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.

Outpatient surgical procedures are now more common than inpatient procedures, given the development of less invasive techniques, the drive for health care efficiency, and improvements in anesthesia and pain management. ^1–4 Postoperative pain management after outpatient procedures often includes low-potency or low-dose opioids.⁵ Codeine use is widespread in this setting and codeine remains the most commonly prescribed opioid in many countries, including Canada.^6–9 However, its efficacy is variable, its potency is low and its use is associated with risks of severe adverse effects and misuse.¹⁰ Amid the ongoing opioid crisis, management of pain and potential opioid misuse is important across all medical and dental specialties.¹¹Nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to low-potency opioids. The potency, effects and toxicity of NSAIDs depend on the degree to which they inhibit cyclooxygenase 1 and 2 activity. Their main adverse effects are gastrointestinal bleeding, renal impairment and myocardial infarction with long-term use.^12–15 Postoperative pain can be effectively managed with NSAIDs, and NSAIDs have been shown to reduce opioid consumption in postoperative patients.¹⁶Given how commonly these medications are used, and the uncertainty in their comparative efficacy and safety, we sought to compare pain and safety outcomes for codeine-based medications and NSAIDs among adults who underwent outpatient surgery through a systematic review and meta-analysis of randomized controlled trials (RCTs).