Optimizing pediatric premedication for general anesthesia: A comprehensive Bayesian network meta-analysis

Abstract

Study objective: To identify the most effective premedication strategies for improving mask acceptance, parental separation acceptance, and intravenous cannulation acceptance in pediatric patients undergoing general anesthesia.

Design: A systematic review and Bayesian network meta-analysis of randomized controlled trials.

Setting: Elective pediatric surgeries under general anesthesia.

Patients: Children aged 1-12 years, classified as American Society of Anesthesiologists (ASA) I-III, who received premedication with midazolam, dexmedetomidine, ketamine, or other relevant agents and combinations.

Measurements: Two main analyses were conducted using a Bayesian framework to generate comparative efficacy rankings. A primary analysis considered every unique combination of drug, dose, route, and timing as a distinct intervention. A secondary analysis grouped interventions solely by the pharmacological agent(s) used, regardless of dose, route, or timing. This dual approach allowed specific comparisons of route and dose while also providing a broader assessment of each drug or combination. Outcomes were satisfactory acceptance of mask application, parental separation, and intravenous cannulation. Meta-regression, sensitivity analyses, and assessment of risk of bias were also undertaken.

Main results: Sixty-nine trials encompassing 5794 pediatric patients were included. In the primary analysis, only mask acceptance could be evaluated. Combinations of dexmedetomidine, midazolam, and ketamine demonstrated the highest probabilities of satisfactory mask acceptance, with intranasal administration at shorter premedication intervals (15-30 min) showing greater efficacy. Clonidine, melatonin, and diazepam were comparatively less effective. In the secondary analysis, mask acceptance, intravenous cannulation acceptance, and parental separation acceptance yielded similar findings, with pharmacological combinations based on dexmedetomidine and midazolam ranking highest, while clonidine, melatonin, and diazepam remained less effective.

Conclusions: Dexmedetomidine-, midazolam-, and ketamine-based combinations offer superior preoperative cooperation in pediatric patients, as demonstrated by higher success rates of mask acceptance, intravenous cannulation acceptance, and parental separation acceptance. Routes, doses, and timing are critical factors influencing success.

Keywords: Dexmedetomidine; Ketamine; Midazolam; Network meta-analysis; Pediatric anesthesia; Premedication; Sedation.