体外循环对成人芬太尼药代动力学的影响

lencho83

Anesthesiology. 2003 Oct;99(4):847-54.   Related Articles, Links


Cardiopulmonary bypass has minimal effects on the pharmacokinetics of fentanyl in adults.

Hudson RJ, Thomson IR, Jassal R, Peterson DJ, Brown AD, Freedman JI.

Department of Anesthesia, St. Boniface General Hospital, University of Manitoba, Winnipeg, Canada. [email protected]

BACKGROUND: Although fentanyl has been widely used in cardiac anesthesia, no complete pharmacokinetic model that has assessed the effect of cardiopulmonary bypass (CP[img=http://img.dxy.cn/images/smiles/smile_blackeye.gif]Black Eye[/img] and that has adequate predictive accuracy has been defined. The aims of this investigation were to determine whether CPB had a clinically significant impact on fentanyl pharmacokinetics and to determine the simplest model that accurately predicts fentanyl concentrations during cardiac surgery using CPB. METHODS: Population pharmacokinetic modeling was applied to concentration-versus-time data from 61 patients undergoing coronary artery bypass grafting using CPB. Predictive ability of models was assessed by calculating bias (prediction error), accuracy (absolute prediction error), and measured:predicted concentration ratios versus time. The predictive ability of a simple three-compartment model with no covariates was initially compared to models with premedication (lorazepam vs. clonidine), sex, or weight as covariates. This simple model was then compared to 18 CPB-adjusted models that allowed for step changes in pharmacokinetic parameters at the start and/or end of CPB. The predictive ability of the final model was assessed prospectively in a second group of 29 patients. RESULTS: None of the covariate (premedication, sex, weight) models nor any of the CPB-adjusted models significantly improved prediction error or absolute prediction error, compared to the simple three-compartment model. Thus, the simple three-compartment model was selected as the final model. Prospective assessment of this model yielded a median prediction error of +3.8%, with a median absolute prediction error of 15.8%. The model parameters were as follows: V1, 14.4 l; V2, 36.4 l; V3, 169 l; Cl1, 0.82 l. min-1; Cl2, 2.31 l x min-1; Cl3, 1.35 l x min-1. CONCLUSIONS: Compared to other factors that cause pharmacokinetic variability, the effect of CPB on fentanyl kinetics is clinically insignificant. A simple three-compartment model accurately predicts fentanyl concentrations throughout surgery using CPB.
体外循环对成人芬太尼药代动力学的影响
尽管芬太尼广泛应用于心血管手术的麻醉，但是目前为止还没有一个完整的药代动力学模型可以准确的评估体外循环（CPB）对芬太尼药代动力学的影响，并且能够准确预测芬太尼的药物浓度。加拿大学者Hudson RJ博士及其协作者研究了CPB是否能够影响芬太尼的药代动力学，并且建立了一种最简的三室模型来预测CPB过程中芬太尼的血药浓度。利用总体药代动力学模型绘制61名在CPB下行冠状动脉搭桥术患者的时间－药物浓度曲线。应用以下参数评价模型的预测能力，包括计算偏差（预测误差）、准确度（绝对预测误差）和测量值与预测值之间的比值。将简单的没有协变量的三室模型与以术前药、性别和体重作为协变量的模型进行比较。这个简单模型与18种CPB校正模型相比较，这些校正模型在CPB开始和结束时对药代动力学的参数加以调整。以比较以后最好的模型做为最终模型，在另外29例病人检测该模型的预测能力。结果发现，协变量模型和所有的CPB校正模型与简单的三室模型相比都没有明显的改善预测误差和绝对预测误差。因此将简单的三室模型做为最终的模型。该模型的预测误差是+3.8%，绝对预测误差是15.8%。该模型的参数如下：V1, 14.4 l; V2, 36.4 l; V3, 169 l; Cl1, 0.82 l/min; Cl2, 2.31 l  /min; Cl3, 1.35 l/min。总之与其它影响因素相比CPB对芬太尼药代动力学的影响不具有临床显著性。简单的三室模型就可以较准确的预测CPB过程中芬太尼的血药浓度。
Anesthesiology. 2003 Oct;99(4):847-54.