Update in Anaesthesia PDF

Available at: www.wfsahq.
org/resources/update-in-anaesthesia
Education for anaesthesia providers worldwide
Volume 35 February 2020
Editors: Christina Lundgren and Victoria Howell ISSN 1353-4882
Update in Anaesthesia
• Implementation of the WHO surgical safety checklist in a West African teaching hospital:
a quality improvement initiative
• Postoperative pain management in Timor-Leste
• Comprehensive review of laryngospasm
• Perioperative myocardial ischaemia in non-cardiac surgery
• Saddle Block
• Erector spinae plane block
• Tranexamic acid
• Intrathecal tranexamic acid during spinal anaesthesia for caesarean delivery
• Ketamine: Recent evidence and current uses
• Complications associated with intraoperative use of irrigation fluid for endoscopic procedures
• Case report: Posterior Reversible Encephalopathy Syndrome (PRES)
• Letter: OxyContin - a tale of advertisement and addiction
• Letter: Sphenopalatine ganglion block - management of PDPH after caesarean section
The Journal of the World Federation of Societies of Anaesthesiologists

UPDATE TEAM
Editors-in-chief
Christina Lundgren (SA)
Victoria Howell (UK)
Editorial Board of Update in Anaesthesia

Douglas Bacon (USA)
Martin Chobli (Benin)
Dr Aboudoul-Fataou Ouro-Bang’na Maman (Togo)
Dr David Pescod (Australia)
Dr Jeanette Thirlwell (Australia)
Dr Isabeau Walker (UK)
SS Harsoor (India)
Kazuyoshi Hirota (Japan)
Zhanggang Xue (China)
Jing Zhao (China)
The WFSA would like to thank Baxter for their financial support of
this edition of Update in Anaesthesia
Typeset and printed by Sumographics Ltd
© World Federation of Societies of Anaesthesiologists 2020. This issue may be freely reproduced for the purposes of private research and study and
extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction
is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: World Federation of Societies of
Anaesthesiologists, Dean Bradley House, 52 Horseferry Rd, London SW1P 2AF, UK.
Disclaimer
The WFSA takes all reasonable care to ensure that the information contained in Update in Anaesthesia is accurate. We cannot be held responsible
for any errors or omissions and take no responsibility for the consequences of error or for any loss or damage which may arise from reliance on
information contained.
Contents
Contents
Implementation of the WHO surgical safety checklist in a West
African teaching hospital: a quality improvement initiative............................................................... 5
Postoperative pain management in Timor-Leste....................................................................................... 11
Comprehensive review of laryngospasm....................................................................................................... 15
Perioperative myocardial ischaemia in non-cardiac surgery.............................................................. 19
Saddle Block....................................................................................................................................................................... 24
Erector spinae plane block....................................................................................................................................... 27
Tranexamic acid............................................................................................................................................................... 34
Intrathecal tranexamic acid during spinal anaesthesia for caesarean delivery....................... 39
Ketamine: recent evidence and current uses............................................................................................... 43
Complications associated with intraoperative use of irrigation fluid

for endoscopic procedures...................................................................................................................................... 49
Case report: Posterior Reversible Encephalopathy Syndrome (PRES)........................................... 54
Letter: Oxycontin - a tale of advertisement and addiction.................................................................. 56
Letter: Sphenopalatine block ganglion bloc - management of PDPH after

caesarean section........................................................................................................................................................... 58
© World Federation of Societies of Anaesthesiologists 2020. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report)
may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for
commercial reproduction should be addressed to: World Federation of Societies of Anaesthesiologists, Dean Bradley House, 52 Horseferry Rd, London SW1P 2AF, UK. 3
Editor’s Notes
The editorial team of Update in Anaesthesia hopes No matter what your area of interest is in Anaesthesia,
you have all had a good start to 2020, and that it there really is something for everyone with many
Editorial
proves to be a year filled with safe anaesthesia, and excellent speakers and interesting workshops.
satisfactory personal achievement. Registration for the Congress is now open and we look
forward to seeing you there. www.wcaprague2020.com
In this edition we have research articles, reviews, case
reports and letters, from colleagues all over the world on As you will have read in the last edition of Update
a variety of anaesthesia topics. We have also reprinted in Anaesthesia, Dr Victoria Howell and I have taken
(with permission) an article from the South African over as Editors-in-Chief. However, despite the change
Medical Journal, as well as 5 ATOTWs (Anaesthesia of leadership, the aims and objectives of Update in
Tutorials of the Week), which are relevant to anaesthesia Anaesthesia remain the same; that is to produce high-
practice everywhere. Whether you practice in the most quality, clinically relevant educational articles that can
sophisticated first world scenario, or a poorly equipped be used by anaesthesia practitioners the world over.
rural district hospital in a low middle income country, We aim to produce one themed edition a year and
we trust that you will enjoy reading UIA volume 35, an edition with a variety of anaesthesia topics as we
and that you will find something of relevance to your have in this edition. We welcome your contributions
practice. to the journal, and if you have any suggestions about
the journal or manuscripts that you would like to be
Looking ahead, the World Congress of Anaesthesiologists
published, please do not hesitate to get in touch. You
will be held in Prague in the Czech Republic from 5th-
can find contributor guidelines and submit manuscripts
9th September 2020. These quadrennial congresses
directly through our online submission system at:
organised by the WFSA are an amazing opportunity to
meet fellow anaesthesiologists from around the world, www.wfsahq.org/uia-authors-page
as well as being of great scientific and educational value.
Christina Lundgren
Co-Editor-in-Chief
[email protected]
4 www.wfsahq.org/resources/update-in-anaesthesia
Implementation of the WHO surgical safety checklist
in a West African teaching hospital: a quality
improvement initiative
Research
A Matei*, Mohammed Mouhajer, Harry Tontoh, Nelson Ampah, Elizabeth
M. Quartson, Ronald B. George, Heather Scott and Vernon H. Ross
*Correspondence email: [email protected]
WFSA-D-19-00012R1
Dr. Anca Matei md frcsc
Assistant Professor,
Abstract Department of Obstetrics
and Gynecology
Background: This study aimed to evaluate the implementation of a surgical safety checklist (SSCL) at an academic Dalhousie University
hospital in Ghana. CANADA
Methods: The WHO SSCL was locally adapted and introduced in all surgical cases at Cape Coast Teaching Hospital Mohammed Mouhajer
Department of Obstetrics
(CCTH), Ghana. A chart audit of 2.5% of surgical cases over 12 months was conducted. The main outcome measures and Gynecology,
included: 1. Percentage of cases where the SSCL was present, 2. Percentage complete, 3. Where the SSCL was Dalhousie University
Halifax
incomplete, percentage complete at each critical point (before induction of anesthesia, before skin incision, and CANADA
before leaving the operating theater), 4.Information missing in incomplete charts.
Harry Tontoh
Results: One hundred surgical cases were evaluated. The SSCL was present in 93% (95% CI 88%-98%) of cases Department of Obstetrics
reviewed, but complete in only 21% (95% CI 10.5%- 29.0%) of all cases, and 3.6% (95% CI -3.3%-13.0%) of C-sections. and Gynecology,
Cape Coast Teaching Hospital
The last part of the checklist was most likely to be completed. The most common missing information was patient Cape Coast
demographics. GHANA
Conclusion: The SSCL was introduced at CCTH over 1.5 years. While uptake was high, the majority of cases were Nelson Ampah
Department of Anesthesia,
incomplete. This QI activity informed a revision of the SSCL and a strategy for periodic evaluation to facilitate its Cape Coast Teaching Hospital
sustainable use. Cape Coast
GHANA
Key Words: patient safety, quality improvement, anaesthesia Elizabeth M Quartson

Department of Obstetrics
and Gynecology
INTRODUCTION Korle-Bu Teaching Hospital
Accra
Kybele Inc. is a non-profit organization based in deliveries representing 33% of total surgeries at GHANA
North America dedicated to improving maternal care CCTH. Institutional surgical deaths were defined (at
worldwide. Kybele has demonstrated improvements CCTH) as deaths in the operating theatre or recovery Ronald B George
Department of Nursing
in maternal and neonatal care in low middle-income room. There were eight in 2015.2 Cape Coast Teaching Hospital
countries by implementing successful changes in the Cape Coast
The local hospital management identified a need to
local environments.1 It has had a prominent presence GHANA
improve maternal care and pursued a collaboration
in Ghana since 2004.
with Kybele Inc. This collaboration was designed to Heather Scott
Cape Coast Teaching Hospital (CCTH) is located address maternal and newborn health, anesthesiology Department of Anesthesia Pain
Management and
in Cape Coast, Central Region, in Ghana. In 2015, and critical care needs at CCTH. The program was Perioperative Medicine
it completed its transition from a community to an expansion of an existing collaboration between Dalhousie University
a teaching hospital. That year, there were 2854 Kybele, Inc. and the Ghana Health Service (GHS) Halifax
births. Maternal mortality ratio (MMR) was 1,111 which began in January 2007.1 The two cooperated CANADA
per 100,000 live births, an increase from 772 per in the development of a quality improvement Vernon H Ross
100,000 live births in 2014.2 By comparison, the initiative at CCTH which resulted in the Maternal Department of Anesthesia
country-wide MMR in 2015 was 319.2 The primary and Newborn Quality Improvement Action Group Wake Forest School
causes of maternal deaths were hypertensive disorders of Medicine,
(MNQIAG). The ultimate objective of this group
Winston Salem,
of pregnancy, hemorrhage and sepsis, accounting is to reduce maternal and newborn morbidity and North Carolina
for over 90% of MMR. There were 984 caesarean mortality through an innovative, systematic quality UNITED STATES
improvement approach designed to build local organizational Obstetrics and Gynecology, the project evolved to include all surgical
capacity and health facility systems. The purpose of the MNQIAG cases. The current quality improvement initiative was developed in
is to coordinate quality improvement initiatives related to Maternal order to evaluate the process of implementation of the SSCL at CCTH
Newborn care at CCTH. One such strategy was the introduction of and to develop strategies for improved uptake and completion of the
the surgical safety checklist in caesarean deliveries. SSCL. The current report adheres to the SQUIRE 2.0 (Standards for
Quality Improvement Reporting Excellence) guidelines.6
The World Health Organization set out the “Safe Surgery Saves
Lives” programme in 2008 detailing a number of goals to improve Materials and Methods
surgical safety.4 As part of this programme, WHO encouraged the Context: This was a quality improvement activity intended to
use of a surgical safety checklist (SSCL) in a model that is simple, introduce the surgical safety checklist to Cape Coast Teaching
widely applicable and measurable. The SSCL is a cost-effective tool Hospital and to evaluate its implementation over time to completion.
that aims to enhance patient safety by improving communication A multidisciplinary team consisting of an obstetrician/gynaecologist
in the operating room. Use of the SSCL has been shown to reduce (MM), certified registered anaesthetist (HT) and an operating room
surgical morbidity by one third and surgical mortality by half.5 nurse (EMQ) at CCTH led the CCTH/Kybele adaptation of the
Despite this evidence, there are still places in the world where it has checklist4 to suit the specific context of CCTH. For the remainder
not been introduced. CCTH is a center where the checklist had not of the manuscript, “SSCL” will be used to refer to the version of the
been implemented. surgical safety checklist that was implemented at CCTH.
Based on previous evidence5, the WHO Surgical Safety Checklist The resulting checklist was piloted in three elective caesarean
was proposed as a process to improve the delivery of care while deliveries of varying levels of complexity and one pediatric general
reducing inefficiencies within the CCTH operating theaters. Initially surgery case. This took place in February 2016 during one of the two
its introduction was planned for caesarean deliveries only due to the annual visits from the Kybele team. The SSCL team demonstrated
focus of the collaboration with Kybele on improving obstetrical its use before induction of anesthesia (the circulating nurse confirms
care. Based on feedback from the Departments of Anesthesia and the patient’s identity and procedure and conducts the first portion of
Figure 1: Initial Surgical Safety Checklist developed at CCTH (February 2016)
PATIENT DETAILS BEFORE SKIN INCISION BEFORE PATIENT LEAVES OPERATING ROOM
Last name: Quiet Time-Out (Nurse, anaesthetist and surgeon)
First name: (Nurse, anaesthetist and surgeon)
Date of birth: Name of th eprocedure confirmed
Folder number: Has the patient’s name, procedure and incsion Instrument, sponge and needle counts
Procedure: site been confirmed? o completed o
Have all team members introduced themselves Specimen labelled (read specimen labels aloud,
BEFORE INDUCTION OF ANAESTHESIA
by name and role? o including patient name) o
(with at least nurse and anesthesia)
Are there any allergies? Are any equipment problems to be addressed?
Has the patient confirmed her identity, Has antibiotic prophylaxis been given within Yes No
procedure and consent? o the last 60 minutes? Yes Not applicable If yes, please specify:
Is the anaesthesia machine and medication How long will the case take?
check complete? o Is there a risk of >10cc/kg of blood loss? Yes No
Does the patient need transfucion
Is the pulse oximeter on the patient and If yes, is the patient crossmatched? Yes No
postopertaively? Yes No
functioning? o
Are there any patient-specific concerns? If yes, is the patient crossmatched? Yes No
Are there any allergies? Yes No
Is there a difficult airway or aspiration risk?
Are there any anticipated critical events?
Yes No Yes No
If yes, is there equipment/assistance If yes, wehat are they?
available? o
Is there a risk of >500ml blood loss? Yes No To Nursing Team:
If Yes, is IV access adequate and is the patient Are the packs sterile? o
crossmatched? o Are there any equipment issues or any
concerns? Yes No
Specific to Cesarean Section:
Is fetal heart beat present? Yes No Is tubal litigation to be performed? Yes No
Is cord blood necessary? Yes No
DATE (DDMMYY): _________________________ NAME: ____________________________ SIGNATURE: ______________________________
the checklist), before skin incision (the surgeon conducts the second Analysis: Use of the SSCL was evaluated and the results calculated as
portion of the checklist), and before the patient leaves the operating percentage of charts where the SSCL was present and percentage of
room (the circulating nurse finalises the checklist). After the checklist charts where the SSCL was present and complete. The incomplete
was piloted, changes were made to further adapt the content to SSCLs were then evaluated in order to distinguish if particular parts
CCTH. The resulting SSCL is shown in Figure 1. of the SSCL are more likely than others to be utilized.
The checklist was then used by CCTH clinical staff as part of usual Among those charts where the SSCL was incomplete, we examined
clinical care for all surgical patients and was printed on the back each critical point in time (before induction of anesthesia, before skin
of surgical sponge count sheets, which were present already in all incision, before the patient leaves the theater). Completion at each of
surgical cases, to facilitate its use. these critical times was calculated as percentage of those charts where
the checklist was used but was incomplete. Statistical significance
Measures: To assess the use of the SSCL after its introduction, a post-
was determined using McNemar’s test for dependent proportions,
implementation review of randomly selected surgical charts was
with a p-value less than 0.05 representing statistical significance. The
conducted from November 2016 to November 2017. Approximately
most common areas of missing information were assessed and the
300 surgeries were performed per month at CCTH in 2016. In
results shown as percentage of cases where the SSCL was present on
order to not overwhelm the evaluation team, but to create enough
the chart but was incomplete.
knowledge of the process of implementation, we set out to audit the
use of the SSCL in approximately 2.5% of cases per month over Results
a 12-month period, which would amount to approximately eight We randomly selected 120 chart numbers to audit, of which 20
cases per month.7 In 2016, 1113 caesarean deliveries were performed charts were missing. We evaluated the use of the SSCL in 100 total
at CCTH.2 As part of our audit, we set out to evaluate 2.5% of surgical charts, which met our criteria of approximately 2.5% of
caesarean deliveries, amounting to 2-3 charts per month over a 12 surgical cases. Out of these, 28 were caesarean deliveries, which also
months period. met our criteria of 2.5% of caesarean section cases, and the rest were
The Kybele team also observed four additional cases after a mix of surgical specialties including general surgery (24 cases),
implementation of the checklist (in November 2017) and otolaryngology (12 cases), urology (12 cases), orthopedic surgery
documented qualitatively any deficiencies in adherence. A load of (12 cases), and other (plastic surgery, ophthalmology, neurosurgery
four cases was felt to be realistic in the context of the short visits for a total of 24 cases). The chart review included both elective and
by the Kybele team and the breadth of the Kybele mission (thus emergency surgeries.
limiting the human and time resources that can be dedicated to a The SSCL was present on 93% (95% CI 88%-98%) of the charts,
single project). Two members of the Kybele team (AM, VR) directly 92.9% (95% CI 83.5%-102.5%) of C-sections and 93.1% (95%
observed the four cases and recorded how the SSCL was used in real CI 87.1%-98.9%) of non-C-section charts. It was complete in only
time. 21% (95% CI 10.5%-29.0%) of cases, which included 3.6% (95%
Ethical approval: Approval of this quality improvement project CI -3.3%-13.0%) of Cesareans and 27.8% (95% CI 17.5%-38.1%)
was provided by the Cape Coast Teaching Hospital Ethical of non-Cesareans cases.
Review Committee on November 30th, 2017, reference number We analyzed the charts where the checklist was present but
CCTHERC/RS/EC/2017/47. Informed consent was not required as incomplete. In those cases, Part 1, conducted before induction of
this was part of a quality assurance activity. anesthesia, was complete in 31.9% of cases (95% CI 21.2%-42.7%;
Funding: This quality improvement activity is part of an ongoing n=72). Part 2, conducted before skin incision, was completed in
collaboration between Kybele Inc. and CCTH to reduce maternal 34.7% (95%CI 23.7%-45.7%). Part 3, before the patient leaves the
and neonatal mortality. No additional funding was contributed for operating theater, was complete in 65.3% of cases (95% CI 54.3%-
this project specifically. 76.3%). While there was no difference between completion rates of
Table 2: Utilization of the SSCL when it was incompletely filled out
Part 1 (Before Induction Part 2 (Before Skin Incision) Part 3 (Before leaving the
of Anaesthesia) theater)
All cases (N=72) 31.9% (21.2%-42.7%) 34.7% (23.7%-45.7%) 65.3% (54.3%-76.3%)*
C-sections (N=25) 28.0% (10.4%-45.6%) 28.0% (45.6%-10.4%) 68.0% (49.7%-86.3%)*
Non C-sections (n=47) 34.0% (20.5%-47.6% 38.3% (24.4%-52.2%) 63.8% (50.8%-76.9%*
a
Proportions represent number of cases where the checklist was filled out at a critical point divided by cases where the checklists was present on the
chart but incomplete and shown as n% (95% CI)
*p<0.05 (McNemar’s test for dependent proportions)
Part 1 and Part 2, Part 3 was significantly more likely to be completed have led to an overestimation of its use. Lastly, evaluating 2.5% of
than either Part 1 (OR 3.0, 95% CI 1.5-5.8) or Part 2 (OR 4.1, 95% surgical charts randomly did not overwhelm the evaluation team and
CI 1.8-9.4). This trend persisted when we analyzed Cesareans and allows for a process of continuous evaluation by the local staff even
non-Cesarean cases separately (Table 1). after the collaboration with Kybele concludes.
The most common themes in incomplete charts are shown in Table Interpretation: The high uptake on charts was probably largely
2. Date of birth was not completed most often. Critical information due to local Anesthesia leadership, who oversaw that the physical
such as estimated blood loss, antibiotic prophylaxis, documentation checklist was added to the charts. Unfortunately, in most of these,
of allergies, patient specific concerns and need for postoperative the SSCL was incomplete. Particularly in Cesarean sections, the
transfusion was also found to be incomplete. SSCL was complete in only 3.6% suggesting that there was little buy
in from the surgical team. Cesareans are the most common surgery
The Kybele team directly observed four randomly selected cases
performed at CCTH. In the two emergency Cesareans we reviewed,
(two cesarean sections, a limb amputation and a nephrectomy) and
the SSCL was not present on the chart. We discussed this finding
documented qualitatively how the checklist was conducted. It was
with the obstetrical team, who felt that in an emergency setting there
found that the checklist was not conducted at the appropriate pause
is no time to do the checklist. With ongoing education and use, the
times in the case. Additionally, not everyone paused to attend to the
perception around the time commitment to do the SSCL, and its
checklist. Some checklist items were filled out on paper without actual
importance especially in emergency or complex cases, will become
verbal communication about it amongst team members. Often, the
more apparent and will lead to improved utilization over time.
surgeon would leave the theater before Part 3 was completed. These
findings were consistent across the cases observed. When the SSCL was used suboptimally, it was Part 3 that was most
likely to be filled out (before the patient left the operating room).
DISCUSSION Observation of four randomly chosen cases showed that the surgeon
Summary: This study illustrates a model of implementation of a WHO often left the room first and the checklist was done by the circulating
adapted surgical safety checklist at an academic referral hospital in nurse. It is possible that the circulating nurse felt more comfortable
West Africa. The staff were provided with information and training requesting the attention of the room after the surgeon left, alluding
and subsequently a locally-developed checklist was introduced. The to hospital hierarchy as a possible barrier to proper use. Other
local staff took on an active role in the development and distribution contextual factors may have contributed to this finding, including
of the checklist and printed it on the back of sponge count sheets lack of familiarity with the SSCL, a perception that the SSCL is
which were already present on all surgical charts, making the SSCL not important, and time pressures. The exact wording and cultural
more convenient and cost-effective. Subsequently, we found high relevance of the SSCL may also have been a factor. We explored the
uptake of the SSCL on the charts reviewed. Unfortunately, we found themes that were incomplete most often and altered the SSCL based
that in most cases the SSCL was not complete and adherence in on the results of this QI initiative, in order to improve compliance.
practice was suboptimal. Date of birth was missing in 35% of total surgical charts evaluated.
Recording patient demographics ensures that the procedure is done
An important strength of this project was the involvement of the
on the correct patient. At CCTH, many patients may not know their
local team in its development and implementation. In addition,
date of birth, therefore the local partners suggested replacing this item
charts were selected randomly over a year which provided a more
with age. Critical considerations such as estimated blood loss and
accurate representation of its true use. Selecting charts from a shorter
patient specific concerns were frequently missing in surgical charts.
period of time just before or during a visit by the Kybele team may
Table 2: Themes in Incomplete Charts
Theme N charts % of charts*

