不同剂量咪达唑仑与异丙酚催眠效应的相互作用

目的 评价不同剂量咪达唑仑与异丙酚催眠效应的相互作用.方法 择期全麻病人120例,ASA Ⅰ或Ⅱ级,年龄18～60岁,体重40～80 kg,随机分为4组(n=30),各组分别随机分为6个亚组,M组和P组各亚组分别静脉注射咪达唑仑0.04、0.06、0.08、0.10、0.12、0.15 mg/kg、异丙酚0.8、1.0、1.2、1.5、1.8、2.2 mg/kg;MP1组和MP2组各亚组分别按咪达唑仑与异丙酚ED50等效比1:13(咪达唑仑剂量分别为0.022、0.028、0.033、0.039、0.044、0.055 mg/kg)和临床常用比例1:10(咪达唑仑剂量分别为0.03、0.04、0.045、0.05、0.055、0.06 mg/kg)行麻醉诱导.M组、P组、MP1组和MP1组分别于注药后3、1,1、1 min时行警觉,镇静(OAA/S)评分,催眠有效标准:OAA/S评分≤2分.采用加权概率单位法计算半数有效剂量(ED50)及其95%可信区间(95%CI);采用等辐射分析法判断两药催眠效应的相互作用.结果 M组、MP1.2组咪达唑仑催眠效应的ED50及其95%CI分别为0.088(0.066～0.110)、0.031(0.026～0.036)、0.045(0.040～0.049)mg/kg;P组、MP1.2组异丙酚催眠效应的ED50及其95%CI为1.142(0.933～1.350)、0.421(0.343～0.480)、0.450(0.399～0.491)mg/kg.结论 麻醉诱导时咪达唑仑与异丙酚按ED50等效剂量比1:13给药,两药催眠效应为协同作用;按临床常用剂量比1:10给药时两药催眠效应为相加作用.

Hypnotic interaction between midazolam and different doses of propofol

Objective To evaluate the hypnotic interaction between midazolam and different doses of propofol. Methods One hundred and twenty ASA Ⅰor Ⅱpatients (43 male, 77 female) aged 18-60 yr weighing 40-80 kg undergoing elective surgery were randomly divided into 4 groups (n=30 each):group Ⅰmidazolam (M); group Ⅱ propofol (P) and group Ⅲ, Ⅳ midazolam + propofol (MP1, MP2). Six doses of midazolam (0.04, 0.06, 0.08, 0.1, 0.12, 0.15 mg/kg) and propofol (0.8, 1.0, 1.2, 1.5, 1.8 mg/kg) were given iv in group M and P respectively. OAA/S scale was used to assess the level of sedation (5=alert, 1=only responds to squeezing deltoid muscle). The hypnotic end point was defined as an OAA/S score ≤2. The level of sedation was assessed at 3 min after midazolam administration in group M and at 1 min after propofol administration in group P, MP1and MP2 . ED50 (95 % confidence intervals,95 % CI) of midazolam and propofol were determined by probit analysis in group M and P. Isobolographic analysis was used to analyze the interaction between the two drugs. The ratio of ED50 of midazolam to ED50 of propofol was 1:13 in group MP1 and 1:10 in group MP2 . Results The ED50 (95 % CI) of midazolam for hypnosis was 0.088 (0.066-0.110), 0.031 (0.026-0.036) and 0.045 (0.040-0.049) mg/kg respectively in group M, MP1 and MP2. The ED50 (95% CI) of propofol for hypnosis was 1.142(0.933-1.350), 0.421 (0.343-0.480), 0.450 (0.399-0.491) mg/kg respectively in group P, MP1,MP2. Isobolographie analysis confirmed that midazolam and propofol interacted synergistically at the ratio of 1: 13in group MP1 and additively at the ratio of 1:10 in group MP2 . Conclusion Midazolam and propofol interact synergistically at the ratio of 1:13 but additively at the ratio of 1:10.