Managing postoperative pain in adult outpatients: a systematic review and meta-analysis comparing codeine with NSAIDs

BACKGROUND: Analgesics that contain codeine are commonly prescribed for postoperative pain, but it is unclear how they compare with nonopioid alternatives. We sought to compare the effectiveness of codeine and nonsteroidal anti-inflammatory drugs (NSAIDs) for adults who underwent outpatient surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing codeine and NSAIDs for postoperative pain in outpatient surgery. We searched MEDLINE and Embase from inception to October 2019 for eligible studies. Our primary outcome was the patient pain score, converted to a standard 10-point intensity scale. Our secondary outcomes were patient-reported global assessments and adverse effects. We used random-effects models and grading of recommendations assessment, development and evaluation (GRADE) to assess the quality of evidence. RESULTS: Forty studies, including 102 trial arms and 5116 patients, met inclusion criteria. The studies had low risk of bias and low-to-moderate heterogeneity. Compared with codeine, NSAIDs were associated with better pain scores at 6 hours (weighted mean difference [WMD] 0.93 points, 95% confidence interval [CI] 0.71 to 1.15) and at 12 hours (WMD 0.79, 95% CI 0.38 to 1.19). Stronger NSAID superiority at 6 hours was observed among trials where acetaminophen was coadministered at equivalent doses between groups (WMD 1.18, 95% CI 0.87 to 1.48). NSAIDs were associated with better global assessments at 6 hours (WMD -0.88, 95% CI -1.04 to -0.72) and at 24 hours (WMD -0.67, 95% CI -0.95 to -0.40), and were associated with fewer adverse effects, including bleeding events. INTERPRETATION: We found that adult outpatients report better pain scores, better global assessments and fewer adverse effects when their postoperative pain is treated with NSAIDs than with codeine. Clinicians across all specialties can use this information to improve both pain management and opioid stewardship.