JUNE 2011

Brought to You by

REPORT
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Multimodal Management
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Of Acute Pain:
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The Role of IV NSAIDs

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United States,2 this translates into

A cute pain is common in hos-
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pitalized patients, particu- a high absolute number of patients

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Faculty
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larly in postoperative patients. In affected. Despite advances in pain

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fact, postoperative pain often is Raymond S. Sinatra, MD, PhD medicine, including IV and epi-
undertreated and is associated dural patient-controlled analge-
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Professor Emeritus of Anesthesiology

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with poor outcomes, higher costs sia, pain management continues

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Acute Pain Management Service

of care, poor patient satisfaction, to pose a challenge for clinicians.
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Yale School of Medicine

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and an increased risk for devel- Several studies have investi-

New Haven, Connecticut
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oping chronic pain syndromes. gated the epidemiology of acute

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The failure to treat postoperative Jonathan S. Jahr, MD pain in postoperative patients.

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pain adequately is at least in part For example, Apfelbaum and col-

Professor of Clinical Anesthesiology
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due to the reliance on monother- leagues conducted telephone sur-

apy with opioid analgesics.1 For- David Geffen School of Medicine
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veys with a random sample of 250

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tunately, the increasing use of University of California, Los Angeles adults who had undergone sur-
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multimodal analgesia is resulting Los Angeles, California gical procedures recently in the
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in improved pain control for post- United States.1 Survey questions

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operative patients. focused on the severity of postsur-

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This monograph discusses the concept of multimodal gical pain, education received, treatment, satisfaction with
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analgesia and preemptive analgesia and presents new pain medication, and overall perceptions about postoper-
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data concerning IV nonsteroidal anti-inflammatory drugs ative pain and treatment.1 The researchers reported that
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(NSAIDs) and how they can be used to treat acute pain approximately 80% of patients experienced acute pain
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effectively in hospitalized patients. after surgery, and of these patients, 86% had moderate,
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severe, or extreme pain.1 Additionally, experiencing post-

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Prevalence and Severity of Acute Pain operative pain was the most common concern (59%) of
patients before surgery, and these concerns even caused
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In Hospitalized Patients
some patients to postpone surgery.1
Acute pain in hospitalized patients is most commonly Warfield and Kahn reported similar results in a study
related to surgical procedures. With more than 45 million using telephone questionnaire surveys of patients who had
nonambulatory surgeries being performed annually in the undergone surgery in teaching or community hospitals.3

Supported by
 REPORT

Again, approximately 77% of patients reported experiencing The psychological effects of uncontrolled pain, including
pain after surgery, and 80% of these patients rated pain after insomnia, depression, and anxiety, also may contribute to poor
surgery as moderate to extreme.3 patient outcomes and decreased patient satisfaction.12
Other studies suggest that pain can persist for several A frequently unrecognized risk associated with under-
days following surgery. Lynch and colleagues assessed pain treatment of acute postoperative pain is the potential to
after elective noncardiac surgery through the use of question- develop chronic pain syndromes.13 In fact, Perkins reported
naires and a 10-cm visual analog scale in 276 patients.4 They that postoperative pain was the main predictor for develop-
reported that the mean maximum pain score on postopera- ment of chronic pain syndromes and that improved postop-
tive day 1 was 6.3 (moderate pain) and decreased only slightly erative analgesia reduced the incidence of this complication.13
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to 5.6 by postoperative day 3.4 Furthermore, using a ques- Poorly managed postoperative pain also results in increased
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tionnaire survey, Beauregard and colleagues assessed pain in resource utilization and health care costs. For example, Morri-
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89 patients undergoing ambulatory surgery and found that 40% son and colleagues studied 411 patients undergoing surgical
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reported moderate to severe pain during the first 24 hours after repair of a hip fracture and reported that patients with higher
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discharge; pain decreased over time but was severe enough to postoperative pain scores had significantly longer hospital
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interfere with daily activities, even several days after surgery.5 length of stay, were significantly less likely to be ambulating by
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day 3, took significantly longer to move past a bedside chair,

