Esketamine for Postoperative Multimodal Analgesia in Laparoscopic Surgery: A Systematic Review and Meta-Analysis

Postoperative pain management after laparoscopic surgery remains challenging. Esketamine, a potent N-methyl-D-aspartate receptor antagonist, may improve multimodal analgesia while mitigating opioid-related side effects. This meta-analysis evaluates the efficacy and safety of perioperative intravenous esketamine in adults undergoing laparoscopic surgery.

We conducted a systematic review and meta-analysis of randomized controlled trials according to PRISMA guidelines. Databases were searched from inception to October 1, 2025. Primary outcomes were postoperative pain intensity (at rest and during movement at 24 hours) and 24-hour opioid consumption. Secondary outcomes included rescue analgesia, postoperative nausea and vomiting (PONV), hallucinations, and depressive symptoms. Data were pooled using random-effects models, and evidence certainty was assessed with GRADE.

Twenty-eight RCTs (3160 patients), all conducted in China, were included. Esketamine significantly reduced pain at rest (SMD -0.65, 95% CI -0.90 to -0.40) and during movement (SMD -0.64, 95% CI -1.09 to -0.19), and decreased 24-hour opioid consumption (SMD -16.83, 95% CI -31.60 to -2.05). It also reduced rescue analgesia requirements (RR 0.51, 95% CI 0.35 to 0.76) and PONV incidence (RR 0.76, 95% CI 0.63 to 0.93) without increasing hallucinations (RR 1.11, 95% CI 0.41 to 3.03). A reduction in postoperative depressive symptoms was observed (SMD -0.67, 95% CI -1.29 to -0.05). Subgroup analyses suggested greater analgesic benefit with low-dose regimens (<0.5 mg/kg) and in biliary surgeries. Evidence certainty was low to very low for primary outcomes. Twenty-eight RCTs (3160 patients), all conducted in China, were included, which may limit the generalizability of the findings. Esketamine was associated with reductions in pain at rest (SMD -0.65, 95% CI -0.90 to -0.40) and during movement (SMD -0.64, 95% CI -1.09 to -0.19), and decreased 24-hour opioid consumption (SMD -16.83, 95% CI -31.60 to -2.05), although substantial heterogeneity was observed. It also reduced rescue analgesia requirements (RR 0.51, 95% CI 0.35 to 0.76) and PONV incidence (RR 0.76, 95% CI 0.63 to 0.93) without increasing hallucinations (RR 1.11, 95% CI 0.41 to 3.03). A reduction in postoperative depressive symptoms was observed (SMD -0.67, 95% CI -1.29 to -0.05). Subgroup analyses suggested greater analgesic effects with low-dose regimens (<0.5 mg/kg) and in biliary surgeries. Evidence certainty was low to very low for primary outcomes.

Perioperative intravenous esketamine may be associated with improvements in postoperative pain, opioid requirements, rescue analgesia, and PONV in laparoscopic surgery without increasing neuropsychiatric adverse events. However, the certainty of the evidence is low and substantial heterogeneity limits confidence in these estimates. Therefore, these findings should be interpreted with caution, and high-quality, international RCTs are needed to confirm efficacy and establish optimal dosing.