ED90 of Intravenous remimazolam for alleviating preoperative anxiety in children: a prospective dose-finding study

Abstract

Background: Children's minds are immature, making them more susceptible to severe anxiety when separated from their parents before surgery. Alleviating preoperative anxiety in children is essential for providing comfort-oriented healthcare. Remimazolam is a novel ultra-short-acting benzodiazepine. Existing studies have identified the effective dose for 50% of patients (ED50) when administering intravenous remimazolam to alleviate preoperative anxiety in children.However,the 90% effective dose (ED90) is clinically more meaningful. This study aims to determine the ED90 of intravenous remimazolam in alleviating preoperative anxiety in pediatric patients aged 1 to 6 years. Methods:From April to August 2025, pediatric patients undergoing elective surgery under general anesthesia were enrolled and stratified into two age groups: a younger group (YG, aged 1 to <4 years) and an older group (OG, aged 4–6 years inclusive). We employed the biased coin design (BCD) to determine target doses, defining a positive response as effective relief of preoperative anxiety [Parent Separation Anxiety Scale (PSAS) score < 3]. The initial dose for the first patient was 0.2 mg/kg. For subsequent pediatric patients, the dose was adjusted by increasing or decreasing by 0.05 mg/kg based on sedation response of the previous case. Isotonic regression and bootstrapping methods were used to estimate the ED90 and 90% confidence interval(CI), respectively. Results: Eighty children completed the study, 40 in YG group and 40 in OG group . Statistical analysis indicated that the ED90 (90% CIs) values for remimazolam used for alleviating preoperative anxiety in pediatric patients were 0.20 mg/kg(0.17–0.24)in the YG group and 0.15 mg/kg(0.11–0.17)in the OG group. Given that the 83% CIs for the ED90 showed no overlap between the YG group (0.18–0.24) and the OG group (0.12–0.17), the difference between the two groups is considered statistically significant. Conclusion:The ED90 of intravenous remimazolam for preoperative anxiolysis was 0.20 mg/kg in children aged 1 to <4 years and 0.15 mg/kg in those aged 4 to 6 years. Notably, older children require even lower weight-based doses.