Skip Navigation LinksHome > November 2003 - Volume 99 - Issue 5 > Cyclooxygenase-2 Inhibitors in Postoperative Pain Management...
Anesthesiology:
Review Article

Cyclooxygenase-2 Inhibitors in Postoperative Pain Management: Current Evidence and Future Directions

Gilron, Ian M.D., M.Sc., F.R.C.P.C.*; Milne, Brian M.D., M.Sc., F.R.C.P.C.†; Hong, Murray Ph.D.‡
Section Editor(s): Warltier, David C. M.D., Ph.D., Editor

Free Access
Article Outline
Collapse Box

Author Information

NONSTEROIDAL antiinflammatory drugs (NSAIDs) have been shown to reduce pain and opioid consumption and often accelerate recovery after surgery. However, perioperative inhibition of prostaglandin synthesis by NSAIDs may cause complications, including renal injury, gastric ulceration, and bleeding. Recent molecular studies distinguishing between constitutive cyclooxygenase-1 (COX-1) and inflammation-inducible cyclooxygenase-2 (COX-2) enzymes have led to the exciting hypothesis that the therapeutic and adverse effects of NSAIDs could be uncoupled. The purpose of this article is to review the mechanistic differences between nonselective NSAIDs and selective COX-2 inhibitors (COX-2Is) and to examine currently available COX-2I clinical trials to consider the role of these drugs in postoperative pain management.
Back to Top | Article Outline

Safety and Analgesic Efficacy of NSAIDs

The administration of NSAIDs is one of the most common nonopioid analgesic techniques currently used for postoperative pain management. 1 The efficacy of NSAIDs for postoperative pain has been repeatedly demonstrated in many analgesic clinical trials. 2,3 The efficacy of traditional NSAIDs can be summarized by results from recent meta-analyses of postoperative single-dose trials showing numbers needed to treat (to obtain one patient with at least 50% pain relief) of 2.6 for 10 mg oral ketorolac, 4 2.4 for 1,200 mg oral acetylsalicylic acid, 5 and 2.4 for 400 mg oral ibuprofen. 6 Unlike opioids, which preferentially reduce spontaneous postoperative pain, 7,8 NSAIDs have comparable efficacy for both spontaneous and movement-evoked pain, 9–11 the latter of which may be more important in causing postoperative physiologic impairment. 12,13 Furthermore, NSAIDs have been shown to reduce postoperative opioid consumption 14,15 and accelerate postoperative recovery 16,17 after certain types of surgery and are thus thought to be an important component of balanced postoperative analgesic regimens. 18
The majority of data about adverse effects of NSAIDs come from the setting of chronic use for arthritis. 19,20 However, perioperative inhibition of cyclooxygenase (also called prostaglandin H synthase) by NSAIDs may also cause serious complications, including renal injury, gastric ulceration, and excessive bleeding. 21 Brief perioperative NSAID use in healthy adults does not seem to cause important renal dysfunction, 22 but clinicians continue to be cautioned by occasional but recurring reports of perioperative NSAID-related renal failure. 23–28 Similarly, cases of gastrointestinal ulceration or bleeding have been reported after brief NSAID use, 29–33 making this an important risk to consider when using NSAIDs for postoperative pain. Finally, the potential for excessive, and infrequently catastrophic, perioperative blood loss due to NSAID use has been well documented as yet another hazard of these drugs. 34–38 Careful patient screening for renal dysfunction, gastritis, gastric ulcers, or bleeding diathesis and judicious administration of NSAIDs may largely prevent these major complications. Rare NSAID-related problems, which are also thought to be due to cyclooxygenase inhibition, include hepatocellular injury, 39 asthma exacerbation, anaphylactoid reactions, tinnitus, and urticaria. 40
Back to Top | Article Outline

Mechanisms of Analgesia and NSAID-related Adverse Effects

Fig. 1
Fig. 1
Image Tools
Traditional NSAIDs comprise a chemically diverse 41 group of compounds (e.g., salicylates, benzothiazines, and indoleacetic, pyrrolacetic, and propionic acids) which, among other actions, inhibit prostaglandin synthesis 42 by competing with arachidonic acid for binding to the cyclooxygenase active site. 43 Until recently, NSAIDs have been thought mainly to suppress the peripheral nociceptive manifestations of postinjury inflammation. 44 After the conversion of membrane phospholipids to arachidonic acid by phospholipase A2 in the periphery, cyclooxygenase converts arachidonic acid to the cyclic endoperoxide prostaglandin G2 (fig. 1) and then acts as a peroxidase to reduce prostaglandin G2 to the cyclic endoperoxide prostaglandin H2. 41 Several synthases then convert prostaglandin H2 to other prostaglandins (e.g., prostaglandin D2, prostaglandin E2, prostaglandin F2-alpha, prostaglandin I2) and to thromboxane A2. 45 It has been observed that cyclooxygenase inhibition results in shunting of arachidonic acid to lipoxygenase pathways, resulting in increased leukotriene synthesis, a putative mechanism of NSAID-induced bronchospasm. 41 NSAIDs are thought to reduce postoperative pain by suppressing cyclooxygenase-mediated production of prostaglandin E2, which is thought to be the primary inflammatory prostaglandin that directly activates and also up-regulates the sensitivity of peripheral nociceptors to cause pain. 41 Prostaglandins have also been shown to play a role in spinal nociception, 46–48 thus contributing to a growing body of evidence supporting a spinal analgesic mechanism of NSAIDs. 49 NSAID-mediated suppression of prostaglandins and thromboxanes, which play a homeostatic role in the stomach (prostaglandin E2 and prostaglandin I2), 50 kidney (prostaglandin E2), 51 and platelets (prostaglandin I2 and thromboxane A2), 52 is also thought to be the primary mechanism by which NSAIDs cause some of the adverse effects described above. In addition to these three major complications, inhibition of prostaglandin synthesis by NSAIDs is also thought to be the primary mechanism underlying NSAID-induced asthma 53 and the suppression of heterotopic bone formation. 54
Back to Top | Article Outline

COX-1 and COX-2 Isoforms of Cyclooxygenase

Table 1
Table 1
Image Tools
Subsequent to cloning the gene that encodes for cyclooxygenase in 1988, 55 several studies yielded the discovery of a second form of cyclooxygenase and distinguished between the constitutive COX-1 and the inducible COX-2 isoforms of cyclooxygenase. 56,57 The advent of new selective COX-2Is has allowed the investigation of differential inhibition of COX-1 versus COX-2 58 such that NSAIDs, new and old, can be evaluated 59–61 with respect to their COX-1/COX-2 inhibitory profile (table 1). The data shown in table 1 indicate that all NSAIDs have at least some effect on both COX-1 and COX-2 isoenzymes and that there are, as yet, no specific values that define a drug as a purely selective COX-2 inhibitor. COX-1 is active and present at a constant concentration in most tissues, particularly in the kidney, stomach, and platelets, where it plays a homeostatic and protective role through the production of prostaglandin E2 and prostaglandin I2. 62 COX-2, however, is normally present in only very low concentrations but is induced peripherally under conditions of inflammation. 63 This functional distinction has led to the exciting hypothesis that selective COX-2Is could uncouple the therapeutic and adverse effects of traditional NSAIDs. However, it is important to note that some exceptions do exist, i.e., COX-2 plays a homeostatic role in the renal medulla, and COX-1 may produce some prostaglandins that contribute to inflammation. 41 Also of great interest in pain management, recent work has shown that COX-2 is constitutively expressed in brain and spinal cord and is further up-regulated after persistent noxious inputs such that spinal COX-2 inhibition may be an important mechanism for reducing postinjury hyperalgesia. 49 Finally, COX-2 inhibition results in selective suppression of prostaglandin I2 without affecting thromboxane A2, 41 and this imbalance may explain the potential for cardiovascular toxicity discussed in the section entitled “Safety of Selective COX-2 Inhibitors in the Treatment of Chronic Arthritis.”
Back to Top | Article Outline

