甲苯磺酸瑞马唑仑全身麻醉诱导ED50及ED95的测定

The determination of ED50 and ED95 induced by remimazolam tosylate under general anesthesia

目的 观察不同剂量甲苯磺酸瑞马唑仑对喉罩插管全身麻醉诱导期患者镇静效能及起效时间的变化,确定其诱导的药物ED50及ED95值.方法 选择全身麻醉手术的可喉罩插管全身麻醉的患者27例,采用改良序贯(Dixon)法测定甲苯磺酸瑞马唑仑用药效果.设定起始诱导剂量为0.1mg/kg,下一例患者的剂量根据上一例患者诱导出现的结果而定,阴性反应标准,患者诱导后改良警觉/镇静评分(MOAA/S评分)≤1分,BIS≤60时间均<1min.如患者出现阴性反应,下一例患者的诱导剂量下降一个浓度梯度,浓度梯度差值为0.025mg/kg,直至患者出现阳性反应.以此类推,出现6次阴性与阳性交叉后终止研究.结果 甲苯磺酸瑞马唑仑ED50为0.168mg/kg(95%CI:0.137~0.216),ED95为0.297mg/kg(95%CI:0.226~0.828),全身麻醉诱导成功的12例患者中SBP、MAP、DBP呈下降趋势,麻醉诱导前5min(T0)高于其他各时点,在诱导后3min血压降至低点,差异有统计学意义(P<0.05),但血压下降程度均≤30%.诱导后MOAA/S评分≤1分时间为(33.08±9.18)s,BIS≤60时间为(37.42±10.97)s,BIS在1min内降至最低值,随后上升,但插管期间均BIS<60.HR随时间推移呈上升趋势,在用药后2min升至高点,与T0比较,差异有统计学意义(P<0.05).结论 甲苯磺酸瑞马唑仑ED50为0.168mg/kg、ED95为0.297mg/kg,可以安全应用于麻醉诱导期,达到类似丙泊酚起效时间,对循环、心率影响小,能提供足够的镇静时间,减少副作用.

Objective To investigate the ED50 and ED95 values of Rimimazolam tosylate during induction period of general anesthesia with laryngeal mask intubation.Methods 27 patients of American Society of Anesthesiologists(ASA)physical status(I-II)under general anesthesia with laryngeal mask intubation were selected,and the Modified Dixon sequential method was used to determine the dose of remimazolam in the next patient.O.I mg/kg was set as the initial induction dose,and the dose of the next patient was determined according to the results of the previous patient induction.The standard of negative reaction was that the time of Modified Observer's Assessment of Alertness/Sedation score(MOAA/S score)≤1 point after induction,and the time of BIS≤60 were all less than I minute.If the patient showed a negative response,the induced dose of the next patient was lowered by a concentration gradient of 0.025 mg/kg until the patient showed a positive response.By analogy,the study was terminated after six negative and positive crossings.Results The ED50 and ED95 of Rimimazolam was 0.168 mg/kg(95%CI:0.137~0.216 mg/kg)and 0.297 mg/kg(95% CI:0.226~0.828 mg/kg),respectively.The SBP,MAP and DBP in 12 paticnts with succcssful induction of general anesthesia showed a downward trend,which of TO were highcr than other time points.The blood pressure dropped to a low point at 3 min after induction.The difference was statistically significant(P<0.05),but the degree of blood pressure decline was≤30%.After the induction,the time of MOAA/S score≤1 minute was 33.08±9.18 seconds,and the time of BIS score≤60 was 37.42±10.97 seconds.The BIS values decreased to the lowest within 1 min and then increased,but all of them were lower than 60 during intubation.The HR showed an increasing trend over time,which reached the highest point at 2 minutes after treatment(T2),and the difference was statistically significant compared with T0(P<0.05).Conclusion ED50 and ED95 of Rimimazolam is 0.168 mg/kg and 0.297 mg/kg and can be safely applied in the induction period of anesthesia,which can achieve the onset time similar to propofol.It has litle influence on circulation and heart rate,and can provide enough sedation time and reduce side effects.