med 2010;35:422-426
22. Perlas A, Chan VWS, Simons M: Brachial plexus examination and localization using ultrasound and electrical
stimulation. Anesthesiology 2005; 99: 429-435
23. Sites B, Chan VW, Neal JM, Weller R, Grau T, Koscielniak-Nielsen Z, Ivani G. The American Society of
Regional Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and Pain Therapy
joint committee recommendations for education and training in ultrasound-guided regional anesthesia. Reg
Anesth Pain Med 2010;35: S74-S80

Disclosure

307
Page 1
Lower Extremity Nerve Blocks: What is New?
Admir Hadzic, M.D., PhD. New York, New York
The purpose of this refresher course lecture is to discuss trends, common techniques, indications, management and
means of preventing complications with lower extremity peripheral nerve blocks. The techniques of US guided
lower extremity NBs are still evolving. The techniques to four most common PNBs presented in this syllabus were
agreed upon by a group of 26 international collaborators/universities. The full listing of the contributors can be
found at: http://www.nysora.com/peripheral_nerve_blocks/3347-our-contributors.html

307
Page 2
FEMORAL NERVE BLOCK
Indications: Surgery on femur, anterior thigh, and knee
Abbreviations: FN= Femoral Nerve, FA= Femoral Artery, FV= Femoral Vein
Transducer Placement Cross-Sectional Anatomy

Ultrasound Images
Patient Position: Supine
Transducer: 8-16 MHz, linear array
Transducer placement: Femoral crease, parallel
and inferior to inguinal ligament.
Needle: 22G 5cm short bevel needle (8-10 cm for
obese patients)
Nerve stimulation response: Quadriceps muscle
contraction
Tips:
When FN is not seen, track fascia iliaca medially
towards FA to identify FN.
For analgesia, catheters may be placed underneath
fascia iliaca.
Beware: Risk of falls due to motor weakness of
quadriceps muscle.
US Initial depth setting: 4 cm.
Local Anesthetic (LA): 15-20 mL
Ideal view: Fascia Iliaca and FN
Key Anatomy: Femoral nerve lateral to femoral
artery, below fascia iliaca
Technique:
Needle Insertion: In plane, lateral to medial, (out
of plane less common)
Ideal spread of LA: Beneath fascia iliaca around
femoral nerve
Number of injections: One

307
Page 3
SCIATIC NERVE BLOCK
Indications: Surgery at and below the knee
Abbreviations: GMM= Gluteus Maximus Muscle, ScN= Sciatic Nerve, IT= Ischial Tubercle, GT= Greater
Trochanter

Ultrasound Images

Patient Position: Prone, lateral or oblique
(shown)
Transducer: 6-16 MHz, Linear (shown) or curved
in larger patients
Transducer Placement: Gluteal crease, the
highest crease if more than one
Needle: 21 G 10cm short bevel needle
Nerve stimulation response: Twitch of foot or
calf
Tips:
Needle should enter the sheath of the ScN either at
the lateral or medial aspect of nerve.
Significant amount of transducer pressure may be
required to image ScN.
The cross-sectional anatomy shown can be used as
a reference for both transgluteal and subgluteal
techniques.

US Initial depth setting: 5cm (highly dependent
on patient size)
Ideal view: Sciatic nerve in epineural sheath (grey
arrows)
Key anatomy: Sciatic nerve, gluteus maximus
muscle
Technique:
Needles insertion: In plane, lateral to medial, (out
of plane in larger patients)
Ideal spread of LA: Around the nerve
Number of injections: One to two.

307
Page 4
POPLITEAL BLOCK
Indications: Surgery on ankle, achilles tendon, and foot
Abbreviations: BFM= Biceps Femoris Muscle, CPN=Common Peroneal Nerve, PA=Popliteal Artery, PV= Popliteal
Vein, ScN=Sciatic Nerve, SmM= Semimembranosus Muscle, StM=Semitendinosus Muscle, TN=Tibial Nerve


Ultrasound Images

Patient Position: Prone, oblique (shown) or
supine
Transducer Placement: Transverse at the base of
the popliteal fossa 4-5cm above popliteal crease
Needle: 22 G 5-8cm short bevel needle
Nerve stimulation response: Twitch of foot or
toes

Tips:
Injection can be made also more proximally at
either medial or lateral aspect of ScN under
epineural sheath.
After injection, scan proximally-distally to assure
the LA spread around TN and CPN.
Catheter best placed within epineural sheath.

US Initial depth setting: 4cm
Ideal View: Where ScN starts diverging into TN
and CPN
Key Anatomy: Popliteal artery, ScN superficial
and lateral to it, femur, common epineural sheath
of ScN
Technique:
Needle insertion: In plane or out of plane
Ideal spread of LA: Around ScN, or between TN and
CPN
Number of injections: One or two
X-Needle path for out of plane approach

307
Page 5
SAPHENOUS NERVE BLOCK
Indications: Supplement to popliteal or sciatic blocks for surgery below the knee.
Abbreviations: FA= Femoral Artery, Mediallas M. (Vastus), SaM= Sartorius Muscle, SaN= Saphenous Nerve


Ultrasound Images

Patient Position: Supine with leg abducted and
externally rotated
Transducer Placement: Transverse view at
medial aspect of lower thigh to mid-thigh level
Needle: 22 G 5-8cm short bevel needle
Nerve stimulation response: If used, paresthesia
of medial aspect of lower leg can be elicited
Tips:
When localization of FA proves difficult, start
scanning more proximally and trace FA to mid-
thigh.
Consider out of plane approach in larger patients.
A simple infiltration of LA at the site of incision is
simple and often adequate for surgery on foot and
ankle.

US Initial depth setting: 3cm
Local Anesthetic (LA); 10-15 mL
Ideal view: Artery below the sartorius muscle
Key Anatomy: Femoral artery below Sartorius
muscle, nerve often not visualized

Technique:
Needle Insertion: In plane
Ideal spread of LA: Around or underneath the
artery, between vastus medialis and sartorius muscle
Number of injections: One or two

307
Page 6

TREATMENT OF LOCAL ANESTHETIC TOXICITY, MONITORING OF NEEDLE PLACEMENT &
INJECTION

Treatment of Local Anesthetic Toxicity:
1) Airway, hyperventilation, 100% 02
2) Abolish convulsions (Diazepam, Midazolam, Propofol)
3) Intralipids (1.5 mL/kg over 1 minute (~100mL), then continuous infusion 0.25mL/kg/min (~500 mL over
30 mins)
4) CPR/ ACLS, consider cardiopulmonary bypass

:

307
Page 7

Dermatomes

Disclosure
BBraun, Self, ConsultingFees; Pacira, Self, Funded Research; Macosta Medical USA, Self, Royalties

312
Page 1
Continuous Peripheral Nerve Blocks
Brian M. Ilfeld, M.D., MS (Clinical Investigation) San Diego, California
Introduction. Continuous peripheral nerve blocks (CPNB) consists of a catheter that is percutaneously inserted
adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter. Therefore, the terms
perineural local anesthetic infusion and CPNB are often used synonymously. The maximum duration of a single-
injection peripheral nerve block is currently 8-24 hours. Therefore, when a prolonged neural blockade is desired,
CPNB provides an option.
Indications. CPNB is used to prolong intraoperative surgical anesthesia; treat intractable hiccups; induce
sympathectomy and vasodilation to increase blood flow following a vascular accident, digit transfer/replantation or
limb salvage; alleviate the vasospasm of Raynaud's disease; and treat peripheral embolism. CPNB can provide
analgesia during transportation following trauma, or waiting for surgical treatment. Reports describe CPNB to treat
chronic pain, such as intractable phantom limb pain, pain from terminal cancer and trigeminal neuralgia, and
complex regional pain syndrome. However, the most common indication is providing postoperative analgesia (the
only indication validated with randomized, controlled clinical trials [RCT]).
Most providers use CPNB exclusively for surgical procedures that are expected to result in pain not easily controlled
with less-invasive analgesic techniques because there are intrinsic risks with the techniques,
1
or in patients with an
intolerance to alternative analgesics (e.g., opioid-induced nausea). Although recommendations for the use of various
catheter locations for specific surgical procedures exist, there is little published data specifically illuminating this
issue. In general, axillary, cervical paravertebral (CPVB), infraclavicular, or supraclavicular infusions are used for
surgical procedures involving the hand, wrist, forearm, and elbow (infraclavicular the most effective); interscalene,
CPVB and intersternocleidomastoid catheters are used for surgical procedures involving the shoulder or proximal
humerus (interscalene optimal risk-benefit ratio); thoracic paravertebral catheters are used for breast or thorax
procedures; psoas compartment catheters are used for hip surgery; fascia iliaca, femoral, and psoas compartment
catheters are used for knee or procedures thigh (occasionally hip surgery, although this is somewhat controversial);
and popliteal or subgluteal catheters are used for surgical procedures of the leg, ankle, and foot (popliteal optimal
risk-benefit ratio). CPNB has been described in hundreds of pediatric patients, although it is not as thoroughly
validated as in adults.
Patient Selection. Little published data is available regarding the balancing of potential perineural infusion risks
and benefits for patients with significant comorbidities. Investigators often exclude patients with known hepatic or
renal insufficiency, in an effort to avoid local anesthetic toxicity. For infusions that may effect the phrenic nerve and
ipsilateral diaphragm function (e.g. interscalene or cervical paravertebral catheters), patients with heart or lung
disease are often excluded since continuous interscalene local anesthetic infusions have been shown to cause
frequent ipsilateral diaphragm paralysis. Although the effect on overall pulmonary function may be minimal for
relatively healthy patients,
2
practitioners must be aware of the possible related risks and be prepared to manage
complications.
Catheter Insertion (Nerve Stimulation). Various catheter insertion techniques have been used, inducing
paresthesias, eliciting a facial click, and fluoroscopic guidance. However, most reports involve electrical
stimulation. One common technique involves giving a bolus of local anesthetic via an insulated needle to provide a
surgical block, followed by the introduction of a nonstimulating catheter. Many studies report a high success rate
using this procedure,
3-6
but the catheter tip may be unknowingly misplaced during insertion.
7,8
To help counter this
risk, the perineural catheter may be first inserted, followed by a local anesthetic bolus via the catheter itself.
9-12

312
Page 2
Unfortunately, this technique requires waiting at least 15 minutes for block onset/failure, followed by removal of the
catheter/dressing, re-preparation, and catheter reinsertion for failed a failed insertion.
13
In addition, a partial block is
possible suggesting the catheter tip is not optimally located, but often precluding replacement using electrical
current.
Alternatively, catheters which deliver current to their tips have been developed in an attempt to improve initial
placement success rates.
14
These catheters provide feedback on the positional relationship of the catheter tip to the
target nerve prior to local anesthetic dosing. There is data to suggest that in the area of the popliteal fossa, using
stimulation during catheter advancement results in the catheter tip being placed closer to sciatic nerve.
15-18
The
clinical relevance is questionable femoral and interscalene catheters.
19-27
Regrettably, stimulating catheters
guarantee neither a complete surgical block nor an effective postoperative infusion.
21,28-30
Furthermore, an
acceptable muscle contraction may not always be obtained during catheter insertion;
21,31-34
and, stimulating catheters
often require an increased insertion time and cost more than their non-stimulating counterparts,
18
resulting in many
questioning their cost-benefit ratio. Finally, the minimal acceptable current resulting in a muscle contraction remains
unknown.
Also remaining unknown is the optimal distance to insert the catheter past the needle tip. However, increasing the
insertion distance is correlated with an increased the risk of catheter coiling, and perhaps the ultimate distance
between the catheter and target nerve.
35
With catheter insertion over 5 cm, numerous catheter knots have been
reported;
36
and, a maximum insertion of 5 cm appears warranted. Likewise, remaining unknown is the optimal
minimum insertion distance; but, studies suggests that 0-1 cm results in a minimal risk of secondary block failure,
6

but possibly an increased risk of subsequent dislodgement.
Catheter Insertion (Ultrasound). The limited length of this article precludes an in-depth discussion of ultrasound-
guided perineural catheter insertion; but, the information is available elsewhere.
37
While ultrasound guidance would
intuitively seem to increase the accuracy of catheter tip location, identifying the catheter tip is often challenging.
Multiple practitioners observe the location of injected fluid,
38
an agitated fluid/air mixture,
39
or simply air.
40,41
For
most anatomic locations, ultrasound-guided insertion decreases insertion time and associated discomfort compared
with an electrical technique (and provide at least similar analgesia).
31,32,34,42-45
The majority of reports of combining
ultrasound and nerve stimulation suggest little benefit,
39,46-50
Currently, insufficient data are available to determine
either the optimal techniques/equipment for these insertion modalities, as well as their associated risks and
benefits.
37

Infusates. The majority of perineural infusion publications have involved bupivacaine or ropivacaine, although
levobupivacaine and shorter acting agents have been reported. While the available data suggests bupivacaine and
levobupivacaine are more potent than ropivacaine,
51
all three provide similar analgesia within human trials, although
the ropivacaine concentration is often increased up to 50% to compensate for decreased potency.
51,52
When a
bupivacaine perineural infusion is paused, the motor and sensory effects greatly outlast those of ropivacaine.
52
This
is often important when titrating dose to limit undesired CPNB effects. Also unknown is whether the primary
determinant of CPNB effects is only local anesthetic dose/mass, or if volume (rate) and/or concentration have an
influence.
53-55
Currently, additional research is warranted, and no optimal concentration/rate combination may be
recommended for all anatomic locations.
56
For bupivacaine/levobupivacaine and ropivacaine, the most-commonly-
cited concentrations are between 0.1-0.125% and 0.1-0.2%, respectively. Unfortunately, no adjuvantssuch as
clonidine, epinephrine, and opioidshave been found to improve analgesia and/or decrease undesirable CPNB-
related side effects; and infusing solely long-acting local anesthetic appears warranted.
Local Anesthetic Delivery Regimens. Currently available data suggest that following procedures producing
moderate-to-severe pain, providing patients with the ability to self-administer local anesthetic doses increases
perioperative benefits and/or decreases local anesthetic consumption. Unfortunately, insufficient information is
available to base recommendations on the optimal basal rate, bolus volume, or lockout period accounting for the
many variables that my effect these values (e.g. catheter type, location, surgical procedure). Until recommendations
based on prospectively-collected data are published, practitioners should be aware that investigators have reported
successful analgesia using the following with ropivacaine (0.2%) or bupivacaine (0.125%): a basal rate of 5 (lower
extremity) or 8 (upper extremity) mL/h; a bolus volume of 2 5 mL; and a lockout duration of 20 60 min.
Additionally, the maximum safe dose remains unknown. However, multiple investigations involving patients free of
312
Page 3
renal or hepatic disease have reported blood concentrations within acceptable limitsand an absence of toxicity
symptoms/signsfollowing multiple weeks of perineural infusion with similar dosing schedules.
57,58

Infusion Pumps. There is no single optimal infusion pump for every clinical scenario; and, therefore, pump
preference is usually dictated by desired device characteristics.
59
Although elastomeric infusion pumps cannot match
their electronic counterparts in delivering a basal infusion rate within 5% expected for the entire infusion duration,
whether the increased variability is clinical significantor in which clinical situations it is relevantremains
unknown.
59
Providing an adjustable basal infusion rate permits titration of local anesthetic dose for inadequate
analgesia, an insensate extremity, undesired side effects (e.g., muscle weakness),
60
or maximizing infusion duration
(e.g., ambulatory patients with a set reservoir volume). Furthermore, multiple clinical benefits are provided with a
patient-controlled bolus option, such as increasing analgesia and decreasing opioid consumption. Electronic pumps
provide an adjustable basal rate, patient-controlled bolus doses, and a variable bolus lock-out period.
59
And, while
most elastomeric devices include a fixed basal infusion rate, a few provide similar flexibility to electronic pumps.
Elastomeric pumps are often preferred for their smaller size and lighter weight; lack of audible alarms; disposability;
and silent operation (electronic pumps may disturb patient sleep). In addition, elastomeric devices with no bolus
dose capability and a manufacturer-fixed basal rate are usually less costly. However, inexpensive disposable
cassettes provide sterile infusion for individual patients utilizing reusable electronic pumps. A few disposable
electronic pumps are available. At least within the United States, the infusion pump/reservoir must now be filled
under a laminar flow workbench.
61
Of note, at least within the United States, there are no national guidelines
regarding the maximum safe CPNB duration.
61

Ambulatory Perineural Infusion. While length limitations of this article preclude an extensive discussion of
ambulatory CPNB, this information is available elsewhere.
59
Ambulatory perineural infusion may be provided to
outpatients using a portable pump. Perineural infusion is often provided for ambulatory surgery without an overnight
hospital stay;
59
but may also shorten hospitalization duration,
62,63
and/or bestow benefits following discharge to
either a rehabilitation facility or home.
6,58
Ultrasound guidancewith its demonstrated decreased insertion timeis
often beneficial in high-turnover ambulatory centers where time constraints are often severe.
31,34,45,64
Patient
selection criteria are often more stringent for ambulatory CPNB since outpatients are rarely directly monitored; and
not all patients desire or are capable of accepting the additional responsibility of caring for the catheter and pump
system. Patients with hepatic or renal insufficiency are often excluded from ambulatory CPNB to decrease the risk
of local anesthetic toxicity. Caution is warranted during interscalene and cervical paravertebral infusion (frequently
induce diaphragm weakness) for obese individuals and those with heart/lung disease who may not be able to
compensate for mild hypoxia and/or hypercarbia.
Ambulatory perineural infusion may reduced time until discharge readiness;
6,29,62,65
and, in select cases, actual
discharge.
62,63
Early discharge after total knee arthroplasty may decrease hospitalization-related costs.
66
However,
caution is warranted prior to allowing discharge with a continuous posterior lumbar plexus and femoral nerve block
given that these catheters are associated with an increased risk of falling.
67
Nonetheless, relatively small published
series document the feasibility of total joint arthroplasty with only a single-night hospital stayor even on an
outpatient basiswhen patients are provided CPNB at home.
68-72

Benefits. The most-common indication for CPNB is to provide postoperative pain control, and it appears that most
CPNB benefits are dependent upon successfully improving analgesia.
56
RCT-documented benefits include decreased
postoperative pain, supplemental analgesic requirements, opioid-related side effects, sleep disturbances,
dissatisfaction, discharge readiness, actual discharge, and inflammatory markers. In addition, an accelerated
resumption of passive joint range-of-motion is documented following total knee arthroplasty procedures with 48-72
hours of continuous femoral perineural infusion. Analgesia is most impressive when the perineural infusion effects
the entire innervation of the surgical site; as is often the case for shoulder and foot procedures (interscalene and
sciatic perineural catheters, respectively).
4,7,62
Unfortunately, even though brachial plexus infusions (theoretically)
cover the entire surgical site for procedures at or distal to the elbow, they provide less impressive analgesia.
73
.
Severely lacking are RCT-documented benefits of continuous axillary,
74
supraclavicular,
75
and transversus
abdominus plane blocks.
56
And, while the benefits of infraclavicular infusion are validated,
73
analgesia is often less-
than-optimal unless a high enough dose of local anesthetic is administered, frequently rendering the extremity
insensate. Similarly, for surgical sites innervated by multiple nerves (such as the knee, hip and ankle), a single
perineural usually provide less-than-optimal analgesia without the concurrent use of additional analgesics.
6,29,55

312
Page 4
While a lumbar epidural provides roughly equivalent analgesia to femoral perineural infusion for hip and knee
arthroplasty, CPNB results in a more-favorable side-effect profile without the risk of epidural hematoma during
concomitant anticoagulant administration.
76-78

While the evidence for CPNB benefits during the infusion is vast,
56
there are few studies documenting benefits
following catheter removal. Exceptions include increased health-related quality-of-life in one study
79
(but not five
others);
80-84
improved analgesia after a few days
5,85,86
or six months;
87
faster tolerance of passive knee flexion
resulting in earlier discharge from rehabilitation centers;
77,78,85
and more-rapid resumption of lavatory use and
unassisted standing.
85
Noticeably absent is evidence of medium- or long-term improvements in measures of health-
related quality-of-life.
80-84,88

Complications. Relatively minor CPNB-related complications occur at a frequency similar to single-injection
peripheral nerve blocks.
89
In contrast, severe and permanent infusion-related injuries are uncommon. Unfortunately,
generalizations are difficult given the multiple anatomic locations for perineural infusion as well as diverse
equipment and techniques. For example, the incidence of secondary block (infusion) failure reported by three
different trials includes 1%,
90
20%,
7
and 50%.
9
Catheter insertion-related complications include inaccurate catheter
tip placement; andin extremely rare casesintraneural, intrathecal, epidural, intravascular, and even interpleural
catheter insertion. Complications during the perineural infusion include catheter obstruction or dislodgement;
catheter site fluid leakage; infusion pump disconnection, malfunction, or undesired pause; allergic reaction or simply
skin irritation to the catheter dressing and/or liquid adhesive; and, catheter-induced brachial plexus irritation. One of
the most common complications is an insensate extremity that may be unnerving to patients, hinders rehabilitation,
and often believed to be a risk factor for injury.
54,55
In such cases, pause the infusion until sensory perception
returns, and then restarted the infusion at a lower basal rate. Conversely, breakthrough pain or persistent inadequate
analgesia may be treated with patient-controlled bolus doses and increasing the basal infusion, respectively.

More seriousand remarkably uncommoncomplications include systemic local anesthetic toxicity; myonecrosis
with repeated large boluses of bupivacaine; retroperitoneal and peri-catheter hematoma formation; catheter knotting,
retention, shearing, or breakage; a prolonged Horners syndrome; and lower lobe collapse during infusions affecting
the phrenic nerve. In patients with preexisting neuropathy and/or diabetes, limited evidence suggests that prolonged
local anesthetic exposure may increase the risk of nerve injury. Infusions affecting the femoral nerve is associated
with an increased risk of falling following knee and hip arthroplasty.
67
Catheter site infection and abscess are rare
(infection incidence 0-3%;
91,92
but most reports <1%),
11,89,93
although inflammation (3-4%)
1,90,94
and bacterial
colonization (6%-57%) are more common. Risk factors include the absence of perioperative antibiotic prophylaxis,
male sex, axillary/femoral catheter insertion, and presence in an intensive care unit.
1
The infection risk is also
correlated with infusion duration;
1
but, nevertheless, a minimal incidence of infection has been reported for CPNB
during inter-continental transportation for up to 34 days
95
and provided at home for up to 83 days.
58

Because all surgical procedures are associated with a variable incidence of nerve injuryregardless of the
application of a regional anesthetic/analgesicit is often problematic to determine what percentage (if any) of a
new-onset neurologic deficit is attributable to CPNB. Keeping this limitation in mind, the incidence of transient
adverse neurologic symptoms associated with CPNB is 0-1.4% for interscalene,
1,11,89,90
0.4-0.5% for femoral,
1,96
and
0-1.0% for sciatic catheters.
1,90,96,97
Another study reported a 0.2% incidence of neurologic deficits lasting longer
than 6 weeks in nearly 3,500 catheters from multiple anatomic locations.
90
In this latter study, it remains unknown
if the deficits resolved after the 6-week study period; but multiple prospective investigations report that the
overwhelming majority of neurologic symptoms present at 4-6 weeks resolve spontaneously within three months of
surgery.
1,11,89
Long-term and/or permanent nerve injury has occurred.
98
Five large,
1,11,89,96,97
prospective series that
followed patients for at least three months reported 3 cases of unresolved adverse neurologic events.
89,96,97
These
investigations combined (4,148 total subjects) suggests the risk of neurologic injury lasting longer than nine months
associated with CPNB is 0.07% (all of the risk may not be conclusively attributed to the perineural
infusion).
1,11,89,96,97
While ultrasound-guidance may decrease the incidence of many/most of these reported
complications,
99
to date there are few data supporting this proposition;
100,101
and case reports suggest that completely
abolishing such events is unlikely.
102-104

312
Page 5
References.

Greatly abbreviated due to space requirements, although the entire list is available elsewhere.
56

1. Capdevila X, et al: Continuous Peripheral Nerve Blocks in Hospital Wards after Orthopedic Surgery: A
Multicenter Prospective Analysis of the Quality of Postoperative Analgesia and Complications in 1,416
Patients. Anesthesiology 2005; 103: 1035-1045
2. Borgeat A, Perschak H, Bird P, Hodler J, Gerber C: Patient-controlled interscalene analgesia with ropivacaine
0.2% versus patient-controlled intravenous analgesia after major shoulder surgery: effects on diaphragmatic
and respiratory function. Anesthesiology 2000; 92: 102-108
3. Grant SA, et al: Continuous peripheral nerve block for ambulatory surgery. Reg Anesth Pain Med 2001; 26:
209-214
4. Ilfeld BM, et al: Continuous popliteal sciatic nerve block for postoperative pain control at home: a randomized,
double-blinded, placebo-controlled study. Anesthesiology 2002; 97: 959-965
5. Williams, et al: Reduction of verbal pain scores after anterior cruciate ligament reconstruction with 2-day
continuous femoral nerve block: a randomized clinical trial. Anesthesiology 2006; 104: 315-327
6. Ilfeld BM, et al: Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-
center, randomized, triple-masked, placebo-controlled trial. Anesthesiology 2008; 109: 491-501
7. Ilfeld BM, et al: Continuous interscalene brachial plexus block for postoperative pain control at home: a
randomized, double-blinded, placebo-controlled study. Anesth Analg 2003; 96: 1089-1095
8. Salinas FV: Location, location, location: Continuous peripheral nerve blocks and stimulating catheters. Reg
Anesth Pain Med 2003; 28: 79-82
9. Ganapathy S, et al: Modified continuous femoral three-in-one block for postoperative pain after total knee
arthroplasty. Anesth.Analg. 1999; 89: 1197-1202
10. Borgeat A, Blumenthal S, Lambert M, Theodorou P, Vienne P: The feasibility and complications of the
continuous popliteal nerve block: a 1001-case survey. Anesth Analg 2006; 103: 229-33
11. Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L: Evaluation of the lateral modified approach for continuous
interscalene block after shoulder surgery. Anesthesiology 2003; 99: 436-442
12. Capdevila, et al: Continuous psoas compartment block for postoperative analgesia after total hip arthroplasty:
New landmarks, technical guidelines, & clinical evaluation. Anesth Analg 2002;94:1606
13. Torkki PM, et al: Use of anesthesia induction rooms can increase the number of urgent orthopedic cases
completed within 7 hours. Anesthesiology 2005; 103: 401-405
14. Boezaart, et al: A new technique of continuous interscalene nerve block. Can J Anaesth 1999; 46: 275
15. Casati A, et al: Using stimulating catheters for continuous sciatic nerve block shortens onset time of surgical
block and minimizes postoperative consumption of pain medication after halux valgus repair as compared with
conventional nonstimulating catheters. Anesth Analg 2005; 101: 1192-7
16. Rodriguez J, Taboada M, Carceller J, Lagunilla J, Barcena M, Alvarez J: Stimulating popliteal catheters for
postoperative analgesia after hallux valgus repair. Anesth Analg 2006; 102: 258-262
17. Paqueron X, et al: A randomized, observer-blinded determination of the median effective volume of local
anesthetic required to anesthetize the sciatic nerve in the popliteal fossa for stimulating and nonstimulating
perineural catheters. Reg Anesth Pain Med 2009; 34: 290-295
18. Casati A, et al: Stimulating or conventional perineural catheters after hallux valgus repair: a double-blind,
pharmaco-economic evaluation. Acta Anaesthesiol.Scand. 2006; 50: 1284-1289
19. Salinas, et al: Prospective comparison of continuous femoral nerve block with nonstimulating catheter
placement versus stimulating catheter-guided perineural placement in volunteers. RAPM 2004;29:212
20. Stevens MF, et al: Does interscalene catheter placement with stimulating catheters improve postoperative pain
or functional outcome after shoulder surgery? Anesth Analg. 2007; 104: 442-447
21. Brull R, et al: Is a patella motor response necessary for continuous femoral nerve blockade performed in
conjunction with ultrasound guidance? Anesth Analg 2011; 112: 982-6
22. Morin, et al: Does femoral nerve catheter placement with stimulating catheters improve effective placement?
A randomized, controlled, and observer-blinded trial. Anesth Analg 2005; 100: 1503-10
23. Hayek SM, et al: Continuous femoral nerve analgesia after unilateral total knee arthroplasty: stimulating
versus nonstimulating catheters. Anesth Analg. 2006; 103: 1565-1570
24. Barrington MJ, et al: Stimulating catheters for continuous femoral nerve blockade after total knee arthroplasty:
a randomized, controlled, double-blinded trial. Anesth Analg 2008; 106: 1316-21