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Consequences of Acute Postoperative and had lower locomotion scores at 6 months.9 Furthermore,
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Coley and colleagues reported that postoperative pain was the

Pain in Hospitalized Patients
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most frequent reason for hospital readmission after discharge.14

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Inadequate pain management can have profound and long-

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lasting implications. Ischemic events are well documented in Management of Acute Pain
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patients following surgery and are thought to be indicative of

In Hospitalized Patients
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the risk for postoperative morbidity, including serious arrhyth-

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mia, myocardial infarction, congestive heart failure, intracranial Opioid monotherapy remains a widely used mode of post-
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hemorrhage, and death.6,7 The stresses of surgery and post- operative analgesia.15 Opioids are potent analgesics and are
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operative stress are thought to be contributing factors to isch- available in a wide variety of formulations, including IV, oral,
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emic events. Inadequate pain management is a major trigger and transdermal, which is useful in the postoperative setting as
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of the sympathetic nervous system and therefore is viewed as well as for medication transitions at time of hospital discharge.
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a strong contributor to postoperative stress.6 Beattie followed Although monotherapy with these agents can be effective in
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55 patients with 2 or more risk factors for ischemia (coro- some cases, opioids have various idiosyncratic or dose-limiting
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nary artery disease, high blood pressure, history of myocardial side effects that curtail their practical efficacy as well as expose
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infarction, etc) for 24 hours following noncardiac surgery.6 His patients to dangerous adverse events (AEs).15,16 The central
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results indicate stress as a contributing factor to the early isch- nervous system (CNS) effects (eg, sedation, somnolence,
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emic events observed in this study because tachycardia often respiratory depression) associated with opioids are particu-
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was observed along with ischemia. larly dangerous and increase the risk for aspiration, respiratory
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Other short-term consequences of acute pain include splint- failure, decreased mobility, and falls (Table 1).15,16 Other AEs
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ing, which can lead to atelectasis and pneumonia,8 as well as are common even at low doses of opioids and include con-
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delayed mobilization,9 which can increase the risk for deep stipation and ileus, which can result in significant discomfort,
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venous thrombosis and subsequent pulmonary embolism.10,11 longer hospital stays, and nausea and vomiting, which can lead
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to wound dehiscence and delayed recovery.15,16 Because opi-

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oid-induced nausea and vomiting is dose-dependent, a reduc-

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Table 1. Adverse Effects Associated With

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tion in opioid burden while maintaining optimal pain relief offers

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Opioid Monotherapy for Postoperative Pain clinical benefits.17

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The limitations of opioid monotherapy combined with the

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Allergic reactions
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evidence of undertreatment of postoperative pain have led sev-

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eral medical societies and quality assurance groups to issue

Gastrointestinal effects
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guidelines and launch initiatives to improve the management

of postoperative pain. As part of a comprehensive initiative,
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Hypotension the Agency for Health Care Policy and Research issued guide-
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lines for acute pain management in 1992.18 The guidelines pro-

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Nausea/vomiting
mote aggressive treatment of acute pain and educate patients
about the need to communicate unrelieved pain. In 2004, the
Respiratory depression/failure
American Society of Anesthesiologists released an update to
Sedation, confusion its 1994 guidelines for acute pain management in the periop-
erative setting.19 These guidelines promote standardization of
Urinary retention procedures and the use of epidurals and patient-controlled
analgesia pumps.19 They also recommend that proactive plan-
Based on Oderda GM, Said Q, Evans RS, et al. Opioid-related ning—including obtaining pain history and preoperative, intra-
adverse drug events in surgical hospitalizations: impact on costs operative, and postoperative pain treatment—be a part of the
and length of stay. Ann Pharmacother. 2007;41(3):400-406.
institution’s interdisciplinary care plan.19 More recent initiatives

2
 REPORT

1a Surgical and Postsurgical 1b Postsurgical Analgesia

Intensity Afferent Input A

Duration Nociceptor Input Nociceptor Input

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of Surgery
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Hypersensitivity Hypersensitivity
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Duration
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1c 1d
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Presurgical Analgesia Pre/Postsurgical Analgesia

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A A A
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A A
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Nociceptor Input Nociceptor Input

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Hypersensitivity Hypersensitivity
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Figure 1. Preemptive analgesia may reduce wound hypersensitivity.