Evidence Suggesting Potential Advantages of COX-2 Inhibitors

Administration of aspirin to arthritis patients resulted in decreased platelet aggregation, whereas the COX-2I celecoxib failed to inhibit platelet aggregation. 64 Consistent with animal studies showing that COX-1 inhibition but not COX-2 inhibition leads to gastric ulceration, 65,66 multicenter arthritis trials have reported decreased incidences of gastrointestinal ulceration with COX-2Is in comparison with nonselective NSAIDs. 67,68 Although these data do not come from the postoperative setting, they do provide further support for the theoretical advantages of COX-2Is.
Back to Top | Article Outline

Safety of Selective COX-2 Inhibitors in the Treatment of Chronic Arthritis

The majority of postmarketing data about COX-2Is comes from experience with celecoxib and rofecoxib, which were approved in the United States in 1998 and 1999, respectively. 69 Other COX-2Is available in Europe include meloxicam and nimesulide. 41 The COX-2Is nimesulide and meloxicam were marketed in Europe long before the discovery of COX-2 and have since been used as molecular precursors for the development of newer COX-2Is. 62 Currently, the major indication of chronic COX-2I use is for the treatment of arthritic pain, although early studies may suggest promise for the prevention of colorectal cancer 70 and Alzheimer disease. 71 Evidence gathered to date suggests that COX-2Is are safer than traditional NSAIDs with respect to gastrointestinal ulceration and bleeding but not renal dysfunction, and furthermore, COX-2Is may confer increased risk for cardiovascular events (e.g., cerebrovascular accident, angina, or myocardial infarction). 69 Preclinical studies demonstrating the role of COX-2 in the kidney have been echoed by human data indicating that COX-2Is can cause sodium retention and decreased glomerular filtration rate and thus warrant similar precautions that are followed for traditional NSAIDs. 72 Gastrointestinal safety data comes largely from two studies, the Vioxx Gastrointestinal Outcomes Research trial (VIGOR) 67 and the Celecoxib Long-term Arthritis Safety Study (CLASS). 68 In the VIGOR trial, rofecoxib was shown to cause a significantly lower incidence of upper gastrointestinal perforation, ulceration and bleeding as compared to naproxen. 67 In the CLASS study, there was no difference in gastrointestinal toxicity between celecoxib and traditional NSAIDs across patients who were also taking low-dose aspirin; however, in patients not taking aspirin, celecoxib did demonstrate a lower incidence of symptomatic ulcers and ulcer complications compared to traditional NSAIDs. 68 It was suggested that aspirin's gastrointestinal risks eliminated celecoxib's benefits. 68 Important recent reports have suggested that COX-2Is cause an increased risk of thrombotic cardiovascular events. 67,69 It has been postulated that COX-2Is may unfavorably alter the thromboxane-prostacyclin balance by inhibiting the vasoprotective prostacyclin (prostaglandin I2) but not the procoagulant thromboxane (thromboxane A2). 69 In the VIGOR trial, rofecoxib caused a fourfold increase in the incidence of myocardial infarction compared to naproxen, 67 whereas no increase in risk was observed for celecoxib in the CLASS trial. 68 However, in the CLASS study, 22% of patients were taking low-dose aspirin for cardioprotection, and this trial did not include patients with rheumatoid arthritis, who have an increased risk of cardiovascular complications. 68 This remains a critical issue that requires further investigation, and until resolved, the potential for cardiovascular toxicity should be considered when using COX-2Is in patients at risk for coronary artery disease. Using the example that even brief perioperative β blockade may significantly reduce mortality, 73 the potential for postoperative COX-2I administration, however brief, to cause cardiovascular complications must be addressed. Further concerns regarding potential cardiovascular effects of COX-2Is are raised by a recent study in hypertensive osteoarthritis patients demonstrating that the COX-2I rofecoxib but not the NSAID namebutone increased nocturnal blood pressure. 74
Back to Top | Article Outline

Selective COX-2 Inhibitors and Postoperative Pain

In contrast to chronic treatment of arthritis, routine perioperative pain management generally occurs over a period of less than 4 weeks. However, surgery is associated with a set of special situations and problems, including blood loss, fluid shifts, risks of infection and thrombosis, and concomitant administration of anesthetic, analgesic, anticoagulant, and antibiotic drugs. For these reasons, the study and implementation of COX-2Is in the setting of perioperative pain require a unique perspective.
Back to Top | Article Outline

