title: Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis.
abstract: The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: van Vliet
authors.forename: W H
authors.initials: WH
authors.lastname: Hackeng
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: S G
authors.initials: SG
authors.lastname: Meuwissen
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D002216:Captopril / Q000009:adverse effects / Q000592:standards*; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000009:adverse effects / Q000592:standards*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000009:adverse effects / Q000592:standards*
chemical_list: D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D005665:Furosemide; D009320:Atrial Natriuretic Factor; D002216:Captopril; D012964:Sodium; D003404:Creatinine; D012083:Renin; D006152:Cyclic GMP