Attenuation of midazolam-induced EEG activation in rats by both flumazenil and hyperbaric oxygen.
Sedative doses of benzodiazepines, i.e., midazolam, can cause electroencephalography (EEG) activation, which is reversed by the benzodiazepine antagonist flumazenil. Hyperbaric oxygen (HBO) can cause acute cerebral toxicity with sensory and motor abnormalities, including seizures. Benzodiazepines are also administered for anxiolysis, sedation, and seizure prophylaxis to patients receiving HBO treatments. Because of possible interactions on monitored neuroelectric activity, we decided to evaluate the effects of midazolam on the EEG and cortical somatosensory evoked potentials (CEPs) in rats exposed to HBO, as well as to compare this to the effects of flumazenil. Thirty-six Sprague-Dawley rats were studied. Analog 2-channel and computerized EEG analysis (compressed spectral array with spectral edge, power spectrum, and power bands) and CEPs were monitored. Studies were divided into two phases. In phase 1, after baseline recordings, 16 rats were randomly assigned to receive midazolam, 0.1 mg.kg-1 intravenously, then compression to 1,824 mm Hg of O2 (n = 8), or 1,824 mm Hg of O2 followed by the midazolam (n = 8). In phase 2, after baseline recordings, rats were randomly assigned to four (n = 5) groups: midazolam, 0.1 mg.kg-1 intravenously, then compression to 1,824 mm Hg of O2; midazolam, then flumazenil, 0.05 mg.kg-1 intravenously; compression, then midazolam; or flumazenil, then midazolam. Recordings of EEG and CEPs were compared by analysis of variance and the Student's t test. In phase 1, midazolam first showed EEG activation in six (75%) rats, which was reversed by HBO. The HBO first activated the EEG in two rats (25%); midazolam then given had no effect. The CEPs were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Russell
G B
GB
Department of Anesthesia, Penn State University College of Medicine, Hershey, USA.
Vance
W T
WT
Graybeal
J M
JM
D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D018496:Hyperoxia / Q000503:physiopathology; D008874:Midazolam / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects
D018686:Anesthetics, Intravenous; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D008874:Midazolam