Skip to main content
Log in

Flumazenil in the treatment of portal systemic encephalopathy —an overview

  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Hepatic encephalopathy is a complex neuropsychiatric syndrome associated with acute, subacute and chronic liver failure, involving increased neural inhibition by activation of the GABA/benzodiazepine inhibitory neurotransmitter system. Improvement by GABA and benzodiazepine receptor antagonists as well as by chloride ionophore blockers has been shown in animal experiments. Recent reports indicate that flumazenil may improve hepatic encephalopathy in man. To date 46 episodes of HE in 41 patients have been treated with flumazenil with a short term success rate of 72%. Most of the patients were screened for exogenous benzodiazepines and found negative. These interesting observations should now be investigated in a randomised doubleblind controlled study in patients with HE to evaluate the efficiency of this therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Basile AS, Gammal SH (1988) Evidence for the involvement of the benzodiazepine receptor complex in hepatic encephalopathy. Clin Neuropharmacol 11:401–422

    Google Scholar 

  2. Jones EA, Gammal SH (1988) Hepatic encephalopathy. In: Arias IM, Jakoby WB (eds) The liver: biology and pathobiology, 2nd edn, chap 56. Raven Press, New York, pp 985–1105

    Google Scholar 

  3. Jones EA, Skolnick P, Gammal SH, Basile AS, Mullen KD (1989) The α-amino-butyric acid (GABA) a receptor complex and hepatic encephalopathy. Some recent advances. Ann Intern Med 110:532–546

    Google Scholar 

  4. Geiger A, Magnes J, Taylor RM, Veralli M (1954) Effect of blood constituents on uptake of glucose and on metabolic rate of the brain in perfusion experiments. Am J Physiol 177:138–149

    Google Scholar 

  5. Roche-Sicot J, Sicot C, Peignoux M, Bourdiau D (1974) Acute hepatic encephalopathy in the rat: the effect of cross-circulation. Clin Sci Molec Med 47:609–615

    Google Scholar 

  6. Record CO, Al Mardini H, Bartlett K (1982) Blood and brain mercaptan concentrations in hepatic encephalopathy. Hepatology 2:144

    Google Scholar 

  7. Zieve L (1981) The mechanism of hepatic coma. Hepatology 1:360–365

    Google Scholar 

  8. Windus-Podehl G, Lyftogt C, Ziewe L, Brunner G 1983) Encephalopathic effect of phenol in rats. J Lab Clin Med 101:586–592

    Google Scholar 

  9. Fischer JE, Baldessarini RJ (1971) False neurotransmitters and hepatic failure. Lancet II:75–79

    Google Scholar 

  10. Schafer DF (1987) Hepatic coma: studies on the target organ. Gastroenterology 93:1131–1132

    Google Scholar 

  11. Ferenci P, Kleinberger G, Schafer DF, Hoofnagle JH, Jones EA (1983) Serum levels of gamma-aminobutyric-acid like activity in acute and chronic hepatocellular disease. Lancet II:811–814

    Google Scholar 

  12. Schafer DF, Fowler JM, Brody LE, Jones EA (1980) Hepatic coma and inhibitory neurotransmission: the enteric bacterial flora as a source of aminobutyric acid. Gastroenterology 79:1052

    Google Scholar 

  13. Schafer DF, Jones EA (1982) Hepatic encephalopathy and the α-aminobutyric-acid neurotransmitter system. Lancet I:18–20

    Google Scholar 

  14. Schafer DF, Pappas SC, Brody LE, Jacobs R, Jones EA (1984) Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas. Gastroenterology 86:540–545

    Google Scholar 

  15. Minuk GY, Winder A, Burgess ED, Sarjeant EJ (1985) Serum gamma-amino-butyric acid (GABA) levels in patients with hepatic encephalopathy. Hepatogastroenterology 32:171–174

    Google Scholar 

  16. Maddison JE, Dodd PR, Johnston GAR, Farrell GC (1986) Brain GABA receptor binding and plasma GABA-like activity in a model of chronic hepatic encephalopathy in rats. Hepatology 6:1126

    Google Scholar 

  17. Jones DB, Mullen KD, Roessle M, Maynard T, Jones EA (1987) Hepatic encephalopathy: application of visual evoked responses to test hypothesis of its pathogenesis in rats. J Hepatol 4:118–126

    Google Scholar 

  18. Bassett ML, Mullen KD, Skolnick P, Jones EA (1987) Amelioration of hepatic encephalopathy by pharmacologic antagonism of the GABA benzodiazepine receptor complex in a rabbit model of fulminant hepatic failure. Gastroenterology 93:1069–1077

    Google Scholar 

  19. Scollo-Lavizzari G, Steinmann E (1985) Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet I:1324–1325

    Google Scholar 

  20. Bansky G, Meier PJ, Ziegler WH, Walser H (1985) Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet I:1324–1325

    Google Scholar 

  21. Meier R, Gyr K (1988) Treatment of hepatic encephalopathy (HE) with the benzodiazepine antagonist flumazenil: a pilot study. Eur J Anaesthesiol [Suppl 2]:139–146

    Google Scholar 

  22. Basile AS, Gammal SH, Mullen KD, Jones EA, Skolnick P (1988) Differential responsiveness of cerebellar Purkinje neurons to GABA and benzodiazepine receptors ligands in an animal model of hepatic encephalopathy. J Neurosci 8:2414–2421

    Google Scholar 

  23. Mullen KD, Mendelson WB, Martin JV, Bassett ML, Jones EA (1988) Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy? Lancet I:457

    Google Scholar 

  24. Olasmaa M, Guidotti A, Costa E, Rothstein JD, Goldman ME (1989) Endogenous benzodiazepines in hepatic encephalopathy. Lancet I:491–492

    Google Scholar 

  25. Jones A, Gammal S (1988) The liver. Biology and pathobiology, 2nd edn Arias IM, Jackoby WB, Popper H, Schachter D, Shafritz DA (eds). Raven Press, New York

    Google Scholar 

  26. Grimm G, Katzenschlager R, Schneeweiss B, Lenz K, Ferenci P (1988) Improvement of hepatic encephalopathy treated with flumazenil. Lancet II:1392

    Google Scholar 

  27. Burke DA, Mitchell KW, Al Mardini H, Record CO (1988) Reversal of hepatic coma with flumazenil in improvement in visual evoked potentials. Lancet II:505–506

    Google Scholar 

  28. Sutherland LR, Minuk GY (1988) Ro 15-1788 and hepatic failure. Ann Intern Med 108:158

    Google Scholar 

  29. Ferenci P, Grimm G, Meryn S, Gangl A (1989) Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil. Gastroenterology 96:240–243

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gyr, K., Meier, R. Flumazenil in the treatment of portal systemic encephalopathy —an overview. Intensive Care Med 17 (Suppl 1), S39–S42 (1991). https://doi.org/10.1007/BF01731153

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01731153

Key words

Navigation