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

Elizabeth H. Sinz, W. Andrew Kofke, Robert H. Garman

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1443-1449
Number of pages7
JournalAnesthesia and analgesia
Issue number6
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine


Dive into the research topics of 'Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats'. Together they form a unique fingerprint.

Cite this