Perioperative Clinical Trials of COX-2Is

Literature searches of perioperative analgesic clinical trials of COX-2Is were conducted using the Cochrane Controlled Trials Register (third quarter 2002) and MEDLINE Database (1966 to February 2003). The database search strategy involved a Boolean search of [celecoxib OR etoricoxib OR flosulide OR meloxicam OR nimesulide OR parecoxib OR rofecoxib OR valdecoxib] AND [postoperative pain OR surgery OR surgical] AND [randomized controlled trials]. Trials reported in abstract form at recent scientific congresses were not included, given their preliminary nature and sometimes limited peer review. It has been well recognized that the use of a placebo control in analgesic trials serves to minimize the risk of false-positive and false-negative results. 75,76 Only double-blind, randomized, placebo-controlled trials were evaluated in this review for these reasons. For differing measures of analgesic efficacy and side effects across these trials, statistically significant differences (P < 0.05) between treatments (e.g., COX-2I, NSAID comparator, placebo) were reported in this review. Most studies use multiple analgesic efficacy measures (e.g., analgesic use, pain intensity, pain relief). Only the outcome measure that demonstrated a difference was reported on in studies showing significant differences between treatment groups.
Table 2
Table 2
Image Tools
Table 2
Table 2
Image Tools
Table 3
Table 3
Image Tools
The above database search yielded a total of 27 publications of COX-2I trials, one of which described 6 trials, for a total of 32 controlled trials reported (table 2). These included 25 single-dose and 7 multidose trials (number of trials/drug) of rofecoxib (19), celecoxib (6), parecoxib (5), valdecoxib (3), nimesulide (1), and meloxicam (1). Some trials included more than one COX-2I among their treatment arms. Surgical procedures studied in these trials included minor oral surgery, gynecologic surgery, prostatectomy, lumbar discectomy, spinal fusion, and major joint arthroplasty. Reported efficacy measures also varied across studies and included pain intensity, pain relief, and consumption of other analgesics (table 3).
Back to Top | Article Outline
Analgesic Efficacy
Table 4
Table 4
Image Tools
Of the 19 rofecoxib trials, 17 demonstrated superior efficacy of rofecoxib to placebo, 77–88 whereas two trials showed no difference. 89,90 Five of the six celecoxib trials showed superiority to placebo, 81,85,91–93 and one showed no difference. 94 Parecoxib (the parenteral prodrug of valdecoxib), 95–99 valdecoxib, 80,100,101 nimesulide, 102 and meloxicam 103 were found to be superior to placebo in all reported trials. A recent meta-analysis of five rofecoxib trials that investigated 1,118 patients (of whom 211 received placebo and 464 received 50 mg rofecoxib) reported a number needed to treat of 2.3. 104 Of 23 trial comparisons with nonselective NSAIDs (17), acetaminophen (3), or opioids (3), 13 NSAID 81–83,92,97,99,102 and 1 opioid 91 comparator were no different than the studied COX-2I (table 4). The studied COX-2I was observed to be more efficacious than the comparator NSAID 79 or opioid 78,91,97 in four comparative trials and less efficacious in two trials. 81,93 It should be noted that the reported comparative studies are mostly single-dose trials that do not necessarily address relative potency of the drugs being compared. Thus, although one drug may be more potent than another, that drug can only be said to be more efficacious if optimal doses of each drug are being compared. Three trials compared COX-2Is to each other, two of which showed that rofecoxib is more efficacious than celecoxib, 81,85 and the third of which demonstrated that valdecoxib is more efficacious than rofecoxib. 80 One orthopedic trial by Reuben et al.86 showed that 50 mg rofecoxib given 1 h preoperatively was more effective at reducing postoperative pain than the same dose given 15 min postoperatively, suggesting that, as with traditional NSAIDs, COX-2Is may have preemptive analgesic effects.
Back to Top | Article Outline
Postoperative Analgesic Dose–Response Studies
Table 5
Table 5
Image Tools
The analgesic dose–response relation of COX-2Is has been studied in trials of rofecoxib, 83,84 parecoxib, 95–99 valdecoxib, 100,101 and nimesulide 102 (table 5). Rofecoxib was studied at 7.5, 12.5, 25, 50, 100, and 200 mg orally in the six controlled trials reported by Morrison et al.83, and, whereas 50 mg was significantly more efficacious than 7.5, 12.5, and 25 mg, no differences were noted between 50 mg and 100 or 200 mg, suggesting an analgesic ceiling at approximately 50 mg. During the multidose segment (postoperative days 2–5) of the orthopedic rofecoxib trial by Reicin et al., 84 daily doses of 50 mg rofecoxib but not 25 mg resulted in significantly less consumption of supplemental analgesic medication (hydrocodone–acetaminophen). In the parecoxib trial by Desjardins et al., 96 40 mg intravenously was more efficacious than 20 mg but indistinguishable from 80 mg. Rasmussen et al.97 also observed that 40 mg parecoxib was more effective than 20 mg after knee surgery, but higher doses were not studied. Postoperative differences between 20 and 40 mg intravenous parecoxib were not as pronounced in the oral surgery study by Daniels et al.95 Camu et al.100 and Tang et al.98 showed no difference in pain scores or analgesic consumption between 20 and 40 mg oral valdecoxib or between 20 and 40 mg intravenous parecoxib in two other postoperative trials. A recent study of valdecoxib by Desjardins et al.101 demonstrated dose-dependent analgesia between 10 and 40 mg but no difference between 40 and 80 mg, suggesting an analgesic ceiling also for valdecoxib. Finally, the oral surgery study by Ragot et al.102 showed no difference between 100 and 200 mg nimesulide. In summary, these data suggest that COX-2Is, at least in the case of rofecoxib, parecoxib, and valdecoxib, have a postoperative analgesic dosage ceiling similar to that of traditional NSAIDs 41 (table 5).
Back to Top | Article Outline
Safety of COX-2Is in the Postoperative Setting
Evaluation and reporting of adverse effects varied considerably across studies from no measures at all to spontaneous patient reporting to specific measures of nausea, vomiting, or blood loss (table 3). All but six trials reported no difference between the studied COX-2I and placebo or active comparator in the overall incidence of adverse effects. However, it should be noted that all COX-2I trials included here were designed and statistically powered with analgesia, not adverse effects, as the primary outcome. One trial did not report adverse effects, 86 and in two trials, a significantly greater incidence of postdental extraction alveolitis (“dry socket”) was observed with 50 mg oral rofecoxib as compared to placebo. 80,83 Four trials reported significantly fewer adverse effects with the studied COX-2I in comparison with placebo or the active comparator. 78,81,91,94 Only three perioperative studies incorporated specific measures of blood loss in the trial design (table 3), and none of these three reported any difference in blood loss between the studied COX-2I and placebo. 85,87,90 In addition to adverse effects reported in the postoperative trials cited in this review, single isolated cases of celecoxib-induced oliguria 105 and rofecoxib-induced aseptic meningitis 106 after brief postoperative use have been recently reported.
Back to Top | Article Outline
Side Effect Profiles from Postoperative COX-2I Trials
Common (5–28%) treatment-emergent signs and symptoms associated with COX-2Is (rofecoxib, parecoxib, and valdecoxib) from postoperative clinical trials that tabulated adverse effects 79,80,84,95–97,100 include headache, nausea, vomiting, dizziness, and postdental extraction alveolitis. However, only one of these, postdental extraction alveolitis, occurred more frequently with rofecoxib than with placebo, 80 which was also observed in one of the trials reported by Morrison et al.83
Back to Top | Article Outline