312
Page 6
25. Dauri, et al: Efficacy of continuous femoral nerve block with stimulating catheters versus nonstimulating
catheters for anterior cruciate ligament reconstruction. RAPM 2007; 32: 282-287
26. Ilfeld BM, Wright TW, Sessler DI, Chmielewski TL: Valid and relevant outcome measures are critical for
objective hypothesis-testing. Anesth Analg 2008; 107: 722-723
27. Chelly JE, Casati A: Are nonstimulating catheters really inappropriate for continuous nerve block techniques?
Reg Anesth Pain Med 2003; 28: 483
28. Ilfeld BM, Morey TE, Enneking FK: Infraclavicular perineural local anesthetic infusion: a comparison of three
dosing regimens for postoperative analgesia. Anesthesiology 2004; 100: 395-402
29. Ilfeld BM, et al: Ambulatory continuous femoral nerve blocks decrease time to discharge readiness after
tricompartment total knee arthroplasty. Anesthesiology 2008; 108: 703-713
30. Pham-Dang, et al: Continuous peripheral nerve blocks with stimulating catheters. RAPM 2003; 28:83
31. Mariano ER, Ilfeld BM, et al: Ultrasound guidance versus electrical stimulation for infraclavicular brachial
plexus perineural catheter insertion. J Ultrasound Med 2009; 28: 1211-1218
32. Mariano, Ilfeld, et al: A trainee-based randomized comparison of stimulating interscalene perineural catheters
with a new technique using ultrasound guidance alone. J Ultrasound Med 2010; 29: 329-336
33. Mariano, Ilfeld, et al: Comparative efficacy of ultrasound-guided and stimulating popliteal-sciatic perineural
catheters for postoperative analgesia. Can.J.Anaesth. 2010; 57: 919-926
34. Mariano, Ilfeld, et al: Ultrasound guidance versus electrical stimulation for femoral perineural catheter
insertion. J Ultrasound Med 2009; 28: 1453-1460
35. Capdevila X, et al: Continuous three-in-one block for postoperative pain after lower limb orthopedic surgery:
where do the catheters go? Anesth Analg 2002; 94: 1001-1006
36. Offerdahl MR, et al: Successful removal of a knotted fascia iliaca catheter: principles of patient positioning for
peripheral nerve catheter extraction. Anesth Analg 2004; 99: 1550-1552
37. Ilfeld BM, Fredrickson MJ, Mariano ER: Ultrasound-guided perineural catheter insertion: three approaches but
few illuminating data. Reg Anesth Pain Med 2010; 35: 123-126
38. Antonakakis, et al: Ultrasound-guided posterior approach for the placement of a continuous interscalene
catheter. Reg Anesth Pain Med 2009; 34: 64-68
39. Dhir S, Ganapathy S: Use of ultrasound guidance and contrast enhancement: a study of continuous
infraclavicular brachial plexus approach. Acta Anaesthesiol.Scand. 2008; 52: 338-342
40. Swenson JD, Davis JJ, DeCou JA: A novel approach for assessing catheter position after ultrasound-guided
placement of continuous interscalene block. Anesth Analg 2008; 106: 1015-6
41. Sandhu, et al: Ultrasound-guided infraclavicular brachial plexus block. Br J Anaesth 2002;89:254-259
42. Fredrickson, et al: Ambulatory continuous femoral analgesia for major knee surgery: a randomised study of
ultrasound-guided femoral catheter placement. Anaesth.Intensive Care 2009; 37: 758-766
43. Fredrickson, et al: A prospective randomized comparison of ultrasound and neurostimulation as needle end
points for interscalene catheter placement. Anesth Analg 2009; 108: 1695-1700
44. Bendtsen, et al: Ultrasound guidance improveds a continuous popliteal sciatic nerve block when compared
with nerve stimulation. Reg Anesth Pain Med 2011; 36: 181-4
45. Mariano, Ilfeld, et al: Electrical stimulation versus ultrasound guidance for popliteal-sciatic perineural catheter
insertion: a randomized controlled trial. Reg Anesth Pain Med 2009; 34: 480-485
46. Dhir, et al: Comparative evaluation of ultrasound-guided continuous infraclavicular brachial plexus block with
stimulating catheter and traditional technique. Acta Anaesthesiol Scand 2008;52:1158
47. Mariano, Ilfeld, et al: Continuous interscalene brachial plexus block via an ultrasound-guided posterior
approach. Anesth Analg 2009; 108: 1688
48. van Geffen GJ, Gielen M: Ultrasound-guided subgluteal sciatic nerve blocks with stimulating catheters in
children: a descriptive study. Anesth Analg 2006; 103: 328-33
49. van Geffen, et al: Ultrasound-guided bilateral continuous sciatic nerve blocks with stimulating catheters for
pain relief after bilateral lower limb amputations. Anaesthesia 2006;61:1204
50. Niazi AU, Prasad A, Ramlogan R, Chan VW: Methods to ease placement of stimulating catheters during in-
plane ultrasound-guided femoral nerve block. Reg Anesth Pain Med 2009; 34: 380-381
51. Borghi, et al: Pain relief and motor function during continuous interscalene analgesia after open shoulder
surgery. Eur J Anaesthesiol 2006; 23: 1005-1009
52. Borgeat, et al: Patient-controlled interscalene analgesia with ropivacaine 0.2% versus bupivacaine 0.15% after
major open shoulder surgery. Anesth Analg 2001; 92: 218-223
53. Ilfeld, et al: Continuous Peripheral Nerve Blocks: Is Local Anesthetic Dose the Only Factor, or Do
Concentration and Volume Influence Infusion Effects as Well? Anesthesiology 2010; 112: 347-354

312
Page 7
54. Ilfeld, et al: The effects of local anesthetic concentration and dose on continuous infraclavicular nerve blocks:
a multicenter, randomized, observer-masked, controlled study. Anesth Analg 2009;108:345
55. Ilfeld, et al: The effects of varying local anesthetic concentration and volume on continuous popliteal sciatic
nerve blocks: a dual-center, randomized, controlled study. Anesth Analg 2008; 107: 701-707
56. Ilfeld: Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg, In Press
57. Bleckner, et al: Serum ropivacaine concentrations and systemic local anesthetic toxicity in trauma patients
receiving long-term continuous peripheral nerve block catheters. Anesth Analg 2010;110:630
58. Borghi, et al: The use of prolonged peripheral neural blockade after lower extremity amputation: the effect on
symptoms associated with phantom limb syndrome. Anesth Analg. 2010; 111: 1308-1315
59. Ilfeld BM, Enneking FK: Continuous peripheral nerve blocks at home: A review. Anesth Analg 2005; 100:
1822-1833
60. Charous MT MS, Suresh PJ, Sandhu NS, Loland JV, Mariano ER, Donohue MC, Dutton PH, Ferguson EJ,
Ilfeld BM: Continuous femoral nerve blocks: varying local anesthetic delivery method (bolus vs. basal) to
minimize quadriceps motor block while maintaining sensory block. Anesthesiology 2011: E-pub
61. Head S, Enneking FK: Infusate contamination in regional anesthesia: what every anesthesiologist should
know. Anesth Analg 2008; 107: 1412-1418
62. Ilfeld, et al: Ambulatory continuous interscalene nerve blocks decrease the time to discharge readiness after
total shoulder arthroplasty. Anesthesiology 2006; 105: 999-1007
63. White, et al: The use of a continuous popliteal sciatic nerve block after surgery involving the foot and ankle:
does it improve the quality of recovery? Anesth Analg 2003; 97: 1303-1309
64. Mariano ER, Loland VJ, Ilfeld BM: Interscalene perineural catheter placement using an ultrasound-guided
posterior approach. Reg Anesth Pain Med 2009; 34: 60-63
65. Ilfeld, et al: A multicenter, randomized, triple-masked, placebo-controlled trial of the effect of ambulatory
continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on
general orthopaedic wards. Pain 2010; 150: 477-484
66. Ilfeld, et al: Hospitalization costs of total knee arthroplasty with a continuous femoral nerve block provided
only in the hospital versus on an ambulatory basis: a retrospective, case-control, cost-minimization analysis.
67. Ilfeld BM, Duke KB, Donohue MC: The association between lower extremity continuous peripheral nerve
blocks and patient falls after knee and hip arthroplasty. Anesth Analg 2010; 111: 1552-4
68. Ilfeld, et al: Total knee arthroplasty as an overnight-stay procedure using continuous femoral nerve blocks at
home: A prospective feasibility study. Anesth Analg 2006; 102: 87-90
69. Ilfeld, et al: Total hip arthroplasty as an overnight-stay procedure using an ambulatory continuous psoas
compartment nerve block: A prospective feasibility study. Reg Anesth Pain Med 2006; 31: 113
70. Ilfeld, et al: Total shoulder arthroplasty as an outpatient procedure using ambulatory perineural local anesthetic
infusion: A pilot feasibility study. Anesth Analg 2005; 101: 1319-1322
71. Ilfeld, et al: Total elbow arthroplasty as an outpatient procedure using a continuous infraclavicular nerve block
at home: a prospective case report. Reg Anesth Pain Med 2006; 31: 172-176
72. Swenson, et al: Outpatient management of continuous peripheral nerve catheters placed using ultrasound
guidance: an experience in 620 patients. Anesth Analg. 2006; 103: 1436-1443
73. Ilfeld, et al: Continuous infraclavicular brachial plexus block for postoperative pain control at home: a
randomized, double-blinded, placebo-controlled study. Anesthesiology 2002; 96: 1297-1304
74. Salonen, et al: Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial
plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia. Reg Anesth Pain Med
2000; 25: 47-51
75. Mariano, Ilfeld, et al: A randomized comparison of infraclavicular and supraclavicular continuous peripheral
nerve blocks for postoperative analgesia. Reg Anesth Pain Med 2011; 36: 26-31
76. Singelyn FJ, Ferrant T, Malisse MF, Joris D: Effects of intravenous patient-controlled analgesia with
morphine, continuous epidural analgesia, and continuous femoral nerve sheath block on rehabilitation after
unilateral total-hip arthroplasty. Reg Anesth Pain Med 2005; 30: 452-457
77. Singelyn, et al: Effects of intravenous patient-controlled analgesia with morphine, continuous epidural
analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total
knee arthroplasty. Anesth.Analg. 1998; 87: 88-92
78. Capdevila, et al: Effects of perioperative analgesic technique on the surgical outcome and duration of
rehabilitation after major knee surgery. Anesthesiology 1999; 91: 8-15

312
Page 8
79. Carli, et al: Analgesia and functional outcome after total knee arthroplasty: periarticular infiltration vs
continuous femoral nerve block. British journal of anaesthesia 2010; 105: 185-95
80. Ilfeld, et al: Health-related quality of life after hip arthroplasty with and without an extended-duration
continuous posterior lumbar plexus nerve block: a prospective, 1-year follow-up of a randomized, triple-
masked, placebo-controlled study. Anesth Analg 2009; 109: 586-91
81. Ilfeld, et al: Health-related quality of life after tricompartment knee arthroplasty with and without an extended-
duration continuous femoral nerve block: a prospective, 1-year follow-up of a randomized, triple-masked,
placebo-controlled study. Anesth Analg 2009; 108: 1320-1325
82. Ilfeld, et al: Long-term pain, stiffness, and functional disability after total knee arthroplasty with and without
an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-up of a multicenter,
randomized, triple-masked, placebo-controlled trial. Reg Anesth Pain Med 2011; 36: 116
83. Kadic L, Boonstra MC, MC DEWM, Lako SJ, J VANE, Driessen JJ: Continuous femoral nerve block after
total knee arthroplasty? Acta anaesthesiologica Scandinavica 2009; 53: 914-20
84. Williams, et al: General health & knee function outcomes from 7 days to 12 weeks after spinal anesthesia and
multimodal analgesia for ACL reconstruction. Anesth Analg 2009;108:1296
85. Martin, et al: Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic
evaluation. Anesthesiology 2008; 109: 484-490
86. Salinas FV, Liu SS, Mulroy MF: The effect of single-injection femoral nerve block versus continuous femoral
nerve block after total knee arthroplasty on hospital length of stay and long-term functional recovery within an
established clinical pathway. Anesth Analg 2006; 102: 1234-1239
87. Blumenthal, et al: Additional femoral catheter in combination with popliteal catheter for analgesia after major
ankle surgery. Br J Anaesth 2011; 106: 387-93
88. Shum CF, Lo NN, Yeo SJ, Yang KY, Chong HC, Yeo SN: Continuous femoral nerve block in total knee
arthroplasty: immediate and two-year outcomes. The Journal of arthroplasty 2009; 24: 204-9
89. Borgeat A, Ekatodramis G, Kalberer F, Benz C: Acute and nonacute complications associated with
interscalene block and shoulder surgery: a prospective study. Anesthesiology 2001; 95: 875-880
90. Neuburger, et al: [Complications and adverse events in continuous peripheral regional anesthesia Results of
investigations on 3,491 catheters]. Anaesthesist 2006; 55: 33-40
91. Capdevila, et al: Infectious risk of continuous peripheral nerve blocks. Anesthesiology 2009;110:182
92. Neuburger, et al: Inflammation and infection complications of 2285 perineural catheters: a prospective study.
Acta Anaesthesiol.Scand. 2007; 51: 108-114
93. Borgeat A, Blumenthal S, Karovic D, Delbos A, Vienne P: Clinical evaluation of a modified posterior
anatomical approach to performing the popliteal block. Reg Anesth Pain Med 2004; 29: 290-296
94. Borgeat A, Capdevila X: Neurostimulation/ultrasonography: the Trojan war will not take place.
95. Stojadinovic, et al: Responding to challenges in modern combat casualty care: innovative use of advanced
regional anesthesia. Pain Med 2006; 7: 330-338
96. Wiegel, et al: Complications and adverse effects associated with continuous peripheral nerve blocks in
orthopedic patients. Anesth Analg. 2007; 104: 1578-82
97. Compere, et al: Major complications after 400 continuous popliteal sciatic nerve blocks for post-operative
analgesia. Acta Anaesthesiol Scand 2009; 53: 339-345
98. Dullenkopf A, Zingg P, Curt A, Borgeat A: [Persistent neurological deficit of the upper extremity after a
shoulder operation under general anesthesia combined with a preoperatively placed interscalene catheter].
Anaesthesist 2002; 51: 547-551
99. Swenson JD, Davis JJ: Ultrasound-guided regional anesthesia: why can't we all just stay away from the nerve?
100. Neal JM: Ultrasound-guided regional anesthesia and patient safety: An evidence-based analysis. Reg Anesth
Pain Med 2010; 35: S59-S67
101. Hebl JR: Ultrasound-guided regional anesthesia and the prevention of neurologic injury: fact or fiction?
102. Neal JM, Wedel DJ: Ultrasound guidance and peripheral nerve injury: is our vision as sharp as we think it is?
103. Reiss W, Kurapati S, Shariat A, Hadzic A: Nerve injury complicating ultrasound/electrostimulation-guided
supraclavicular brachial plexus block. Reg Anesth Pain Med 2010; 35: 400-401
104. Cohen JM, Gray AT: Functional deficits after intraneural injection during interscalene block. Reg Anesth Pain
Med 2010; 35: 397-399

312
Page 9

Disclosure
Baxter Healthcare, Self, Funded Research; Summit Medical, Self, Funded Research; AcelRx, Self, Funded
Research; Pacira Pharmaceuticals, Self, Funded Research

320
Page 1
Local Anesthetics: Mechanisms, Toxicities, and Controversies From a Clinical Perspective
John F. Butterworth, IV, M.D.
Richmond, Virginia
General Considerations
Local and regional anesthesia were introduced to clinical medicine in 1884 when Kller and Gartner reported
topical cocaine anesthesia of each others corneas and Halsted reported brachial plexus and mandibular nerve
blocks.
1-3
Advances in the field continue as safer local anesthetic compounds (LAs), better LA adjuncts, better
needles and infusion devices, more reliable techniques for nerve localization (sometimes with reduced LA doses),
safer sedation medications and techniques, and more effective resuscitation, techniques have been introduced. This
review will focus on recent information regarding LA mechanisms, pharmacodynamics, and toxicity, highlighting
the potential clinical implications when they are apparent.
LA Structures and Chirality
The drugs typically used for local and regional anesthesia have many features in
common, notably a substituted benzene ring at one end of the molecule and a tertiary
amine nitrogen at the opposite end (Figure 1).
2-5
Chiral carbons are designated with
an asterix (*) on Figure 1. The designation as an ester or an amide is determined by a
chemical link in the middle portion of the molecule. All LAs other than ropivacaine
and levobupivacaine are provided as racemic mixtures (e.g. mepivacaine) or have no
chiral carbons (e.g. lidocaine). Other compounds that produce local or regional
anesthesia have widely varying structures. Many of these compounds have been
shown to inhibit voltage-gated Na
v
channels, confirming that their mechanism of
clinical action could be the same as classical LAs. These compounds include:
general anesthetics, !
2
agonists, tricyclic antidepressants, alcohols, and nerve
toxins.
4-12
Perhaps one of these non-traditional Na
v
channel antagonists will prove
safer or more effective than traditional LAs.
13,14

Voltage-gated Na (Na
v
) Channels
When applied to a peripheral nerve LAs bind Na
v
channels on axons, preventing
Na
v
channels from opening and inhibiting initiation and propagation of Na currents
and action potentials.
4,5
Taylor demonstrated that LAs inhibit Na currents in 1959 yet
anesthesia textbooks continued to include other discredited mechanisms of LA action
for more than 30 years!

Na
v
channels are large, integral membrane proteins
containing 1 larger !-subunit and 1 or 2 smaller "-subunits. The !-subunit, the site of ion conduction and drug
binding, includes roughly 2000 amino acids and 4 domains, each with 6 !-helical, membrane-spanning segments.
5

"-subunit forms regulating multiple channel activities have been identified. Some "-subunit forms regulate channel
insertion into the plasma membrane, and the voltage-dependence and kinetics of !-subunit gating.
15,16
Humans have 7 functional genes that code for neuronal Na
v
channel !-subunits and 2 that code for Na
v
!-
subunit isoforms in muscle.
17,18
Separate, specific Na
v
isoforms (gene products) predominate on unmyelinated axons,
nodes of Ranvier, and small dorsal root ganglion nociceptors, and unique forms are found in skeletal (Na
v
1.4) and
cardiac muscle (Na
v
1.5). Variations in SCN5A gene (SCN5A codes for Na
v
1.5) promoter haplotypes can influence
the therapeutic range for drug concentrations.
19
Na
v
isoforms may have differing drug affinities.
17
Alternative
splicing of gene products can yield additional variation, as was demonstrated for Nav 1.7 channels in human DRG.
20

Some isoforms may be particularly important in the pathophysiology of both inherited and acquired chronic pain
syndromes or in small-fiber neuropathy.
21
Na
v
1.7 accumulates in painful human neuromas.
22
Na
v
1.8 increases in
DRG in animal models of inflammatory pain. Increased numbers of Na
v
1.9 appear in painful diabetic neuropathy.
Na
v
1.3 expression increases in dorsal root ganglia after peripheral nerve injury and in human neuromas formed after
injury. Na
v
1.6 may underlie repetitive firing in lumbar DRG neurons with inflammation and knockdown of this
channel eliminates abnormal spontaneous DRG electrical activity and pain behavior in animals.
23

320
Page 2
Na
v
channels exist in at least 3 states in vivo: resting, open, and inactivated, as was first described by
Hodgkin and Huxley.
4,5
During action potentials Na
v
channels open briefly, allowing Na ions to flow into the cell,
depolarizing the plasma membrane. After a few milliseconds, Na
v
channels inactivate and Na flux ceases.
Mammalian myelinated fibers require no contribution from K currents for membrane repolarization, and

Na
v

channels return to the resting conformation with repolarization.
4,5
Such voltage gating of channel states likely
results from small movements of paddle-shaped, voltage-sensing amino acid sequences..
21,23
Patients with genetic
Na
v
variants in which resurgent Na currents appear during repolarization, presumably from a lack of conventional
inactivation, may present with a paroxysmal extreme pain disorder (Na
v
1.7), paramyotonia congenital (Na
v
1.4),
and long-QT3/sudden infant death (Na
v
1.5), depending on which isoform is abnormal.
18

Mechanisms of Local Anesthesia by Classical LAs
LA binding has been associated with specific regions of the !-subunit.
24
,
14,15
Some Na
v
isoforms are more LA
resistant than others.
25
LA inhibition of Na currents increases with repetitive depolarizations, often called use-
dependent block., a phenomenon believed to underlie antiarrhythmic and antiepileptic effects.
4,5
Repetitive
depolarizations increase the likelihood that a LA will encounter open" or inactivated Na
v
channels rather than
resting channels with less LA affinity.
4,5,17
Alternatively, LAs may preferentially
modulate Na
v
channel movements associated with opening events.

When the quaternary lidocaine derivative QX-314 is applied intracellularly, this
membrane impermeant agent powerfully inhibits Na currents.
4,5
Compare the structures
in Figure 2, noting QX-314s positively-charged nitrogen (note the +) and QX-314s
extra ethyl moiety. Studies suggest that QX-314 and other drugs may gain entrance to
the cytoplasm through vanilloid TRPV1 channels, after these channels are activated by
pain, lidocaine or capsaicin.
26-29
TRPV1 channel activation underlies nociception in
primary sensory afferent fibers.
30

LA Actions at Sites Unrelated to Na
v
Channels or Nerve Block
LAs have limited potency and are relatively nonselective. LAs solubilize and
disrupt membranes. LAs bind and inhibit a variety of channels (including K
ATP
, Ca
release, voltage-gated K, Ca, and HERG), enzymes (including mitogen activated
kinases, adenylyl cyclase, and phosphorylases), receptors (nicotinic acetylcholine,
NMDA, "-adrenergic, TRPV1, bradykinin B2, 5-HT3), and signaling mechanisms (G-protein-mediated
signaling).
4,31-33
LA binding to these sites could contribute to spinal or epidural anesthesia, positive or negative
effects of systemically absorbed LAs, or could have no importance whatsoever!
33
Circulating LAs have profound
effects on coagulation, inflammation, microcirculation; immune responses to infection and malignancy,
postoperative gastrointestinal function, and analgesia.
34
Infused LAs relieve neuropathic pain, and improve
analgesia.
35
Infused LAs shorten hospital lengths of stay as effectively as epidural analgesia. Lidocaine inhibits
cardiac ischemia and reperfusion injury in mice by an antiapoptotic effect.
36
Conversely, LAs inhibit kinesis and
promote apoptosis, effects that could reduce cancer metastasis or promote chondrolysis after prolonged intraarticular
infusion, respectively.
37

LA Pharmacodynamics
LA Volumes and Concentrations during Nerve Block
During clinical regional blocks, only a vanishingly small fraction of the injected LA molecules will be bound by
Na
v
channels specifically or even by neurons generally.
38
Most drug molecules will be bound by other tissues or
removed by the blood stream. Clinical regional anesthesia will not arise unless conduction is blocked over a
sufficient length of nerve. This critical length exceeds 2 cm (far longer than the 3 Ranvier nodes specified in
textbooks) except at very increased LA concentrations.
39
Extent and duration of LA effects can be loosely correlated
with LA content of nerves in animal experiments.
38,40-42
There is debate as to whether volume, concentration, or
mass (volume x concentration) of drug is paramount in determining the success of blocks. In rat sciatic nerve blocks,
lower volumes of more concentrated lidocaine produce shorter latencies and longer durations.
42
Nevertheless, human
studies generally find that anesthesia quality improves with increasing mass of drug, whether achieved by increasing
volume or concentration!
43,44
Despite the increasing use of ultrasound, accidental intravenous injection remains a
risk, despite direct visualization of injections and reduced volumes of injectate.
Maximum doses
It is ridiculous to speak of one, universal, safe maximal dose of a LA compound, yet textbooks and regulatory
agencies persist in this folly.
45
The maximal tolerable dose depends on many factors, including the site, rate, and

320
Page 3
duration of LA administration, additives, patient weight and body habitus, pregnancy, and the presence of disease.
The same LA dose given for intercostal blocks produces greater peak LA concentrations than when given for plexus
or epidural blocks.
3,46
A LA concentration in blood produced by a sudden, accidental bolus iv injection may produce
CNS toxicity; the same concentration gradually produced by slow absorption of LA during a perineural infusion
may have no discernible adverse effects.
LA Potency and Duration
Nerve-blocking potency of LAs increases with increasing molecular weight and increasing lipid solubility.
46-48

Larger, more lipid-soluble LAs bind Na
v
channels with greater affinity, are highly protein-bound in blood, and less
readily washed out from nerves than smaller, less lipid-soluble LAs. Increased lipid solubility also associates with
increased protein binding, longer duration of action, and an increased potency at CV toxicity. Think of the profound
reduction in potency, onset delay, and duration of block that result from a methyl for butyl substitution (mepivacaine
vs bupivacaine, see Figure 1).
LA Speed of Onset
Generally, the onset of clinical regional anesthesia slows with increasing LA lipid solubility (compare
mepivacaine to bupivacaine and chloroprocaine to tetracaine). Curiously, many textbooks view pKa as inversely
related to delay of onset despite contradictory data!
4,46
Chloroprocaine, the agent with the largest pKa, has the
shortest delay of onset of all.
49

Differential Sensory Nerve Block
A nerve block sufficient to block incisional pain will impair motor function.
2-4
Greater LA concentrations are
required to block impulses in C fibers than in A# or A" fibers.
40,50
Smaller fibers can be blocked at lower
concentrations of LA than larger fibers of the same type.
2
Bupivacaine and ropivacaine are relatively selective for
sensory fibers.
51
As previously noted, differing Na
v
channel forms have distinct affinities for LAs and other
compounds, and specific Na
v
channel gene products are found in unmyelinated nerves, motor nerves, and dorsal root
ganglia, offering the tantalizing possibility of selective drugs.
24,52,53

Other Factors Influencing LA Activity
Many factors influence the quality of local and regional anesthesia, including the dose, site of administration,
temperature, pregnancy, and additives. In general, the fastest onset and shortest duration of anesthesia occur with
intrathecal or subcutaneous injections; a slower onset and longer duration are obtained with plexus and peripheral
nerve blocks.
4,46
Pain on injection of warmed LAs is less than with room temperature LAs, which hurt less than
refrigerated LAs.
54
Pregnancy increases both spread of neuraxial anesthesia and neuronal susceptibility to LAs.
4,55,56

Is There Convincing Evidence for Preemptive Effects of Local Anesthetics?
Many studies show postoperative analgesia from peripheral nerve blocks or local anesthetic infusions that
persists for multiples of the local anesthetic elimination half-life, during which time the need for opioids and other
agents is greatly reduced, It is likely that absorbed local anesthetic may contribute to analgesia following nerve
blocks; however, most studies indicate that actual nerve blocks provide better analgesia than local anesthetic
infusions. Finally, whether nerve blocks are administered before or immediately after the surgical procedure does
not appear to be of major importance.
35

LA Additives and LA Mixtures
The most popular LA additives in anesthesia practice (epinephrine, clonidine, opioids, NaHCO
3
, dextrose, and
steroids) are variously added to increase the safety, quality, distribution, duration, and speed of onset of anesthesia,
and to reduce blood loss.
3,4,46
Clonidine and other !
2
-adrenergic agonists have LA properties and prolong the
duration of nerve blocks produced by lidocaine and mepivacaine.
3,11
NaHCO
3
increases the fraction of LA molecules
that are uncharged, increases the apparent LA potency, and speeds the onset of some nerve blocks.
3,5,57
Bicarbonate
also reduces the pain of local infiltration.
58
Opioids are commonly added to spinal or epidural LAs. Mixing of LAs
has long been popular; e.g., mepivacaine is often mixed with bupivacaine in the hope of decreasing the latters onset
delay. Nevertheless, data are sparse and most often indicate that mixtures yield onset delays and durations
approximating the mean of the component LAs. Toxicity of mixed LAs appears to be additive.
59

There are persisting misconceptions about epinephrine. One is that LA-epinephrine solutions are unsafe in
patients at risk for coronary artery disease. However, in high-risk patients, epinephrine reduces LA concentrations
in blood without producing tachycardia, arrhythmias, or myocardial ischemia.
60
Another misconception is that
epinephrine is unsafe in digital nerve blocks. Review of the published medical literature shows no amide LA-
epinephrine combination ever having been linked to gangrene after digital block. LA solutions containing
epinephrine are now widely used by dermatologists and hand surgeons for digital nerve blocks.
61

