Partial reversal of the cerebral effects of isoflurane in the dog by the benzodiazepine antagonist flumazenil

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Abstract
Six dogs initially anaesthetized with isoflurane–N2O–O2for surgery with cannulation of the sinus sagittalis for direct measurement of cerebral blood flow (CBF) and maintained with 1% isoflurane–N2–O2anaesthesia, were given two 2–mg doses of the benzodiazepine antagonist flumazenil with an interval of 10 min. This was accompanied by a significant increase in the cerebral metabolic rate for oxygen (CMRo2) 10 min after the first 2–mg dose, and 5, 10 and 15 min after the second 2–mg dose, the increase varying in mean value from 9% to 14%. EEG was recorded in five of the six dogs and administration of flumazenil converted the EEG from a sleep pattern to an awake pattern in two of them. There were no significant changes in the CBF or mean arterial blood pressure (MABP) values. In the brain biopsies taken at the end of the study there were no significant changes in the adenylate energy charge (EC) and the lactate/pyruvate ratio (L/P) when compared to five other dogs not given flumazenil. It is concluded that flumazenil in this study demonstrated a partial antagonism of the cerebral effects of isoflurane.