Up-and-Down Sequential Allocation Study Comparing the Median Effective Dose of Remimazolam Versus Propofol for...

Remimazolam is a novel ultra-short-acting benzodiazepine used for general anesthesia. Compared with propofol, it offers reversibility with flumazenil and lacks injection pain. However, its optimal bolus dose for anesthesia induction in pediatric patients remains unclear. The aim of this study was to determine the effective dose of remimazolam for loss of consciousness during anesthesia induction in children aged 2 to 14 years.

A prospective, randomized, controlled trial using the Dixon up-and-down sequential design was conducted. It comprised two separate, parallel dose-finding studies, in which a total of fifty children undergoing elective surgery were randomly allocated to receive either remimazolam or propofol for anesthesia induction, respectively. The primary outcome was the ED₅₀ and ED₉₅ of each drug. Secondary outcomes included bispectral index (BIS) values, hemodynamic changes, and adverse events within 5 min after drug administration.

The ED₅₀ and ED₉₅ of remimazolam were 0.17 mg/kg (95% CI 0.16-0.19) and 0.26 mg/kg (95% CI 0.23-0.29). Both drugs effectively reduced BIS values, with a significant group-time interaction. Heart rate was more stable in the remimazolam group. No respiratory depression, hypotension, or other serious adverse events were observed in either group.

Using a sequential up-and-down design, this study provides the first determination of the ED₅₀ (0.17 mg/kg) of a single intravenous bolus of remimazolam for inducing loss of consciousness in pediatric patients aged 2-14 years. These findings offer a practical dosing reference for remimazolam induction in children.

Chinese Clinical Trial Registry: ChiCTR 2200067112.