320
Page 4
LA Blood Concentrations, Protein Binding, Metabolism, and Pharmacokinetics
In blood, all LAs are partially protein-bound, primarily to !
1
-acid glycoprotein (AAGP) and secondarily to
albumin.
2,46
LA affinity for AAGP increases with hydrophobicity and decreases with protonation.
62
Extent of protein
binding increases with increasing concentrations of AAGP. Protein binding and AAGP concentrations decline
during pregnancy.
63
During longer infusions of LA, concentrations of serum binding proteins progressively
increase.
64
There is considerable first-pass uptake of LAs by lung.
65
Ester LAs undergo rapid hydrolysis in blood,
catalyzed by pseudocholinesterase.
2,3,46
Procaine and benzocaine are metabolized to p-aminobenzoic acid (PABA).
Amide LAs undergo oxidative N-dealkylation in the liver (by cytochrome P450).
2,3,46
Amide LA clearance depends
on hepatic blood flow, hepatic extraction, and enzyme function; clearance is reduced by drugs and conditions that
decrease hepatic blood flow such as "-adrenergic or H
2
-receptor blockers, and heart or liver failure.
2,3,46

Toxic Side Effects of LAs
LAs can produce a long list of toxic side effects of which the following types seem to be associated with the
greatest frequency of misconception and confusion.
Methemoglobinemia
Generations of textbooks have described the unique and predictable production of methemogloblinemia at
prilocaine doses >600 mg in adults.
46
In fact, lower doses given to healthy patients will produce toxic
methemoglobinemia.
66
Perioperative methemogloblinemia in North America more commonly results from
benzocaine, dehydration, or and other drugs than from prilocaine!
67
Thus, topical benzocaine (formerly ubiquitous
in endoscopy suites) has been removed from the formularies of many hospitals.
Allergy
Textbooks state (without providing data) that there is greater risk of allergy to ester than amide LAs,
particularly to those LAs metabolized to p-aminobenzoic acid (procaine and benzocaine).
46
True LA allergy is rare.
Despite an apparent allergic or even anaphylactoid reaction, only a rare tested patient will have a IgE immune
responses to preservative-free LAs.
68-70
Allergy to LAs must be distinguished from allergy to other agents (e.g. latex,
antibiotics, paralytics, blood products) and other conditions that are common in the perioperative patient.
71

Cardiovascular (CV) Toxicity
LA-associated death after cocaine or tetracaine topical anesthesia was formally studied by a national
commission in the 1930s. After eighty years many important, fundamental issues remain unsettled, including: 1.
What are the mechanisms of LA CV toxicity? 2. Do all LAs produce CV toxicity by one mechanism? 3. Which
animal model best mimics clinical LA systemic toxicity (LAST)?
72,73

Laboratory studies provide insight into why bupivacaine appears to have a greater propensity to produce severe
LAST than most other LAs. Bupivacaine binds cardiac Na
v
channels more avidly and longer than lidocaine.
3-5
R(+)
isomers bind cardiac Na
v
channels more avidly than S(-) isomers (levobupivacaine and ropivacaine).
74
LAs inhibit
cardiac conduction with the same rank order of potency as for nerve block.
75
LAs produce myocardial depression.
LAs bind and inhibit cardiac Ca and K channels, but at concentrations greater than needed to inhibit Na
v

channels.
3.4,76
LAs bind "-adrenergic receptors and antagonize epinephrine stimulation of adenylyl cyclase.
77,78
LAs
produce CNS excitation, tachycardia, and hypertension at lower doses and concentrations than those associated with
cardiac depression. In animal experiments, most LAs will only produce CV toxicity at blood concentrations greatly
exceeding those producing seizures; however, experimental and clinical reports suggest a reduced margin of safety
for bupivacaine.
2,3,79
In dogs, supraconvulsant doses of bupivacaine more commonly produce arrhythmias than
supraconvulsant doses of ropivacaine or lidocaine.
79
Animals premedicated with midazolam or diazepam (or
receiving general anesthesia) may manifest bupivacaine LAST as CV collapse without convulsions.
80

In animals, the rank order of potency for cardiac toxicity appears to be the same as for nerve block.
81,82
Both
programmed electrical stimulation and epinephrine elicit more arrhythmias with bupivacaine than with lidocaine or
ropivacaine.
83-85
When given LAs to the point of extreme hypotension, dogs given lidocaine were resuscitated, but
required continuing infusion of epinephrine to counteract LA-induced myocardial depression. After bupivacaine or
ropivacaine, some dogs required only electrical defibrillation; others could not be resuscitated using the full ACLS
armamentarium.
83-85
Studies in pigs also show that bupivacaine (compared to lidocaine) may have a greater relative
potency for producing both arrhythmias and myocardial depression, but that the potency ratio for producing
arrhythmias is much greater (16:1) as compared to their relative potency at producing nerve block .
86

Chondrotoxicity
In recent years there has been increasing use of LA infusions into surgical wounds for postoperative pain control.
Some patients who have received LA infusions into joint spaces have developed long term adverse outcomes related
to chondromalacia, and this has resulted in litigation against physicians, and suppliers of LAs and wound infusion

320
Page 5
pumps. There is an increasingly large literature on the adverse effects of LA infusions on articular cartilage and a
growing consensus that prolonged exposure (days) of articular cartilage to LAs may be ill-advised.
87-89

Treatment of LA Toxicity
Serious degrees of methemoglobinemia are treated with oxygen and methylene blue 1 mg/kg IV. Anaphylactoid
reactions may require epinephrine, fluid resuscitation, and steroids. Minor LA reactions usually will terminate
spontaneously. Severe LAST requires active treatment in which adherence to a check-list protocol will likely
increases patient safety.
90
LA-induced seizures require maintenance of adequate ventilation and oxygenation and
protection of the patient from injury. Seizures may be terminated with IV midazolam (0.05-0.10 mg/kg), propofol
(0.5-1 mg/kg), or perhaps intravenous lipid.
3,73,91,92
If LA intoxication produces hypotension it may be treated by
infusion of vasopressors (phenylephrine 0.5-5 mcg/kg/min, norepinephrine 0.02-0.2 mcg/kg/min, or vasopressin 2-
20 units IV). If cardiac arrest is present, it is reasonable to follow the guidelines for Advanced Cardiac Life
Support.
93
Epinephrine and/or vasopressin may be required, and there is controversy as to which is the better choice
in this setting.
92,94
A survey of academic anesthesia departments in the USA confirmed inadequate understanding
and no consensus regarding resuscitation drugs for LAST.
95

With unresponsive LA CV toxicity, IV lipid should be administered and cardiopulmonary bypass (or other
forms of mechanical cardiopulmonary support) should be considered.
96-98
Animal experiments and human case
reports describe the ability of lipid infusion to resuscitate animals from bupivacaine LAST, even after
"conventional" resuscitative efforts (including ventilation with oxygen, chest compressions, and ACLS drugs) have
proven unsuccessful.
96,97
Lipids mechanism of action is not clear, although the prevailing opinion is that the LA is
absorbed into a lipid sink.There is also evidence that certain lipids may antagonize the binding of LAs to the Na
v

channel.
99
In animal studies, administration of long-chain lipids (e.g. Intralipid
TM
) for LAST was associated with
fewer episodes of asystole and with reduced myocardial local anesthetic concentrations than mixed long- and
medium-chain lipid emulsion.
100
On the other hand, in vitro experiments suggest that mixed long- and medium-
chain emulsions more effectively extract local anesthetics from human serum than long-chain emulsions.
101
Lipid
appears effective for over-dosage with lipophilic compounds other than LAs such as bupropion and lamotrigine, and
has also been used for lidocaine overdoseage in the critical care unit.
102
Some now speculate that lipid therapy
should be initiated for incipient LA toxicity (e.g. for CNS symptoms) before conventional drug treatments.

No toxic
side effects of lipid resuscitation have been reported in adults.

Summary
After 125 years the place of both LAs and regional blocks in medical practice remains secure. Some features of
local and regional anesthesia are well understood. Peripheral nerve blocks almost certainly result from LA inhibition
of Na
v
channels in axonal membranes. On the other hand, the relative clinical potency of the various LAs remains
poorly defined,
103
and the mechanisms of spinal and epidural anesthesia are unclear. LAs may produce CV toxicity
by more than 1 mechanism: more potent agents (bupivacaine) have greater propensity for arrhythmias and
conduction disturbances than less potent agents (lidocaine); all LAs at increased concentrations will produce
myocardial depression. Avoiding LAST is clearly preferable to treating it, and ultrasound guidance may help us
reduce (but not remove) the risk during regional nerve blocsk.
104
Finally, the reports of successful lipid resuscitation
suggest that we have a simple and safe treatment for LAST at hand.

References
1. Calatayud J, Gonzlez A. Anesthesiology 98:1503-8, 2003
2. Strichartz GR, ed. Local Anesthetics: Handbook of Experimental Pharmacology vol 81, 1987
3. Hadzik A, ed. Textbook of Regional Anesthesia and Acute Pain Management. New York: McGraw Hill, 2007
4. Butterworth JF IV, Strichartz GR. Anesthesiology 72:711-34, 1990
5. Hille B. Ion Channels of Excitable Membranes, 3rd ed. Sunderland, MA: Sinauer Associates, Inc., 2001
6. Wang GK, Calderon J, Wang SY. Mol Pharmacol. 73:940-8, 2008
7. Lim TK, Macleod BA, Ries CR, Schwarz SK. Anesthesiology 107:305-11, 2007
8. Ries CR et al. Anesthesiology 111:122-6, 2009
9. Sudoh Y et al. Pain 103:49-55, 2003
10. Kohane DS et al. Reg Anesth Pain Med 25:52-59, 2000
11. Butterworth JF IV, Strichartz GR. Anesth Analg 76:295-301, 1993
12. Horishita T, Harris RA. J Pharmacol Exp Ther 326:270-7, 2008
13. Rodriguez-Navarro AJ et al. Reg Anesth Pain Med 36:103-9, 2011
14. Butterworth JF IV. Reg Anesth Pain Med 36:101-2, 2011

320
Page 6
15. David M et al. Biochem Biophys Res Commun. 368:761-6, 2008
16. Lopez-Santiago LF et al. J Neuroscience 26:7984-7994, 2006
17. Zakon HH. Proc Nat Acad Sci USA 109:10619-25, 2012
18. Waxman SG. J Physiol 590:2601-12, 2012
19. Doki K et al. Pharmacokinetics and Genomics (in press) 2013
20. Chatelier A et al. J Neurophysiol. 99:2241-50, 2008
21. Dib-Hajj SD et al. Ann Rev Neurosci 33:325-47, 2010
22. Dib-Hajj SD et al. Nat Rev Neurosci 14:49-62, 2013
23. Xie W et al. Pain (in press), 2013
24. Mike A, Lukacs P. Curr Mol Pharmacol 3:129-44, 2010
25. Leffler A et al. J Pharmacol Exp Ther 320:354-364, 2007
26. Kistner K et al. Pflugers Arch 459:751-763, 2010
27. Binshtok AM, Bean BP, Woolf CJ. Nature 449:607-10, 2007
28. Butterworth J, Oxford GS. Anesthesiology 111:12-4, 2009
29. Binshtok AM, et al. Anesthesiology 111:127-37, 2009
30. ONeill J et al. Pharmacol Rev 64:939-71, 2012
31. Yanagidate F, Strichartz G. Handb Exp Pharmacol 177:95-127, 2007
32. Siebrands CC, Friederich P. Anesthesiology 106:523-31, 2007
33. Butterworth JF 4th. Reg Anesth Pain Med. 32:459-61, 2007
34. Hahnenkamp K et al. Anesth Analg 94:1441-7, 2002
35. Barreveld A, et al. Anesth Analg 116:1141-61, 2013
36. Kaczmarek DJ et al Anesthesiology 110:1041-9, 2009
37. Villarruel EQ et al. Cell Biol Int. 35:783-8, 2011
38. Popitz-Bergez FA et al. Anesthesiology 83:583-92, 1995
39. Raymond SA et al. Anesth Analg 68:563-70, 1989
40. Huang JH et al. J Pharmacol Exp Ther 282:802-811, 1997
41. Sinnott CJ et al. Anesthesiology 98:181-8, 2003
42. Nakamura T et al. Anesthesiology 99:1189-97, 2003
43. Liu SS, Ware PD, Rajendran S. Anesthesiology 86:1288-1293, 1997
44. Krenn H et al. Eur J Anaesthesiol 20:21-25, 2003
45. Rosenberg PH, Veering BT, Urmey WF. Reg Anesth Pain Med 29:564-75, 2004
46. Covino BG, Vasallo HG. Local Anesthetics. New York: Grune & Stratton, 1976
47. Sanchez V, Arthur GR, Strichartz GR. Anesth Analg 66:159-65, 1987
48. Strichartz GR et al. Anesth Analg 71:158-70, 1990
49. Kouri ME, Kopacz DJ. Anesth Analg 98:75-80, 2004
50. Gokin AP, Philip B, Strichartz GR. Anesthesiology 95:1441-54, 2001
51. Butterworth J et al. Br J Anaesth 81:515-21, 1998
52. Lang PM, Hilmer VB, Grafe P. Anesthesiology 107:495-501, 2007
53. Amir R et al. J Pain 7:S1-S29, 2006
54. Tomlinson PJ, Field J. J Hand Surg 35:232-3, 2010
55. Butterworth JF IV, Walker FO, Lysak SZ. Anesthesiology 72:962-5, 1990
56. Popitz-Bergez FA et al. Reg Anesth 22:363-71, 1997
57. Butterworth JF IV, Lief PA, Strichartz GR. Anesthesiology 68:501-6, 1988
58. Davies RJ. Emerg Med 15:81-8, 2003
59. Munson ES, Paul WL, Embro WJ. Anesthesiology 46:179-83, 1977
60. Harwood TN et al. J Cardiothorac Vasc Anesth 13:703-6, 1999
61. Krunic AL et al. J Am Acad Dermatol. 51:755-9, 2004
62. Taheri S et al. J Pharmacol Exp Ther 304:71-80, 2003
63. Fragneto RY, Bader AM, Rosinia F, et al. Anesth Analg 79:295-7, 1994
64. Thomas JM, Schug SA. Clin Pharmacokinet 36:67-83, 1999
65. Rothstein P et al. Anesth Analg 65:625-32, 1986
66. Guay J. Anesth Analg 108:837-45, 2009
67. Ash-Bernal R, Wise R, Wright SM. Medicine 83:265-73, 2004
68. Berkun Y et al. Ann Allergy Asthma Immunol 91:342-5, 2003
69. Jacobsen RB, Borch JE, Bindslev-Jensen C. Allergy 60:262-4, 2005
70. Harboe T et al. Acta Anaesthesiol Scand. 54:536-42, 2010

320
Page 7
71. Ewan PW et al. Clin Exp Allergy 40:15-31, 2010
72. Butterworth JF IV. Reg Anesth Pain Med 35:167-76, 2010
73. Wolfe JW, Butterworth JF. Curr Opin Anaesthesiol. 24:561-6, 2011
74. Nau C, Strichartz GR. Anesthesiology 97:495-502, 2002
75. Heavner JE. Reg Anesth Pain Med 27:545-55, 2002
76. McCaslin PP, Butterworth J. Anesth Analg 91:82-8, 2000
77. Butterworth JF IV et al. Anesthesiology 79:88-95, 1993
78. Butterworth J, James RL, Grimes J. Anesth Analg 85:336-42, 1997
79. Feldman HS, Arthur GR, Covino BG. Anesth Analg 69:794-801, 1989
80. Bernards CM et al. Anesthesiology 70:318-23, 1989
81. Ohmura S et al. Anesth Analg 93:743-8, 2001
82. Chang DH et al. Br J Pharmacol 132:649-58, 2001
83. Groban L et al. Anesth Analg 91:1103-11, 2000
84. Groban L et al. Anesth Analg 92:37-43, 2001
85. Groban L et al. Reg Anesth Pain Med 27:460-8, 2002
86. Nath S et al. Anesth Analg 65:1263-70, 1986
87. Yeh PC, Kharrazi FD. J Am Acad Orthop Surg 20:102-12, 2012
88. Piper SL et al. Am J Sports Med. 39:2245-53, 2011
89. Wiater BP et al. J Bone Joint Surg Am. 93:615-25, 2011
90. Neal JM, Mulroy MF, Weinberg GL. Reg Anesth Pain Med. 37:16-8, 2012
91. Butterworth JF. Reg Anesth Pain Med 34:187-8, 2009
92. Neal JM et al. Reg Anesth Pain Med 35:152-61, 2010
93. see: http://circ.ahajournals.org/content/122/18_suppl_3.toc (accessed 31 May2013)
94. Mayr VD et al. Anesth Analg 106:1566-71, 2008
95. Corcoran W et al. Anesth Analg 103:1322-6, 2006
96. Weinberg G. Anesthesiology 117:180-7, 2012
97. see: http://www.lipidrescue.org/ (accessed 31 May 2013)
98. Soltesz EG, van Pelt F, Byrne JG. J Cardiothorac Vasc Anesth 17:357-358, 2003
99. Mottram AR, Valdivia CR, Makielski JC. Clin Toxicol (Phila). 49:729-33, 2011
100. Li Z et al. Anesthesiology 115:1219-28, 2011
101. Ruan W et al. Anesthesiology 116:334-9, 2012
102. Mottram AR, Page RL. Circulation 126:991-1002, 2012
103. Butterworth JF 4th. Reg Anesth Pain Med 33:1-3, 2008
104. Neal JM. Reg Anesth Pain Med 35(2 Suppl):S59-67, 2010

Disclosure

holders.
326
Page 1
Regional Anesthesia and the Trauma Patient
Laura Clark M.D. Louisville, Kentucky
Objectives:
1. Choose techniques of never blockade that would be applicable to the trauma patient
2. Explain the current rationale of the beneficial effects of pain relief to the trauma patient
3. Discuss the practical problems in the trauma population such as compartment syndrome, nerve injury
4. Apply continuing catheters and multiple catheters in the trauma patient with multiple injuries and operations
Overview of Trauma Physiology
1. Why pain relief is important
i) Minimize opioid need
(1) Minimize side effects
(2) Respiratory depression
(3) Excessive sedation precluding assessment
ii) Minimize immune suppression
2. Physiology of pain in the trauma patient
i) Hormonal , biochemical
ii) Hypermetabolic response
iii) Proinflammatory state
(1) NF-Kappa Beta
iv) Neurochemistry
(1) Neurotransmitters
(2) Inflammatory mediators
(a) Interleukins
(b) Cytokines
3. The differences in the pain in trauma versus pain in elective surgery
i) Advantages of regional anesthesia : How regional anesthesia and analgesia can be beneficial
ii) The role of multimodal therapy in pain relief in trauma
4 . Additional benefits of regional anesthesia and local anesthetics on perioperative outcome
v) Alternative effects systemic absorption
(1) Intravenous effects of local anesthetics
holders.
326
Page 2
Regional Anesthesia in Other Environments
i) Ambulance
ii) Emergency Room
iii) Battlefield
Chronic Pain in the Trauma Patient
i) Traumatic Amputation
(1) Phantom Limb Pain
ii) TheChronic Pain Patient with Acute Pain
Practical Problems in Trauma Patients
(1) Consent
(2) Positioning
(3) Performing Regional Anesthesia in the presence of nerve injury
(4) The trauma patient with Coagulopathy
(5) Compartment syndrome
Situations Unique to the Trauma Patient
(1) Thoracic Trauma
(a) Treatment of Pain from Rib fractures
(i) Paravertebral
(ii) Epidural
Peripheral Nerve Block and Peripheral Catheters
(1) Single Shot vs Continuous Catheter(s)
(a) Indications
(2) Upper Extremity Blocks and Catheters
(3) Lower Extremity Blocks and Catheters
(4) Ultrasound and Nerve Stimulators \
(5) Complications
Case Examples of Application of Regional Analgesia
(1) Multiple Catheters and Blocks in the Polytrauma Patient
(2) Case of Traumatic Amputation with Prolonged Quad Catheters
(3) Simultaneous Surgery on Bilateral Upper Extremity Trauma
BIBLIOGRAPHY
1. Whitten, C.W. & Greilich, P.E. Thromboelastography (R): Past, Present, and Future. Anesthesiology 92, 1226
(2000).
2. Wu, C.L. & Fleisher, L.A. Outcomes research in regional anesthesia and analgesia. Anesthesia & Analgesia
91,1232 (2000).
3. Wu, C.L. et al. The effect of pain on health-related quality of life in the immediate postoperative period.
Anesthesia & Analgesia 97, 1078 (2003).
holders.
326
Page 3
4. Wu, C.L. et al. Effect of postoperative epidural analgesia on morbidity and mortality following surgery in
medicare patients. Regional anesthesia and pain medicine 29, 525-533 (2004).
5. Wu, C.L. et al. Correlation of postoperative epidural analgesia on morbidity and mortality after colectomy in
Medicare patients. Journal of clinical anesthesia 18, 594-599 (2006).
6. Perkins, F.M. & Kehlet, H. Chronic pain as an outcome of surgery: a review of predictive factors.
Anesthesiology 93, 1123 (2000).
7. Popping, D.M. et al. Effectiveness and safety of postoperative pain management: a survey of 18 925
consecutive patients between 1998 and 2006 (2nd revision): a database analysis of prospectively raised data.429
Page 9 British Journal of Anaesthesia 101, 832 (2008).
8. Cashman, J.N. & Dolin, S.J. Respiratory and haemodynamic effects of acute postoperative pain management:
evidence from published data. British Journal of Anaesthesia 93, 212 (2004).
9. Malchow, R.J. & Black, I.H. The evolution of pain management in the critically ill trauma patient: Emerging
concepts from the global war on terrorism. Critical care medicine 36, S346 (2008).
10. Cohen, S.P., Christo, P.J. & Moroz, L. Pain management in trauma patients. American Journal of Physical
Medicine & Rehabilitation 83, 142 (2004).
11. Holte, K. & Kehlet, H. Epidural anaesthesia and analgesia-effects on surgical stress responses and implications
for postoperative nutrition. Clinical nutrition 21, 199-206 (2002).
12. Rodgers, A. et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results
from overview of randomised. British Medical Journal 321, 1493 (2000).
13. Richman, J.M. et al. Does continuous peripheral nerve block provide superior pain control to opioids? A
metaanalysis. Anesthesia & Analgesia 102, 248 (2006).
14. Tziavrangos, E. & Schug, S.A. Regional anaesthesia and perioperative outcome. Current Opinion in
Anesthesiology 19, 521 (2006).
15. Evans, H., Steele, S.M., Nielsen, K.C., Tucker, M.S. & Klein, S.M. Peripheral nerve blocks and continuous
catheter techniques. Anesthesiology Clinics of North America 23, 141-162 (2005).
16. Wu, C.L. et al. Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus
intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology 103, 1079 (2005).
17. Werawatganon, T. & Charuluxananan, S. Patient controlled intravenous opioid analgesia versus continuous
epidural analgesia for pain after intra-abdominal surgery. Anesthesia & Analgesia 100, 1536 (2005).
18. Schug, S.A. The effect of neuraxial blockade on peri-operative mortality and major morbidity: an updated meta-
analysis. Anesth Intens Care 33, 675 (2005).
19. Jrgensen, H., Wetterslev, J., Miniche, S. & Dahl, J.B. Epidural local anaesthetics versus opioid-based
analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane
Database Syst Rev CD001893 (2000).doi:10.1002/14651858.CD001893
20. Steinbrook, R.A. Epidural anesthesia and gastrointestinal motility. Anesthesia and analgesia 86, 837-844 (1998).
21. Turner, J.A., Cardenas, D.D., Warms, C.A. & McClellan, C.B. Chronic pain associated with spinal cord
injuries: A community survey*. Archives of physical medicine and rehabilitation 82, 501-508 (2001).
22. Joshi, G.P. & Ogunnaike, B.O. Consequences of inadequate postoperative pain relief and chronic persistent
postoperative pain. Anesthesiology Clinics of North America 23, 21-36 (2005).
23. Hahnenkamp, K., Herroeder, S. & Hollmann, M.W. Regional anaesthesia, local anaesthetics and the surgical
stress response. Best Practice & Research Clinical Anaesthesiology 18, 509-527 (2004).
24. Mikawa, K. et al. Effect of lidocaine pretreatment on endotoxin-induced lung injury in rabbits. Anesthesiology
81, 689 (1994).
25. Schmidt, W., Schmidt, H., Bauer, H., Gebhard, M.M. & Martin, E. Influence of lidocaine on endotoxin-induced
leukocyte-endothelial cell adhesion and macromolecular leakage in vivo. Anesthesiology 87, 617 (1997).
26. Gallos, G., Jones, D.R., Nasr, S.H., Emala, C.W. & Lee, H.T. Local anesthetics reduce mortality and protect
against renal and hepatic dysfunction in murine septic peritonitis. Anesthesiology 101, 902 (2004).
27. Thompson, G.E. Anesthesia for battle casualties in Vietnam. JAMA 201, 215-9 (1967).
28. Jenicek, J.A., Perry, L.B. & Thompson, G.E. Armed Forces anesthesiology comes of age. Anesthesia and
analgesia 46, 822
29. Jowitt, M.D. & Knight, R.J. Anaesthesia during the Falklands campaign. Anaesthesia 38, 776-783 (2007).
30. Buckenmaier III, C.C. et al. Continuous peripheral nerve block in combat casualties receiving low-molecular
weight heparin. British Journal of Anaesthesia 97, 874 (2006).
31. Raja, S.N. Is an ounce of preoperative local anesthetic better than a pound of postoperative analgesic? Regional
anesthesia 21, 277
holders.
326
Page 4
32. Castillo, R.C., MacKenzie, E.J., Wegener, S.T. & Bosse, M.J. Prevalence of chronic pain seven years following
limb threatening lower extremity trauma. Pain 124, 321-329 (2006).
33. Urquhart, D.M. et al. Outcomes of patients with orthopaedic trauma admitted to level 1 trauma centres. ANZ
JSurg 76, 600-606 (2006).
34. Jenson, M.G. & Sorensen, R.F. Early use of regional and local anesthesia in a combat environment may prevent
the development of complex regional pain syndrome in wounded combatants. Mil Med 171, 396-398 (2006).
35. Schley, M. et al. Continuous brachial plexus blockade in combination with the NMDA receptor antagonist
memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain 11, 299-308 (2007).429
Page 10
36. Prantl, L., Schreml, S., Heine, N., Eisenmann-Klein, M. & Angele, P. Surgical treatment of chronic phantom
limb sensation and limb pain after lower limb amputation. Plastic and reconstructive surgery 118, 1562 (2006).
37. Bredahl, C., Kristensen, A.K. & Christensen, K.S. Treatment of reflex dystrophy with continuous
peripheralnerve block. Ugeskrift for laeger 169, 59 (2007).
38. Dadure, C. et al. Continuous peripheral nerve blocks at home for treatment of recurrent complex regional pain
syndrome I in children. Anesthesiology 102, 387 (2005).
39. Horlocker, T.T. et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA
Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Regional anesthesia and pain medicine 28,
172 (2003)updated 2010
40. Kariya, N., Oda, Y., Yukioka, H. & Fujimori, M. [Effective treatment of a man with head injury and multiple rib
fractures with epidural analgesia]. Masui 45, 223-226 (1996).
41. Flagel, B.T. et al. Half-a-dozen ribs: the breakpoint for mortality. Surgery 138, 717-725 (2005).
42. Holcomb, J.B., McMullin, N.R., Kozar, R.A., Lygas, M.H. & Moore, F.A. Morbidity from rib fractures
increases after age 45. Journal of the American College of Surgeons 196, 549 (2003).
43. Karmakar, M.K. et al. Continuous thoracic paravertebral infusion of bupivacaine for pain management in
patients with multiple fractured ribs. Chest 123, 424 (2003).
44. Dhole, S., Mehta, Y., Saxena, H., Juneja, R. & Trehan, N. Comparison of continuous thoracic epidural and
paravertebral blocks for postoperative analgesia after minimally invasive direct coronary artery bypass
surgery.Journal of cardiothoracic and vascular anesthesia 15, 288-292 (2001).
45. Matthews, P.J. & Govenden, V. Comparison of continuous paravertebral and extradural infusions of
bupivacaine for pain relief after thoracotomy. British journal of anaesthesia 62, 204 (1989).
46. Perttunen, K. et al. Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain.
BritishJournal of anaesthesia 75, 541 (1995).
47. Grass, J.A. Surgical outcome. Regional anaesthesia and analgesia versus general anaesthesia. Anaesth Rev
20,117-125 (1993).
48. Capdevila, X., Ponrouch, M. & Choquet, O. Continuous peripheral nerve blocks in clinical practice.
CurrentOpinion in Anesthesiology 21, 619 (2008).
49. Telion, C. & Carli, P. Prehospital and emergency room pain management for the adult trauma patient.
Techniques in Regional Anesthesia and Pain Management 6, 2-9 (2002).
50. Ritsema, T.S., Kelen, G.D., Pronovost, P.J. & Pham, J.C. The national trend in quality of emergency
department pain management for long bone fractures. Academic Emergency Medicine 14, 163-169 (2007).
51. Buckenmaier III, C.C. & Bleckner, L.L. Continuous peripheral nerve blocks and anticoagulation. British
Journal of Anaesthesia 101, 139 (2008).
52. Perlas, A. et al. Ultrasound-guided supraclavicular block: outcome of 510 consecutive cases. Regional
Anesthesia and Pain Medicine 34, 171 (2009).
53. Elliott, K.G.B. & Johnstone, A.J. Diagnosing acute compartment syndrome. Journal of Bone & Joint Surgery,
British Volume 85, 625 (2003).
54. Wiegel, M., Gottschaldt, U., Hennebach, R., Hirschberg, T. & Reske, A. Complications and adverse
effectsassociated with continuous peripheral nerve blocks in orthopedic patients. Anesthesia & Analgesia 104,
1578(2007).
DISCLOSURE
Covidien ,Honoraria ; Cadence ,Honoraria
332
Page 1
Hemorrhagic and Infectious Complications of Neuraxial Anesthesia
Terese T. Horlocker, M.D. Rochester, Minnesota
Spinal Hematoma
The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with
neuraxial blockade is unknown; however, recent epidemiologic studies suggest the incidence is increasing (1).

