Kuipers J A, Boer F, Olofsen E, Olieman W, Vletter A A, Burm A G, Bovill J G
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Anesthesiology. 1999 Apr;90(4):1146-57. doi: 10.1097/00000542-199904000-00030.
Cardiac output (CO) is likely to influence the pharmacokinetics of anesthetic drugs and should be accounted for in pharmacokinetic models. The influence of CO on the pharmacokinetic parameters of alfentanil in pigs was evaluated using compartmental and recirculatory models.
Twenty-four premedicated pigs were evaluated during halothane (0.6-2%) anesthesia. They were assigned randomly to one of three groups. One group served as control. In the other groups, the baseline CO was decreased or increased by 40% by pharmacologic intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and indocyanine green (25 mg) were injected into the right atrium. Blood samples were taken for 150 min from the right atrium and aortic root. Arterial concentration-time curves of indocyanine green and alfentanil were analyzed using compartmental models (two-stage and mixed-effects approach) and a recirculatory model, which can describe lung uptake and early distribution.
The CO of individual pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2 = 0.54), fast peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 = 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO.
Cardiac output markedly influences the pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the predictive value of pharmacokinetic models of alfentanil.
心输出量（CO）可能会影响麻醉药物的药代动力学，药代动力学模型应予以考虑。使用房室模型和再循环模型评估了CO对猪体内阿芬太尼药代动力学参数的影响。
对24只预先用药的猪在氟烷（0.6 - 2%）麻醉期间进行评估。它们被随机分配到三组中的一组。一组作为对照组。在其他组中，通过药物干预（普萘洛尔或多巴酚丁胺）使基线CO降低或升高40%。将阿芬太尼（2毫克）和吲哚菁绿（25毫克）推注到右心房。从右心房和主动脉根部采集血样150分钟。使用房室模型（两阶段和混合效应方法）和再循环模型分析吲哚菁绿和阿芬太尼的动脉浓度 - 时间曲线，该再循环模型可描述肺摄取和早期分布。
个体猪的心输出量在1.33至6.44升/分钟之间变化。三室模型显示，CO是中央室容积（V1，r2 = 0.54）、快速外周室容积（V2，r2 = 0.29）、稳态分布容积（Vss，r2 = 0.29）、快速分布清除率（Cl12，r2 = 0.39）和消除清除率（Cl10，r2 = 0.51）的决定因素。再循环模型显示，CO是总分布容积（r2 = 0.48）、消除清除率（r2 = 0.54）和一些分布清除率的决定因素。肺分布容积与CO无关。
心输出量显著影响猪体内阿芬太尼的药代动力学。因此，考虑CO可提高阿芬太尼药代动力学模型的预测价值。
