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


METHODS
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 Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects.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.
Silva
Guillermo
G
Clínica Las Condes, University of Chile, Santiago, Chile. mjpc@entelchile.net
Segovia
Roberto
R
Ponce
Rodrigo
R
Backhouse
Claudia
C
Palma
Mariana
M
Roblero
Juan Pablo
JP
Abadal
José
J
Quijada
Carmen
C
Troncoso
Mónica
M
Iturriaga
Hernán
H
D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology; D012083:Renin / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D011433:Propranolol; D012083:Renin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate