Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil.

A patient with portal-systemic encephalopathy refractory to standard therapy (40-g protein diet, oral neomycin and lactulose, supplementation of diet with branched chain amino acids) following extensive liver resection and construction of a portacaval shunt was treated with 25 mg of flumazenil twice daily by mouth. Before treatment with flumazenil she was encephalopathic and experienced 12 attacks of coma within 2 yr. When treated with flumazenil all signs of encephalopathy abated in spite of an unrestricted dietary intake of protein. Two days after discontinuation of flumazenil treatment she became comatose again. She remained chronically encephalopathic and had four further episodes of coma during the subsequent 3 mo. Since reinstitution of flumazenil treatment she has been well for 14 mo during follow-up without any signs of encephalopathy while on an unrestricted protein diet. Furthermore, flumazenil therapy reversed abnormalities of recordings of multimodality evoked potentials that were associated with hepatic encephalopathy. The striking remission of encephalopathy by treatment with flumazenil suggests that this benzodiazepine antagonist may be valuable in the long-term management of portal-systemic encephalopathy.