Efficacy and Safety of Different Preoperative Sedative Regimens in Alleviating Pediatric Preoperative Anxiety: A Systematic Review and Network Meta‐Analysis

ABSTRACT Background Pediatric preoperative anxiety (PPA) is a prevalent condition that exhibits significant effects on the psychological and physiological status of children both preoperatively and postoperatively. Methods We conducted systematic review and network meta‐analysis. PubMed, Embase, Web of Science Core Collection, and The Cochrane Library were searched up to December 1, 2024. RCTs of pediatric patients (0–14 years) receiving preoperative sedatives were included. Primary outcome was Parental Separation Anxiety Scale (PSAS); secondary outcomes were Mask Acceptance Scale (MAS), postoperative nausea/vomiting (PONV), and delirium/agitation (PODA). Results Seventy studies (16,626 participants) were included. Five sedatives including midazolam, dexmedetomidine, ketamine (oral, intranasal, nebulized), clonidine (oral, intranasal), and melatonin (oral) were compared with placebo. Data from 20 interventions (5581 patients) assessed PPA. Intranasal dexmedetomidine (ID) showed highest single‐drug efficacy (SUCRA: PSAS 68.1%, MAS 48.8%, PONV 65.7%, PODA 67.8%). Oral ketamine (OK) and midazolam (OM/IM) were effective alternatives. Combined regimens were promising but inconclusive. Conclusions ID significantly alleviated PPA with minimal adverse effects in single‐drug regimens (optimal dose: 1–2 µg/kg). OK, OM or IM served as potential alternative options for clinical application. While combination regimens (notably OM+OK) demonstrated superior efficacy across outcomes, small sample sizes necessitate cautious interpretation, underscoring the need for future comparative studies.