Supplementary file 1_The effective sedative dose of remimazolam for BIS <60 during general anesthesia induction between elderly and non-elderly patients-A randomized controlled trial.doc

BackgroundThere is lack research about the effect of sufentanil on the effective dose of remimazolam during general anesthesia in both elderly and non-elderly patients scheduled for day surgery. This study was conducted to estimate the 95% effective dose (ED95) of remimazolam with low dose of sufentanil for BIS <60 during general anesthesia in both elderly and non-elderly patients scheduled for day surgery.
MethodsPatients scheduled for elective gynecological day procedures were randomly allocated to one of four dosage groups receiving 0.1, 0.2, 0.3, or 0.4 mg/kg of remimazolam, with 25 participants per group. All patients received a concurrent intravenous dose of sufentanil (0.1 μg/kg) during anesthesia induction. Successful sedation was defined as achieving a BIS score of <60 within 5 minutes of remimazolam administration. The ED50 and ED95 of remimazolam for BIS <60 during general anesthesia induction were calculated. Secondary outcomes included the incidence of hypotension, respiratory depression, and adverse events.
ResultsIn elderly patients, the estimated ED50 of remimazolam was determined to be 0.156 mg/kg, with a 95% confidence interval (CI) ranging from 0.110 to 0.190 mg/kg. For non-elderly individuals, the corresponding ED50 was 0.218 mg/kg (95% CI: 0.179–0.253 mg/kg). Additionally, the dose required to achieve 95% efficacy (ED95) was calculated as 0.336 mg/kg (95% CI: 0.286–0.437 mg/kg) in the elderly cohort and 0.418 mg/kg (95% CI: 0.361–0.528 mg/kg) in the non-elderly cohort. Hypotension occurred significantly more often in elderly patients (P < 0.05), but not for the incidence of bradycardia or respiratory depression between groups (P > 0.05).
ConclusionUnder BIS monitoring during gynecological day surgery, the estimated ED95 of remimazolam with 0.1 μg/kg sufentanil was 0.336 mg/kg (95% CI: 0.286–0.437 mg/kg) for elderly patients and 0.418 mg/kg (95% CI: 0.361–0.528 mg/kg) for non-elderly patients.
Clinical Trial RegistrationThis study is registered with ClinicalTrials.gov as ChiCTR2400091138.

【背景】目前针对择期日间手术老年与非老年患者，其全身麻醉期间舒芬太尼（sufentanil）对瑞马唑仑（remimazolam）有效剂量影响的相关研究尚属匮乏。本研究旨在评估择期日间手术老年与非老年患者全身麻醉时，联合低剂量舒芬太尼的前提下，瑞马唑仑达到脑电双频指数（Bispectral Index, BIS）<60的95%有效剂量（ED95）。
【方法】本研究纳入择期妇科日间手术患者，按随机分组原则分为4个剂量组，分别给予0.1、0.2、0.3、0.4 mg/kg的瑞马唑仑，每组纳入25名受试者。所有患者在麻醉诱导期间均同步静脉给予舒芬太尼（0.1 μg/kg）。镇静成功定义为瑞马唑仑给药后5分钟内脑电双频指数（BIS）评分<60。本研究计算了全身麻醉诱导期间，瑞马唑仑达到BIS<60的半数有效剂量（ED50）与95%有效剂量（ED95）。次要结局指标包括低血压、呼吸抑制的发生率及不良事件发生情况。
【结果】老年患者中，瑞马唑仑的半数有效剂量（ED50）估算值为0.156 mg/kg，95%置信区间（confidence interval, CI）为0.110~0.190 mg/kg；非老年患者对应的ED50为0.218 mg/kg（95% CI：0.179~0.253 mg/kg）。此外，老年队列中达到95%有效镇静所需的瑞马唑仑剂量（ED95）为0.336 mg/kg（95% CI：0.286~0.437 mg/kg），非老年队列则为0.418 mg/kg（95% CI：0.361~0.528 mg/kg）。老年患者低血压发生率显著更高（P<0.05），但各组间心动过缓及呼吸抑制的发生率无显著差异（P>0.05）。
【结论】在妇科日间手术的脑电双频指数（BIS）监测下，联合0.1 μg/kg舒芬太尼时，老年患者瑞马唑仑的ED95估算值为0.336 mg/kg（95% CI：0.286~0.437 mg/kg），非老年患者则为0.418 mg/kg（95% CI：0.361~0.528 mg/kg）。
【临床试验注册】本研究已在ClinicalTrials.gov平台注册，注册编号为ChiCTR2400091138。