Date of birth 33 35%
Other identifying patient information 20 22%
Estimated blood loss 22 24%
Patient specific conerns/anticpated critical events 11 12%
Equipment concerns 11 12%
Antibiotic prophylaxis 9 10%
Specimen labelling 8 9%
Sterile packs 6 6%
Need for postopertaive transfusion 4 4%
Postoperative conerns 3 3%
*Percentages are calculated as proportion of total surgical cases where the checklist was present on the chart
Antibiotic prophylaxis was often not documented, a relevant point reported on a four-day pilot to implement the SSCL at Dolisie
at CCTH where 26% of maternal deaths are attributed to sepsis [8]. Hospital in the Congo.16 They were unable to evaluate uptake but
Estimated blood loss was missing in 24% of evaluated charts. It was commented that the most important barriers to implementation
felt that a more clinically relevant question would be: “Is there a were lack of support and differences between training and actual
risk of excessive blood loss?”. Whether there were patient specific surgical milieu. At Felege Hiwot hospital in Ethiopia, Ellis et al.
concerns and/or anticipated critical events was not documented in (2017) implemented a stepwise SSCL program that resulted in an
12% of charts evaluated. They were listed as two separate items, both uptake rate of 94% in general surgery cases and 100% in OBGYN
prior to skin incision, and the local team felt that this was redundant. cases at one year.17 Similar to our project, their strategy was also
The item “Are there any anticipated critical events?” was removed. locally driven, and the authors identified local support as one of
Specimen labelling was not documented in 9% of charts. To ensure the key components of a successful program. A prospective study of
this item was checked even in surgeries where a specimen was not elective general surgeries in Karachi, Pakistan showed checklist use in
sent to pathology, the answer option for this question was changed 20% of cases at 1 year. At four years, use increased to 90%.18
to include a checkbox for “not applicable”. Lastly, the checklist was
The literature on implementation of a surgical safety checklist in
reformatted to allow for more writing space when postoperative
LMICs is sparse. However, existing studies typically found high
concerns are identified before the patient leaves the room. The revised
uptake, in keeping with our results. But to be effective, the SSCL
SSCL is shown in Figure 2. Using this QI project as template, an
must not only be present, but must be fully completed, at the
evaluation team was developed that will periodically assess how the
appropriate times in the surgical process, by the appropriate members
SSCL is used and adjust it as needed to better serve the local patient
of the surgical team and there must be real time communication
population after the collaboration with Kybele concludes.
prior to checking it off. When problems are identified, the SSCL
The WHO Surgical Safety Checklist has been adopted in a number should trigger a management plan. Further research is needed on
of hospitals across the world however most reports come from upper compliance with the checklist in real time and on strategies to
middle and high-income countries.9,10,11,12,13,14,15 Few studies report improve adherence and patient outcomes.
on its implementation in low income settings. White et al. (2017)
Figure 2: Revised surgical safety checklist (November 2017). The modified sections based on local feedback are highlighted
PATIENT DETAILS BEFORE SKIN INCISION BEFORE PATIENT LEAVES OPERATING ROOM
Last name: Quiet Time-Out (Nurse ,anaesthetist and (Nurse, anaesthetist and surgeon)
First name: surgeon)
Age: Name of th eprocedure confirmed
Folder number: Has the patient’s name, procedure and incsion Instrument, sponge and needle counts
Procedure: site been confirmed? o completed o
Have all team members introduced themselves Specimen labelled (read specimen labels aloud,
BEFORE INDUCTION OF ANAESTHESIA
by name and role? o including patient name) Yes NA
(with at least nurse and anesthesia)
Are there any allergies? Are any equipment problems to be addressed?
Has the patient confirmed her identity, Has antibiotic prophylaxis been given within Yes No
procedure and consent? o the last 60 minutes? Yes Not applicable If yes, please specify:
Is the anaesthesia machine and medication How long will the case take?
check complete? o Is there a risk of excessive blood loss? Yes No Are there any concerns in the immediate
Is the pulse oximeter on the patient and If yes, is the patient crossmatched? Yes No postoperative period? Yes No
functioning? o If yes, please specify:
Are there any allergies? Yes No Are there any patient-specific concerns?
If yes what are they?
Is there a difficult airway or aspiration risk?
Yes No
If yes, is there equipment/assistance
available? o Does the patient need transfucion
Is there a risk of excessive blood loss? Yes No To Nursing Team: postopertaively? Yes No
If Yes, is IV access adequate and is the patient Are the packs sterile? o If yes, is the patient crossmatched? Yes No
crossmatched? o Are there any equipment issues or any
concerns? Yes No
Specific to Cesarean Section:
Is fetal heart beat present? Yes No Is tubal litigation to be performed? Yes No
Is cord blood necessary? Yes No
DATE (DDMMYY): _______________________ NAME: _____________________________ SIGNATURE: _______________________________
Limitations: This is a small QI activity with inherent limitations. In REFERENCES
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www.hqontario.ca/Portals/0/Documents/qi/qi-measurement-primer-en.pdf .
Conclusions: This quality improvement activity demonstrated a Accessed December 19, 2017.
model of implementation of the SSCL in an under-resourced area
8. Cape Coast Teaching Hospital (2017) Annual Performance Report 2016 (authors
where it had not been used before. A key aspect in SSCL program
not listed)
development is local leadership and multidisciplinary support. The
SSCL represents a low-cost strategy to reduce surgical morbidity 9. Erestam S, Haglind E, Bock D. Changes in safety climate and teamwork in the
operating room after implementation of a revised WHO checklist: A prospective
and mortality but current literature is lacking in reports of its interventional study. Patient Saf Surg 2017; 11:4-14.
implementation in LMICs. The CCTH model can be adapted in
10. Gagne JF, Labidi M, Turmel A. Internal audit of compliance with a perioperative
other settings to introduce the SSCL, monitor its utilization over checklist in a tertiary care neurosurgical unit. Can J Neurol Sci 2016; 43(1):87-92.
time, develop a data collection system and enhance surgical care
11. Khorshidifar A, Kadkhodaee H, Zamen Z. Degree of observance of the WHO
without placing undue burden on local resources. We encourage
surgical safety checklist. Trauma Mon 2012; 17(3):315-318.
researchers in LMICs to use the current model or develop new
strategies of implementation of the SSCL and to report on their 12. Lacassie HJ, Ferdinand C, Guzman S, Camus L, Echevarria GC. World Health
Organization (WHO) surgical safety checklist implementation and its impact
findings. on perioperative morbidity and mortality in an academic medical center in
Chile. Medicine (Baltimore) 2016; 95(23):e3844-48.
Authors contributions: AM, MM, HT, RG, HS and VR contributed to
all aspects of the design. AM had overall responsibility for this project 13. O’Leary JD, Wijeysundera DN, Crawford MW. Effect of surgical safety checklists
and VR had supervising responsibility. AM and VR conducted the on pediatric surgical complications in Ontario. CMAJ 2016; 188(9):e191-8.
data analysis. RG coordinated the collaboration between CCTH and 14. Santana HT, de Freitas MR, Ferraz EM, Evangelista MS. WHO safety surgical
Kybele Inc., including this project. MM, HT, BQ and NA developed checklist implementation evaluation in public hospitals in the Brazilian federal
district. J Infect Public Health 2016; 9(5):586-599.
the SSCL and coordinated its printing and distribution. All authors
gave approval for the final version of the manuscript. 15. Yu X, Huang Y, Guo Q, and the Relaunch and Implementation of Operating
Room Surgical Safety Checklist (RIORS) study group. Clinical motivation and the
Acknowledgements: The authors would like to acknowledge the surgical safety checklist. Br J Surg 2017; 104(4):472-479.
contributions of Dr. Daniel Asare (CEO, CCTH), Dr. Eric Ngyedu 16. White MC, Peterschmidt J, Callahan J, Fitzgerald JE, Close KL. Interval follow
(Director of Medical Affairs, CCTH), Dr. Margaret Casey and Dr. up of a 4-day pilot program to implement the WHO surgical safety checklist at
Hilary MacCormick (Department of Anesthesia, Pain Management, a Congolese hospital. Global Health 2017; 13(1):42-51.
and Perioperative Medicine, Dalhousie University, Halifax, Canada) 17. Ellis R, Izzuddin Mohamad Nor A, Pimentil I, Bitew Z, Moore J. Improving surgical
for their assistance with data acquisition. and anesthesia practice: Review of the use of the WHO safe surgery checklist in
Felege Hiwot referral hospital, Ethiopia. BMJ Qual Improv Rep 2017; 6(1):10.
18. Anwer M, Manzoor S, Muneer N, Qureshi S. Compliance and effectiveness o
WHO surgical safety check list: A JPMC audit. Pak J Med Sci 2016; 32(4):831-835
Post-operative pain management at
Hospital Nacional Guido Valadares, Dili, Timor-Leste
R.F. Grace
Research
*Correspondence: [email protected]
WFSA-D-18-00024
Abstract
After decades of turmoil Timor-Leste is re-building its healthcare system. Resource limitations are severe. Opiates
are unavailable on the wards and used sparingly in theatres. Minimal staff training, inadequate medication supply
and cultural acceptance result in poor pain management. This audit examines post-operative pain management in
85 patients thought reasonably to require post-operative analgesia. Despite medication being charted 20 patients
(24%) received no post-operative analgesia, (before review). This group had a mean verbal numeric pain score of
5.8+/-2.2, median 6, range 2-9. Thirty-four patients (41%) received some of their charted analgesics. This group
had a mean pain score of 5.1+/-2.2, median 5, range 1-9. The remaining 31 patients received their analgesics as
charted and, unsurprisingly, had the lowest pain scores, mean 4.3+/-2.3, median 4, range 1-8. No patient received
prn analgesia. More than 40% of patients reported pain scores greater than 5, with 15% reporting pain scores of 8
or 9. Forty-seven patients (55%) were unsatisfied with their pain relief. Fifty-one patients (60%) received additional
analgesia as a result of review. Despite cultural expectations Timorese patients would welcome additional post-
operative analgesia. To achieve this there are significant hurdles to overcome in training, drug availability and
attitudes towards pain relief.
INTRODUCTION
Following decades of occupation, warfare and political Tramadol, paracetamol and ibuprofen in various
turmoil The Democratic Republic of Timor-Leste combinations are the backbone of post-operative
became a sovereign nation in 2002. In the years analgesia. Unfortunately anecdotal clinical observation
immediately prior to this virtually all the country’s also suggests there is an unrealistic fear of the
infrastructure was damaged. Government institutions consequences and frequency of paracetamol overdose,
were destroyed or ceased to function. The health with the standard adult dose charted as 500mg tds.
sector was no exception. The country had few trained Medications are frequently not administered so patients
doctors or nurses. Hospitals and Health Centres were are not only under prescribed but miss doses as well.
run down, poorly funded and many simply unstaffed. All this leads to poor post-operative pain management.
Government revenue was, and remains, minimal. However it is within the current capability of the
Timor-Leste is reported to spend less than any other Hospital Nacional Guido Valadares (HNGV) to
country on healthcare with only 2.4% of government improve on this situation. It is with this in mind and a
revenue reserved for health.1 Post-independence the view to teaching and decreasing the level of unnecessary
government urgently needed medical officers and suffering that the following audit of post-operative pain
large numbers of medical students were sent to Cuba management in HNGV was undertaken.
for training . This has been a mixed blessing. Cabral
et al in their article stress that such scaling up of METHODS
numbers is not in itself enough . Junior medical staff Over a 3 month period, (following institutional
require ongoing training. These medical graduates approval), consecutive general, urological,
gynaecological and orthopaedic patients 17 years and R.F. Grace
have come back with minimal clinical experience and
m.b.b.s., f.a.n.z.a., f.r.a.c.p.,
receive limited or no mentorship on their return. High older were selected for review of their post-operative
m.med., graddiphlthecon
quality nursing staff are also in desperately short supply. pain management. Patients were selected pre- Department Anaesthesia
The standard of nurse training is low. Opiates are operatively on the basis that their surgery was thought Hospital Nacional Guido
unavailable on the ward. Discussion with staff suggests reasonably likely to require post-operative analgesia. Valadares
there is an unrealistic fear of the dangers of opioid use, Emergency and elective cases were included but each Dili
in particular respiratory depression and addiction. patient was only reviewed once. There was no upper age TIMOR-LESTE
limit. Patients were not selected for a single anaesthetist or surgeon, morphine. The mean morphine dose was 6.1+/-3.5mg. Thirteen cases
i.e. all patients were eligible for review regardless of the anaesthetist reported lignocaine infiltration into the surgical wound.
or surgeon. The caring anaesthetist recorded details of the anaesthesia
Overall the mean analogue pain score on arrival in recovery was 3.3+/-
and analgesia given intra-operatively. In recovery patients were asked
2.6. For patients post spinal anaesthesia mean recovery pain score was
to verbally rate their pain (0 being no pain at all, 10 being worst
2.4+/-2.5. For patients post general anaesthesia recovery pain score
pain imaginable). The result was recorded by recovery staff as soon as
was 4.2+/-2.5. Thirty-six patients (42%) received analgesia in recovery.
practicable on arrival and then again immediately prior to departure
Twelve received morphine, mean dose 5.8+/2.8mg. Twenty-three
for the ward. On the first post-operative morning between 10 and 12
received tramadol, of which 95% was 100mg intramuscularly. Prior
o’clock a single observer (author) visited each patient on the ward with
to ward discharge the overall mean pain score was 3.0+/-2.1.
a local medical officer interpreter. The latter varied depending on the
day. Each patient had a record kept. This comprised basic demography, On review the following morning overall mean pain score was 5.0+/-
the procedure, the nature of anaesthesia, (spinal vs general), details 2.2, median 5, range 1-9. Table 2 contains the frequency distribution
of duration and analgesics given in theatre and recovery, pain score of pain scores. More than 40% of patients reported pain scores greater
in recovery and details about post-operative analgesics charted. The than 5, with 15% reporting pain scores of 8 or 9.
following morning each patient was attended as above. They were Of the patients post spinal anaesthetic mean pain score the next day was
again asked to verbally rate their pain on a numeric scale between 4.7+/-2.2, median 5, range 1-9. For patients post general anaesthetic
0-10. Patients were also asked if they were satisfied with their pain mean pain score was 5.2+/-2.2. As a result of review 17(43%) of the
relief and if they would like more pain relief. The patient’s ward chart post-spinal anaesthetic patients 17(43%) and 28(62%) of the post
was also inspected to see if they had been administered analgesics as general anaesthetic patients were given additional pain relief.
charted, this was corroborated with the patient and staff where possible.
Where appropriate results are reported as mean +/- standard deviation. No patient was given prn analgesia prior to review. Table 3 shows next
day pain scores for patients given their analgesics either as charted,
RESULTS partially or not all. It was observed that many patients were fasted 6
Eighty-five patients were reviewed; 47 males,38 females. The mean hours post-operatively, whether they needed it or not. Additionally in
age was 36.4 +/- 16.6 years. 48 patients were general surgical, 12 the face of nausea nursing staff were frequently observed to withhold
orthopaedic, 14 urological, 10 gynaecological and 1 maxillofacial. analgesia but not provide alternative pain relief. Both these situations
Table 1 contains the operative procedures. Operative time was recorded led to further incidences of missed oral analgesics.
for 49 cases; mean 105+/-50mins. Overall 47 patients (55%) were unsatisfied with their post-operative
Forty cases (47%) were performed under spinal anaesthesia. Of pain relief. Fifty-one (60%) received additional analgesia as a result
these 5(12.5%) used intrathecal fentanyl. Thirteen spinals (32.3%) of post-operative review.
required supplementation with intravenous ketamine and 4(10%)
were converted to general anaesthesia. DISCUSSION
Forty-five cases were performed under general anaesthesia with all but This is one of the first papers involving direct clinical observation
4 using fentanyl. The mean fentanyl dose was 102.8+/-38.5mcg. Rarely of acute care patients to come out of Hospital Nacional Guido
did a patient receive a second dose of intra-operative fentanyl. Thirty- Valadares (HNGV). Its completion was challenging. Patients and staff
two (80%) of the general anaesthetic cases were given intravenous were unfamiliar with the research process and required education,
encouragement and reassurance. Additionally, as has been known
for many years and highlighted by many authors, pain, its expression
Table 1: Operative Procedures and treatment are heavily influenced by culture. Peacock and Patel
summarize this: “A cultural group’s expectations4,5,6 and acceptance
Procedure Count of pain as a normal part of life will determine whether pain is seen as
Appendicectomy 19
Laparotomy 14 Table 2: Pain Score Day One Frequency Distribution
Major Open Urological 14 Pain Score Day 1 Frequency

Miscellaneous 9 1 3 (3.6%)
Major ORIF Lower Limb 8 2 13 (15.5%)
Abdominal Hysterectomy 5 3 8 (9.5%)
Open Inguinal Hernia 5 4 13 (15.5.%)
Open Cholecsytectomy 4 5 13 (15.5.%)
ORIF Upper Limb 3 6 10 (11.9.%)
Mastectomy 2 7 11 (13.1.%)
Thoracotomy 1 8 8 (9.5.%)
Thyroidectomy 1 9 5 (5.9.%)
Table 3: Pain score day one vs Analgesic Medication Given As Charted
Charted Analgesic Pain Score Pain Score Extra analgesia

Medication Given Mean+/-StDev Median, Range Given on review
No 5.8+/-2.2 6, 2-9 85%
Partially 5.1+/-2.2 5, 1-9 85%
Yes 4.3+/-2.3 4, 1-8 65%
a clinical problem”. Further they suggest, “The relationship between received analgesia in recovery but only 14% received morphine.
pain and ethnicity is shaped by experience, learning and culture”. The Intramuscular tramadol was the recovery analgesic of choice. For
comparatively recent experience of the Indonesian occupation,7 the those in severe pain post-operatively intravenous opioids would likely
war of resistance and the violence around independence and again in be a better choice.
2006 mean that nearly everyone in Timor-Leste has a story; everyone
Once patients left recovery and returned to the wards opiates were
has suffered and acceptance of pain as a part of life is commonplace.
unavailable. On the one hand this indicates what can be achieved,
The incidence of post-traumatic stress disorder amongst the general
managed or maybe just tolerated with tramadol and paracetamol, and
population is reported to be high.8,9 All this manifests itself in the
some ibuprofen. On the other hand it reflects on the likely unmet
attitudes of patients and staff at HNGV towards pain.
need for strong analgesics on the ward. One in seven patients reported
However, this is just part of the background to the cultural approach pain scores of 8 or 9. The frequency of tramadol use was surprising as
to pain in Timor-Leste. Medical personnel are held in high esteem it represents a more expensive option than most opioids.
and there is a significant power imbalance between patients and staff.
The biggest finding was the frequency with which patients were
Interpreters were able to provide several comments in this regard.
receiving no analgesia whatsoever on the ward. “As required” analgesia
Examples include “They (patients) are afraid that you will keep them
is also a concept that is not embraced. This may be due to perceived
in hospital,” or “They do not want to ask in case they get in trouble”
powerlessness amongst nursing staff and/or lack of education. Nearly
or “They do not want to appear weak”. Similarly nursing staff when
a quarter of patients received no analgesia post-operatively. The causes
requested if they could provide more analgesia for a patient would
of this are complex. Some are attitudinal and educational as discussed
frequently state, “They have already had pain relief ”, as if to say a
above, some are a failure in nursing care standards and finally some
single dose of analgesia was all the patient required and would last the
are logistic. Getting medication to the ward is unnecessarily complex;
entire post-operative period. The observed common practice of fasting
the wards do not hold impress and have to procure medication from
patients post-operatively, and withholding analgesia in the presence
pharmacy for each patient. Sadly all the above are common in low to
of nausea led to further incidences of missed oral analgesics. Overall
middle income countries.
these factors combined to produce the impression that patients in
general under-reported the degree of pain they were experiencing. At HNGV the responsibility for prescription of post-operative
Even so more than half the patients reported being unhappy with analgesia rests with the surgical team. Doses prescribed are often low
their post-operative analgesia and 60% received additional pain relief and inappropriately infrequent, for example the observed standard
as an outcome of their review. charted adult paracetamol dose is 500mg tds. Provided this is given
it is probably better than nothing. However as the local experts it
Spinal anaesthesia is the first option for anaesthesia at HNGV. It is
would seem appropriate that anaesthetic staff take over responsibility
cheap and requires minimal equipment. In recovery these patients did
for prescribing post-operative analgesia.
marginally better from a pain perspective than those who underwent
general anaesthesia. This trend appeared to continue through to the Myles et al suggest that a visual analogue pain scale of 33 or less on
following day. However this likely reflects the nature of the surgery a 100mm scale signifies acceptable pain after surgery.10 There is no
performed under spinal rather than the nature of the anaesthesia. For immediately apparent reason to suggest that verbally reported pain
example lower limb fractures etc can be performed under spinal and are scores should be any different. The mean pain score on review here
likely to be better tolerated post-operatively than major laparotomies, was 5.0, with 71% of patients reporting pain scores in excess of 3.
or cholecystectomy which require general anaesthesia. A third of Fifty-five% of patients reported being dissatisfied with their pain relief.
spinals required supplementation with ketamine towards the end of Given the likely cultural bias towards underreporting this figure is at
the procedure and a tenth were converted to general anaesthesia. These least comparable and provides some vindication of the accuracy of
findings suggest that spinals are potentially being used in situations the findings.
where a general anaesthetic may be more desirable.
In its simplest interpretation this audit highlights that patients given
Within operating theatres opiate use was sparing. Regardless of the analgesia have less pain than those who aren’t given analgesia. So
length, size or nature of the procedure 100mcg of fentanyl was the what potentially can be done to improve the delivery of analgesia?
standard dose. This suggests there is little titration of opioid to the Paracetamol, ibruprofen and morphine are all relatively cheap. Nursing
clinical circumstances. For those undergoing general anaesthesia the staff are available. Surgical and medical staff are present and operating.
mean morphine dose was 6mg. Plain bupivacaine is not available at As highlighted by Morriss and Roques “there is a treatment gap (in low
HNGV. Lignocaine infiltration of the surgical wound was a relatively to middle income countries) between what could be done and what is
new concept and employed sparingly. Forty-two percent of patients actually being done. Because of this gap, there are many opportunities
to dramatically improve pain management using simple, cost-effective results indicate that Timorese patients would welcome additional
strategies.”11 This is the case at HNGV. All the elements for improved post-operative pain relief. The capacity for improvement is there with
post-operative pain management are present but they do not translate significant hurdles to be overcome in training, drug availability and
into better analgesia for patients. Potential recommendations for general attitudes towards post-operative pain relief.
improvement might include:
ACKNOWLEDGEMENTS
1) Education of resident medical and nursing staff on the importance
of pain relief, dispelling unrealistic fears associated with analgesic The author wishes to thank the anaesthetic and recovery staff of
use and instruction on the appropriate dosing regimens of HNGV for their help in researching this paper.
common analgesics; in particular changing from paracetamol
500mg tds to 1gm qid for normal sized adults. REFERENCES
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use in theatre and recovery George, P Pietroni and J Stubbs.
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analgesia
4. Richardson G. Pain Expression in Different Cultures. A qualitative study of the
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of Applied Sciences Finland. www.theseus.fi/bitstream/handle/10024/43628
fasting
GraceRichardson.pdf?sequence=1
6) Daily post-operative pain rounds by the anaesthetic team. 5. Campbell CM, Edwards R. Ethinic Differences in pain and pain management.
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The institution of such measures is not easy but even some progress
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will decrease the amount of unnecessary suffering amongst Timorese Pain. AORN Journal August 1987 Vol46 Issue 2:273-281.
patients at HNGV. The International Association for the Study
7. Peacock S, Patel S. Cultural Influences on Pain. Rev Pain. 2008 Mar; 1(2):6-9.
of Pain (IASP) has called 2018 the Global Year of Excellence in
Pain Education.12 It is hoped that conduct of this audit has been 8. Hawkins Z. A decade of mental health services in Timor-Leste. International
Psychiatry. Vol7(1), Jan 2010. 11-13.
an educational opportunity for at least some of the staff at HNGV
9. Silove D, Liddell B, Rees S, et al. Effects of recurrent violence on post-traumatic
and opened the door for change. Visiting International teams have
stress disorder and severe distress in conflict affected Timor-Leste: a 6-year
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operative analgesia and education on post-operative pain by visiting 10. Myles PS, Myles DB, Galagher W, Boyd D, Chew C, MacDonald N, Dennis A.
surgical teams will go some way to combatting culturally held myths Measuring acute postoperative pain using the visual analog scale: the minimal
at HNGV and help provide a lasting legacy in the form of improved clinically important difference and patient acceptable symptom state. Br J
pain management for the people of Timor-Leste. Anaesth 2017 Mar1; 118(3):424-429
11. Morriss W.W., Roques C.J. Pain management in low- and middle- income
The standard of post-operative pain management at HNGV is low. countries. BJA2018 Sept18(9):265-270.
The findings presented here suggest approximately 70% of patients
12. International Society for the Study of Pain. http://www.iasp-pain.org/ accessed
are experiencing a level of post-operative pain greater than that Aug 2018
recommended as acceptable.10 Despite cultural expectations the
Comprehensive Review of Laryngospasm
Catarina R. Silva*, Teresa Pereira, Diana Henriques and Filipa Lanca

WFSA-D-18-00036
Review
Abstract
Laryngospasm is a well-known entity occurring during the perioperative period, most commonly during
intubation or extubation. Clinical signs are the consequence of patient effort to breath against a closed glottis.
Risk factors can be related to patient, surgery or anesthesia. They should be managed pre-operatively in order
to prevent this occurrence, together with preventative drugs such as iv (intravenous) lidocaine and magnesium
sulphate, iv propofol induction instead of the inhalational route in children and laryngeal aspiration before
extubation.
Prompt diagnosis and management is the key to success and includes Continuous Positive Airway Pressure
(CPAP) with 100% oxygen, manual maneuvers (subluxation of the temporomandibular joint and Larson’s
maneuver), increasing depth of anesthesia and muscle relaxation. If these measures do not succeed, forced
orotracheal intubation or even cricothyroidectomy/tracheostomy are the emergency steps
INTRODUCTION
Perioperative laryngospasm is a life threatening It is important to exclude other differential diagnoses
complication during the perioperative period with an such as: bronchospasm, supraglottic obstruction,
incidence of 0.78-5% depending on the surgical type, psychogenic cause in anxious patients, vocal cord
patient age, pre-existing conditions and anesthetic palsy, tracheomalacia, hematoma, foreign body,
technique.1 laryngeal edema or tracheal collapse.
It is defined by a sustained closure of the vocal cords PATHOPHYSIOLOGY

as a primitive protective airway reflex to prevent
Causes of laryngospasm may be mechanical, chemical
tracheobronchial aspiration after an offending
or thermal occurring around the glottis. They trigger
stimulus. The prolongation of this initial beneficial
the afferent fibers of the internal branch of the superior
reflex after the stimulus has ceased, results in
laryngeal nerve. The receptors are distributed along
inadequate ventilation due to airway obstruction.
the glottis with the majority found on the laryngeal
It occurs most frequently during intubation or
surface of the epiglottis.
extubation due to a superficial level of anesthesia.2
Innervation of the supraglottic region is by the
The diagnosis can only be made if the closed glottis superior laryngeal nerve, while below the vocal cords Catarina R Silva md
and vocal cords are visualized which is not possible in it is by the recurrent laryngeal nerve. They converge Hospital Universitario
the great majority of cases. So usually it depends on in the brainstem at the tract solitary nucleus, which de Santa Maria
Lisbon
the anesthesiologist’s clinical judgement. Clinical signs plays an essential role in the genesis of the upper
PORTUGAL
include inspiratory stridor, paradoxical respiratory airway reflexes.
movements, suprasternal and supraclavicular Teresa Pereira md
Lateral cricoarytenoids, thyroarytenoids and
retractions and rapidly decreasing oxygen saturation. Anaesthesiology Resident
cricothyroids muscles (intrinsic laryngeal muscles)
As the obstruction progresses to a complete airway are responsible for adduction of vocal cords. All of Diana Henriques md
obstruction, the chest movements may be excessive them are innervated by the recurrent laryngeal nerve Anaesthesiology Consultant
but there is no movement of the reservoir bag and no except the cricothyroid, which is supplied by the Filipa Lanca md
capnogram reading. Desaturation is the most common external branch of the superior laryngeal nerve. Their Anaesthesiology Consultant
manifestation. Other manifestations are bradycardia motor neurons are located in the ambiguous nucleus Centro Hospitalar Lisboa Norte
(6%), negative pressure pulmonary oedema (4%), and adjacent to the retroambigualis nucleus which Hospital Santa Maria
cardiac arrest (0.5%), pulmonary aspiration (3%), explains why stimulation of the upper airway mucosa Lisbon
arrhythmias and death.3 PORTUGAL
also produces cardiovascular alterations (bradycardia, changes in the endotracheal tube. It delays/prevents desaturation in the first 5
arterial pressure) indicating that not only skeletal muscles but also minutes after extubation and expels residual secretions in the airway
smooth muscles are involved in these reflexes.4 decreasing the potential for vocal cord irritation.13
During a laryngospasm episode, either true vocal cords alone or both
MANAGEMENT AND TREATMENT
true and false vocal cords can be involved.5
The first step is to remove the laryngospasm stimulus, followed by a
RISK FACTORS firm and vigorous mobilization of the jaw backwards with extension
The actual known risk factors can be divided in three categories of neck and head, and apply CPAP with 100% oxygen via a face
enumerated in Table 1.6,7 mask. The use of CPAP can inflate the stomach and increase the
risk of gastric regurgitation. Some authors prefer the application of
PREVENTION moderate intermittent pressure. Although airway devices can be a
In order to reduce the incidence of laryngospasm, propofol induction trigger for laryngospasm, a Guedel cannula of correct size may be
is the best approach as it reduces the laryngeal reflexes, particularly in helpful in providing CPAP.
children with history of asthma. Propofol in a subhypnotic dose of 0.25-0.8mg.kg-1 iv usually
It was proven that lidocaine 1-2mg.kg iv can be a preventive and
-1 breaks the spasm. If it does not, the next step is administration
corrective drug 2 minutes before extubation.8 Topicalisation of of succinylcholine 0.1mg.kg-1 iv allowing preservation of
the vocal cords with this agent has also been proven to be effective spontaneous ventilation.14 It has a quick onset because its ED95 is
to prevent laryngospasm during general anesthesia in children.9 0.3mg.kg-1. Rocuronium also has an ED95 of 0.3 and will have as
Magnesium sulfate 15mg.kg-1 iv before tracheal extubation has the rapid an onset as succinylcoline and could be an option in patients
ability to decrease airway reflexes and cough and may play a role in who are not able to tolerate succinylcoline. Other drugs useful
laryngospasm prevention.10 for treatment are alfentanil and meperidine, especially when the
laryngospasm trigger was a painful stimulus. Doxapram 1.5mg.kg-1 can
Another important measure is removing all secretions or blood until suppress laryngospasm by increasing respiratory depth. Nitroglicerin
the larynx is completely cleared before extubation. 4mcg.kg-1 has also been reported as effective but only acts on the
It is debated whether tracheal extubation should be performed in smooth muscle and not on the skeletal muscle of vocal cords.15
awake or deeply anesthetized patients to decrease laryngospasm.11 The application of gentle pressure in the thoracic midline at a rate
The literature describes the “No touch technique” which comprises of 20-25 compressions per minute can reverse the spasm.16 The real
the extubation of a spontaneously breathing and awakening patient, mechanism is unknown but some theories have been put forward.
without any kind of stimulation during the emergence from general In the case of partial laryngospasm where only the true cords are
anesthesia.12 involved, chest compressions will force the air through a small lumen
The artificial cough maneuver has also been described as onesingle left open at the posterior commissure of the vocal cords, ensuring
lung inflation with 100% oxygen immediately before the removal of ventilation and gas exchange and fast relief of partial laryngeal spasm.
Table 1. Known risk factors for larynogospasm
Patient-related Surgery-related Anaesthesia-related

Obesity Nasal, oral or pharyngeal surgeries Laryngeal mask/Guedel airway device
(adenoidectomy and tonsillectomy)
Young age GI endoscopy Extubation
Active and passive smoking Bronchoscopy Suction catheter
ASA IV Appendicetomy Light anaesthesia plan
Gastroesophageal reflux Anal or cervical dilatation Blood/secretions in the airway
Obstructive sleep apnoea Mediastinoscopy Regurgitation
Upper airway infection Inferior urologic surgery Desflurane
Hypocalcaemia Skiin transplant Ketamine and thiopental induction
Asthma Nociception Nasogastric tube
Difficult airway Surgical stimulus Inexperience of anaesthesiologist
Movement Failed intubation
Recurrent laryngeal nerve damage Laryngoscopy
Esophageal stimulation
Iatrogrnic removal of parathyroid glands
In complete laryngospasm, in which both true and false vocal cords The second way is the so called Larson’s Maneuver, with limited
are opposed, this technique could help in converting to a partial scientific evidence regarding its therapeutic use. It consists of bilateral
spasm as air forced from below can push the area above the false vocal pressure application on the mastoid processes at the level of styloid
cords away from each other, opening the entrance of larynx. Another processes, between the posterior branch of the mandible and the
mechanism is the stimulation of the Hering-Breuer deflation reflex anterior mastoid process. This results in laryngospasm cessation by
that, via the vagus nerve, may induce vocal cords relaxation.17 provoking pain and relaxing the vocal cords.18
Inspiratory stridor Diagnosis of laryngospasm

Paradoxial respiratory
movements
Decreasing SpO2 Identification and removal of the triggering stimulus
Use of accessory muscles of
ventilation
No capnogram Lift chin, jaw thrus
Temporomandibular sublaxation
Oropharyngeal airway
Gentle CPAP with 100% oxygen
Call for help, communicate and delegate functions to other members of the team
Assess airway entry

