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Benzodiazepine receptor antagonists for hepatic encephalopathyAls-Nielsen B, Gluud LL, Gluud C SummaryFlumazenil causes short-term improvement of hepatic encephalopathy in patients with chronic liver diseaseHepatic encephalopathy refers to changes in mental state, ranging from minor signs of altered brain function to deep coma occurring in patients with liver failure. Hepatic encephalopathy may be caused by an activation of a receptor-complex in the brain. Flumazenil, which inhibits this receptor-complex, might ameliorate the symptoms. This review found that flumazenil leads to a short-term improvement of hepatic encephalopathy in some patients with chronic liver disease and a highly favourable prognosis.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2009 Issue 2, Copyright © 2009 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This version first published online:
October 23. 2001 AbstractBackgroundHepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy. ObjectivesTo evaluate the beneficial and harmful effects of benzodiazepine receptor antagonists for patients with hepatic encephalopathy. Search strategyEligible trials were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE and EMBASE (last search: January 2004), reference lists of relevant articles, authors of trials, and pharmaceutical companies. Selection criteriaRandomised trials comparing any benzodiazepine receptor antagonist versus placebo or no intervention for hepatic encephalopathy. Data collection and analysisTwo reviewers independently included trials and extracted data. Binary outcomes are reported as risk difference (RD) with 95% confidence intervals (CI) based on a random effects model. Statistical heterogeneity was explored by a chi-squared test with significance set at P < 0.1. The inconsistency across trials was assessed by I2. Potential sources of heterogeneity were explored through subgroup analyses. Main resultsThirteen randomised trials with 805 patients were included. Eight trials used a crossover design. All trials were double-blind and assessed flumazenil versus placebo. Data on all outcomes could not be extracted from all trials. The included patients had a favourable prognosis (361/390 [93%] survived in the flumazenil group versus 345/376 [92%] in the placebo group). Flumazenil had a significant beneficial effect on improvement of hepatic encephalopathy at the end of treatment (RD 0.28; 95% CI 0.20 to 0.37, eight trials). Flumazenil had no significant effect on recovery (RD 0.13; 95% CI -0.09 to 0.36, two trials) or mortality RD 0.01; 95% CI -0.05 to 0.07, 10 trials). Flumazenil may be associated with adverse events, but trial results were heterogeneous. Authors' conclusionsFlumazenil had a significant beneficial effect on short-term improvement of hepatic encephalopathy in patients with cirrhosis and a highly favourable prognosis. Flumazenil had no significant effect on recovery or survival. Considering the fluctuating nature of hepatic encephalopathy, future trials should use a parallel design and assess if treatment with flumazenil leads to a sustained improvement or increased recovery and survival. Until this has been demonstrated, flumazenil may be considered for patients with chronic liver disease and hepatic encephalopathy, but cannot be recommended for routine clinical use. |