Most perioperative analgesia trials report a pain score. This systematic review asked a better question: does the pain interfere with daily living. It screened 9,071 citations and included 38 randomised trials with 5,424 adults comparing systemic perioperative selective cyclooxygenase-2 inhibitors against placebo, opioids or usual care, with the primary outcome a validated multidimensional instrument such as the Brief Pain Inventory within one month.
COX-2 inhibitors reduced acute pain-related interference by 1.1 points on the Brief Pain Inventory (95% CI -1.4 to -0.8, 7 trials, moderate certainty) — above the minimal clinically important difference of 1.0. Chronic pain incidence fell (odds ratio 0.44, 0.21 to 0.93, 5 trials, low certainty) though chronic pain intensity did not (one trial, very low certainty). Quality of Recovery-9 improved by 0.84 points (0.33 to 1.35, low certainty). Intraoperative blood loss was 22 mL lower. There was no signal of excess acute renal failure, gastrointestinal bleeding, impaired bone healing, myocardial infarction, stroke or death.
The safety result deserves emphasis because it is the reason these drugs are often withheld. Across 38 trials the feared harms did not appear — although trials exclude the patients in whom we most fear them, so this is reassurance about routine use, not permission in advanced kidney disease or active peptic ulceration. Where a COX-2 inhibitor is affordable and not contraindicated, this is a well-supported component of multimodal analgesia, and the benefit is measured in function rather than in a score that changes nothing.
- Include a COX-2 inhibitor in multimodal analgesia unless there is a specific contraindication.
- Check renal function, volume status and ulcer history before prescribing — trials excluded these patients.
- The benefit was on interference with function, so ask patients what they can do, not only what they score.
- Lower blood loss is a small bonus, not a reason to choose the drug.
- The chronic pain signal is low certainty from five trials; do not promise it to a patient.
The statistics, in plain English
Reporting against a prespecified minimal clinically important difference of 1.0 is what makes the -1.1 meaningful; a mean difference smaller than that would be statistically real and clinically invisible. Moderate certainty on the primary outcome from seven trials sits alongside very low certainty on chronic pain intensity from one — those two conclusions do not carry equal weight and should not be quoted together. Absence of a harm signal in trials is weaker evidence than a demonstrated absence of harm.
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