In a
review of the literature between 1906 and 1994, Vandermeulen et al. (2) reported 61 cases of spinal hematoma associated
with epidural or spinal anesthesia. In 87% of patients, a hemostatic abnormality or traumatic/difficult needle placement
was present. More than one risk factor was present in 20 of 61 cases. Importantly, although only 38% of patients had
partial or good neurologic recovery, spinal cord ischemia tended to be reversible in patients who underwent laminectomy
within eight hours of onset of neurologic dysfunction.
It is impossible to conclusively determine risk factors for the development of spinal hematoma in patients
undergoing neuraxial blockade solely through review of the case series, which represent only patients with the
complication and do not define those who underwent uneventful neuraxial analgesia. However, large inclusive
surveys that evaluate the frequencies of complications (including spinal hematoma), as well as identify subgroups of
patients with higher or lower risk, enhance risk stratification. In the series by Moen et al. (3) involving nearly 2 million
neuraxial blocks, there were 33 spinal hematomas. The methodology allowed for calculation of frequency of spinal
hematoma among patient populations. For example, the risk associated with epidural analgesia in women undergoing
childbirth was significantly less (1 in 200,000) than that in elderly women undergoing knee arthroplasty (1 in 3600,
p<0.0001). Likewise, women undergoing hip fracture surgery under spinal anesthesia had an increased risk of spinal
hematoma (1 in 22,000) compared to all patients undergoing spinal anesthesia (1 in 480,000).
Overall, these series suggest that the risk of clinically significant bleeding varies with age (and associated
abnormalities of the spinal cord or vertebral column), the presence of an underlying coagulopathy, difficulty during
needle placement, and an indwelling neuraxial catheter during sustained anticoagulation (particularly with standard
heparin or LMWH). They also consistently demonstrate the need for prompt diagnosis and intervention. Practice
guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a
prospective-randomized study, and there is no current laboratory model. As a result, the consensus statements developed
by the American Society of Regional Anesthesia and Pain Medicine represent the collective experience of recognized
experts in the field of neuraxial anesthesia and anticoagulation (4). They are based on case reports, clinical series,
pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is
essential to patient management.
Oral Anticoagulants
Clinical experience with patients who, congenitally, are deficient in factors II, IX, or X suggests that a factor
activity level of 40% for each factor is adequate for normal or near-normal hemostasis. Bleeding may occur if the level
of any clotting factor is decreased to 20% to 40% of baseline. The PT is most sensitive to the activities of factors VII
and X and is relatively insensitive to factor II. During the first few days of therapy, the PT reflects primarily a
reduction of factor VII, the half-life of which is approximately 6 hrs. After a single dose, marked prolongation of the
INR may occur, although adequate factor levels are still present. However, with additional doses, an INR greater than
1.4 is typically associated with factor VII activity less that 40% (and the potential for inadequate clotting) (5).
Few data exist regarding the risk of spinal hematoma in patients with indwelling epidural catheters who are
anticoagulated with warfarin. The optimal duration of an indwelling catheter and the timing of its removal also remain
controversial. Odoom and Sih (6) performed 1000 continuous lumbar epidural anesthetics in vascular surgical patients
who were receiving oral anticoagulants preoperatively. The thrombotest (a test measuring factor IX activity) was
decreased (but not below 10% activity) in all patients prior to needle placement. Heparin was also administered
intraoperatively. Epidural catheters remained in place for 48 hours postoperatively. There were no neurologic
complications. While these results are reassuring, the obsolescence of the thrombotest as a measure of anticoagulation
combined with the unknown coagulation status of the patients at the time of catheter removal limit the usefulness of these
results. Therefore, except in extraordinary circumstances, spinal or epidural needle/catheter placement and removal
should not be performed in fully anticoagulated patients.
332
Page 2
There were no symptomatic spinal hematomas in two smaller series with a total of nearly 700 patients
undergoing neuraxial block in combination with warfarin anticoagulation perioperatively (6-8). In both studies,
epidural catheters were left indwelling approximately two days. The mean international normalized ratio (INR) at the
time of catheter removal was 1.4, although in a small number of patients the INR was therapeutic (2.0-3.0). A large
variability in patient response to warfarin was also noted, demonstrating the need for close monitoring of the
coagulation status. There were no spinal hematomas in a series of 11,235 patients receiving epidural analgesia after
total knee replacement (9). Patients received warfarin (5-10 mg) starting the night of surgery. Epidural catheters were
removed within 48 hrs. The mean INR in a subset of 1030 patients at the time of catheter removal was 1.5 (range, 0.9-
4.3); the INR was less than 1.5 in nearly 40% of patients. These series suggest that not only the INR but also the
duration of warfarin therapy must be considered and that prolongation within the first 48 hrs may represent a
significant increase in risk.
Intravenous and Subcutaneous Standard Heparin
The safety of neuraxial techniques in combination with intraoperative heparinization is well documented, providing no
other coagulopathy is present. In a study involving over 4000 patients, Rao and El-Etr

(10) demonstrated the safety of
indwelling spinal and epidural catheters during systemic heparinization during vascular surgery. However, the heparin
was administered at least 60 minutes after catheter placement, level of anticoagulation was closely monitored, and the
indwelling catheters were removed at a time when circulating heparin levels were relatively low. A subsequent study in
the neurologic literature by Ruff and Dougherty

(11) reported spinal hematomas in 7 of 342 patients (2%) who underwent
a diagnostic lumbar puncture and subsequent heparinization. Traumatic needle placement, initiation of anticoagulation
within one hour of lumbar puncture and concomitant aspirin therapy were identified as risk factors in the development of
spinal hematoma in anticoagulated patients. Subsequent studies using similar methodology have verified the safety of this
practice, provided the monitoring of anticoagulant effect and the time intervals between heparinization and catheter
placement/removal are maintained.
Low-dose subcutaneous standard (unfractionated) heparin is administered for thromboprophylaxis in patients
undergoing major thoracoabdominal surgery and in patients at increased risk of hemorrhage with oral anticoagulant or
low molecular weight heparin (LMWH) therapy. There are nine published series totaling over 9,000 patients who
have received this therapy without complications(12), as well as extensive experience in both Europe and United
States without a significant frequency of complications. There are only five case reports of neuraxial hematomas,
four epidural (2,13) and one subarachnoid,(14) during neuraxial block with the use of subcutaneous heparin.
The largest study of thrice daily unfractionated heparin involved 768 epidural catheter placements. Sixteen
patients from this group had a positive match for hemorrhage codes on their discharge records, with none of the
episodes being identified within a major hemorrhage category. Laboratory value analysis failed to reveal changes in
the aPTT values of significance (4). The safety of neuraxial blockade in patients receiving doses greater than 10,000 U
of UFH daily or more than twice-daily dosing of UFH has not been established. Although the use of thrice-daily UFH
may lead to an increased risk of surgical-related bleeding, it is unclear whether there is an increased risk of spinal
hematoma. If thrice-daily unfractionated heparin is administered, techniques to facilitate detection of new/progressive
neurodeficits (eg, enhanced neurologic monitoring occur and neuraxial solutions to minimize sensory and motor
block) should be applied.
Low Molecular Weight Heparin
Extensive clinical testing and utilization of LMWH in Europe over the last ten years suggested that there was not an
increased risk of spinal hematoma in patients undergoing neuraxial anesthesia while receiving LMWH
thromboprophylaxis perioperatively (2,15). However, in the five years since the release of LMWH for general use in the
United States in May 1993, over 60 cases of spinal hematoma associated with neuraxial anesthesia administered in the
presence of perioperative LMWH prophylaxis were reported to the manufacturer (16,17). Many of these events occurred
when LMWH was administered intraoperatively or early postoperatively to patients undergoing continuous epidural
anesthesia and analgesia. Concomitant antiplatelet therapy was present in several cases. The apparent difference in
incidence in Europe compared to the United States may be a result of a difference in dose and dosage schedule. For
example, in Europe the recommended dose of enoxaparin is 40 mg once daily (with LMWH therapy initiated 12 hours
preoperatively), rather than 30 mg every twelve hours. However, timing of catheter removal may also have an impact. It
is likely that the lack of a trough in anticoagulant activity associated with twice daily dosing resulted in catheter removal
occurring during significant anticoagulant activity. Importantly, there are no data to suggest that the risk of spinal
hematoma is increased with specific LMWH formulations (16). The incidence of spinal hematoma in patients
undergoing neuraxial block in combination with LMWH has been estimated at 1 in 40,800 spinal anesthetics and 1 in
3100 continuous epidural anesthetics (18). It is interesting in that the frequency of spinal hematoma in this series is
similar to that reported by Moen et al (3) for women undergoing total knee replacement with epidural analgesia.
Indications for thromboprophylaxis as well as treatment of thromboembolism or MI have been introduced.
These new applications and corresponding regional anesthetic management warrant discussion (19). Several off-label

332
Page 3
applications of LMWH are of special interest to the anesthesiologist. LMWH has been demonstrated to be efficacious
as a bridge therapy for patients chronically anticoagulated with warfarin, including parturients, patients with
prosthetic cardiac valves, a history of atrial fibrillation, or preexisting hypercoagulable condition. The doses of
LMWH are those associated with DVT treatment, not prophylaxis, and are much higher. An interval of at least 24
hours is required for the anticoagulant activity to resolve.

Dabigatran
Dabigatran etexilate is a prodrug that specifically and reversibly inhibits both free and clot-bound thrombin. The
drug is absorbed from the gastrointestinal tract with a bioavailability of 5%(20). Once absorbed it is converted by
esterases into its active metabolite, dabigatran. Plasma levels peak at two hours. The half-life is eight hours after a
single dose and up to 17 hours after multiple doses. It is likely that once daily dosing will be possible for some
indications because of the prolonged half-life. Because 80% of the drug is excreted unchanged by the kidneys, it is
contraindicated in patients with renal failure(21). Dabigatran prolongs the aPTT, but its effect is not linear and
reaches a plateau at higher doses. However, the ecarin clotting time (ECT) and thrombin time (TT) are particularly
sensitive and display a linear dose response at therapeutic concentrations. Reversal of anticoagulant effect is
theoretically possible through administration of recombinant factor VIIa, although this has not been attempted
clinically(21). Indeed, product labeling suggests that dialysis may be considered for patients with significant
bleeding due to dabigatran.

Rivaroxaban
Rivaroxaban is a potent selective and reversible oral activated factor Xa inhibitor, with an oral bioavailability of
80%. After administration, the maximum inhibitory effect occurs one to four hours, however, inhibition is
maintained for 12 hours. The antithrombotic effect can be monitored with the PT, aPTT and Heptest, all of which
demonstrate linear dose effects. Rivaroxaban is cleared by the kidneys and gut. The terminal elimination half-life is
nine hours in healthy volunteers and may be prolonged to 13 hours in the elderly due to a decline in renal function
(hence a need for dose adjustment in patients with renal insufficiency and contraindicated in patients with severe
liver disease).
Rivaroxaban was approved in the United States for thromboprophylaxis following total hip or knee
replacement in 2011. Overall, clinical trials comparing rivaroxaban (5- 40mg mg daily, with the first dose six to
eight hours after surgery) with enoxaparin (40 mg, beginning 12 hours before surgery) demonstrate similar rates of
bleeding and comparable efficacy. While a regional anesthetic was performed in over half of the patients included
in the clinical trials, no information regarding needle placement or catheter management was included. Although
there have been no reported spinal hematomas, the lack of information regarding the specifics of block performance
and the prolonged half-life warrants a cautious approach.

332
Page 4

Table 1 Recommendations for Management of Patients Receiving Neuraxial Blockade and Anticoagulant
Drugs
Warfarin Discontinue chronic warfarin therapy 45 days before spinal procedure and evaluate INR.
INR should be within the normal range at time of procedure to ensure adequate levels of all
vitamin K-dependent factors. Postoperatively, daily INR assessment with catheter removal
occurring with INR< 1.5
Antiplatelet
medications
No contraindications with aspirin or other NSAIDs. Thienopyridine derivatives
(clopidogrel and prasugrel) should be discontinued 5-7 days and ticlopidine 14 days prior
to procedure. GP IIb/IIIa inhibitors should be discontinued to allow recovery of platelet
function prior to procedure (8 hours for tirofiban and eptifibatide, 2448 hours for
abciximab).
Thrombolytics/
fibrinolytics
There are no available data to suggest a safe interval between procedure and initiation or
discontinuation of these medications. Follow fibrinogen level and observe for signs of
neural compression.
LMWH Delay procedure at least 12 hours from the last dose of thromboprophylaxis LMWH dose.
For "treatment" dosing of LMWH, at least 24 hours should elapse prior to procedure.
LMWH should not be administered within 24 hours after the procedure. Indwelling
epidural catheters should be maintained only with once daily dosing of LMWH and strict
avoidance of additional haemostasis altering medications, including NSAIDs.
Unfractionated SQ
heparin
There are no contraindications to a neuraxial procedure if total daily dose is less than
10,000 units. For higher dosing regimens, increase neurologic monitoring and cautiously
co-administer antiplatelet medications.
Unfractionated IV
heparin
Delay needle/catheter placement 24 hours after last dose, document normal aPTT.
Heparin may be restarted 1 hour following procedure. Sustained heparinization with an
indwelling neuraxial catheter associated with increased risk; monitor neurologic status
aggressively.
Dabigatran Discontinue 5-7 days prior to procedure; for shorter time periods, document normal TT.
First postoperative dose 24 h after needle placement and 6 hours post catheter removal
(whichever is later).
Rivaroxaban According to European guidelines, 22-26 hours should elapse between discontinuation of
rivaroxaban and neuraxial block in patients with normal renal function. Longer intervals
are required in patients with renal insufficiency. Indwelling neuraxial catheters are
contraindicated due to the boxed warning. Four to six hours is recommended between
spinal block and initiation of rivaroxaban therapy postoperatively.

Antiplatelet Medications
Antiplatelet medications are seldom used as primary agents of thromboprophylaxis. However, many orthopedic
patients report chronic use of one or more antiplatelet drugs. Although Vandermeulen et al (2) implicated
antiplatelet therapy in 3 of the 61 cases of spinal hematoma occurring after spinal or epidural anesthesia, several
large studies have demonstrated the relative safety of neuraxial blockade in both obstetric, surgical and pain clinic
patients receiving these medications (22-24). In a prospective study involving 1000 patients, Horlocker et al (24)
reported that preoperative antiplatelet therapy did not increase the incidence of blood present at the time of
needle/catheter placement or removal, suggesting that trauma incurred during needle or catheter placement is neither
increased nor sustained by these medications. The clinician should be aware of the possible increased risk of spinal
hematoma in patients receiving antiplatelet medications who undergo subsequent heparinization (11). Ticlopidine
and clopidogrel are also platelet aggregation inhibitors. These agents interfere with platelet-fibrinogen binding and
subsequent platelet-platelet interactions. The effect is irreversible for the life of the platelet. Platelet dysfunction is
present for 5-7 days after discontinuation of clopidogrel and 10-14 days with ticlopidine.
Prasugrel is a new thienopyridine that inhibits platelets more rapidly, more consistently, and to a greater
extent than do standard and higher doses of clopidogrel. In the United States, the only labeled indication is for acute
coronary syndrome in patients intended to undergo percutaneous coronary intervention. After a single oral dose,
50% of platelets are irreversibly inhibited, with maximum effect two hours after administration. Platelet aggregation
normalizes in 7-9 days after discontinuation of therapy. The labeling recommends that the drug be discontinued at
least 7 days prior to any surgery.Platelet glycoprotein IIb/IIIa receptor antagonists, including abciximab (Reopro !),

332
Page 5
eptifibatide (Integrilin !) and tirofiban (Aggrastat !), inhibit platelet aggregation by interfering with platelet-
fibrinogen binding and subsequent platelet-platelet interactions. Time to normal platelet aggregation following
discontinuation of therapy ranges from eight hours (eptifibatide, tirofiban) to 48 hours (abciximab). Increased
perioperative bleeding in patients undergoing cardiac and vascular surgery after receiving ticlopidine, clopidogrel and
glycoprotein IIb/IIIa antagonists warrants concern regarding the risk of anesthesia-related hemorrhagic complications.

Anesthetic Management of the Anticoagulated Patient
The decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient
receiving thromboprophylaxis should be made on an individual basis, weighing the small, though definite risk of
spinal hematoma with the benefits of regional anesthesia for a specific patient. Alternative anesthetic and analgesic
techniques exist for patients considered to be at an unacceptable risk. The patients coagulation status should be
optimized at the time of spinal or epidural needle/catheter placement, and the level of anticoagulation must be
carefully monitored during the period of epidural catheterization (Table 1). It is important to note that patients respond
with variable sensitivities to anticoagulant medications. Indwelling catheters should not be removed in the presence of
a significant coagulopathy, as this appears to significantly increase the risk of spinal hematoma (2,3). In addition,
communication between clinicians involved in the perioperative management of patients receiving anticoagulants for
thromboprophylaxis is essential in order to decrease the risk of serious hemorrhagic complications. The patient should
be closely monitored in the perioperative period for signs of cord ischemia. If spinal hematoma is suspected, the
treatment of choice is immediate decompressive laminectomy. Recovery is unlikely if surgery is postponed for more
than 10-12 hours; less than 40% of the patients in the series by Vandermeulen et al. (2) had partial or good recovery of
neurologic function.

Meningitis and Epidural Abscess
Bacterial infection of the central neuraxis may present as meningitis or cord compression secondary to abscess
formation. Possible risk factors include underlying sepsis, diabetes, depressed immune status, steroid therapy,
localized bacterial colonization or infection, and chronic catheter maintenance. Bacterial infection of the central neural
axis may present as meningitis or cord compression secondary to abscess formation. The infectious source for
meningitis and epidural abscess may result from distant colonization or localized infection with subsequent
hematogenous spread and CNS invasion. The anesthetist may also transmit microorganisms directly into the CNS by
needle/catheter contamination through a break in aseptic technique or passage through a contiguous infection. An
indwelling neuraxial catheter, though aseptically sited, may be colonized with skin flora and consequently serve as a
source for ascending infection to the epidural or intrathecal space.
Historically, the frequency of serious CNS infections such as arachnoiditis, meningitis, and abscess following
spinal or epidural anesthesia was considered to be extremely low- cases were reported as individual cases or small
series (25,26). However, recent epidemiologic series from Europe suggest that the frequency of infectious
complications associated with neuraxial techniques is increasing (3,27). In a national study conducted from 1997 to
1998 in Denmark, Wang et al (28) reported the incidence of epidural abscess after epidural analgesia was 1:1930
catheters. Patients with epidural abscess had an extended duration of epidural catheterization (median 6 days, range 3-
31 days). In addition, the majority of the patients with epidural abscess were immunocompromised. Often the
diagnosis was delayed; the time to first symptom to confirmation of the diagnosis was a median of five days. S. aureus
was isolated in 67% of patients. Patients without neurologic deficits were successfully treated with antibiotics, while
those with deficits underwent surgical decompression, typically with only moderate neurologic recovery. It is difficult
to determine why the frequency of symptomatic epidural abscess was so high in this series. Since perioperative
antithrombotic therapy was involved in most cases, it is possible that the epidural abscesses were infected micro
epidural hematomas, but this is not strongly supported by the diagnostic imaging studies and neurosurgical findings.
In the series by Moen et al (3) there were 42 serious infectious complications. Epidural abscess occurred in 13
patients; nine (70%) were considered immunocompromised as a result of diabetes, steroid therapy, cancer or
alcoholism. Six patients underwent epidural block for analgesia following trauma. The time from placement of the
epidural catheter to first symptoms ranged from 2 days to 5 weeks (median 5 days). Although prevailing symptoms
were fever and sever backache, five developed neurologic deficits. All seven positive cultures isolated S. aureus.
Overall neurologic recovery was complete in 7 of 12 patients. However, four of the five patients with neurologic
symptoms did not recover. Meningitis was reported in 29 patients for an overall incidence of 1:53,000. A documented
perforation of the dura (intentional or accidental) occurred in 25 of 29 cases. In the 12 patients in whom positive
cultures were obtained, alpha-hemolytic streptococci were isolated in 11 patients and S. aureus in one.
These large epidemiologic studies represent new and unexpected findings regarding the demographics,
frequency, etiology and prognosis of infectious complications following neuraxial anesthesia. Epidural abscess is most
likely to occur in immunocompromised patients with prolonged durations of epidural catheterization. The most

332
Page 6
common causative organism is S. aureus, which suggests the colonization and subsequent infection from normal skin
flora as the pathogenesis. Delays in diagnosis and treatment result in poor neurologic recovery, despite surgical
decompression. Conversely, patients who develop meningitis following neuraxial blockade typically are healthy and
have undergone uneventful spinal anesthesia. Furthermore, the series by Moen et al (3) validates the findings of
individual case reports of meningitis after spinal anesthesia- the source of the pathogen is mostly likely to be the upper
airway of the proceduralist.

While the frequency of serious infectious complications is much higher than reported
previously, the results may be due to differences in reporting and/or clinical practice (asepsis, perioperative antibiotic
therapy, duration of epidural catheterization)

Meningitis after Dural Puncture and Neuraxial Anesthesia
Dural puncture has long been considered a risk factor in the pathogenesis of meningitis. Exactly how bacteria cross from
the blood stream into the spinal fluid is unknown. The presumed mechanisms include introduction of blood into the
intrathecal space during needle placement and disruption of the protection provided by the blood-brain barrier. Initial
investigations were performed over 80 years ago (29). Subsequent clinical studies reported conflicting results regarding
the causal relationship between dural puncture during bacteremia and meningitis However, the protective effect of
antibiotic administration prior to lumbar puncture was suggested (30,31).

Epidural Abscess after Epidural Anesthesia
Several relevant studies have specifically examined the risk of epidural abscess in patients receiving epidural anesthesia
and/or analgesia. Bader et al. (32) investigated the use of regional anesthesia in women with chorioamnionitis. Three
hundred nineteen women were identified from a total of 10,047 deliveries. Of the 319 women, 100 had blood cultures
taken on the day of delivery. Eight of these had blood cultures consistent with bacteremia. Two hundred ninety-three of
the 319 patients received a regional anesthetic, in 43 patients antibiotics were administered prior to needle or catheter
placement. No patient in the study, including those with documented bacteremias, had infectious complications. In
addition, mean temperatures and leukocyte counts in patients who received blood cultures showed no significant
differences between bacteremic and nonbacteremic groups. These authors continue to administer spinal and epidural
anesthesia in patients with suspected chorioamnionitis because the potential benefits of regional anesthesia outweigh the
theoretical risk of infectious complications.
The safety of epidural analgesia in 75 patients admitted to the intensive care unit was prospectively evaluated by
Darchy et al (33). There were no epidural abscesses. However, five of nine patients with positive cultures of the catheter
insertion site also had positive catheter tip cultures (epidural catheter infection); Staphylococcus epidermidis was the most
commonly cultured microorganism. Local infection of the catheter site was treated with catheter removal, but antibiotic
therapy was not specifically prescribed. Concomitant infection at other sites, antibiotic prophylaxis, and duration of
epidural analgesia were not risk factors for epidural-analgesia related infections. The authors noted that the presence of
both erythema and local discharge is a strong predictor of local and epidural catheter infection.
Epidural anesthesia and analgesia in a patient with a known systemic or localized infection remains controversial.
Jakobsen et al (34) retrospectively reviewed the records of 69 patients with abscesses or wound infections who underwent
epidural catheter placement for surgical debridement over a seven year-period. Several patients had more than one catheter
inserted. Catheters were left indwelling for a mean of nine days. On 12 occasions (eight patients) the catheter was
removed because of local infection. None of the patients demonstrated signs or symptoms of neuraxial infection. The
authors concluded that epidural anesthesia is relatively safe for patients requiring repeated surgical treatment of localized
infection. In contrast, Bengtsson et al. (35) reported three epidural catheter-related infections in patients with cutaneous
wounds over a four year-period. All patients were treated with antibiotic therapy; one patient underwent transcutaneous
drainage of an epidural abscess. However, there were no neurologic deficits. It is difficult to determine the actual risk of
epidural abscess in patients with chronic localized infections who undergo epidural catheter placement due to the small
number of patients studied and the rarity of this complication. Therefore, the clinician must maintain vigilance in
neurologic monitoring to assure early recognition and treatment.

Neuraxial Blockade in the Immunocompromised Patient
Large series have demonstrated that patients with immunodeficiencies are at increased risk for infectious
complications compared to those with intact immune function. However, there are few investigations which have
evaluated the frequency of meningitis or epidural abscess within a specific immunodeficient population (3,27,36).

332
Page 7

Table 2. Infectious Complications following Neuraxial Anesthesia in the Immunocompromised Patient
The attenuated inflammatory response within the immunocompromised patient may diminish the clinical signs
and symptoms often associated with infection and result in a delay in diagnosis and treatment.
The range of microorganisms causing invasive infection in the immunocompromised host is much broader than
that affecting the general population and includes atypical and opportunistic pathogens.
Early and effective therapy is paramount in optimizing neurologic outcome- consultation with an infectious
disease specialist is advised.
Prolonged antibiotic therapy (weeks-months) is often required because of persistent and immunologic
deficiencies.
Since eradication of infection is difficult once established, prevention of infection is paramount in caring for
immunocompromised patients.
From: Horlocker, et al 2006, with permission

Herpes Simplex Virus
Herpes simplex virus type 2 (HSV-2) infection is an incurable, recurrent disease characterized by asymptomatic periods
alternating with recrudescence of genital lesions. The primary infection is associated with viremia and can be accompanied
by a variety of symptoms, including fever, headache, and rarely aseptic meningitis. In contrast, recurrent or secondary
infections present as genital lesions without evidence of viremia. When obstetric patients present for delivery with
evidence of active HSV-2 infection, cesarean section is recommended to avoid exposing the neonate to the virus during
vaginal delivery. Neuraxial block in these patients is controversial because of the theoretical potential of introducing the
virus into the CNS. However, there are little data to support these concerns.

Human Immunodeficiency Virus
The risk of performing neuraxial block in patients infected with human immunodeficiency virus (HIV) is largely
undetermined. Approximately 40% of patients with the diagnosis of acquired immune deficiency syndrome (AIDS)
have clinical signs of neuropathy, and 70% to 80% have neuropathic changes present at autopsy. Since the virus infects
the CNS early in the disease, it is unlikely that neuraxial block would result in new CNS transmission. However, the
neurologic symptoms associated with HIV infection such as aseptic meningitis, headache, and polyneuropathy would be
indistinguishable from those related to regional technique. Hughes et al. (37) reported safe administration of neuraxial
block to 18 HIV-infected parturients. The patients studied showed no postpartum change in immune, infectious or
neurologic status. Avidan et al. (38) and Bremerich et al.(39) also reported a low complication rate for parturients
with HIV infection on antiretroviral therapy who underwent spinal anesthesia. However, in all three series (with a
combined total of 117 patients), the patients were relatively healthy and in the early stage of their disease. The
effects of anesthesia on patients with more advanced disease are unreported.

