Efficacy of intraoperative ketamine/esketamine in the prevention of postoperative delirium: a systematic review and meta-analysis.

Background: Postoperative delirium (POD) is associated with higher risks of postoperative complications ‌and‌ mortality (2- to 3-fold increase). Studies investigating the effect of intraoperative ketamine on POD risk have yielded conflicting results. This study aimed to assess the effects of intraoperative ketamine and its more potent version, esketamine, on POD.

Design: Systematic review and meta-analysis.

Objective: To evaluate the effect of intraoperative ketamine/esketamine on the incidence of POD.

Methods: We adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and searched the PubMed, Embase, Medline (Ovid), Cochrane, Scopus, and Web of Science databases for the MeSH terms "ketamine" and "emergence delirium" from database inception to July 10, 2024. The primary outcome was POD incidence following general anesthesia. Data were analyzed using a common effects model, with between-study heterogeneity tested using the I ² statistic, and relative risk (RR) with 95% confidence intervals (CIs) for dichotomous data was used as the effect measure.

Results: A total of 18 studies with a total of 1571 participants met eligibility criteria. A meta-analysis of all studies suggests that the intraoperative use of ketamine/esketamine may reduce the incidence of POD (RR = 0.71, 95% CI: 0.56, 0.90, p < 0.01). In the drug subgroup, esketamine demonstrated enhanced efficacy in preventing POD compared to ketamine (RR = 0.59, 95% CI: 0.38, 0.90, p = 0.02). In addition, subanesthetic doses of ketamine/esketamine (⩽0.5 mg/kg) contributed to POD prevention (RR = 0.52, 95% CI: 0.34, 0.79, p < 0.01), whereas higher doses (>0.5 mg/kg) showed no statistically significant effect (RR = 0.89, 95% CI: 0.66, 1.21, p = 0.46). Further analysis revealed additional benefits of ketamine/esketamine in reducing POD incidence in cardiac surgery (RR = 0.46, 95% CI: 0.31, 0.68, p < 0.01), in the elderly (RR = 0.68, 95% CI: 0.52, 0.91, p < 0.01), and in the first 24 h post-surgery (RR = 0.52, 95% CI: 0.29, 0.94, p = 0.03).

Conclusion: Our findings suggest that perioperative administration of ketamine/esketamine had a protective effect against the incidence of POD, with esketamine demonstrating superior efficacy compared to ketamine. The treatment effect exhibited a dose-response relationship, with subanesthetic doses showing greater efficacy. Furthermore, ketamine/esketamine may offer additional benefits for patients with specific risk factors.