Drug design, development and therapy · 2026
Age-Stratified ED9 5 of Remimazolam Tosilate for Moderate Sedation in Pediatric Patients: A Biased Coin Design Study.
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Zhu Bingqing, Meng Wenjun, Pan Kunyun, Peng Li, Chen Xu, Wang Sheng, Yang Chengwei
Аннотация
BACKGROUND: 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. ED9 5 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 ED9 5 (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 ED9 5 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).
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. ED9 5 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 ED9 5 (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 ED9 5 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).