Summary

Postoperative pain management has gone through revolutionary innovations over the past century with the widespread clinical introduction of systemic and neuraxial opioids, regional local anesthetic techniques, patient-controlled analgesia, and coanalgesic therapies such as NSAIDs. 107 Current needs for improvement in postoperative pain management include (1) more effective relief of pain and suffering for all postoperative patients 108,109; (2) preventing and/or treating other postoperative symptoms (which may or may not be related to analgesic therapies) such as nausea, pruritus, sedation, and cognitive dysfunction 110; and (3) promoting recovery from surgery by preventing and/or treating postoperative physiologic dysfunction such as atelectasis and ileus. 111,112 Thus, therapeutic improvements in postoperative pain management should advance at least one of these goals without impeding the others. In the interest of relieving postoperative pain for all patients, further attention needs to be given to special populations such as patients undergoing tonsillectomy, ocular procedures, spinal fusion, and other surgeries for which nonselective NSAIDs have a relative contraindication.
Current evidence published to date does not suggest that COX-2Is provide a major advantage over traditional NSAIDs. However, it is possible that their development will lead to specific drugs with a superior therapeutic profile. For example, after oral surgery, valdecoxib was recently shown to be significantly more effective than rofecoxib, 80 which in turn was shown to be more effective than codeine–acetaminophen 78 or diclofenac. 79 It remains to be determined whether these differences in analgesic efficacy can be replicated using multidose trials with equipotent dose comparisons and after other, more painful procedures. However, such observations lead to the anticipation that future advances in drug development may result in COX-2Is with clinically important advantages over traditional NSAIDs.
Several COX-2I trials have demonstrated an opioid-sparing effect after surgery, 85,100 and comparisons with opioids have reported fewer postoperative side effects. 78,91 Thus, COX-2Is are at least as effective as nonselective NSAIDs in reducing opioid requirements and/or opioid-related adverse effects after surgery. Provided that recent evidence of fewer gastrointestinal complications with COX-2Is from arthritis studies 67,68 holds true in the postoperative setting, it is hoped that patients with gastrointestinal risk factors (e.g., previous gastritis, ulcers), in whom NSAIDs are contraindicated, may safely benefit from the addition of a COX-2I to their postoperative analgesic regimen. Both experimental and clinical evidence suggest that NSAIDs impair bone healing. 113,114 Thus, spinal fusion surgery patients present another group who may be denied the benefits of NSAIDs because of fear of postoperative deleterious effects on bone graft healing. Early evidence from a rabbit model 115 and a small spinal fusion clinical trial 85 suggesting that COX-2Is do not interfere with bone healing has led to the optimistic proposal that COX-2Is may be a useful alternative for these patients. 116 More recent data does in fact support a role for COX-2 in bone healing, 117 and further clinical investigation is needed to address this problem. 118
Issoui et al.94 were unable to demonstrate any difference in postoperative recovery times across postoperative patients receiving acetaminophen, celecoxib, their combination, or placebo. No study has been reported to date that compares COX-2Is to nonselective NSAIDs with respect to postoperative recovery or postoperative physiologic impairment. Such investigations as have been previously conducted with nonselective NSAIDs 119 are needed to identify whether COX-2Is have any advantage.
Cardiovascular risks of COX-2Is discussed above remain controversial, and more recent evidence suggests that COX-2Is may not confer greater cardiovascular danger than nonselective NSAIDs. 120,121,122 However, comparative postoperative studies that carefully track cardiovascular outcomes are needed to resolve this controversy.
Table 6
Table 6
Image Tools
Discovery of the COX-2 enzyme and subsequent development of selective COX-2Is has contributed to a resurgence of therapeutic research in postoperative pain. However, whether these developments have resulted in any tangible improvements in patient care requires further study. Comparative COX-2I trials published to date generally suggest similar analgesic efficacy to nonselective NSAIDs in postoperative pain. Also, these mostly single-dose studies suggest similar safety and tolerability as compared to currently used NSAIDs. Additional data from larger, multicenter, multidose comparative trials could determine whether individual COX-2Is are more efficacious, cost-effective, and/or safe versus nonselective NSAIDs with respect to gastric, renal, and coagulation problems and whether COX-2Is confer greater cardiovascular risk in the postoperative setting. Multiple unresolved questions (table 6) remain to be answered. Until then, cost–benefit considerations 123 will likely guide therapeutic choices in the absence of strong evidence supporting any major advantage of COX-2Is.
The authors thank Allan Bell, B.Sc. (Medical Student, University of Toronto, Toronto, Ontario, Canada), for his technical assistance and Dr. Tanveer Towheed, M.D., M.Sc., F.R.C.P.C. (Assistant Professor, Division of Rheumatology, Queen's University, Kingston, Ontario, Canada) for thoughtful comments made on previous versions of this manuscript.
Back to Top | Article Outline

References

1. White PF: The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg 2002; 94: 577–85

2. Bloomfield SS, Gaffney TE, Howett M: Comparative analgesic efficacy of chlorphenesin carbamate and acetylsalicylic acid after episiotomy. Anesth Analg 1967; 46: 515–20

3. Hackl J: Treatment of postoperative pain with mefenamic acid. Med Welt 1967; 46: 2796–9

4. Smith LA, Carroll D, Edwards JE, Moore RA, McQuay HJ: Single-dose ketorolac and pethidine in acute postoperative pain: Systematic review with meta-analysis. Br J Anaesth 2000; 84: 48–58

5. Edwards JE, Oldman AD, Smith LA, Carroll D, Wiffen PJ, McQuay HJ, Moore RA: Oral aspirin in postoperative pain: A quantitative systematic review. Pain 1999; 81: 289–97

6. Po AL, Zhang WY: Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: A meta-analysis. Eur J Clin Pharmacol 1998; 53: 303–11

7. Tverskoy M, Oren M, Dashkovsky I, Kissin I: Alfentanil dose-response relationships for relief of postoperative pain. Anesth Analg 1996; 83: 387–93

8. Wilder-Smith CH, Hill L, Wilkins J, Denny L Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. A nesthesiology 1999; 91: 639–47

9. Keenan DJ, Cave K, Langdon L, Lea RE: Comparative trial of rectal indomethacin and cryoanalgesia for control of early postthoracotomy pain. BMJ 1983; 287: 1335–7

10. Pavy TJ, Gambling DR, Merrick PM, Douglas MJ: Rectal indomethacin potentiates spinal morphine analgesia after caesarean delivery. Anaesth Intensive Care 1995; 23: 555–9

11. Gilron I, Max MB, Lee G, Booher SL, Sang CN, Chappell AS, Dionne RA: Effects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain. Clin Pharmacol Ther 2000; 68: 320–7

12. Richardson J, Sabanathan S, Shah R: Post-thoracotomy spirometric lung function: The effect of analgesia: A review. J Cardiovasc Surg 1999; 40: 445–56

13. Gilron I, Tod D, Goldstein DH, Parlow JL, Orr E: The relationship between movement-evoked versus spontaneous pain and peak expiratory flow after abdominal hysterectomy. Anesth Analg 2002; 95: 1702–7

14. Parker RK, Holtmann B, Smith I, White PF: Use of ketorolac after lower abdominal surgery: Effect on analgesic requirement and surgical outcome A nesthesiology 1994; 80: 6–12

15. Reuben SS, Connelly NR, Lurie S, Klatt M, Gibson CS: Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery. Anesth Analg 1998; 87: 98–102

16. Ogilvie-Harris DJ, Bauer M, Corey P: Prostaglandin inhibition and the rate of recovery after arthroscopic meniscectomy: A randomised double-blind prospective study. J Bone Joint Surg Br 1985; 67: 567–71

17. Place RJ, Coloma M, White PF, Huber PJ, Van Vlymen J, Simmang CL: Ketorolac improves recovery after outpatient anorectal surgery. Dis Colon Rectum 2000; 43: 804–8

18. Kehlet H, Werner M, Perkins F: Balanced analgesia: What is it and what are its advantages in postoperative pain? Drugs 1999; 58: 793–7

19. Cuthbert MF: Adverse reactions to non-steroidal antirheumatic drugs. Curr Med Res Opin 1974; 2: 600–10

20. O'Brien WM, Bagby GF: Rare adverse reactions to nonsteroidal antiinflammatory drugs. J Rheumatol 1985; 12: 785–90

21. Souter AJ, Fredman B, White PF: Controversies in the perioperative use of nonsteroidal antiinflammatory drugs. Anesth Analg 1994; 79: 1178–90

22. Lee A, Cooper MG, Craig JC, Knight JF, Keneally JP: The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on postoperative renal function: A meta-analysis. Anaesth Intensive Care 1999; 27: 574–80

23. Miller FC, Schorr WJ, Lacher JW: Zomepirac-induced renal failure. Arch Intern Med 1983; 143: 1171–3

24. Perazella MA, Buller GK: NSAID nephrotoxicity revisited: Acute renal failure due to parenteral ketorolac. South Med J 1993; 86: 1421–4

25. Quan DJ, Kayser SR: Ketorolac induced acute renal failure following a single dose. J Toxicol Clin Toxicol 1994; 32: 305–9

26. Haragsim L, Dalal R, Bagga H, Bastani B: Ketorolac-induced acute renal failure and hyperkalemia: Report of three cases. Am J Kidney Dis 1994; 24: 578–80