Bag movement?
Deepen anaesthesia Gentle thoracic pressure

Propofol iv <0.8mg.kg-1 Larson maneuver
Muscular relaxation
Succinylcholine
iv 0.1mg.kg-1
intralingual 2mg.kg-1
intramuscular 4mg-kg-1
Consider atropine 10-20mcg/kg

for associated bradycardia
Yes No Orotracheal intubation

Resolution Increasing SpO2
Cricothyroidectomy
Tracheostomy
Recovery ward under close
observation to exclude
secondary complications
Figure 1. Simplified flowchart for laryngospasm management
One of the last measures is tracheal intubation, even with the vocal 10. Marzban S, Haddadi S, Naghipour M, Varg Z, Nabi B. The Effect of Intravenous
cords closed, producing trauma but rescuing the airway urgently. Magnesium Sulfate on Laryngospasm After Elective Adenotonsillectomy
Surgery in Children. Anesth Pain Med. 2014; 4(1).
Cricothyroidotomy or tracheostomy are valuable procedures in
11. Elwood , Elwood T, Peterson D, Rampersad S. Risk factors for adverse events
extreme urgency. (Figure 1)
in children with colds emerging from anesthesia: A logistic regression. Paediatr
Anaesth. 2007; 17(154-61).
FOLLOW-UP
12. Sheta S, Abdelhalim AA, Nada E. Evaluation of “no touch” extubation on airway
These patients should be under observation for 2-3 hours in the related complications during emergence from general anesthesia. Saudi J
recovery ward to confirm a clear airway and to exclude possible Anaesth. 2011; 5(2): 125-31.
complications such as pulmonary aspiration and post-obstructive 13. Von Ungern BS, Boda K, Chambers NA. Risk assessment for respiratory
pulmonary oedema. This can be a particularly harmful consequence complication in pediatric anaesthesia. A prospective cohort study. Lancet.
of marked negative intrathoracic pressures due to the airway 2010; 376(9743): 773-83.
obstruction and may require intubation, ventilation and management 14. Gavel G, Walker R. Laryngospasm in anesthesia. 2013; 26: 1-5.
in an ICU.1 15. Johnstone RE. Laryngospasm treatment an explanation. Anesthesiology. 1999;
91: 581.
CONCLUSION 16. Al-Metwalli RR, Mowafi HA, Ismail SA. Gentle chest compression relieves
Identifying risk factors and planning appropriate anesthetic extubation laryngospasm in children. J Anesth. 2010; 24(6): 854-7.
management is the most rational approach to reduce laryngospasm 17. Hannam S, Ingram DM, Rabe-Hesketh S, Milner AD. Characterization of the
incidence and severity. Hering-Breuer deflation reflex in the human neonate. Respir Physiol. 2000; 124:
1112-4.
When it occurs during the perioperative period, the priority is the 18. Shinjo T, Satoki I. Two cases in which the effectiveness of “Laryngospasm notch”
prompt recognition and management according to a structured pressure against laryngospasm was confirmed by imaging examination.
flowchart in order to minimize morbidity and mortality. Journal of Anesthesi. 2013; 27(5): 761-63.
19. Alalami AA, Ayoub CM, Barata AS. Laryngospasm: Review of the different
REFERENCES prevention and treatment modalities. Paediatr Anaesth. 2004; 18: 281-8.
1. Visvanathan T, Kluger MT, Westhorpe RN. Crisis management during anesthesia: 20. Simsek E, Karaman Y, Gonullu M, Tekgul Z, Cakmak M. The effect of passive
laryngospasm. Qual Saf Health. 2005; 14e3. exposure to tobacco smoke on perioperative respiratory complications and
the duration of recovery. Rev Bras Anestesiol. 2016; 66(5): 492-98.
2. Cortez E. Update on the management of laryngospasm. Journal of Anesthesia
& Critical Care. 2018; 8(2): 1-6. 21. Olsson GL, Hallen B. Laryngospasm during anaesthesia. A computer-aided
incidence study in 136,929 patients. Acta Anaesthesiol Scand. 1984; 28: 567
3. von Ungern-Sternberg BS, Boda K, Chambers NA, Rebmann C, Sly pD, Sly
75.
PD, et al. Risk assessment for respiratory complication in paediatric anesthesia:
A prospectie cohort study. Lancet. 2010; 376: 773-83. 22. Miller R. Anesthesia for eye, ear, nose and throat surgery. 8th ed. Philadelphia:
Elsevier; 2015.
4. Nishino T. Physiological and pathophysiological implications of upper airway
reflexes in humans. Jpn J Physiol. 2000; 50: 3-14. 23. Gimenez LM. Vocal cord dysfunction: An updated review. Ann Allergy Ashtma
Immunol. 2011; 106(4): 267-74.
5. Cheng EY, Mazzeo AJ, Bosnjak KJ, Coon RL, Kampine JP. Direct relaxant effects
of intravenous anesthetics on airway smooth muscle. Anesth Analg. ; 83(1): 24. Betra YK, Ivanova M, Ali SS. The efficacy of a subhypnotic dose of propofol in
162-8. preventing laryngospasm following tonsillectomy and adenoidectomy in
children. Pediatr Anesth. 2005; 15(12): 1094-97.
6. Bauman NM, Sandler AD, Schmidt C. Reflex laryngospasm induced by
stimulation of distal esophageal afferents. Laryngoscope. 1994; 104(29): 25. Burgoyne LI, Anghelescu DL. Interventon steps for treating laryngospasm in
209-14. pediatric patients. Paediatr Anaesth. 2008; 18(4): 297-302.
7. Cavallieri BS. Complicaciones anestésicas en el postoperatorio en el paciente 26. Al-alami AA, Zestos MM, Baraka AS. Pediatric laryngospasm: Prevention and
pediátrico México: Editorial Prado; 2014. Treatment. Current Opinion in Anesthesiology. 2009; 22(3): 388-96.
8. Mihara T, Uchimoto K, Morita S. The efficacy of lidocaine to prevent 27. Defalque RJ, Wright AJ. Who invented the JAW Thrust? Anesthesiology. 2003;
laryngospasm in children. Anaesthesia. 2014; 69(12): 1388-96. 99(6): 1463-64.
9. Mihara T, Uchimoto K, Goto T. The efficacy of lidocaine to prevent laryngospasm
in children: a systematic review and meta-analysis. Anaesthesia. 2014; 69(12).
Perioperative Myocardial Ischaemia
Clinical Article
in Non-cardiac Surgery
Originally published as Anaesthesia Tutorial of the Week
Dr Heather Short
Correspondence email: [email protected]
SUMMARY
• Perioperative myocardial ischaemia is an important entity with prognostic implications.
• Preoperatively, patients should have their perioperative risk clarified, and be optimised where time permits.
• Intraoperative management consists of appropriate monitoring and anaesthetic technique, preventing
myocardial oxygen supply-demand imbalances and identifying and treating intraoperative myocardial
ischaemia.
• Postoperative considerations will depend on intraoperative events and the risk category of the patient, but
may involve intensive monitoring and cardiology review.
Key Points
• Perioperative myocardial ischaemia may increase 30-day mortality when it results in myocardial infarction.
• Optimise at-risk patients preoperatively where time allows.
• Aim to match myocardial supply and demand intraoperatively and monitor for evidence of ischaemia during
the perioperative period.
INTRODUCTION
Myocardial ischaemia can proceed to myocardial risk factors. Lee’s Revised Cardiac Risk Index is a
infarction (MI), this is important as perioperative simple, validated, and widely used scoring system that
MI is associated with a significant increase in 30- predicts major cardiac complications in major elective
day mortality.1 This article will discuss preoperative, non-cardiac surgery2. The 6 independent factors are
intraoperative, and postoperative strategies for listed in Table 1.
prevention and management of perioperative Predicted cardiac event rate increases with increasing
myocardial ischaemia. number of risk factors present, ranging from 0.4%-
11%: 0 points- 0.4%; 1 point- 0.9%; 2 points- 6.6%;
PREOPERATIVE CONSIDERATIONS ≥ 3 points - 11%.2
Risk-Evaluation Scoring Systems Lee’s cardiac risk index is only validated for elective
Multiple scoring systems are available that predict the surgery and does not encompass all risk factors for
risk of major adverse cardiac events.2 They tend to major adverse cardiac events. Of note, the outcome
focus on a patient’s past medical history and surgical is a composite endpoint, not specific to myocardial
Table 1. The Lee Revised Cardiac Risk Index

Criteria Points
High-risk surgery (e.g., emergency surgery, major thoracic procedures, cardiac 1
procedures, aortic/major vascular procedures, procedures . 4 hours)
Ischemic heart disease 1
History of congestive heart failure 1 Dr Heather Short
Clinical Fellow
History of cerebrovascular disease 1 Thoracic Anaesthesia
Insulin therapy for diabetes 1 University Hospitals
Bristol NHS Trust
Perioperative serum creatinine >2.0mg/dL (>177lmol/L) 1 UNITED KINGDOM
ischaemia or infarction. Other important risk factors include recent • Patient has an elevated perioperative risk of major adverse
MI, recent insertion of coronary stents, elevated preoperative high- coronary events.
sensitivity troponin-I, valvular heart disease, decompensated heart • Testing will impact decision making for perioperative care.3,5
failure, and arrhythmias. This article will discuss some of these risk
factors in greater detail. Patients with excellent functional capacity (>10 METs) need not
have exercise stress testing. Guidance is less clear regarding those
Recent Percutaneous Coronary Intervention (PCI) patients with elevated cardiac risk and moderate to good functional
Subsequent to PCI, there is a known risk of in-stent thrombosis, capacity (4-10 METs), for whom ‘‘...it may be reasonable to forgo
which decreases with time after the procedure. In-stent thrombosis further exercise testing...and proceed to surgery.’’3
may result in myocardial ischaemia and is associated with a high
Coronary Revascularisation
mortality. In order to reduce this risk, patients are commenced on
dual antiplatelet agents for the highest-risk period; the duration of Indications for preoperative coronary artery revascularisation in
therapy is specific to the type of stent placed. patients at risk of myocardial ischaemia are similar to the indications
outside of the perioperative setting.3,5
Dual antiplatelet therapy increases the susceptibility to bleeding
perioperatively. The risk of bleeding must be balanced against the In particular, no benefit has been shown for preoperative prophylactic
risk of in-stent thrombosis relative to early cessation of antiplatelet revascularisation in patients with stable or asymptomatic coronary
agents. Because of these factors the 2014 American Heart artery disease.6 Revascularisation with either PCI or surgery has
Association/American College of Cardiology (AHA/ACC) guideline not been shown to improve outcomes with the caveat that studies
recommends that elective surgery be delayed (Table 2) and that invariably excluded patients with a strong indication for cardiac
urgent or emergency surgery have a multidisciplinary discussion surgery, such as left main stem disease or its equivalent.
regarding the risk and benefit of continuing or ceasing antiplatelet
agents perioperatively.3 Aspirin should be continued where MEDICATION CONSIDERATIONS
possible. Beta-Blockers
Existing literature on perioperative use of beta-blockers has been
Recent MI muddied by fraudulent research. Guidelines suggest continuing
A recent MI increases the risk of perioperative MI and mortality.4 beta-blockers for those already taking them, and uncertainty exists
As time since the MI occurred increases, the risk of reinfarction about starting patients who are at risk of perioperative myocardial
decreases. A retrospective study showed that the risk of reinfarction ischaemia on beta-blockers de novo.3,5 Careful titration to heart rate
decreased from 32.8% when surgery occurred within 0-30 days of in high-risk patients may be beneficial and physiologically attractive.
MI compared with 5.9% when surgery occurred 91-180 days post- However, in adopting a one size fits all approach, whilst reducing MI,
MI.4 The likelihood of reinfarction and mortality clearly fall with starting patients on beta-blocker could lead to increased mortality
increasing time from MI, but it is not currently possible to give an and stroke risk, likely due to drug-induced hypotension.
accurate estimate of risk at a given time point following infarction.
Aspirin
American guidelines recommend delaying elective surgery for at least
Continuing aspirin perioperatively is contentious subsequent to a
60 days post-MI where possible to mitigate this risk.3
recent large randomised controlled trial (RCT) that showed an
Optimisation increased rate of significant bleeding without improved mortality
or reduced nonfatal MI.7 Current consensus guidelines recommend
Non-invasive Cardiac Stress Testing
that for patients that are on aspirin the decision to continue aspirin
• The 2014 European Society of Cardiology/European Society of should be based on individual risk of perioperative bleeding relative
Anaesthesia (ESC/ESA) and the AHA/ACC guidelines propose
preoperative stress testing if all the following criteria are met: Table 3: Determinants of Myocardial Oxygen Demand and Supply
• Surgery is elective.
Physiological Goals to Physiological Goals to Decrease
• Patient has poor functional capacity limited by angina or Increase Myocardial Myocardial Oxygen Demand
shortness of breath (4 Metabolic equivalents (METs), or with Oxygen Supply
unknown functional capacity). Low-normal heart rate Low-normal heart rate
High oxygen content of Low myocardial wall tension or
blood ( SaO2, Hb) afterload (avoid hypertension and
Table 2: Recommended Timing of Elective Noncardiac Surgery Following excessive fluid administration)
Percutaneous Coronary Intervention (PCI)3 High-normal aortic pressure Avoid increased myocardial
contractility
Type of PCI Timing of Noncardiac Surgery after PCI
Reduced coronary vascular
Balloon angioplasty 14 days resistance
Bare-metal stent 30 days Reduced coronary vascular
Drug-eluting stent 180 - 365 days resistance
to risk of thrombotic complications.3,5 Separate guidelines exist for Oxygen
those who have had recent acute coronary syndrome (ACS) or PCI. Emerging evidence from the non-perioperative setting suggests that
Angiotensin-converting enzyme inhibitors (ACEis) and hyperoxia can increase infarct size in acute ST-elevation MI.8 in
angiotensin-receptor blockers (ARBs) the perioperative setting, a non–statistically significant association
Controversy exists regarding use of ARBs and ACEis perioperatively. between high FiO2 and acute coronary syndrome has been
American guidelines suggest it is reasonable to continue their use,3 demonstrated.9 Although further evidence is required, a pragmatic
whereas European guidelines suggest discontinuing therapy if the approach would be to maintain normal oxygen saturations, using the
indication is for hypertension.5 lowest possible FiO2.
Statins Heart Rate

Statins may reduce the incidence of perioperative MI. Statins should Large doses of prophylactic heart rate–reducing agents given
be continued if patients are already on them and could be initiated in preoperatively have not proved to be beneficial.10 However, avoiding
patients undergoing vascular surgery at least 2 weeks preoperatively,5 tachycardia with careful titration of analgesia and beta-blockers
although there are no large-scale prospective trials to confirm this makes theoretical sense and has not been sufficiently studied to
approach. discredit.
Clonidine Transfusion Thresholds

There is no evidence of benefit from prophylactic use of preoperative Weak evidence suggests a higher transfusion threshold (such as
clonidine. Hb >100g/dL) might result in better outcome for patients with
acute coronary syndrome11; however, no survival benefit has been
Emergency Surgery demonstrated in higher transfusion thresholds for those at risk of
Elective surgery allows time for a thorough workup and optimisation cardiovascular disease perioperatively.12 The National Institute
of high-risk patients. This benefit is sometimes outweighed by the for Health and Care Excellence (NICE) guidelines recommend
consequences of delaying emergency surgery. In these circumstances, a restrictive transfusion threshold of 70g/L unless the patient has
the AHA/ACC guidelines recommend proceeding using ‘‘appropriate acute coronary syndrome, in which case the more liberal threshold
monitoring and management strategies based on the clinical of 80g/L is recommended. Further research is needed to clarify the
assessment.’’3 appropriate transfusion threshold for patients with stable coronary
artery disease; however, patients with signs of ischaemia or who
INTRAOPERATIVE CONSIDERATIONS are particularly high risk may theoretically warrant a transfusion
Physiological Goals threshold of 90 or 100g/L.
Two main mechanisms are postulated to cause perioperative Temperature Control
myocardial ischaemia—acute coronary artery plaque rupture or Some studies suggest mild hypothermia is associated with increased
instability and myocardial oxygen supply-demand imbalances (often perioperative myocardial ischaemia and cardiac events when
in the presence of stable coronary artery disease). The proportional compared with normothermia. The mechanism for this is not clearly
contribution of each mechanism is contentious. Contributing factors understood.
include increasing myocardial oxygen demand from sympathetic
response to pain, trauma, and inflammation, and reduction in ANAESTHETIC TECHNIQUE
myocardial oxygen supply from anaemia, hypoxia, hypotension, and There is no strong evidence to support a specific anaesthetic technique
arterial thrombosis from perioperative hypercoagulability. in preventing myocardial ischaemia.
It is the myocardial supply-demand imbalance that can be modified General Anaesthesia vs Regional/Neuraxial
intraoperatively to prevent myocardial ischaemia. Myocardial Although some controversy exists, the majority of the evidence
oxygen supply is governed by the oxygen content of blood and would suggest there is no statistically significant difference between
coronary blood flow. Blood oxygen content is mainly determined general, neuraxial, or regional anaesthetic technique.13–15 Whether
by haemoglobin concentration and SaO2 and coronary blood flow is this is because the studies are underpowered or represent a true
increased by increasing diastolic time (inversely proportional to heart finding is unclear. A confounding issue is that high-risk patients,
rate), mean arterial blood pressure and calibre of coronary arteries. such as those who have had a recent MI or PCI, are more likely to be
The calibre of the coronary arteries is largely controlled by metabolic on antiplatelet therapy, which may preclude neuraxial and regional
autoregulation to meet the demands of the myocardium and by the techniques, thus resulting in overrepresentation of high-risk patients
myocardial wall tension. In pathological states, the calibre can be in the general anaesthesia groups.
decreased by atherosclerosis.
Nitrous Oxide
Myocardial oxygen demand is increased with increasing heart rate,
The addition of nitrous oxide to a general anaesthetic does not appear
afterload, myocardial wall tension, and myocardial contractility.
to increase mortality at 1 year or cardiovascular complications at 30
Although techniques to match myocardial oxygen supply and
days in patients at risk of cardiovascular complications.16
demand would seem prudent in the patient with ischaemic heart
disease, not all have supporting evidence for improved outcomes.
Volatile compared with Total Intravenous Anaesthesia (TIVA) DIAGNOSIS OF ISCHAEMIA AND INFARCTION
There is insufficient evidence to recommend TIVA or volatile as Acute Myocardial Ischaemia (or Acute Coronary Syndrome)
a preferred option in the prevention of myocardial ischaemia in
Myocardial ischaemia is identified by a patient’s symptoms and
noncardiac surgery.
signs or from ECG abnormalities. Symptoms of ischaemia (such as
Cyclooxygenase-2 (COX-2) Inhibitors pain in the chest, mandible, or upper extremity) may be absent in
There is a view that selective COX-2 enzyme inhibitors result in a the perioperative setting where anaesthesia or strong analgesia has
prothrombotic state which increases the risk of MI. Two large meta- been administered.21 Other signs of ischaemia include tachycardia,
analyses17 have supported this view with increased risk of MI for haemodynamic instability, and evidence of pulmonary congestion
those taking COX-2 inhibitors compared with a placebo. (such as reduced oxygen saturations, lung compliance, or wheeze).
ECG criteria to diagnose acute myocardial ischaemia require at least
INTRAOPERATIVE MONITORING 2 anatomically contiguous lead with the following22:
Each patient will have a given baseline risk of perioperative myocardial i. ST elevation at the J point of at least 1mm (depending on
ischaemia (as discussed earlier) and monitoring should initially be location) or
dictated by this. Specific monitoring options include the following: ii. ST depression of at least 0.5mm, and/or T wave inversion of at
Electrocardiogram (ECG) least 1mm.
ECG monitoring is a standard of care according to the Association Acute MI
of Anaesthetists of Great Britain and Ireland (AAGBI) MI is defined as myocardial cell death due to prolonged myocardial
Recommendations for Standards of Monitoring During Anaesthesia ischaemia. It is diagnosed by22 a rise of cardiac biomarker value above
and Recovery. ECG is a cheap, easy, and noninvasive means of the 99th percentile limit with at least 1 of the following:
monitoring for myocardial ischaemia. The addition of precordial i. Symptoms of ischaemia,
leads to the standard 3-lead ECG for patients at risk of myocardial
ii. New ST-segment T wave changes or new left bundle branch
ischaemia increases its sensitivity. A small intraoperative study
block,
indicated that in isolation, leads V5 and V4 were most sensitive
(75% and 61+% respectively). Combining leads increases sensitivity, iii. New pathological Q waves,
with V4 and V5 having a 90% sensitivity, leads II and V5 having iv. Imaging evidence of new loss of viable myocardium or new
80% sensitivity, and leads II, V4, and V5 having a sensitivity of regional wall motion abnormality
96%.18 A more recent study showed that 2 or more precordial leads v. Identification of an intracoronary thrombus by angiography or
are required to achieve a sensitivity for MI or ischaemia of 95% autopsy
or more.19 Automated ST-segment analysis, while not as good at
OR: Cardiac death with symptoms suggestive of myocardial
detecting ischaemia, can alert the anaesthetist to ECG changes.
ischaemia.
Blood Pressure Measurement
It is important to note that the above diagnostic criteria have not
Intraoperative hypotension has an association with adverse been created for the perioperative setting. An elevated troponin
cardiac events.20 Mean arterial blood pressure is also one of the after noncardiac surgery, even without other features of ischaemia
determinants of myocardial oxygen supply. It would follow that independently increases the risk of 30-day mortality.21 With this in
accurate measurement and timely treatment of hypotension (and mind, a new perioperative diagnosis has been created—myocardial
hypertension) is important in those at risk of myocardial ischaemia. injury after noncardiac surgery (MINS). MINS is diagnosed
Arterial line placement gives accurate real-time blood pressure by a postoperative peak troponin T of 0.03ng/mL or greater due
measurement to aid these objectives. The potential for adverse to myocardial ischaemia.21 Although a diagnosis of MINS has
consequences of hypotension means that invasive blood pressure prognostic significance, the clinical utility remains uncertain.
monitoring should be considered in high-risk patients.
Management of Myocardial Ischaemia
Transoesophageal Echocardiography (TOE)
Once myocardial ischaemia is suspected, management strategies are
TOE detects myocardial ischaemia by identifying regional wall
as follows:
motion abnormalities. TOE has associated risks and costs, and
it requires an experienced operator. For these reasons routine Confirm Diagnosis
TOE monitoring for those at risk of myocardial ischaemia is not i. Obtain 12-lead ECG.
recommended except for in response to persistent intraoperative
ii. Consider transoesophageal or transthoracic echocardiogram if
haemodynamic instability.3
haemodynamic instability is detected.
Pulmonary Artery Catheter iii. Obtain baseline and 4-hour troponin levels.
Routine use of pulmonary artery catheters in high-risk patients is not
recommended.3,5
Optimise Myocardial Oxygen Supply-and-Demand Balance 3. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline
on perioperative cardiovascular evaluation and management of patients
i. Pause surgery if appropriate while the situation is stabilized. undergoing noncardiac surgery: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines.
ii. Achieve physiologic goals as mentioned earlier: low/normal heart J Am Coll Cardiol. 2014; 64(22):e77-e137.
rate, normal blood pressure, normal oxygen saturations with the
4. Livhits M, Ko CY, Leonardi MJ, Zingmond DS, Gibbons MM, de Virgilio C.
least FiO2 possible, avoid hypothermia, avoid excessive fluid. Risk of surgery following recent myocardial infarction. Ann Surg.
iii. Administer medications: beta-blockers to achieve low or normal 2011; 253(5):857-864.
heart rate provided no hypotension, consider giving aspirin (via 5. Kristensen SD, Knuuti J, Saraste A, et al. 2014 ESC/ESA Guidelines on non-cardiac
nasogastric tube if under general anaesthesia), and a glyceryl surgery: cardiovascular assessment and management. Eur Heart J.
2014: ehu282.
trinitrate (GTN) infusion.
6. McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revascularization before
iv. Consider use of intra-aortic balloon pump, as guided by elective major vascular surgery. N Engl J Med. 2004; 351(27):2795-2804.
cardiologists.
7. Devereaux P, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing
Consider Abandoning Surgery noncardiac surgery. N Engl J Med. 2014; 370(16):1494-1503.
This will be situation-specific and involve a multidisciplinary 8. Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment elevation
myocardial infarction. Circulation. 2015; 131(24):2143-2150.
discussion. Considerations include the following:
9. Fonnes S, G ögenur I, Søndergaard ES, et al. Perioperative hyperoxia—long
i. How unstable is the patient? term impact on cardiovascular complications after abdominal surgery, a post
ii. How urgent is the surgery? hoc analysis of the PROXI trial. Int J Cardiol. 2016; 215:238-243.
iii. Can the surgery stop rapidly if the patient deteriorates? 10. Group PS. Effects of extended-release metoprolol succinate in patients
undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
Lancet. 2008; 371(9627):1839-1847.
If the surgery is continued, having an experienced surgeon to ensure
11. Carson JL, Brooks MM, Abbott JD, et al. Liberal versus restrictive transfusion
shortest surgical time might be of benefit to the patient. thresholds for patients with symptomatic coronary artery disease. Am Heart J.
2013; 165(6):964-971. e961.
Consult Cardiologist
12. Carson JL, Sieber F, Cook DR, et al. Liberal versus restrictive blood transfusion
If evidence of ST-elevation MI is present on ECG, or there strategy: 3-year survival and cause of death results from the FOCUS randomised
is haemodynamic instability, emergent cardiology opinion is controlled trial. Lancet. 2015; 385(9974):1183-1189.
recommended to consider need for PCI. Thrombolysis is usually 13. Guay J, Parker MJ, Gajendragadkar PR, Kopp S. Anaesthesia for hip fracture
contraindicated if surgical incision has been made. surgery in adults. Cochrane Library. 2016. Feb 22; 2:CD000521.
14. Group GTC. General anaesthesia versus local anaesthesia for carotid surgery
POSTOPERATIVE CONSIDERATIONS (GALA): a multicentre, randomised controlled trial. Lancet. 2009; 372(9656):2132
2142.
Postoperative management will be patient-specific but considerations
include the following: 15. Chu C-C, Weng S-F, Chen K-T, et al. Propensity score–matched comparison of
postoperative adverse outcomes between geriatric patients given a general
• Postoperative placement: consider more intensive monitoring as or a neuraxial anesthetic for hip surgery: a population-based study.
appropriate, including need for telemetry. Anesthesiology. 2015; 123(1):136-147.
• Consider need for serial ECGs or troponins depending on index 16. Myles PS, Leslie K, Chan MT, et al. The safety of addition of nitrous oxide to
of suspicion of MI. general anaesthesia in at-risk patients having major non-cardiac surgery
(ENIGMA-II): a randomised, single-blind trial. Lancet. 2014; 384(9952):1446
• Ensure cardiology follow-up or in-patient review if infarct is 1454.
suspected. 17. Chen LC, Ashcroft DM. Risk of myocardial infarction associated with selective
• Ensure good analgesia, euvolaemia, and the addition of beta- COX-2 inhibitors: meta-analysis of randomised controlled trials.
Pharmacoepidemiol Drug Saf. 2007; 16(7):762-772.
blockers (blood pressure allowing) to minimise tachycardia.
18. London MJ, Hollenberg M, Wong MG, et al. Intraoperative myocardial
• Maintain normal oxygen saturations with judicious oxygen ischemia: localization by continuous 12-lead electrocardiography.
therapy. Anesthesiology. 1988;69(2):232-241.
• Commence aspirin and consider PGY12 inhibitor as guided by 19. Landesberg G, Mosseri M, Wolf Y, Vesselov Y, Weissman C. Perioperative
cardiology opinion. myocardial ischemia and infarction identification by continuous 12-lead
electrocardiogram with online ST-segment monitoring. Anesthesiology.
2002; 96(2):264-270.
REFERENCES AND FURTHER READING 20. Walsh M, Devereaux PJ, Garg AX, et al. Relationship between intraoperative
1. Devereaux P, Xavier D, Pogue J, et al. Characteristics and short-term prognosis mean arterial pressure and clinical outcomes after noncardiac surgery toward
of perioperative myocardial infarction in patients undergoing noncardiac an empirical definition of hypotension. Anesthesiology. 2013; 119(3):507-515.
surgery: a cohort study. Ann Intern Med. 2011; 154(8):523-528. 21. Botto F, Alonso-Coello P, Chan M, et al. Myocardial injury after noncardiac
2. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective surgery: a large, international, prospective cohort study establishing diagnostic
validation of a simple index for prediction of cardiac risk of major noncardiac criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology.
surgery. Circulation. 1999; 100(10):1043-1049. 2014; 120(3):564-578.
22. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third
universal definition of myocardial infarction. Circulation. 2012; 126(16):2020
2035.
Saddle block
Marc Gentilli
WFSA-D-19-00002
Review
Summary
Saddle block is a spinal anaesthetic restricted to the perineal area, or that part of the body in touch with a saddle.
It is achieved by using a small dose of hyperbaric solution of local anaesthetic and maintaining the patient
in a seated position after injection. One of the major advantages is avoiding hypotension. It also allows rapid
mobilization of the patient for the surgical procedure. Certain surgical procedures have an increased risk of urinary
retention when performed under saddle block.
INTRODUCTION Table 1:
Spinal anaesthesia was first described more than a Procedures for saddle block
century ago and remains a popular technic. While
Hemorrhoid excision, fistulas, sphincterectomies,
it is difficult to produce a unilateral anaesthesia with condyloma excision
successful results,1,2 saddle block is a spinal anaesthesia
Soft tissue surgery at the perianal and gluteal level
located mainly at perineal territory and was described
after the Second World War. It was widely used in Pilonidal cyst
Anglo-Saxon countries until the 1960s, especially Localized abscess
in obstetrics, before being replaced by more flexible Coccyx surgery
epidural anesthesia.3 Saddle block provides anaesthesia
Prostate biopsy
of the perineum, tip of the coccyx, medial and bottom
of the buttocks and posteromedial part of the thighs Surgery of the urethra
covering an area that for a rider would correspond Interventional hysteroscopy
to that in contact with a saddle. Such anaesthesia is Obstetric delivery and associated procedures
obtained by injecting a small dose of hyperbaric local
anaesthetic (LA) in a patient maintained in sitting Performance of the Saddle Block
position for a few minutes to facilitate preferential Spinal puncture is performed in a monitored patient
impregnation of sacred roots (S1 to S5) responsible in the sitting position. The needle is inserted in the
for innervation of perineum, external genitalia and lower lumbar region, i.e. the interspinous space L4-15
anus. The saddle block causes a parasympathetic or L5-S1. Using a Whitacre® type pencil needle of 25
blockade at the bladder level which may result in or 27 Gauge reduces the incidence of headache after
bladder and rectal atony which is advantageous puncture of the dura mater. The distal eyelet of this
because of sphincteric relaxation for the operator. needle needs to be directed downward or caudally.
With clear CSF flow, the hyperbaric solution of LA
Proctologic surgery (eg hemorrhoid excision, fistulas,
is injected as slowly as possible, without air bubbles,
sphincterectomies, condyloma excision) is one of
to deliver as much local anaesthetic as possible to
main indications of saddle block. The anaesthesia it
sacral territory. To “fix” the block without extension,
provides is particularly suitable for this very painful
the patient is kept in a sitting position for at least ten
surgery that additionally requires a fully relaxed
minutes. However, with lower the doses of LA, the
sphincter. A slightly extended block decreases, as
patient should remain longer in the sitting position.
much as possible, the risk of acute retention of urine,
The baricity of the LA solution and the position of the
a common complication after this surgery.
patient after the injection affect the caudal or cephalic
Marc Gentilli md, phd Opioids should be avoided in combination with LA diffusion of anaesthesia4 so hyperbaric anaesthesia
Centre Hospitalier as they increase the incidence of urinary retention. is used to insure a caudad block. When sitting is
Prive Saint Gregoire Indications for the saddle block are noted in Table 1 difficult for a patient due to painful lesions, sedation
Saint-Grégoire and it is especially useful in outpatient surgery. with low doses of opioids may be useful.
FRANCE
Solutions and doses of local anaesthetic Interest of saddle block
Central to the successful saddle block is the use of a hyperbaric The saddle block is technically simple to perform. The limited
solution of LA, i.e. a solution whose density at 37oC is greater than duration of the block is adapted to short procedures usually less than
that of CSF. Commonly all solutions with a density greater than an hour and often performed on an outpatient basis. Furthermore,
1.013 are considered hyperbaric. In a seated patient, the LA naturally functional recovery from the block is fast. Schmittner et al. compared
flows in the caudal direction in the CSF, bathing the sacral roots. 201 patients with perianal surgery, in two groups: SB (with 5mg of
With the limited cephalic extension, better hemodynamic tolerance bupivacaine) to an intravenous general anaesthetic (GA) (Propofol /
of the block is obtained. Otherwise duration of the block is shorter fentanyl).10 Time in PACU averaged five minutes (1-45) in the SB
than with an isobaric solution (Table 2). group and 44 minutes (4-148) in the GA group. The patients were
able to eat more quickly in the SB group, and required less analgesics;
For 20 years, many studies have implicated lidocaine in the occurrence
30% vs 58% in GA group. Time to void and mobilization were
of root irritation syndrome: transient pain and paresthesia essentially
identical in both groups. In most cases, the patients in the SB group
at lumbar level and in lower limbs that is regressive in a few hours
did not have lower limb motor block. Propofol sedation on demand
or days.9 The frequency of root irritative syndromes is 8% with 4%
has been proposed to improve the comfort of patients during surgery
mepivacaine compared to 22% with 5% lidocaine. Even with a
with SB however, an increase in the incidence of nausea and a longer
decreased frequency, mepivacaine, like lidocaine is not recommended
delay for mobilization and spontaneous urination were noted.11
for this block. Bupivacaine 0.5% is therefore the anesthetic agent
of choice. Ropivacaine is not currently commercially available in Saddle block induces few hemodynamic changes requiring fluid
hyperbaric solution. It is possible to increase the baricity of the resuscitation, and in such case, use of a vasoconstrictor is preferred.
solution by the addition of 10% glucose. The risk of urinary retention is related to surgery (proctology), age
The most commonly used dose in proctology is 4 to 6mg of (> 70 years), urological history, sex (male) and the use of intrathecal
bupiviacine; this provides a block of one-hour duration.4 The lower morphine.12
the dose of LA, the shorter the duration of the block. Increasing
Ambulatory surgery
the dose shortens the onset of the block but lengthens the duration
and increases its cephalad extension. Some anaesthetic teams used Saddle block is particularly suitable for surgery ambulatory. The
very low doses of bupivacaine to obtain a very short block limited duration of PACU stay is very short. The immediate postoperative
to perianal area. Wassef et al. compared two groups of 40 patients analgesia it provides can be supplemented by infiltration techniques
receiving either 1.5mg or 6mg of bupivacaine. With the dose of and the use of parenteral or intravenous analgesics which themselves
1.5mg, they obtained a quality sensory block without motor block, cause of side effects and may delay home discharge. In proctologic
with a shorter duration (98min vs. 147min), a decreased time to surgery where there is risk of urinary retention regardless of the mode
voiding (121min vs. 236min) and a faster discharge (126min vs. of anaesthetic technique, the patient should be discharged only in
249min).5 case of confirmed voiding.13
The potency of ropivacaine is approximately 60% of bupivacaine Conclusion

with a very low incidence (0.1%) of nerve root irritation around. The Saddle block is appropriate for perineal surgery, procedures on the tip
pharmacological profile of ropivacaine fulfills all the prerequisites for of the coccyx, the medial and inferior portions of the buttocks and the
ambulatory surgery. Ropivacaine was compared with lidocaine in posteromedial aspect of the root of the thighs. It provides excellent
outpatient anorectal surgery with an interesting clinical profile.6 Two relaxation of the anal sphincter and is preferred in proctologic
other short action LA, articaine and 2-chloroprocaine, are currently surgery. Due to its simplicity, efficiency and postoperative analgesia,
used in Anglo-Saxon countries without reports of transient irritation this technique is particularly suited to ambulatory care. There is a
syndrome or neurological lesions. Articaine at a dose of 50-80mg risk of urinary retention that can be assessed by use of bladder scan.
provides 60 minutes anaesthesia with complete resolution at 150
minutes. Two-chloroprocaine at the dose of 40-50mg provides 45
minutes anaesthesia with complete resolution at 103 minutes.7,8
Table 2:
Density and baricity of solutions
Density Baricity
Water 0,9937 0,9931
CSF* 1,0003 1,0000
Isobaric bupivacaine 0,9993 0,9990
Hyperbaric bupivacaine 1,0210 1,0207
*CSF cerebrospinal fluid
REFERENCES
1. Valanne JV, Korhonen A, Jokela RM, Ravaska P, Korttila KK. Selective spinal 8. Casati A, Fanelli G, Danelli G, Berti M, Ghosi D, Brivio M, et al. Spinal anesthesia
anesthesia: a comparison of hyperbaric bupivacaine 4 mg versus 6 mg for with lidocaine or preservative free 2-chloroprocaine for out-patient
outpatient knee arthroscopy. Anesth Analg 2001; 93:1377–9. arthroscopy: a prospective randomized double-blinded comparison. Anesth
Analg 2007; 104: 959-64.
2. Kuusniemi KS, Pihlajamaki KK, Pitkanen MT. A low dose of plain or hyperbaric
bupivacaine for unilateral spinal anesthesia. Reg Anesth Pain Med 2000; 25: 9. Pollock JE, Liu SS, Neal JM, Stephenson CA. Dilution of spinal lidocaine does
605–10. not alter the incidence of transient neurologic symptoms. Anesthesiology
1999; 90: 445-50.
3. Schaupp KL, Durfee RB. Saddle block and caudal block analgesia for the control
of pain in labor. Calif Med 1949; 70: 211-5. 10. Schmittner MD, Schreiber H, Janke A, Weiss C, Blunk J, Bussen DG, et al.
Randomized clinical trial of perianal surgery performed under spinal saddle
4. Ariyama J, Hayashida M, Sugimoto Y, To-Oyma Y, Kitamura A. Spread of spinal
block versus total intravenous anesthesia. Br J Surg 2010; 97: 12-20.
anesthesia in patients having perianal surgery in the jackknife position: effects
of baricity of 0.5 % bupivacaine and positioning during and after induction of 11. Schmittner MD, Janke C, Limmer ME, Weiss C, Bussen DG, Beck GC. Influence
spinal anesthesia. J Clin Anesth 2009; 21: 408-13. of sedation on patients’ perceptions and recovery in patients undergoing
minor perianal procedures under spinal saddle block. Med Princ Pract 2010; 19:
5. Wassef MR, Michaels Al, Rangel JM, Tsyrlin AT. Spinal perianal block: a
51-6.
prospective, randomized, double blind comparison with spinal saddle block.
Anesth Analg 2007; 105: 1515-6. 12. Baldini G, Bagry H, Aprikian A, Carli F. Postoperative urinary retention. Anesthetic
and perioperative considerations. Anesthesiology 2009; 110: 1139-57.
6. Buckenmaier CC, Nielsen KC, Pietrobon R, Klein SM, Martin AH, Greengrass RA,
et al. Small dose intrathecal lidocaine versus ropivacaine for anorectal surgery 13. Saranga Bharathi R, Sharma V, Dabas AK, Chakladar A. Evidence based switch
in an ambulatory setting. Anesth Analg 2002; 95: 1253-7. to perianal block for ano-rectal surgeries. Int J Surg 2010; 8: 29-31.
7. Kallio H, Snall EV, Luode T, Rosenberg PH. Hyperbaric articaine for day—case
spinal anesthesia. Br J Anaesth 2006; 97: 704-9.
The Erector Spinae Plane Block:
Clinical Article
A Review of Current Evidence
Araz Pourkashanian*, Madan Narayanan, Arun Venkataraju

Summary
• From the evidencewe have available, the ESP block should be considered an alternative analgesic option for
patients with acute or chornic pain of the trunk
• Most of the favourable data for the ESP block relies on its use as part of a multimodal analgesic package, and
this should be considered when planning a patient’s care.
• Further research needs to be conducted to determine its true effectiveness compared with other regional
techniques as well as optimal dosing regimens.
KEY POINTS
• The erector spinae plane block is an easy-to-perform regional anaesthesia technique with a wide range of
clinical applications.
• Most of the current research has focused on its use in thoracic and trunk surgery.
• Many experts now consider the erector spinae plane block an alternative analgesic option to thoracic epidural
analgesia and paravertebral blocks, especially where these techniques are contraindicated.
• The block has a good safety profile with very few reported complications.
INTRODUCTION
Interfascial plane blocks are the current hot topic many clinical practitioners. In addition, Blanco’s
in regional anaesthesia. The 19th-century German 2007 publication of a ‘‘no pops’’ ultrasound-guided
surgeon Carl Ludwig Schleich is seen by many as transversus abdominus plane (TAP) technique has led
the father of infiltration anaesthesia. His work from researchers to explore various planes for interfascial
1899 titled ‘‘Painless Operations. Local Anaesthesia blocks.2 Currently, the greatest volume of work
With Indifferent Liquids’’ described the use of local produced in this field is focused on truncal interfascial
anaesthetic (LA) agents to relax the muscles of the plane blocks, one of which is the erector spinae plane
anterior abdominal wall and provide analgesia to aid (ESP) block.3
surgery.1 This was the origin of a procedure that is
This tutorial will look at the current research and
now practiced worldwide, the rectus sheath block.
evidence in the clinical application of the ESP block.
These techniques have had to bide their time for use in
We will explore its inception through to the results
clinical care as their safety, efficacy, and reproducibility
of recently published randomised controlled trials
have been difficult to assess. However, several factors
and postulate what the future holds for this novel
have led to a seemingly exponential growth in fascial
technique. The technique itself will be described in Araz Pourkashanian
plane block research, description, and utility. The
detail in the Anaesthesia Tutorial of the Week article Regional Anaesthesia Fellow
advent of readily available ultrasound technology Frimley Park Hospital
on ESP.
in modern-day health care and the production of UNITED KINGDOM
longer-acting amide LAs have had a major impact. A ESP BLOCK: WHAT IS IT?
greater driver has probably been the desire, and some Madan Narayanan
The ESP block is a novel interfascial paraspinal plane Anaesthetic Consultant
would argue necessity, to move away from traditional
technique that was initially used by Forero et al4 for Frimley Park Hospital
neuraxial techniques used in the perioperative care of
2 patients with severe chronic thoracic neuropathic UNITED KINGDOM
patients undergoing thoracic and abdominal surgery.
pain and 2 patients undergoing video-assisted
With surgical techniques becoming less invasive, Arun Venkataraju
thoracoscopic surgery. The authors described 2
the introduction of enhanced recovery pathways, Anaesthetic Consultant
techniques for this block. One was in a patient with
and the increased use of anticoagulation therapies, Hampshire Hospital NHS Trust
neuropathic pain from metastatic seeding to the ribs,
the use of epidural anaesthesia has decreased among UNITED KINGDOM
As with any novel regional anaesthesia technique, the initial interest
in the block led to an abundance of clinicians attempting to replicate
the effects in their own patients. The result was a wealth of case
reports with a wide range of clinical applications. Tsui et al5 recently
performed a pooled review of 242 cases relating to the ESP block.
After applying inclusion criteria to their search, they found that
90.5% of publications were either case reports or case series, 5.5%
were anatomical cadaver studies, and only 2.4% were randomised
controlled trials. Most publications originated from Turkey (25%),
with Canada and Japan producing the second and third most articles,
respectively.
ANATOMICAL STUDIES AND PROPOSED MECHANISM

OF ACTION
As with all fascial plane blocks, the aim of the ESP block is
compartmental spread; its efficacy relies on the LA agent passively
distributing within the plane to reach target nerves. Absorption and
diffusion of LA across tissue planes also appear to play a role in the
extent and quality of the block.
The working theory is that because of the discontinuity of the
intercostal muscles, LA diffuses anteriorly to the ventral and dorsal
rami of the spinal nerves and through the intertransverse connective
tissue to enter the thoracic paravertebral space (Figure 4).
Is the ESP Block a Surrogate for the Paravertebral Block? How

Far Does the Injectate Spread?
Further imaging studies have been performed to determine the extent
of LA spread as a means of explaining the true mechanism of action.
In Forero’s publication, the authors expanded on the case series by
Figure 1. Red highlighted structures indicate the 3 columns of the analysing the spread of injectate both on computerized tomography
erector spinae muscles. Medial to lateral: spinalis, longissimus, iliocostalis. (CT) imaging and in cadavers.4 In 1 patient, after 25mL of solution
Source: Henry Vandyke Carter [public domain], image reproduced from
Gray’s Anatomy (figure 389; ‘‘Deep Muscles of the Back’’). CC BY 3.0.
where they injected LA into the plane between the rhomboid major
and erector spinae (ES; ie, superficial to the ES). The patient had
complete resolution of pain. In the other 3 cases, LA was deposited
deep to the ES, which similarly produced the desired analgesic effect
but also provided a cutaneous sensory block.
The standard practice for performing an ESP block today uses
ultrasound to deposit LA deep to the 3 columns of ES muscles
(iliocostalis, longissimus, spinalis), which run the length of the spine
from the base of the skull to the medial crest of the sacrum (Figures
1 and 2). They all have attachments to the transverse processes, the
level of which is dependent on the specific muscle. Overlying the ES
complex are 2 further layers of muscle: the trapezius and rhomboid
major (Figure 2).
HAS THE ESP BLOCK CAUGHT ON? WHAT DOES THE

LITERATURE SAY? Figure2. (A, B) Demonstration of the muscle layers and bony landmarks
seen on ultrasound when performing an erector spinae plane block at
Since Forero’s publication in Regional Anesthesia and Pain Medicine
the thoracic level. Layers from superficial to deep: skin/subcutaneous fat,
in September 2016,4 there has been wide interest in the ESP block. trapezius, rhomboids, erector spinae, transverse process. (C, D) Needle
In the 2 years that followed, there had been close to 100 relevant entry seen through the muscle layers on the vector from the upper left
publications (Figure 3), and based on a literature search conducted to lower right of the image. Local anaesthetic has been infiltrated deep
in June 2019 via EMBASE, Medline, and PubMed, that number has to the erector spinae (*). The hypoechoic area produced as a result is
far been exceeded. indicated by the white marked area.
The cadaveric work by Adhikary et al7 analysed the spread of
radiocontrast dye deep to the ES muscle complex in 3 fresh cadavers.
Their results confirmed that seen with Forero et al4 with craniocaudal
spread up to 9 vertebral levels along the paraspinal muscles and in
the intercostal space (Figure 5). There was also dye seen in the neural
foramina and epidural space.
The case report by Schwartzmann et al8 of ESP block using gadolinium
clearly showed the spread of contrast into the paravertebral space,
through the neuroforamina, and a resultant circumferential epidural
spread over 7 thoracic levels (Figure 6).
All of these results suggest that the ESP block may be an alternative
Figure 3. Graphical representation of the rapid growth in publications analgesia option to the paravertebral block (PVB), with some
relating to erector spinae plane block. evidence demonstrating injectate diffusing into the paravertebral
space to also exert its analgesic effects.
was injected superficially to the ES muscles, CT imaging revealed
cephalocaudad spread from T1 to T11 with minimal lateral spread. However, not all cadaveric studies have had such extensive spread of
In their cadaveric work, they injected methylene blue dye superficial dye. Yang et al observed only minimal spread into the paravertebral
to the ES muscle bilaterally in one cadaver and deep to ES bilaterally space, and Ivanusic et al failed to demonstrate any spread into the
in another. Dissection of the former cadaver demonstrated staining paravertebral space.9,10 Ivanusic et al9 performed an ESP block deep
of the lateral branches of the spinal root dorsal rami in a longitudinal to the ES muscle with 20mL of dye on 10 cadavers (ie, 20 total
fashion but no anterior spread beyond the intercostal muscles. With injections). Like previous studies, there was extensive lateral and
the second cadaver, and injection deep to the ES muscle, the spread craniocaudal spread of dye around the ES complex. But only 1 of the
of the dye was much greater and included the area deep to the injections led to staining of the ventral rami, and there was no spread
intercostal muscles, through the costotransverse foramina, and close anteriorly to the paravertebral space. They did, however, acknowledge
to the spinal nerve root ventral and dorsal rami. the tissue tension limitations of cadaveric studies in replicating the
spread of LA in vivo and postulated that the intrathoracic pressure
Chin et al6 demonstrated in a cadaveric study that with 20 mL of dye
changes present in the living may explain the anterior spread into the
injected at the transverse process of T7 (below the ES muscle), spread
paravertebral space.
was seen cranially up to the lower cranial/upper thoracic vertebrae
and caudally as low as the third lumbar vertebra.
Figure 5. Visible craniocaudal spread of methylene blue dye in cadavers

after 20-mL injection at the T5 vertebral level. Good spread (range 5-9
vertebral levels) seen in the intercostal spaces. Dye also visualised in the
Figure 4. Brown highlighted structures indicate erector spinae muscles. epidural space and neural foramina in all 3 cadavers. Reproduced from
The green highlighted area indicates local anaesthetic (LA) deposited Adhikary SD, Bernard S, Lopez H, Chin KJ. Erector spinae plane block
below the erector spinae complex. The LA injection spreads into the versus retrolaminar block: a magnetic resonance imaging and anatomical
paravertebral space because of the discontinuity of the intercostal study. Reg Anesth Pain Med. 2018;43(7):756-762, with permission from
muscles. Source: Henry Vandyke Carter [public domain], image BMJ Publishing Group Ltd (license 4614451453587).
reproduced from Gray’s Anatomy (figure 819; ‘‘Diagram of the Course
and Branches of a Typical Intercostal Nerve’’). CC BY 3.0.
and up to 72 hours post block. All patients received multimodal
analgesia prior to block performance. Most (53%) had between 5
and 7 fractured ribs, and 77% of patients received an ESP catheter
to allow a continuous LA infusion into the myofascial plane, with
the remaining receiving a single-injection technique. The catheters
remained sited until the acute pain team deemed the pain could
be managed with oral analgesia alone (mean duration, 3.7 days;
range, 0.6-9.3 days). Incentive spirometry volumes nearly doubled
from baseline during the first 24 hours, with a mean increase of 545
mL. Moreover, this effect was maintained over 72 hours. Maximum
NRS pain scores were statistically significantly reduced, and 12-
hour opioid consumption was reduced in patients who received a
continuous technique (but this did not reach statistical significance).
There was no change in mean arterial blood pressure in any of the
patients. Those who had a single-injection ESP block showed less
convincing results overall. The authors concluded that the ESP block
has become the primary regional intervention for rib fracture patients
at their institution. They also suggested its benefit in safety profile
for patients with contraindications to neuraxial and perineuraxial
techniques (ie, anticoagulated patients).
Figure 6. Gadolinium magnetic resonance image at 45 minutes after left
erector spinae plane block. White arrows: circumferential epidural spread. Thoracic Surgery
Dashed arrows: paravertebral spread. Asterisks: bilateral neuroforaminal
Retraction of ribs and incision of chest wall muscles can make thoracic
spread. Reproduced from Schwartzmann A, Peng P, Antunez Maciel M, et
al. Bilateral erector spinae plane block (ESPB) epidural spread. Reg Anesth
surgery extremely painful in the postoperative period. The impact on
Pain Med. 2019;44:131, with permission from BMJ Publishing Group Ltd respiratory mechanics is the same as those with rib fractures described
(license 4613860141186). above, and these patients will experience the same complications if
pain is not adequately managed. Again, currently available evidence
WHAT DOES THE EVIDENCE SAY? (LARGER STUDIES) leads many clinicians to employ a multimodal analgesic approach
Spread of methylene blue dye and contrast medium in cadavers is with the use of thoracic PVB or neuraxial analgesia (thoracic epidural
informative, but do these anatomical studies translate to a meaningful analgesia [TEA] or intrathecal opioid). However, this will not be
clinical effect? To best answer this question, we need to identify the appropriate management for every patient, and reported failure rates
larger clinical trials. Again, because of the relative infancy of the for PVB and TEA are quoted as high as 15%.13
ESP block, the literature is limited, but below are the key clinical
To date, 1 randomized study has been published looking at the use of
areas that have produced data from randomised controlled trials.
ESP blocks in adults undergoing video-assisted thoracoscopic surgery
Unsurprisingly, much of this work centres on truncal surgery. From
(VATS). In their randomized controlled trial, Ciftci et al14 compared
the pooled review by Tsui et al5 of the published literature, nearly
opioid consumption and pain scores of single-shot ESP blocks with a
90% of the ESP blocks were performed in the thoracic, 9% in the
control group (no block). The data showed statistically lower opioid
lumbar, and, 1% in the cervical region. Eighty percent were single
consumption (176.66lg 6 88.83lg vs 717.33lg 6 133.98lg) and pain
shot-techniques, and 20% were catheter techniques.
scores in the ESP group. They also found statistically lower rates of
Rib Fractures nausea and itching in the ESP group (nausea; P ¼ .010). This study
suggests that the ESP block is a suitable opioid-sparing block for
Mortality from rib fractures has been reported to be as high as 33%.11
patients undergoing VATS, but pain scores were measured only up
A dangerous downward spiral results from disruption of respiratory
to 24 hours, and there are no studies comparing PVB/TEA with this
mechanics and pain, culminating in significant morbidity and
technique in this patient cohort.
mortality. For patients with preexisting respiratory comorbidities
and/or opioid sensitivity, regional anaesthesia is often life-saving For open thoracic surgery, there are several case reports and case
therapy. Thoracic epidural analgesia was long revered as the gold series describing the successful use of ESP catheters for posterolateral
standard for patients with traumatic rib fracture pain, but myofascial thoracotomy analgesia.15,16
plane blocks (eg, serratus anterior, ES) and PVBs have now become Breast Surgery
alternative options.
ESP blocks are showing promise as a regional technique for breast
A retrospective cohort study at a level 1 trauma centre in Pennsylvania surgery analgesia. Small randomized controlled trials have shown
looked at the analgesic outcomes and the effect on respiratory effective analgesia and reduced postoperative opioid consumption
volumes when performing ESP blocks in patients with traumatic when compared with standard care in patients undergoing surgery
rib fractures.12 For 79 patients, incentive spirometry volumes, 12- for breast cancer (including mastectomy).17,18 However, 1 prospective
hour opioid consumption, and highest numeric rating scale (NRS) randomized trial in radical mastectomy surgery showed lower pain
static pain scores were recorded at baseline (ie, pre-ESP block) scores and postoperative tramadol consumption if a modified
pectoral nerve block was performed rather than an ESP block.19 Tulgar et al24 performed a double-blinded, randomized, controlled,
Larger comparator studies need to be conducted to assess the true prospective study comparing ESP and subcostal TAP blocks in
efficacy and benefit for this surgical cohort. laparoscopic cholecystectomy surgery performed at a tertiary
university hospital in Turkey. Sixty patients were recruited and
Cardiac Surgery randomized into 3 equal groups: bilateral subcostal TAP, bilateral
Several studies have been performed using ESP blocks for patients ESP, and control. All patients received standard multimodal analgesia
undergoing open cardiac surgery. This is a surgical speciality with and an intraoperative remifentanil infusion, and those who received
procedures that require high intraoperative doses of anticoagulant a block had this performed at the end of surgery. A standard mix of
agents, and so regional anaesthesia has traditionally been avoided. 40mL LA was used for all patients. No patients received LA at the
Patients undergoing elective cardiac surgery with cardiopulmonary surgical site. Tulgar et al24 found that patients in the 2 block groups
bypass had significantly lower pain scores (up to 12 hours had significantly lower rest and dynamic pain scores in the first 3
postextubation) if bilateral ESP blocks were performed rather than postoperative hours (P.001) and a lower overall 24-hour analgesic
standard therapy alone with intravenous paracetamol and tramadol.20 requirement.
A patient-matched, controlled before-and-after study showed similar
Another randomized controlled study, in Egypt, assessed the efficacy
results but also found that postoperative adverse events, time to chest
of the ESP block for postoperative analgesia in total abdominal
drain removal, and time to first mobilization were all significantly
hysterectomy.25 The authors demonstrated that the patients who had
lower if ESP blocks were performed.21 When comparing TEA and
blocks had significantly lower fentanyl consumption in the first 24
bilateral continuous ESP blocks for cardiac surgery, 1 study found
postoperative hours and significantly lower pain scores in the first
comparable pain scores, incentive spirometry, intensive care unit
12 hours.
duration, and number of ventilator days.22
Lower Limb Surgery
Abdominal Surgery
A randomized, controlled, double-blind study looked at the
Rectus sheath (RS) catheters have gained huge popularity as an
analgesic efficacy of lumbar ESP blocks used for patients undergoing
analgesic technique for postoperative midline laparotomy pain.
hip and femur surgery.26 When compared with standard intravenous
However, this block provides only somatic analgesia to the midline
analgesia, the authors found that the patients with ESP blocks had
from T6 to T11. For patients who have transverse incisions, stomas,
significantly lower pain scores within the first 6 hours and lower total
and drains, RS blocks will not provide analgesia. Alternatives
24-hour tramadol consumption (control ¼ 226mg 6 35.89mg, ESP
that have been explored include TAP blocks and, more recently,
block ¼ 130mg 6 50.99mg; P , .001). ESP block was also compared
quadratus lumborum blocks. A perceived key benefit of the ESP
with quadratus lumborum blocks, and both showed similar results
block over other interfascial blocks for abdominal procedures (RS,
overall. The data produced suggest that lumbar ESP blocks may
TAP) is the anterior spread of injectate into the paravertebral and
provide effective analgesia for hip and femur surgery as part of a
epidural space. This would block not only spinal nerve roots but also
multimodal analgesic strategy.
rami communicantes transmitting sympathetic fibres, thus leading
to relief from visceral pain. This was highlighted in the small case Given the potential spread of LA into the epidural space, it is
series by Chin et al23 with significant relief of visceral pain after feasible that lumbar approaches to the ESP block lead to lower
ESP blocks seen in 3 bariatric patients undergoing laparoscopic limb weakness. Selvi and Tulgar27 published a case report describing
abdominal surgery. transient bilateral lower limb weakness after a T11 ESP block.
The literature points to a wide spectrum of indications for ESP blocks Novel Uses
when considering abdominal procedures. These include laparotomy, There is an abundance of case reports and small case series in the
nephrectomy (laparoscopic and open), renal transplant, radical literature with positive outcomes. Clinicians have investigated the
prostatectomy, percutaneous nephrolithotripsy, herniorrhaphy, effectiveness of the ESP block on patients undergoing surgery on the
gastric bypass, gastrectomy, and caesarean delivery, to name a few. upper limbs and spine.28
Table 1. Weight-Based Local Anaesthetic Concentration and Volume Guide for Erector Spinae Plane Block in Rib Fractures
Weight-Based Dosing
Drug 50-kg Patient 70-kg Patient 100þ-kg Patient
Unilateral
0.25% bupivacaine, mL 30 40 40
0.5% bupivacaine, mL 20 (max dose) 20 30
Bilateral
0.25% bupivacaine, mL 20 per side (40 total) 25 per side (50 total) 30 per side (60 total)
0.5% bupivacaine, mL Not advised, not enough volume Not advised, not enough volume Not advised, not enough volume
There is even a case report suggesting the effectiveness of the studies will need to clarify the decision to perform the block at
technique for a refractory tension headache.29 2 levels if a noncatheter technique is being employed.
Several articles have suggested the ESP block may be used for chronic • Tulgar et al33 demonstrated lower postoperative pain scores and
shoulder pain and surgery on the upper arm.30 opioid use in thoracotomy patients if 2-level ESP blocks were
performed rather than single-level blocks.
CLINICAL QUESTIONS
• Multiple published case reports also describe the successful use of
There remain several clinical questions that require further research.
a bilevel approach.34,35
What Are the Optimal Volume and Concentration of LA?
• There have been no studies to date directly comparing the clinical
• Fascial plane blocks rely on a high-volume, low-concentration efficacy of single-level with multilevel injections/catheters.
technique for optimal efficacy.
• Multilevel injections/catheter insertions may have a role when
• In a mini review, De Cassai and Tonetti31 determined that 3.6 mL extensive analgesia of the trunk is desired.
of an LA agent per desired vertebral level spread was adequate in
ESP blocks. However, at present, there are no data relating this What Is the Optimal Approach?
volume to duration of action. The classically described approach to the ESP block is a parasagittal
ultrasound probe position with in-plane needling. Some clinicians
• Luftig et al32 specifically looked at the volume and concentration
report an out-of-plane technique with the same probe position.
used in 16 ESP block articles (49 cases) when indicated for rib
fracture analgesia, to determine optimal regimes. Based on the • A documented problem with the parasagittal approach is
findings, they created a weight-based guide for ESP block in ‘‘lamination’’—injection between the muscle fibers producing
these patients (Table 1). an ultrasound image consistent with spread within the fascial
plane (Figure 7).36 This occurs because of the longitudinal
Single Level Versus Multilevel
orientation of the muscle fibers in the ES complex.
• As shown, cadaveric and anatomical studies show extensive
spread of injectate around the ES complex with varied degrees • The authors observed this phenomenon to occur more frequently
of spread into the neural foramina and epidural space. Further when needling for catheter insertion with 16-gauge Tuohy
needles.
• With a transverse approach, lamination will not be seen after
intramuscular injection.
• The authors of this article recommend first performing a single-
shot ESP block with the transverse approach to create a target
space for catheter insertion. The catheter can then be sited using
a parasagittal or transverse approach. Block success and correct
catheter placement rates may be higher with this technique.
Caveats
• Publication bias: When the outcome of cases and clinical trials is
not in favour of an intervention, they may not be submitted for
consideration of publication. This means for a new technique
such as the ESP block, the already relatively small pool of
evidence may suffer from reporting biases.
• As the technique remains in its infancy with most data coming
Figure 6. T5 vertebral level parasagittal (A, B) and transverse (C, from case reports, there is currently no consensus on dosing
D) approach to the erector spinae plane block. Needle trajectory regimes for various indications. This makes comparison between
indicated by arrow heads. In images A and B, the needle tip is located studies more difficult.
between the muscle fibers, which run parallel to the ultrasound
beam in the parasagittal probe orientation. When fluid is injected REFERENCES
here (*), the ultrasound appearance may replicate that seen with an
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intramuscular injection. With a transverse approach, as shown in images 2. Blanco R. Tap block under ultrasound guidance: the description of a ‘‘no pops’’
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5. Tsui BCH, Fonseca A, Munshey F, McFadyen G, Caruso TJ. The erector spinae 21. Macaire P, Ho N, Nguyen T, et al. Ultrasound-guided continuous thoracic
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with decreased opioid consumption and improved patient postoperative
6. Chin KJ, Adhikary S, Sarwani N, Forero M. The analgesic efficacy of pre-operative rehabilitation after open cardiac surgery—a patient-matched, controlled
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repair. Anaesthesia. 2017; 72:452-460.
22. Nagaraja PS, Ragavendran S, Singh NG, et al. Comparison of continuous thoracic
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23. Chin KJ, Malhas L, Perlas A. The erector spinae plane block provides visceral
8. Schwartzmann A, Peng P, Maciel MA, et al. Mechanism of the erector spinae abdominal analgesia in bariatric surgery a report of 3 cases. Reg Anesth Pain
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24. Tulgar S, Kapakli MS, Kose HC, et al. Evaluation of ultrasound-guided erector
9. Ivanusic J, Konishi Y, Barrington MJ. A cadaveric study investigating the spinae plane block and oblique subcostal transversus abdominis plane block
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2018; 43(6):567-571. Anesth Essays Res. 2019; 13:50-56.
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Tranexamic Acid
Clinical Article
Dr Charlotte Earnshaw* and Dr Melanie Poole

