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Anesth Analg 2005;100:996-1002
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000146517.17910.54

ANESTHETIC PHARMACOLOGY

The Effect of Mild Hypothermia on Plasma Fentanyl Concentration and Biotransformation in Juvenile Pigs

Harald G. Fritz, MD*, Martin Holzmayr{dagger}, Bernd Walter, MD{dagger}{ddagger}, Klaus-Uwe Moeritz, PhD||, Amelie Lupp, MD§, and Reinhard Bauer, MD, PhD{dagger}

Departments of *Anesthesiology and Intensive Care Medicine and {dagger}Pathobiochemistry, Institute for Pathophysiology and Pathobiochemistry, {ddagger}Department of Neurosurgery and §Institute for Pharmacology and Toxicology, Friedrich-Schiller-University, Jena; and || Institute of Pharmacology, Ernst Moritz Arndt University, Greifswald, Germany

Address correspondence and reprint requests to Harald G. Fritz, MD, Department of Anesthesiology and Intensive Care Medicine, Martha-Maria Hospital Halle D*lau gGmbH, Roentgenstr. 1, D-06120 Halle/S., Germany. Address e-mail to harald_fritz_2000{at}yahoo.de.

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 ± 1.1 kg) were anesthetized by IV fentanyl (15 µg · kg–1 · h–1) and midazolam (1.0 mg · kg–1 · h–1). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6° ± 0.2°C for 6 h and were then rewarmed and kept normothermic at 37.7° ± 0.3°C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% ± 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% ± 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.




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[Abstract] [Full Text] [PDF]


Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2005 by the International Anesthesia Research Society.