Hepatic encephalopathy flumazenil

The GABA-receptor complex, the primary inhibitory neural network within the central nervous system, is associated with HE. This receptor complex is composed of a GABA-binding site, and a benzodiazepine receptor site, which mediate chloride conductance. Based on evidence of an increase in benzodiazepine receptor ligands in patients with hepatic encephalopathy, flumazenil has been evaluated in uncontrolled studies and has demonstrated significant clinical improvement, with one case report documenting long-term benefit. In these reports, discontinuation of flumazenil resulted in prompt clinical deterioration. 

Adverse effects of flumazenil include agitation, confusion, dizziness, and nausea. Flumazenil may cause a severe precipitated abstinence syndrome in patients who have developed physiologic benzodiazepine dependence. In patients who have ingested benzodiazepines with tricyclic antidepressants, seizures and cardiac arrhythmias may occur following flumazenil administration. Transient improvement in mental status has been reported with flumazenil when used in patients with hepatic encephalopathy. 

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled... 

Cadranel, J.F., El Younsi, M., Pidoux, B., Zylberberg, P., Benhamou, Y., Valla, D., Opolon, P. Flumazenil therapy for hepatic encephalopathy in cirrhotic patients a double-blind pragmatic randomized, placebo study. Eur. X. Gastroenterol. Hepatol. 1995 7 325-329... 

Laccetti, M., Manes, G., Uomo, G., Lioniello, M., Rabitti, P.G., Balz-ano. A. Flumazenil in the treatment of acute hepatic encephalopathy... 

Flumazenil (Mazicon) is a new competitive antagonist at benzodiazepine receptors. Used clinically to reverse benzodiazepine sedation or overdose and as part of the treatment for hepatic encephalopathy. Resedation occurs in about 10% of reversals. Seizures infrequently occur with reversal, usually following multi-drug overdose. ... 

Flumazenil has been used as a non-specific treatment in patients with hepatic encephalopathy [88, 89. However, it was effective in only some subjects in a double-blind, placebo-con-trolled, crossover study in 527patients with cirrhosis and hepatic encephalopathy grade III and IVa, of whom 265 received flumazenil and 262 received placebo [90 ]. There was improvement of the neurological score in 18% of the patients with grade III encephalopathy and in 15% of those with grade IVa compared with 3.8% and 2.7% respectively of those who received placebo electroencephalography improved in 28% and 22% compared with... 

Psychiatric Oral flumazenil was used in a woman who had had several episodes of hepatic encephalopathy, in an attempt to prevent deterioration into coma, but after 2 days she had an acute psychosis the symptoms resolving rapidly when flumazenil w os withdrawn [IIT]. 

Meier R, Gyr K. Treatment of hepatic encephalopathy (HE) with the benzodiazepine antagonist flumazenil a pilot study. Eur J Anaesthesiol Suppl 1988 2 139-46. 

Francavilla R, Barbarini G. Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis an Italian multicenter double-blind, placebo-controlled, cross-over study. Hepatology 1998 28(2) 374-8. 

Seebach J, lost R. Flumazenil-induced psychotic disorder in hepatic encephalopathy. Lancet 1992 339 488-9. 

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