Quantitative electroencephalography for measurement of central nervous system responses to diazepam and the benzodiazepine antagonist, flumazenil, in isoflurane-anaesthetized dogs

Quantitative EEG was assessed in six dogs anaesthetized with 1.8% end-tidal isoflurane concentration and following diazepam (0.2 mg/kg i.v.) administration. Ventilation was controlled to maintain normocapnia. Five dogs were subsequently given the benzodiazepine antagonist, flumazenil (0.04 mg/kg i.v.), and quantitative EEG was recorded. One dog received a saline injection following diazepam (as a control) and quantitative EEG was recorded for an additional 2.5 h. Heart rate, arterial blood pressure, esophageal temperature, arterial pH and blood gas tensions, end-tidal CO2 tension and end-tidal isoflurane concentration were monitored throughout the study. A 21 lead linked-ear montage was used for recording EEG. Quantitative EEG data were stored on an optical disc for analysis at a later date. Values for absolute power of EEG were determined for theta, delta, alpha, and beta frequencies. Cardiovascular parameters remained stable throughout the study. Diazepam administration was associated with decreased absolute power in all frequencies of EEG at all electrode sites. The duration of diazepam-induced decreased absolute power of EEG was at least 3 h in one dog. Administration of flumazenil antagonized diazepam-induced decreased absolute power of EEG in all frequencies at all electrode sites. We conclude that quantitative EEG provides a relatively non-invasive, objective measure of diazepam- and flumazenil-induced changes in cortical activity during isoflurane anaesthesia.