Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients

Abstract

The pharmacokinetics of propofol were determined in nine patients (seven men, two women, (mean +/- SD) 55.8 +/- 21.2 yr, 65.2 +/- 8 kg) requiring prolonged mechanical ventilation of their lungs. After an initial dose of 1-3 mg/kg, propofol was administered iv at 3 mg/kg/h for 72 h. Arterial blood samples were collected at selected times during and up to 72 h after infusion. Propofol whole blood concentrations were determined by high-performance liquid chromatography with fluorescence detection. Individual pharmacokinetic parameters were estimated by noncompartmental analysis. Derived pharmacokinetic parameters showed a long terminal phase (T1/2 = 1878 +/- 672 min), a large volume of distribution at steady state (Vdss = 1666 +/- 756 l), and a high total body clearance (Cl = 1.57 +/- 0.56 l/min). While the propofol terminal elimination half-life is longer than that previously reported, emergence from sedation after prolonged administration will be governed by both redistribution mechanisms arising from the large distribution volumes and elimination from the body.