MILD HYPOTHERMIA ALTERS PROPOFOL PHARMACOKINETICS AND INCREASES THE DURATION OF ACTION OF ATRACURIUM

Mild intraoperative hypothermia is common. We therefore studied the ef fects of mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atra curium duration of action in healthy volunteers. Six yo ung volunteers were studied on two randomly assigned days, at either 3 4 degrees C or 37 degrees C. Anesthesia was induced with thiopental, 3 mg/kg, and maintained with 70% N2O and 0.6% isoflurane. Core hypother mia was induced by conductive and convective cooling. On the other stu dy day, normothermia was maintained by a Bair Hugger(R) (Augustine Med ical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lea n body mass (LBM), then was given, followed by a 4-h infusion at 5 mg . kg(-1). h(-1). After 2 h, atracurium 0.5 mg/kg was administered as a n intravenous bolus. Indocyanine green was administered for estimation of hepatic blood flow. Arterial blood was assayed for propofol and in docyanine green concentration. Pharmacokinetic analysis was performed using NON-MEM. Results are reported as means +/- SEM. Propofol blood c oncentrations averaged approximate to 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 m amillary model fitted the data best. Inclusion of hepatic blood flow c hange from the prepropofol baseline as a covariate for total body clea rance significantly improved the fit. The intercompartmental clearance s were decreased in the presence of hypothermia. Core hypothermia prol onged the time to recovery of the first twitch in the train-of-four to 10% of its control value (TI = 10%) after atracurium administration b y approximate to 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 pro longed atracurium duration of action. Hepatic blood flow was decreased during propofol administration, and this change was a significant pre dictor of propofol clearance, indicating that the effect of propofol o n hepatic blood flow impairs the clearance of propofol itself.