Clinical Pharmacokinetics of Propofol in Postoperative Sedation after Orthotopic Liver Transplantation

Abstract

The pharmacokinetics of propofol, administered as a constant rate 3 mg/kg/h intravenous 24-hour infusion for maintenance of sedation in patients undergoing mechanical ventilation after orthotopic liver transplantation, were studied during infusion and 24 hours after its termination. The concentrations obtained at steady-state (1.3 ± 0.5 mg/L) were slightly higher than those commonly reported upon recovery (1.1 mg/L). At the end of infusion, blood concentrations of propofol declined rapidly according to a triexponential function. The distribution half-life in the central compartment (t½α: 2.4 ± 2.2 minutes) was equal to the value observed after bolus administration. The distribution half-life in the deep peripheral compartment (t½β: 76.2 ± 42.1 minutes) and the elimination half-life (t½γ: 1102 ± 470 minutes) were longer than values obtained after bolus or short infusion, but were about the same as those determined after prolonged infusion. The volume of distribution calculated during the terminal phase (Vz: 3074 ± 1828L) was very large, showing extensive distribution in peripheral tissues. Total clearance (129 ± 78 L/h) remained unchanged compared with the data in the literature. The pharmacokinetics of propofol in patients who underwent a liver transplantation 48 hours previously were the same as parameters calculated at the end of a prolonged infusion in patients without liver disease. It is the duration of infusion that increases the volume of distribution and prolongs the elimination half-life of this agent and not some hypothetical dysfunction in the newly transplanted liver.