ED90 of intravenous remimazolam for alleviating preoperative anxiety in children: a prospective dose-finding study
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Published on: July 30, 2009
Xu-Ming Zhu1, Xiao-Yong Wei1, Qian-Yu Guo1
1Department of Anesthesiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Insights
The 90% effective dose (ED90) of remimazolam for reducing preoperative anxiety in children aged 1 to 6 years was determined. Younger children (1-3 years) required a higher ED90 of 0.20 mg/kg compared to older children (4-6 years) at 0.15 mg/kg.
Area of Science:
- Anesthesiology
- Pediatric Pharmacology
- Clinical Trial Research
Background:
- Pediatric patients exhibit heightened susceptibility to preoperative anxiety due to immature emotional regulation.
- Effective management of preoperative anxiety in children is crucial for patient-centered care.
- Remimazolam, an ultra-short-acting benzodiazepine, presents a potential solution for pediatric anxiolysis.
Purpose of the Study:
- To determine the 90% effective dose (ED90) of intravenous remimazolam for alleviating preoperative anxiety in pediatric patients.
- To compare the ED90 of remimazolam between younger (1-<4 years) and older (4-6 years) pediatric age groups.
- To establish a clinically relevant dosage for remimazolam in pediatric surgical settings.
Main Methods:
- A biased coin design (BCD) was utilized to ascertain target remimazolam doses.
- Patients were stratified into two age groups: younger (YG, 1-<4 years) and older (OG, 4-6 years).
- The ED90 was estimated using isotonic regression and bootstrapping, with effective anxiety relief defined as a Parent Separation Anxiety Scale score < 3.
Main Results:
- The study included 80 pediatric patients (40 in YG, 40 in OG).
- The estimated ED90 for remimazolam was 0.20 mg/kg (90% CI: 0.17-0.24) in the YG and 0.15 mg/kg (90% CI: 0.11-0.17) in the OG.
- A statistically significant difference in ED90 was observed between the two age groups, with no overlap in their 83% confidence intervals.
Conclusions:
- The ED90 of intravenous remimazolam for preoperative anxiolysis is 0.20 mg/kg for children aged 1 to <4 years and 0.15 mg/kg for children aged 4-6 years.
- Older pediatric patients require lower weight-based doses of remimazolam for effective preoperative anxiety relief.
- These findings provide crucial data for optimizing remimazolam dosing in pediatric anesthesia.
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 1-6 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 4-6 years. Notably, older children require even lower weight-based doses.
Clinical Trial Registration:
https://www.chictr.org.cn/bin/project/edit?pid=252632, identifier ChiCTR2500098747.
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