Comparative acceptability and immediate behavioral response to different pediatric premedications: A systematic review and network meta-analysis.

STUDY

OBJECTIVE

To compare the acceptability and immediate behavioral response of different premedications, considering routes and formulations.

DESIGN

Systematic review and Bayesian network meta-analysis of randomized controlled trials

SETTING

Elective procedures involving pediatric patients undergoing general anesthesia or sedation PATIENTS: Children aged 1-12 years, classified as ASA physical status I-III, receiving premedication with midazolam, dexmedetomidine, clonidine, ketamine, or related agents.

MEASUREMENTS: Two separate Bayesian network meta-analyses were performed. The first evaluated premedication acceptability (the child's willingness to take the drug), and the second assessed the immediate behavioral response after administration. Each intervention was classified by drug, formulation, and route of administration. Outcomes were ranked using SUCRA values. Risk of bias, node-splitting, and model diagnostics were assessed to evaluate robustness and consistency MAIN

RESULTS

Twenty-four trials comprising 1858 patients were included in the quantitative synthesis. Both oral midazolam in commercial syrup and oral midazolam using the intravenous formulation mixed with syrup showed the highest acceptability. Interventions with low acceptability included nebulized ketamine, midazolam, and dexmedetomidine. For immediate behavioral response, the most favorable responses were observed with oral or intranasal clonidine, followed by oral midazolam mixed with syrup. Intranasal midazolam consistently showed the poorest behavioral response among all interventions. Commercial midazolam syrup could not be analyzed.

CONCLUSIONS

Syrup-based oral midazolam offers a favorable balance between acceptability and behavioral response, making it a practical option for pediatric premedication. Intranasal clonidine and dexmedetomidine demonstrated moderate behavioral performance, with dexmedetomidine also showing moderate acceptability. In contrast, nebulized formulations were poorly accepted, and intranasal midazolam, despite good acceptability, was poorly tolerated. These findings provide comparative evidence on acceptability and tolerability, which should be integrated with existing evidence on efficacy and safety when selecting premedication strategies in pediatric anesthesia.

REGISTRATION: PROSPERO ID: CRD420251048872.