Determination of the 90% effective dose of remimazolam for anesthesia induction in children undergoing ophthalmic procedures: A biased-coin design up-and-down sequential trial

Background Remimazolam has been used in clinical practice of general anesthesia and sedation for more than five years, and the first report on pediatric anesthesia was published in 2024. However, the dosage regimen for children was still unclear. The objective of our trial was to determine the 90% effective dose (ED ₉₀ ) of remimazolam for pediatric anesthesia induction. Methods Our trial enrolled 45 pediatric patients undergoing ophthalmic procedures from June 2024 to September 2024. The initial induction dose was 0.2mg/kg and the sedation depth was assessed by means of the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scale. The basic rule of our dose-response trial was that the dose for each patient depended on the response of the previous patient, the dose increased by 0.05mg/kg if the previous patient got a MOAA/S score greater than 1, otherwise the current dose was maintained or reduced by 0.05mg/kg at a rate of 9:1 randomly. The anesthesiologist, who assessed sedation in three minutes, was blind to the dose allocation. Subsequently, the ED ₉₀ of remimazolam for pediatric anesthesia induction was calculated. Additionally, the basic vital signs and adverse events during the induction were recorded. Results 45 participants were enrolled, among which 2 were excluded due to parental refusal to participate and 43 completed the trial, 35 participants achieved positive outcomes, while 8 participants had negative outcomes. The ED ₉₀ of intravenous remimazolam for anesthesia induction was 0.29mg/kg (95% CI, 0.26-0.31mg/kg). The mean induction time was 125.37 ± 33.34 seconds (mean ± SD). Conclusion The ED ₉₀ of intravenous remimazolam for anesthesia induction in children was 0.29mg/kg (95% CI, 0.26-0.31mg/kg). The dose is safe and efficient for anesthesia induction in pediatric participants. Trial registration: The study was registered in Chinese Clinical Trial at chictr.org.cn, and the principal investigator was Hongyuan Ren. Registration date: May 24 ^th 2024, First participant enrolled date: June 1 ^th 2024, Number: ChiCTR2400084790 URL:https://www.chictr.org.cn/showproj.html?proj=228251&u_atoken=8044a6d97e7d2997c5f6ab4b33f5cf20&u_asig=1a0c380817295931459096250e00e5