Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content

Abstract

ABSTRACT— 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 antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy – 115 hospitalized patients with non‐azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K‐canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous 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 spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K‐canrenoate ≤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 Two patients were withdrawn from the protocol due to diuretic side‐effects.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. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment. The use of low‐sodium diet did not enhance the efficacy of the medical treatment of non‐azotemic cirrhotic ascites and a washout period from diuretics improved renal function and natremia. Antimineralocorticoids up to 400 mg/day were successful in over 2/3 of cases and the improvement in efficacy obtained by a further increase in dose was small. Endogenous creatinine clearance and plasma aldosterone significantly influenced treatment efficacy. The therapeutic regimen employed in this study was highly effective and had a very low incidence of side effects.

Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial

“…Nevertheless, it is worth observing that the study by Santos et al included a large proportion of previously untreated patients with cirrhosis and ascites, who are not commonly seen at tertiary referral centres. This is the main reason why in our hands7 and in the hands of other authors8 spironolactone alone is effective in mobilising ascites in only 56% and 77% of non-azotaemic patients with cirrhosis, respectively. As a result, a significant proportion of patients with cirrhosis and ascites should experience further steps of sequential diuretic treatment, prolonging both the time to achieve the effective step and, overall, the time to achieve the mobilisation of ascites 7 8.…”

“…This is the main reason why in our hands7 and in the hands of other authors8 spironolactone alone is effective in mobilising ascites in only 56% and 77% of non-azotaemic patients with cirrhosis, respectively. As a result, a significant proportion of patients with cirrhosis and ascites should experience further steps of sequential diuretic treatment, prolonging both the time to achieve the effective step and, overall, the time to achieve the mobilisation of ascites 7 8. Therefore, an open randomised clinical study was performed by comparing sequential diuretic therapy versus combined diuretic therapy in the treatment of moderate ascites in non-azotaemic patients with cirrhosis as regards their efficacy and safety.…”

Pathophysiologic basis for the medical management of portal hypertension

“…Aquaretic agents that involve vasopressin antagonists (e.g., tolvaptan [69] ) are now under investigation for the management of hyponatremia (for a recent review, see Gines [70] ). Approximately 5 -10% of patients develop refractory ascites, defined as ascites that does not respond to diuretics [71] . In these patients, repeated large volume paracentesis (i.e., removal of 5 l of fluid) is employed (for review, see Sandhu [29] ).…”

Ernährung bei Leberzirrhose

“…Mehrere Studien konnten allerdings keinen signifikanten Unterschied zwischen einer strikt kochsalzarmen Diät (50 mmol Na bzw. 3 g NaCl/d) und einer diuretischen Therapie im Hinblick auf Mobilisierung von Ödemen finden [110][111][112]. Außerdem muss beachtet werden, dass eine strenge Natriumrestriktion neben Complianceproblemen oft mit einer reduzierten Proteinzufuhr vergesellschaftet ist [24].…”