Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans

摘要: If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible induce ameliorations syndrome by pharmacologically antagonizing a component GABA/benzodiazepine receptor complex. To test this possibility we administered benzodiazepine antagonist flumazenil intravenous injection 14 patients with encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements mental status in 71% patients. The degree improved from stage IV II 4 III 2 all less advanced (3 III, 1 II) also improved, these responses were clinically impressive. arousal effect occurred within minutes after lasted for h. Furthermore, was associated significant increase mean electroencephalographic frequency 4.2 5.2 cycle/s. Of 8 who ultimately discharged hospital, 7 had responded flumazenil. No patient died 48 h receiving shown any effect. These findings strongly favor prominent pathogenetic role GABAergic tone humans suggest that positive response might prognostic value predicting short-term survival encephalopathic liver disease.