Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis

An Italian multicenter double-blind, placebo-controlled, cross- over study

Gluseppe Barbaro, Gabriella Di Lorenzo, Maurizio Soldini, Giuseppe Giancaspro, Giorgio Bellomo, Giancarlo Belloni, Benvenuto Grisorio, Mauro Annese, Donato Bacca, Ruggiero Francavilla, Giorgio Barbarini

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The rationale for use of benzodiazepine receptor antagonists is based on the so-called benzodiazepine pathogenetic hypothesis of hepatic encephalopathy (HE). To assess the efficacy of flumazenil, a specific benzodiazepine receptor antagonist, in a large and selected population of cirrhotic patients with severe HE, we conducted a double-blind, placebo- controlled, cross-over trial on 527 cirrhotic patients with HE grade III and IVa admitted to Intensive Care Units over a 5-year period; among them, 265 (132 of grade III and 133 of grade IVa) received flumazenil, whereas 262 (130 of grade III and 132 of grade IVa) received placebo. Treatment was begun within 15 minutes of randomization; the response to treatment was assessed by neurological score and by continuous electroencephalographic (EEG) recordings. Improvement of the neurological score was documented in 17.5% of grade III patients treated with flumazenil and in 14.7% of grade IVa patients, compared, respectively, with 3.8% and 2.7% of the patients of both groups treated with placebo. Improvements in EEG tracings were observed in 27.8% of grade III patients and in 21.5% of grade IVa patients, compared, respectively, with 5% and 3.3% of the patients of both groups treated with placebo. Benzodiazepines were detected in the serum of 10 patients (4 in grade III group and 6 in grade IVa group). Flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with severe HE still remains to be determined.

Original languageEnglish
Pages (from-to)374-378
Number of pages5
JournalHepatology
Volume28
Issue number2
DOIs
Publication statusPublished - 1998

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Flumazenil
Hepatic Encephalopathy
Cross-Over Studies
Fibrosis
Placebos
GABA-A Receptors
Benzodiazepines
Random Allocation
Intensive Care Units
Therapeutics

ASJC Scopus subject areas

  • Hepatology

Cite this

Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis : An Italian multicenter double-blind, placebo-controlled, cross- over study. / Barbaro, Gluseppe; Di Lorenzo, Gabriella; Soldini, Maurizio; Giancaspro, Giuseppe; Bellomo, Giorgio; Belloni, Giancarlo; Grisorio, Benvenuto; Annese, Mauro; Bacca, Donato; Francavilla, Ruggiero; Barbarini, Giorgio.

In: Hepatology, Vol. 28, No. 2, 1998, p. 374-378.

Research output: Contribution to journalArticle

Barbaro, G, Di Lorenzo, G, Soldini, M, Giancaspro, G, Bellomo, G, Belloni, G, Grisorio, B, Annese, M, Bacca, D, Francavilla, R & Barbarini, G 1998, 'Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: An Italian multicenter double-blind, placebo-controlled, cross- over study', Hepatology, vol. 28, no. 2, pp. 374-378. https://doi.org/10.1002/hep.510280212
Barbaro, Gluseppe ; Di Lorenzo, Gabriella ; Soldini, Maurizio ; Giancaspro, Giuseppe ; Bellomo, Giorgio ; Belloni, Giancarlo ; Grisorio, Benvenuto ; Annese, Mauro ; Bacca, Donato ; Francavilla, Ruggiero ; Barbarini, Giorgio. / Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis : An Italian multicenter double-blind, placebo-controlled, cross- over study. In: Hepatology. 1998 ; Vol. 28, No. 2. pp. 374-378.
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