Age-Stratified ED95 of Remimazolam Tosilate for Moderate Sedation in Pediatric Patients: A Biased Coin Design Study

Bingqing Zhu,* Wenjun Meng,* Kunyun Pan,* Li Peng, Xu Chen, Sheng Wang, Chengwei Yang Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng Wang, Email iamsheng2020@ustc.edu.cn Chengwei Yang, Email yangcw1108@ustc.edu.cnBackground: Providing safe sedation in pediatric patients remains challenging because of age-dependent physiological variations. This study aimed to identify the age-stratified 95% effective dose (ED95) of remimazolam tosilate for achieving moderate sedation in children.Methods: This study enrolled children aged 1– 12 years with ASA physical status I–II scheduled for elective surgery. Participants were stratified into three age groups: toddlers (1– 3 years), preschoolers (3– 6 years), and school-aged children (6– 12 years), with 40 patients in each group. The initial dose of remimazolam tosilate was 0.2 mg·kg− 1, with subsequent 0.05 mg·kg− 1 adjustments using a biased coin design up-and-down sequential method based on patient response. Sedation depth was evaluated using the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scale. An MOAA/S score ≤ 3 at 3 minutes after drug administration was defined as successful sedation. ED95 values were estimated using isotonic regression. Perioperative variables, including sedation onset time, operation time, total anesthesia time, and wake-up time, were recorded. Adverse events, including hypotension, bradycardia, and oxygen desaturation, were monitored during the observation period.Results: Of the 142 children screened, 120 completed the study. The estimated ED95 (95% confidence interval) of remimazolam tosilate was 0.415 mg·kg− 1 (0.311– 0.437) in toddlers, 0.389 mg·kg− 1 (0.258– 0.440) in preschoolers, and 0.362 mg·kg− 1 (0.228– 0.396) in school-aged children. Toddlers had the longest median wake-up time (32.5 min; IQR: 25.3– 40.8). Hypotension was reported in 0.8% of patients (n=1), whereas bradycardia and oxygen desaturation were each observed in 5.8% of patients (n=7).Conclusion: This study establishes age-specific ED95 reference doses of remimazolam tosilate for moderate sedation in children. Although remimazolam demonstrated an overall favorable safety profile, individualized dose titration remains essential, particularly given the 17.5% incidence of bradycardia observed in toddlers, which warrants closer monitoring.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300075986).