EFFICACY AND SAFETY OF THE STEPPED CARE MEDICAL-TREATMENT OF ASCITES IN LIVER-CIRRHOSIS - A RANDOMIZED CONTROLLED CLINICAL-TRIAL COMPARING 2 DIETS WITH DIFFERENT SODIUM CONTENT

In order to clarify debated issues of the medical treatment of ascites in cirrhosis - the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocort icoid to be reached before the addition of a loop diuretic, identifica tions of factors influencing treatment efficacy - 115 hospitalized pat ients with non-azotemic cirrhosis and ascites were recruited and rando mized to receive a diet providing either 40 or 120 mmol of sodium dail y. After a washout period from the outpatient diuretic regimen for 7 d ays (Step 1), increasing dosages of K-canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing sponta neous diuresis (Step 2). Upon the failure of Step 2, K-canrenoate (400 mg/day) and furosemide at increasing dosage (25-50-100 mg every other day) were given (Step 3). Nine percent of patients underwent spontane ous diuresis, and 77% developed a negative sodium balance by the end o f Step 2 (69% with a dosage of K-canrenoate less-than-or-equal-to 400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side-effects. Univariate analysis showed that the type of diet did not influence the response to treatment. Th e washout period led to a significant increase in endogenous creatinin e clearance; natremia significantly rose in hyponatremic patients. Mul tivariate analysis showed that creatinine clearance and plasma aldoste rone were independent predictive factors of the response to treatment. The use of low-sodium diet did not enhance the efficacy of the medica l treatment of non-azotemic cirrhotic ascites and a washout period fro m diuretics improved renal function and natremia. Antimineralocorticoi ds up to 400 mg/day were successful in over 2/3 of cases and the impro vement in efficacy obtained by a further increase in dose was small. E ndogenous creatinine clearance and plasma aldosterone significantly in fluenced treatment efficacy. The therapeutic regimen employed in this study was highly effective and had a very low incidence of side effect s.