ED95 of esketamine for reducing preoperative anxiety in children of different ages

The 95% effective dose (ED95) of esketamine for reducing preoperative anxiety in children aged 1–4 years is 0.86 mg/kg, and for children aged 4–6 years it is 0.43 mg/kg, indicating that older children require a lower dose. The study included 80 children undergoing elective general anesthesia, divided into two age groups. Doses were adjusted using a biased coin design, and isotonic regression with bootstrapping calculated the ED95 and 95% confidence intervals. The ED95 values are clinically relevant for covering 95% of patients.

Study at a glance

Abstract

Abstract Background: The incidence of preoperative anxiety in children is significantly higher than in adults. Esketamine, the dextrorotatory enantiomer of ketamine, has been shown to alleviate preoperative anxiety in children effectively. Previous studies have established the effective dose (ED 50 ) of esketamine for reducing anxiety in pediatric patients. However, the 95% effective dose (ED 95 ) covers 95% of patients and has greater clinical relevance. This study aims to determine the ED95 of esketamine for reducing preoperative anxiety in pediatric patients aged 1 to 6 years. Methods: This study included 112 pediatric patients undergoing elective general anesthesia from June to November 2024, divided into two age groups: younger group (group L, 1 ≤ age < 4 years) and older group (group H, 4 ＜age ≤ 6 years). 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]. Initial doses for the first patient were 0.413 mg/kg in the L group and 0.283 mg/kg in the H group. Doses were adjusted according to the patient's response to sedation, with adjacent dose ratios established at 1.25. Isotonic regression and bootstrapping methods were used to calculate the ED95 and 95% confidence interval, respectively. Results: 80 children completed the study, 40 in the L group and 40 in the H group. Our meticulous statistical analysis, which we conducted with the utmost care, indicated that the ED 95 (95% CI) values for esketamine used for reducing preoperative anxiety in pediatric patients were 0.86 mg.kg -1 (0.49–1.02) in the L group and 0.43 mg.kg -1 (0.28–0.61) in the H group. Conclusion: The ED 95 for esketamine as a preoperative anxiolytic in children aged 1–4 years was 0.860 mg.kg -1 , while the ED 95 for children aged 4–6 years was 0.430 mg.kg -1 , indicating a reduced required dose of esketamine for preoperative anxiolysis in older children. Trial Registration: This study was registered with the China Clinical Trial Registry on February 18, 2025 (retrospective registration, ChiCTR2500097368).