患儿七氟醚药效学模型的建立：脑电双频谱指数  

Establishment of pharmacodynamic model of sevoflurane in pediatric patients： bispectral index

作　　者：宋蕴安 黄悦[1] 林琳[1] 张马忠[1] 牛静 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心麻醉科(儿童临床药理研究室),200127

出　　处：《中华麻醉学杂志》2013年第11期1342-1345,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81202597）;上海高校选拔培养优秀青年教师科研专项基金（jdy09150）

摘　　要：目的以脑电双频谱指数（BIS）为效应指标，建立患儿七氟醚药效学模型。方法选择行非心脏手术患儿13例，年龄4～9岁，体重12～39kg，ASA分级Ⅰ或Ⅱ级。患儿经面罩顺序吸人七氟醚1％、5％和1％，每个浓度维持15min。每间隔10s自动记录BIS值、HR、BP、SpO2。基于非线性混合效应模型、采用NONMEM软件建立群体药效学模型，依据向前选择和向后消除法分析年龄对药效学参数的影响。模型改善的判断标准：目标函数值减少大于3．84。结果12名患儿纳入研究，年龄4．0～8．5岁、体重12．8～38．0kg、身高92～135cIn，纳人数据共2964个有效浓度一时间．BIS数据点。将协变量（年龄、身高、体重）引入药效学模型，模型拟合后差异无统计学意义（P〉0．05）。最终建立的七氟醚药效学模型参数为：效应位消除速率常数0．516／min；EC50=2．11％；浓度．效应关系曲线的斜率2．46，无药物作用时的基础值74．6，药物作用的最大效应11．2。结论以BIS作为效应指标，成功建立了患儿七氟醚药效学模型，从模型的各项参数分析提示，与成人比较，患儿对七氟醚的敏感性较低，但药物的血脑平衡时间短，起效和恢复更为迅速。Objective To establish the pharmacodynamic model of sevoflurane with bispectral index （BIS） as the effective index in pediatric patients.Methods Thirteen ASA physical status Ⅰ or Ⅱ pediatric pa- tients, aged 4-9 yr, weighing 12-39 kg, undergoing non-cardiac surgery, were selected in the study. The pediatric patients sequentially inhaled 1%, 5 % and 1% sevoflurane via a face mask and each concentration was inhaled for 15 min. BIS value, HR, BP and SpO2 were automatically recorded every 10 s. Based on nonlinear mixed effect modeling, the population pharmacodynamie mode/of sevotlurane was established using NONMEM software. The ef- fdet of age on the pharmacodynamie parameters was evaluated using a stepwise forward addition then backward elimination modeling approach. The standard for model improvement was defined as a decrease in the value of the objective function by more than 3.84.Results Twelve pediatric patients, aged 4.0-8.5 yr, weighing 12.8-38.0 kg, wilh body height of 92-135 cm, were enrolled in this study and the data which were enrolled comprised 2964 effective eoncentration-time-BIS points. The model was not improved significantly with any covariates （age, body height, and body weight） introduced （P 〉 0.05）. The estimated parameters of the final pharmacodynamic model of sevoflurane were as follows： ke0 = 0.516/rain; ECs0 （ BISs0 ） = 2.11% ; 7 = 2,46 ; E0 = 74.6 ; EMAX = 11.2. Conclusion The pharmacodynamic model of sevoflurane is successfully established with BIS as the effective index in pediatric patients, and the analysis for each parameter of the model indicates that the sensitivity to sevofluraffe is lower, but the blood-brain equilibration time of the drug is shorter and the onset and recovery are faster in childrenthan in adults.

关 键 词：麻醉药 吸入 药理学 临床 脑电描记术 

分 类 号：R726.1[医药卫生—儿科]