Efficacy of intraoperative low dose intravenous Esketamine for acute postoperative pain control: Meta-analysis of randomized controlled trials

To evaluate the effect of intraoperative low-dose intravenous esketamine (<1 mg/kg) on acute postoperative pain, opioid consumption, adverse events, and anesthetic requirements through a systematic review and meta-analysis of randomized controlled trials.

We systematically searched PubMed, Cochrane Central, and Embase (to Apr 28, 2025) for RCTs on intraoperative low dose IV esketamine (<1 mg/kg) for acute postoperative pain. Data was analyzed in R using mean differences or risk ratios (95% CIs). Risk of bias followed Cochrane methods. Sensitivity used leave-one-out and meta-regression.

Thirty-five RCTs (3831 patients; 1663 control, 2168 esketamine) showed low-dose IV esketamine significantly reduced pain at rest at 4 h (MD -1.40; p < 0.0001), 12 h (-0.84; p < 0.0001), 24 h (-0.54; p < 0.0001), and 48 h (-0.39; p = 0.0014). Pain on movement was lower at 12 h (-0.62; p = 0.0111), 24 h (-0.63; p = 0.0003) and 48 h (MD -0.40, 95% CI -0.74 to -0.06; p = 0.0212; I² = 75.5%). No significant differences in overall or individual adverse events (nausea, agitation, dizziness, hallucinations) were observed between groups. Postoperative morphine consumption was reduced at 4, 24 and 48 h, with no significant difference at 12 h. Rescue analgesia requirements were reduced (RR 0.52; p = 0.0001), and intraoperative propofol use was modestly lower (-18.47 mg; p = 0.0047). No significant dose-response relationship was identified (p = 0.0571).

Intraoperative low-dose esketamine modestly reduces postoperative pain at rest (4-48 h) and during movement (12-48 h), decreases opioid and rescue analgesia requirements, and slightly lowers propofol use. However, the magnitude and consistency of these effects are uncertain due to heterogeneity and study limitations. Adverse events did not differ significantly, though evidence remains limited. Esketamine may be considered as an adjunct in perioperative pain management with appropriate monitoring.