27. Patel NY, Landercasper J: Ketorolac-induced postoperative acute renal failure: A case report. Wis Med J 1995; 94: 445–7

28. Sivarajan M, Wasse L: Perioperative acute renal failure associated with preoperative intake of ibuprofen. A nesthesiology 1997; 86: 1390–2

29. McCann KJ, Irish J: Postoperative gastrointestinal bleeding: A case report involving a non-steroidal anti-inflammatory drug. J Can Dent Assoc 1994; 60: 124–8

30. Wolfe PA, Polhamus CD, Kubik C, Robinson AB, Clement DJ: Giant duodenal ulcers associated with the postoperative use of ketorolac: Report of three cases. Am J Gastroenterol 1994; 89: 1110–1

31. Yarboro TL Sr: Intramuscular Toradol, gastrointestinal bleeding, and peptic ulcer perforation: A case report. J Natl Med Assoc 1995; 87: 225–7

32. Buchman AL, Schwartz MR: Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication. J Clin Gastroenterol 1996; 22: 224–6

33. Alcaraz A, Lopez-Herce J, Serina C, Bueso-Inchausti A, Saez MJ, Sancho L: Gastrointestinal bleeding following ketorolac administration in a pediatric patient. J Pediatr Gastroenterol Nutr 1996; 23: 479–81

34. Fauno P, Petersen KD, Husted SE: Increased blood loss after preoperative NSAID: Retrospective study of 186 hip arthroplasties. Acta Orthop Scand 1993; 64: 522–4

35. Robinson CM, Christie J, Malcolm-Smith N: Nonsteroidal antiinflammatory drugs, perioperative blood loss, and transfusion requirements in elective hip arthroplasty. J Arthroplasty 1993; 8: 607–10

36. Splinter WM, Rhine EJ, Roberts DW, Reid CW, MacNeill HB: Preoperative ketorolac increases bleeding after tonsillectomy in children. Can J Anaesth 1996; 43: 560–3

37. Wierod FS, Frandsen NJ, Jacobsen JD, Hartvigsen A, Olsen PR: Risk of haemorrhage from transurethral prostatectomy in acetylsalicylic acid and NSAID-treated patients. Scand J Urol Nephrol 1998; 32: 120–2

38. Schmidt A, Bjorkman S, Akeson J: Preoperative rectal diclofenac versus paracetamol for tonsillectomy: Effects on pain and blood loss. Acta Anaesthesiol Scand 2001; 45: 48–52

39. Lewis JH: Hepatic toxicity of nonsteroidal anti-inflammatory drugs. Clin Pharm 1984; 3: 128–38

40. Stevenson DD: Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol 1984; 74: 617–22

41. Myoshi HR: Systemic nonopioid analgesics, Bonica's Management of Pain, 3rd edition. Edited by Loeser JD, Turk D, Chapman CR, Butler S. Philadelphia, Williams & Wilkins, 2001, pp 1667–81

42. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231: 232–5

43. Smith WL, DeWitt DL, Garavito RM: Cyclooxygenases: Structural, cellular, and molecular biology. Annu Rev Biochem 2000; 69: 145–82

44. Dahl JB, Kehlet H: Non-steroidal anti-inflammatory drugs: Rationale for use in severe postoperative pain. Br J Anaesth 1991; 66: 703–12

45. Goetz EJ, An S, Smith WL: Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases. FASEB J 1995; 9: 1051–8

46. Taiwo YO, Levine JD: Indomethacin blocks central nociceptive effects of PGF2 alpha. Brain Res 1986; 373: 81–4

47. Malmberg AB, Yaksh TL: Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science 1992; 257: 1276–9

48. Milne B, Hall SR, Sullivan ME, Loomis C: The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase inhibition during strychnine-induced allodynia. Anesth Analg 2001; 93: 728–33

49. Svensson CI, Yaksh TL: The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol 2002; 42: 553–83

50. Mahmud T, Scott DL, Bjarnason I: A unifying hypothesis for the mechanism of action of NSAID related gastrointestinal toxicity. Ann Rheum Dis 1996; 55: 211–3

51. Ruilope LM, Garcia Robles R, Paya C, Alcazar JM, Miravalles E, Sancho-Rof J, Rodicio J, Knox FG, Romero JC: Effects of long-term treatment with indomethacin on renal function. Hypertension 1986; 8: 677–84

52. Schafer AI: Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol 1995; 35: 209–19

53. Szczeklik A: The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J 1990; 3: 588–93

54. Tornkvist H, Nilsson OS, Bauer FC, Lindholm TS: Experimentally induced heterotopic ossification in rats influenced by anti-inflammatory drugs. Scand J Rheumatol 1983; 12: 177–80

55. Merlie JP, Fagan D, Mudd J, Needleman P: Isolation and characterization of the complementary DNA for sheep seminal vesicle prostaglandin endoperoxide synthase (cyclooxygenase). J Biol Chem 1988; 263: 3550–3

56. Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA 1992; 89: 7384–8

57. O'Banion MK, Winn VD, Young DA: cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci USA 1992; 89: 4888–92

58. Pairet M, van Ryn J: Experimental models used to investigate the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2 by non-steroidal anti-inflammatory drugs. Inflamm Res 1998; 47: 93–101

59. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR: Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci USA 1993; 90: 11693–7

60. Patrignani P, Panara MR, Sciulli MG, Santini G, Renda G, Patrono C: Differential inhibition of human prostaglandin endoperoxide synthase-1 and −2 by nonsteroidal anti-inflammatory drugs. J Physiol Pharmacol 1997; 48: 623–31

61. Chan CC, Boyce S, Brideau C, Charleson S, Cromlish W, Ethier D, Evans J, Ford-Hutchinson AW, Forrest MJ, Gauthier JY, Gordon R, Gresser M, Guay J, Kargman S, Kennedy B, Leblanc Y, Leger S, Mancini J, O'Neill GP, Ouellet M, Patrick D, Percival MD, Perrier H, Prasit P, Rodger I, Tagari P, Therien M, Vickers P, Visco D, Wang Z, Webb J, Wong E, Xu LJ, Young RN, Zamboni R, Riendeau D: Rofecoxib [Vioxx, MK-0966; 4-(4′-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: A potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther 1999; 290: 551–60

62. Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998; 38: 97–120

63. Funk CD: Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science 2001; 294: 1871–5

64. Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, Isakson PC, Geis GS: Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: Efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998; 41: 1591–602

65. Hirata T, Ukawa H, Yamakuni H, Kato S, Takeuchi K: Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs. Br J Pharmacol 1997; 122: 447–54

66. Chan CC, Boyce S, Brideau C, Ford-Hutchinson AW, Gordon R, Guay D, Hill RG, Li CS, Mancini J, Penneton M: Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745, 337: A novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J Pharmacol Exp Ther 1995; 274: 1531–7

67. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR study group. N Engl J Med 2000; 343: 1520–8

68. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study. A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284: 1247–55

69. Brune K: Non-opioid (antipyretic) analgesics, Pain 2002: An Updated Review. Edited by Giamberardino MA. Seattle, IASP Press, 2002, pp 365–79

70. Giovanucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE: Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995; 333: 609–14

71. Stewart WF, Kawas C, Corrada M, Metter EJ: Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997; 48: 626–32

72. Brater DC: Renal effects of cyclooxygenase-2-selective inhibitors. J Pain Symptom Manage 2002; 23: S15–20

73. Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, Baars HF, Yo TI, Trocino G, Vigna C, Roelandt JR, van Urk H: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 1999; 341: 1789–94

