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Clinical Trial
. 2025 Sep 1;179(9):979-986.
doi: 10.1001/jamapediatrics.2025.2181.

Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial

Daniel S Tsze  1 , Hilary A Woodward  2 , Son H McLaren  1 , Cheng-Shiun S Leu  3 , April M R Venn  1 , Nina Y Hu  1 , Pamela L Flores-Sanchez  1 , Bianca R Stefan  1 , Sripriya T Shen  1 , Mina J Ekladios  1 , Joseph P Cravero  4 , Peter S Dayan  1
Affiliations
Clinical Trial

Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial

Daniel S Tsze et al. JAMA Pediatr. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Tsze reported grants from Emergency Medicine Foundation during the conduct of the study and grants from National Institute of Neurological Disorders and Stroke (NINDS) and Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Dr Woodward reported grants from Emergency Medicine Foundation during the conduct of the study. Dr Leu reported grants from Emergency Medicine Foundation during the conduct of the study. Dr Dayan reported grants from Columbia University Emergency Medicine Foundation during the conduct of the study and grants from Columbia University, Health Resources and Services Administration, and NINDS outside the submitted work. No other disclosures were reported.

References

    1. Tsze DS, Ieni M, Fenster DB, et al. Optimal volume of administration of intranasal midazolam in children: a randomized clinical trial. Ann Emerg Med. 2017;69(5):600-609. doi: 10.1016/j.annemergmed.2016.08.450 - DOI - PMC - PubMed
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    1. Kumar K, Ali S, Sabhaney V, et al. ; Pediatric Emergency Research Canada . Anxiolysis for laceration repair in children: a survey of pediatric emergency providers in Canada. CJEM. 2022;24(1):75-83. doi: 10.1007/s43678-021-00210-y - DOI - PubMed
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