Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as part of a combined approach to postoperative pain management because their lack of respiratory depression or sedation in comparison to opioid drugs. The peri-operative use of NSAIDs has been limited due to the associated gastrointestinal, coagulation, and renal side effects. Selective COX-2 inhibitors (coxibs) are specifically designed to inhibit the cyclooxygenase-2 isoenzyme and have been prescribed increasingly for the treatment of chronic arthritis and acute pain. Research suggests a reduced incidence of gastrointestinal side effects compared with non-selective NSAIDs in chronic use. However, this evidence has limited application to the use of coxibs in postoperative pain. This systematic review evaluated the comparative analgesic efficacy and tolerability of single-dose coxibs used in postoperative pain management.

Methods

Randomised controlled trials (RCTs) were identified by computerised searches of MEDLINE (1966-March 2003), EMBASE (1980-2003) and the Cochrane Library (issue 4 2001). Studies with postoperatively single-dose treatment groups of coxibs versus placebo, double blind design, adult patients, baseline moderate to severe pain, pain measured by standard visual analogue scale or verbal analogue relief scale with standard wording, were included. The area under the pain relief versus time curve over 6 hours was used to evaluate the proportion of patient achieving at least 50% pain relief using validated equations [1]. The proportions of patients experiencing any adverse event or specific adverse events were also examined. Summary estimates of the effects and their 95% confidence interval (95%CI) from each trial were pooled using a random effects model [2].

Results

In all, 18 RCTs were included which contained 2783 patients. The results from dental pain models suggested oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and the rate ratio (RR) was 2.11 (95%CI: 1.6-2.75). Valdecoxib 40 mg was also more effective than oxycodone/paracetamol 10/1000 mg (RR: 1.34, 95%CI: 1.11-1.62). There was no significant differences between other oral coxibs and non-selective NSAIDs, except that celecoxib 200 mg was less effective than ibuprofen 400 mg (RR: 0.66, 95%CI: 0.48-0.90) and rofecoxib 50 mg (RR: 0.65, 95%CI: 0.49-0.87). The results from orthopaedic pain model showed no significant difference between rofecoxib 50 mg and naproxen sodium 550 mg (RR: 1.04, 95%CI: 0.73-1.49). The adverse effects of single-dose coxibs used in short-term postoperative pain management were generally mild and less than non-selective NSAIDs, though there was no significant difference.

Conclusions

The analgesic efficacy and tolerability of single-dose COX-2 inhibitors were more effective than opioid-containing analgesics and similar to non-selective NSAIDs in postoperative pain management. Further studies are needed to examine the efficacy and tolerability of COX-2 inhibitors compared against active comparators over a longer duration to assess whether these short-term effects are mirrored by longer-term outcomes and to determine their ultimate risk-benefit profile.

References

1. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: verification from independent data. Pain 1997; 69(1-2):127-130.
2. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials 1986; 7(3): 177-188.