Analgesic effect of intravenous nefopam for postoperative pain in spine surgery: a meta-analysis of RCTs.

BACKGROUND AND

OBJECTIVE

For the management of postoperative pain, opioids have typically been half their efficacy, but they are associated with notable side effects such as sedation, nausea, and respiratory depression. Nefopam is a non-opioid analgesic, within the benzoxazocine class, that has been suggested as an important adjunctive analgestic in multimodal analgesia (MMA). However, the extent to which analgesics outside of opioids are accepted as part of Enhanced Recovery After Surgery (ERAS) programs is controversial. The difficulty of predicting pain management outcome, considering the variability in postoperative pain, means that study of the analgesic effect of intravenous nefopam given different strategies, is essential in the use of nefopam for spinal surgery.

METHODS

We completed a systematic search of PubMed, Scopus, and Google Scholar until July 20, 2025. We included randomized controlled trials (RCTs) that assessed intravenous nefopam for treating postoperative pain in patients who had spine surgery. The extracted data were pooled, and we performed a random-effects meta-analysis. Subgroup analyses were planned to compare bolus use, infusion use, and bolus plus infusion use.

RESULTS

Seven RCTs, involving a total of 471 patients, were included in the eligibility criteria. The overall pooled analysis found no differences in postoperative pain scores between the nefopam and control conditions. The standardized mean difference (SMD) was -0.28 (95% confidence interval [CI]: -0.74 to 0.18), which indicated no difference in efficacy. The sub-group analysis found that bolus administration had the greatest analgesic effect (SMD = -0.70) and infusion or bolus + infusions had little or no clinical benefit. The infusion sub-group had the greatest heterogeneity (I2 = 86.9%) suggesting variability in studies for this delivery method.

CONCLUSION

The use of intra-venous nefopam offers a small analgesic benefit in spine surgery, which is best seen when applied intermittently or as a bolus rather than as a continuous infusion. Though it is not particularly effective as a standalone agent, bolus does have potential as an adjunct and should be included as part of a more multimodal analgesia approach. Further high quality RCTs with larger sample sizes are warranted to better define the optimal application of nefopam and dosing in patients undergoing spinal surgery.