What is the role of Aldactone (spironolactone) in managing ascites in patients with liver disease?

Aldactone (Spironolactone) in Ascites

Spironolactone is the cornerstone first-line diuretic for cirrhotic ascites because it directly antagonizes the secondary hyperaldosteronism that drives fluid retention, achieving superior natriuresis compared to loop diuretics alone. 1, 2

Why Spironolactone is Superior

• Spironolactone demonstrates 95% response rate versus only 52% for furosemide monotherapy in non-azotemic cirrhotic patients with ascites 2
• Secondary hyperaldosteronism is the primary pathophysiologic mechanism driving ascites formation in cirrhosis, making aldosterone antagonism the most rational therapeutic target 2, 3
• Loop diuretics as monotherapy are explicitly not recommended—they are ineffective without aldosterone blockade 2, 4

Recommended Dosing Strategy

For Grade 2 (Moderate) Ascites:

• Start with spironolactone 100 mg/day as monotherapy combined with sodium restriction (2 g or 90 mmol/day) 1
• Titrate upward every 3-5 days if weight loss is inadequate (target 0.5 kg/day without edema, 1 kg/day with edema) 1, 5
• Maximum dose: 400 mg/day 1

For Recurrent or Refractory Ascites:

• Combination therapy from the outset is superior: spironolactone 100 mg + furosemide 40 mg as single morning dose 1, 5
• This 100:40 mg ratio maintains normokalemia and provides faster ascites control with lower hyperkalemia risk 5, 4
• Increase both drugs simultaneously every 3-5 days up to maximum doses (spironolactone 400 mg/day + furosemide 160 mg/day) 1, 5

For Grade 3 (Tense) Ascites:

• Large-volume paracentesis with albumin (8 g per liter removed) is first-line treatment, followed by initiation of spironolactone-based diuretic therapy to prevent reaccumulation 1, 4

Critical Monitoring Requirements

Check these parameters intensively during the first month: 1, 5

• Serum potassium and creatinine at 3 days, 1 week, then monthly for first 3 months 5
• Daily body weight 1, 4
• Serum sodium weekly for first month 5

Suspend or discontinue diuretics if: 1, 4

• Hyperkalemia >6.0 mmol/L 1
• Severe hyponatremia <120-125 mmol/L 1
• Serum creatinine >2.0 mg/dL 1
• Hepatic encephalopathy develops 1

Important Clinical Pitfalls

• NSAIDs convert diuretic-sensitive patients to refractory—they reduce urinary sodium excretion and induce azotemia; avoid completely 1, 3
• Fluid restriction is unnecessary unless serum sodium drops below 120-125 mmol/L 1
• Give as single morning dose to maximize compliance and minimize nocturia 5, 4
• Food increases spironolactone bioavailability by 95%—establish consistent pattern with regard to meals 3

Managing Side Effects

Antiandrogenic effects (gynecomastia, decreased libido) occur commonly but can be managed by switching to amiloride or eplerenone 1, 2

Muscle cramps may respond to: 1

• Baclofen 10 mg/day, increased weekly by 10 mg up to 30 mg/day
• Albumin 20-40 g/week
• Correction of hypokalemia and hypomagnesemia

When to Escalate Care

Consider liver transplantation evaluation in all patients who develop ascites, as this represents advanced liver disease with poor prognosis 1

Refractory ascites (unresponsive to maximum doses or rapidly recurring) occurs in <10% of patients and requires serial therapeutic paracentesis, TIPS consideration, or transplant evaluation 1

Special Populations

In cirrhotic patients, initiate spironolactone in the hospital due to risk of sudden electrolyte shifts precipitating hepatic encephalopathy 3

Start with lowest doses and titrate slowly in cirrhosis, as clearance of spironolactone and metabolites is reduced and half-life is prolonged 3