Aseptic Technique
Although previous publications have repeatedly recommended meticulous aseptic technique, only recently have
standards for asepsis during the performance of regional anesthetic procedures been defined (40) (Table 3).
Handwashing remains the most crucial component of asepsis; gloves should be regarded as a supplement to- not a
replacement of- handwashing (41). The use of an antimicrobial soap reduces bacterial growth and reduces the risk of
bacteria being released into the operative field should gloves become torn or punctured during the procedure. An
alcohol-based antiseptic provides the maximum degree of antimicrobial activity and duration. Prior to washing, all
jewelry (rings, watches, etc) should be removed; higher microbial counts have been noted in health care workers
who do not routinely remove these items before handwashing. Sterile gloves protect not only patients from
contamination, but also health care workers from blood-borne pathogens and are required by the Occupational
Safety and Health Administration (40). Glove leaks are more likely to occur with vinyl compared to latex gloves
(24% vs. 2), with contamination of the health care workers hands noted following the leaks in 23% of cases (42).
Conversely, the use of gowns does not further reduce the likelihood of cross contamination in an intensive care unit
setting compared to gloves alone. At this time, there are insufficient data to make recommendations regarding
routine use for single injection or temporary neuraxial/peripheral catheter placement. However, placement of an
indwelling permanent device, such as a spinal cord stimulator, warrants the same asepsis as a surgical procedure,
including gowns, hats, and antibiotic pretreatment (40,43).
Surgical masks, initially considered a barrier to protect the proceduralist from patient secretions and blood,
are now required by the Center for Disease Control due to the increasing number of cases of post spinal meningitis,
many of which result from contamination of the epidural or intrathecal space with pathogens from the operator's
buccal mucosa (3,44-47). A recent ASA Practice Advisory also recommends the wearing of masks (48).

332
Page 8
Antiseptic Solutions
Controversy still exists regarding the most appropriate and safe antiseptic solution for patients undergoing neuraxial
and peripheral techniques. Povidone iodine and chlorhexidine gluconate (with or without the addition of isopropyl
alcohol) have been most extensively studied (49,50). In nearly all clinical investigations, the bactericidal effect of
chlorhexidine was more rapid and more effective (extending its effect hours following its application) than povidone
iodine. The addition of isopropyl alcohol accelerates these effects. Chlorhexidine is effective against nearly all
nosocomial yeasts, and bacteria (gram-positive and gram-negative); resistance is extremely rare. It also remains
effective in the presence of organic compounds, such as blood. It must be noted that chlorhexidine-alcohol labeling
contains a warning against use as a skin preparation prior to lumbar puncture. The FDA has not formally approved
chlorhexidine for skin preparation prior to lumbar puncture because of the lack of animal and clinical studies
examining the neurotoxic potential of chlorhexidine, not due to a number of reported cases of nerve injury. Indeed, it
is important to note that there are no cases of neurotoxicity with either chlorhexidine or alcohol (40). Therefore, as a
result of its superior effect, alcohol-based chlorhexidine solutions are considered the antiseptic of choice for skin
preparation before any regional anesthetic procedure (40).

Anesthetic Management of the Infected or Febrile Patient
In summary, several clinical and laboratory studies have suggested an association between dural puncture during
bacteremia and meningitis. The data are not equivocal, however. The clinical studies are limited to pediatric patients
who are historically at high-risk for meningitis. Many of the original animal studies utilized bacterial counts that were
far in excess of those noted in humans in early sepsis, making CNS contamination more likely. Despite these
conflicting results, it is generally recommended that except in the most extraordinary circumstances, central neuronal
block should not be performed in patients with untreated bacteremia. Patients with evidence of systemic infection may
safely undergo spinal anesthesia, if antibiotic therapy is initiated prior to dural puncture, and the patient has demonstrated a
response to therapy, such as a decrease in fever. Placement of an indwelling epidural (or intrathecal) catheter in this group
of patients remains controversial; patients should be carefully selected and monitored for evidence of epidural infection
(51).
The attenuated inflammatory response within
the immunocompromised patient, including patients
with HSV and HIV, may diminish the clinical signs
and symptoms often associated with infection.
Likewise, the range of microorganisms causing
invasive infection in the immunocompromised host is
much broader than that affecting the general
population and includes atypical and opportunistic
pathogens. Consultation with an infectious disease
specialist is advised to facilitate initiation of early and
effective therapy (36). Meticulous aseptic technique,
including hand-washing with chlorhexidine, wearing
of mask and sterile gloves by the proceduralist, skin asepsis with chlorhexidine and antibiotic pretreatment for the
placement of permanent devices, is critical to the prevention of infectious complications related to regional
anesthesia (40).
All patients with an established local or systemic infection should be considered at risk for developing infection
of the CNS. A delay in diagnosis and treatment of even a few hours significantly worsens neurologic outcome. Bacterial
meningitis is a medical emergency. Mortality is approximately 30%, even with antibiotic therapy. The clinical course of
epidural abscess progresses from spinal ache and root pain, to weakness (including bowel and bladder symptoms) and
eventually paralysis. The initial back pain and radicular symptoms may remain stable for hours to weeks. However, the
onset of weakness often progresses to complete paralysis within 24 hours. Although the diagnosis was historically made
with myelogram, radiologic examination such as CT scan, or more preferably MRI, is currently recommended. A
combination of antibiotics and surgical drainage remains the treatment of choice. As with spinal hematoma, neurologic
recovery is dependent on the duration of the deficit and the severity of neurologic impairment before treatment.

References

1. Tryba M. [Epidural regional anesthesia and low molecular heparin: Pro]. Anasthesiol Intensivmed Notfallmed
Schmerzther 1993;28:179-81.
2. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg
1994;79:1165-77.

332
Page 9
3. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades in Sweden
1990-1999. Anesthesiology 2004;101:950-9.
4. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or
thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines
(Third Edition). Reg Anesth Pain Med 2010;35:64-101.
5. Benzon HT, Avram MJ, Benzon HA, et al. Factor VII levels and international normalized ratios in the early
phase of warfarin therapy. Anesthesiology 2010;112:298-304.
6. Odoom JA, Sih IL. Epidural analgesia and anticoagulant therapy. Experience with one thousand cases of
continuous epidurals. Anaesthesia 1983;38:254-9.
7. Horlocker TT, Wedel DJ, Schlichting JL. Postoperative epidural analgesia and oral anticoagulant therapy.
8. Wu CL, Perkins FM. Oral anticoagulant prophylaxis and epidural catheter removal. Reg Anesth 1996;21:517-
24.
9. Parvizi J, Viscusi ER, Frank HG, Sharkey PF, Hozack WJ, Rothman RR. Can epidural anesthesia and warfarin
be coadministered? Clin Orthop Relat Res 2007;456:133-7.
10. Rao TL, El-Etr AA. Anticoagulation following placement of epidural and subarachnoid catheters: an evaluation
of neurologic sequelae. Anesthesiology 1981;55:618-20.
11. Ruff RL, Dougherty JH, Jr. Complications of lumbar puncture followed by anticoagulation. Stroke
1981;12:879-81.
12. Liu SS, Mulroy MF. Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain
Med 1998;23:157-63.
13. Sandhu H, Morley-Forster P, Spadafora S. Epidural hematoma following epidural analgesia in a patient
receiving unfractionated heparin for thromboprophylaxis. Reg Anesth Pain Med 2000;25:72-5.
14. Greaves JD. Serious spinal cord injury due to haematomyelia caused by spinal anaesthesia in a patient treated
with low-dose heparin. Anaesthesia 1997;52:150-4.
15. Bergqvist D, Lindblad B, Matzsch T. Low molecular weight heparin for thromboprophylaxis and
epidural/spinal anaesthesia--is there a risk? Acta Anaesthesiol Scand 1992;36:605-9.
16. Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia
and thromboprophylaxis. Reg Anesth Pain Med 1998;23:164-77.
17. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks
(the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med
2003;28:172-97.
18. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain
Med 1998;23:183-9.
19. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S.
20. Weitz JI, Hirsh J, Samama MM. New antithrombotic drugs: American College of Chest Physicians Evidence-
Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:234S-56S.
21. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct
thrombin and factor xa inhibitors in development. Clin Pharmacokinet 2009;48:1-22.
22. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364
pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. Lancet
1994;343:619-29.
23. Horlocker TT, Bajwa ZH, Ashraf Z, et al. Risk assessment of hemorrhagic complications associated with
nonsteroidal antiinflammatory medications in ambulatory pain clinic patients undergoing epidural steroid
injection. Anesth Analg 2002;95:1691-7.
24. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of
spinal hematoma associated with regional anesthesia. Anesth Analg 1995;80:303-9.
25. Baker AS, Ojemann RG, Swartz MN, Richardson EP, Jr. Spinal epidural abscess. N Engl J Med 1975;293:463-
8.
26. Ready LB, Helfer D. Bacterial meningitis in parturients after epidural anesthesia. Anesthesiology 1989;71:988-
90.
27. Ericsson M, Algers G, Schliamser SE. Spinal epidural abscesses in adults: review and report of iatrogenic cases.
Scand J Infect Dis 1990;22:249-57.
28. Wang LP, Hauerberg J, Schmidt JF. Incidence of spinal epidural abscess after epidural analgesia: a national 1-
year survey. Anesthesiology 1999;91:1928-36.

332
Page 10
29. Weed LH, Wegeforth P, Ayer JB, Felton LD. The production of meningitis by release of cerebrospinal fluid
during an experimental septicemia. JAMA 1919;72:190-3.
30. Carp H, Bailey S. The association between meningitis and dural puncture in bacteremic rats. Anesthesiology
1992;76:739-42.
31. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children with bacteremia. N
Engl J Med 1981;305:1079-81.
32. Bader AM, Gilbertson L, Kirz L, Datta S. Regional anesthesia in women with chorioamnionitis. Reg Anesth
1992;17:84-6.
33. Darchy B, Forceville X, Bavoux E, Soriot F, Domart Y. Clinical and bacteriologic survey of epidural analgesia
in patients in the intensive care unit. Anesthesiology 1996;85:988-98.
34. Jakobsen KB, Christensen MK, Carlsson PS. Extradural anaesthesia for repeated surgical treatment in the
presence of infection. Br J Anaesth 1995;75:536-40.
35. Bengtsson M, Nettelblad H, Sjoberg F. Extradural catheter-related infections in patients with infected cutaneous
wounds. Br J Anaesth 1997;79:668-70.
36. Horlocker TT, Wedel DJ. Regional anesthesia in the immunocompromised patient. Reg Anesth Pain Med
2006;31:334-45.
37. Hughes SC, Dailey PA, Landers D, et al. Parturients infected with human immunodeficiency virus and regional
anesthesia. Clinical and immunologic response. Anesthesiology 1995;82:32-7.
38. Avidan MS, Groves P, Blott M, et al. Low complication rate associated with cesarean section under spinal
anesthesia for HIV-1-infected women on antiretroviral therapy. Anesthesiology 2002;97:320-4.
39. Bremerich DH, Ahr A, Buchner S, et al. [Anesthetic regimen for HIV positive parturients undergoing elective
cesarean section]. Anaesthesist 2003;52:1124-31.
40. Hebl JR. The importance and implications of aseptic techniques during regional anesthesia. Reg Anesth Pain
Med 2006;31:311-23.
41. Saloojee H, Steenhoff A. The health professional's role in preventing nosocomial infections. Postgrad Med J
2001;77:16-9.
42. Olsen RJ, Lynch P, Coyle MB, et al. Examination gloves as barriers to hand contamination in clinical practice.
Jama 1993;270:350-3.
43. Rathmell JP, Lake T, Ramundo MB. Infectious risks of chronic pain treatments: injection therapy, surgical
implants, and intradiscal techniques. Reg Anesth Pain Med 2006;31:346-52.
44. Couzigou C, Vuong TK, Botherel AH, et al. Iatrogenic Streptococcus salivarius meningitis after spinal
anaesthesia: need for strict application of standard precautions. J Hosp Infect 2003;53:313-4.
45. Molinier S, Paris JF, Brisou P, et al. [2 cases of iatrogenic oral streptococcal infection: meningitis and
spondylodiscitis]. Rev Med Interne 1998;19:568-70.
46. Schneeberger PM, Janssen M, Voss A. Alpha-hemolytic streptococci: a major pathogen of iatrogenic meningitis
following lumbar puncture. Case reports and a review of the literature. Infection 1996;24:29-33.
47. Trautmann M, Lepper PM, Schmitz FJ. Three cases of bacterial meningitis after spinal and epidural anesthesia.
Eur J Clin Microbiol Infect Dis 2002;21:43-5.
48. Horlocker TT, Birnbach DJ, Connis RT, et al. Practice advisory for the prevention, diagnosis, and management
of infectious complications associated with neuraxial techniques: a report by the American Society of
Anesthesiologists Task Force on infectious complications associated with neuraxial techniques. Anesthesiology
2010;112:530-45.
49. Birnbach DJ, Stein DJ, Murray O, et al. Povidone iodine and skin disinfection before initiation of epidural
anesthesia. Anesthesiology 1998;88:668-72.
50. Kinirons B, Mimoz O, Lafendi L, et al. Chlorhexidine versus povidone iodine in preventing colonization of
continuous epidural catheters in children: a randomized, controlled trial. Anesthesiology 2001;94:239-44.
51. Wedel DJ, Horlocker TT. Regional anesthesia in the febrile or infected patient. Reg Anesth Pain Med
2006;31:324-33.

Disclosure

408
Page 1
Perioperative analgesia and effect on patient outcomes
Spencer S. Liu, M.D. Seattle, Washington
Introduction
Provision of high quality perioperative analgesia has become recognized as an important goal. However,
ability of analgesia to improve outcomes remains controversial.
1
A key component of this continuing controversy
is that individual clinical trials need large patient sample sizes due to the current relatively low incidences of major
postoperative morbidity. Thus, this lecture will focus on studies with large subject samples to evaluate effects of
postoperative analgesia on major postoperative outcomes. Most discussed evidence involves epidural analgesia, as
this is the most studied regional anesthesia/analgesia technique for major postoperative outcomes. Furthermore, the
lecture will discuss effects of regional analgesia on patient oriented outcomes. As anesthesia and perioperative care
become increasingly safe, these patient oriented outcomes may assume greater importance.
Effect of regional analgesia on major morbidity
Epidural analgesia
Mortality
Meta-analyses: The largest meta-analysis of RCTs was published in 2000 (CORTRA) and included 141 RCTs
(through Jan 1, 1997) with 9,559 patients undergoing a variety of surgical procedures
2
. This meta-analysis
examined effects of neuraxial block (spinal anesthesia, epidural anesthesia, and epidural analgesia) vs general
anesthesia, but results from this meta-analysis likely apply to perioperative epidural analgesia as 66 of the RCTs
with 4,498 of the patients utilized epidural anesthesia and analgesia. This meta-analysis observed a reduction in
mortality with neuraxial blockade (1.9% vs 2.8%, OR 0.7 with 95% CI 0.54 to 0.9) and specifically for thoracic
epidural blocks (1.5% vs 2.9%) and orthopedic procedures. An smaller meta-analysis of mixed but primarily major
vascular surgery by Beattie et al in 2001 noted a non-significant reduction in mortality (3.1 vs 4.4%)
3
.
Several procedure specific meta-analyses have been conducted, and all report inconclusive effects on
mortality with epidural analgesia for open abdominal aortic surgery
4
, coronary artery bypass grafting
5
, abdominal
surgery
6
, and hip and knee replacement surgery
7
.
Randomized Controlled Trials: The most recent large RCT was conducted in 2011 in 654 patients undergoing
cardiac surgery that were randomized to combined general/thoracic vs general anesthesia.
8
This RCT did not note
any differences between groups in mortality (0.6 vs 0.3%). 2 large RCTs have been performed in non-cardiac
surgery patients. In 2001, the Veterans Affairs Cooperative Studies Program (VACS) randomized 984 patients (all
or mostly men) undergoing 4 types of surgery (aortic, gastric, biliary, or colon) to combined general/epidural
anesthesia followed by epidural morphine vs general anesthesia followed by systemic opioid treatment
9
.
Approximately 85% of the epidurals were placed at the thoracic level. Overall mortality rates were similar between
groups (4 vs 3.4%). In 2002, the Multicentre Australian Study of Epidural Anesthesia (MASTER) trial
10
enrolled
915 high risk patients (prospectively defined in the protocol) who had undergone mixed abdominal surgical
procedures and were randomized to combined general/epidural anesthesia followed by 72 hours of postoperative
epidural analgesia (low thoracic or high lumbar placement) with local anesthetic and opioids vs general anesthesia
followed by systemic opioid treatment. This RCT was limited by poor protocol compliance, as only 225/447
patients fully adhered to the epidural analgesia protocol. Overall mortality rates were again similar between groups
(5.1 vs 4.3%).
Clinical registries: In 2008, a propensity score analysis of a single institution electronic registry of 259,037 patients
undergoing mixed surgery reported a significant reduction in 30 day mortality in patients selected for epidural
anesthesia/analgesia (n=56,556) of 1.7% vs 2%.
11
In 2004, a 5% random sample of the Medicare claims database.
Patients undergoing a variety of surgical procedures were stratified to the presence (n=12,780 subjects) or absence
408
Page 2
(n=55,943) of coding for postoperative epidural analgesia.
12
After adjusting for comorbidities, age, gender, and
hospital size, regression analysis revealed that the presence of postoperative epidural analgesia was associated with a
significantly lower incidence for both 7-day (0.5 vs 0.8%, OR = 0.52 with 95% CI 0.38 to 0.73) and 30-day (2.1 vs
2.5%, OR = 0.74 with 95% CI 0.63 to 0.89) mortality
12
. There was a significantly lower mortality in patients who
received postoperative epidural analgesia for higher-risk procedures (e.g., lung resection, colectomy) but not lower-
risk procedures (e.g., total knee replacement, hysterectomy) or in patients with lower comorbidity indices. Although
the number of patients from these registry analyses is impressive, these data are limited by retrospective nature,
accuracy of coding for complications, and degree of association between epidural analgesia and outcomes.
Summary statement: There is modest but consistent evidence for reduction of mortality with epidural analgesia
for non-cardiac procedures. The largest meta-analysis observed a reduction with neuraxial block. Procedure
specific meta-analyses and individual RCTs have not noted an effect from epidural analgesia but lack sufficient
sample size due to the relatively low incidence of mortality (0.2-5%). Analysis of clinical registries offers large
patient numbers and a modest association between epidural analgesia and reduced mortality.
Cardiovascular
Approximately 100 million adults worldwide undergo non-cardiac surgery annually, and nearly half of the
patients are estimated to have cardiac risk factors
13
. As such, it is estimated that nearly 500,000-900,000 patients
will suffer a perioperative cardiovascular complication
13
. Uncontrolled postoperative pain may contribute to
cardiac morbidity through activation of the sympathetic nervous system, surgical stress response and coagulation
cascade. Experimental data suggest that thoracic epidural anesthesia with local anesthetics can reduce sympathetic
activation and provide a favorable balance of myocardial oxygen, but lumbar epidural anesthesia may not provide
the same physiologic benefits as thoracic epidural anesthesia
14,15
.
Meta-analyses: Six meta-analyses were identified that examined efficacy of epidural analgesia on cardiovascular
events
2,3,16-18
. The largest was the previously described CORTRA meta-analysis that reported a non-significant
decrease in the risk of myocardial infarction (0.9% vs 1.3%). It should be noted that the majority of patients
received lumbar epidural or spinal anesthesia, which may not provide the physiologic benefit of TEA.
Three smaller but more specific meta-analyses examining the efficacy of postoperative epidural analgesia
and cardiovascular events suggest a benefit for epidural analgesia and TEA in particular for open major vascular
procedures. The meta-analysis by Popping in 2008 in abdominal and thoracic procedures noted a significant
reduction in myocardial infarction with primarily thoracic epidural analgesia (2.6 vs 4.6%). Beattie et al noted a
significantly lower incidence of myocardial infarction in those who received epidural analgesia (rate difference = -
3.8% with 95% confidence interval of -7.4% to -0.2%; p = 0.049) primarily in vascular surgery patients (579 out of
632 patients), and analgesic subgroup analysis revealed that TEA but not LEA provided a significant reduction in
the rate of myocardial infarction (3.6% vs 8.5%, rate difference = -5.3% with 95% CI of -9.9% to -0.7%). A similar
but more procedure specific meta-analysis of open abdominal aortic surgery with 1,224 patients (through June 2004)
noted significant reduction in risk of cardiovascular complications (RR 0.74 with 95% CI 0.56-0.97) and myocardial
infarction (RR 0.52 with 95% CI 0.29 to 0.93) with epidural vs systemic analgesia
4
. Subgroup analysis again
indicated that only TEA and not lumbar epidural analgesia was associated with reduced risk of myocardial
infarction. These findings would support the experimental data demonstrating physiologic cardiac benefits of
thoracic but not necessarily lumbar epidural analgesia. Another procedure specific meta-analysis examined 28
RCTs with 2731 patients undergoing coronary artery bypass surgery with or without TEA.
5
Myocardial infarction
was not reduced with an odds ratio of 0.81, but significant reduction in risk of dysrhythmias was noted with TEA
(RR 0.68 with 95% CI 0.5-0.93). Other procedure specific meta-analyses examining effects of epidural analgesia on
abdominal, and hip and knee replacement surgery concluded that there was insufficient evidence to analyze
cardiovascular complications.
6,7,17

Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in myocardial infarction (4.9% in both groups).
8
The VACS trial did not note a
significant reduction in cardiovascular complications (myocardial infarction, heart failure, dysrhythmias, severe
hypotension) with use of epidural morphine (8.6 vs 11.2%) for all patients
9
. However, the abdominal aortic surgery
subgroup (n=374) had significantly lower incidences of cardiovascular complications (9.8 vs 17.9%, p=0.03)
primarily due to reduction in myocardial infarction (2.7 vs 7.9%, p=0.05). The MASTER trial did not note
significant differences between groups.

408
Page 3
Summary statement: There is consistent evidence that thoracic epidural analgesia may reduce the risk of
cardiovascular complications, especially myocardial infarction, in patients undergoing open major vascular surgery
and dysrhythmias in patients undergoing cardiac surgery. This is likely due to a higher underlying rate of
cardiovascular complications for this surgical population (4-37%).

Pulmonary
Postoperative pulmonary complications (PPCs) are as common as cardiac complications for patients
undergoing non-cardiac procedures, and may carry the same risk of increased mortality and length of hospital stay
19
. The pathophysiology of postoperative pulmonary complications (PPC) after surgery is multifactorial and may
include disruption of normal respiratory muscle activity from either surgery or anesthesia, a reflex inhibition of
phrenic nerve activity with subsequent decrease in diaphragmatic function, and uncontrolled postoperative pain
20
.
Epidural analgesia will confer superior analgesia thus improving voluntary pulmonary function
21
. Segmental block
from thoracic epidural anesthesia may result in increased tidal volume and vital capacity related in part to improved
pain control and also to interruption of the reflex inhibition of phrenic nerve activity, thus improving diaphragmatic
activity.

Meta-analysis: In the CORTRA study, neuraxial block in mixed surgical procedures was associated with
significantly decreased risk of pneumonia (3.1% vs 6%, OR 0.61 with 95% CI 0.48-0.76) especially with TEA (OR
0.48 with 95% CI 0.35 to 0.67) vs spinal anesthesia or lumbar epidural anesthesia (OR 0.76 with 95% CI 0.55-1.04)
2
. This finding would support the underlying potential physiologic benefit for TEA for reducing PPCs. This finding
was confirmed in the 2008 meta-analysis (n=5,904) by Popping et al that noted a significant reduction in pneumonia
with primarily thoracic epidural analgesia (8 vs 12%) in patients undergoing abdominal or thoracic surgery.
18

More procedure specific meta-analyses were also identified. Use of TEA in coronary artery bypass surgery
(n=2,731) was associated with significantly decreased risk of PPC (RR 0.53 with 95% CI 0.4 to 0.69).
5
Use of TEA
in open abdominal aortic surgery (N= 861) was associated with significantly decreased risk of respiratory failure
(RR 0.63 with 95% CI 0.51-0.79)
4
.

Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in pulmonary complications (9.2 vs 5.8%).
8
The VACS study observed a non-significant
reduction in respiratory failure for all patients in the epidural group (9.9% vs 14%)
9
. However, subgroup analysis
of the abdominal aortic surgery subgroup (n=374) noted a significant reduction in respiratory failure with use of
epidural analgesia (14% vs 28%, p<0.01). The MASTER study (N=915) found observed similar findings with a
lower incidence of respiratory failure in the epidural analgesia group for high risk patients undergoing mixed
abdominal surgical procedures (23 vs 30%, p=0.02)
10
. As described above, most epidurals were placed at the
thoracic level for both RCTs.

Summary statement: There is consistent evidence from meta-analyses and large RCTs that thoracic epidural
analgesia reduces risk of postoperative pulmonary complications, especially in high risk surgery.

Gastrointestinal
Postoperative ileus is very common after abdominal surgery (>90% in many series) and may increase
resource utilization by prolonging hospital stay
22
. Although the pathophysiology of postoperative ileus is
multifactorial, primary mechanisms include neurogenic (spinal, supraspinal adrenergic pathways), inflammatory
(i.e., local inflammatory responses initiate neurogenic inhibitory pathways), and pharmacologic (e.g., opioids)
mechanisms
23
. Epidural analgesia provides superior pain control and marked sparing of opioid consumption
21
.
Sympathetic block from epidural local anesthetics may attenuate postoperative reflex inhibition of GI motility.
Suppression of the surgical stress response and systemic absorption of epidural local anesthetics may reduce the
inflammatory response to attenuate postoperative ileus
22,23
. Consistent with these mechanisms, experimental data
consistently indicate that epidural analgesia with local anesthetics shortens time of intestinal paralysis, increases the
strength of colonic contractions, and does not impair anastomotic healing or increase risk of anastomotic leakage
24
.

Meta-analysis: A Cochrane Library meta-analysis that included 22 RCTs with 1,023 patients undergoing
abdominal surgery
25
and a meta-analysis from 2007 (n=806) both noted consistent reduction in postoperative ileus
with epidural analgesia with local anesthetics.

408
Page 4
Summary statement: There is consistent evidence from meta-analysis that epidural analgesia with local
anesthetics hastens return of postoperative GI function after abdominal surgery by 24 to 37 hours.

Cancer recurrence
The immune system is critical for ability to detect and eliminate cancer cells. Current evidence suggests a
primary role for NK cells for elimination, equilibrium, escape process. The immune system is initially able to
eliminate cancer cells. However, natural selection over time results in resistant cancer cells that are contained in an
equilibrium state. Disruption to the immune system, such as surgical stress, may tip the equilibrium into an escape
phase that allows metastases. Multiple perioperative factors may be involved in the equilibrium/escape phase, and
regional anesthesia/analgesia may play a protective role.
26
Laboratory evidence indicates that acute pain suppresses
NK cell activity, increase adrenergic activity, and is associated with tumor development in animals. Conversely,
relief of postoperative pain reduces postoperative metastasis in rats. Proposed mechanisms for beneficial effects of
regional anesthesia/analgesia include attenuation of perioperative immunosuppression, decreased use of volatile and
opioid agents, and improved tissue oxygenation. There are currently no prospective large scale RCTs specifically
designed to support or refute this theoretical benefit. Most current evidence is either observational or post-hoc re-
analysis of a RCT designed for a different hypothesis. Initial data were very favorable for the ability of regional
anesthesia/analgesia to reduce risk of cancer metastasis, however subsequent data, including minimally invasive
surgery patients, were more equivocal.
27,28

Summary statement: There is a lack of evidence from well designed prospective studies to support or refute a role
for regional anesthesia/analgesia and cancer recurrence.

Effect of regional analgesic technique on patient oriented outcomes
As risk of major perioperative complications decrease, patient oriented outcomes are increasingly being
viewed as valuable. Indeed, patient oriented outcomes such as postoperative pain or nausea are consistently rated as
top priorities in patient surveys. Unfortunately, there are few validated tools for measuring patient evaluation of
such outcomes, as most tools are uni-dimensional and do not recognize patient preferences for different
combinations of outcomes and linked side effects.
29

Epidural Analgesia
Analgesia: Two meta-analyses have compared epidural analgesia to systemic analgesia for mixed surgical
procedures.
9,10
For both meta-analyses, epidural analgesia (compared to systemic opioids including intravenous
patient-controlled analgesia [IV PCA]) provided statistically superior analgesia at rest and with activity for all types
of surgery through postoperative day (POD) 4. Greater improvements were noted when the regimen included local
anesthetics and when level of epidural catheter matched site of surgery (e.g., thoracic catheter for thoracic surgery).
Multiple procedure specific meta-analyses have also been published
13-16
, and all consistently note statistically
significantly lower pain scores with epidural techniques.

Side effects: The meta-analyses from 2003 and 2005 also reported on incidences of side effects. As expected
epidural and IV PCA analgesia offered different profiles of side effects with epidural analgesia associated with
significantly reduced risk of nausea and sedation but significantly higher incidences of pruritus, urinary retention,
and motor block. When continuous epidural analgesia was compared to patient controlled epidural analgesia,
patient controlled epidural analgesia offered a reduced risk of side effects with significantly lower incidences of
nausea and motor block but greater incidence of pruritus.

