The effect of esketamine on postoperative delirium in patients undergoing general anesthesia: a systematic review and meta-analysis.

Background: Postoperative delirium (POD), a prevalent neurological complication, is strongly associated with adverse clinical outcomes. This meta-analysis aimed to evaluate the efficacy of esketamine in preventing POD among patients receiving general anesthesia. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, clinical trial registries and major conference proceedings for randomized controlled trials (RCTs) examining esketamine's impact on POD in general anesthesia patients, from inception through 30 June 2025. Statistical analyses were performed using RevMan 5.4 and Stata 12.0. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI), while continuous variables were analyzed via mean differences (MD). Study bias was assessed with the Cochrane ROB 2.0 tool. Results: Thirteen RCTs involving 1,873 elective surgery patients under general anesthesia were included. Esketamine administration was associated with a lower POD incidence (RR: 0.66; 95% CI: 0.49-0.91; P < 0.05). Subgroup analyses revealed potentially significant reductions in adult populations and cardiac surgery cohorts. The postoperative nausea and vomiting (PONV) rate decreased in the esketamine group. Additionally, esketamine was associated with reduced pain scores at 24 h postoperatively. Conclusion: Our findings suggest that esketamine may be associated with a lower POD risk following general anesthesia. Further large-scale trials are warranted to validate these preliminary findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/recorddashboard.