Summary
Tranexamic acid significantly reduces peri-operative blood loss in a wide variety of surgical specialties and
improves survival in haemorrhage from trauma and birth. In cardiac patients it carries a risk of seizures, especially
with higher doses, and theoretically may predispose to thromboembolic disease but clinically relatively few side
effects are observed. It is highly cost-effective and requires minimal training to administer. As such the World
Health Organisation now include it on the essential medicines list. Future research to clarify dosing regimens,
especially in the cardiac and paediatric populations, as well as usage in other surgical disciplines and intracranial
haemorrhage is expected.
KEY POINTS
• Tranexamic acid reduces bleeding and reduces the need for blood transfusion. It is used in the management
of major trauma, haemorrhage, and as prophylaxis in surgery.
• Standard dose is 1g intravenously, over a minimum of 10 minutes.
• The main mechanism of action is anti-fibrinolytic activity. It also possesses anti-inflammatory effects and may
help attenuate the systemic inflammatory response syndrome in cardiac patients.
• There has been no evidence of thrombotic events with tranexamic acid use, but theoretical concerns remain,
and caution is advised in patients with recent or significant history of venous thromboembolism.
• In cardiac patients it has been shown to increase the risk of seizures, and manufacturers advise against using
in any patient with a history of seizures.
INTRODUCTION
Tranexamic acid was introduced in the 1960s, The ATACAS trial (2018) studied the effect of
it reduces bleeding by competitively inhibiting tranexamic acid in cardiac surgery and, consistent
fibrinolysis. It was initially prescribed for heavy with the effect seen in other surgical specialties,
menstrual bleeding but is now recommended in a blood loss was reduced. Relatively high doses
variety of elective surgical procedures to reduce blood (50-100mg/kg) were administered and post-operative
loss, and also for the treatment of major haemorrhage. seizure rate was increased with tranexamic acid
It has relatively few contraindications, is well-tolerated compared to placebo.3 Some evidence links higher
and cheap to use. As such, its use continues to expand doses with larger reductions in peri-operative blood
into other specialties and surgeries. loss but at the expense of increased seizure rate.
Tranexamic acid is also commonly used in orthopaedic
The CRASH2 trial (2010) is the largest study to date surgeries as a 1g prophylactic pre-incision dose in
on tranexamic acid demonstrating a significant (1.5%) total knee and total hip arthroplasty.4 Research into its
Charlotte Earnshaw
mortality benefit when 1g of intravenous tranexamic benefits in spinal surgery, intra-cranial haemorrhage,
Anaesthetic
Speciality trainee acid, compared to placebo, was given within 3 hours liver resection and paediatrics is ongoing.
North Bristol NHS Trust of injury to trauma patients with suspected major
UNITED KINGDOM haemorrhage.1 In the WOMAN trial (2017) 1g After reviewing the pharmacology, contraindications
Melanie Poole of intravenous tranexamic acid was given for the and side effects, this article will consider the use of
Locum Consultant treatment of post-partum haemorrhage resulting in tranexamic acid in clinical practice across various
Anaesthetist, reduced deaths due to bleeding (0.4%), with a greater specialties.
North Bristol NHS Trust survival benefit when tranexamic acid is given as close
UNITED KINGDOM as possible to the onset of post-partum haemorrhage.2
Figure 1: The clotting and fibrinolytic systems
FIBRINOLYSIS AND MECHANISM OF ACTION OF

TRANEXAMIC ACID
Tranexamic acid has beneficial actions on fibrinolysis, platelet blood clot (a mass of red blood cells, white blood cells, platelets,
function and the systemic inflammatory syndrome.5 fibrinogen, fibrin and plasminogen). To prevent uncontrolled
growth of the blood clot, fibrinolysis is also initiated. Fibrinolysis
Following trauma, surgery, or exposure to extracorporeal circulations
is activated locally by plasminogen-activators found in endovascular
the body’s ability to regulate local fibrinolysis is exceeded and
endothelium as well as being produced by macrophages that convert
generalised fibrinolysis can occur leading to a coagulopathy. Vascular
plasminogen to plasmin and promote fibrinolysis at the site of clot
endothelial wall stress activates the clotting cascade leading to
formation.5
platelet activation and plug formation, large amounts of thrombin
production and later fibrin cross-links that strengthen the developing
Table 1: Dose Adjustment in Renal Impairment
Serum Creatinine (lmol/l) eGFR (ml/min) Dose (IV) Frequency of Administration

120-249 20-50 10mg/kg 12 hourly
250-500 10-20 10mg/kg 24 hourly
>500 <10 5mg/kg 24 hourly
Tranexamic acid is a synthetic derivative of the amino acid lysine and concentrations are 1/10 that of plasma and with minimal
inhibits fibrinolysis by reversibly binding to lysine-binding sites on concentrations in breast milk (1/100), it is considered safe in breast
plasminogen, thereby preventing the cleavage of fibrin.5,6 (See Figure feeding.6
1)
Metabolism and Elimination
Plasmin acts on platelets to reduce platelet aggregation and adhesion Tranexamic acid is excreted unchanged in the urine and 90% is
and therefore tranexamic acid, by reducing the formation of plasmin, excreted within the first 24 hours after an intravenous dose.6 Doses
helps to preserve platelet function.5 Plasmin and plasminogen should be adjusted in renal insufficiency.
also demonstrate pro-inflammatory effects including monocyte
activation and cytokine production and whilst the role of tranexamic Routes of Administration, Storage and Compatibility
acid in reducing inflammation is not fully elucidated the expression Oral, topical and intravenous formulations exist but intra-cerebral
of several pro-inflammatory genes is altered in the cardiac setting and intrathecal use are contraindicated due to seizure activity
following the administration of tranexamic acid and it demonstrates in animals. It has a long shelf-life of 3 years and can be stored at
a reduction in the systemic-inflammatory-response-syndrome room temperature. Intravenous tranexamic acid is compatible with
and subsequent vasopressor use.7 It has also been shown to inhibit electrolyte, glucose and amino acid solutions as well as with heparin.6
complement.6 (See Table 1)
There is limited evidence that some patients experience a fibrinolytic SIDE EFFECT PROFILE
shutdown scenario whereby they increase their own plasminogen-
activator inhibitor activity and thus would not benefit from Seizures
tranexamic acid and may become pro-thrombotic if tranexamic acid Administration of topical tranexamic acid directly to the central
is given to this subset of patients. This is an ongoing area of research nervous system in animals provokes seizures. Clinically, tranexamic
and currently has not impacted clinical guidance on usage.7 acid has been shown to increase the risk of seizures in patients
PHARMACOKINETICS undergoing cardiac surgery, largely when moderate and high doses
(more than 10mg/kg) are used. Possible causal mechanisms include
Absorption inhibition of GABA-A and glycine inhibitory receptors leading
Maximum plasma concentrations of tranexamic acid are attained to stimulation of excitatory pathways, as well as an increased
within 3 hours of an oral dose and absorption is not slowed by a susceptibility of cardiac patients to post-operative seizures due to
full stomach. Peak concentrations occur rapidly after intravenous emboli introduced during surgery.3 Increased risk of seizures has not
injection and fall in a multi-exponential manner.6 been observed in other clinical settings. However, manufacturers
advise avoidance of tranexamic acid in all patients with a history of
Distribution convulsions.6
Tranexamic acid has a volume of distribution of 9-12L and is 3%
plasma-protein bound. It has good penetration of joint fluid and Thrombo-embolism
synovial membranes as well as crossing the placenta and blood- There is a theoretical basis for concerns that tranexamic acid could
brain barrier. In both cerebrospinal fluid and aqueous humour, promote thrombus formation, and this is supported by in vivo
Table 2: Side effects of tranexamic acid
Side effect Frequency

Gastrointestinal Diarrhoea, vomiting, nausea Common
Central nervous system Seizures Unknown
Associated with high doses
Cardiovascular system Hypotension (fast injection), malaise, VTE Unknown
Immune system Hypersensitivity Unknown
Eye disorders Visual disturbance Unknown
Skin Dermatitis Uncommon
animal studies showing a dose-dependent increase in thrombus and Trauma
risk of thrombo-embolism.7 However, multiple meta-analyses have Trauma is a major contributor to death worldwide with haemorrhage
failed to show an increased risk of myocardial infarction, stroke, causative in 1/3 of in-hospital trauma deaths. Early clotting
pulmonary embolism or deep vein thrombosis with tranexamic acid abnormalities, including hyperfibrinolysis, occur frequently in
compared to placebo.5,7,8 Subsequently, it is recommended that an trauma patients and substantially contribute to mortality. A large
acute venous thromboembolism is an absolute contraindication to study found that 1g of intravenous tranexamic acid, compared
tranexamic acid, and a risk/benefit analysis must be undertaken if to placebo, reduced risk of death from bleeding by 15% with no
there is a personal history of VTE.6 (See Table 2) increased risk of any adverse events.1 However, treatment benefit
decreases by 10% for every 15 minute delay after the first hour
CLINICAL USES
following onset of haemorrhage and therefore should be given as
Tranexamic acid reduces blood loss in patients with both normal soon as possible but certainly within 3 hours. After 3 hours it should
fibrinolysis and hyperfibrinolysis.6 Hyperfibrinolysis can occur be omitted unless there is clear evidence of hyperfibrinolysis on
following surgery, trauma, tissue damage or exposure to extracorporeal blood results10.
circulations where the body’s natural ability to regulate local
fibrinolysis is exceeded and fibrinolysis becomes systemic, leading Obstetrics
to coagulopathy. Additionally, during clot formation fibrinogen is Postpartum haemorrhage is the leading cause of maternal mortality
consumed rapidly and early tranexamic acid preserves fibrinogen worldwide. Within 1 hour of birth the concentration of plasminogen
stores during haemorrhage. Therefore, clinicians should aim to doubles leading to activation of fibrinolysis. Despite not showing
prevent, rather than treat, coagulopathy and administer tranexamic a reduction in the volume of blood loss or transfusion rate, the
acid as early as possible. WOMAN trial demonstrated that intravenous tranexamic acid,
It is a cost-effective intervention for preventing bleeding during major compared to placebo, reduced the risk of death from bleeding by
surgery across a broad spectrum of surgical procedures, reducing almost 1/3 with no increase in adverse events for mother or baby.2
average peri-operative blood loss, and subsequent transfusion, by It should therefore be given as a 1g intravenous bolus as close as
34% and 39% respectively.9 Blood transfusion is costly and scarce, possible to bleeding onset (birth) and a further 1g intravenous dose
especially in areas with limited resources and poses multiple risks to can be repeated 30 minutes later if bleeding continues. It is not to
patients including transfusion-related reactions, immunomodulation be given if more than 3 hours has elapsed since birth due to lack of
and transfusion transmitted infection. (See Table 3) treatment benefit.
Table 3. Summary Dosing Table
Loading Dose (No Faster Maintenance Dose Other Considerations

than 100mg/minute)
Trauma 1g IV 1g IV over 8 hours Continue 1g 8 hourly if
bleeding ongoing
Post-partum haemorrhage 1g IV 1g IV bolus 30 minutes after
initial dose, if bleeding continues
Cardiac 1g or 5-10mg/kg IV 1-5mg/kg/hour
Orthopaedic 1g IV pre-incision Consider further 1g IV bolus if
ongoing bleeding or blood loss
500mls
Spinal 1g or 10mg/kg IV pre-incision
All other types of surgery 1g or 10mg/kg IV pre-incision
(with risk of >500mls 1g or 10mg/kg IV pre-incision
peri-operative blood loss)
Haemophilia (both haemorrhage 1g orally 8 hourly for several
and following minor surgery, days prior to procedure
dental extraction)
Hereditary angioedema 1-1.5g orally 8 hourly Continue 1-1.5g orally 8 hourly
for 2-5 days following procedure
prophylactically several days
prior to planned procedures
Cardiac
Tranexamic acid has several beneficial actions in patients undergoing differences have not yet shown to be statistically significant. As
cardiac surgery. These patients are at high risk of blood loss, and there have been no adverse outcomes alongside increasing evidence
subsequent transfusion, due to the highly invasive nature of in most other surgical specialties tranexamic acid is recommended
cardiac surgery, high dose anticoagulation and blood lost within in all spinal surgery that carries a risk of major bleeding (>30%
the extracorporeal cardiopulmonary bypass circuit. Exposure to total estimated blood volume) and/or surgery involving fusion at 3
the extracorporeal circuit activates the fibrinolytic system and vertebral levels.12
causes platelet dysfunction, thus in addition to its’ antifibrinolytic
activity tranexamic acid helps preserve platelet function during Other Uses
cardiopulmonary bypass.3 Patients undergoing major cardiac surgery Tranexamic acid has been introduced prophylactically across a wide
often suffer a profound systemic inflammatory response syndrome range of other conditions and procedures including haemophiliacs
leading to shock and multiorgan failure and tranexamic acid has undergoing any surgery, hereditary angioedema, and prostatectomy.
been shown to alter the expression of several inflammatory genes, It should be used, unless contraindicated, in any other major surgery
dampening this inflammatory response.5 at risk of more than 500ml blood loss or loss of 10% circulating blood
Tranexamic acid reduces the rate of blood loss, risk of reoperation due volume. It is also recommended for treatment of major bleeding from
to haemorrhage (which carries increased morbidity and mortality) haemoptysis and gastrointestinal haemorrhage.7,8 Currently a large
and the need for blood transfusion with no increased risk of death or multicentre trial (HeLiX) is investigating the impact of tranexamic
thrombotic complications in patients undergoing on-pump or off- acid on perioperative blood transfusion in patients undergoing liver
pump surgery.3 However, it does cause an increased risk of seizures resection.13
demonstrating a dose-dependent relationship. Therefore lower dose
tranexamic acid (5-10mg/kg) is being increasingly used in UK REFERENCES AND FURTHER READING
cardiac centres with less post-operative seizures observed as a result. 1. CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular
Seizures generally occur within hours of surgery and are grand-mal occlusive events, and blood transfusion in trauma patients with significant
haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet
in nature. Those who have post-operative seizures are subsequently 2010; 376:23-3
more at risk of stroke or death. The risk of seizures is particularly 2. WOMAN trial collaborators. Effect of early tranexamic acid administration
high in the elderly, those with pre-existing renal failure and those on mortality, hysterectomy, and other morbidities in women with post-partum
undergoing open-heart surgery.3 haemorrhage (WOMAN): an international, randomised, double-blind, placebo
controlled trial. Lancet 2017; 389:2105-16
Orthopaedic 3. Myles PS, Smith JA, Forbes A, et al. Tranexamic Acid in Patients Undergoing
Coronary-Artery Surgery. N Engl J Med 2017; 376:136-48
Prosthetic implantation and use of a tourniquet activates fibrinolysis
and haemorrhage is common post arthroplasty. Patients presenting 4. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The Efficacy of Tranexamic Acid
in Total Hip Arthroplasty: A Network Meta-Analysis. J Arthroplasty 2018;33:3083
for hip and knee joint replacement are often elderly with multiple 3089.e4 https://www.arthroplastyjournal.org/article/S0883-5403(18)30593-X
co-morbidities such as anaemia and ischaemic heart disease, that fulltext. Accessed September 8, 2018.
render them more susceptible to bleeding-related morbidity and 5. Levy JH, Koster A, Quinones QJ, Milling TJ, Key NS. Anti-fibrinolytic therapy and
mortality. Tranexamic acid significantly reduces blood loss in total perioperative considerations. Anesthesiology 2018; 128:657-670
hip and knee replacement. Intravenous delivery appears to provide 6. Datapharm electronics Medicines Compendium (eMC). Pfizer Limited
the most benefit but both oral and combination topical/intravenous Cyklokapron Injection Summary of product characteristics. https://www
medicines.org.uk/emc/product/1077/smpc. Accessed July 2, 2018.
preparations are favourable to placebo.4 Tranexamic acid has excellent
7. Ng W, Jerath A, Wasowicz M. Tranexamic acid: a clinical review. Anaesthesiol
joint penetration and its use has been fully embedded in total knee Intensive Ther 2015; 47:339-50
and hip arthroplasty fast track protocols in many centres. Similar
8. Kozek-Langenecker SA, Ahmed AB, Afshari A, et al. Management of severe
usage is expected in the future in all types of major arthroplasty. perioperative bleeding: guidelines from the European Society of
Anaesthesiology. Eur J Anaesthesiol 2017; 34:332-395
Intra-cranial Haemorrhage 9. Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising
In spontaneous haemorrhage tranexamic acid can reduce haematoma perioperative allogeneic blood transfusion. Cochrane database of systematic
expansion and leads to fewer deaths at 7 days with no increased risk of reviews 2011. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.
CD001886.pub4/full. Accessed July 21, 2018.
seizures or other adverse events but with no significant improvement
10. Gayet-Ageron A, Prieto-Merino D, Ker K, et al. Effect of treatment delay on
in neurological or mortality outcomes at 90 days.11 Therefore it effectiveness and safety of anti-fibrinolytics in acute severe haemorrhage.
is not currently recommended in clinical practice but results are Lancet 2018; 391:125-132
anticipated from an ongoing study (STOP-AUST) into the benefit 11. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary
of tranexamic acid in a subset of these patients and a meta-analysis of IntraCerebral haemorrhage (TICH-2): an international randomised, placebo
ongoing multiple smaller trials is planned. controlled, phase 3 superiority trial. Lancet 2018; 391:2107-15.
12. Colomina MJ, Koo M, Basora M, Pizones J, Mora L and Bago J. Intraoperative
Spinal Surgery tranexamic acid use in major spine surgery in adults: a multicentre, randomized,
placebo-controlled trial. Br J anaesth 2017; 118:380-90
Research in spinal surgery and tranexamic acid has largely been
13. U.S. National Library of Medicine. Clinical trials.gov. https://clinicaltrials.gov
on smaller studies showing a slight reduction in blood loss and ct2/show/NCT02261415. Accessed May 22, 2019.
transfusion rate following administration of tranexamic acid but
Intrathecal tranexamic acid during spinal
anaesthesia for caesarean deliver
Case Report
Reprinted with permission from the authors and the South African Medical Journal
D G Bishop*, A C Lundgren, N F Moran, I Popov and J Moodley

Summary
The National Committee on Confidential Enquiries into Maternal Deaths recently received notification of a death
in South Africa caused by inadvertent intrathecal administration of tranexamic acid (TXA). TXA is increasingly used
during caesarean delivery following updated recommendations from the World Health Organization in 2017. D G Bishop mb chb, da, fca, phd
Department of Anaesthesia
However, its greater availability has led to an international rise in drug errors during obstetric spinal anaesthesia.
School of Clinical Medicine
This case highlights a growing clinical risk, of which all operating theatre staff should be aware. Review of existing College of Health Sciences
operating theatre drug handling practices is required in order to decrease this risk. Recommendations are made University of Kwazulu-natal
Pietermaritzburg
that aim to minimise drug errors associated with the use of this potentially life-saving intervention.
SOUTH AFRICA
INTRODUCTION A C Lundgren, mb, chb, da, ffa, phd

msc med (health haw and bioethics)
The National Committee on Confidential Enquiries middle-income settings such as SA. The WHO states 4
Steve Biko Centre for Bioethics
into Maternal Deaths recently received notification of that ‘regardless of the level of health system resources, Faculty of Health Sciences
a death in South Africa (SA) caused by inadvertent TXA should be recognized as a lifesaving intervention University of the Witwatersrand
intrathecal administration of tranexamic acid (TXA). and be made readily available for the management of Johannesburg
This case highlights a growing clinical risk, of which postpartum haemorrhage in settings where emergency SOUTH AFRICA
all operating theatre staff should be aware. Review of obstetric care is provided’.3
existing operating theatre drug handling practices is N F Moran, bm bch, ma, fcog
required in order to minimise this risk. SA TXA RECOMMENDATIONS KwaZulu-Natal Department
of Health and Department of
TXA is included in the World Health Organization It has been suggested that the high number of deaths
Obstetrics and Gynaecology
(WHO) essential medicines list (EML)1 as well due to obstetric haemorrhage (OH) at or after CD School of Clinical Medicine
as the SA National Department of Health EML.2 in SA is a national emergency,5 and despite a recent College of Health Sciences
It is a synthetic lysine analogue that acts to reduce downward trend, OH remains the third most common University of KwaZulu-Natal
fibrinolysis through competitive inhibition of cause of maternal mortality at ~17%.6 Accordingly, the Durban
nationally endorsed training programme for obstetric SOUTH AFRICA
plasminogen binding sites. TXA is increasingly being
used in the perioperative setting as a result of recently emergencies (Essential Steps in the Management of
Obstetric Emergencies: ESMOE)7 has been revised I Popov, mc, fcog (sa)
updated WHO guidelines recommending early use Department of Gynaecology
of intravenous TXA during caesarean delivery (CD) to recommend early intravenous administration of
and Obstetrics
when excessive bleeding occurs.3 The key messages 1g TXA for bleeding during or after CD. Excessive
Port Shepstone
from this guideline are summarised in Table 1. This bleeding is now defined as >500mL in the suction Regional Hospital
change in practice is largely due to the results of bottle, or a decrease in blood pressure accompanied KwaZulu-Natal
the WOMAN trial, a landmark multicentre study by a rise in heart rate associated with bleeding, as SOUTH AFRICA
including 20,000 patients that showed reduced detected by the anaesthetist. This is earlier than the
traditional description of at least 1,000mL blood loss J Moodley, mb chb, frcog, md
maternal mortality due to bleeding with the early
during CD, and TXA is therefore being used with Women’s Health and HIV
administration of TXA in the setting of postpartum
greater frequency. While there may be a role for the Research Group
haemorrhage.4 The WOMAN trial showed that if Department of Obstetrics
TXA was given intravenously within 3 hours of administration of TXA before CD,8,9 there is not
and Gynaecology
bleeding following normal vaginal delivery or CD, yet enough evidence from high-quality research to
School of Clinical Medicine
maternal mortality was reduced by 31%, although the recommend such prophylaxis at a national level.10 In College of Health Sciences
absolute reduction was small (1.7 - 1.2%, risk ratio particular, there is no evidence that prophylactic TXA University of KwaZulu-Natal
0.69, 95% confidence interval 0.52 - 0.91; p=0.008). before CD reduces maternal death. Durban
These benefits were most pronounced in low- and SOUTH AFRICA
Table 1: Key messages adapted from the updated World Health Organization recommendations on TXA for the treatment of postpartum
haemorrhage3
Bleeding during CD is defined as a clinical estimate of blood loss >1 000 mL, or blood loss sufficient to cause haemodynamic instability
Early use of TXA (within 3 hours of birth), in addition to standard care, is recommended. The use of TXA >3 hours after birth is not supported
Administer TXA 1g IV over 10 minutes, with a repeat dose if bleeding continues after 30 minutes, or if bleeding restarts within 24 hours of the first
dose. Only IV use is currently supported
TXA should be given in all cases of postpartum haemorrhage, regardless of cause
TXA should not be given when a clear contraindication exists, such as thromboembolic disease during pregnancy.
TXA = tranexamic acid; CD = caesarean delivery; IV = intravenous
With increased availability and use of TXA during and immediately bleeding complications.16 With a lower recommended threshold for
following CD, the risk of drug error increases. Our case of maternal the use of TXA, it is likely that the drug will be given in >6% of cases.
death was assessed by independent experts to be due to intrathecal The benefits clearly outweigh the risks: the focus therefore needs to
TXA, and occurred in the context of a disturbing international trend. be on minimising or eliminating drug error.
A recent review in Anaesthesia11 highlighted 21 such cases between
1988 and 2018, 10 of which were fatal. Twenty were due to ‘ampoule MINIMISING THE RISK OF INTRATHECAL DRUG ERROR
error’. An accompanying editorial12 entitled ‘Spinal tranexamic acid The incidence of perioperative drug errors ranges from one in 133
– a new killer in town’ highlighted the dramatic increase in the anaesthetics in retrospective studies17 to one in two operations in
number of cases since 2009. Seven cases involved CD, 6 of which prospective studies (one in 20 drug administrations).18 Obstetric
resulted in death: it appears that mortality is higher following CD neuraxial drug administration errors in particular may result in
than following other surgery. The authors mention anecdotal reports devastating consequences.19 There is a lack of randomised controlled
of further cases that have not been formally reported, making the true trials that examine specific techniques and their ability to reduce
incidence hard to estimate. Clinicians are understandably reluctant drug error; recommendations are therefore based on expert opinion
to submit case reports relating to serious medical error. Additionally, and best available evidence.20,21
cases such as ours that come to light through a confidential enquiry
All health facilities should ensure that they have clearly written
process cannot be published in detail owing to requirements to
policies that minimise medication errors, and then audit and appraise
maintain anonymity. The incidence is therefore probably far higher
errors that do occur.22 This approach should nurture a culture of drug
than currently reported.
safety, including multidisciplinary involvement, ongoing education
CONSEQUENCES OF INTRATHECAL TXA ADMINISTRATION and specific evidence-based interventions.22 However, despite
vociferous calls for changes in practice, merely exhorting doctors
Intrathecal TXA is a potent neurotoxin and neurological sequelae
to be more careful is often inadequate.23 Ideally, system changes
dominate the clinical presentation, usually with refractory seizures.
should make it impossible for error to occur. A similar problem has
Massive sympathetic stimulation frequently occurs, often leading to
been encountered with epidural anaesthesia, where the use of Luer
lethal cardiac arrhythmias such as ventricular fibrillation. Treatment
universal connectors has allowed for cross-connectivity, resulting
is mainly supportive and should occur in an intensive care setting,
in drug errors. This problem is easily preventable with the use of
including antiepileptics such as diazepam, thiopentone and
non-Luer connectors, although uptake has been slow.23 Non-Luer
magnesium sulphate13 and appropriate antiarrhythmic medication.
connectors will not prevent a single-shot spinal anaesthesia drug
Early cerebrospinal fluid (CSF) lavage is also recommended,
error, however, as occurs with TXA.
following success in the management of similar cases.11,14,15 CSF
lavage consists of removing 10mL of CSF and replacing this with 10 The risk of accidental use of the wrong drug increases when ampoules
mL of saline, repeated up to four times.14,15 The increased mortality look similar, or are physically available in close proximity.24 There
rate in the obstetric population following intrathecal TXA is possibly are now a large number of generic versions of TXA, and changes
due to decreased CSF volume in pregnancy, leading to increased in supplier and the appearance of ampoules are increasingly
drug concentrations.11 common. Human error is to some degree unavoidable, and rather
than attempting to eliminate all mistakes, strategies should aim to
Given the consequences of inadvertent intrathecal TXA
reduce predictable errors. Solutions that minimise the possibility of
administration, is the increased risk justifiable? TXA has become
human error should be given highest priority.24 Technology-assisted
an integral part of the management of OH: the WOMAN trial4
drug identification, using barcode readers, is one such intervention,
suggested that a maternal life could be saved with every 267 usages
although it is unlikely to be immediately available in SA facilities. Pre-
following OH. The potential ‘number needed to harm’ is difficult
filled syringes may be another, although this may be problematic for
to estimate: Palanisamy and Kinsella12 estimate the risk due to
manufacturers, as each drug must be tested for stability in a pre-filled
drug error to be <1 in 10,000 spinal anaesthetics, although this
syringe. Other solutions include the careful reading and labelling of
is necessarily based on a large degree of conjecture. In Africa, the
syringes, and a second person or device checking the drug.19 More
incidence of severe bleeding during or after CD is almost 6%, while
costly methods, such as commercially prepared spinal anaesthesia
70% of all complications and 25% of all deaths are secondary to
Table 2: Recommendations for preventing TXA drug errors during and immediately after caesarean delivery
Raise awareness in health facilities (private and public), both written and verbal. Display a clinical alert warning in operating theatres.
Ensure that warnings reach all cadres of staff involved in CDs, whether in an anaesthetic, surgical, nursing or pharmaceutical roles
Conduct regular in-service training of all health professionals on how to avoid drug errors. In the SA context, this should be included in the ESMOE/
EOST anaesthesia module.
Avoid buying drug ampoules that are similar in appearance, and standardise individual drug appearance.
Colour-code syringes/drugs where possible.
Use bar coding and scanner identification or pre-filled syringes if capacity exists.
Physically separate TXA from a dedicated spinal anaesthesia trolley (consider a drug cupboard outside the operating theatre).
Ensure appropriate drug checking practices: careful reading of labels with a second person checking, and minimise distractions during medication
preparation.
Report and review all adverse drug events through an incident reporting system.
Minimise staff fatigue.
TXA = tranexamic acid; CDs = caesarean deliveries; SA = South African; ESMOE = Essential Steps in the Management of Obstetric Emergencies; EOST =
Emergency Obstetric Simulation Training.
intrathecally; we need to ensure that TXA is one of these. Avoiding

