Influence of the prone position on propofol pharmacokinetics

Abstract

Cardiac output (CO) is decreased in the prone position under general anaesthesia [1]. Although propofol is a high-clearance drug whose pharmacokinetics can be influenced by CO, there have been no investigations of its pharmacokinetics in the prone position. We investigated the effect of prone positioning on plasma propofol concentrations. Following institutional approval, informed consent was obtained from 10 ASA I–II patients undergoing spinal surgery under general anaesthesia (4 male and 6 female; age 25–65 years; height 159–178 cm; weight 45–95 kg). Anaesthesia was induced with vecuronium and propofol, and maintained with 60% nitrous oxide in oxygen and a target-controlled infusion of propofol (Diprifuser, AstraZeneca International, Wilmington, DE) to achieve a plasma propofol concentration of 6.0 μg.ml−1 at intubation, and 2.0 μg.ml−1 thereafter. When the predicted plasma propofol concentration of 2.0 μg.ml−1 was achieved at a constant infusion rate, and haemodynamic stability was established (± 20% of preinduction values for heart rate and blood pressure), CO was measured using the indocyanine green method, and a sample of blood collected for measurement of plasma propofol concentration. Thirty minutes after prone positioning using a chest roll and before the start of the operation, CO was measured again and blood collected again to determine the plasma propofol concentration. After prone positioning, CO decreased from 5.20 ± 0.80 to 4.30 ± 1.00 l.min−1. The plasma propofol concentration increased from 2.05 ± 0.20 to 2.38 ± 0.28 μg.ml−1. Myburgh et al. [2] and Kurita et al. [3] have investigated the influence of CO on propofol concentrations during continuous infusion, demonstrating an inverse relationship between CO and propofol concentrations. In this study, we demonstrated that propofol concentrations were greater than predicted as a result of the decrease of CO in the prone position. This study suggests the possibility of propofol overdosage in the prone position.