Summary statement: Epidural analgesia provides superior analgesia to any form of systemic opioid including IV
PCA delivery for at least the first 3 POD for a variety of surgical procedures. Use of local anesthetics can maximize
this efficacy. Side effect profiles differ between regimens

Continuous peri-neural analgesia
Analgesia and side effects
A meta analysis published in 2006 (19 RCTs with 603 patients) compared continuous peri-neural analgesia
vs. mixed systemic opioids (13 of 19 RCTs used IV PCA).
25
Peri-neural analgesia, which can be used on an

408
Page 5
ambulatory basis
27
, provided statistically superior analgesia at rest and with activity for 48-72 hours with a reduction
in risk of nausea, sedation, pruritus but increased risk of motor block.

Functional outcomes
Several recent RCTs suggest that use of perineural analgesia can be used to shorten length of stay of major
orthopedic procedures such as total shoulder, knee, and hip replacement by nearly 30 %.
30-32
After total shoulder
replacement, patients were randomized to saline or ropivacaine via an interscalene catheter. Patients receiving
ropivacaine achieved prospectively defined discharge criteria in 21 vs 51 hrs (p<0.001). After total knee
replacement surgery, patients were randomized to saline or ropivacaine via a femoral nerve catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 25 vs 71 hrs (p<0.001). After total hip
replacement surgery, patients were randomized to saline or ropivacaine via a lumbasr plexus catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 29 vs 51 hrs (p<0.001). Long term
investigations have also followed these same patients out for a year after surgery to determine if early superiority in
functional outcomes with regional analgesia is preserved. However, no differences in health related quality of life
were noted between groups.
33
A recent RCT randomizing patients to TEA/GA vs GA for off-pump CABG noted
that TEA resulted in better analgesia, less sedation, faster time to tracheal extubation, and shorter length of ICU and
hospital stay.
34

Ambulatory surgery now comprises 60-70% of surgical volume. Regional analgesia also appears to have
similar salutatory effects for ambulatory surgery. Patients undergoing shoulder or foot/ankle ambulatory surgery
were randomized to receive either patient controlled regional analgesia with ropivacaine (via interscalene or
popliteal catheter) versus patient controlled intravenous analgesia with morphine. Patients receiving regional
analgesia had statistically superior pain control, less side effects, and greater degrees of independent activity for the
first 3 days after surgery.
35
Indeed, recent case series suggest that use of perineural analgesia can convert total
shoulder, hip, and knee replacement from fully hospitalized to ambulatory surgery stays.
36-38

Summary statement: Meta analysis indicates that continuous peri-neural analgesia provides superior analgesia for
up to 48 hours after surgery with reduced side effects when compared to systemic opioids. Recent clinical trials
suggest use of perineural analgesia may decrease hospital stay for major orthopedic procedures and improve
functional status at home after ambulatory surgery.

Summary and Future Directions
Regional analgesia has modest beneficial effect on mortality. Epidural analgesia reduces cardiopulmonary
complications in major open procedures such as open aortic repair. Epidural analgesia with local anesthetic
containing solutions consistently reduces duration of ileus after open abdominal procedures. Beneficial effects have
been reduced by current low rates of postoperative complications and increased use of minimally invasive surgery
such as laparoscopic colectomy.
39
Effects of regional anesthesia/analgesia on cancer recurrence are of great interest
but await high quality prospective data. Patient oriented outcomes have become an increasingly important field for
investigation. Epidural analgesia consistently provides superior analgesia to systemic opioids and a different
package of side effects. Perineural analgesia consistently provides superior analgesia and reduced side effects
compared to systemic analgesia and may reduce length of stay after major orthopedic procedures.

408
Page 6
References

1. Liu SS, Wu CL: Effect of postoperative analgesia on major postoperative complications: a
systematic update of the evidence. Anesth Analg 2007; 104: 689-702
2. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, Sage D, Futter M, Saville G,
Clark T, MacMahon S: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia:
results from overview of randomised trials. BMJ 2000; 321: 1493
3. Beattie WS, Badner NH, Choi P: Epidural analgesia reduces postoperative myocardial infarction:
a meta-analysis. Anesth Analg 2001; 93: 853-8
4. Nishimori M, Ballantnye JC, Low JHS: Epidural pain relief versus systemic opioid based pain
relief for abdominal aortic surgery. Cochrane Database Syst Rev In Press
5. Svircevic V, van Dijk D, Nierich AP, Passier MP, Kalkman CJ, van der Heijden GJ, Bax L: Meta-
analysis of thoracic epidural anesthesia versus general anesthesia for cardiac surgery. Anesthesiology 2011; 114:
271-82
6. Werawatganon T, Charuluxanun S: Patient controlled intravenous opioid analgesia versus
continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev 2005: CD004088
7. Choi PT, Bhandari M, Scott J, Douketis J: Epidural analgesia for pain relief following hip or knee
replacement. Cochrane Database Syst Rev 2003: CD003071
8. Svircevic V, Nierich AP, Moons KG, Diephuis JC, Ennema JJ, Brandon Bravo Bruinsma GJ,
Kalkman CJ, van Dijk D: Thoracic epidural anesthesia for cardiac surgery: a randomized trial. Anesthesiology 2011;
114: 262-70
9. Park WY, Thompson JS, Lee KK: Effect of epidural anesthesia and analgesia on perioperative
outcome: a randomized, controlled Veterans Affairs cooperative study. Ann Surg 2001; 234: 560-9
10. Rigg JR, Jamrozik K, Myles PS, Silbert BS, Peyton PJ, Parsons RW, Collins KS: Epidural
anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359: 1276-82
11. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A: Epidural anaesthesia and survival
after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet 2008; 372: 562-9
12. Wu CL, Hurley RW, Anderson GF, Herbert R, Rowlingson AJ, Fleisher LA: Effect of
postoperative epidural analgesia on morbidity and mortality following surgery in medicare patients. Reg Anesth
Pain Med 2004; 29: 525-33
13. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH: Perioperative cardiac events
in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the
events and methods to estimate and communicate risk. CMAJ 2005; 173: 627-34
14. Taniguchi M, Kasaba T, Takasaki M: Epidural anesthesia enhances sympathetic nerve activity in
the unanesthetized segments in cats. Anesth Analg 1997; 84: 391-7
15. Meissner A, Rolf N, Van Aken H: Thoracic epidural anesthesia and the patient with heart disease:
benefits, risks, and controversies. Anesth Analg 1997; 85: 517-28
16. Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after
coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004; 101: 153-61
17. Marret E, Remy C, Bonnet F: Meta-analysis of epidural analgesia versus parenteral opioid
analgesia after colorectal surgery. Br J Surg 2007; 94: 665-73
18. Popping DM, Elia N, Marret E, Remy C, Tramer MR: Protective effects of epidural analgesia on
pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008; 143: 990-9;
discussion 1000
19. Qaseem A, Snow V, Fitterman N, Hornbake ER, Lawrence VA, Smetana GW, Weiss K, Owens
DK, Aronson M, Barry P, Casey DE, Jr., Cross JT, Jr., Sherif KD, Weiss KB: Risk assessment for and strategies to
reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from
the American College of Physicians. Ann Intern Med 2006; 144: 575-80
20. Warner DO: Preventing postoperative pulmonary complications: the role of the anesthesiologist.
21. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, Lin EE, Liu SS:
Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-
controlled analgesia with opioids: a meta-analysis. Anesthesiology 2005; 103: 1079-88; quiz 1109-10
22. Mythen MG: Postoperative gastrointestinal tract dysfunction. Anesth Analg 2005; 100: 196-204
23. Bauer AJ, Boeckxstaens GE: Mechanisms of postoperative ileus. Neurogastroenterol Motil 2004;
16 Suppl 2: 54-60

408
Page 7
24. Fotiadis RJ, Badvie S, Weston MD, Allen-Mersh TG: Epidural analgesia in gastrointestinal
surgery. Br J Surg 2004; 91: 828-41
25. Jorgensen H, Wetterslev J, Moiniche S, Dahl JB: Epidural local anaesthetics versus opioid-based
analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane
Database Syst Rev 2000: CD001893
26. Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M: Review article: the role of the
perioperative period in recurrence after cancer surgery. Anesth Analg 2010; 110: 1636-43
27. Day A, Smith R, Jourdan I. Retrospective analysis of the effect of postoperative analgesia on
survival in patients after laparoscopic resection of colorectal cancer. BJA 2012:109:185-90
28. Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI: Perioperative epidural analgesia for
major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ 2011; 342: d1491
29. Liu SS, Wu CL: The effect of analgesic technique on postoperative patient-reported outcomes
including analgesia: a systematic review. Anesth Analg 2007; 105: 789-808
30. Ilfeld BM, Le LT, Meyer RS, Mariano ER, Vandenborne K, Duncan PW, Sessler DI, Enneking
FK, Shuster JJ, Theriaque DW, Berry LF, Spadoni EH, Gearen PF: Ambulatory continuous femoral nerve blocks
decrease time to discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked,
placebo-controlled study. Anesthesiology 2008; 108: 703-13
31. Ilfeld BM, Vandenborne K, Duncan PW, Sessler DI, Enneking FK, Shuster JJ, Theriaque DW,
Chmielewski TL, Spadoni EH, Wright TW: Ambulatory continuous interscalene nerve blocks decrease the time to
discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.
32. Ilfeld BM, Ball ST, Gearen PF, Le LT, Mariano ER, Vandenborne K, Duncan PW, Sessler DI,
Enneking FK, Shuster JJ, Theriaque DW, Meyer RS: Ambulatory continuous posterior lumbar plexus nerve blocks
after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology 2008; 109:
491-501
33. Ilfeld BM, Shuster JJ, Theriaque DW, Mariano ER, Girard PJ, Loland VJ, Meyer S, Donovan JF,
Pugh GA, Le LT, Sessler DI, Ball ST: Long-term pain, stiffness, and functional disability after total knee
arthroplasty with and without an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-
up of a multicenter, randomized, triple-masked, placebo-controlled trial. Reg Anesth Pain Med 2011; 36: 116-20
34. Caputo M, Alwair H, Rogers CA, Pike K, Cohen A, Monk C, Tomkins S, Ryder I, Moscariello C,
Lucchetti V, Angelini GD: Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump
coronary artery bypass surgery: a prospective, randomized, controlled trial. Anesthesiology 2011; 114: 380-90
35. Capdevila X, Dadure C, Bringuier S, Bernard N, Biboulet P, Gaertner E, Macaire P: Effect of
patient-controlled perineural analgesia on rehabilitation and pain after ambulatory orthopedic surgery: a multicenter
randomized trial. Anesthesiology 2006; 105: 566-73
36. Ilfeld BM, Wright TW, Enneking FK, Mace JA, Shuster JJ, Spadoni EH, Chmielewski TL,
Vandenborne K: Total shoulder arthroplasty as an outpatient procedure using ambulatory perineural local anesthetic
infusion: a pilot feasibility study. Anesth Analg 2005; 101: 1319-22
37. Ilfeld BM, Gearen PF, Enneking FK, Berry LF, Spadoni EH, George SZ, Vandenborne K: Total
hip arthroplasty as an overnight-stay procedure using an ambulatory continuous psoas compartment nerve block: a
prospective feasibility study. Reg Anesth Pain Med 2006; 31: 113-8
38. Ilfeld BM, Gearen PF, Enneking FK, Berry LF, Spadoni EH, George SZ, Vandenborne K: Total
knee arthroplasty as an overnight-stay procedure using continuous femoral nerve blocks at home: a prospective
feasibility study. Anesth Analg 2006; 102: 87-90
39. Levy BF, Scott MJ, Fawcett W, Fry C, Rockall TA: Randomized clinical trial of epidural, spinal
or patient-controlled analgesia for patients undergoing laparoscopic colorectal surgery. Br J Surg 2011; 98: 1068-78

Disclosure

417
Page 1
Practical Regional Anesthesia: Making It Work in the Real World
Michael F. Mulroy, M.D. Seattle, Washington
Introduction Despite many documented advantages of regional anesthesia (RA), its utilization remains at the
15-30% level in current practice.
1
Reasons cited are the additional time and expertise required for this skill, often
leading to resistance by surgeons and hospitals concerned with operating room (OR) efficiency. This review will
address some of the reasons we should pursue greater application of regional techniques, as well as practical tips to
improve your personal success and your institutional and surgical acceptance.
Why should we work to make it work? Reasons to do regional more often
Although general anesthesia has become easier and safer with modern drugs and monitoring devices,
regional anesthesia offers significant advantages to offset the additional work required to perform blocks.
Old News- There is at least one meta-analysis that suggests that intraoperative use of regional techniques can
reduce mortality and morbidity
2
, but the majority of data focuses on the improved benefits in the perioperative
period when regional techniques are used or continued for post-operative analgesia. The evidence is established that
epidural opioid-local anesthetic infusions provide superior post-operative pain relief compared to traditional
systemic opioids after major abdominal, vascular and thoracic surgery
3

4

5
, and appear to reduce cardiac
6
,
respiratory
7
, and gastrointestinal
8
morbidity. For peripheral procedures, the most recent meta-analysis has shown
similar superiority of peripheral nerve block techniques for superior analgesia and opioid sparing compared to
systemic opioids.
9
After major orthopedic joint replacements, analysis of a database of 382,000 cases showed that
neuraxial techniques reduce mortality, complications and length of stay compared to general anesthesia.
10

11

Likewise, nerve blocks and continuous peripheral nerve catheters consistently provide superior analgesia and
improved rehabilitation for these increasingly common painful operations in our aging population
12

13
and may even
reduce hospital costs.
14
In outpatient surgery (now over 60% of our volumes), regional provides better analgesia and
less nausea
15
, and has the potential to provide faster discharge.
16

17
The use of long-acting blocks and continuous
catheters provides superior analgesia in this population also
18

19
, and allows faster return to normal sleep and activity
patterns.
20 21
Recent Developments- There is a suggestion that development of chronic pain
22
or cancer recurrence
23
can be
reduced when RA is used. Chronic pain is reported to develop in 10-50% of patients after hernia, thoracotomy, or
breast surgery, and the incidence appears to be reduced if aggressive effective multimodal analgesia techniques
(including RA) are employed compared to standard opioid therapy. More recent interest has focused on the
potential role of RA in modifying cancer progression. The natural stress response to surgery inhibits cellular
immunity and increases pro-angiogenic factors that may reduce resistance to cancer spread or growth. RA may
reverse these tendencies: reports have suggested a reduction in recurrence or mortality in breast
24
, melanoma
25
, and
colon
26
cancer operations, though the data are equivocal for prostate and other cancers; further research is ongoing.
Breaking News-. The Centers for Medicare and Medicaid Services (CMS) has developed an incentive pay system
that rewards performance on several perceived quality measures, including 12 clinical process based scores and 8
patient-experienced based scores. Thirty percent of scores used for Value Based Purchasing (VBP) are derived
from 18 patient satisfaction questions, 6 of which relate to pain control experiences.
27
In an increasingly
competitive hospital reimbursement environment, we may actually see hospital administrations (and surgeons!)
expressing more interest in superior pain control regimens. Recent ASA Guidelines for Acute Pain Management
28

help show the path to improvement, and they include RA extensively. And many hospital administrators are asking
if RA analgesia techniques can help reduce post-operative delirium and falls (recent interests of the Joint
Commission) by avoiding opioids.
Also looming in our futures is the implementation of Accountable Care Organizations mandated by the Patient
Protection and Affordable Care Act (PPACA). While the definition of this concept is still in flux, it appears that
the outcomes of care will become increasingly relevant rather than just the process. The role of team members in
improving recovery, rehabilitation, and eliminating complications will increasingly play into the compensation

417
Page 2
The 6 Ps for improvement
Improve personal proficiency
1. Plan for success
2. Prepare beforehand
3. Practice, Practice, Practice
4. Persist
Align the institution
5. enlist the Personnel you need
6. establish standard Processes
picture. Our contribution to the perioperative hospital management of high-risk patients may have an impact on the
division of revenue in future integrated organizations.

Table 1. Meta-Analyses of Regional Anesthesia Outcomes
Overall Morbidity Lower morbidity, 30% lower mortality Rodgers et al., BMJ 2000
Liu, Wu, Anesth Analg 2007
Pain relief Epidural superior, esp. thoracic Block et al. , JAMA 2003
Wu et al, Anesthes 2005
Cardiac
complications
Lower incidence of myocardial infarction with
thoracic infusions
Beattie et al., AA 2001
Respiratory Fewer complications, infections with epidural Ballantyne et al, AA 1998
Gastrointestinal Faster return of function Steinbrook et al. AA 1998
Continuous
Catheters
Better pain relief with catheters, faster
rehabilitation in European experience
Richman et al, AA 2006
Ilfeld, AA 2011

Then Why Dont We Use More RA? Reasons Regional is Challenging
Despite the advantages, however, surveys suggest regional techniques are employed in less than 30% of
surgical procedures.
1

29
Surveys of post-operative pain scores suggest that there has been no improvement in patient
analgesia despite the availability of these superior techniques in the last 15 years.
30

31

32
Despite the superior pain
relief for outpatients, nerve blocks are used in less than 15% of knee operations and less than 25% of shoulder
surgeries.
33

As mentioned above, the main reasons are the issue of time and surgeon acceptance. Surgeon acceptance
can be improved if we overcome the time issues as well as documenting the advantages listed above. A 2004 survey
of Canadian orthopedic surgeons revealed that although they recognized the advantages of better pain control and
fewer complications, they encouraged their patients to have regional blocks only 40% of the time, based on
perceived delays in induction.
34
Surgeons were more likely to recommend regional anesthesia for procedures for
which they themselves would prefer regional!
35
In our practice we have found that they are more likely to accept RA
when they find that they get fewer postoperative phone calls. We will discuss several steps that can help overcome
all these issues in this presentation.

Opportunities for Improvement
We can make RA a more saleable package if we focus on its
advantages and remove the barriers of time and acceptance by
improving our own skills and enhancing our institutional
efficiency and support. There are six ps that can help us
improve personally, and as a team/institution.
Improve our personal proficiency. The first step for most of us
is to improve our own success rates so that we are more efficient
and reliable, and our surgeons are more willing to accept regional
interventions. This lecture is not an attempt to improve
performance on specific blocks: there are multiple presentations
and workshops that provide that function in the program. Many other opportunities are also available now in terms
of workshops, especially with the recent increasing popularity of ultrasound guidance for nerve blocks. Workshops
and courses are available virtually every month in every corner of the country (see ASA website Calendar of
Meetings, www.asra.com/education, as well as www.nysora.com).
A frequent question: should you incorporate ultrasound? Nerve stimulation is still an efficient technique
and traditional surface and bony landmarks are still the basis of spinal and epidural anesthesia. Ultrasound guidance
has not risen to be the standard, but there are increasing data that it facilitates speed and accuracy of block
performance,
36

37
although further information is needed to assess the potential improved safety possible when the
needle is visualized directly. There are now excellent reviews of ultrasound technology
38

39
, and a plethora of
companies competing to produce high quality imaging devices. Many anesthesiologists have gained renewed
confidence in blocks because of the ability to visualize the nerves, and an improved success rate when they have the
chance to see live the variations of anatomy that may have accounted for previous failures with traditional
techniques.

417
Page 3
Efficiency Steps:
1) Create standard work
2) Make the plan transparent to
the entire team
3) Perform blocks away from the
operating room
4) Centralize equipment to block
area
Some basic principles can improve success regardless of the technique used:
a) Plan for success. Choose simple and reliable blocks at the start, such as spinal, femoral and axillary (and
even supraclavicular with ultrasound). Avoid the complex techniques requiring a knowledge of Euclidian geometry,
such as the traditional infraclavicular and proximal sciatic. Also, pick blocks that fit your surgeons needs, such as
femoral or saphenous blocks for the total knee replacements, thoracic (rather than lumbar) epidurals for upper
abdominal surgery, and popliteal fossa blocks for the painful foot surgeries that benefit from prolonged analgesia.
When appropriate, use fast onset local anesthetics, such as chloroprocaine or lidocaine. With lidocaine or
mepivacaine, though the data are confusing, consider adding 1 mL NaHCO3 to each 10 mL of local anesthetic to
speed onset (dont try this with bupivacaine!).
40
Recognize that despite your expertise, local anesthetic blocks
require time to set up, and your success might be improved by using a light general anesthetic for the case and rely
on the block to provide the postoperative analgesia.
b) Prepare yourself and your work area before doing your first attempt.
i) Know the anatomy of the nerve and its surroundings first, particularly the easily identifiable landmarks such as
prominent bones (C6 tubercle for interscalene) or arteries (axillary and femoral). Review the anatomy books,
websites and recent articles on techniques and hazards, and go to one of the many workshops mentioned above.
ii) Prepare your equipment beforehand. Have your drugs, gloves, trays, and resuscitation equipment all in one area
on a cart so that you do not waste time assembling them (or forget an essential item).
iii) This includes a workspace, such as a block room or corner of the PACU where monitors, oxygen and
equipment are available.
c) Practice as much as possible. Develop an efficient style. With either nerve stimulator or paresthesia
technique, search for the nerve in a logical fashion, usually confining the needle movement to small steps in one
plane that is perpendicular to the perceived path of the nerve (useful for interscalene, distal sciatic). Or start next to
an artery (axillary, femoral) and walk in small steps away from it. For ultrasound techniques, use the phantom
models to acquire dexterity with needle visualization, and practice scanning the anatomy on yourself, your
colleagues, and your partners. More IS better.
d) Finally, Persist. All new technical procedures have an inevitable failure rate
41
on the initial learning
curve, including ultrasound.
42
Acknowledge early failures and move rapidly to plan B, but dont give up after the
first ten attempts. Particularly, dont succumb to the temptation to try another approach they all work pretty well
when you get past the first struggles, and you will only be climbing onto the bottom rung of another learning curve!

Improve our team proficiency Two other ps
e) Personnel are critical. You will need help with the blocks, at several stages.
i) First, education of the patient is critical, and if it is done preoperatively, it is a great time saver. This may require
enlisting your pre-anesthesia clinic staff or a partner to explain the procedure and prepare the patient before arrival.
Or even on the day of surgery, a discussion before the rushed start of a block is helpful. In the best scenarios, your
surgeon will tell the patient about the block.
ii) Secondly, you will need hands to help position, monitor, and sedate the patient, and perhaps even to inject local
anesthetic when your hands are busy with needle and ultrasound probe. This may be a partner or a PACU or
Admitting nurse, most of whom are very interested in participating in procedures, especially when they see it will
make their job in PACU easier. Additional personnel (such as a floating anesthesia staff or a designated block
team in a large or academic practice) can allow the block to start even earlier.
iii) Finally, you will need a team to follow up with your patients at home or on the wards. Creating a successful
perioperative pain management program requires a 24/7 commitment, which is far easier when you have colleagues
or a team nurse who are equally committed to ensuring adequate relief and correction of any defects in doses,
pumps, or side effects.
f) Finally, Processes are essential. Success in initiating an
ongoing RA program depends on procedural steps to reduce the time for
placement of blocks and allow for onset of local anesthetic action. General
principles for efficiency can be adapted from business models, like the
Toyota Production System that Boeing has adopted.
i) First, create Standard work and expectations. Establish, for example,
a pattern that every knee replacement gets a nerve block. Then the
surgeon starts that discussion in his or her office, and the patient arrives
expecting a block. The anesthesia pre-operative visit confirms and
explains the plan, and the admitting nurse on the day of surgery knows that
the patient needs to be on a stretcher, the team needs to be called early, and

417
Page 4
the necessary equipment is ready when the anesthesiologist arrives. The block is done in the same way, with the
same equipment and drugs, every day, so the same supplies are stocked and ready. The OR, PACU, and ward
nurses are not surprised by a numb limp extremity, and the physical therapists know to test for return of motor
function before starting ambulation. Every patient has one, every care provider knows. This saves time on a daily
basis, and potentially improves safety because everyone is aware of the pathway.
ii) The process must be Transparent. The surgeons pre-op orders confirm the request for the block. The
anesthesia plan confirms it, documents standard information in a standard form, and has a template in the
computerized orders for management of the patient monitoring, drug administration, and infusion maintenance. The
process is visible and clear to all the participants.
iii) Externalizing the set-up away from operating room is essential to improving efficiency. The exact mechanism
will vary depending on local situations, but there are many opportunities: the Cleveland Clinic has published their
pathway for arthroplasties as one example.
43
A central principle is that to avoid any delays in the operating room
process, the block is performed in a separate area a block room
44
, the admitting area, or a corner of the PACU
where necessary monitors and equipment are already available. The use of the block room actually decreases the
anesthesia controlled time in the operating room itself
45
and does not significantly delay the transfer of the patient
to the operating room.
46
If standard equipment is ready, in many hospitals the block can be performed by the same
anesthesia team while the operating room is being cleaned and instruments opened.
iv) A critical component of this process is measuring the actual times involved. In our institution, the known time
for admission, IV placement, and block performance is added together and then subtracted from the anticipated time
the OR will be ready, thus dictating the time the patient will arrive and the anesthesia team will start working. If this
is before the previous patient leaves the OR, obviously alternative teams are needed. And a system has to be in
place to signal the anesthesia technicians (or other support) to assemble the block cart and ultrasound, and call the
anesthesiologist to begin the process.
Two examples of Standard Processes in our practice:
Total Knee Arthroplasty. Our pathway has grown out of a collaboration of anesthesiologists, surgeons,
physical therapists, and floor nurses. The primary goals were adequate analgesia with little reliance on opioids (to
reduce nausea and delirium) with early return of motor function to enhance physical therapy and reduce the potential
for falls. We now rely heavily on adductor canal catheters for post-operative analgesia rather than femoral blocks
because of the significantly less motor blockade.
47

48
The pathway includes
a) oral pre-operative multimodal analgesics (acetaminophen, gabapentin, celecoxib), continued postop
b) spinal anesthesia for surgery, with intraoperative sedation
c) postoperative adductor canal infusion with ropivacaine 0.2% for 48 hours
d) transition to oral analgesics and initiation of physical therapy on day of surgery
e) aggressive antiemetic therapy ondansetron and scopolamine patch
This protocol has allowed better analgesia, earlier ambulation, and reduced discharge time by 12 hours. It is highly
successful because all patients (regardless of surgeon) are told to expect it. The Admitting Area knows there will be
two blocks, and the patients are brought in earlier for that. A special team of residents performs all the peripheral
blocks, with anesthesia technicians who know exactly what equipment will be needed and when. The floor nurses
and physical therapists know to check for (unlikely) motor block, and move aggressively with ambulation because
of the effective analgesic regimen.
Rotator Cuff Surgery, This is usually performed on an outpatient basis, and the protocol was developed in
conjunction with our surgeons and their (grateful) Physicians Assistants. Patients are advised in the surgeons office
preoperatively that they will get a block and have a numb arm for 48 hours. The pathway includes:
a) preoperative acetaminophen and celecoxib (no gabapentin)
b) preoperative interscalene catheter in holding area by peripheral nerve block team, with initial lidocaine
dose and start of continuous ropivacaine infusion.
c) intraoperative general anesthesia with LMA
d) transfer to PACU with arm in sling,
e) written instructions and contact phone number before discharge
f) daily call by RN on Pain Service
g) removal of catheter at home, or on return for physical therapy.
This protocol has produced dramatic improvement in analgesia, minimal opioid use, and dramatic reduction in
phone calls to primary team.

417
Page 5
Selling RA: Apply Efforts Efficiently pick the best returns for the time. In the process of introducing RA into
a practice where it is not used frequently, choose the procedures with the highest benefits and fewest drawbacks- the
low-hanging fruit. You can use some of the data from consensus recommendations, like the PROSPECT project
49

(www.postoppain.org), or just look at your own practice and see the easiest opportunities.
a) Frequently this is the orthopedic service, where the surgeons find that traditional analgesia limits their
patients rehabilitation and causes many adjustments of medication (i.e., phone calls) to produce analgesia without
debilitating nausea and vomiting, not to mention the dreaded delirium and falls. They are grateful if you can help,
and this usually means starting with simple single-injection femoral nerve or psoas compartment blocks with long-
acting drugs for total hip and knee replacements. Once this procedure is recognized to have advantages, adding a
continuous catheter technique to prolong the benefits is much easier to negotiate with the orthopedic team.
b) Thoracic epidural analgesia requires more time, but is so clearly advantageous to the major vascular and
thoracic surgery patient that the surgeons often request it. Given the recent emphasis on Enhanced Recovery After
Surgery (ERAS) for abdominal operations, surgeons should also be receptive to the advantages of epidural
infusions in improving analgesia and speeding return of bowel function.
50
Expanding the use of epidural analgesia
is usually dependent on the efficiency steps described above, but a post-operative pain service with epidural
infusions as the mainstay is usually rapidly recognized by ward nurses, administration, and surgeons as being worth
the additional time required for the initial insertion for a catheter.
c) Outpatient surgery, particularly orthopedic procedures, is another opportunity for increasing the use of
regional techniques. For the painful outpatient procedures (anterior cruciate ligament repair, rotator cuff surgery,
complex foot surgery, open fracture repairs), single injection femoral (or saphenous), popliteal fossa or interscalene
blocks can again be done quickly before the procedure, and allow a comfortable first night for most patients.
Initially (if a block room is not available) it is often expedient to place a block with a long-acting anesthetic and then
proceed with a quick general or spinal anesthetic rather than waiting for the slower onset of the block. With this
approach, the surgery begins rapidly, but narcotics are avoided and patients arrive in PACU alert and pain-free,
ready for rapid discharge. Again, once this advantage is recognized (as well as the risks of intraarticular
infusions
51
), many orthopedic surgeons are delighted to accept a slightly longer time for the insertion of a
continuous catheter as in the rotator cuff example above which can extend the analgesia (and the period in which
they do not get phone calls for inadequate pain relief). Once these practices are in place, it becomes easier to
advance the use of regional techniques to many other procedures.

