Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis.
OBJECTIVE
Recent reports have suggested that the vasodilating beta-blocker carvedilol may have beneficial acute haemodynamic effects in cirrhotic portal hypertension. However, no data exist on chronic use or renal effects in this patient group. The aim of this study was to assess the acute and chronic haemodynamic and renal effects of carvedilol in cirrhotic patients.


METHODS
Seventeen cirrhotic patients (mean age 55.2+/-2.8, mean Child-Pugh score 7.4+/-0.5) were studied. Hepatic venous pressure gradient, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate and hepatic blood flow were measured before and 1 h after 25 mg carvedilol. After 4 weeks of therapy with carvedilol 25 mg daily, these measurements were repeated before and after rechallenge with carvedilol. Urine volume, sodium excretion and creatinine clearance were also measured before and after 4 weeks of therapy.


RESULTS
Seven patients did not complete the 4-week carvedilol therapy due to hypotension or poor compliance. Hepatic venous pressure gradient fell by 20.8% acutely (p<0.001) and by 16.3% after 4 weeks of therapy (p<0.002). Heart rate, mean arterial pressure and cardiac output fell after acute administration of carvedilol, but only heart rate fell significantly after 4 weeks of treatment. Hepatic blood flow, urine volume, sodium excretion and creatinine clearance remained unchanged after therapy.


CONCLUSIONS
Carvedilol has beneficial effects on splanchnic haemodynamics following acute and chronic administration in cirrhosis, without compromising hepatic blood flow or renal function. However, a substantial number of patients cannot tolerate 25 mg daily.
Stanley
A J
AJ
Department of Medicine, Royal Infirmary of Edinburgh, UK.
Therapondos
G
G
Helmy
A
A
Hayes
P C
PC
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011412:Propanolamines / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol