Neue Möglichkeiten in der Therapie der hepatischen Enzephalopathie?

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome associated with acute or chronic liver disease. It is generally considered a metabolic and potentially reversible syndrome. An important component of HE is increased neuro-inhibition caused by reduced hepatic metabolism of gut-derived nitrogenous substances and by activation of the postsynaptic GABAA-receptor complex in the central nervous system. Effective conventional therapy of HE includes prevention of precipitating factors, restriction of dietary protein an administration of lactulose (or lactitol) and possibly also of antibiotics. In addition, animal studies and uncontrolled clinical studies indicate that the benzodiazepine antagonist flumazenil effectively diminishes the increased neuroinhibition in certain patients with HE. However, these favourable flumazenil effects must be confirmed in larger randomized and placebo-controlled multicenter studies before flumazenil can be regarded as a useful new addition to current management of patients with acute or chronic hepatic encephalopathy

Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans

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

Hepatische Manifestationen des erwobenen Immunmangelsyndroms (AIDS)

Hepatic manifestations of acquired immunodeficiency syndrome (AIDS) were analyzed in 76 consecutive patients. Serological markers of hepatitis B were found in 84%. All instances of biopsy-proven chronic hepatitis were associated with delta infection. One patient with intestinal cryptosporidiosis had a severe cholestasis. In the majority of patients histological examination of the liver revealed non-specific alterations, but in several cases was diagnostic of mycobacterial disease. The study of liver disease in HIV-infected patients could lead to a better understanding of diseases such as chronic hepatitis B and sclerosing cholangitis

Specific treatment of benzodiazepine overdose.

Intentional benzodiazepine (BZD) overdose is usually a benign condition frequently encountered in the emergency department of hospital. Twenty-one patients, who were suspected of BZD overdose, were treated with the antagonist of the central type BZD-receptors Ro 15-1788. Samples for toxicological analysis were taken before and after treatment. The patients were divided into three groups. In the first group (pure BZD overdose, n = 9), rapid and complete awakening was observed in all the patients (9/9) with 3.5 +/- 1.5 mg Ro 15-1788. In the second group of patients with multiple drugs poisoning (including BZD, n = 6), CNS depression improved in all the patients despite incomplete awakening. In the last group (n = 6), where no BZD were detected in toxicological samples, none of the comatous patients improved significantly during Ro 15-1788 administration, except one patient with pure ethanol intoxication. No undesirable effects are reported, except mild transitory withdrawal syndrome in three cases following rapid injection. This study supports the introduction of Ro 15-1788 as a useful antidote in the diagnosis and the treatment of drug-induced coma.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effect of Flumazenil On Basal and Naloxone-Stimulated Acth and Cortisol Release in Humans

1. Endogenous benzodiazepine receptor ligands are thought to influence the human hypothalamic-pituitary-adrenal (HPA) axis and naloxone, a known stimulator of adrenocorticotropic hormone (ACTH) release, is thought to act via release of hypothalamic corticotropin-releasing hormone