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Several perioperative analgesic dosing regimens and their effect on nociceptor activity and wound site hypersensitivity.
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Figure 1a: The non-treatment regimen, in which a patient receives no analgesic intervention and subsequently develops high-grade
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hypersensitivity.
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Figure 1b: The analgesic is administered postsurgically after central sensitization has already occurred. This reduces pain intensity for a
short time. However, it has no long-term effect on the development or magnitude of hypersensitivity.
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Figure 1c: Preoperative administration of the analgesic decreases both nociceptor input and the magnitude of hypersensitivity.
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Figure 1d: The preoperative dose of the analgesic is followed by additional doses administered at regular intervals during postsurgical
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recovery. This is the most effective regimen for prevention of central sensitization and wound site hypersensitivity.
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A, analgesia
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Adapted with permission from Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician.
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2001;63(10):1979-1984, and Woolf CK, Chong MS. Preemptive analgesia—treating postoperative pain by preventing the establishment of
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central sensitization. Anesth Analg. 1993;77(2):362-367.

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to improve management of postoperative pain cite the potential Modern multimodal analgesia consists of the use of sys-
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efficacy of multimodal analgesia and preemptive analgesia.19 temic and local pharmacologic agents as well as regional
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anesthesia and perineural blockade.12,21,22 Ideal components

Multimodal Analgesia
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of pharmacologic multimodal analgesia include those agents

Multimodal analgesia is defined as the simultaneous use of with potency for modulating one or more discrete mechanisms
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different classes or modes of analgesics that modulate differ- of pain transmission and those agents that possess a good
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ent pathways and receptors in order to provide superior pain safety profile (eg, minimal bleeding risk).12,22 Furthermore, the
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control. Multimodal analgesia provides several types of bene- availability of an analgesic in an IV formulation is critical in the
fits to postoperative patients.12,20-22 First, use of agents with dif- immediate postoperative period for various reasons, includ-
ferent analgesic mechanisms can result in synergistic effects ing improved bioavailability and earlier onset of analgesic
and thereby produce greater efficacy.21 Second, the syner- effect, and because these patients may experience postoper-
gism between these agents allows use of lower doses of each ative nausea and vomiting.21 It is also beneficial because the
respective agent, thereby limiting dose-related AEs, particu- enteral route may be compromised by the nature of the sur-
larly when these regimens allow for lower doses of opioids.12,22 gery, thereby precluding oral drug administration.22 Among IV
These actions, in turn, may facilitate earlier mobilization and agents used in multimodal analgesia are the opioids, NSAIDs,
rehabilitation after surgery, earlier transition to the outpatient acetaminophen, α2-agonists (eg, clonidine), and N-methyl-D-
setting, and decreased costs of care.12 aspartate receptor antagonists (eg, ketamine).12,20,21

