The safety and efficacy of peri-operative nefopam for analgesia in hip and knee arthroplasty: A systematic review and meta-analysis.

PURPOSE: Opioid-related adverse effects have prompted interest in opioid-sparing strategies in joint arthroplasty. This systematic review evaluates the safety and efficacy of perioperative nefopam, a non-opioid, non-NSAID analgesic, in patients undergoing hip and knee arthroplasty. METHODS: Medline, Cochrane, Embase, and Scopus were searched from database inception to September 2025. For meta-analysis, continuous outcomes were pooled as mean differences (MD) with 95% confidence intervals (CI), and dichotomous outcomes as risk ratios (RR). Certainty of evidence was assessed using GRADE. RESULTS: Four unique randomised control trials (n = 425) were included. Nefopam was not associated with significant reductions in opioid consumption at 24 h (4 studies, 425 patients, MD - 6.73 mg; 95% CI - 18.56 to 5.09 mg; GRADE: +). However, nefopam significantly reduced pain during movement at 24 h (3 studies, 225 patients, MD - 8.24; 95% CI - 13.52 to - 2.96; GRADE: +++) but not 24-hour pain score at rest (4 studies, 425 patients; MD -4.96; 95% CI -12.78 to 2.87; GRADE: +). Nefopam was also associated with improved knee range of motion at 24 h postoperatively (2 studies, 177 patients, MD 7.78°; 95% CI 7.33° to 8.24°; GRADE: +++). No significant differences were observed for length of hospital stay, patient satisfaction, or adverse-event outcomes. CONCLUSION: Nefopam reduced pain during movement and improved early knee range of motion at 24 h but did not reduce acute opioid consumption or drug-related adverse effects after hip or knee arthroplasty.