74. Reitblat T, Zamir D, Estis L, Priluk R, Drogenikov T, Viskoper JR: The different patterns of blood pressure elevation by rofecoxib and nabumetone. J Hum Hypertens 2002; 16: 431–4

75. Max MB, Laska EM: Single-dose analgesic comparisons, Advances in Pain Research and Therapy. Vol 18. Edited by Max M, Portenoy R, Laska E. New York, Raven Press, 1991

76. Food and Drug Administration: Guideline for the Clinical Evaluation of Analgesic Drugs. Rockville, U.S. Department of Health and Human Services, 1992

77. Bekker A, Cooper PR, Frempong-Boadu A, Babu R, Errico T, Lebovits A: Evaluation of preoperative administration of the cyclooxygenase-2 inhibitor rofecoxib for the treatment of postoperative pain after lumbar disc surgery. Neurosurgery 2002; 50: 1053–7

78. Chang DJ, Fricke JR, Bird SR, Bohidar NR, Dobbins TW, Geba GP: Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial. Clin Ther 2001; 23: 1446–55

79. Chang DJ, Desjardins PJ, Chen E, Polis AB, McAvoy M, Mockoviak SH, Geba GP: Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: A randomized, placebo-controlled clinical trial. Clin Ther 2002; 24: 490–503

80. Fricke J, Varkalis J, Zwillich S, Adler R, Forester E, Recker DP, Verburg KM: Valdecoxib is more efficacious than rofecoxib in relieving pain associated with oral surgery. Am J Ther 2002; 9: 89–97

81. Malmstrom K, Daniels S, Kotey P, Seidenberg BC, Desjardins PJ: Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: A randomized, placebo- and active-comparator-controlled clinical trial. Clin Ther 1999; 21: 1653–63

82. Morrison BW, Christensen S, Yuan W, Brown J, Amlani S, Seidenberg B: Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: A randomized, controlled trial. Clin Ther 1999; 21: 943–53

83. Morrison BW, Fricke J, Brown J, Yuan W, Kotey P, Mehlisch D: The optimal analgesic dose of rofecoxib: Overview of six randomized controlled trials. J Am Dent Assoc 2000; 131: 1729–37

84. Reicin A, Brown J, Jove M, deAndrade JR, Bourne M, Krupa D, Walters D, Seidenberg B: Efficacy of single-dose and multidose rofecoxib in the treatment of post-orthopedic surgery pain. Am J Orthop 2001; 30: 40–8

85. Reuben SS, Connelly NR: Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000; 91: 1221–5

86. Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J: The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002; 94: 55–9

87. Reuben SS, Fingeroth R, Krushell R, Maciolek H: Evaluation of the safety and efficacy of the perioperative administration of rofecoxib for total knee arthroplasty. J Arthroplasty 2002; 17: 26–31

88. Turan A, Emet S, Karamanlioglu B, Memis D, Turan N, Pamukcu Z: Analgesic effects of rofecoxib in ear-nose-throat surgery. Anesth Analg 2002; 95: 1308–11

89. Huang JJ, Taguchi A, Hsu H, Andriole GL Jr, Kurz A: Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: A prospective, randomized, double-blinded, placebo-controlled trial. J Clin Anesth 2001; 13: 94–7

90. Pickering AE, Bridge HS, Nolan J, Stoddart PA: Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children. Br J Anaesth 2002; 88: 72–7

91. Gimbel JS, Brugger A, Zhao W, Verburg KM, Geis GS: Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Clin Ther 2001; 23: 228–41

92. Khan AA, Brahim JS, Rowan JS, Dionne RA: In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model. Clin Pharm Ther 2002; 72: 44–9

93. Doyle G, Jayawardena S, Ashraf E, Cooper SA: Efficacy and tolerability of nonprescription ibuprofen versus celecoxib for dental pain. J Clin Pharmacol 2002; 42: 912–9

94. Issioui T, Klein KW, White PF, Watcha MF, Coloma M, Skrivanek GD, Jones SB, Thornton KC, Marple BF: The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngologic surgery. Anesth Analg 2002; 94: 1188–93

95. Daniels SE, Grossman EH, Kuss ME, Talwalker S, Hubbard RC: A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a post-oral surgery pain model. Clin Ther 2001; 23: 1018–31

96. Desjardins PJ, Grossman EH, Kuss ME, Talwalker S, Dhadda S, Baum D, Hubbard RC: The injectable cyclooxygenase-2-specific inhibitor parecoxib sodium has analgesic efficacy when administered preoperatively. Anesth Analg 2001; 93: 721–7

97. Rasmussen GL, Steckner K, Hogue C, Torri S, Hubbard RC: Intravenous parecoxib sodium for acute pain after orthopedic knee surgery. Am J Orthop 2002; 31: 336–43

98. Tang J, Li S, White PF, Chen X, Wender RH, Quon R, Sloninsky A, Naruse R, Kariger R, Webb T, Norel E: Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. A nesthesiology 2002; 96: 1305–9

99. Barton SF, Langeland FF, Snabes MC, LeComte D, Kuss ME, Dhadda SS, Hubbard RC: Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery. A nesthesiology 2002; 97: 306–14

100. Camu F, Beecher T, Recker DP, Verburg KM: Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. Am J Ther 2002; 9: 43–51

101. Desjardins PJ, Shu VS, Recker DP, Verburg KM, Woolf CJ: A single preoperative oral dose of valdecoxib, a new cyclooxygenase-2 specific inhibitor, relieves post–oral surgery or bunionectomy pain. A nesthesiology 2002; 97: 565–73

102. Ragot JP, Monti T, Macciocchi A: Controlled clinical investigation of acute analgesic activity of nimesulide in pain after oral surgery. Drugs 1993; 46( suppl 1): 162–7

103. Thompson JP, Sharpe P, Kiani S, Owen-Smith O: Effect of meloxicam on postoperative pain after abdominal hysterectomy. Br J Anaesth 2000; 84: 151–4

104. Barden J, Edwards JE, McQuay HJ, Moore R: Single-dose rofecoxib for acute postoperative pain in adults: A quantitative systematic review. BMC Anesthesiol 2002; 2: 4

105. Smiles J, Walker R: Selective cyclo-oxygenase-2 inhibitor-induced oliguria: A postoperative complication. Intern Med J 2001; 31: 497–8

106. Bonnel RA, Villalba ML, Karwoski CB, Beitz J: Aseptic meningitis associated with rofecoxib. Arch Intern Med 2002; 162: 713–5

107. Cousins M, Power I: Acute and postoperative pain, Textbook of Pain, 4th edition. Edited by Wall PD, Melzack R. Edinburgh, Churchill Livingstone, 1999

108. Mather LE, Cousins MJ: The pharmacological relief of pain: Contemporary issues. Med J Aust 1992; 156: 796–802

109. Hill CS Jr: When will adequate pain treatment be the norm? JAMA 1995; 274: 1881–2

110. Woodhouse A, Mather LE: Nausea and vomiting in the postoperative patient-controlled analgesia environment. Anaesthesia 1997; 52: 770–5

111. Kehlet H: Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997; 78: 606–17

112. Ballantyne JC, Carr DB, deFerranti S, Suarez T, Lau J, Chalmers TC, Angelillo IF, Mosteller F: The comparative effects of postoperative analgesic therapies on pulmonary outcome: Cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: 598–612

