Abstract:
:If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Bansky G,Meier PJ,Riederer E,Walser H,Ziegler WH,Schmid Mdoi
10.1016/0016-5085(89)90647-1subject
Has Abstractpub_date
1989-09-01 00:00:00pages
744-50issue
3eissn
0016-5085issn
1528-0012pii
0016-5085(89)90647-1journal_volume
97pub_type
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