Effectiveness of Selective Cyclooxygenase-2 Inhibitors for Postoperative Pain Management Using Multidimensional Pain Assessment: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Why clinicians should know about it

• Picked for Anesthesiology and Pain Medicine (top studies of the week, 13 September 2026): COX‑2 inhibitors systematic review of postoperative pain
• Picked for Surgery (top studies of the week, 13 September 2026): COX‑2 inhibitors lower acute pain, improve recovery
• Picked for Epidemiology (top studies of the week, 13 September 2026): Systematic review of COX‑2 RCTs, not observational epidemiology
• Picked for Nephrology (top studies of the week, 13 September 2026): Meta‑analysis of COX‑2 inhibitors for postoperative pain, includes renal safety

Abstract

BACKGROUND: Although selective cyclooxygenase-2 (COX‑2) inhibitors are commonly used in perioperative pain management, it is uncertain whether these anti-inflammatory agents meaningfully improve postoperative recovery, including the impact of pain on daily functioning. METHODS: This study systematically searched MEDLINE, Embase, and Cochrane CENTRAL for randomized controlled trials comparing systemic perioperative selective COX‑2 inhibitors with placebo, opioids, or usual care in adults. The primary outcome was postoperative acute pain, assessed using any validated multidimensional instrument evaluating pain‑related interference with daily living (e.g., Brief Pain Inventory; 0 to 10 scale, minimal clinically important difference = 1.0) within 1 month after surgery. Secondary outcomes included chronic pain, quality of recovery, and adverse events. Two reviewers independently performed study selection, data abstraction, risk of bias and certainty of evidence assessments. Clinical significance was assessed by estimating the difference between groups in the proportion of participants achieving the minimal important difference. RESULTS: A total of 9,071 citations were screened, and 38 randomized controlled trials (5,424 participants) met eligibility criteria. Selective COX-2 inhibitors were associated with a reduction in acute pain‑related interference (Brief Pain Inventory mean difference [MD], -1.1; 95% CI, -1.4 to -0.8; n = 7; moderate certainty) and in chronic pain incidence (odds ratio, 0.44; 95% CI, 0.21 to 0.93; n = 5; low certainty), but no significant effect was found on chronic pain intensity (MD, -1.0; 95% CI, -2.7 to 0.7; n = 1; very low certainty). The modeled risk difference for achieving a clinically important analgesic effect showed a substantial benefit of COX-2 inhibitors for acute pain. Quality of recovery improved with the intervention (Quality of Recovery-9 [0 to 18 scale] MD, 0.84; 95% CI, 0.33 to 1.35; n = 7; low certainty). Intraoperative blood loss was lower (MD, -22 ml; 95% CI, -40 to -4; n = 3; low certainty), and no differences were observed in other adverse events (i.e., acute renal failure, gastrointestinal bleeding, impaired bone healing, myocardial infarction, stroke, and death). CONCLUSIONS: Perioperative selective COX‑2 inhibitors likely provide a clinically meaningful reduction in acute pain-related interference with daily function and may improve chronic pain and quality of recovery.

Abstract as published, via PubMed.