瑞马唑仑预防老年患者依托咪酯全麻诱导所致肌阵挛的半数有效剂量

Median effective dose of remimazolam to prevent etomidate-induced myoclonus in elderly patients

目的测定老年男性和女性患者瑞马唑仑预防依托咪酯全麻诱导所致肌阵挛的半数有效剂量(ED_(50))。方法选取2022年1月至2022年6月在中国人民解放军联勤保障部队第九六〇医院行全麻手术的老年患者43例。按性别分为男性组21例和女性组22例。采用序贯法确定瑞马唑仑的剂量,相邻剂量间隔为0.05 mg/kg。2组患者瑞马唑仑首次静脉注射剂量均为0.2 mg/kg,1.5 min后注射依托咪酯0.3 mg/kg,待患者意识消失后给予舒芬太尼0.2μg/kg和罗库溴铵0.4 mg/kg,诱导完成后置入喉罩。记录2组患者依托咪酯麻醉诱导前基础状态(T0)、静脉输注即刻(T1)、静脉输注后1min(T2)及静脉输注后3min(T3)患者的平均动脉压(MAP)、心率及脉搏血氧饱和度。记录患者恶心、呕吐及误吸等不良反应的发生情况。采用SPSS 28.0统计软件处理数据。根据数据类型,组间比较采用独立样本t检验或秩和检验。用Probit法计算ED_(50)、95%有效剂量(ED_(95))及相应95%可信区间(CI),建立线性回归方程。采用GraphPad软件制作量效关系图。结果瑞马唑仑预防老年男性和女性患者依托咪酯全麻诱导所致肌阵挛的ED_(50)分别为0.12 mg/kg(95%CI 0.067~0.169)和0.17 mg/kg(95%CI 0.127~0.215)、ED_(95)分别为0.19 mg/kg(95%CI 0.153~0.665)和0.24 mg/kg(95%CI 0.202~0.580)。男性组T3时刻MAP较T0时刻显著下降,差异有统计学意义[(87.10±6.53)和(99.99±7.84)mmHg;P<0.05];女性组T3时刻MAP[(85.50±7.03)和(102.95±4.03)mmHg]及心率[(69.6±5.41)和(76.00±6.65)beats/min]较T0时刻显著下降,差异均有统计学意义(均P<0.05)。但下降幅度均未超过麻醉前T0时刻基础值的20%。T1、T2及T3时刻均无恶心、呕吐及误吸等不良反应发生。结论瑞马唑仑预防老年男性和女性患者依托咪酯全麻诱导中所致肌阵挛的ED_(50)分别为0.12 mg/kg和0.17 mg/kg,且老年男性患者的ED_(50)低于女性患者。诱导过程中血流动力学平稳,无不良反应发生。

Objective To determine the median effective dose(ED_(50))of remimazolam to prevent etomidate-induced myoclonus in elderly male and female patients.Methods A total of 43 elderly patients who underwent general anesthesia surgery in our hospital from January 2022 to June 2022 were recruited in this study.There were 21 cases assigned in the male group and 22 cases in the female group.The dose of remimazolam was determined through sequential administration,with an interval of 0.05 mg/kg.Remimazolam was given intravenously at a dose of 0.2 mg/kg for the first time,and etomidate was given at 3 mg/kg in 1.5 min later,followed by 0.2μg/kg sufentanil and 0.4 mg/kg rocuronium after disappearance of patient′s consciousness.Then laryngeal mask was placed after induction.Mean arterial pressure(MAP),heart rate and pulse oxygen saturation of patients in the two groups were recorded before induction of etomidate anesthesia(T0),immediately after intravenous infusion(T1),1 min after intravenous infusion(T2)and 3 min after intravenous infusion(T3).The occurrence of adverse reactions such as nausea,vomiting and aspiration was recorded.SPSS statistics 28.0 was used to process the data.Based on data type,independent sample t-test or rank sum test was adopted for inter-group comparison.ED_(50),95%effective dose(ED_(95))and corresponding 95%confidence interval(CI)were calculated with Probit model to establish a linear regression equation.Then GraphPad software was adopted to draw a dose-effect relationship diagram.Results The ED_(50) of remimazolam in prevention of myoclonus induced by etomidate was 0.12(95%CI 0.067-0.169)and 0.17 mg/kg(95%CI 0.127-0.215)respectively for the elderly male and female patients,and the ED_(95) was 0.19(95%CI 0.153-0.665)and 0.24 mg/kg(95%CI 0.202-0.580),respectively.In the male group,MAP at T3 was decreased significantly than that at T0(87.10±6.53 vs 99.99±7.84 mmHg;P<0.05).In the female group,both MAP[(85.50±7.03)vs(102.95±4.03)mmHg]and heart rate[(69.6±5.41)vs(76.00±6.65)beats/min]were obviously reduced at T3 than T0(P<0.05).However,the decline was not larger than 20%of the base value at T0 before anesthesia.No adverse reactions such as nausea,vomiting and aspiration occurred at T1,T2 and T3.Conclusion The ED_(50) of remimazolam for preventing etometon-induced myoclonus is 0.12 and 0.17 mg/kg respectively in elderly male and female patients during induction of general anesthesia,and the dose is lower in eldly male than in elderly female.The hemodynamics is stable and no adverse reactions occur during induction.