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Anesth Analg 1983; 62:305-313
© 1983 International Anesthesia Research Society
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Effects of Fentanyl, Naloxone, and Clonidine on Hemodynamics and Plasma Catecholamine Levels in Dogs

J. W. Flacke, MD, W. E. Flacke, MD, B. C. Bloor, PhD, and S. Olewine, BS

Department of Anesthesiology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90024.

Abstract

A 50-µ/kg dose of fentanyl, given intravenously in divided doses to dogs under enflurane-nitrous oxide anesthesia caused sharp decreases in heart rate (HR), arterial blood pressure (AP), left ventricular dP/dt, and plasma levels of catecholamines. Naloxone, 20 µg/kg given 65--70 min later, completely and rapidly reversed these changes. Because the cardiovascular effects of fentanyl and naloxone occurred in unparalyzed animals under surgical anesthesia without eliciting any motor responses, it seems unlikely that they can be ascribed to changes in awareness and surgical stimulation, especially pain. The brief duration of exposure to the narcotic makes it improbable that the naloxone respone is due to acute dependence and precipitated withdrawal. Pretreatment with 20 µg/kg of atropine only attenuated the decrease in HR, indicating a minor role of vagal mechanisms under these conditions. Administration of 20 µg/kg of clonidine by slow infusion after fentanyl further reduced sympathetic activity and greatly attenuated the naloxone response. Injection of 5 mg/kg of tolazoline after administration of clonidine produced massive cardiovascular stimulation by antagonizing clonidine and unmasking the naloxone reversal of fentanyl. Thus, in fully anesthetized dogs, fentanyl decreased the level of cardiovascular function mainly by reducing sympathetic activity. This effect does not seem to be secondary to analgesia or other sensory depressant effects of the narcotic, but rather to an action on central opioid-sensitive mechanisms regulating cardiovascular function.

Key Words: ANALGESICS: fentanyl • ANTAGONISTS, Narcotic: naloxone




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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 © 1983 by the International Anesthesia Research Society.