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Epidural Blockade Affects the Pharmacokinetics of Propofol in Surgical Patients

Sitsen, Elske MD; Olofsen, Erik MSc; Lesman, Agnes MD; Dahan, Albert MD, PhD; Vuyk, Jaap MD, PhD

doi: 10.1213/ANE.0000000000001090
Anesthetic Pharmacology: Research Report

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Published ahead of print December 8, 2015

From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

Accepted for publication September 29, 2015.

Published ahead of print December 8, 2015

Funding: The Department of Anesthesiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.

The authors declare no conflicts of interest.

This report was previously presented, in part, at the American Society of Anesthesiologists Washington 2012, which was the subject of an article in Best Clinical Abstract session congress book and at the Dutch Anesthesiology Meeting, May 2013.

Reprints will not be available from the authors.

Address correspondence to Elske Sitsen, MD, Department of Anesthesiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Address e-mail to mesitsen@lumc.nl.

© 2016 International Anesthesia Research Society