a drug substitution error mandates meticulous attention to drug
checking systems, and above all ensuring that TXA is not kept on or
near the spinal anaesthesia trolley. Consideration should be given to
storing TXA out of theatre, provided that the drug will be available
immediately when requested.
We have made recommendations in Table 2 summarising key
interventions aimed at reducing drug error from the relevant
literature.
Importantly, this clinical alert applies equally to both the private
and public sectors in SA, where different versions and appearances
of the drug ampoules are available. Figure 1 illustrates the current
appearances of TXA and bupivacaine in the state sector in KwaZulu-
Figure 1. Tranexamic acid, hyperbaric bupivacaine and isobaric Natal Province. Figure 2 illustrates the TXA used by one of the
bupivacaine.
private hospitals in KwaZulu-Natal. This image was taken after
discovering these ampoules in the same container, illustrating the
potential for drug error.
CONCLUSIONS
The indications for TXA during and after CD continue to expand.
The increased use and availability of the drug have led to a concerning
increase in inadvertent intrathecal administration worldwide – an
error that always results in harm. We need to urgently raise awareness
of this potentially lethal mistake and take steps to ensure that we
have no further such cases in SA. The first step is to store TXA in a
separate location from spinal bupivacaine, and ensure that the drug
is never present on the spinal anaesthesia trolley.
REFERENCES
1. World Health Organization. WHO Model List of Essential Medicines. 2017.
https://www.who.int/medicines/publications/essentialmedicines/en/
Figure 2. Tranexamic acid and spinal bupivacaine stored in the same (accessed 23 June 2019).
container in a private hospital.
2. Republic of South Africa. Essential Drugs Programme. Standard Treatment
trays including bupivacaine, are unlikely to represent solutions for Guidelines and Essential Medicines List: Hospital Level (Adults). 4th ed.
Pretoria: National Department of Health, 2015. http://www.health.gov.za/index
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who.int/reproductivehealth/publications/tranexamic-acid-pph-treatment/en/ doi.org/10.1213/01.ane.0000095152.81728.dc
(accessed 23 June 2019). 15. Ting HY, Tsui BC. Reversal of high spinal anesthesia with cerebrospinal lavage
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on mortality, hysterectomy, and other morbidities in women with post-partum Can J Anaesth 2014; 61(11):1004-1007. https://doi.org/10.1007/s12630-014
haemorrhage (WOMAN): An international, randomised, double-blind, placebo 0219-5
controlled trial. Lancet 2017; 389(10084):2105-2116. https://doi. org/10.1016 16. Bishop D, Dyer RA, Maswime S, et al. Maternal and neonatal outcomes after
S0140-6736(17)30638-4 caesarean delivery in the African Surgical Outcomes Study: A 7-day prospective
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Mothers 2014 - 2016: Seventh Triennial Report on Confidential Enquiries into 2001; 29(5):494-500. https://doi. org/10.1177/0310057X0102900508
Maternal Deaths in South Africa: Executive Summary. Pretoria: National 18. Nanji KC, Patel A, Shaikh S, Seger DL, Bates DW. Evaluation of perioperative
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20. Wahr JA, Abernathy JH 3rd, Lazarra EH, et al. Medication safety in the operating
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org/10.1016/j.ijoa.2015.11.006
Ketamine: Recent Evidence and Current Uses
Clinical Article
Dr Alistair Gales* and Dr Stuart Maxwell

Summary
Ketamine is a versatile drug with a unique profile that allows it to be successfully used for a multitude of situations
worldwide. Its variable dosing means it can be used both as an induction agent with a good haemodynamic profile
or in lower doses as a reliable sedative or analgesic drug. It has a vital role in prehospital and emergency medicine.
As an adjunct during routine anaesthesia it can help reduce opioid requirements postoperatively. Its use in critical
care includes sedation and management of refractory asthma; however, further research is required to elucidate
its role in trauma and head injury patients. In the developing world, it is a vital and highly valued drug that allows
performance of interventions and operations that may otherwise prove impossible, especially when resources are
limited.
Ketamine still suffers from traditional stigma from doctors and the public alike and it is often neglected due to
concerns about psychological side effects. Increased availability of preparations of pure S-(þ)-isomer ketamine may
help increase its popularity.
KEY POINTS
• Ketamine is a dissociative anaesthetic agent that at differing doses can be utilised as an analgesic, sedative,
anaesthetic induction and anaesthetic maintenance agent.
• Ketamine has specific advantages over some of the other sedative and anaesthetic agents. Airway reflexes
and tone are often preserved during ketamine sedation and it has an excellent haemodynamic profile.
• Ketamine has a unique role in prehospital, emergency and critical care medicine and is commonly used by
anaesthetists all over the world.
• Research has suggested that use of optical isomers of ketamine may help reduce unwanted side effects.
• Ketamine appears to have beneficial anti-inflammatory, bronchodilatory and neuroprotective properties.
INTRODUCTION
Ketamine is a potent analgesic and dissociative as procedural sedation for both routine and complex
anaesthetic agent that has been used since its discovery procedures in theatres, emergency departments and
and synthesis in 1962. Ketamine’s popularity is critical care units.
due to its unique ability to produce rapid sedative,
Despite the potential advantages of ketamine, it has
analgesic and amnesic effects together with its
not proved universally popular, due to its potentially
beneficial secondary features. The latter include
troublesome ‘‘emergence’’ phenomena, its potential as
bronchodilation and maintenance of both airway
a drug of abuse and the introduction of other sedative
reflexes and sympathetic nervous system tone.1 Recent Dr Alistair Gales
and analgesic drugs.
studies have also suggested previously unrecognised Clinical Fellow
neuroprotective2 and anti-inflammatory3 properties. Research using isomers of ketamine, such as ‘S-(+)- Royal Cornwall Hospitals
Due to ketamine’s unique properties and versatility ketamine,’ a more potent N-methyl-D-aspartate NHS Trust
it has gained increasing popularity in prehospital and receptor (NMDA) binder, has enabled the use of lower UNITED KINGDOM
emergency medicine as well as being used extensively dosing for similar effects.4 This reportedly results in a
lower incidence of the traditional psychoactive side Dr Stuart Maxwell
by anaesthetists and anaesthetic assistants throughout Anaesthetic Trainee,
the world. Newer uses include low-dose analgesic effects, whilst maintaining the beneficial effects of the
Royal Cornwall Hospitals
protocols, adjuvant therapy in local anaesthetic nerve drug.5 NHS Trust
blocks, applications in reactive airways disease, as well UNITED KINGDOM
This article will review the pharmacology and varied uses of ketamine
with reference to the current literature. CH3
PHARMACOLOGY
O
Ketamine is a derivative of the cyclo-hexamine (phencyclidine) HN
anaesthetic agents used extensively in the 1950s. It is a noncompetitive
NMDA receptor antagonist, which blocks the phencyclidine binding
site on the NMDA receptor thereby stopping depolarisation of the
neurone. These NMDA receptors are located at the spinal, thalamic,
limbic and cortical levels. Ketamine therefore interferes with sensory
input to higher centres of the central nervous system, affecting pain
and emotional responses as well as memory, hence it is referred to as a
‘‘dissociative anaesthetic.’’6 Ketamine also has some secondary effects CI
on opioid receptors, which help to propagate its analgesic effect, as
well as catecholamine, alpha and beta receptors.
Figure 1. Chemical structure of ketamine. There is a chiral centre in the
Structural Formula cyclohexanone ring giving the S and R isomers
Ketamine (Figure 1) contains a chiral centre at the C-2 carbon of the
cyclohexanone ring; this means there are two optical isomers; S-(+)-
ketamine and R-(-)-ketamine. The S isomer is pharmacologically pressure. Therefore, it should be used with caution in those with
more active. ischaemic heart disease. The exact mechanism of this is not known;
however, it is proposed that ketamine may inhibit reuptake of
In the UK, ketamine is generally available as a racemic solution, a circulating catecholamines. It has been noted in patients with chronic
mixture of R (-) and S (+) isomers in equal amounts. It is available in catecholamine depletion, such as the critically ill, that ketamine
a variety of concentrations: 10, 50 and 100mg.ml-1. Optical-isomer alone actually produces a negative inotropic effect. In patients with
S-(þ)-ketamine (5 and 25mg.ml-1 concentrations) is not currently normal autonomic control the direct negative inotropic effect is
available in the UK but is available in a number of European often overridden by the central sympathetic response,1 producing an
countries. overall increase or maintenance of blood pressure.6
PHARMACOKINETICS Respiratory
Distribution In contrast to other available sedative and anaesthetic agents, airway
tone and both pharyngeal and laryngeal reflexes are often preserved
Ketamine is highly lipid soluble but has low protein-binding ability.
during ketamine use. However, in children younger than 12 months,
This allows rapid transfer across the blood brain barrier, leading to
airway reflexes are more variable and unpredictable.7 Ketamine may
concentrations there that are generally 4 to 5 times greater than in
have a slight respiratory depressive effect via a decrease in the usual
the plasma. The distribution half-life is around 7 to 11 minutes.
respiratory stimulant effect of raised PaCO2 levels. This is especially
noticeable after administration of large IV boluses, where transient
Metabolism and Elimination
periods of apnoea have been reported.8 Ketamine has also been
Ketamine is mostly metabolised in the liver (80%) into norketamine, shown to cause bronchodilation, making it the induction agent of
which in itself has weak analgesic properties, around 20%to 30% choice for patients with life-threatening asthma requiring mechanical
the potency of ketamine. Peak levels of norketamine appear within ventilation.
the blood around 30 minutes after intravenous (IV) administration.
Norketamine is then primarily hydroxylised via glucuronoconjugation Other Effects
and excreted in urine and bile.5 Ketamine increases muscle tone, blood glucose and plasma cortisol
and prolactin levels.6 A potentially troublesome side effect is
PHARMACOKINETICS increased salivation and some authors advocate coadministration of
Central Nervous System antisialagogues, commonly atropine.9
Ketamine produces a trance-like cataleptic state in which there is USES AND CURRENT EVIDENCE
potent analgesia and sedation. Emergence symptoms affect 30% to
50% of people. The incidence is more common with higher doses. Sedation
Symptoms can include a sense of unease, hallucinations, vivid Ketamine is increasingly being used in prehospital and emergency
dreams, floating sensations and delirium. medicine for analgesia and sedation. It is ideally suited for the
management of traumatic events such as reduction of fractures and
Cardiovascular the treatment of burns. The characteristic dissociative state seen
Ketamine appears to stimulate the sympathetic nervous system with ketamine can be achieved with a dose range between 0.25 and
leading to increased cardiac output, tachycardia and increased blood 1.5mg.ml-1 IV.
Route of Administration Bioavailability Starting Dosea
Intravenous 100% 0.25-1mg.kg-1 (adult)b
0.25-2mg.kg-1 (children)b
1-2mg.kg-1c
Intraosseous 100% 0.5-1mg.kg-1b
1-2mg.kg-1c
Intramuscular 93% 4-5mg.kg-1b
8-10mg.kg-1c
Oral 16%-20% 500 mg max (adult)b
3-15mg.kg-1 (children)b
Nasal 45%-50% 0.25-4 mg.kg-1b
3-9mg.kg-1c
Rectal 24%-30% 50mgb
8-15mg.kg-1c
Table 1. Routes of administration of ketamine and dose range in children and adults (Reproduced from Marland and Ellerton4) The doses quoted
above produce a continuum of effects from mild sedation through to full anaesthetic induction. As with administration of any sedative medication,
relevant expertise and adequate monitoring is required. In children, variable dosing has been proposed for intranasal, intraosseous and intramuscular
routes and there is a lack of consensus in the literature on specific dosing. Examples of paediatric dosing regimes are provided in some of the
referenced articles.29
Note: a Ketamine should be titrated to the required clinical effect. b Analgesic and sedation dose. c Anaesthetic dose.
Note: there is some overlap in dosing between sedation and anaesthetic doses.
For procedural sedation in the emergency department, a loading Table 1). Oral use of ketamine, either alone or in combination
dose administered over 30-60 seconds is recommended. This with paracetamol and diazepam, can be used for dressing changes,
produces sedation within 1 minute, lasting 5-10 minutes. Large especially in burn patients, thus minimising visits to theatre. There is
variation exists for recommended loading doses, from 0.25 to some degree of tachyphylaxis with repeat use.
1.0mg.ml-1 IV for adults and 0.25 to 2.0mg.ml-1 IV for children.4 It
should be noted that doses at the higher range are commonly used The main side effects limiting ketamine’s use during shorter
for induction of general anaesthesia. A single dose is adequate for procedures are agitation and emergence symptoms. Both are more
shorter procedures, but for longer procedures, the dissociative state common with higher doses. Benzodiazepines have been shown to
can be maintained with intermittent boluses of 0.5mg.ml-1. Detailed be effective at reducing the incidence of emergence phenomena. Use
clinical practice guidelines have been produced for using ketamine of midazolam (0.07-0.1mg.kg-1), diazepam (0.15-0.3mg.kg-1and
in the emergency department10 but as with the use of any sedative lorazepam (2-4mg) have all been described.8 Recovering patients
drugs, relevant expertise and adequate monitoring are required. in a quiet and controlled environment with ample reassurance has
Minimum monitoring, where available, consists of continuous also been shown to reduce the incidence and severity of emergence
electrocardiogram, non-invasive blood pressure, oxygen saturation symptoms following ketamine sedation.
and end tidal CO2 monitoring. Induction and Maintenance of Anaesthesia
Ketamine can be used safely in combination with other drugs such Ketamine is also being increasingly commonly used in hospital
as propofol for induction or sedation. Coadministration of these and prehospital environments as an anaesthetic induction and
drugs reduces the required dose of each by around 50%,4 reducing maintenance agent for emergency situations. In rapid sequence
the incidence and severity of the side effects of both agents. It is induction an IV dose of 1 to 2mg.kg-1 produces dissociative
proposed that through its sympathomimetic actions, ketamine anaesthesia within 1 to 2 minutes of administration. This is generally
reduces propofol-induced hypotension, whilst coadministration longer than the short ‘arm-to-brain’ time for rapid unconsciousness
of propofol reduces the incidence of postprocedure agitation seen seen with more traditional IV induction agents such as propofol
with ketamine alone. Randomised control trials have recently shown or thiopentone. However, in circumstances where haemodynamic
improved sedation when both drugs are used together compared control is important, such as trauma or sepsis, ketamine has significant
with propofol alone.11 advantages. It has also been shown to have other important benefits
For cases where IV access is difficult, the use of intramuscular, oral including allowing for improved preoxygenation in agitated patients
or intranasal ketamine has been described with good effect. Time when reduced doses (0.25-0.5mg.kg-1 IV) may be given prior to full
of onset of effect is usually longer for these routes when compared induction of anaesthesia.12 A reduced dose of ketamine for induction
with IV administration and doses required show greater variability should be considered in shocked patients due to concerns about
due to variations in vascularity and gastrointestinal absorption (see inadequate sympathomimetic action within this patient group.
CASE STUDY 1: PREHOSPITAL CARE
A normally fit and well 6-year-old girl was witnessed to have fallen 6 feet from a wall onto concrete and is complaining of severe
pain in her right ankle. She is 45 minutes from the closest hospital and a specialist paramedic ambulance crew is in attendance. She
did not lose consciousness and there is no report of any head injury. Primary survey findings are as follows:
<C>: no catastrophic haemorrhage
A + B: Patent airway, self-ventilating, oxygen saturation 99% on air.
C: Haemodynamically stable, all peripheral pulses present but prolonged capillary refill time in her right foot (5 second versus
2 seconds for other peripheries).
D: Glasgow Coma Scale 15, equal and reactive pupils, blood sugar level normal.
E: Fracture dislocation of right ankle, no other obvious injuries.
Due to the diminished perfusion of her foot and the distance from hospital the decision is made to reduce the fracture on scene.
Consider the available options for sedation and analgesia to allow manipulation.
In this case a combination of fentanyl and ketamine was used to induce a dissociative state. After commencement of full
monitoring (Electrocardiogram, pulse oximetry non-invasive blood pressure and end tidal CO2) initial doses of 0.5mcg.kg-1 of
fentanyl and 0.2mg.kg-1 of ketamine were given. Gentle traction was applied but this was not tolerated due to pain. Therefore, a
further 0.25mcg.kg-1 of fentanyl and 0.2mg.kg-1 of ketamine was given with good effect, allowing for successful reduction, dressing
and splinting with a vacuum splint. Onward transfer was uneventful.
The use of ketamine for total intravenous anaesthesia (TIVA) in however, it does not conclude on optimal dosing or method of
combination with muscle relaxants has been described less frequently delivery. In one randomised controlled trial of postoperative patients
in the literature. Ketamine use has been reported both as a sole agent following major abdominal surgery who were monitored in the
and in conjunction with other hypnotics such as propofol and intensive care unit, ketamine was administered with an initial IV
benzodiazepines. Potential indications for ketamine TIVA include bolus of 0.5mg.kg-1 followed by an infusion of 2mcg.kg-1.min-1
cardiogenic shock, hypovolaemia and pericardial tamponade, for the first 24 hours, followed by 1mcg.kg-1.min-1 for the next 24
particularly in low-resource areas where access to vasoactive drugs hours.15 This resulted in a significant reduction of morphine use
may be limited. Ketamine TIVA has also been described in paediatric postoperatively.
anaesthesia with good effect.8
In the emergency department and prehospital environment, low-dose
Anaesthesia can be maintained using intermittent boluses of ketamine regimes have also been described for pain management.
IV ketamine (0.5mg.kg-1), or by continuous infusion at 10 to Typically suggested doses are between 0.1 and 0.2mg.kg-1 IV. In
30mcg.kg-1.min-1 titrated according to effect. Discontinuing the one study, a bolus dose of 0.1mg.kg-1 IV ketamine was given in
infusion 20 to 30 minutes prior to the end of surgery allows adequate conjunction with opioids to patients with a variety of presentations,
clearance. It is worth noting that electroencephalography and including abdominal pain, lacerations, fractures and dislocations.16
bispectral index monitoring have no role in monitoring the depth of This produced effective analgesia over 120 minutes and reduced
anaesthesia induced by ketamine. opioid requirements and, although some side effects were noted in
the group treated with ketamine, most were considered minor and
Analgesia tolerable.
Ketamine is a potent analgesic. It acts as an NMDA antagonist, which Through desensitisation of central pain pathways, there is some
as discussed previously, produces dissociative analgesia. However, at evidence to suggest that ketamine may be helpful in patients
lower doses it has been shown to desensitise central pain pathways undergoing surgery who are chronic opioid users. Several studies
and modulate opioid receptors.13 Studies have demonstrated that in these populations have shown a reduction in opioid use over 48
administration of small doses of ketamine perioperatively can reduce hours and improved pain scores at 6 weeks following intraoperative
opioid requirements by up to 50%.14 IV ketamine.17 Recently there has also been interest in using
Examples of perioperative analgesia regimes include intraoperative intraoperative ketamine to prevent chronic postsurgical pain. A
ketamine infusions, postoperative infusions, low-dose bolus regimes recent meta-analysis looked at studies using low-dose ketamine
and patient-controlled analgesia. All have been described in detail in versus placebo intraoperatively and followed patients up at 3, 6 and
a Cochrane review from 2006.14 This review provides evidence of the 12 months.18 The results showed postsurgical pain was reduced at 3
efficacy of perioperative ketamine in providing effective analgesia; and 6 months, although there was no significant difference between
the groups at 12 months. Although initial studies are promising, effect, reducing the systemic effects of sepsis including hypotension
larger, more rigorous studies are required to explore the potential and metabolic acidosis.22
role that ketamine plays in persistent postsurgical pain.
Ketamine was initially thought to be contraindicated in patients with
traumatic brain injuries or raised intracranial pressure. However, some
Reactive Airways Disease
studies have shown that ketamine can be helpful as a sedative within
Ketamine has bronchodilatory effects and has been shown to be these patient groups. Its use has been associated with maintenance
effective in patients with acute bronchospasm. Ketamine’s effect on of cerebral perfusion pressure during stimulating interventions in a
the airways is thought to be through modulation of the inflammatory critical care population with brain injuries.23 Its use in traumatic head
cascade. A recent review has shown that there may be a role for injury remains contentious but current evidence (rated Oxford level
ketamine in asthma that is unresponsive to conventional treatment.19 2b, GRADE C) suggests that ketamine does not increase intracranial
The authors noted that patients who received ketamine improved pressure in severe traumatic brain injury patients that are sedated and
clinically, had lower oxygen requirements and in some cases avoided ventilated and may in fact lower it.24 Further research is required in
invasive ventilation. Mechanically ventilated patients who received this field before its use can be widely recommended.
ketamine for severe bronchospasm showed improved gas exchange,
reduced inspiratory pressures, improved minute ventilation and often Cautions and Limitations
went on to be successfully weaned off ventilation. No major adverse
Ketamine is considered to have a very good safety profile. Ketamine
effects with ketamine were reported in this review of 244 patients.
overdose has been manifested as prolonged sedation in case studies
The review included a mix of case reports, case series, observational
of children inadvertently receiving 5 to 100 times the recommended
studies and randomised controlled trials. Highly variable loading
dosage.6 A few isolated case studies of severe respiratory depression
doses from 0.1 to 2.0mg.kg-1 were used in the studies and depending
have been noted during routine administration of ketamine with
upon the initial response, the dose used for continuous infusion
other medications; however, mostly only transient apnoeic episodes
ranged from 0.15 to 2.5mg.kg-1.hr-1. Due to the small sample size
have been reported following large IV boluses.
and wide variety of loading and infusion doses, further research is
needed in this area. Absolute contraindications to IV ketamine as listed by the British
National Formulary25 are hypertension, preeclampsia or eclampsia,
Uses in Critical Care severe cardiac disease, stroke, raised intracranial pressure and acute
Ketamine has a number of potential applications within critical porphyria. Ketamine is also not recommended in children aged, 3
care medicine, including sedation, analgesia and the treatment months and in patients with schizophrenia. Please refer to earlier
of persistent bronchospasm. Ketofol (ketamine and propofol in sections within this article for further detail on the use of ketamine
combination) has been shown to be effective for short-term sedation in patients with raised intracranial pressure and/or traumatic brain
in a critical care population.20 It is important to appreciate that in injury.
critically unwell patients ketamine’s direct negatively inotropic
effect agent may predominate over ketamine’s usual positive or Developing World
neutral cardiovascular response. There have been reported incidents Ketamine is currently used extensively throughout the world due to
of unexpected decreases in blood pressure and/or cardiac output its versatility, availability and low side-effect profile. There has been
following ketamine administration in some critically unwell patients; discussion about its potential for misuse and whether greater controls
however, a large multicentre study of critically unwell septic patients worldwide are required. The World Health Organisation in 2015
revealed no adverse effects when using ketamine.21 It has even been concluded that due to the reliance on ketamine in some countries
suggested that ketamine may have potential advantages compared to ‘‘controlling ketamine internationally could limit access to essential
other agents in patients with severe sepsis (see case study 2). There is and emergency surgery, which would constitute a public health crisis
evidence to suggest that it may exert a protective anti-inflammatory in countries where no affordable alternatives exist.’’
CASE STUDY 2: SEPSIS

A 67-year-old man presents to the emergency department with a 2-day history of productive cough, confusion and fever. He is
haemodynamically unstable with hypotension and tachycardia. He is diagnosed with a septicaemia secondary to presumed severe
community-acquired pneumonia (CURB65 ¼ 4). Initial treatment consists of IV fluids and appropriate antibiotic therapy. Despite
this, his clinical condition continues to deteriorate with worsening hypoxia, hypotension and metabolic acidosis. He is transferred to
critical care for commencement of mechanical ventilation and cardiovascular support.
Consider the available induction agents along with the risks and benefits of using each.
In this case, the anaesthetic agent chosen was ketamine at a dose of 1.5mg.kg-1. This was because of its cardiovascular stability
when compared with alternative induction agents. There is also some evidence to suggest that ketamine has some anti-
inflammatory properties.
Ketamine is one of the most available anaesthetic agents in low- to 11. Andolfatto G, Abu-Laban RB, Zed PJ, et al. Ketamine propofol combination
middle-income countries (LMICs).26 A recent report found that in (ketofol) versus propofol alone for emergency department procedural sedation
and analgesia: a randomized double-blind trial. Ann Emerg Med.
12 LMICs, only 53% of facilities had reliable access to a functioning 2012; 59(6):504-512.
anaesthesia machine and only 52% had continuous access to pulse 12. Mosier JM, Joshi R, Hypes C, Pacheco G, Valenzuela T, Sakles JC. The
oximetry. On average 21% to 45% lacked basic airway management physiologically difficult airway. West J Emerg Med. 2015; 16(7):1109-1117.
equipment. In this survey general inhalational anaesthesia was offered 13. Sleigh J, Harvey M, Voss L, Denny B. Ketamine—more mechanisms of action
by only 58% of respondents but between 70% and 90% reported than just NMDA blockade. Trends Anaesth Crit Care. 2014; 4(2):76-81.
reliable access to ketamine. 14. Bell RF, Dahl JB, Moore RA, Kalso EA. Perioperative ketamine for acute
postoperative pain. Cochrane Database Syst Rev. 2006;Jan 25(1):CD004603.
A study attempting to quantify ketamine use in LMICs found a serious 15. Guillou N, Tanguy M, Seguin P, et al. The effects of small-dose ketamine on
complication rate (i.e., death, cardiac arrest, apnoea, laryngospasm morphine consumption in surgical intensive care unit patients after major
and aspiration) of only 0.15% in over 12,000 administrations of abdominal surgery. Anesth Analg. 2003; 97(3):843-847.
ketamine during routine and emergency surgeries.27 This low rate of 16. Bowers KJ, McAllister KB, Ray M, Heitz C. Ketamine as an adjunct to opioids
complications was often in the setting of variable practitioner skill for acute pain in the emergency department: a randomized controlled trial.
Acad Emerg Med. 2017; 24(6):676-685.
and monitoring, suggesting that the safety margin of using ketamine
17. Gorlin AW, Rosenfeld DM, Ramakrishna H. Intravenous sub-anesthetic ketamine
in these situations is high.
for perioperative analgesia. J Anaesthesiol Clin Pharmacol. 2016;32(2):160-167.
Additional examples showing the varied uses of ketamine including 18. McNicol ED, Schumann R, Haroutounian S. A systematic review and meta
use in LMICs can be found in the ATOW 27 by Craven and analysis of ketamine for the prevention of persistent post-surgical pain. Acta
Anaesthesiol Scand. 2014; 58(10):1199-213.
Alkhafaji.28
19. Goyal S, Agrawal A. Ketamine in status asthmaticus: a review. Ind J Critl Care
Med. 2013;17(3):154-161.
REFERENCES
20. Hamimy W, Abdelaal A. The application of a new regimen for short term
1. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in sedation in ICU (ketofol)—case series. Egypt J Anaesth. 2012; 28(3):179-182.
anesthesia, pain and critical care. Anesth Essays Res. 2014; 8(3):283-290.
21. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid
2. Ori C, Freo U, Merico A, et al. Effects of ketamine-enantiomers anesthesia on sequence intubation in acutely ill patients: a multicentre randomised
local glucose utilization in the rat. Anesthesiology. 1999; 91(3A)A772. controlled trial. Lancet. 2009; 374(9686):293-300.
3. Kawasaki T, Ogata M, Kawasaki C, et al. Ketamine suppresses pro-inflammatory 22. Yoon SH. Concerns of the anesthesiologist: anesthetic induction in severe
cytokine production in human whole blood in vitro. Anesth Analg. sepsis or septic shock patients. Korean J Anesthesiol. 2012; 63(1):3-10.
1999; 89(3):665-669.
23. Bar JG, Guilburd Y, Guilburd J. Ketamine effectively prevents intracranial pressure
4. Marland S, Ellerton J. Ketamine: use in anesthesia. Review. CNS Neurosci Ther. elevation during endotracheal suctioning and other distressing interventions
2013; 19(6):381-389. in patients with severe traumatic brain injury. Crit Care Med. 2009; 37(12):A402.
5. Luft AN, Mendes FF. Low S(þ) ketamine doses: a review. Rev. Bras. Anestesiol. 24. Zeiler FA, Teitelbaum J, West M, et al. The ketamine effect on ICP in traumatic
2005; 55 (4):460-469. brain injury. Neurocrit Care. 2014;21(1):163-173.
6. Best W, Bodenschatz C, Beran D. World Health Organisation Critical Review of 25. Joint Formulary Committee. British National Formulary. http://www
Ketamine. 36th WHO Expert Committee on Drug Dependence report, 6.2. medicinescomplete.com. Accessed October 26, 2017.
Geneva, Switzerland: World Health Organisation. 2014.
26. Dong TT, Mellin-Olsen J, Gelb AW. Ketamine: a growing global health-care
7. Dolansky G, Shah A, Mosdossy G, Rieder M. What is the evidence for the safety need. Br J Anaesth. 2015; 115(4):491-493.
and efficacy of using ketamine in children? Paediatr Child Health.
2008; 13(4):307-308. 27. Green SM, Clem, KJ, Rothrock SG. Ketamine safety profile in the developing
world. Acad Emerg Med. 1996; 3(6):598-604.
8. Pai A, Heining M. Ketamine. Cont Educ Anesth Crit Care Pain: CEACCP
2007; 7(2):59-63. 28. Craven R, Alkhafaji R. Ketamine in Anaesthetic Practice, ATOTW 27. World
Anaesthesia Tutorial of the week. 2006.
9. Heinz P, Geelhoed GC, Wee C, Pascoe EM. Is atropine needed with ketamine
sedation? A prospective, randomised, double blind study. Emerg Med J: EMJ. 29. Poonai N, Canton K, Ali S, et al. Intranasal ketamine for procedural sedation and
2006; 23(3):206-209. analgesia in children: A systematic review. Ma Z-L, ed. PLoS ONE. 2017;12(3)
10. Green SM, Roback MG, Kennedy RM et al. Clinical practice guideline for
emergency department ketamine dissociative sedation: 2011 update. Ann
Emerg Med. 2011; 57(5):449-461.
Complications Associated with Intraoperative use of
Clinical Article
Irrigation Fluid for Endoscopic Procedures
Dr Gerund Yik-Nang Cheung, Dr Samuel Tempany and

Dr Mandy Hiu Man Chu*
Summary
With greater understanding of the complications of irrigation fluids and the correlated pathophysiology,
anaesthesiologists should be better able to stratify risk and improve the quality of perioperative care.
Irrigation fluid–associated complications, including TURP syndrome, may present subtly, necessitating a low
threshold to initiate focused physical examination and investigations. Supportive treatment is the mainstay of
initial intervention.
Key words:
• A range of fluids are used to improve surgical visibility during endoscopic procedures; examples include
saline, glycine, mannitol, and sorbitol solutions.
• Systemic absorption of irrigation fluid can produce a range of electrolyte, cardiovascular, neurological, and
other manifestations, depending on fluid type and volume absorbed.
• Rate of fluid absorption is dependent on the pressure gradient between irrigation fluid and blood vessels in
the operative field, as well as duration and extent of vascular exposure.
• Transurethral resection of the prostate (TURP) syndrome is associated with hypotonic fluid absorption during
TURP and other procedures, causing visual disturbance, headache, nausea, and vomiting, and in severe cases,
hyponatraemia, pulmonary oedema, seizures, and coma.
• Measures to reduce the risk of TURP syndrome include monitoring of fluid balance and electrolytes, limiting
surgical resection time, and limiting irrigation fluid infusion pressure.
• Management of TURP syndrome is supportive and can include airway support, oxygen, and ventilation,
vasopressors, and in severe cases, diuretics, hypertonic saline, and intensive care unit admission. Dr Gerund Yik-Nang
Cheung
INTRODUCTION IDEAL IRRIGATION FLUID Resident Anesthesiologist
Pamela Youde Nethersole
With the ever-increasing prevalence of minimally An ideal irrigation fluid should provide a practical and Eastern Hospital
invasive surgical techniques come heightened risks reliable surgical field and cater to the physiological Hong Kong SAR
specific to these approaches. While some laparoscopic needs of the patient. It should be1 CHINA
surgeries use humidified carbon dioxide for
• transparent,
insufflation, other procedures such as transurethral Dr Samuel Tempany
resection of the prostate (TURP), transurethral • electrically nonconductive for minimal dispersion Anaesthetic Registrar
resection of bladder tumour, transcervical resection of of diathermy current, Frankston Hospital
endometrium, endometrial ablation, and arthroscopy Victoria
• isotonic and nontoxic to avoid haemolysis and AUSTRALIA
rely on fluids as primary agents for irrigation and
organ impairment through fluid or electrolyte
maintenance of surgical visual field.
shift, and Dr Mandy Hiu Man Chu
In the interest of perioperative safety, complications Associate Consultant,
• simple and inexpensive to produce and sterilise. Pamela Youde Nethersole
should be anticipated where possible. Understanding
the properties and potential risks associated with At this time such an ideal solution has not been Eastern Hospital
identified. Hong Kong SAR
specific surgical irrigation fluids is the key to guiding
CHINA
management of these complications.
COMMON IRRIGATION FLUIDS fluid extravasation, including abdominal compartment syndrome,
There are several types of irrigation fluid used commonly in clinical has been reported after hip arthroscopy.16
practice. This article will discuss the pharmacology and osmolality Significant uptake of irrigation fluid results in rapid expansion of the
of several commonly used irrigation solutions2 (see Tables 1 and 2). intravascular volume leading to fluid overload, as well as dilutional
hyponatraemia. This rapidly developing hyponatraemia, if severe
CHOICES OF IRRIGATION FLUIDS enough to cause significant osmotic shift, provokes a net fluid shift
Electrolyte-free hypotonic solutions such as glycine, mannitol, and away from the intravascular compartment in the brain, resulting in
sorbitol solutions are used as distending media to enable monopolar cerebral oedema and raised intracranial pressure. Where glycine is
electrical systems to be used for coagulation and tissue resection. used, hepatic metabolism may result in significantly elevated serum
However, with the low viscosities, these irrigation fluids bear ammonia, which may contribute to neurological deficits in affected
potential risks of rapid fluid absorption resulting in fluid overload, patients. It may also provoke seizures by potentiating glutamate
dilutional hyponatremia, and subsequent side effects. Nowadays, activity at the N-methyl D-aspartate receptor, and directly depress
with the advancement in technology, bipolar electrical systems can the myocardium.
be used in new operative arthroscopic and hysteroscopic equipment.
The presentation of TURP syndrome varies, with symptoms
This enables electrolyte-containing isotonic solutions, for example,
developing any time from 15 minutes to 24 hours after the
normal saline and lactated Ringer solution, to be used as irrigation
operation.10 Symptoms include headache, burning sensation in the
media. This reduces complications of electrolytes disturbance by
face and hands, restlessness, and tachypnea. Visual disturbances, such
irrigation fluids. However, the risks of fluid overload or surrounding
as blurred vision and transient blindness, can occur. If left untreated,
tissue oedema remain.
patients can deteriorate with features of nausea and vomiting,
respiratory distress, pulmonary oedema, confusion, convulsions, and
MECHANISM OF IRRIGATION FLUID ABSORPTION
coma.1 Hypothermia is another important factor to consider in cases
Rate of fluid absorption is driven primarily by the gradient between of suspected TURP syndrome, given the systemic absorption of large
irrigation pressure and venous pressure (or the pressure of the volumes of physiologically hypothermic solutions.17
operating cavity). In general, irrigation fluid is absorbed at a rate
of 10 to 30mL per minute during procedures.10 Peripheral venous The treatment of TURP syndrome is largely supportive, with
pressure is approximately 1.5kPa and intra-abdominal pressure is early recognition of the developing syndrome being critical to
0.5kPa (1kPa ¼ 7.5mmHg). Volume of irrigation fluid absorbed into best outcomes. Supplemental oxygen should be provided, with
the circulation increases with time spent with a pressure gradient in application of positive-pressure ventilation if required for pulmonary
excess of 2kPa (15mmHg),11 and a gradient of 4kPa (30mmHg) has oedema. Blood pressure monitoring should be made available via an
been identified as a threshold for massive absorption.12 Intravenous arterial line and inotropes or vasopressors administered if needed.
infusion of irrigation solutions has been shown to induce tissue Affected patients should be warmed if hypothermic and may require
oedema. Changes in serum osmolality may reflect this tissue oedema, antiemetics for nausea and vomiting, or benzodiazepines for seizures.
but only when mannitol is used; glycine and sorbitol enter cells and Serum sodium should be corrected slowly and monitored closely.
water will follow so that when these solutions are used, tissue oedema Concurrent diuresis might have an impact on the rate of sodium
will be greater than suggested by the serum osmolality. correction and should be done with caution. A 4 to 6mmol/L increase
in serum sodium concentration is adequate in the most seriously ill
Smoking is an important patient factor known to be associated
patients in a 24-hour period.18 Hypertonic saline (3%) is indicated
with large-scale fluid absorption during TURP.13 Fluid absorption
when there is severe hyponatremia (some authors1 have suggested,
increases with resection extent and longer operation time. The
120mmol/L). Diuretics are usually only used when acute pulmonary
exposure of venous sinuses in the prostate provides ready access of
oedema is prominent because both mannitol and furosemide can
irrigation fluid to the circulation, putting these patients at particular
cause sodium loss and worsening hyponatraemia.
risk. During transcervical resection of the endometrium, fluid
absorption is greater if resection of fibroids is performed. Irrigation Similar presentations can be seen in other procedures utilising
fluid can be absorbed directly across intact endometrium, as well as irrigation fluid, such as transcervical resection of the endometrium.2
being extravasated via the Fallopian tubes,14 but prior sterilisation
In the event of any serious complication, the anaesthesiologist should
does not enhance absorption.
ensure clear documentation of the incident and treatment responses.
The anaesthesiologist should take part in further discussion with the
IRRIGATION FLUID COMPLICATIONS
surgeon on the risk factors involved and should advise on future
Complications of endoscopic procedures with irrigation are widely management during endoscopic surgery. Clear communication with
varied and relatively frequent, occurring in around 21% of cases.15 the patient and relatives regarding the event is important.
Absorption of irrigating fluids can result in fluid overload. Fluid
extravasation into the surrounding tissues can create loco-regional MEASURES TO MINIMISE COMPLICATIONS
and systemic mass effects. For example, in shoulder arthroscopic
Minimising negative outcomes relies on limiting the absorption rate
surgery, chest wall and neck swelling may lead to airway oedema
of irrigation fluid, recognising complications early, and providing
and respiratory compromise requiring intubation, percutaneous
prompt resuscitation.
drainage of fluid, diuresis, and the use of steroids. Intra-abdominal
Table 1. Pharmacology of Common Irrigation Solutions Abbreviations: T1/2, half-life; T1/2 dist, distribution half-life; T1/2 elim, terminal half-life; CNS, central
nervous system; NMDA, N-methyl D-aspartate; TURP, transurethral resection of the prostate; TCRE, transcervical resection of endometrium
Solution: Pharmacokinetics Pharmacodynamics

Indications for Use
Normal saline: • T1/2 ¼ 110 minutes3 • It contains more chloride than extracellular fluid. Sodium
arthroscopy, transurethral remains extracellular because of the sodium pump. Rapid
• Iso-osmotic with the extracellular fluid
procedures infusion of large amount of normal saline could cause
• Distributed 25% intravascularly and 75% hyperchloraemic acidosis.4
in interstitial fluid
Lactated Ringer solution: • T1/2 ¼ 50 minutes • Hydrogen ions are consumed and a relative excess of
arthroscopy bicarbonate ions is produced reducing acidosis in a
• Hepatic metabolism of lactate by
controlled fashion.
gluconeogenesis (70%)
• Some critically ill patients may develop alkalosis and
hypokalaemia due to failure to excrete excess bicarbonate
from lactate metabolism.5
Glycine 1.5%: • T1/2 dist ¼ 6 minutes (dose-dependent • Glycine is the second most widespread amino acid in
TURP or TCRE due to intracellular accumulation) human enzymes and proteins. It is an important inhibitory
neurotransmitter in the CNS and retina.
• Limited penetration into the CNS
• Glycine toxicity may cause prickling sensations, facial
• T1/2 elim 40 minutes to several hours
warmth, headache, nausea, malaise, and retinal
• Hepatic metabolism to ammonia dysfunction including transient blindness.6
• 5%–10% of an infused load is excreted • Glycine may directly provoke myocardial depression.
unchanged by kidneys
• Glycine potentiates the NMDA receptor, which may
precipitate convulsions and encephalopathy.
• High serum ammonia levels may result in
neurological disturbance.
• Glycine protects against kidney injury induced by a brief
period of ischemia in laboratory animals, but it does not
attenuate severe renal damage caused by longer periods
of ischemia.7
Mannitol 3%: • T1/2 dist ¼ 10 minutes; spread throughout • Mannitol rapidly expands intravascular volume and can
TURP or other transurethral extracellular space potentially lead to fluid overload, pulmonary oe-dema, and
procedures cardiac failure in susceptible patients.
• T1/2 elim approximately 100 minutes
• Elevated plasma concentration can be associated with
• Renal excretion which promotes
bradycardia and hypotension.
osmotic diuresis (prolonged T1/2 in
patients with renal impairment) • Some studies found few symptoms after absorption of
mannitol 5%; this is possibly due to the isotonic nature of
the more concentrated solution.8
• Allergic reactions to mannitol are rare.
Sorbitol 3.5%: • T1/2 dist 6 minutes • Unabsorbed ingested sorbitol can provoke diuretic and
urologic irrigation fluid laxative effects.
• T1/2 elim 33 minutes
• Excessive intravenous administration may cause
• Hepatic metabolism to fructose and
hyperglycaemia, or potentially lactic acidosis from its
lactate
metabolite fructose.
• 5%–10% of an infused load undergoes
• Paradoxically, hypoglycaemia can develop in young
renal excretion
patients with fructose-1,6-diphosphatase deficiency.9
Sorbitol infusion has led to death in patients with fructose
intolerance due to aldolase B enzyme insufficiency.
Table 2. Physical Properties of Common Irrigation Solutions aTonicity: the measure of the osmotic pressure gradient between two solutions, only
influenced by solutes that cannot cross the semipermeable membrane. bOsmolality: the measure of solute concentration per unit mass of solvent.
Solution Concentration (%) Tonicitya Osmolalityb

Saline 0.9 Isotonic 308
Saline 3 Hypertonic 900
Lactated Ringer - Isotonic 273
Glycine 1.5 Hypotonic 220
Mannitol 3 Hypotonic 179
Mannitol 5 Isotonic 298
Sorbitol 3.5 Hypotonic 165
General principles include the following:

• Ensuring adequate fluid status and using vasopressors such • Monitoring of perioperative fluid balance is of paramount
as phenylephrine to maintain venous pressure. Low venous importance. Vigilance for early signs of mass effect and fluid
pressure enhances irrigation fluid absorption. overload should reduce perioperative morbidity.
• Reducing operative duration where possible, preferably limiting • Using meticulous surgical techniques to avoid fluid extravasation
it to less than 1 hour. and visceral perforation and minimise blood loss.
• Delivering irrigation fluid at the lowest required pressure, and Traditionally, spinal anaesthesia was thought to be beneficial
warming where possible. Using warmed irrigation fluid does not compared to general anaesthesia, though little evidence supports any
increase blood loss by regional vasodilation. significant difference in outcomes between the two techniques.
CASE SCENARIO
A 54-year-old man with carcinoma of the bladder was scheduled for a transurethral resection of a bladder tumour. He was obese and had a
history of a prior stroke. His baseline serum sodium was 137mmol/L. He was very anxious about the procedure and refused a neuraxial block. The
surgery therefore proceeded under general anaesthesia. The operation duration was 75 minutes. This was partly due to the extensive bladder
infiltration by carcinoma which required more traumatic resection. Glycine 1.5% solution was used as irrigation fluid. A net irrigation fluid balance of
þ1.6 L was noted, though intraoperative irrigation pressure was not documented. Minimal blood loss was reported, and the surgery was considered
uneventful by the surgeons. Only 500mL of intravenous 0.9% saline was given intraoperatively. Reversal of neuromuscular blockade was given
when a train-of-four count of 3/4 was achieved. Restlessness and respiratory distress were noted shortly after extubation.
The patient was postured upright in a sitting position and was found to be
responsive to supplemental oxygen. His oxygen saturation reached 88% to
92% with oxygen delivered at 8L/min via Hudson mask, and increased to 95%
with 100% oxygen via a non-rebreather mask. Wheeze was noted throughout
his left chest and ABG showed type 1 respiratory failure with mild metabolic
acidosis (Table 3).
The patient was treated with inhaled salbutamol and 10 mg of intravenous
furosemide. His oxygen requirements diminished, saturating at 95% on 6L/min
and he was transferred to the intensive care unit for ongoing management
without need for reintubation.
A chest x-ray was ordered and showed obscured bilateral lower lung fields
consistent with pulmonary oedema (Figure 1). Postoperative blood results
showed serum sodium 128mmol/L, potassium 3.5mmol/L, and haemoglobin
85g/L. He was put on fluid restriction in the intensive care unit, with
maintenance of 0.9% NaCl titrated to serum sodium level.
Table 3. ABG Results
1. pH 7.35
2. Base excess -3mmol/L
3. Bicarbonate 22.4mEq/L
4. pO2 48mmHg, SaO2 82%
5. pCO2 40.6mmHg
REFERENCES
In this scenario, the patient developed hyponatremia with
1. O’Donnell AM, Foo ITH. Anaesthesia for transurethral resection of the prostate.
pulmonary oedema after transurethral resection of a bladder Contin Educ Anaesth Crit Care Pain. 2009; 9:92-96.
tumour. There were several risk factors identified for fluid overload.
2. Hahn RG. Fluid absorption in endoscopic surgery. Br J Anaesth. 2006; 96:8-20.
The operation lasted more than 60 minutes. The prolonged
operation increased this patient’s exposure to continuous irrigation 3. Hahn RG, Lyons G. The half-life of infusion fluids: an educational review. Eur J
Anaesthesiol. 2016; 33:475-482.
with associated increased fluid absorption. Additionally, the
4. Schafer M, Von Ungern-Sternberg BS, Wight E, Schneider MC. Isotonic fluid
unanticipated extent of the surgical insult may have exposed more
absorption during hysteroscopy resulting in severe hyperchloremic acidosis.
blood vessels for circulatory absorption. Failure to recognize the Anesthesiology. 2005; 103:203-204.
pathology may have led to further deterioration with seizures and 5. White SA, Goldhill DR. Is Hartmann’s the solution? Anaesthesia. 1997; 52:422
shock. 427.
Early recognition of the extent of the bladder tumour may 6. Creel DJ, Wang JM, Wong KC. Transient blindness associated with transurethral
have prompted more meticulous monitoring and heightened resection of the prostate. Arch Ophthalmol. 1987;105:1537-1539.
communication with the surgeon around the recognised risk. 7. Yin M, Zhong Z, Connor HD, et al. Protective effect of glycine on renal injury
induced by ischemia-reperfusion in vivo. Am J Physiol Renal Physiol.
This may have prompted the team to take extra precaution by
2002; 282:417-423.
minimising irrigation pressures and surgical trauma. In this case,
8. Allgen LG, Norlen H, Kolmert T, et al. Absorption and elimination of mannitol
the choice between a general or regional technique was complicated solution when used as an isotonic irrigating agent in connection with
by a history of anxiety. The use of regional anaesthesia may have transurethral resection of the prostate. Scand J Urol Nephrol. 1987; 21:177-184.
allowed earlier detection of hyponatremia and pulmonary oedema 9. Schulte MJ, Lenz W. Fatal sorbitol infusion in patient with fructose-sorbitol
through clinical signs such as change in conscious level and intolerance. Lancet. 1977; 2:188.
difficulty in breathing. Where general anaesthesia is unavoidable, 10. Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a
intraoperative vigilance should be employed, observing for review of the pathophysiology and management. Anesth Analg. 1997; 84:438
increase in airway pressure or oxygen requirement. Point-of-care 446.
monitoring including ABG and electrolytes may assist in providing 11. Hahn RG. Intravesical pressure during irrigating fluid absorption in transurethral
an early and more complete picture of the patient’s physiological resection of the prostate. Scand J Urol Nephrol. 2000; 34:102-108.
state. 12. Madsen PO, Naber KG. The importance of the pressure in the prostatic fossa
and absorption of irrigating fluid during transurethral resection of the prostate.
Spinal anaesthesia offers advantages in monitoring and postoperative J Urol. 1973; 109:446-452.
analgesia. The ability to detect early signs of TURP syndrome makes 13. Hahn RG. Smoking increases the risk of large-scale fluid absorption during
transurethral prostatic resection. J Urol. 2001; 166:162-165.
spinal anaesthesia the technique of choice for many anaesthesiologists.
14. Olsson J, Berglund L, Hahn RG. Irrigating fluid absorption from the intact uterus.
Laser techniques for TURP are gaining popularity. The reduced Br J Obstet Gynaecol. 1996; 103:558-561.
risk of bleeding and the use of saline as irrigation fluid, make this a 15. Silva JM Jr, Barros MA, Chahda MA, et al. Risk factors for perioperative
favourable technique, particularly for elderly or debilitated patients. A complications in endoscopic surgery with irrigation. Braz J Anesthesiol.
review of monopolar versus bipolar TURP has shown bipolar TURP 2013; 63:327-333.
offers some advantages over monopolar TURP, including reduced 16. Kocher MS, Frank JS, Nasreddine AY, et al. Intra-abdominal fluid extravasation
incidence of TURP syndrome related to avoidance of hypotonic during hip arthroscopy: a survey of the MAHORN group. Arthroscopy.
2012; 28:1654-1660.e2.
irrigation solutions.19
17. Jin Y, Tian J, Sun M, et al. A systematic review of randomised controlled trials of
Patients’ blood pressure, oxygen saturation, and electrocardiograms the effects of warmed irrigation fluid on core body temperature during
should be monitored in the standard way. When alert, patients’ endoscopic surgeries. J Clin Nurs. 2011; 20:305-316.
complaints and changes in mental status may be the first signs of 18. Sterns RH, Hix JK, Silver S. Treatment of hyponatremia. Curr Opin Nephrol
early electrolyte imbalance. Information on patients’ vital signs, Hypertens. 2010; 19:493-498.
input and output of irrigation fluid, blood loss, and investigation 19. Tang Y, Li J, Pu C, et al. Bipolar transurethral resection versus monopolar
results (blood glucose, electrolytes, haemoglobin, arterial blood gases transurethral resection for benign prostatic hypertrophy: a systematic review
and meta-analysis. J Endourol. 2014; 28:1107-1114.
[ABG], and ammonia) should be collected and analysed if clinical
concern of evolving TURP syndrome develops. Exhaled or serum 20. Hahn RG, Larsson H, Ribbe T. Continuous monitoring of irrigating fluid
absorption during transurethral surgery. Anaesthesia. 1995; 50:327-331.
ethanol concentration can also be measured as an index of fluid
absorption in cases in which ethanol has been added to the irrigation
fluid.20 Upon suspicion of deterioration, supportive treatment should
be commenced, and potential causes investigated.
Posterior Reversible Encephalopathy
Syndrome (PRES)
Case Report
Wael Hassan
WFSA-D-18-00026
DEFINITION
Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological syndrome of heterogeneous
etiologies that are grouped together because of similar findings on neuro-imaging studies.
It was first described by Hinchey et al. in 1996 based on 15 cases1
This condition has been known by various names previously (reversible posterior leukoencephalopathy syndrome,
reversible posterior cerebral edema syndrome and reversible occipital parietal encephalopathy). PRES is now the
widely accepted term.2
This clinical syndrome is increasingly recognized commonly because of improvement and availability of brain
imaging.
Pathophysiology
There are two main hypotheses; one involves impaired brain stem, occipital, parietal, frontal and
cerebral autoregulation responsible for an increase in temporal lobes.
cerebral blood flow (CBF), whereas the other involves 2. Superior frontal sulcus pattern; showing bilateral
endothelial dysfunction with cerebral hypoperfusion. vasogenic edema in a non-confluent patterns
Under both hypotheses, the result of the cerebral involving the frontal sulcus area and, to a lesser
blood perfusion abnormalities is blood brain barrier degree, the white matter of the parietal, occipital,
dysfunction with cerebral vasogenic edema.2 and temporal lobes.
3. Dominant parietal-occipital pattern ‘the classic
Clinical findings
pattern’; showing bilateral vasogenic edema in the
It presents with rapid onset of symptoms including white matter of the occipital and parietal lobes.
headache, seizures, altered consciousness, and
4. Partial and/or asymmetric expression of the three
visual disturbance. It is often associated with acute
primary patterns.
hypertension.
PRES is most commonly occuring with preeclampsia, Differential Diagnosis
eclampsia, hypertensive crisis, sepsis, autoimmune The non-specific clinical manifestations and
disease, cytotoxic chemotherapy, and transplantation.3 multiplicity of radiological patterns raise diagnostic
challenges. Many conditions may resemble PRES
Radiological findings including;2
PRES has become synonymous with a unique pattern 1. Ictal or post-ictal state (with or without status
of brain vasogenic edema seen on CT or MR brain epilepticus),
imaging studies. It was believed to consistently produce
2. Progressive multifocal leukoencephalopathy
bilateral and symmetric regions of edema typically
(PML),
located in the white matter and predominating in
the posterior parietal and occipital lobes4, hence the 3. Severe leukoaraiosis,
name. Recently, it was found to present in a variety of 4. Cerebral autosomal dominant arteriopathy with
radiological patterns;2 subcortical infarcts,
Wael Hassan edaic, fcai 1. Holohemispheric watershed pattern; showing 5. Infectious encephalitis,
Sligo University Hospital bilateral vasogenic edema in a linear pattern
6. Acute disseminated encephalomyelitis,
Sligo involving the white matter of the cerebellum,
IRELAND
7. Mitochondrial myopathy encephalopathy lactacidosis and Discussion
stroke-like episodes syndrome (MELAS), Posterior reversible encephalopathy syndrome (PRES) diagnosis
8. Vasculitis, basically depends on specific radiological features and clinical
findings. The exact pathophysiological mechanism of the syndrome
9. Creutzfeld-Jakob disease,
is still not fully understood but it may be explained by disruption
10. Cerebral venous sinus thrombosis, of endothelial blood - brain barrier which leads to fluid and protein
11. Ischemic stroke (watershed or posterior cerebral artery territory). transudation in the brain.
High level of suspicion and early management are the key elements
Prognosis of recovery.
If promptly recognized and treated, the clinical syndrome usually Although our case did not suffer of pregnancy related hypertension
resolves within a week, and the changes seen in magnetic resonance or preeclampsia during her pregnancy, hypertension was discovered
imaging (MRI) resolve over days to weeks. Patient usually recovers on the 10th day post-delivery after her second presentation to A&E.
but permanent disability is possible.5 This raises the concern of following up parturients post-delivery for
the possible development of new onset preeclampsia. It is worth
Case Report mentioning that preeclampsia can present as late as 4 to 6 weeks
A 34-year-old female presented to the emergency department 5 postpartum according to American College of Obstetricians and
days after uneventful normal delivery complaining of neck pain and
Gynecologists guidelines.6
headache. The patient did not receive epidural analgesia for her PRES can be one of the complications that could result from
delivery. She has no medical or surgical history of significance. untreated preeclampsia. Better outcome can be attained by early
diagnosis and prompted treatment.
Blood investigations revealed raised WCC (12.7/uL), CRP (51.9mg/L)
and D-dimer (19.8ug/ml). She had been discharged home after 2 CONCLUSION
days as all investigations including CSF analysis, CTPA and MRI brain
PRES should be considered in patients who present with seizures,
appeared to be normal. altered consciousness, visual disturbance, or headache, particularly
3 days later, she was brought again to emergency department in the context of acute hypertension. It should not be missed as one
with 2 episodes of tonic clonic convulsions and hypertension with of differential diagnoses of postpartum headache and convulsions.
Fortunately, if it is promptly recognized and treated, the clinical
protein in urine of +1. MRI was done showing multifocal vasogenic
syndrome usually resolves within a week.
edema in the subcortical white matter consistent with posterior
reversible encephalopathy syndrome (PRES). REFERENCES
The patient symptoms had improved over 3 days of receiving 1. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible
posterior leukoencephalopathy syndrome. New Engl J Med 1996; 334:494-500.
treatment in the intensive care unit with anticonvulsants and
2. Legriel S.,Pico F.,Azoulay E. Understanding Posterior Reversible Encephalopathy
antihypertensives. She was then transferred to the normal Syndrome. Annual update in intensive care and emergency medicine 2011;
ward where she repeated MRI brain which revealed significant 631-53.
improvement of radiological picture. 3. Sudulagunta SR, Sodalagunta MB, Kumbhat M, Nataraju AS. Posterior Reversible
Encephalopathy Syndrome. Oxford Medical Case Reports 2017; 4: 43-46.
4. Bartynski WS. Posterior Reversible Encephalopathy Syndrome, Part 1:
Management Fundamental Imaging and Clinical Features. AJNR Am J Neuroradiol 2008;
Management of the syndrome is focused on the treatment of the 29:1036-42.
underlying condition (e.g. eclampsia) and supportive treatment such 5. Hobson EV, Craven I, Blank SC. Posterior reversible encephalopathy syndrome:
as anticonvulsive agents. a truly treatable neurologic illness. Peritoneal Dialysis International 2012;
32:590-594.
6. [Guideline] American College of Obstetricians and Gynecologists, Report of\
the American College of Obstetricians and Gynecologists Task Force on
Hypertension in pregnancy. Obstet. Gynecol 2013
Nov. 122 (5):1122-31.
OxyContin: A Tale of Advertisement and Addiction
Amy Jiang, MD
WFSA-D-20-00003
Letter
Summary
Purdue Pharma is under scrutiny for its role in North America’s opioid crisis with its widely marketed narcotic
OxyContin. Released in 1995, the same year as the American Pain Society announced their Pain is the Fifth Vital
Sign campaign, OxyContin quickly became a blockbuster drug through aggressive advertisement. Purdue Pharma
sponsored tens of thousands of pain management education programs, funded influential organizations, and
marketed directly to physicians. They publicized research that downplayed the risk of addiction, suppressed early
reports of drug abuse, and led physicians to believe that iatrogenic narcotic addiction was rare. By 2004, OxyContin
had become the most prevalent prescription opioid abused in the USA.
Purdue Pharma has since acknowledged misleading regulators, doctors and patients about OxyContin’s risk of
addiction and abuse. The company recently filed for bankruptcy, as thousands of jurisdictions are now seeking to
recover costs associated with the opioid crisis. This story demonstrates how vulnerable physicians are to marketing
and misinformation, and the importance of critical appraisal when new drugs, technologies, and practice patterns
are introduced to our practice.
Key Words
Opioid epidemic, oxycodone, opioid-related disorders, analgesia, advertising
Purdue Pharma is widely scrutinized for its role in announced pain management standards emphasizing
North America’s opioid crisis. How its blockbuster the use of quantitative pain assessments. Physicians
opioid OxyContin came to generate over $31 billion to prescribe more opioids. After implementation of
in revenue is a story of how physicians, the public, a mandatory pain score in the Mayo Clinic Hospital
and medical institutions are vulnerable to marketing PACU, opioid use increased on average from 6.5 to
and misinformation. 10.5mg of morphine equivalents.2 Purdue Pharma’s
revenues soared.
In the 19th century, opioids were in vogue for ailments
including pain, insomnia, diarrhea, and cough. The Purdue Pharma funded over 20,000 pain-related
early 20th century saw advances in public health and educational programs between 1996 and 2002. They
the invention of nonopioid analgesics. Iatrogenic provided financial support to influential organizations
opioid dependence became a concern in the 1920s; including the American Pain Society and the Joint
opioid overprescribing was considered a hallmark of Commission. OxyContin was extensively marketed
the out of date physician.1 By the 1980s, clinicians directly to physicians. Purdue advertised in medical
Amy Jiang, MD began to question whether their pain management was journals, sponsored pain websites, and recruited
Queen’s University adequate. Purdue released OxyContin, a long acting specialists to spread word about an epidemic of
Department of Anesthesia oxycodone, in 1995. In the same year, the American untreated chronic pain. They sent pharmaceutical
and Perioperative Medicine
Pain Society announced their Pain is the Fifth Vital representatives across the country to provide samples
Kingston Health Sciences
Centre Sign campaign, urging healthcare providers to take and distribute branded marketing products. From
Victory 2 pain as seriously as other vital signs. The Veteran’s 1997 to 2002, the annual number of OxyContin
76 Stuart Street Kingston Health Association, the largest healthcare system in prescriptions for cancer increased from 250,000
Ontario America, adopted the campaign in 1999. The Joint to over 1 million; prescriptions for noncancer pain
CANADA Commission, which accredits hospitals in the US, increased from 670,000 to 6.2 million.3
Purdue promoted OxyContin as less addictive and less prone to 2019, a tentative agreement was reached: Purdue Pharma would
abuse than other opioid medications due to its controlled release be dissolved; a publicly overseen company would sell OxyContin
mechanism. They promoted literature that downplayed the risk of and pay the plaintiffs with the profits. Purdue would donate drugs
addiction to opioids. A 1980 paper by Porter and Jick was heavily for addiction treatment and overdose reversal. The Sackler family
referenced.4 Only 5 sentences long, this study has been cited over would pay $3 billion over 7 years. The deal is estimated to be
600 times and has its own Wikipedia page.5 In 12,000 inpatients worth $10 to 12 billion.13 Purdue Pharma subsequently filed for
who received narcotics, “there were only four cases of reasonably bankruptcy; further negotiations are ongoing.
well documented addiction”. Their study used healthcare provider
The story of OxyContin provides insight into our medical culture
documentation to define addiction instead of applying diagnostic
and how easily influenced we are as healthcare practitioners. It
criteria, thereby underestimating its prevalence. The subjects
demonstrates the importance of critical appraisal when new drugs,
were inpatients who received as little as a single narcotic dose
technologies, and practice patterns are introduced in order to
administered by hospital personnel. In contrast, most patients
best serve our patients. Many patients are first exposed to opioids
using OxyContin self-medicated at home over long periods of
perioperatively; the incidence of new persistent opioid use after
time. Despite the lack of external validity, Purdue cited the risk of
surgery is 5.9 to 6.5%.14 It is the author’s hope that revisiting the
addiction as less than 1%. The original OxyContin package insert
story of OxyContin and Purdue Pharma will serve as a learning
stated that iatrogenic addiction to opioids legitimately used in the
opportunity for our community.
management of pain is “very rare”.6
A later investigation found that Purdue Pharma’s sales representatives REFERENCES
had written the words “street value,” “crush,” or “snort” in 117 1. Kolodny A, Courtwright DT, Hwang CS, Kreiner P, Eadie JL, Clark TW,
internal notes from visits to medical professionals from 1997 to Alexander GC. The prescription opioid and heroin crisis: a public health
approach to an epidemic of addiction. Annu Rev Public Health 2015; 36: 559
1999, suggesting they were aware of abuse as early as 1997.7 By 74.
early 2000, media reports of OxyContin abuse surfaced. Users
2. Stein C, Frasco PE, Sprung J, Trentman TL. The impact of the Joint Commission
evaded the controlled release mechanism by crushing the tablets for Accreditation of Healthcare Organizations pain initiative on perioperative
and snorting or dissolving and injecting them. Purdue Pharma opiate consumption and recovery room length of stay. Anesth Analg 2005;
created a plan to combat abuse, but significant damage had already 100: 162-168.
been done. The Drug Enforcement Agency reported 146 deaths 3. Prescription drugs: OxyContin abuse and diversion and efforts to address
the problem. Washington, DC: General Accounting Office; December 2003.
nationally involving OxyContin in 2000 and 2001.3 By 2004,
Publication GAO-04-110.
OxyContin was the most prevalent prescription opioid abused in
4. Porter J, Jick, H. Addiction rare in patients treated with narcotics. N Engl J
the USA.6 In Canada, the addition of long-acting oxycodone to Med 1980; 302: 123.
provincial drug formularies was associated with a 5-fold increase in 5. Leung PTM, Macdonald EM, Stanbrook MB. A 1980 letter on the risk of opioid
oxycodone-related mortality between 1994 to 2004.8 addiction. N Engl J Med 2017; 376: 2194-2195.
In 2010, Purdue Pharma released a tamper resistant OxyContin. 6. Van Zee A. The promotion and marketing of OxyContin: commercial
triumph, public health tragedy. Am J Public Health 2009; 99: 221-227.
Abuse decreased by 48% in the three years following reformulation;
7. Meier B. Origins of an epidemic: Purdue Pharma knew its opioids were
overdose fatalities reported to the manufacturer decreased by 65%.9 widely abused. New York Times. 2018 May 29. Available at: https://www
However, reformulation may have had collateral damage. A survey nytimes.com/2018/05/29/health/purdue-opioids-oxycontin.html
of 10,000 patients with opioid use disorder found that heroin use 8. Dhalla IA, Mamdani MM, Sivilotti MLA, Kopp A, Qureshi O, Juurlink DN.
increased after reformulation; reformulation perhaps hastened Prescribing of opioid analgesics and related mortality before and after the
the transition from prescription opioid to heroin abuse.10 In introduction of long-acting oxycodone. CMAJ 2009; 181: 891-896.
Canada, long acting oxycodone was dropped from provincial drug 9. Coplan PM, Chilcoat HD, Butler SF, Sellers EM, Kadakia A, Harikrishnan
V, Haddox JD, Dart RC. The effect of an abuse-deterrent opioid formulation
formularies in 2012. The next year, Canada’s first fentanyl seizure (OxyContin) on opioid abuse-related outcomes in the postmarketing
occurred when police arrested two men shipping a microwave setting. Clin Pharmacol Ther 2016; 100: 275-286.
containing 10,000 fentanyl tablets. In 2017, there were almost 10. Cicero TJ, Ellis MS. Abuse-deterrent formulations and the prescription opioid
4,000 opioid related deaths in Canada; 72% involved fentanyl or abuse epidemic in the United States: lessons learned from OxyContin. JAMA
fentanyl analogues. One form of street fentanyl is put through a Psychiatry 2015; 72: 424-430.
pill press and dyed green to resemble 80mg OxyContin tablets.11 11. Craig S. Timeline of the opioid crisis in Canada. The Link Newspaper. 2019 Jan
8. Available at: https://thelinknewspaper.ca/article/timeline-of-the-opioid
Legal action against Purdue Pharma gathered momentum. In crisis-in-canada
2007, three Purdue executives and Purdue Frederick, a Purdue 12. Lovelace B. Nearly every US state is now suing OxyContin maker Purdue
Pharma holding company, pled guilty to criminal charges that they Pharma. CNBC. 2019 Jun 4. Available at: https://www.cnbc.com/2019/06/04
nearly-every-us-state-is-now-suing-oxycontin-maker-purdue-pharma.html
had misled regulators, doctors and patients about OxyContin’s
risk of addiction and abuse. Perdue Frederick paid $600 million 13. Hoffman J. Purdue Pharma tentatively settles thousands of opioid cases. New
York Times. 2019 Sept 11. Available at: https://www.nytimes
in fines; the executives paid $34.5 million.7 As of 2019, 48 of 50 com/2019/09/11/health/purdue-pharma-opioids-settlement.html
US states have sued Purdue Pharma.12 Municipalities, counties, 14. Brummet CM, Waljee JF, Goesling J. New persistent opioid use after minor
and first nations tribes have also filed lawsuits. Over 2600 lawsuits and major surgical procedures in US adults. JAMA Surgery 2017; 162:
against the company and their owners, the Sackler family, were e170504.
bundled into a giant civil case in federal court. In September
Sphenopalatine Ganglion Block: Management
of Post-dural Puncture Headache After Cesarean
Section
Ece Yamak Altınpulluk*, Nilgün Çolakoğlu and Lale Yüceyar

Letter

WFSA-D-19-00016
Abstract
The sphenopalatine ganglion is a parasympathetic ganglion and has been blocked for various types of headaches
and facial pain. We have reported a patient with severe post-dural puncture headache after cesarean section who
showed rapid symptomatic improvement after a single sphenopalatine ganglion block.
Dear Editor
The Sphenopalatine ganglion (SPG) is a parasympathetic ganglion. SPG block has been applied for various types
of headaches and facial pain.1-3 Here, we report a patient with severe post-dural puncture headache (PDPH) after
cesarean section who showed rapid symptomatic improvement after a single sphenopalatine ganglion block. The
written consent from the patient for this case report to be written up as well as for her photograph to be taken
has been obtained.
The patient was a 22 year-old pregnant woman (165 cm, 68kg) at 37 weeks’ gestation, who underwent
emergency cesarean delivery. She ate her last meal 15 minute prior to the surgery. Informed written consent was
obtained for spinal anesthesia. Spinal anesthesia was performed with a 25G Quincke spinal needle at the L3–L4
Ece Yamak Altınpulluk
interpace with heavy bupivacaine 0.5% 13mg.
Anaesthesiologist in
Istanbul University The patient complained of a severe headache on the first postoperative day. The visual analog scale (VAS) score
Cerrahpasa Medical Faculty was evaluated as 10/10 and aggravated by movement. After detailed examination a diagnosis of PDPH was made.
Research Fellow Outcomes
Movement was restricted and bed rest was prescribed. Paracetamol 1gram and 50 mg caffeine orally every 6
Research Department
Anesthesiology Institute hours was administered, as well as an intravenous infusion of 200mg theophylline were administered. Normal
Cleveland Clinic OH saline infusion was started at the rate of 2ml/kg/h. However, the next day the patient showed no improvement
USA of symptoms and was agitated. SPGB was suggested to the patient. After obtaining written consent, the patient
was made to lie in the supine position with her neck slightly extended. SPG block was performed by a trans-nasal
Nilgün Çolakoğlu, M.D.
approach. A total of 2 puffs of Lidocaine 10 % spray was applied through both nares with an applicator. (Figure1).
Department of
Anesthesiology and Approximately 5-10 minute after the trans-nasal injection the patient described significant relief of symptoms of
Reanimation her headache. The VAS score was evaluated as 0/10. The following day the patient was able to sit up and eat. The
Istanbul University patient remained in hospital for 4 days with no further complaint of headache.
Cerrahpasa Medical Faculty
Istanbul The sphenopalatine ganglion is located in the pterygopalatine fossa posterior to the middle turbinate. The tip
TURKEY of the applicator does not come into direct contact with ganglion, but the local anesthetic infiltrates around it.
The connective tissue and mucus membrane make topical application of local anesthetic effective. 4 After dural
Prof. Dr.Lale Yüceyar puncture cerebrospinal fluid is lost continuously. Compensatory vasodilation occurs and this vasodilatation causes
Department of a headache. If the parasympathetic activity is blocked with a SPG block uncontrolled vasodilation is prevented
Anesthesiology and
Reanimation, Istanbul and patients feel symptomatic relief. 5 Trans nasal SPG block is an effective technique for pain control in patients
University Cerrahpasa with PDPH and this technique appears to be a simple, generally safe method. It, however, needs further study and
Medical Faculty Istanbul investigation regarding its efficacy.
TURKEY
Figure 1. Position of applicator in the nare
REFERENCES
1. Channabasappa SM, Manjunath S, Bommalingappa B, Ramachandra S, 4. Yang lY, Oraee S. A novel approach to transnasal sphenopalatine ganglion
Banuprakash S. Transnasal sphenopalatine Ganglion block for treatment of injection. Pain Physician. 2006; 9: 131–4.
postural heaadache following spinal anesthesia. Saudi J Anaesth. 2017; 11: 5. Piagkou M, Demesticha T, Troupis T, Vlasis K, Skandalakis P, Makri A, et al. The
362-3 pterygopalatine ganglion and its role in various pain syndromes: From
2. Sanders M, Zuurmond WW. Efficacy of sphenopalatine ganglion blockade anatomy to clinical practice. Pain Pract. 2012; 12: 399–412.
in 66 patients suffering from cluster headache: A 12- to 70-month follow-up
evaluation. J Neurosurg. 1997; 87: 876–80.
3. Varghese BT, Koshy RC. Endoscopic transnasal neurolytic sphenopalatine
ganglion block for head and neck cancer pain. J Laryngol Otol. 2001; 115: 385
7.
Update in
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Chief with a proposed title and a brief (200 word) summary of the
scope and content. Manuscript Types
Manuscripts are screened by the editorial staff and are sent to As an official journal of the WFSA, UIA is the appropriate forum for
independent reviewers who are not informed of the identity of the publication of articles describing anaesthesia patient care, original
author(s). The reviewers’ comments and suggested revisions will be research and audit conducted in, and specifically relevant to, low and
forwarded to the corresponding author. Manuscripts will be reviewed middle income resource settings.
with plagiarism detection software. Manuscripts may not have been Manuscripts describing clinical care, research, procedures, techniques
published in whole or any part in another journal. or equipment adapted by anaesthetists to the limited resource setting
Some readers of UIA may not use English as their first language. It in which they care for patients are welcome in any of the following
is therefore important to keep text straightforward and to avoid long formats:
sentences and complex terminology. Explain words and abbreviations • Review article - Basic Science or Clinical (3000 words maximum)
that may not be universally standardised.
• Original Research (3000 words maximum)
Aim to include the full range of therapies available worldwide. • Case Report/Clinical Overview (1500 words maximum)
Provide detailed descriptions of therapies available in resource-
limited settings. When appropriate, discuss older medications, such • UIA Short Reports (750 words maximum)
as Halothane and Thiopentone that may still be used around the • Editorials (1200 words maximum) - Editorials are usually by
world. invitation of the Editor-in-Chief. Proposals for Editorials may be
sent to the Editor-in-Chief for consideration and potential
Authors must acknowledge any financial support received or conflict
invitation.
of interest related to the contents of a submitted manuscript.
• Review of Books or other Educational Materials (eg web app)
Contributions to the, 1) clinical care or research described in a
(750 words maximum)
manuscript or 2) preparation of a manuscript made by persons other
than the authors may be acknowledged.
• Letters to the Editor (1000 words maximum) - Correspondence Examples of the recommended format for references are noted
is welcome on any topic, article or editorial that has appeared in below and can be found at https://www.nlm.nih.gov/bsd/uniform_
UIA or is of interest to individuals providing anaesthesia patient requirements.html
care. 1. Reynolds F, O ‘Sullivan G. Lumbar puncture and headache. ‘Atraumatic
needle’ is a better term than ‘blunt needle’. Br Med J 1998; 316: 1018.
COMPONENTS OF THE MANUSCRIPT
2. Costigan SN, Sprigge JS. Dural puncture: the patients’ perspective.
Title page that includes: A patient survey of cases at a DGH maternity unit 1983–1993. Acta
• Title of the article Anaesthesiol Scand 1996; 40: 710–14.
• Name and affiliation of each author 3. Spriggs DA, Burn DJ, French J, Cartlidge NE, Bates D. Is bedrest useful
after diagnostic lumbar puncture? Postgrad Med J 1992; 68: 581–3.
• Email, postal address and telephone contact details of the
corresponding author References to textbooks should give book title, place of publication,
publisher and year; those of multiple authorship should also include
• Key words using terms from the Medical Subject Headings chapter title, first and last page numbers, and names and initials of
(MeSH) of Index Medicus https://www.nim.nih.gov/mesh editors. For example:
• Abstract that includes no more than 200 words 1. Roberts F. Chapter 22: Ear, nose and throat surgery. In: Allman KG,
For research manuscripts note Background, Methods, Results, and Wilson IH, eds. Oxford handbook of Anaesthesia (1st edition) Oxford:
Conclusions Oxford University Press, 2001: 506-39.
Unpublished manuscripts in preparation or submitted yet not
ILLUSTRATIONS / FIGURES accepted for publication and personal communications and
Tables, figures, graphs and illustrations should be submitted as unpublished observations should be referred to as such in the text.
electronic versions of drawings (black on white) or as black and
Articles accepted and not yet published should be included in the
white or color picture files in JPEG format. If computer or internet
references, with the abbreviated journal name, followed by ‘(in press).
access is unavailable, print versions may be submitted. If facilities to
produce drawings are unavailable, contact the Editor-in-Chief for MEDICATIONS
assistance. Text accompanying tables, figures, graphs and illustrations
should be supplied on a page separate from the image. Use international units, e.g. mg.kg -1 rather than mg/kg. Use SI
notation for g, mg, mcg etc. Use internationally accepted non-
Tables, figures, graphs and illustrations copied from other proprietary generic medication names, e.g. furosemide, epinephrine
publications must be accompanied by a statement that permission and avoid trade names.
for reproduction has been obtained from the publisher. A footnote
acknowledging permission to reproduce must accompany the copied Manuscripts should be submitted to:
table, figure, graph or illustration and the full reference of the original https://www.editorialmanager.com/wfsa/default.aspx
source included in the reference list.
UIA’s Editorial Team will be delighted to help with the preparation
If patients appear in an identifiable photo, a copy of their consent to of articles. Please contact the Editors-in-Chief for any assistance.
the use of their image must be submitted.
• Christina Lundgren
REFERENCES [email protected]
A minority of UIA readers have extensive access to journals. • Victoria Howell
References, therefore, should in general be limited to those that are [email protected]
considered ‘desirable supplemental reading’, and should not exceed If you are unable to upload your manuscript to the online submission
25 references. Number the references in the order they appear in the system, please email them directly to the editors.
text, using the reference number as a superscript at the relevant point
in the text. Alternatively manuscripts may be sent to:
Reference style should adhere to the format set forth in the Uniform World Federation of Societies of Anaesthesiologists (WFSA)
Requirements for Manuscripts Submitted to Biomedical Journals Dean Bradley House,
prepared by the International Committee of Medical Journal Editors 52 Horseferry Rd,
http://www.icmje.org London
SW1P 2AF
Abbreviations for journal titles should follow Index Medicus format England
https://www.ncbi.nlm.nih.gov/nlmcatalog/journals
Education for anaesthesia providers worldwide
Volume 35 February 2020
4 Editors Notes
Clinical Articles
5 Implementation of the WHO surgical safety 39 Case report: Intrathecal tranexamic

checklist in a West African teaching hospital: a acid during spinal anaesthesia for
quality improvement initiative caesarean delivery: a lethal drug error
A Matei* Mohammed Mouhajer, Harry Tontoh, D G Bishop, A C Lundgren, N F Moran,
Nelson Ampah, Elizabeth M. Quartson, I Popov and J Moodley
Ronald B. George, Heather Scott and Vernon H. Ross
43 Ketamine: recent evidence and
11 Postoperative pain management in Timor-Leste current uses
R.F Grace Dr Alistair Gales and Dr Stuart Maxwell
15 Comprehensive review of laryngospasm 49 Complications associated with

Catarina R. Silva, Teresa Pereira, Diana Henriques intraoperative use of irrigation fluid for
and Filipa Lanca endoscopic procedures
Dr Gerund Yik-Nang Cheung,
19 Perioperative myocardial ischaemia in Dr Samuel Tempany and
non-cardiac surgery Dr Mandy Hiu Man Chu
Dr Heather Short
54 Case report: Posterior Reversible
Encephalopathy Syndrome (PRES)
24 Saddle Block Wael Hassan
Marc Gentilli
56 Letter: OxyContin - a tale of advertisement

27 Erector spinae plane block and addiction
Araz Pourkashanian, Madan Narayanan, Ami Jiang
Arun Venkataraju
58 Letter: Sphenopalatine ganglion block

34 Tranexamic acid management of PDPH after caesarean
Dr Charlotte Earnshaw and Dr Melanie Poole section
Ece Yamak Altınpulluk, Nilgün Çolakoğlu
and Lale Yüceyar
Design and printing: Sumographics Ltd. e: [email protected]
Disclaimer
The WFSA takes all reasonable care to ensure that the information contained in Update is accurate.
We cannot be held responsible for any errors or omissions and take no responsibility for the consequences of error
or for any loss or damage which may arise from reliance on information contained.

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Education for anaesthesia providers worldwide

Volume 35 February 2020

Editors: Christina Lundgren and Victoria Howell ISSN 1353-4882

The Journal of the World Federation of Societies of Anaesthesiologists

Editorial Board of Update in Anaesthesia

Typeset and printed by Sumographics Ltd

Postoperative pain management in Timor-Leste....................................................................................... 11

Comprehensive review of laryngospasm....................................................................................................... 15

Perioperative myocardial ischaemia in non-cardiac surgery.............................................................. 19

Erector spinae plane block....................................................................................................................................... 27

Intrathecal tranexamic acid during spinal anaesthesia for caesarean delivery....................... 39

Ketamine: recent evidence and current uses............................................................................................... 43

Complications associated with intraoperative use of irrigation fluid

Case report: Posterior Reversible Encephalopathy Syndrome (PRES)........................................... 54

Letter: Oxycontin - a tale of advertisement and addiction.................................................................. 56

Letter: Sphenopalatine block ganglion bloc - management of PDPH after

Key Words: patient safety, quality improvement, anaesthesia Elizabeth M Quartson

Figure 1: Initial Surgical Safety Checklist developed at CCTH (February 2016)

DATE (DDMMYY): _________________________ NAME: ____________________________ SIGNATURE: ______________________________

Table 2: Utilization of the SSCL when it was incompletely filled out

*p<0.05 (McNemar’s test for dependent proportions)

Table 2: Themes in Incomplete Charts

Theme N charts % of charts*

DATE (DDMMYY): _______________________ NAME: _____________________________ SIGNATURE: _______________________________

Major Open Urological 14 Pain Score Day 1 Frequency

Charted Analgesic Pain Score Pain Score Extra analgesia

Catarina R. Silva*, Teresa Pereira, Diana Henriques and Filipa Lanca

It is defined by a sustained closure of the vocal cords PATHOPHYSIOLOGY

Table 1. Known risk factors for larynogospasm

Patient-related Surgery-related Anaesthesia-related

Inspiratory stridor Diagnosis of laryngospasm

Assess airway entry

Deepen anaesthesia Gentle thoracic pressure

Consider atropine 10-20mcg/kg

Yes No Orotracheal intubation

Figure 1. Simplified flowchart for laryngospasm management

Table 1. The Lee Revised Cardiac Risk Index

Statins Heart Rate

Clonidine Transfusion Thresholds

The potency of ropivacaine is approximately 60% of bupivacaine Conclusion

Araz Pourkashanian*, Madan Narayanan, Arun Venkataraju

ANATOMICAL STUDIES AND PROPOSED MECHANISM

Is the ESP Block a Surrogate for the Paravertebral Block? How

HAS THE ESP BLOCK CAUGHT ON? WHAT DOES THE

Figure 5. Visible craniocaudal spread of methylene blue dye in cadavers

Originally published as Anaesthesia Tutorial of the Week

Dr Charlotte Earnshaw* and Dr Melanie Poole

FIBRINOLYSIS AND MECHANISM OF ACTION OF

Serum Creatinine (lmol/l) eGFR (ml/min) Dose (IV) Frequency of Administration

Table 2: Side effects of tranexamic acid

Side effect Frequency

Table 3. Summary Dosing Table

Loading Dose (No Faster Maintenance Dose Other Considerations

D G Bishop*, A C Lundgren, N F Moran, I Popov and J Moodley

INTRODUCTION A C Lundgren, mb, chb, da, ffa, phd

intrathecally; we need to ensure that TXA is one of these. Avoiding

Dr Alistair Gales* and Dr Stuart Maxwell

<C>: no catastrophic haemorrhage

DATE (DDMMYY): _ NAME: SIGNATURE: ______

DATE (DDMMYY): _________ NAME: _ SIGNATURE: _________________