Effects of Esketamine on Emergence Delirium in Children Undergoing Sevoflurane Anesthesia: A Systematic Review, Meta‐Analysis, and Trial Sequential Analysis

Abstract

BACKGROUND: Emergence delirium is a frequent and distressing postoperative complication in children, particularly following sevoflurane-based anesthesia. Despite its clinical importance, the optimal preventive strategy remains under investigation. This study aims to systematically evaluate the efficacy and safety of esketamine in preventing emergence delirium in pediatric patients undergoing sevoflurane-based general anesthesia. METHODS: We systematically searched seven databases and registries through 27 March 2026. Randomized controlled trials that compared esketamine with placebo in children undergoing surgical procedures were included. The primary outcome was the incidence of emergence delirium. Secondary outcomes were postoperative pain scores, extubation time, post-anesthesia care unit stay, and postoperative nausea and vomiting. Data were synthesized using random-effects models, with risk ratios for dichotomous outcomes and mean differences or standardized mean differences for continuous outcomes. Meta-regression and trial sequential analysis were performed. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials, and the certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Eight randomized controlled trials involving 916 patients were included. Esketamine significantly reduced the incidence of emergence delirium versus placebo (risk ratio = 0.35; 95% confidence interval: 0.26-0.48; p < 0.0001). No significant differences were observed between dosing regimens, surgical types, routes of administration, or timing of administration. Pain scores were significantly lower with esketamine (standardized mean difference = -0.58; 95% confidence interval: -0.79 to -0.37; p < 0.0001). Extubation time was modestly prolonged (mean difference = 1.72 min; 95% confidence interval: 0.20-3.24; p = 0.0267). Meta-regression revealed a statistically significant association between emergence delirium risk ratios and anesthesia duration (β = 0.98, p = 0.042), with no other significant associations observed for the other covariates. Post-anesthesia care unit stay showed no statistically significant difference, while postoperative nausea and vomiting was significantly reduced with esketamine (risk ratio = 0.69; 95% confidence interval: 0.49-0.97; p = 0.0304). No study was at high-risk of bias; four studies raised some concerns. Certainty of evidence was moderate, except for extubation time, which was low. CONCLUSIONS: Esketamine demonstrates promising efficacy for preventing emergence delirium and improving postoperative pain in children. PROSPERO: CRD420251230407.