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

TL;DR

This study finds the effective dose of remimazolam needed to reduce anxiety in children before surgery, showing that younger children need higher doses than older ones.

Contribution

The study determines the ED90 of intravenous remimazolam for preoperative anxiety in children, stratified by age groups.

Findings

The ED90 for children aged 1 to <4 years is 0.20 mg/kg.

The ED90 for children aged 4–6 years is 0.15 mg/kg.

The effective doses differ significantly between the two age groups.

Abstract

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 1–6 years.

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.

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.

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 4–6 years. Notably, older children require even lower weight-based doses.

https://www.chictr.org.cn/bin/project/edit?pid=252632, identifier ChiCTR2500098747.

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