瑞马唑仑用于高龄患者全身麻醉诱导的有效剂量及效果评价

Effective dose and efficacy evaluation of remimazolam for induction of general anesthesia in superelderlypatients

目的评价瑞马唑仑用于高龄患者全身麻醉诱导有效剂量及有效性和安全性。方法试验Ⅰ选择浙江省人民医院2022年1月至2022年3月择期行全身麻醉手术的患者,年龄≥80岁,BMI 18~25 kg/m^(2),ASA分级Ⅰ-Ⅲ级,性别不限。首例患者静脉注射瑞马唑仑0.12 mg/kg或丙泊酚0.8 mg/kg,根据改良Dixon序贯法确定下一例患者瑞马唑仑或丙泊酚的剂量。瑞马唑仑相邻剂量差值为0.01 mg/kg,丙泊酚相邻剂量差值为0.05 mg/kg。阳性反应定义为给药后5 min内达到BIS值≤65。出现阳性反应时下一例患者减少1个剂量梯度;否则选择增加1个剂量梯度。采用probit法计算瑞马唑仑和丙泊酚的半数有效剂量(ED_(50))和90%有效剂量(ED_(90))及其95%可信区间(CI)。试验Ⅱ选择浙江省人民医院2023年4月至2023年10月择期行全身麻醉手术患者146例,年龄≥80岁,BMI 18~25 mg/kg,ASA分级Ⅰ-Ⅱ级,性别不限,采用随机数字表法分为2组(n=73):瑞马唑仑组(R组)和丙泊酚组(P组)。R组静脉注射瑞马唑仑ED_(90)、P组静脉注射丙泊酚ED_(90)行麻醉诱导,注射时间均为30 s。给药后5 min时BIS值仍大于65,R组每次静脉追加瑞马唑仑0.05 mg/kg,P组每次静脉追加丙泊酚0.5 mg/kg,直至患者BIS值≤65。记录麻醉诱导成功情况、麻醉诱导成功时间及补救镇静情况。记录术中注射痛、高血压、低血压、心动过缓、低氧血症、术中知晓和术后谵妄、恶心呕吐等的发生情况。结果试验Ⅰ瑞马唑仑的ED_(50)(95%CI)为0.148(0.139~0.157)mg/kg,ED_(90)(95%CI)为0.160(0.153~0.202)mg/kg;丙泊酚的ED_(50)(95%CI)为0.824(0.726~0.983)mg/kg,ED_(90)(95%CI)为0.916(0.860~2.472)mg/kg。试验Ⅱ与P组比较,R组麻醉诱导成功时间延长,术中注射痛和低血压发生率降低(P<0.05),麻醉诱导成功率、补救镇静率、术中高血压、心动过缓、低氧血症、术后谵妄和恶心呕吐发生率差异无统计学意义(P>0.05)。结论瑞马唑仑用于高龄患者全身麻醉诱导的ED_(50)、ED_(90)分别为0.148和0.160 mg/kg。相对于丙泊酚而言,瑞马唑仑用于高龄患者全麻诱导时,虽然起效时间略延长,但其安全性更高。

Objective:To evaluate the effective dose,efficacy and safety of remimazolam for induction of general anesthesia in super-elderly patients.Methods:TrialⅠAmerican Society of Anesthesiologists Physical Status classificationⅠ-Ⅲpatients of either sex,aged≥80 yr,with body mass index of 18-25 kg/m^(2),undergoing elective surgery with general anesthesia in the Zhejiang Provincial People′s Hospital from January to March 2022,were selected.Remimazolam 0.12 mg/kg or propofol 0.8 mg/kg was intravenously injected in the first patient,and the dose of remimazolam or propofol in the next patient was determined by using the modified Dixon′s up-and-down method.The difference between the two successive doses was 0.01 mg/kg for remimazolam and 0.05 mg/kg for propofol.A positive response was defined as achieving an anesthesia depth(BIS value≤65)within 5 min of administration.If the response was positive,the next patient received a lower dose,or conversely if negative,a higher dose was given in the next patient.The 50%effective dose(ED_(50))and 90%effective dose(ED_(90))of remifentanil and propofol and their 95%confidence intervals(CIs)were calculated by Probit method.TrialⅡOne hundred and forty-six American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲelderly patients of either sex,aged≥80 yr,with a body mass index of 18-25 mg/kg,scheduled for elective surgery with general anesthesia from April to October 2023 in Zhejiang Provincial People′s Hospital,were selected and divided into 2 groups(n=73 each)by using a random number table method:remimazolam group(R group)and propofol group(P group).R group was induced with intravenous remimazolam ED_(90)and P group was induced with intravenous propofol ED_(90),and the injection time was both 30 s.If the BIS value was still greater than 65 at 5 min after administration,remimazolam 0.05 mg/kg was intravenously added each time in R group and propofol 0.5 mg/kg was intravenously added each time in P group until the patient′s BIS value≤65.The success of anesthesia induction,time for successful induction of anesthesia and rescue sedation were recorded.The occurrence of intraoperative injection pain,hypertension,hypotension,bradycardia,hypoxemia,intraoperative awareness and postoperative delirium,nausea and vomiting was also recorded.Results:TrialⅠThe ED_(50)(95%CI)of remimazolam was 0.148(0.139-0.157)mg/kg,and the ED_(90)(95%CI)was 0.160(0.153-0.202)mg/kg;the ED_(50)(95%CI)of propofol was 0.824(0.726-0.983)mg/kg,and the ED_(90)(95%CI)was 0.916(0.860-2.472)mg/kg.TrialⅡCompared with group P,the time for successful induction of anesthesia was significantly prolonged,the incidence of intraoperative injection pain and hypotension was decreased(P<0.05),and no significant change was found in the success rate of anesthesia induction,rate of rescue sedation,intraoperative hypertension,bradycardia,hypoxemia,postoperative delirium,and nausea and vomiting in group R(P>0.05).Conclusions:The ED_(50)and ED_(90)of remimazolam for induction of general anesthesia are 0.148 and 0.160 mg/kg,respectively,in super-elderly patients.Compared to propofol,remimazolam has a slightly longer onset time,but it is safer when used for induction of general anesthesia in super-elderly patients.