The safety and efficacy of perioperative nefopam for analgesia in spine surgery: A systematic review and meta-analysis of randomised controlled trials

Clinical Snapshot

Key Findings

• P Value: Not significant

• Effect Size: MD -1.47 mg

• Primary Outcome: 24-hour morphine consumption

• Nnt Or Sensitivity: No clinically meaningful reduction in opioid consumption

• Confidence Interval: 95% CI: -3.86 to 0.92 mg

Clinical Application

Limited by suboptimal dosing in most studies and lack of clear benefit over standard care Nefopam available on PBS for specific indications; results suggest limited evidence for routine use in spine surgery without dose optimisation studies Adult patients undergoing spine surgery requiring multimodal analgesia

Abstract

OBJECTIVE: Moderate-to-severe pain is common after spine surgery. While opioids remain standard analgesia, their adverse effects have prompted opioid-sparing strategies. This systematic review evaluates the safety and efficacy of nefopam, a non-opioid and non-NSAID, as adjuvant perioperative analgesia in spine surgery. METHODS: Medline, Embase, Scopus and Cochrane databases were searched from inception to May 9, 2025. RevMan V5.4 was used to analyse mean differences (MD) or standardised mean differences (SMD) and 95% confidence intervals (CIs) for continuous outcomes and risk ratios (RR) with 95% CIs for dichotomous outcomes. The GRADE framework was used to assess the certainty of evidence. RESULTS: Seven randomised controlled trials (n = 553) were included. Nefopam did not reduce 24-hour morphine use (MD -1.47 mg; 95% CI: -3.86 to 0.92 mg; GRADE moderate), 24-hour incisional pain (SMD, -0.01; 95% CI -0.22 to 0.20; GRADE moderate), 48-hour incisional pain (SMD, -0.24; 95% CI -0.50 to 0.02; GRADE low), 24-hour neuropathic pain (SMD, -0.19; 95% CI -0.49 to 0.10; GRADE low), 72-hour neuropathic pain (SMD, -0.33; 95% CI -1.02 to 0.36; GRADE very low), or length of stay (MD, 0.08days; 95% CI -0.73 to 0.88days; GRADE Low). There were no significant differences in drug-related adverse effects (sedation (RR 1.30), nausea/vomiting (RR 1.03), dizziness (RR 1.14), and urinary retention (RR 2.36)), (GRADE: very low to low). CONCLUSION: Perioperative nefopam did not reduce acute morphine use, pain scores, hospital stay, or drug-related adverse events in spine surgery, though most studies used doses below the median effective dose, limiting conclusions on its efficacy and safety.

References

1. 1.Osunronbi, T., Okechukwu, H., Adeyeye, E., Abbou, Z., Mtemeri, J., & Karmi, Z. (2026). The safety and efficacy of perioperative nefopam for analgesia in spine surgery: A systematic review and meta-analysis of randomised controlled trials. Neurosurgical Review. https://doi.org/10.1097/00000542-200506000-00022