3
 REPORT

Preemptive Analgesia prolonged post-stimulus sensory disturbances that include

An additional pain management strategy, originally pro- continuing pain, an increased sensitivity to noxious stimuli,
posed more than 20 years ago, is preemptive analgesia. This and pain following innocuous stimuli.12,25,26 This may result
requires a comprehensive understanding of the mechanism of from either a reduction in the thresholds of skin nociceptors
pain transmission and the subsequent adaptive or maladaptive (peripheral sensitization) or an increase in the excitability of
responses of the nervous system.23 the CNS (central sensitization), which can cause exaggerated
The peripheral nervous system and the CNS are essential responses to stimuli (Figure 1).24-26
in perceiving pain.24-26 Peripheral nociceptors play an impor- Based on these observations, investigators have stud-
tant role in translating noxious stimuli by sending signals along ied and reported good efficacy for preemptive administra-
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myelinated A and unmyelinated C fibers in the dorsal root gan- tion of analgesics to block transmission of noxious stimuli
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glion.24 Synapses occur between the axons in the dorsal horn and thereby preclude the cascade of events that leads to
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of the spinal cord and send signals along the spinothalamic peripheral and central sensitization. 25-27 This preemptive
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tract of the spinal cord to the brain.24 strategy results in improved pain control in the postopera-
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Noxious stimuli that are sufficiently intense to produce tis- tive context and related improvements in a variety of outcome
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sue injury, as occurs during surgery, characteristically generate measures. 26,27

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Pluripotent Effects of IV
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NSAIDs for Postoperative

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Pain Control
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Peripheral inflammation Central cytokine release NSAIDs have been used for the treatment
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of pain for decades, and investigators increas-

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ingly are recognizing the particular utility of

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these agents for improved control of post-

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COX-2 upregulation in operative pain. The primary mechanism by

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COX-2 upregulation in
dorsal horn neurons and which NSAIDs exert their effects is via inhibi-
inflammatory cells
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supporting cells tion of the arachidonic acid–cyclooxygenase

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(COX) pathways.28 This cascade consists of

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2 distinct pathways mediated through COX-1

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Acetaminophen and COX-2.28 Although the detrimental effects

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of some NSAIDs (eg, renal dysfunction, gas-

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trointestinal [GI] mucosal compromise, plate-

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NSAIDs let inhibition) are mediated by inhibition of the

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COX-1 pathway, the analgesic effect and anti-

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inflammatory effects are attributable primarily

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to inhibition of COX-2.28-30 This is consistent

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Prostaglandin Prostaglandin
production production with experimental evidence showing that
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prostaglandin E2 (PGE2), which is generated

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by the COX-2 pathways, plays a critical role

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Constitutive
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in the induction of both peripheral and cen-

COX-1
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tral sensitization.31-34 Thus, the specificity of

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certain NSAIDs for the different COX enzymes

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has significant implications in terms of clini-

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Action on peripheral Action on PGE2 receptors cally analgesic potency as well as the prob-
terminal PGE2 receptors on dorsal horn neurons
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ability of AEs.
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NSAIDs modulate pain pathways in multiple

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ways.35 NSAIDs reduce inflammatory hyperal-

gesia and allodynia by reducing prostaglandin
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Enhanced depolarization
Peripheral synthesis; they can decrease the recruitment
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of secondary sensory
sensitization of leukocytes and consequently their derived
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neurons
inflammatory mediators; and they cross the
blood–brain barrier to prevent prostaglan-
dins (ie, pain-producing neuromodulators)
Figure 2. Mechanism of analgesic action of cyclooxygenase in the spinal cord.36 In this manner, NSAIDs
inhibitors. reduce local inflammation and may prevent
COX, cyclooxygenase; NSAID, nonsteroidal anti-inflammatory drug; both peripheral and central sensitization (Fig-
PGE 2 , prostaglandin E2 ure 2).36 Opioids do not modulate PGE 2 or
Adapted from Golan DE. Principles of Pharmacology: The Pathophysiologic Basis inflammatory pathways, whereas acetamino-
of Drug Therapy. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2008. phen acts centrally but does not act at periph-
eral sites.37 Additionally, IV NSAIDs can act as

4
 REPORT

Table 2. Properties of Parenteral NSAIDs

Ketorolac (Toradol ®) Ibuprofen (Caldolor ®)

Indications Management of moderately severe acute pain that Management of mild to moderate pain
requires analgesia at the opioid level, usually in a Management of moderate to severe
postoperative setting pain as an adjunct to opioid analgesics
Reduction of fever
Dosing
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15-30 mg IV every 6 h as necessary Pain: 400-800 mg IV over 30 min

