The effectiveness of selective COX-2 inhibitors for postoperative pain management using multidimensional pain assessment: A systematic review and meta-analysis of randomized controlled trials

Background: Although selective 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: We systematically searched MEDLINE, Embase, and Cochrane CENTRAL for randomized controlled trials (RCTs) 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 [BPI]; 0-10 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: We screened 9,071 citations and 38 RCTs (5,424 participants) met eligibility criteria. Selective COX-2 inhibitors were associated with a reduction in acute pain‑related interference (BPI mean difference [MD], −1.1; 95% confidence interval [CI], −1.4 to −0.84; 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 0.67; n=1; very low certainty). The modelled 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 [0-18 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.