Flumazenil Does Not Impair Autoregulation of CBF in Dogs When Given With or Without Prior Administration of Midazolam

Abstract

The effects of flumazenil (a benzodiazepine antagonist) on autoregulation of cerebral blood flow (CBF) were examined in dogs receiving midazolam and in dogs not receiving midazolam. Both groups were anesthetized with halothane (0.3% end-expired) and nitrous oxide (66%) in oxygen. Auto-regulation of CBF was assessed by determining the slope relating CBF to cerebral perfusion pressure (CPP). These CBF/CPP slopes were derived from measurements of CBF at each of three CPPs: 65, 80, and 95 mm Hg. The effects of flumazenil on autoregulation were examined by comparing CBF/CPP slopes prior to administration of flumazenil to CBF/CPP slopes after flumazenil doses of 0.0025 and 0.16 mg/kg, both when cerebrospinal fluid (CSF) pressure was normal and when CSF pressure was elevated to 30 mm Hg. Prior to administration of flumazenil, CBF/CPP slopes were not different from zero, indicating intact autoregulation of CBF. CBF/CPP slopes did not change following administration of flumazenil, indicating that autoregulation of CBF was not substantially impaired. In dogs with normal CSF pressure that were receiving midazolam, both doses of flumazenil altered the electroencephalogram and the highest dose of flumazenil decreased cerebral vascular resistance and increased CBF and CSF pressure. No such changes were seen at the other experimental conditions. It is concluded that flumazenil does not severely disturb autoregulation of CBF, although flumazenil 0.16 mg/kg causes a statistically significant increase of CBF in dogs with normal CSF pressure that are receiving midazolam.