The Role of Esketamine in Reducing Propofol-Related Adverse Events During Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis

Propofol is commonly used for sedation in gastrointestinal endoscopy, but its use is associated with dose-dependent adverse effects. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may mitigate these risks when used as an adjunct. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing esketamine plus propofol versus propofol alone in adults undergoing gastrointestinal endoscopy. We systematically searched PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 29, 2025. The primary outcome was the incidence of propofol-related cardiorespiratory adverse events (hypotension, respiratory depression, bradycardia). Data were pooled using a random-effects model. Risk of bias was assessed with the Cochrane risk-of-bias tool for randomized trials (RoB 2). Six RCTs (n = 1,199 patients) were included for qualitative synthesis. Three RCTs (n = 524) provided data for meta-analysis. The pooled analysis demonstrated that esketamine significantly reduced the risk of propofol-related adverse events (relative risk (RR) = 0.43, 95% confidence interval (CI): 0.23-0.82). Heterogeneity was high (I² > 50%). Most studies had a low risk of bias, and sensitivity analysis confirmed the robustness of the findings. Esketamine appears to mitigate propofol-associated adverse events, including hypotension, bradycardia, and respiratory depression, during gastrointestinal endoscopy. Nevertheless, further well-designed, large-scale RCTs are needed to validate these findings and determine optimal dosing strategies.