Summary Regional techniques offer many advantage to our inpatients and outpatients. Simple steps to
improve our efficiency and reliability can lead to greater success and surgeon and patient acceptance, and bring
these documented benefits to a higher percentage of our patients. Equally important, this is an opportunity for
anesthesia providers to assume a more critical and indispensible role in the medical center. As we move to an era of
Accountable Care Organizations (and the concept of a Surgical Home) and more external estimations of the
presumed quality of our care environment, RA can extend our visibility and impact and ensure we are part of the
perceived value of a patient experience.

_____________________________________________________________________________________

417
Page 6
References

1
Tighe PJ, Brennan M, Moser et al. A. Primary payer status is associated with the use of nerve block placement for
ambulatory orthopedic surgery. Reg Anesth Pain Med. 2012; 37:254-61.
2
Rodgers A, Walker N, Schug SA, et al. Regional anaesthesia reduces postoperative mortality and morbidity:
results from an overview of randomized trials. British Medical Journal 2000; 321:1-12.
3
Manion SC, Brennan TJ. Thoracic epidural analgesia and acute pain management. Anesthesiology. 2011;115:181-
8.
4
Liu SS, Wu CL. Effect of postoperative analgesia on major postoperative complications: a systematic update of the
evidence. Anesth Analg. 2007 Mar;104(3):689-702.
5
Wu CL, Cohen SR, Richman JM, et al. Efficacy of postoperative patient-controlled and continuous infusion
epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology.
2005;103:1079-88.
6
Beattie WS, Badner NH, Choi PT. Meta-analysis demonstrates statistically significant reduction in postoperative
myocardial infarction with the use of thoracic epidural analgesia. Anesth Analg. 2003;97:919-20
7
Ballantyne JC, Carr DC, deFerranti S et al. The comparative effects of postoperative analgesic therapies on
pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998;86:598-612.
8
Steinbrook RA. Epidural anesthesia and gastrointestinal motility. Anesth Analg. 1998;86:837-44.
9
Barreveld A, Witte J, Chahal H, Durieux ME, Strichartz G. Review article: preventive analgesia by local
anesthetics: the reduction of postoperative pain by peripheral nerve blocks and intravenous drugs. Anesth
Analg. 2013;116:1141-61.
10
Memtsoudis SG, Sun X, Chiu YL, Stundner O, Liu SS, Banerjee S, Mazumdar M, Sharrock NE.
Perioperative comparative effectiveness of anesthetic technique in orthopedic patients. Anesthesiology.
2013;118:1046-58
11
Memtsoudis SG, Stundner O, Rasul R, Sun X, Chiu YL, Fleischut P, Danninger T, Mazumdar M. Sleep Apnea
and Total Joint Arthroplasty under Various Types of Anesthesia: A Population-Based Study of Perioperative
Outcomes. Reg Anesth Pain Med. 2013 Apr 3. [Epub ahead of print].
12
Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain control to
opioids? A meta-analysis. Anesth Analg. 2006;102:248-57
13
Hebl JR, Dilger JA, Byer DE, Kopp SL, Stevens SR, Pagnano MW, Hanssen AD, Horlocker TT. A pre-emptive
multimodal pathway featuring peripheral nerve block improves perioperative outcomes after major orthopedic
surgery. Reg Anesth Pain Med. 2008;33:510-7
14
Duncan CM, Hall Long K, Warner DO, Hebl JR. The economic implications of a multimodal analgesic regimen
for patients undergoing major orthopedic surgery: a comparative study of direct costs. Reg Anesth Pain Med.
2009;34:301-7.
15
Liu SS, Strodtbeck WM, Richman JM, Wu CL. A comparison of regional versus general anesthesia for
ambulatory anesthesia: a meta-analysis of randomized controlled trials. Anesth Analg. 2005;101:1634-42
16
Hadzic A, Arliss J, Kerimoglu B, Karaca PE, Yufa M, Claudio RE, Vloka JD, Rosenquist R, Santos AC, Thys
DM. A comparison of infraclavicular nerve block versus general anesthesia for hand and wrist day-case surgeries.
Anesthesiology. 2004 ;101:127-32.
17
Mulroy MF, Larkin KL, Hodgson PS, Helman JD, Pollock JE, Liu SS. A comparison of spinal, epidural, and
general anesthesia for outpatient knee arthroscopy. Anesth Analg. 2000;91:860-4.
18
Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011;113:904-
25.
19
Swenson JD, Bay N, Loose E, Bankhead B, Davis J, Beals TC, Bryan NA, Burks RT, Greis PE. Outpatient
management of continuous peripheral nerve catheters placed using ultrasound guidance: an experience in 620
patients. Anesth Analg. 2006;103:1436-43.
20
Capdevila X, Dadure C, Bringuier S, Bernard N, Biboulet P, Gaertner E, Macaire P. Effect of patient-controlled
perineural analgesia on rehabilitation and pain after ambulatory orthopedic surgery: a multicenter randomized trial.
Anesthesiology. 2006;105:566-73
21
Carli F, Mayo N, Klubien K, Schricker T, Trudel J, Belliveau P. Epidural analgesia enhances functional exercise
capacity and health-related quality of life after colonic surgery: results of a randomized trial. Anesthesiology.
2002;97:540-9.
22
De Kock M. Expanding our horizons: transition of acute postoperative pain to persistent pain and establishment of
chronic postsurgical pain services. Anesthesiology. 2009;111:461-3
23
Sessler DI. Long-term consequences of anesthetic management. Anesthesiology. 2009;111:1-4.

417
Page 7

24
Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast
cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660-4.
25
Schlagenhauff B, Ellwanger U, Breuninger H, et a. Prognostic impact of the type of anaesthesia used during the
excision of primary cutaneous melanoma. Melanoma Res. 2000;10:165-9
26
Cummings KC 3rd, Xu F, Cummings LC, Cooper GS. A comparison of epidural analgesia and traditional pain
management effects on survival and cancer recurrence after colectomy: a population-based study. Anesthesiology.
2012;116:797-806
27
Maga J. The safety and financial implications of an acute pain service. ASA Newsletter, April 2012.
28
American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain
management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task
Force on Acute Pain Management. Anesthesiology 2012;116:248-73
29
Hadzic A, Vloka JD, Kuroda MM, et al. The Practice of Peripheral Nerve Blocks in the United States: a national
survey. Reg Anesth Pain Med 1998, 241-6.
30
Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest
postoperative pain continues to be undermanaged. Anesth Analg. 2003;97:534-40.
31
Warfield CA, Kahn CH. Acute pain management. Programs in U.S. hospitals and experiences and attitudes
among U.S. adults. Anesthesiology. 1995;83:1090-4.
32
White PF, Kehlet H. Improving postoperative pain management: what are the unresolved issues? Anesthesiology
2010;112:220-5.
33
Memtsoudis SG, Kuo C, Ma Y, Edwards A, Mazumdar M, Liguori G. Changes in Anesthesia-Related Factors in
Ambulatory Knee and Shoulder Surgery: United States 1996-2006. Reg Anesth Pain Med. 2011.
34
Oldman M, McCartney CJ, Leung A, Rawson R, Perlas A, Gadsden J, Chan VW. A survey of orthopedic
surgeons' attitudes and knowledge regarding regional anesthesia. Anesth Analg. 2004;98:1486-90
35
Masursky D, Dexter F, McCartney CJ, Isaacson SA, Nussmeier NA. Predicting orthopedic surgeons' preferences
for peripheral nerve blocks for their patients. Anesth Analg. 2008;106:561-7
36
Neal JM, Brull R, Chan VW, Grant SA, Horn JL, Liu SS, McCartney CJ, Narouze SN, Perlas A, Salinas FV, Sites
BD, Tsui BC. The ASRA evidence-based medicine assessment of ultrasound-guided regional anesthesia and pain
medicine: Executive summary. Reg Anesth Pain Med. 2010;35(2 Suppl):S1-9.
37
Abrahams MS, Aziz MF, Fu RF, Horn JL. Ultrasound guidance compared with electrical neurostimulation for
peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth.
2009;102:408-17.
38
Sites BD, Brull R, Chan VW, Spence BC, Gallagher J, Beach ML, Sites VR, Hartman GS. Artifacts and pitfall
errors associated with ultrasound-guided regional anesthesia. Part I: understanding the basic principles of ultrasound
physics and machine operations. Reg Anesth Pain Med. 2007;32:412-8
39
Sites BD, Brull R, Chan VW, Spence BC, Gallagher J, Beach ML, Sites VR, Abbas S, Hartman GS. Artifacts
and pitfall errors associated with ultrasound-guided regional anesthesia. Part II: a pictorial approach to
understanding and avoidance. Reg Anesth Pain Med. 2007;32:419-33
40
Capogna G, Celleno D, Laudano D, Giunta F. Alkalinization of local anesthetics. Which block, which local
anesthetic? Reg Anesth. 1995 ;20:369-77
41
Konrad C, Schpfer G, Wietlisbach M, Gerber H. Learning manual skills in anesthesiology: Is there a
recommended number of cases for anesthetic procedures? Anesth Analg. 1998;86:635-9
42
Barrington MJ, Wong DM, Slater B et al.. Ultrasound-guided regional anesthesia: how much practice do novices
require before achieving competency in ultrasound needle visualization using a cadaver model. Reg Anesth Pain
Med. 2012;37:334-9
43
Smith MP, Sandberg WS, Foss J, Massoli K, Kanda M, Barsoum W, Schubert A. High-throughput operating
room system for joint arthroplasties durably outperforms routine processes. Anesthesiology. 2008;109:25-35
44
Armstrong KP, Cherry RA. Brachial plexus anesthesia compared to general anesthesia when a block room is
available. Can J Anaesth. 2004 Jan;51(1):41-4
45
Mariano ER, Chu LF, Peinado CR, Mazzei WJ. Anesthesia-controlled time and turnover time for ambulatory
upper extremity surgery performed with regional versus general anesthesia. J Clin Anesth. 2009;21:253-7
46
Chelly JE, Horne JL, Hudson ME, Williams JP. Factors impacting on-time transfer to the operating room in
patients undergoing peripheral nerve blocks in the preoperative area. J Clin Anesth. 2010;22:115-21
47
Jenstrup MT, Jger P, Lund J, Fomsgaard JS, Bache S, Mathiesen O, Larsen TK, Dahl JB. Effects of adductor-
canal-blockade on pain and ambulation after total knee arthroplasty: a randomized study. Acta Anaesthesiol Scand.
2012;56:357-64.

417
Page 8

48
Jaeger P, Nielsen ZJ, Henningsen MH, Hilsted KL, Mathiesen O, Dahl JB. Adductor canal block versus femoral
nerve block and quadriceps strength: a randomized, double-blind, placebo-controlled, crossover study in healthy
volunteers. Anesthesiology. 2013;118:409-15
49
Joshi GP, Kehlet H. Procedure-specific pain management: the road to improve postsurgical pain management?
Anesthesiology. 2013;118:780-2.
50
Jouve P, Bazin JE, Petit A, Minville V, Gerard A, Buc E, Dupre A, Kwiatkowski F, Constantin JM, Futier E.
Epidural versus continuous preperitoneal analgesia during fast-track open colorectal surgery: a randomized
controlled trial. Anesthesiology. 2013;118:622-30
51
Anderson SL, Buchko JZ, Taillon MR, Ernst MA. Chondrolysis of the glenohumeral joint after infusion of
bupivacaine through an intra-articular pain pump catheter: a report of 18 cases. Arthroscopy. 2010;26:451-61

Disclosure

424
Page 1
The Role of Anesthesiologists in Prevention of Chronic Pain After Surgery
Asokumar Buvanendran, M.D. Chicago. Illinois
Introduction
During the last decade, increased attention has been paid to persistent pain complaints after almost any surgical
operation, with reported incidences ranging between 5-50%. These chronic pain problems represent a major
humanitarian and socioeconomic burden. The pathogenic mechanisms are multiple, and they can be grouped
into preoperative, intraoperative and postoperative factors. This RCL will update and discuss recent
developments with regard to the epidemiology of persistent postoperative pain and the different preoperative,
intraoperative and postoperative risk factors. Based on selected procedure-specific data, we will discuss the
current status of knowledge and future strategies for prevention and treatment.
Definition and Epidemiology of Persistent Postoperative Pain (PPP)
Persistent postoperative pain is a silent epidemic that is in urgent need for understanding of the
pathophysiology. The consequence of PPP can be variable from mild to severe loss of quality of life. The
International Association of the Study of Pain (IASP) defines it as persistent pain after surgery of greater than
three months duration. Although there are several publications on this emerging topic, the definition of PPP
itself has been varied in several of them and as such, the incidence of PPP cannot be truly estimated for the ever
increasing surgical volume in the world.
As an initial step, it is critical that an accepted definition of PPP be agreed on so the true incidence of PPP can
be determined following various surgical procedures. There are several clinical studies that have used the
definition of PPP as pain of two months duration after the surgical insult but this is not based on scientific facts.
Whether it is two or three months, while reporting epidemiological and clinical trials it is vital to select a
conservative time frame and as such three months after the surgical insult seems more clinically relevant. In
addition three months allows for the patient and surgical care team taking care of the patient to undergo various
clinical tests to rule out other pathological causes for the pain at the operated surgical site. Before making a
diagnosis of PPP, it is critical that other common causes for pain from surgery be ruled out. As an example for
patients that had total knee arthroplasty the following algorithm needs to be carried out before labeling a patient
as PPP. An examination has to be performed to evaluate instability of the tibial femoral joint or patellar
maltracking. Plain radiographs has to be reviewed for evidence of prosthetic loosening, malposition and patellar
maltracking, as well as overall axial alignment to ensure coronal alignment is within the range of neutral to 10
deg of valgus. If this evaluation is negative, an erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) measurement has to be obtained as a screening tool for infection. If these indices are abnormal (ESR>30
mm/h; CRP>10!g/mL), an aspiration of the knee has to be performed, including a synovial fluid white blood
cell count with differential and culture to rule out infection. In addition to ruling out common causes of pain, it
is also critical to define in detail the location, characteristic and consequence from PPP on physical and social
function. Future clinical and epidemiological reports should include the degree of disability or decrease health
related quality of life due to PPP. Once the degree of decrease in health related quality of life is estimated the
cost of treatment of PPP can be predicted and the value of prevention of PPP will be appreciated.
In 2010, the Food and Drug Administration (FDA) formed a group called the ACTION (Analgesic Clinical Trial
Innovations, Opportunities and Networks) and requested researchers and industry to undertake basic and clinical
trials on prevention of PPP. The ACTION committee has made some recommendations for conducting clinical
trials for PPP prevention. Clinical trials examining PPP need to include preoperative, intraoperative, and early
and late postoperative parameters and the outcome needs to be assessed at the defined time point. Preoperative
pain is consistently found to be a predictor for PPP, which might reflect an independent risk factor, but could
well be a manifestation of predisposing factors.
The cost for treatment of PPP and the degree of disability from PPP are high and therefore any measures
undertaken to decrease the incidence of PPP will have a significant impact on the health care resources. In a
Danish hysterectomy database review of 1135 women undergoing hysterectomy, PPP was described in 32% of

424
Page 2
patients at one year follow-up. The identified risk factors included preoperative pelvic pain, previous cesarean
section, other pain problems and pain as an indication for hysterectomy. Moderate to severe pain (PPP) was
reported in 9.5% of patients at one year after cosmetic breast augmentation surgery from a survey of 95 patients.
Recent data from Sweden of 1461 patients undergoing femoral hernia repair, about 5.5% of patients had
persistent pain at more than one year that interfered with their concentration on daily activities of living. A
recent study carried out in the UK of 1294 patients undergoing THA and TKA, the incidence of moderate to
severe chronic pain was reported to be 15% and 6% for TKA and THA respectively. Of these patients with
chronic pain about 6% and 1% of the TKA and THA respectively had neuropathic pain at one year after surgery.
In a multicenter cross-sectional survey of 1030 patients undergoing total hip and knee replacement in USA, 46%
of patients reported persistent pain (38% after THA and 53% after TKA) with a median average pain score of
3/10 and worst pain score of 5 after 1 year of surgery.
Preoperative risk factors
Psychosocial factors
It has long been clear that psychosocial factors impact the transition from acute to chronic pain; indeed, many
investigators have suggested that cognitive and emotional processes are among the most influential in shaping
an individuals risk for the development of a chronic pain condition. Over the past several years, reviews have
identified numerous pre-operative factors that contribute to variability in long-term post-surgical pain outcomes.
Despite the use of a variety of assessment measures, the large majority of reports that evaluated the impact of
depression, anxiety, somatization, and passive coping found that these pre-treatment variables predicted poorer
acute and long-term surgical outcomes. A 2009 review noted that the effects of such pre-operative factors on
broad post-operative outcomes such as pain intensity and analgesic consumption have been demonstrated in
rigorous studies including well over 20,000 patients. In addition, recent evidence has identified sleep disruption
(which is associated with indices of negative affect) as an important factor contributing to individual differences
in acute post-operative pain, as well as to persistent pain. Collectively, surgical patients who are anxious,
distressed, depressed, somatically focused, sleeping poorly, and who are not active pain copers are prone to
psychological vulnerability and detrimental post-operative pain outcomes. These findings should hardly be
surprising as a very similar profile of psychosocial factors predicts poor outcomes across a variety of medical
conditions including cardiovascular diseases, cancer, and gastrointestinal disorders.
One specific factor that has emerged as a potent predictor of acute and chronic post-operative pain is
catastrophizing. Catastrophizing is comprised of a set of negative cognitive and affective processes related to
pain; it is typically assessed with self-report items such as: I keep thinking about how much it hurts, and I
feel I can't stand it anymore. The construct of catastrophizing incorporates magnification of pain-related
symptoms, rumination about pain, feelings of helplessness when in pain, and pessimism about pain-related
events. Abundant evidence identifies high pre-operative levels of catastrophizing as a critically-important risk
factor for adverse pain-related outcomes after a variety of surgeries such as spine surgery, joint replacement,
breast surgery, cesarean section, and many others. Indeed, recent evidence suggests that catastrophizing, which
is correlated with more general measures of distress and negative affect, may be the principal psychosocial
driver of postoperative pain. In a sample of over 200 women undergoing hysterectomy, presurgical anxiety level
was initially a highly significant predictor of pain intensity at 48 hours after surgery, but after the inclusion of
catastrophizing in the model, the influence of anxiety was no longer significant while catastrophizing remained
in the multivariate model, fully mediating the effects of anxiety.
Genetic factors
The high degree of inter-individual variability in pain response is multifactorial, and a substantial proportion of
those individual differences appear to be due to genotypic variation. Heritability estimates for pain sensitivity
generally conclude that somewhere between 2070% of the variation in pain experience is explained by genetic
factors.
Nociceptive function
In addition to investigation of the specific role of genetic and psychosocial factors, efforts have been made to
preoperatively quantify the functional status of the nociceptive function by different nociceptive stimuli (heat,
electricity, cold, etc.). The summary of these studies have clearly indicated that the pain response to such
preoperative stimuli may to some extent predict the acute pain response to an operation, and in a few studies the
risk for persistent pain as well. In a recent large prospective trial in inguinal and laparoscopic herniorrhaphy, the
preoperative pain-related functional complaints and the pain response to 47C heat stimulation were the most
significant preoperative risk factors for the development of significant chronic pain complaints 6 months
postoperatively, although intraoperative factors (choice of surgical technique with different risks of nerve
injury) were also important. However, the preoperative nociceptive function tests continued to be an

424
Page 3
independent risk factor for chronification. Other studies have focused on the predictive role of the diffuse
noxious inhibitory controls (DNIC) system for acute and chronic post-thoracotomy pain.
Intraoperative risk factors
In most patients, persistent postoperative pain demonstrates features of neuropathic pain and the highest
incidences of these complaints have been reported from procedures where major nerves cross the surgical field
(amputation, thoracotomy, breast surgery, and groin hernia repair). However, differentiation of neuropathic from
non-neuropathic causes has been difficult, because signs of neurological damage have been reported following
many procedures, in patients both with and without persistent pain. Thus, intraoperative nerve injury may be a
significant risk factor, but additional factors may determine whether a patient with nerve injury will eventually
present with neuropathic pain or not. The interpretation of the few detailed studies with postoperative
quantitative sensory testing has demonstrated a heterogenic pattern of nerve dysfunctions in the skin.
Postoperative risk factors
Does early postoperative analgesic therapies decrease the PPP incidence?
The transition from acute postoperative pain to PPP is a complex and poorly understood process. However,
there are studies that have established an association between the intensity of acute postoperative pain and the
consequent development of chronic persistent pain after breast surgery, heart surgery, inguinal hernia, cesarean
section, and hip replacement. Perioperative factors (i.e. method of anesthesia, perioperative analgesia
management, blood loss) in relation to increased acute postoperative pain and TKA outcomes have been
evaluated, but none have been implicated in the development of chronic persistent pain after TKA. Recently the
perioperative use of oral pregabalin for patients undergoing TKA with a multimodal regime has been
demonstrated to decrease the incidence of chronic and neuropathic pain (0% in the study group and 5.6% in the
placebo group) in 240 patients. Most clinical studies have focused on acute postoperative pain most especially
when the patient is in the hospital. However, there are limited analgesic clinical studies and guideline
recommendations for the sub-acute postoperative pain when patients are rehabilitating from the surgical insult.
It could be that this transition phases of sub-acute postoperative pain that bridges acute postoperative pain to
PPP.
Increased postoperative pain is considered an independent risk factor for PPP. It may well be that patients with
severe acute postoperative pain experience more sensitization and therefore develop more PPP. Another factor
that may influence postoperative pain is preoperative psychological state of the patient. There has been
discussion about postoperative pain trajectories and this tool may serve as a predictor for patients who might
develop PPP. Normally the pain slope with NRS should decrease but if there is an increase or a positive slope
these may be indications for further investigation Recently pain catastrophizing and presurgical anxiety has been
linked to increased acute postoperative pain and PPP in patients undergoing hysterectomy. In the recent review
of Danish database of patients undergoing hysterectomy, high acute postoperative pain was one of the risk
factors for developing PPP at one year after surgery.
Adjuvant therapy
Many patients who have surgery will also receive other treatments. For patients who have cancer, radiotherapy
and chemotherapy will form part of their treatment plan. Both of these treatments undoubtedly have a role in the
management of breast cancer, but both have the potential to produce side effects and complications.
General Treatment Principles
Perhaps the strongest and most consistent risk factor for persistent pain after surgery is highly intense acute
post-operative pain. This state of affairs has led to numerous efforts to design preemptive, and now preventive,
analgesic regimens capable of diminishing the observed rates of persistent pain after a variety of surgeries. Not
surprisingly, since persistent post-surgical pain is a complex, multifactorial phenomenon involving elements of
inflammation, nerve injury, central sensitization, and assorted psychosocial and environmental risk factors, it
has proven difficult to identify single agents whose administration reliably reduces the incidence of long-term
pain following surgery. For example, in a recent meta-analysis investigating the effect of preemptive incisional
or intraperitoneal local anesthetic, the degree of postoperative pain reduction achieved was either minimal or
clinically insignificant. Collectively, recent reviews have therefore emphasized administration of prolonged,
aggressive, and multimodal analgesia, including antihyperalgesic agents, antidepressants, microglial modulators
to reduce central inflammatory responses, cytokine antagonists, etc. Indeed, given the scope of the risk factors
identified above, it may be that combining many pharmacologic treatments with multiple non-pharmacologic
interventions (e.g., targeted exercise regimens, cognitive-behavioral therapy) will provide an enhancement of
current preventive analgesic practices. In order to achieve this goal, large randomized trials (likely multicenter

424
Page 4
trials) which follow at-risk patients (defined on the basis of empirically-validated factors) for at least 6 months
will be required.
Disclosure
Pzifer, NIH; Funded Research
426
Page 1
The Economics of Regional Anesthesia
Brian A. Williams, M.D., MBA Pittsburgh, Pennsylvania
Subtitle: The Value of Single-Injection and Continuous Peripheral Nerve Blocks for Surgical Pain Management as
part of a Perioperative Regional Anesthesia Care Plan (i.e., actively avoiding general anesthesia whenever possible)
Objectives: (i) Distinguish regional from general anesthesia with respect to required time and labor resources both
upstream and downstream from the operating room; (ii) Provide practice management (re-engineering)
principles to maximize the value of investments in a new or existing regional anesthesia program; and (iii) When
applicable, translate known regional anesthesia patient and hospital benefits into monetary values.
Description: When judiciously applied, peripheral nerve blocks placed before surgery require more upstream
workload, with the aim of patient-centered symptom reduction downstream. When preoperative nerve blocks are
coupled with an intraoperative regional anesthesia (RA) and sedation care plan (e.g., for orthopedic surgery),
multiple patient and hospital benefits are achievable. Often, general anesthesia (GA) is used intraoperatively instead
of RA simply because the latter was less convenient even though RA may have been more appropriate. GA with
volatile agents and opioids, via their known hyperalgesic effects during recovery, can undermine the full potential
for process efficiency and patient symptom reduction intended with RA, specifically preoperative peripheral nerve
blocks. Patient symptom reductions and process efficiency improvements, via RA both pre- and intraoperatively,
can lead to significant hospital cost reductions. In the United States, RA procedures and inpatient continuous nerve
block catheter follow-up can lead to significant generation of departmental and hospital revenue, but these revenues
may be threatened with forthcoming changes in reimbursement. This refresher course lecture will introduce and
summarize fundamental principles of care process improvements with RA (and avoidance of volatile agent GA and
opioid avoidance) that can translate into meaningful economic benefits in both monetary and non-monetary terms.
Codifying economic benefits can help to justify building and sustaining RA services when discussing RA services
with hospital administrators who may be unaware of these patient-centered and hospital efficiency nuances.
Suitable Discharge Criteria: Liu et al.(2005) described that with respect to the routine use of RA, Potential
advantagessuch as decreased PACU (post-anesthesia care unit) use, nausea, and postoperative painhave been
proposed to reduce ambulatory surgery unit stay.
1
However, in meta-analysis, neither central neuraxial block nor
peripheral nerve block were associated with reduced ambulatory surgery unit time.
1
Unsuitable discharge criteria
is cited as the primary reason for this discrepancy.
1
To the presenters knowledge, only one suitable discharge
criteria system has been statistically significantly associated with avoided unplanned hospital admission when the
criteria were met for PACU bypass.
2
These associated hospital process benefits (based on suitable discharge
criteria) translate to statistically significant hospital cost savings.
3
These criteria
4
(i) were modified from legacy
5,6

criteria to incorporate nuances of both RA and ambulatory anesthesia, and (ii) include Zero Tolerance criteria
(nausea, vomiting, lightheadedness, shivering, pruritus, and pain out of proportion to preoperative pain scores with
movement). These published criteria have since been given the new title The WAKE Score.
7
Designing
anesthesia care plans to maximize the opportunity for WAKE Score-based PACU Bypass seems central to providing
maximal economic benefit from a regional anesthetic care plan. Avoiding any/all legacy anesthetics/techniques
likely reduce the risk of failure to meet WAKE Score criteria for PACU Bypass, including volatile agents, opioids,
airway devices, and non-depolarizing muscle relaxants for surgeries that do not absolutely require them. Peripheral
orthopedic surgery is the ideal clinical scenario to employ WAKE-based techniques, and to relegate legacy recovery
criteria and legacy anesthetic techniques to be of historical consideration only.

