Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children

Importance: Intranasal (IN) midazolam is commonly used for procedural sedation in children, but the optimal dose is unclear. Insufficient dosing may result in inadequate sedation, leading to short- and long-term consequences associated with poorly managed procedural pain and distress, whereas doses that are too high may be associated with more adverse events. Objective: To determine the optimal dose of IN midazolam for procedural sedation in children undergoing laceration repair. Design, Setting, and Participants: This prospective, double-blind, adaptive selection randomized clinical trial used the Levin-Robbins-Leu sequential selection procedure and was conducted between September 2021 and May 2024 at a tertiary care pediatric emergency department. Participants were children aged 6 months to 7 years with a simple laceration who required IN midazolam to facilitate the repair. The sequential selection procedure eliminated doses when they failed to achieve a prespecified rate of adequate sedation state compared with the best-performing dose. If more than 1 dose survived elimination, secondary outcomes of remaining doses were compared. Data were analyzed from June to August 2024. Interventions: Doses of 0.2, 0.3, 0.4 or 0.5 mg/kg of IN midazolam. Main Outcomes and Measures: The primary outcome was adequate sedation state, defined as Pediatric Sedation State Scale (PSSS) score of 2, 3, or 4 (of 5) for at least 95% of the procedure; no PSSS score of 0 or 1; procedure start within 17 minutes of IN midazolam administration; and procedure completion. Secondary outcomes included ideal sedation state (PSSS score of 2 or 3 for 100% of the procedure), time to onset of minimal sedation, adverse events, time to recovery, and clinician and caregiver satisfaction. Results: Following the sequential selection procedure, a total of 101 children (38 [37.6%] female; median [IQR] age, 3 [2-4] years) were enrolled. The 0.2 and 0.3 mg/kg doses were eliminated, with 19 children receiving 0.2 mg/kg and 24 children receiving 0.3 mg/kg. The 0.4- and 0.5-mg/kg doses remained at enrollment completion, with 29 children receiving 0.4 mg/kg and 29 children receiving 0.5 mg/kg. There were no differences in secondary outcomes between the 2 remaining doses and no serious adverse events with any dose. Conclusions and Relevance: In this randomized clinical trial, the optimal doses of IN midazolam for procedural sedation in children undergoing laceration repair were 0.4 and 0.5 mg/kg. This finding can inform clinical practice and future studies of IN midazolam for procedural sedation. Trial Registration: ClinicalTrials.gov Identifier: NCT04586504.