113. Dimar JR II, Ante WA, Zhang YP, Glassman SD: The effects of nonsteroidal anti-inflammatory drugs on posterior spinal fusions in the rat. Spine 1996; 21: 1870–6

114. Deguchi M, Rapoff AJ, Zdeblick TA: Posterolateral fusion for isthmic spondylolisthesis in adults: Analysis of fusion rate and clinical results. J Spinal Disord 1998; 11: 459–64

115. Long J, Lewis S, Kuklo T, Zhu Y, Riew KD: The effect of cyclooxygenase-2 inhibitors on spinal fusion. J Bone Joint Surg Am 2002; 84: 1763–8

116. Reuben SS: A new class of COX-2 inhibitors offer an alternative to NSAIDs in pain management after spinal surgery. Spine 2001; 26: 1505–6

117. Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ: Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 2002; 109: 1405–15

118. Matsumura J: Considerations in the use of COX-2 inhibitors in spinal fusion surgery. Anesth Analg 2001; 93: 803–4

119. Moiniche S, Hjortso NC, Hansen BL, Dahl JB, Rosenberg J, Gebuhr P, Kehlet H: The effect of balanced analgesia on early convalescence after major orthopaedic surgery. Acta Anaesthesiol Scand 1994; 38: 328–35

120. Chenevard R, Hurlimann D, Bechir M, Enseleit F, Spieker L, Hermann M, Riesen W, Gay S, Gay RE, Neidhart M, Michel B, Luscher TF, Noll G, Ruschitzka F: Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 2003; 107: 405–9

121. White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, Geis GS, Lefkowith JB: Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol 2002; 89: 425–30

122. Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR: Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: An observational cohort study. Lancet 2002; 359: 118–23

123. Issioui T, Klein KW, White PF, Watcha MF, Skrivanek GD, Jones SB, Hu J, Marple BF, Ing C: Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. A nesthesiology 2002; 97: 931–7

124. Pallapies D, Salinger A, Meyer zum Gottesberge A, Atkins DJ, Rohleder G, Nagyivanyi P, Peskar BA: Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo. Life Sci 1995; 57: 83–9

125. Kato M, Nishida S, Kitasato H, Sakata N, Kawai S: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: Investigation using human peripheral monocytes. J Pharm Pharmacol 2001; 53: 1679–85

Cited By:

This article has been cited 41 time(s).

European Journal of Anaesthesiology
A randomized, placebo-controlled study of rofecoxib with paracetamol in early post-tonsillectomy pain in adults
Naesh, O; Niles, LA; Gilbert, JG; Ammar, MM; Phibbs, PW; Phillips, AM; Khrapov, AV; Robert, AJ; McClintock, A
European Journal of Anaesthesiology, 22(): 768-773.

Anesthesia and Analgesia
Perioperative rofecoxib plus local anesthetic field block diminishes pain and recovery time after outpatient inguinal hernia repair
Pavlin, DJ; Pavlin, EG; Horvath, KD; Amundsen, LB; Flum, DR; Roesen, K
Anesthesia and Analgesia, 101(1): 83-89.
10.1213/01.ANE.0000155958.13748.03
CrossRef
Journal of Clinical Anesthesia
A double-blind prospective comparison of rofecoxib vs ketorolac in reducing postoperative pain after arthroscopic knee surgery
Kim, JT; Sherman, O; Cuff, G; Leibovits, A; Wajda, M; Bekker, AY
Journal of Clinical Anesthesia, 17(6): 439-443.
10.1016/j.jclinane.2004.09.008
CrossRef
Drugs
The authors' reply - Multimodal analgesia is here to stay
Gottschalk, A; Ochroch, AE
Drugs, 64(6): 629-630.

Inflammation Research
Effects of high-dose corticosteroids on post-traumatic inflammatory mediators
Reikeras, O; Helle, A; Krohn, CD; Brox, JI
Inflammation Research, 58(): 891-897.
10.1007/s00011-009-0061-3
CrossRef
Regional Anesthesia and Pain Medicine
Management of perioperative pain in patients chronically consuming opioids
Carroll, IR; Angst, MS; Clark, JD
Regional Anesthesia and Pain Medicine, 29(6): 576-591.
10.1016/j.rapm.2004.06.009
CrossRef
Acta Anaesthesiologica Scandinavica
Lack of analgesic effect of parecoxib following laparoscopic cholecystectomy
Puolakka, PAE; Puura, AIE; Pirhonen, RA; Ranta, AU; Autio, V; Lindgren, L; Rorarius, MGF
Acta Anaesthesiologica Scandinavica, 50(8): 1027-1032.
10.1111/j.1399-6576.2006.01116.x
CrossRef
Regional Anesthesia and Pain Medicine
Management of postoperative analgesia in elderly patients
Aubrun, F
Regional Anesthesia and Pain Medicine, 30(4): 363-379.
10.1016/j.rapm.2005.02.006
CrossRef
Anesthesia and Analgesia
Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation surgery: A single-dose, randomized, parallel-group study with methylprednisolone 125 mg, parecoxib 40 mg, and placebo
Romundstad, L; Breivik, H; Roald, H; Skolleborg, K; Haugen, T; Narum, J; Stubhaug, A
Anesthesia and Analgesia, 102(2): 418-425.
10.1213/01.ane.0000194358.46119.e1
CrossRef
Anesthesia and Analgesia
A Randomized, Double-Blind, Controlled Trial of Perioperative Administration of Gabapentin, Meloxicam and Their Combination for Spontaneous and Movement-Evoked Pain After Ambulatory Laparoscopic Cholecystectomy
Gilron, I; Orr, E; Tu, DS; Mercer, CD; Bond, D
Anesthesia and Analgesia, 108(2): 623-630.
10.1213/ane.0b013e318193cd1b
CrossRef
Anesthesia and Analgesia
Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase 2 inhibitor rofecoxib in humans: Sngle and multiple oral drug administration
Buvanendran, A; Kroin, JS; Tuman, KJ; Lubenow, TR; Elmofty, D; Luk, P
Anesthesia and Analgesia, 100(5): 1320-1324.
10.1213/01.ANE.0000150597.94682.85
CrossRef
Acta Anaesthesiologica Scandinavica
Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy
Tiippana, E; Bachmann, M; Kalso, E; Pere, P
Acta Anaesthesiologica Scandinavica, 52(5): 673-680.
10.1111/j.1399-6576.2008.01650.x
CrossRef
Anesthesia and Analgesia
Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats
Martin, TJ; Buechler, NL; Eisenach, JC
Anesthesia and Analgesia, 103(3): 690-695.
10.1213/01.ane.0000226096.46973.39
CrossRef
Anaesthesia and Intensive Care
A teenager with severe asthma exacerbation following ibuprofen
Palmer, GM
Anaesthesia and Intensive Care, 33(2): 261-265.

