Mild Hypothermia Alters Propofol Pharmacokinetics and Increases the Duration of Action of Atracurium

Abstract

Mild intraoperative hypothermia is common.We therefore studied the effects of mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atracurium duration of action in healthy volunteers. Six young volunteers were studied on two randomly assigned days, at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental, 3 mg/kg, and maintained with 70% N2 O and 0.6% isoflurane. Core hypothermia was induced by conductive and convective cooling. On the other study day, normothermia was maintained by a Bair Hugger Registered Trademark (Augustine Medical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lean body mass (LBM), then was given, followed by a 4-h infusion at 5 mg centered dot kg-1 centered dot h-1. After 2 h, atracurium 0.5 mg/kg was administered as an intravenous bolus. Indocyanine green was administered for estimation of hepatic blood flow. Arterial blood was assayed for propofol and indocyanine green concentration. Pharmacokinetic analysis was performed using NONMEM. Results are reported as means +/- SEM. Propofol blood concentrations averaged approximate equals 28% more at 34 degrees C than at 37 degrees C (P < 0.05). Hepatic blood flow decreased 23% +/- 11% in normothermic volunteers during the propofol infusion, and 33% +/- 11% in hypothermic volunteers (P = not significant). A three-compartment mamillary model fitted the data best. Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit. The intercompartmental clearances were decreased in the presence of hypothermia. Core hypothermia prolonged the time to recovery of the first twitch in the train-of-four to 10% of its control value (T1 = 10%) after atracurium administration by approximate equals 60% (P < 0.05), from 44 +/- 4 min to 68 +/- 7 min. In contrast, T1 = 25%-75% remained unchanged. We conclude that 3 degrees C of core hypothermia increased propofol blood concentrations and prolonged atracurium duration of action. Hepatic blood flow was decreased during propofol administration, and this change was a significant predictor of propofol clearance, indicating that the effect of propofol on hepatic blood flow impairs the clearance of propofol itself. (Anesth Analg 1995;80:1007-14)