Intranasal esketamine plus dexmedetomidine versus dexmedetomidine alone for emergence delirium in pediatric patients: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Intranasal dexmedetomidine is commonly used preoperatively in pediatric anesthesia to reduce agitation and emergence delirium. Esketamine, with sedative and analgesic ef-fects and minimal respiratory depression at clinical doses, is also widely used in chil-dren. However, current evidence remains limited regarding the efficacy and safety of combining intranasal esketamine with dexmedetomidine versus dexmedetomidine alone in improving cooperation during anesthesia induction and reducing postoperative complications. METHODS: This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD420251084757). A systematic search of PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Wanfang was conducted up to May 25, 2025. The primary outcome included the incidence of emergence delirium, emergence time, mask acceptance score (MAS), parental separation anxiety score (PSAS), and the incidence of adverse events, with pooled effect estimate reported as proportions and relative risk (RR) with 95% confidence intervals (CIs). Sensitivity analysis were performed to assess the robustness of the results and to identify sources of heterogeneity. RESULTS: Six studies involving a total of 515 pediatric patients were included. Compared with dexmedetomidine alone, intranasal esketamine combined with dexmedetomidine significantly reduces the incidence of emergence delirium (RR = 0.27, 95% CI: [0.17-0.44], P < 0.00001, I² = 0%). The incidence of bradycardia is also significantly lower in the combination group (RR = 0.24, 95% CI: [0.08-0.72], P = 0.01). No statistically significant differences are observed between the two groups in terms of emergence time or the incidence of nausea and vomiting. The combination group shows lower parental separation anxiety scores and better mask acceptance scores, indicating improved cooperation during anesthesia induction. CONCLUSION: Preoperative intranasal administration of esketamine combined with dexmedetomidine significantly reduces the incidence of emergence delirium and bradycardia compared with dexmedetomidine alone.Improved cooperation during anesthesia induction further supports the potential of this combination as a safe and effective alternative to dexmedetomidine monotherapy in pediatric anesthesia. TRIAL REGISTRATION: Not applicable.