Intranasal Dexmedetomidine Versus Esketamine As Premedication for the Sedation of Pediatric Patients: A Systematic Review and Meta-Analysis.

Preoperative anxiety is a common problem in pediatric surgical patients and is a recognized predictor of emergence delirium (ED) and postoperative negative behavioral changes (PNBC). Intranasal premedication has emerged as a preferred route in children. Both dexmedetomidine and esketamine have demonstrated independent efficacy in this context. Their pharmacological complementarity has prompted growing interest in their combined use, yet no systematic review has comprehensively compared their efficacy and safety as monotherapies across pediatric procedural settings. This review aimed to evaluate and compare intranasal dexmedetomidine versus intranasal esketamine in pediatric patients. The study was conducted in accordance with the Cochrane Handbook and reported following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases were searched without date restriction. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for the cohort study. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals were calculated using RevMan 5.4, with fixed- or random-effects models applied based on heterogeneity. The final analysis included five studies (four RCTs, one prospective cohort) with a combined sample of 481 pediatric participants. In elective surgical settings, dexmedetomidine at 2 µg/kg significantly reduced ED incidence compared to esketamine (RR 0.57 (0.38, 0.86); p=0.008) and was associated with significantly lower Pediatric Anesthesia Emergence Delirium (PAED) scale scores (MD -1.28 (-2.36, -0.20); p=0.02). Conversely, esketamine demonstrated significantly lower PAED scores in the bronchoscopy subgroup (MD 2.73 (1.84, 3.62); p<0.00001). Dexmedetomidine was also associated with significantly lower Face Legs Activity Cry Consolability (FLACC) pain scores in the emergency department subgroup (MD -3.25 (-5.64, -0.86); p=0.008). Regarding the primary endpoints, the overall pooled ED incidence did not differ significantly between agents (RR 0.77 (0.37, 1.62); p=0.49), nor did overall FLACC pain scores (MD -0.24 (-1.13, 0.65); p=0.60). Intranasal dexmedetomidine and esketamine demonstrate comparable overall efficacy and safety as pediatric premedication agents, with neither showing a significant pooled advantage over the other. However, their comparative performance is context- and dose-dependent, with dexmedetomidine at 2 µg/kg proving superior in elective surgical settings, and esketamine performing better in bronchoscopy procedures. These findings support individualized agent selection based on procedural context and dosing rather than a universal preference for either agent. Larger, standardized multicenter trials are needed to establish definitive evidence-based premedication recommendations across pediatric surgical settings.