Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats

Citation
Eh. Sinz et al., Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats, ANESTH ANAL, 91(6), 2000, pp. 1443-1449
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIA AND ANALGESIA
ISSN journal
0003-2999 → ACNP
Volume
91
Issue
6
Year of publication
2000
Pages
1443 - 1449
Database
ISI
SICI code
0003-2999(200012)91:6<1443:PMANPA>2.0.ZU;2-3
Abstract
In previous studies, large-dose fentanyl produced electrographic seizure ac tivity and histologically evident brain damage. We assessed whether fentany l-induced brain damage is attenuated by using anticonvulsant drugs. Using h alothane/nitrous oxide anesthesia, 40 Sprague-Dawley rats underwent trachea l intubation, arterial and venous cannulation, and insertion of biparietal electroencephalogram electrodes and a rectal temperature probe. Halothane w as discontinued. The dose of IV fentanyl shown previously to cause maximal brain damage was given to all animals and N2O was discontinued. Control rat s were given fentanyl only. Rats in the three study groups also received mi dazolam, phenytoin, or N2O/naloxone. After characteristic seizure activity began with fentanyl loading the study drug was started. After a 2-h infusio n, wounds were closed, and animals recovered overnight and underwent cerebr al perfusion-fixation. Neuropathologic alterations were ranked on a scale o f 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. Pr otection against opioid neurotoxicity is achieved with midazolam, naloxone, and phenytoin. If opioid neurotoxicity is clinically relevant, a small cha nge in anesthetic practice might reduce any potential neurologic morbidity.