Electroencephalographic study of the effect of a benzodiazepine antagonist in hepatic encephalopathy

Observing animal models of fulminant hepatic failure lead to the hypothesis of a GABAergic origin of the comatose state in hepatic encephalopathy (HE). The hypothesis of hyperstimulation of gamma-aminobutyric acid-benzodiazepine (GABA-BZ) receptors in HE has been tested with a BZ antagonist (flumazenil, Anexate) on 7 patients suffering from severe HE. The standard EEG has been recorded 30 min before and after slow IV perfusion of 1 mg flumazenil. Although we did not observe a complete EEG normalization, a significant improvement of EEG was observed after only a few minutes in 6 out of the 7 cases studied. Modification of the reactivity parallels clinical improvement of encephalopathy. These effects persist mostly 4 h after perfusion. The results are consistent with the hypothesis of hyperstimulation of GABA-BZ receptors in HE. The positive effect of flumazenil on vigilance level should encourage its use in chronic hepatic encephalopathy.