Epidural Blockade Affects the Pharmacokinetics of Propofol in Surgical Patients

Abstract

Neuraxial blockade reduces the dose requirements of sedative agents. It is unclear whether neuraxial blockade affects the pharmacokinetics and/or the pharmacodynamics of IV hypnotics. We therefore studied the influence of epidural blockade on the pharmacokinetics of propofol in patients scheduled for general surgery. Twenty-eight patients were randomly divided into 4 groups, in a double-blind manner, to receive 0, 50, 100, or 150 mg epidural ropivacaine. When the epidural blockade had stabilized, a target-controlled infusion of propofol was started at a target concentration of 1, 2.5, 4, and 6 µg/mL at 0, 6, 12, and 18 minutes, respectively. The infusion was terminated at 24 minutes. Arterial blood samples for blood propofol concentration determination were taken during and up to 150-minute postinfusion. The influence of epidural blockade on propofol pharmacokinetics was determined by mixed-effects modeling. With a ropivacaine dose increasing from 0 to 150 mg, the number of blocked segments (median [range]) increased from 0 (0-3) to 16 (6-21). With increasing epidural dose, blood propofol concentration increasingly exceeded target concentration. An epidural blockade of 20 segments reduced propofol's elimination clearance from 2.64 ± 0.12 to 1.87 ± 0.08 L/min. Adjusting for weight and sex further improved the propofol pharmacokinetic model. Epidural blockade affects the pharmacokinetics of propofol and the performance of a target-controlled infusion of propofol. At an epidural ropivacaine dose that blocks 20 segments, the propofol dosage or target concentration may be reduced by 30% compared with when no epidural blockade is present. An epidural-induced reduction in hepatic and/or renal blood flow may explain this pharmacokinetic interaction.