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every 6 h as necessary
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Fever: 400 mg IV over 30 min, followed

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by 400 mg every 4-6 h or 100-200 mg

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every 4 h as necessary
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Half-life
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5-6 h (racemic mixture) 2.22 h (400 mg)

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2.44 h (800 mg)

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Duration listed in label No more than 5 d Unrestricted

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Black Box Warnings Can cause peptic ulcers, GI bleeding, and/or NSAIDs may increase the risk for
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perforation of the stomach or intestines, which can serious CV thrombotic events, MI, and
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be fatal. These events can occur at any time during stroke, which can be fatal. Risk may
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use and without warning symptoms. Therefore, increase with duration of use. Caldolor
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it is contraindicated in patients with active peptic is contraindicated for the treatment

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ulcer disease, in patients with recent GI bleeding or of perioperative pain in the setting of
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perforation, and in patients with a history of peptic CABG surgery

ulcer disease or GI bleeding. Elderly patients are at
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NSAIDs increase the risk for serious

greater risk for serious GI events
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GI adverse events, including bleeding,

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May cause an increased risk for serious CV ulceration, and perforation of the
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thrombotic events, MI, and stroke, which can be stomach or intestines, which can be
fatal. This risk may increase with duration of use. fatal. Events can occur at any time
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Patients with CVD or risk factors for CVD may be at without warning symptoms. Elderly
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greater risk. It is contraindicated for the treatment of patients are at greater risk
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perioperative pain in the setting of CABG surgery

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Contraindicated in patients with advanced renal

impairment and in patients at risk for renal failure
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due to volume depletion

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Ketorolac inhibits platelet function and is therefore

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contraindicated in patients with suspected or

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confirmed cerebrovascular bleeding, patients with

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hemorrhagic diathesis or incomplete hemostasis, and

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those at high risk for bleeding. It is contraindicated as

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prophylactic analgesic before any major surgery

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Contraindicated in labor and delivery and nursing

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mothers, and in patients currently receiving aspirin

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or other NSAIDs
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CABG, coronary artery bypass graft; CV, cardiovascular; CVD, cardiovascular disease; GI, gastrointestinal; MI, myocardial infarction;
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IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug

Based on Toradol prescribing information. http://www.drugs.com/pro/ketorolac-tromethamine.html, and Intravenous ibuprofen (Caldolor ®)
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prescribing information. http://www.caldolor.com/pdfs/Caldolor_Full_Prescribing_Information.pdf.

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adjunct regional blockade by inhibiting PGE and cytokines in short-term (≤5 days) management of moderately severe acute
addition to suppressing neural responses to noxious injury.35 pain that requires analgesia at the opioid level, usually in a
There are currently 2 parenteral NSAIDs that are approved postoperative setting.38 Numerous studies have documented
for use in the United States: IV ketorolac and IV ibuprofen the efficacy of postoperative use of IV ketorolac for the reduc-
(Table 2).38,39 tion of pain, reduction of opioid use, and facilitation of quicker
recovery and rehabilitation.41,42
IV Ketorolac (Toradol®) Of note, ketorolac has much more potent effect on COX-1
Ketorolac tromethamine is an IV NSAID formulation that was than on COX-2. This has important implications for clinical
approved for use by the FDA in 1989.40 It is indicated for the use.29 The negative effect of NSAIDs on renal function, GI

5
 REPORT

Reduction in Pain Intensity Scores After Orthopedic Surgery

Assessed at Rest Assessed With Movement

90 90

80 32% Hours 6-28 ( P<0.001)

80 26% Hours 6-28 (P <0.001)

Surgery
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70 70
Surgery
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60 60
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VAS (Movement)
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VAS (Rest)
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50 50
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40 40
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30 30
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First Dose Dosing Placebo, N=86 First Dose Dosing Placebo, N=86
Study Every 6 h Study Every 6 h
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800 mg CALDOLOR®, N=99 800 mg CALDOLOR®, N=99

