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NEUROSURGICAL ANESTHESIA

Phenytoin, Midazolam, and Naloxone Protect Against Fentanyl-Induced Brain Damage in Rats

Department of Anesthesiology, West Virginia University, Morgantown, West Virginia

Address correspondence and reprint requests to W. Andrew Kofke, MD, West Virginia University, Department of Anesthesiology, 3618 HSC, PO Box 9134, Morgantown, WV 26506-9134. Address e-mail to akofke{at}wvu.edu

In previous studies, large-dose fentanyl produced electrographic seizure activity and histologically evident brain damage. We assessed whether fentanyl-induced brain damage is attenuated by using anticonvulsant drugs. Using halothane/nitrous oxide anesthesia, 40 Sprague-Dawley rats underwent tracheal intubation, arterial and venous cannulation, and insertion of biparietal electroencephalogram electrodes and a rectal temperature probe. Halothane was discontinued. The dose of IV fentanyl shown previously to cause maximal brain damage was given to all animals and N₂O was discontinued. Control rats were given fentanyl only. Rats in the three study groups also received midazolam, phenytoin, or N₂O/naloxone. After characteristic seizure activity began with fentanyl loading the study drug was started. After a 2-h infusion, wounds were closed, and animals recovered overnight and underwent cerebral perfusion-fixation. Neuropathologic alterations were ranked on a scale of 0–5 for both neuronal death (0 = normal, 5 = more than 75% neuronal death) and for malacia. Significantly fewer rats in the N₂O/Naloxone, Phenytoin, and Midazolam Groups sustained any brain damage compared with controls. Protection against opioid neurotoxicity is achieved with midazolam, naloxone, and phenytoin. If opioid neurotoxicity is clinically relevant, a small change in anesthetic practice might reduce any potential neurologic morbidity.

Implications: Narcotics in large doses can cause brain damage in rats. This brain damage is attenuated by a narcotic antagonist, a sedative, and an antiepileptic drug.

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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