我们研究了猪失血性休克对依托咪酯药理性的影响。16头猪随机分配在对照组和休克组中。休克组出血至平均动脉压为50 mmHg并维持至30 mL/k血被放出。在10分钟内向2组猪输入300μg?kg-1?min-1依托咪酯。在注射开始决定药物浓度后180分钟内取15次动脉血样。每组使用三室模型来评估各组药物动力学参数。脑电双频指数用作药物效应指标.药效学以S状最大抑制效应曲线为特征.数据显示休克组在药物输入10 min时血药浓度增加25%，之后渐下降。药代动力学显示两组变量存在轻差异。两组依托咪酯产生相似的脑电双频指数变化。。本实验显示中等出血性休克对依托咪酯药代动力学影响轻微，而对药效学则无影响，这与出血性休克对大多数其它镇静药或阿片类药物的影响不同。

（论文出处：Anesth Analg 2003;96:1360 –302）
 

The Influence of Hemorrhagic Shock on Etomidate:
A Pharmacokinetic and Pharmacodynamic Analysis

Ken B. Johnson, MD, Talmage D. Egan, MD, Jennifer Layman, BS, Steven E. Kern, PhD, Julia L. White, RN, BS, and Scott W. McJames, MS
Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah

We studied the influence of hemorrhagic shock on the pharmacology of etomidate in swine. Sixteen swine were randomly assigned to control and shock groups. The shock group was bled to a mean arterial blood pressure of 50mmHg and held there until 30 mL/kg blood was removed. Etomidate 300 μg ? kg-1 ? min-1 was infused for 10 min to both groups. Fifteen arterial samples were collected until 180 min after the infusion began to determine drug concentration. Pharmacokinetic variables for each group were estimated by using a threecompartment model. The bispectral index scale was used as a measure of drug effect. The pharmacodynamics were characterized by using a sigmoid inhibitory maximal effect model. The raw data revealed a 25% increase in the plasma etomidate concentration at the end of the 10-min infusion which resolved after termination of the infusion in the shock group. The pharmacokinetic analysis revealed subtle changes in the variable estimates between groups. The etomidate infusion produced a similar Bispectral Index Scale change in both groups. These results demonstrated that, unlike the influence of hemorrhagic shock on other sedative hypnotics and opioids, moderate hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate.
(Anesth Analg 2003;96:1360 –8)