426
Page 2
In addition to the aforementioned Zero Tolerance Criteria of the WAKE Score, the remaining WAKE criteria
(scored zero, one, or two, per parameter) are as listed in Table 1. A score of 8 or higher (out of 10, along with
satisfying the Zero Tolerance Criteria) is required for PACU bypass or PACU discharge, while a score of 9 or higher
is used for patients with diagnosis or suspicion of obstructive sleep apnea (a WAKE score of 9 or higher, with all
Zero Tolerance Criteria being met, and at least 30 consecutive minutes of no apnea when patient is lying
undisturbed).
7
The remainder of this refresher course lecture will direct attention to potential and real economic
benefits of RA (i.e., peripheral nerve blocks superimposed upon an intraoperative neuraxial anesthetic care plan,
when appropriate) when the WAKE Score is established as the care plan target for patient outcome immediately

after surgery. Before monetary benefits are explored, this presentation will first explore time management benefits
of peripheral nerve block-based anesthesia care plans.

Table 1: WAKE Criteria for PACU Bypass (outpatient surgery) or PACU Discharge (inpatient or outpatient
surgery). See text for details regarding (i) accompanying Zero Tolerance Criteria, (ii) required qualifying scoring
thresholds, and (iii) adjustments for obstructive sleep apnea. From Int Anesthesiol Clin 2011; 49: 33-43.
LE: lower extremity; UE: upper extremity

Economic Proxy Measures of Perioperative Resource Use. Hospital cost savings based on WAKE Score-
directed anesthesia care planning (via routine PACU bypass and avoided unplanned hospital admissions) have been
reported.
3
Beyond WAKE-based considerations, this next section will first describe proxy measures of economic
value, such as time management and labor resource intensity. Time management improvements are best
quantified using a standardized time stamp template such as that endorsed by the Association of Anesthesia
Clinical Directors.
8
In an era preceding the routine use of RA induction rooms, RA time allocated in the operating
room (OR) itself was commonly viewed by surgeons and administrators alike as not sufficiently value-adding to
warrant the time increment of un-occupied OR labor resources waiting until RA procedures were completed. In
response, RA induction rooms were instituted such that procedures could be initiated long before OR entry,
simultaneously optimizing longitudinal processing (i.e., patient #2 following patient #1 in a given OR) and
parallel processing (patient #2 receiving preoperative nerve blocks in an induction room while patient #1 is
undergoing surgery itself in the OR). The RA induction room is also used for the placement of spinal anesthesia
when the OR is being set up (start of day) or turned over (between cases). Therefore, the RA induction room allows
for soak time of both peripheral nerve blocks (e.g., interscalene block for shoulder surgery, placed well-before OR
entry) and ipsilateral hyperbaric spinal anesthesia. In the case of the hyperbaric spinal, e.g., femoral and sciatic low-
concentration nerve blocks or perineural catheters for patient #2 placed early during the OR case of patient #1,
Movement Scores:
Purposeful movement of (at least) 1 LE and 1 UE 2
Purposeful movement of at least 1 UE (and neither LE) 1
No purposeful movement 0
Blood Pressure (sitting and supine) Scores:
Within 20% of preoperative baseline, not orthostatic 2
Between 20-40% of preop baseline, not orthostatic 1
Less than 40% of preop baseline, and/or orthostatic 0
Level of Consciousness Scores:
Awake, follows commands; easily aroused when called 2
Arouse to stimuli, protective reflexes, follow commands 1
Obtunded or persistently somnolent; + protective reflexes 0
Respiratory Effort Scores:
Coughs and deep-breathes freely, and/or on command 2
Involuntarily cough only; unsupported airway 1
Tachypnea, dyspnea or apnea,
and/or requiring airway support
0
Oxygen Saturation Scores:
> 95% or (Preop reading minus 2) without supplemental O
2
2
> 95% or (Preop reading minus 2) with supplemental O
2
1
< 95% or (Preop reading minus 2) + supplemental O
2
0

426
Page 3
the spinal placed for patient #2 with approximately 10 minutes of lead time before OR entry of patient #2 is
possible. This re-engineering strategy with RA procedures in the RA induction room is associated with significant
reductions in anesthesia-controlled time in the OR, when compared with general anesthesia (GA) or GA combined
with a preoperative RA technique.
9
During the lecture, schematic slides will be shown illustrating this patient-
process flow scheme. Although such time management strategies should reduce forced overtime among OR
personnel (with formal study of such phenomena being very difficult to appropriately control), it seems unlikely that
such time management and process strategies would actually allow for additional cases to be scheduled at the end of
an otherwise efficient clinical OR day.
10

The second economic proxy measure is nursing labor resource intensity downstream not only from the OR but
also from the PACU. WAKE-based RA planning can lead to reliable PACU bypass in an ambulatory (same-day
discharge home) setting.
2,3
However, after PACU bypass, symptoms from the Zero Tolerance Criteria (from the
aforementioned WAKE Score) can emerge during Phase 2 recovery, which may lead to the undesired outcome of
dumping Phase 1 workload onto Phase 2 nurses.
2
In our experience, most of the symptoms implicated in Phase 2
Dumping are related to postoperative nausea/vomiting (PONV), typically having occurred in patients that only
received PONV prophylaxis commensurate with preoperative risk.
11
When an alternative antiemetic pan-
prophylaxis strategy
12,13
is applied, Phase 2 Dumping of PONV symptoms no longer appear to be an issue, when
the remainder of the anesthesia care plan strategically follows WAKE Score objectives and targets. In other words,
in the WAKE-based care plan, we consider all patients 10% or higher PONV risk as high risk. As a result, we
routinely administer 3 non-sedating off-patent antiemetics (e.g., IV ondansetron 4 mg, IV dexamethasone 4 mg, oral
perphenazine 8 mg, each costing <$1). When doing so, there are no apparent increases in Phase 2 workload after
PACU Bypass.
14

From a pain management perspective, though, reduced nursing labor
2,15,16
and faster discharge times home
2
are
achievable with WAKE-based RA care planning and volatile agent/opioid avoidance. This next description will
involve complex outpatient knee surgery such as anterior cruciate ligament (ACL) reconstruction, multi-ligament
reconstruction for knee dislocation, and tibial osteotomy. In such cases, femoral (typically with sciatic) nerve block
use predicted fewer nursing interventions for pain (odds ratio 0.4, compared with no blocks) and fewer unplanned
hospital admissions (odds ratio 0.4, compared with no blocks).
17
Meanwhile, use of opioids and GA with volatile
agents was an associated independent predictor of more nursing interventions for pain (odds ratio 2.1, compared
with no GA) and more unplanned hospital admissions (odds ratio 3.3, compared with no GA).
17
Hyperalgesia from
volatile anesthetics, reported subsequently
18,19
, renders their use in combination with RA techniques as either
counterintuitive or perhaps simply ill-advised, at least in the context of creating a patient-centered anesthesia care
plan using the WAKE Score as a target for desired outcomes that are win-win for the hospital as well.

Neurolocation. The use versus non-use of ultrasound-guided regional anesthesia (UGRA) has yet to show
differences in patient-centered long-term perineural complications.
20,21
However, there are both demonstrable
benefits in learning curve with UGRA
21-25
versus traditional techniques, and there are fewer proxy complications
with UGRA versus traditional techniques
21,26
, especially in the trainee setting.
21,27
The extent to which learning
curve, complication, and economic benefits can be considered universal is certainly not ubiquitous, especially when
the comparative technique involves peripheral nerve stimulation by a very experienced practitioner.
28
Elegant cost
models specific to United States billing and reimbursement were recently described by Liu and John (2010).
29
They
reported that the primary cost factors for ultrasound were (i) UGRA-generated revenue, (ii) number of patients
examined per ultrasound machine, and (iii) block success rate. Conversely, the most important factors in the cost
model for nerve stimulator use were (i) block success rate, and (ii) the liability costs for failed airways due to rescue
GA. Therefore, in these recent United States reimbursement settings, ultrasound was either a profit center or cost
center.
29
How this will change with bundled reimbursement remains to be seen, but it seems unlikely that
reimbursements will improve for UGRA, and UGRA seems unlikely to remain a profit center. Liu and John
summarized that if UGRA does not generate revenue, the specific clinical scenario dictates UGRA-related costs. In
an ambulatory setting, a nerve stimulator success rate of !96% success rate is required before UGRA becomes more
expensive. In hospitalized patients, UGRA is consistently more expensive when GA use and hospitalization negate
any positive cost effects from greater efficiency with ultrasound.
29
Whether UGRA use coupled with volatile
agent/opioid avoidance (e.g., in a WAKE-based RA care plan) can yield favorable cost effects was not modeled in
this report.

426
Page 4
UGRA-related expenses only occur once a new program acquires the necessary fixed asset equipment. There may
be no compelling reason for highly experienced practitioners of nerve stimulation to purchase new ultrasound
equipment if they had yet to do so, assuming that there were no nerve blocks in their group practice that were
completely ultrasound-dependent without a nerve stimulator option (e.g., rectus sheath, transversus abdominis, etc.).
At the same time, it would seem unlikely for that same group practice to replenish its ranks in years to come with so
many recently-graduated trainees having become ultrasound-dependent in their RA practice.

RA / Peripheral Nerve Block Care Planning and Economic Considerations Today versus the Past 10 Years
Single-injections versus Perineural Catheters: In the past, the presenters algorithm for selecting a single-
injection peripheral nerve block (SINB) versus a continuous peripheral nerve block (CPNB) including a
percutaneously-placed perineural catheter depended on primarily patient-centered criteria. These included baseline
pain score with movement, likely pain intensity (i.e., of moderate-or-higher) with movement, and likely pain
duration (i.e., moderate-or-higher for less than versus more than 24 hr). These nuances will be detailed in the live
presentation. There were several factors assumed in that era that may no longer be true. First, at least in United
States civilian hospitals, there were notable differences in reimbursement for an SINB versus CPNB (i.e., higher for
CPNB). Secondly, the clinical scientific concept of MultiModal PeriNeural Analgesia (MMPNA) was not well-
developed (i.e., perineural additives to local anesthetics in peripheral nerve blocks providing significant analgesic
increments beyond the expected 10-18 hr duration achieved with plain ropivacaine-bupivacaine SINB).

This refresher course lecture is not the appropriate forum to outline recent advances in MMPNA, and the apparent
potential for MMPNA SINB to yield perhaps 40 hr
30
of meaningful analgesia from the patients perspective. But
certainly, the achievable duration of meaningful analgesia with SINB may shift the economic criteria for routine use
of CPNB toward MMPNA SINB. More noteworthy in the economic balance of such decisions, at least in the
United States, is the basis for which such services are reimbursed. In 2008-2009, the basis for CPNB reimbursement
significantly shifted from a CPNB placement-based global fee payment to payment based on CPNB daily
rounding after a minimum payment for catheter placement. Outpatients are not typically candidates for daily
rounding, so the revenue benefits commensurate with the additional effort of CPNB versus SINB in outpatients
suddenly disappeared.
31,32
Even more disturbing than this loss of reimbursement for CPNB placement for
outpatients is the more recent development of Bundled Payment from United States governmental-based health
care reimbursement (i.e., Centers for Medicare/Medicaid, Affordable Care Act, etc.), and repercussions in private
third-party payments which either precede or follow government trends. The presenter will not embellish upon the
dilemma of diminishing reimbursement in the United States, which would seem to be of less interest to the
international audience, but the economic impact of this will be discussed briefly in the live presentation. Certainly,
in a bundled payment environment, attention should be directed to whether subsequent CPNB catheters beyond an
initial catheter (e.g., a sciatic CPNB catheter in addition to a femoral CPNB catheter for a knee replacement patient)
warrant the incremental cost of placement and management if meaningful reimbursement is completely removed
from the economic equation. One wonders if bundling will prompt the clinical advancement of off-label MMPNA
techniques with not-yet-fully-substantiated research. At this point in MMPNA research, converting to this care plan
would only be (at its most optimistic) a good faith best guess.

Before rendering CPNB as an historical relic in the RA armamentarium, it may be useful to re-examine other
economic benefits (i.e., cost saving even if not revenue-generating), with respect to RA versus volatile GA, SINB
versus no block, and CPNB versus SINB.

Other Cost-Saving Opportunities with RA versus volatile GA, with SINB, and with CPNB: Some of the cost
saving benefits of RA (versus volatile GA) were alluded to earlier with respect to PACU Bypass and reduction of
unplanned hospital admissions after what was billed as same day surgery with planned discharge home. Many of
these principles can also be applied to reducing length-of-stay, and facilitating hospital discharge to home, as
opposed to hospital discharge to a nursing home or extended care facility. Other cost saving opportunities include
(i) addressing the costs of disposables used, (ii) right-sizing RA staffing with RA demand, (iii) capturing other
cost-saving opportunities that are associated with RA use / volatile GA avoidance, and (iv) re-defining appropriate
achievable outcomes, and re-defining inpatient policies and procedures to reflect realistic outcomes, for example,
when WAKE-based care plans are strategically used and actively incorporated into hospital policy, replacing legacy
recovery criteria.

426
Page 5
In monetary values reflective of the year 2000, PACU Bypass after ACL reconstruction was associated with a $400
hospital cost savings (P=0.001).
3
Meanwhile, avoiding an unplanned hospital admission was associated with an
additional $400 hospital cost savings (P=0.003).
3
Recently, WAKE Score-derived RA care planning was applied to
total joint replacement (knee, hip) patients at the VA Pittsburgh Medical Center (including spinal anesthesia,
MMPNA SINB analgesia, and avoided GA). In addition to the ~40 hr block durations described above
30
, a limited
sample (n=95) of patient-specific quality improvement data indicates that when compared with opioids and volatile
GA (i.e., with no acknowledgment of WAKE Score-based anesthetic planning, n=35), the MMPNA-SINB (n=59)
WAKE-based technique shows an associated reduced length of hospital stay from an interquartile range of 4-7 days
to a range of 3-5 days (P=0.043). In addition, the MMPNA-SINB cohort had an associated 66% discharge-home
success rate, versus 46% for the volatile GA / opioid group (P=0.044, presenters unpublished data).

Maximizing value-for-cost with consumable supplies has been well-illustrated in the context of ultrasound-guided
RA (UGRA) by Swenson and Davis (2011).
33
In this report, achieving acceptable outcomes with a basal-fixed-
rate infusion device and using low-concentration bupivacaine (instead of more advanced infusion devices with more
expensive ropivacaine) saves their hospital up to $520 per case.
33
Meanwhile, additional cost savings related to
disposable supplies are achievable with standard SINB needles that are neither echogenic nor stimulating ($8-14 of
cost savings, respectively, per case), while incremental cost savings with needle-catheter sets can approach $14-50
per case when neither the needle nor catheter are stimulating (versus a stimulating needle and a stimulating needle-
catheter, respectively).
33

Right-sizing the supply of RA/SINB/CPNB specialists with demand for these services within an institution will not
be explored during the live presentation, but suffice it to say that it is not difficult to predict that an SINB-skilled
practitioner is more likely available (and/or trainable from within an existing group practice
34
) than would be a
CPNB specialist (who would most likely have undergone fellowship training
35
and been recruited from external
applicants).

Other cost-saving opportunities entail the review and reporting of other RA-related benefits that have obvious
implications for the cost of care.
36
Some of these concepts include the evaluation of the potential role of RA
(neuraxial techniques, SINB, and/or CPNB) in reducing surgical site infections, cancer recurrence, blood transfusion
requirements, and chronic postsurgical pain.
36
Anesthetic techniques that prevent vasoconstriction at the surgical
site (RA, along with the prevention of hypothermia) may reduce the occurrence of surgical site infections, but
certainly direct research is needed to trace SSIs to sub-specific RA techniques used (SINB, CPNB, and/or
neuraxial), in addition to associated SSI increases that have already been reported related to the use of volatile GA
(versus merely neuraxial techniques).
37

Anesthetic selection and cancer recurrence is another opportunity for favorably exploiting potentially significant
economic benefits from RA, as opposed to volatile GA/opioids.
36
Whether RA overall or specific RA subtypes
(neuraxial, SINB, CPNB) specifically create potential economic benefits certainly requires detailed study. In a
simple quotation from a recent review
36
, a recent cost analysis addressing breast cancer screening and diagnosis
reported that the median cost per screening is approximately $100, whereas the median costs of diagnosis is
approximately $10,000. The costs of treatment notwithstanding, it follows that the costs of diagnosing and
treating a cancer recurrence far exceed the costs of screening (for recurrence), and if RA use proves to be central
to the prevention of cancer recurrence, then this public health responsibility should not be taken lightly.
36

Reducing transfusion requirements has been of great interest to RA practitioners for many years. It is conceivable
that when economic values are ascribed to avoided transfusion when RA is used, only then will hospital
administrators consider a more active role in promoting RA programs while discouraging volatile GA. Recently
quoted from a review article, Blood product transfusion is expensive. Although the typical acquisition cost of 1 unit
of packed red blood cells (PRBCs) can be priced as low as less than $200/unit (Jonathan Waters, MD, personal
communication), PRBC (transfusion) administered to surgical patients is estimated to have a median cost between
$500 and $1200, when incorporating all the activity-based costs into the complex process of blood banking.
Certainly, any adverse effects of blood product transfusion, such as disease transmission, transfusion-related lung
injury, immunosuppression, allergic reactions, mismatch errors, coagulopathy, hypothermia, and so forth, incur their
own added costs. This reduction in transfusion requirements with RA has to be reconsidered in the climate of
blood-conservation programs for various surgical procedures.
36

426
Page 6
Finally, both preoperative pain and poorly controlled acute postoperative pain are known risk factors for chronic
postsurgical pain (CPSP).
36
Data directed toward the prevention of CPSP are controversial. The American Society
of Anesthesiologists Practice Guidelines for Acute Pain Management in the Perioperative Setting (2012) only
support improved perioperative pain control with RA techniques, but do not explicitly assume or declare that that
RA use leads to less CPSP. However, because poorly controlled perioperative pain predicts the development of
CPSP, then the use of RA techniques for superior postoperative pain management seems to be an appropriate target
for ongoing research, both prospective and retrospective.
36
However, few data appear to investigate the cost of
poorly controlled acute postoperative pain, specifically relating to the use of RA versus volatile GA during the
perioperative experience. Total costs of failure to treat likely relate to (i) the sum of the necessary interventions
aimed at treating acute pain; (ii) the missed cost savings if RA would have been used, if appropriate (i.e., cost of
increased length of stay, readmissions, nursing interventions, etc.), and (iii) patient-centered and societal long-term
costs of chronic pain. Long-term costs include poor work productivity, work-related absenteeism, and disability
payments.
36
It would seem to be a monumental research undertaking to link CPSP and associated loss in work
productivity to the use of volatile GA instead of RA. It would seem to be more logical to address on a preliminary
basis interval proxy measures of such sweeping societal outcomes initially, before taking on more grandiose
research objectives.

Conclusions: In the pharmacoeconomic analysis of the value of RA, several considerations are important. The first
is to distinguish the objectives of outpatient surgery from the objectives for inpatient care. In doing so, it may prove
useful to (i) promulgate a patient care culture that uses suitable discharge criteria, with such criteria being able to
capitalize fully on recent advances in both RA and ambulatory anesthesia, and (ii) use these suitable discharge
criteria as patient care targets for both outpatient and inpatient surgery. Indeed , applying RA and ambulatory
anesthesia care principles to surgical inpatients may have the potential to significantly reduce length of stay and
favorably alter post-hospital discharge disposition (e.g. home vs. nursing home). In other words, even if
emergence from propofol sedation is a little slower than emergence for an experienced user of desflurane, the
hyperalgesic detriments of volatile agents and concomitant opioids will likely continue to show significant
downstream economic detriment as recent reports are beginning to highlight. Anesthesia provider cultural
convenience (thats the way we have always done it) does not translate to patient-centered value. The second
consideration is to recognize that almost every decision made by the anesthesiologist, especially when designing a
care plan predicated on suitable discharge criteria such as the WAKE Score, may have a crucial influence on both
patient outcome and hospital economic benefits not only in the short term (day of surgery), but also potentially in
the long term (duration of hospital stay, possibly longer). The third consideration is for the skilled RA practitioner
to rationally allocate his or her own labor-related resources to ensure that patient-specific and procedure-specific
criteria are met for each and every patient being considered for RA techniques. This is especially true if
reimbursement for more complex services (such as CPNB) is decreasing. One wants to minimize wasted effort on
procedures that are (i) unlikely to benefit patients and (ii) not generate revenue offsetting professional effort.
Finally, awareness of overall cost implications, to both the hospital and to society at large, is required to justify the
expansion of (and reimbursement for) RA services to hospital administrators (and third-party payers or legislative
entities). The evolution of SINBs with MMPNA may dramatically alter the economic landscape of RA care in the
not-too-distant future.

References
1. Liu SS, Strodtbeck WM, Richman JM, Wu CL: A comparison of regional versus general anesthesia for ambulatory
anesthesia: a meta-analysis of randomized controlled trials. Anesth Analg 2005; 101: 1634-42
2. Williams BA, Kentor ML, Williams JP, et al: PACU bypass after outpatient knee surgery is associated with fewer
unplanned hospital admissions but more phase II nursing interventions. Anesthesiology 2002; 97: 981-988
3. Williams BA, Kentor ML, Vogt MT, et al: The economics of nerve block pain management after anterior cruciate
ligament reconstruction: Significant hospital cost savings via associated PACU bypass and same-day discharge. Anesthesiology
2004; 100: 697-706
4. Williams BA: For outpatients, does regional anesthesia truly shorten the hospital stay, and how should we define
postanesthesia care unit bypass eligibility? Anesthesiology 2004; 101: 3-6
5. Aldrete JA: The post-anesthesia recovery score revisited. J Clin Anesth 1995; 7: 89-91
6. Aldrete JA, Kroulik D: A postanesthetic recovery score. Anesth Analg 1970; 49: 924-934
7. Williams BA, Kentor ML: The WAKE(c) score: patient-centered ambulatory anesthesia and fast-tracking outcomes
criteria. Int Anesthesiol Clin 2011; 49: 33-43
8. Donham RT, Mazzei WJ, Jones RL: Association of Anesthesia Clinical Directors' Procedural Times Glossary.
Glossary of times used for scheduling and monitoring of diagnostic and therapeutic procedures. Am J Anesthesiol 1996; 23: 3-12

426
Page 7
9. Williams BA, Kentor ML, Williams JP, et al: Process analysis in outpatient knee surgery: Effects of regional and
general anesthesia on anesthesia-controlled time. Anesthesiology 2000; 93: 529-538
10. Dexter F, Coffin S, Tinker JH: Decreases in anesthesia-controlled time cannot permit one additional surgical operation
to be reliably scheduled during the workday. Anesth Analg 1995; 81: 1263-1268
11. Gan TJ, Meyer TA, Apfel CC, et al: Society for Ambulatory Anesthesia guidelines for the management of
postoperative nausea and vomiting. Anesth Analg 2007; 105: 1615-28
12. Skledar SJ, Williams BA, Vallejo MC, et al: Eliminating postoperative nausea and vomiting in outpatient surgery with
multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable?
ScientificWorldJournal 2007; 7: 959-77
13. Williams BA, Kentor ML, Skledar SJ, et al: Routine multimodal antiemesis including low-dose perphenazine in an
ambulatory surgery unit of a university hospital: a 10-year history. Supplement to: Eliminating postoperative nausea and
vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero
tolerance" achievable? ScientificWorldJournal 2007; 7: 978-86
14. Williams BA, Kentor ML: Fast-track ambulatory anesthesia: impact on nursing workload when analgesia and
antiemetic prophylaxis are near-optimal. Can J Anaesth 2007; 54: 243-4
15. Williams BA, DeRiso BM, Engel LB, et al: Benchmarking the perioperative process: II. Introducing anesthesia clinical
pathways to improve processes and outcomes, and reduce nursing labor intensity in ambulatory orthopedic surgery. J Clin Anesth
1998; 10: 561-569
16. Williams BA, DeRiso BM, Figallo CM, et al: Benchmarking the perioperative process: III. Effects of regional
anesthesia clinical pathway techniques on process efficiency and recovery profiles in ambulatory orthopedic surgery. J Clin
Anesth 1998; 10: 570-578
17. Williams BA, Kentor ML, Vogt MT, et al: Femoral-sciatic nerve blocks for complex outpatient knee surgery are
associated with less postoperative pain before same-day discharge: a review of 1200 consecutive cases from the period 1996 -
1999. Anesthesiology 2003; 98: 1206-1213
18. Cheng SS, Yeh J, Flood P: Anesthesia matters: patients anesthetized with propofol have less postoperative pain than
those anesthetized with isoflurane. Anesth Analg 2008; 106: 264-9
19. Flood P: PRO: accumulating evidence for an outrageous claim. Anesth Analg 2010; 111: 86-7
20. Sites BD, Taenzer AH, Herrick MD, et al: Incidence of local anesthetic systemic toxicity and postoperative neurologic
symptoms associated with 12,668 ultrasound-guided nerve blocks: An analysis from a prospective clinical registry. Reg Anesth
Pain Med 2012; 37: 478-482 10.1097/AAP.0b013e31825cb3d6
21. Neal JM, Brull R, Chan VW, et al: The ASRA evidence-based medicine assessment of ultrasound-guided regional
anesthesia and pain medicine: Executive summary. Reg Anesth Pain Med 2010; 35: S1-9
22. Sites B, Gallagher J, Cravero J, et al: The Learning Curve Associated With a Simulated Ultrasound-Guided
Interventional Task by Inexperienced Anesthesia Residents. Reg Anesth Pain Med 2004; 29: 544-548
23. Sites BD, Spence BC, Gallagher JD, et al: Characterizing novice behavior associated with learning ultrasound-guided
peripheral regional anesthesia. Reg Anesth Pain Med 2007; 32: 107-15
24. Orebaugh SL, Williams BA, Kentor ML: Ultrasound guidance with nerve stimulation reduces the time necessary for
resident peripheral nerve blockade. Reg Anesth Pain Med 2007; 32: 448-454
25. Orebaugh SL, Williams BA, Kentor ML, et al: Interscalene block using ultrasound guidance: impact of experience on
resident performance. Acta Anaesthesiol Scand 2009; 53: 1268-74
26. Gray AT, Laur JJ: Regional anesthesia for ambulatory surgery: where ultrasound has made a difference. Int Anesthesiol
Clin 2011; 49: 13-21
27. Orebaugh SL, Williams BA, Vallejo M, Kentor ML: Adverse outcomes associated with stimulator-based peripheral
nerve blocks with versus without ultrasound visualization. Reg Anesth Pain Med 2009; 34: 251-5
28. Foldes P, Rosenquist RW: Opinion/Editorial and review of recent literature: Where ultrasound has yet to make a
difference in regional anesthesia. Int Anesthesiol Clin 2011; 49: 22-33
29. Liu SS, John RS: Modeling cost of ultrasound versus nerve stimulator guidance for nerve blocks with sensitivity
analysis. Reg Anesth Pain Med 2010; 35: 57-63
30. Ibinson JW, Mangione MP, Williams BA: Local anesthetics in diabetic rats (and patients): Shifting from a known
slippery slope toward a potentially better multimodal perineural paradigm? Reg Anesth Pain Med 2012; 37: 547-576
31. Hudson ME, Chelly JE, Williams BA: Economics: projecting costs and revenue for an interventional pain service in the
ambulatory setting. Int Anesthesiol Clin 2011; 49: 68-83
32. Kim TW, Mariano ER: Updated guide to billing for regional anesthesia (United States). Int Anesthesiol Clin 2011; 49:
84-93
33. Swenson JD, Davis JJ: Getting the best value for consumable supplies in regional anesthesia. Int Anesthesiol Clin
2011; 49: 94-103
34. Kahn RL, Nelson DA: Regional anesthesia group practice in multihospital private practice settings and in orthopedic
specialty hospitals. Int Anesthesiol Clin 2005; 43: 15-24
35. Hargett MJ, Beckman JD, Liguori GA, Neal JM: Guidelines for regional anesthesia fellowship training. Reg Anesth
Pain Med 2005; 30: 218-25
36. Phillips DP, Knizner TL, Williams BA: Economics and practice management issues associated with acute pain
management. Anesthesiol Clin 2011; 29: 213-32

426
Page 8
37. Chang CC, Lin HC, Lin HW, Lin HC: Anesthetic management and surgical site infections in total hip or knee
replacement: a population-based study. Anesthesiology 2010; 113: 279-84

Disclosure

Asa 2013

Uploaded by

Copyright:

Available Formats

Asa 2013

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Asa 2013

Uploaded by

Copyright:

Available Formats

Refresher Course Lectures Anesthesiology 2013 American Society of Anesthesiologists. All rights reserved.

Note: This publication contains

) According to the manufacturer, the SEDASYS

System enables physician/nurse

Computer Assisted Personalized Sedation

System is expected to be introduced on a limited basis

System, and conduct two post-approval studies to monitor the

) would infiltration has been

vaporizing system (on the

was used to assess the effect of both pregnancy and BMI on

and any additional antibodies

You might also like