JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fritz, H. G.
Right arrow Articles by Bauer, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fritz, H. G.
Right arrow Articles by Bauer, R.
Related Collections
Right arrow Pharmacology

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.




This article has been cited by other articles:


Home page
PediatricsHome page
A. Roka, K. T. Melinda, B. Vasarhelyi, T. Machay, D. Azzopardi, and M. Szabo
Elevated Morphine Concentrations in Neonates Treated With Morphine and Prolonged Hypothermia for Hypoxic Ischemic Encephalopathy
Pediatrics, April 1, 2008; 121(4): e844 - e849.
[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.