Tsze DS, Woodward HA, McLaren SH, Leu CS, Venn AMR, Hu NY, Flores-Sanchez PL, Stefan BR, Shen ST, Ekladios MJ, Cravero JP, Dayan PS. Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial. JAMA Pediatr. 2025 Sep 1;179(9):979-986. doi: 10.1001/jamapediatrics.2025.2181. PMID: 40720114; PMCID: PMC12305440.

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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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Mirfazaelian H, Darafshi AS, Sedaghat M, Akbari H. The Effectiveness of Intranasal Ketamine on Intramuscular Ketamine Injection Pain Among Children in the Emergency Department, a Randomized, Controlled Trial. Pediatr Emerg Care. 2025 Dec 1;41(12):e233-e236. doi: 10.1097/PEC.0000000000003485. Epub 2025 Sep 22. PMID: 40976933.

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Abstract
Objective: Children in the emergency department (ED) experience distress due to many factors, such as pain. Although ketamine has analgesic and sedative effects, its parenteral administration causes pain and anxiety. It is notable that ketamine can be administered intranasally for analgesia. We hypothesized that the administration of intranasal (IN) ketamine for analgesia before intramuscular ketamine injection would diminish the injection pain without any adverse effect.

Methods: This study was a randomized, double-blind, placebo-controlled clinical trial conducted in the ED. The IN ketamine group received a dose of 1.5 mg/kg intranasally diluted to 1 mL, while the placebo group received 1 mL of sterile water. Injection pain was assessed using the FLACC scale (0 to 10), encompassing the face, leg, activity, cry, and consolability. Sedation time and adverse effects were also assessed.

Result: Eighty-four patients were enrolled. While the median (IQR) injection pain score in the placebo group was 10 (10 to 10), it was 1 (0 to 5) in the intervention group ( P <0.001). The sedation time in the control group was 80.9±33.6 minutes and 86.4±19.8 in the intervention arm ( P= 0.07). After excluding intraoral procedures, 7 (16.7%) and 2 (4.2%) patients had vomiting in the intervention and placebo groups, respectively. In addition, 3 (7%) patients of the IN-ketamine group had hypoventilation that was resolved with simple airway maneuvers.

Conclusion: Although IN ketamine demonstrated efficacy in reducing injection-related pain, its adverse event profile may limit its practicality in routine settings.