Effects of 5-isosorbide mononitrate and propranolol on subclinical hepatic encephalopathy and renal function in patients with liver cirrhosis

Hepatogastroenterology. 2002 Sep-Oct;49(47):1357-62.

Abstract

Background/aims: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study.

Methodology: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured.

Results: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables.

Conclusions: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Double-Blind Method
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Isosorbide Dinitrate / analogs & derivatives*
  • Isosorbide Dinitrate / pharmacology*
  • Isosorbide Dinitrate / therapeutic use
  • Liver / drug effects*
  • Liver / physiopathology
  • Liver Cirrhosis / physiopathology*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Propranolol / pharmacology
  • Renin / blood
  • Vasodilator Agents / pharmacology*
  • Vasodilator Agents / therapeutic use

Substances

  • Vasodilator Agents
  • Propranolol
  • Renin
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate