Determination of the ED90 of Remimazolam Bolus Dose for Preventing Emergence Delirium in Children with Sevoflurane Anesthesia: A Dose-Finding Study Using Biased-Coin Design Up-and-Down Sequential Method

Purpose: Emergence delirium (ED), a psychomotor agitation state, has a high incidence in children under sevoflurane anesthesia. Single-bolus administration of remimazolam can effectively reduce ED occurrence, similar to continuous infusion. However, the optimal single-bolus dose of remimazolam for preventing ED in children is unknown. Thus, we aimed to identify the 90% effective dose (ED 90 ) of single-bolus dose of remimazolam for preventing ED in pediatric patients under sevoflurane anesthesia. Patients and Methods: Our study included 59 children (aged 2– 12 years) who were scheduled to undergo elective laparoscopic inguinal hernia repair under general anesthesia. The ED 90 of bolus-dose remimazolam was determined according to the biased-coin design up-and-down sequential allocation method, starting from 0.1 mg/kg (interval, 0.02 mg/kg). The primary outcome was ED 90 based on the success or failure of the remimazolam bolus dose in preventing ED. Results: Fifty-six children were enrolled in this study. Remimazolam dose ranged from 0.06 to 0.14 mg/kg. The estimated ED 90 of remimazolam for preventing ED was 0.114 mg/kg (95% confidence interval [CI], 0.098– 0.128 mg/kg). The duration of the surgery was 24.4 ± 10.9 min. The patients’ extubation time, recovery time, and length of stay in the post-anesthesia care unit were 10.2 ± 4.5, 23.3 ± 9.3, and 26.4 ± 7.1 min, respectively. The total incidence of ED across all enrolled patients was 14.3%. No patient experienced adverse events within the tested dose range. Conclusion: For children undergoing laparoscopic inguinal hernia repair surgery under inhalation anesthesia with sevoflurane, the ED 90 of single-bolus remimazolam for preventing ED was 0.114 mg/kg (95% CI, 0.098– 0.128 mg/kg). We believe that this study addresses an important clinical evidence gap in pediatric anesthesia while providing a rigorous methodological reference for future dose-finding research. Clinical Trial Registration: https://www.chictr.org.cn , registration no. ChiCTR2500104472. Keywords: children, dose-finding study, pediatric anesthesia, psychomotor agitation, ultra-short-acting benzodiazepine