10 Hour 0 10 Hour 0
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0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28
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Study Houra Study Houra

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Figure 3. Orthopedic pain study: VAS scores at rest and with movement.
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In this study, patients woke up in less pain and remained in less pain throughout the postoperative period whether assessed at rest or
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with movement.
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VAS, visual analog scale

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Statistical significance was demonstrated at each assessment point.
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Based on Singla N, Rock A, Pavliv L. A multi-center, randomized, double-blind placebo-controlled trial of intravenous-ibuprofen
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(IV-ibuprofen) for treatment of pain in post-operative orthopedic adult patients. Pain Med. 2010;11(8):1284-1293.
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mucosa, and platelet function are mediated primarily through scores or morphine use when comparing those who received
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the COX-1 pathways.28,29 Thus, IV ketorolac is contraindicated ketorolac and those who did not.44 Yet, as demonstrated by
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in patients with renal insufficiency (which is particularly preva- El-Tahan and colleagues in a randomized, double-blind, placebo-
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lent in elderly populations) or a history of GI ulcers or bleeding controlled study assessing hemodynamic and hormonal effects in
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disorders.38 These effects are primary determinants indicating managing pain following cesarean delivery, preemptive use of
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short-term use only.38 ketorolac has optimized postoperative analgesia.45

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Ketorolac has a high degree of COX-1 selectivity of NSAIDs

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IV Ibuprofen (Caldolor®)
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used for acute pain management.29 The potent effect of ketor-

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olac on COX-1 also may result in platelet dysfunction, which A formulation of IV ibuprofen (Caldolor ® ) was approved for
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can increase the risk for bleeding in the perioperative setting.38 use in the United States in June 2009, and it is indicated for
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Indeed, postoperative hematomas and other signs of wound management of mild to moderate pain, management of mod-
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bleeding have occurred in association with the perioperative erate to severe pain as an adjunct to opioid analgesics, and
use of IV ketorolac.38 As such, the prescribing information for reduction of fever.39 Similar to oral ibuprofen, the IV formula-
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IV ketorolac contains a Black Box Warning against its use as a tion can inhibit both COX-1 and COX-2.39 IV ibuprofen has more
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prophylactic analgesic before any major surgery.38 “balanced” affinity for the COX isoenzymes.29,39 In key clinical
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Despite contraindication, IV ketorolac has been studied trials, bleeding, gastric, and renal events were similar to pla-
as a prophylactic analgesic with varying results. Cabell and cebo.39 This has significant implications for the clinical use of
colleagues performed a randomized, double-blind trial of pre- IV ibuprofen.39,46
emptive ketorolac in patients undergoing laparoscopic ambu- The efficacy and safety of IV ibuprofen was studied by
latory surgery and reported that these patients actually had Southworth and colleagues, who conducted a multicenter, ran-
higher postoperative pain scores and greater narcotic use.43 domized, double-blind, placebo-controlled dose-ranging study
Similarly, Vanlersberghe and colleagues conducted a ran- to assess the effects of IV ibuprofen or placebo in 406 patients
domized, double-blind, placebo-controlled trial of preemp- undergoing orthopedic or abdominal surgery.47 Ibuprofen was
tive ketorolac in patients undergoing orthopedic surgery and given at 400 or 800 mg or placebo doses every 6 hours begin-
reported that there was no difference in postoperative pain ning at the initiation of wound closure and continued for 48

