ED50 and ED95 of remimazolam for loss of consciousness in young children: a dose-finding study for induction of anaesthesia

Abstract

Background: The optimal single i.v. bolus dose of remimazolam for induction of general anaesthesia in children is not defined. We aimed to determine the 50% (ED50) and 95% (ED95) effective doses of remimazolam for inducing loss of consciousness in children.

Methods: A total of 120 children, aged 1-12 yr, were divided into three groups, with 40 children in each group: toddler (1 to <3 yr), preschool (≥3 to <6 yr), and school-age group (≥6 to <12 yr). Each child received a single i.v. bolus of remimazolam, with doses determined using a biased coin design up-and-down method. The primary outcome was the ED50 and ED95 of remimazolam for inducing loss of consciousness. Secondary outcomes included the incidence of hypotension, respiratory depression, and adverse events.

Results: The ED50 and ED95 of remimazolam were 0.42 mg kg^-1 (95% confidence interval [CI] 0.37-0.44) and 0.57 mg kg^-1 (95% CI 0.48-0.59), respectively, in the toddler group; 0.41 mg kg^-1 (95% CI 0.35-0.47) and 0.57 mg kg^-1 (95% CI 0.50-0.59), respectively, in the preschool group; and 0.30 mg kg^-1 (95% CI 0.28-0.34) and 0.43 mg kg^-1 (95% CI 0.37-0.44), respectively, in the school-age group. No significant cases of hypotension, respiratory depression, bradycardia, or other adverse events occurred in any of the three groups.

Conclusions: A single i.v. bolus of remimazolam at estimated doses of 0.45-0.60 mg kg^-1 for children aged 1-6 yr and 0.35-0.45 mg kg^-1 for those aged 6-12 yr effectively induces loss of consciousness in children.

Clinical trial registration: ClinicalTrials.gov (NCT06061159).

Keywords: benzodiazepine; children; consciousness; general anaesthesia; remimazolam.