反应曲面法分析丙泊酚和瑞芬太尼对脑电双频指数影响的相互作用  

A response surface analysis of pharmacodynamic interaction between propofol and remifentanil regarding bispectral index

作　　者：钱淑雯[1] 郭旋[1] 张马忠[2] 杨志萍[1] 

机构地区：[1]同济大学附属杨浦医院麻醉科,上海200090 [2]上海交通大学医学院附属上海儿童医学中心麻醉科

出　　处：《国际麻醉学与复苏杂志》2015年第1期1-5,共5页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金资助项目（81202597）

摘　　要：目的以脑电双频指数（bispectral index，BIS）为指标，观察不同丙泊酚端芬太尼浓度组合产生的镇静效应，构建丙泊酚和瑞芬太尼相互作用的反应曲面模型，确定量效关系及相互作用类型，并分析这种相互作用对BIS临床监测的提示。方法采用交叉对照研究；无术前用药、美国麻醉医师协会（ASA）分级Ⅰ～Ⅱ级、择期行全麻手术的患者40例，按随机数字表法分为丙泊酚组（22例）和瑞芬太尼组（18例）。以靶控输注方式分两个阶段递增和递减药物浓度（丙泊酚，1mg／L-5mg／L；瑞芬太尼，1μg，L～7μg／L），经洗脱期后，给予第2种药物。每间隔1min采集BIS指标，采用非线性混合效应模型对研究数据进行分析。结果丙泊酚和瑞芬太尼相互作用对BIS影响的药效学模型以Minto反应曲面模型较好拟合；两药对BIS表现为协同作用（相互作用系数β2〉0）；年龄不影响两药的50％有效浓度（50％effective concentration，EC50），但对斜率（1）有显著影响（P〈0．01）。反应曲面模型的参数分别为EC50．Prop=2．96mg/L，EC50,Rcm=38．1μg／L，1=1．86＋（年龄-50）0．0172,Emax=8．61，E0=90．8，β2=0．83。结论丙泊酚联合瑞芬太尼有镇静协同效应；年龄不影响BIS降低的幅度（Emax不变），也不影响两药联合作用的敏感性（EC50不变），但老年人联合用药时BIS的反应性增加（γ随年龄增加而增加）。Objective Based on bispectral index （BIS） monitoring, the sedative effect produced by the combination of propofol and remifentanil with variable concentrations was observed. In order to construct the pharmacodynamic response surface model of propofol and remifentanil and to determine the dose effect relationship and interaction type. Methods With a cross- control design, forty patients without premedication, ASA Ⅰ -Ⅱ grade, undergoing elective surgery, were randomly divided into propofol group and remifentanil group. Propofol or remifentanil was used with target-controlled infusion system in two phases of increment and decrement drug concentration （propofol 1 mg/L-5 mg/L, remifentanil 1 μg/L-7 μg/L）, after the washout period, giving the second drug. Each collects intervally BIS index every 1 min, use nonlinear mixed effects models to analyze the data for research. Results The concentration-BIS relationship of propofol combined with remifentanil was described well by Minto response surface model, which showed considerable synergy between both drugs for BIS （interaction index β2〉0）. Age does not affect the 50% effective concentration （EC50） of both drugs, but has a significant effect on γ（P〈0.01）. The final pharmacodynamic parameters were followings：EC50.Prp=2.96 mg/L, EC50.Remi=38.1 μg/L, Gamma （γ）=1.86＋（age-50）0.017 2, Ermax=8.61, E0=90.8 and β2=0.83, respectively. Conclusions Propofol-remifentanil shows a synergistic interaction on sedation. Age does not affect the deereasing amplitude（unchanged Emax） and the sensitivity（unchanged EC50） of BIS produced by combination of both drugs, but the elderly have increased BIS reaction （increased gamma with aging） to the combination of both drugs.

关 键 词：丙泊酚 瑞芬太尼 脑电双频指数 药效学模型 反应曲面 

分 类 号：R614[医药卫生—麻醉学]