In a prospective randomized short-term study, the efficacy and safety of
xipamide and a combination of
spironolactone and
furosemide were compared in the treatment of hepatic cirrhotic
ascites. Twenty-two patients were randomized to either
xipamide, 20 mg/day (group I), or
spironolactone, 200 mg/day, combined with
furosemide, 40 mg on alternate days (group II). During the first 4 days of treatment, adequate diuresis, measured as loss of
body weight greater than 1.6 kg, occurred in 7 patients in group I and in 3 in group II. In the latter group, another 4 patients responded satisfactorily after a further 4 days of treatment. Four patients in group I who failed to respond to
xipamide with an adequate loss of
body weight were subsequently treated with the
spironolactone-
furosemide combination, but only one responded. Two patients in group II who failed to respond to the combination of
spironolactone and
furosemide also failed to respond to
xipamide. In both groups, a positive
diuretic response occurred only when the pretreatment fractional
sodium excretion exceeded 0.2%.
Diuretic resistance was overcome only by additional treatments which reduced proximal tubular
sodium reabsorption.
Xipamide commonly induced hypokalaemia; in contrast hyperkalaemia was seen following treatment with the
spironolactone-
furosemide combination. Renal function remained stable in all patients during both
diuretic treatments. An open ongoing 6-month trial of
torasemide, 10-40 mg/day, in combination with
spironolactone, 50-400 mg/day, has also been undertaken in 117 patients with cirrhotic
ascites who showed inadequate responses to
salt and water restriction and
spironolactone alone. Twenty-seven patients have been withdrawn from the study, 9 for the complications of
hepatic coma,
bleeding oesophageal
varices, or hyponatraemia. Twenty-two patients are still being treated and 68 have completed the trial on a mean dose of
torasemide, 15 mg/day.
Body weight was reduced by a mean of 2.3 kg at 6 weeks, 2.6 kg at 14 weeks and 3.2 kg after 6 months. Loss of
body weight was primarily associated with reduction of
ascites and secondarily with reduction of peripheral oedema. There were no untoward adverse reactions with
torasemide, and no significant changes in serum
electrolytes, liver, renal, or haematological variables.