6
 REPORT

hours.47 After that period, additional ibuprofen dosing was satisfaction, impaired rehabilitation, delayed hospital dis-
available as necessary.47 Patients in all 3 groups had access to charge, and an increased risk for developing chronic pain. Fur-
morphine throughout the study.47 thermore, pain often is undermanaged, at least in part because
IV ibuprofen at a dose of 800 mg was associated with of the limitations of opioid monotherapy.
reduced morphine use during the first 24 hours (by 22% vs Optimal pain relief may require a multimodal approach and
placebo; P=0.030) and significant reductions in pain at rest possibly preemptive analgesia. IV NSAIDs address multiple
(30.6% reduction at 24 hours vs placebo; P<0.001) and with mechanisms of pain and can be used in the multimodal man-
movement (18% reduction at 24 hours vs placebo).47 Addition- agement of postoperative acute pain. IV ketorolac is only indi-
ally, IV ibuprofen at a dose of 400 mg was associated with a cated for short-term therapy and is contraindicated for use as a
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nonsignificant reduction in narcotic use and significant reduc- preemptive analgesic. By contrast, IV ibuprofen is effective for
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tions in pain at rest and with movement when compared with use as both a preemptive analgesic and a postoperative anal-
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placebo.47 IV ibuprofen reduced the incidence of fever when gesic without an increased risk for AEs and without restrictions
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compared with placebo and was not associated with signifi- for duration of use. These data suggest that IV ibuprofen is well
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rig ed.

cant increases in AEs, including bleeding and renal toxicities, suited for use in multimodal and preemptive analgesia in hos-
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with the exception of an increased incidence of dizziness with

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pitalized patients with acute pain.

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the 800-mg dose.47 Interestingly, there were significant reduc-

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tions in the proportions of patients who experienced GI disor- References

20

ders, such as nausea or constipation, in the 400- and 800-mg 1. Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experi-
11

IV ibuprofen groups compared with the placebo group (74%

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ence: results from a national survey suggest postoperative pain contin-

and 71%, respectively, vs 84%; P=0.05 and P=0.009).47 ues to be undermanaged. Anesth Analg. 2003;97(2):534-540.
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Another Phase III multicenter, randomized, double-blind,

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2. Centers for Disease Control. Faststats: Inpatient Surgery. http://www.

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placebo-controlled trial evaluated the safety and efficacy of cdc.gov/nchs/fastats/insurg.htm. Accessed March 14, 2011.
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IV ibuprofen (800 mg every 6 hours beginning at the initiation 3. Warfield CA, Kahn CH. Acute pain management. Programs in
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of wound closure, continued for 8 doses, and then as needed U.S. hospitals and experiences and attitudes among U.S. adults.
Anesthesiology. 1995;83(5):1090-1094.
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every 6 hours for up to 5 days following surgery) compared

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with placebo as a postoperative analgesic in 319 patients 4. Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio
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undergoing elective abdominal hysterectomy.48 IV ibuprofen ER. Patient experience of pain after elective noncardiac surgery.
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Anesth Analg. 1997;85(1):117-123.

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was associated with a reduction in morphine requirements over

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5. Beauregard L, Pomp A, Choinière M. Severity and impact of pain after

the first 24 hours (by 19% vs placebo; P<0.001) and resulted
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day-surgery. Can J Anaesth. 1998;45(4):304-311.

in a significant reduction in pain at rest (21% reduction at 24
or

6. Beattie WS, Buckley DN, Forrest JB. Epidural morphine reduces the
hours vs placebo; P=0.011) and with movement (14% reduc-
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risk of postoperative myocardial ischaemia in patients with cardiac risk

in

tion at 24 hours vs placebo; P=0.010).48 Time to ambulation factors. Can J Anaesth. 1993;40(6):532-541.
up
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Perspectives on Pain
To view a presentation by Dr. Sinatra, scan
this QR code with your mobile device or visit
www.PreemptSurgicalPain.com.

Disclaimer: This monograph is designed to be a summary of information. While it is detailed, it is not an exhaustive clinical review. McMahon Publishing,
Cumberland Pharmaceuticals, and the authors neither affirm nor deny the accuracy of the information contained herein. No liability will be assumed for the
use of this monograph, and the absence of typographical errors is not guaranteed. Readers are strongly urged to consult any relevant primary literature.

8 SR1124 PRP1470311 June 2011