Pharmacokinetic Analysis of Propofol Target-Controlled Infusion Models in Chinese Patients with Hepatic Insufficiency
Xinjin Chi, Jingru Pan, Jun Cai, Gangjian Luo, Shangrong Li, Dongdong Yuan, Jianzhong Rui, Wenying Chen, Ziqing Hei
(Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland))
Med Sci Monit 2018; 24:6925-6933
Chinese Clinical Trial Registry # ChiCTR-OCH-12002255
Effects of liver dysfunction on target-controlled infusion (TCI) with Marsh parameters of propofol remain poorly documented. The purpose of this study was to evaluate the performance of propofol TCI in a cohort of Chinese patients with severe hepatic insufficiency.
MATERIAL AND METHODS: We assigned 32 patients who underwent liver transplantation to 3 groups according to Child-Turcotte-Pugh (CTP) score. Anesthesia, preceding liver transplantation, was induced and maintained with TCI of 3 µg/mL propofol. Plasma propofol concentration was assessed. Propofol TCI system performance was analyzed in terms of error size, bias, and divergence. Data on plasma propofol concentrations were analyzed, and population pharmacokinetic parameters of propofol were fitted by NONMEM software.
RESULTS: In the CTP C group, measured concentrations of propofol were much higher than those of predictive concentrations, with significantly higher overshoots compared to CTP A patients. Overall, TCI system performance was significantly lower in CTP C patients. Linear regression equations of Cm vs. Cp and a regression model of pharmacokinetics were obtained.
CONCLUSIONS: Propofol TCI device performance with Marsh parameters was clinically acceptable in CTP A patients but may not be suitable for patients with severe hepatic impairment.
Keywords: Drug Delivery Systems, Liver Diseases, Pharmacokinetics, Propofol