全身麻醉诱导时丙泊酚

1、全身麻醉诱导时丙泊酚、咪哒唑仑之间相互作用及与BIS的相关问题探讨Study of hypnotic interactions and bispectral index between propofol and midazolam肖黎波 吕志平 湘雅二医院摘 要 目的：观察全身麻醉诱导时丙泊酚、咪哒唑仑两药催眠作用，研究两者间互相作用；观察丙泊酚、咪哒唑仑全身麻醉诱导时病人BIS变化，初步探讨BIS作为麻醉镇静深度常用评估指标的准确性。方法：选择病人：ASAI级75例上腹部择期手术病人 ，年龄2050岁，均无精神异常和听觉障碍，无术前用药，按病人随机所给药物种类和剂量分为E（丙泊酚）组、M（咪

2、哒唑仑）、E/M（两药合用组），每组25人。麻醉诱导前给药，E组5个亚组分别给予丙泊酚0.80、1.00、1.25、1.56、1.95mg/kg,M组的5个亚组分别给予咪哒唑仑0.08、0.10、0.13、0.16、0.20mg/kg。E/M组分别给予丙泊酚/咪哒唑仑：0.250/0.035、0.310/0.045、0.390/0.056、0.490/0.070、0.610/0.087 mg/kg。给药2分钟后，判断病人意识：向病人施加睁眼的指令，如果5秒内连续两次对指令无反应，则认为病人进入催眠状态，即记录反应阳性，反之记录阴性。一并记录给药前、给药后1、2、3分钟的SBP、DBP、HR和S

3、pO2等指标；对于记录阴性也就是OAAS评分大于3分的病人，E组和M组分别缓慢增加丙泊酚和咪哒唑仑，直至OAAS评分到达3（即病人对声音刺激反应缓慢）。BIS记录从药物使用开始前记录起，每分钟一次直至麻醉维持水平（连续3次OAAS评分到3及以下）。计算丙泊酚、咪哒唑仑及复合组ED50值，运用等辐射图判定两药催眠相互作用；计算BIS的预测概率PK并加以比较。结果：采用点斜法计算得出在催眠末点E组（丙泊酚）ED50为1.10 mg/kg，95%可信限为0.921.31 mg/kg;M组(咪哒唑仑) ED50为0.12 mg/kg，95%可信限0.090.15 mg/kg；E/M组ED50为0.34

4、/0.05 mg/kg，95%可信限0.300.42/0.050.06 mg/kg。E/M组ED50偏离相加线有显著性差异（P0.05）。BIS数据比较（对声音有反应VS无反应）中发现，对声音有反应者BIS数据与无反应者有明显差距， P 0.05。BIS指标预测概率PK比较显示丙泊酚与咪哒唑仑PK值比较（0.87±0.11VS 0.69±0.01）有明显差异。结论：等辐射分析法表明丙泊酚、咪哒唑仑在全身麻醉诱导时具有催眠协同作用，且丙泊酚对血流动力学影响较咪哒唑仑显著；BIS作为一种麻醉镇静深度指标在丙泊酚、咪哒唑仑两者中能更准确地反映前者，且BIS数值存在个体差异。关键词

5、：药物相互作用，丙泊酚, 咪哒唑仑, 等辐射分析， 脑电双频指数（BIS）ABSTRACTObjectives：To study hypnotic interactions between propofol and midazolam ;To compare the prediction probability between propofol and midazolam。Methods：Seventy-five ASApatients aged 20-50y ,weighing 4080 kg, undergoing elective upper abdominal surgery were

6、 randomized to,propofol(n=25),midazolam(n=25),propofol-midazolam,combination(n=25) group。Each group were further divided into 5 subgroups。Propofol 0.80、1.00、1.25、1.56、1.95mg/kg was given in 5 propofol subgroups respectively。Midazolam 0.08、0.10、0.13、0.16、0.20mg/kg was given in 5 midazolam subgroups r

7、espectively。Propofol/midazolam 0.250/0.035、0.310/0.045、0.390/0.056、0.490/0.070、0.610/0.087 mg/kg was given in 5 propofol-midazolam subgroups respectively。Two minutes after drugs administration ,the patients were asked to open their eyes。Failure to open was taked as the start-point of hypnotic effect

8、。When the patients failed to respond to verbal order twice consecutively, the patient was considered to be in hypnotic state。Those who still got hypnotic effect in E and M group was gived drug by slow titration in increments judged by the investigator to reach an OAAS score of 3。SBP、DBP、HR 、SpO2 and

9、 BIS were monitered every one minute before , during and after drugs administration。ED50 of propofol、midazolam and propofol-midazolam combination for hypnotic effect were calculated。Isobologram was drawn to judge the hypnotic interactions between propofol and midazolam。BIS prediction probalility(PK)

10、 was compared between drugs。 Results：The ED50 for hypnotic effect was 1.10 mg/kg in group E；0.12mg/kg in group M；0.34/0.05 mg/kg in E/M group。The deviation of the location of ED50 of E/M combination from the connecting line was statistically significant。Bispectral Index of responders to voice was si

11、gnificantly different from nonresponders。BIS was a better predictor of propofol sedation than midazolam (PK=0.87±0.11VS 0.69±0.01)。 Conclusions：The hynoptic interaction between propofol and midazolam was synergitic。In terms of hemodynamic stability,propofol had more outstanding influence。BIS was a better predictor of propofol sedation