Anesthesia and Analgesia
The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery
Reuben, SS; Buvanendran, A; Kroin, JS; Raghunathan, K
Anesthesia and Analgesia, 103(5): 1271-1277.
10.1213/01.ane.0000237279.08847.2d
CrossRef
Anesthesia and Analgesia
The role of the anesthesiologist in fast-track surgery: From multimodal analgesia to perioperative medical care
White, PF; Kehlet, H; Neal, JM; Schricker, T; Carr, DB; Carli, F
Anesthesia and Analgesia, 104(6): 1380-1396.
10.1213/01.ane.0000263034.96885.e1
CrossRef
British Journal of Surgery
Cyclo-oxygenase 2 inhibitors and the risk of anastomotic leakage after fast-track colonic surgery
Holte, K; Andersen, J; Jakobsen, DH; Kehlet, H
British Journal of Surgery, 96(6): 650-654.
10.1002/bjs.6598
CrossRef
Molecular Pain
Effects of Parecoxib and Fentanyl on nociception-induced cortical activity
Peng, YZ; Li, XX; Wang, YW
Molecular Pain, 6(): -.
ARTN 3
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion
Reuben, SS; Ablett, D; Kaye, R
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 52(5): 506-512.

Pharmacy World & Science
Cost analysis applied to postoperative analgesia regimens: a comparison between parecoxib and propacetamol
Tilleul, P; Weickmans, H; Sean, PT; Lienhart, A; Beaussier, M
Pharmacy World & Science, 29(4): 374-379.
10.1007/s11096-006-9083-x
CrossRef
Gut
COX-2 chronology
Hawkey, CJ
Gut, 54(): 1509-1514.
10.1136/gut.2005.065003
CrossRef
New England Journal of Medicine
Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery
Nussmeier, NA; Whelton, AA; Brown, MT; Langford, RM; Hoeft, A; Parlow, JL; Boyce, SW; Verburg, KM
New England Journal of Medicine, 352(): 1081-1091.

Pediatric Anesthesia
The use of NSAIDs in pediatric scoliosis surgery - a survey of physicians' prescribing practice
Hayes, J; Pehora, C; Bissonnette, B
Pediatric Anesthesia, 19(8): 756-763.
10.1111/j.1460-9592.2009.03060.x
CrossRef
Journal of Feline Medicine and Surgery
Perioperative administration of vedaprofen, tramadol or their combination does not interfere with platelet aggregation, bleeding time and biochemical variables in cats
Brondani, JT; Luna, SPL; Marcello, GCG; Padovani, CR
Journal of Feline Medicine and Surgery, 11(6): 503-509.
10.1616/j.jfms.2008.12.003
CrossRef
Acta Anaesthesiologica Scandinavica
Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects
Romundstad, L; Breivik, H; Niemi, G; Helle, A; Stubhaug, A
Acta Anaesthesiologica Scandinavica, 48(): 1223-1231.
10.1111/j.1399-6576.2004.00480.x
CrossRef
Anesthesia and Analgesia
The changing role of non-opioid analgesic techniques in the management of postoperative pain
White, PF
Anesthesia and Analgesia, 101(5): S5-S22.

Anesthesia and Analgesia
Upregulation of cerebrospinal fluid and peripheral prostaglandin E-2 in a rat postoperative pain model
Kroin, JS; Buvanendran, A; Watts, DE; Saha, C; Tuman, KJ
Anesthesia and Analgesia, 103(2): 334-343.
10.1213/01.ane.0000223674.52364.5c
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery
White, PF; Sacan, O; Tufanogullari, B; Eng, M; Nuangchamnong, N; Ogunnaike, B
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 54(5): 342-348.

Brain Research
The antinociceptive effects of spinal cyclooxygenase inhibitors on uterine cervical distension
Du, DP; Eisenach, JC; Ririe, DG; Tong, CY
Brain Research, 1024(): 130-136.
10.1016/j.brainres.0204.07.056
CrossRef
Anesthesia and Analgesia
Exacerbation of carpal tunnel syndrome under treatment with valdecoxib
Ruppen, W; Schupfer, GK
Anesthesia and Analgesia, 100(4): 1215-1216.
10.1213/01.ANE.0000146669.40220.54
CrossRef
Journal of Bone and Joint Surgery-American Volume
The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion
Reuben, SS; Ekman, EF
Journal of Bone and Joint Surgery-American Volume, 87A(3): 536-542.
10.2106/JBJS.D.02283
CrossRef
Journal of Surgical Research
Preemptive Analgesia Reduces Pain After Radical Axillary Lymph Node Dissection
Neuss, H; Koplin, G; Haase, O; Reetz, C; Mall, JW
Journal of Surgical Research, 162(1): 88-94.
10.1016/j.jss.2009.01.029
CrossRef
Anaesthesia and Intensive Care
A randomized crossover trial of tenoxicam compared with rofecoxib for postoperative dental pain control
Zacharias, M; De Silva, RK; Herbison, P; Templer, P
Anaesthesia and Intensive Care, 32(6): 770-774.

Laryngoscope
Rofecoxib versus hydrocodone/acetaminophen for postoperative analgesia in functional endoscopic sinus surgery
Church, CA; Stewart, C; O-Lee, TJ; Wallace, D
Laryngoscope, 116(4): 602-606.
10.1097/01.MLG.0000208341.30628.16
CrossRef
Clinical Therapeutics
A Cost-Effectiveness Analysis of Parecoxib in the Management of Postoperative Pain in the Greek Health Care Setting
Athanasakis, K; Petrakis, I; Vitsou, E; Pimenidou, A; Kyriopoulos, J
Clinical Therapeutics, 35(8): 1118-1124.
10.1016/j.clinthera.2013.06.004
CrossRef
Anesthesiology
Central Nervous System Concentrations of Cyclooxygenase-2 Inhibitors in Humans
Dembo, G; Park, SB; Kharasch, ED
Anesthesiology, 102(2): 409-415.

PDF (420)
Anesthesiology
Upregulation of Prostaglandin E2 and Interleukins in the Central Nervous System and Peripheral Tissue during and after Surgery in Humans
Buvanendran, A; Kroin, JS; Berger, RA; Hallab, NJ; Saha, C; Negrescu, C; Moric, M; Caicedo, MS; Tuman, KJ
Anesthesiology, 104(3): 403-410.

PDF (925)
Anesthesiology
Safety and Efficacy of the Cyclooxygenase-2 Inhibitors Parecoxib and Valdecoxib after Noncardiac Surgery
Nussmeier, NA; Whelton, AA; Brown, MT; Joshi, GP; Langford, RM; Singla, NK; Boye, ME; Verburg, KM
Anesthesiology, 104(3): 518-526.

PDF (511)
Anesthesiology
Analgesic Treatment after Laparoscopic Cholecystectomy: A Critical Assessment of the Evidence
Bisgaard, T
Anesthesiology, 104(4): 835-846.

PDF (371)
Current Opinion in Anesthesiology
Pharmacology of cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management
Kaye, AD; Baluch, A; Kaye, AJ; Ralf, G; Lubarsky, D
Current Opinion in Anesthesiology, 21(4): 439-445.
10.1097/ACO.0b013e3283007e8d
PDF (290) | CrossRef
Spine
Effect of Parecoxib on Postoperative Pain After Lumbar Spine Surgery: A Bicenter, Randomized, Double-Blinded, Placebo-Controlled Trial
Jirarattanaphochai, K; Thienthong, S; Sriraj, W; Jung, S; Pulnitiporn, A; Lertsinudom, S; Foocharoen, T
Spine, 33(2): 132-139.
10.1097/BRS.0b013e3181604529
PDF (343) | CrossRef
Back to Top | Article Outline

© 2003 American Society of Anesthesiologists, Inc.

Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Images

Share