Is spironolactone (aldosterone antagonist) alone sufficient for treating grade 2 ascites?

Treatment of Grade 2 Ascites in Cirrhosis

Spironolactone alone is the recommended first-line treatment for patients with the first episode of grade 2 (moderate) ascites in cirrhosis, starting at 100 mg/day and increasing stepwise every 7 days (in 100 mg steps) to a maximum of 400 mg/day if there is no response. 1

Initial Treatment Algorithm

1. First episode of grade 2 ascites:

   • Start with spironolactone monotherapy at 100 mg/day
   • Increase dose in 100 mg increments every 7 days if needed
   • Maximum dose: 400 mg/day
   • Monitor for response (defined as reduction of body weight of at least 2 kg/week)

2. If inadequate response to spironolactone alone:

   • Add furosemide starting at 40 mg/day
   • Increase furosemide in 40 mg increments as needed
   • Maximum furosemide dose: 160 mg/day

3. If hyperkalemia develops on spironolactone:

   • Add furosemide to correct hyperkalemia
   • Consider dose reduction of spironolactone

Evidence Strength and Rationale

The 2010 EASL guidelines provide clear Level A1 evidence supporting spironolactone monotherapy for first episodes of grade 2 ascites 1. This recommendation is further supported by the 2018 EASL update, which clarifies that patients with ascites at first appearance can be confidently treated with anti-mineralocorticoids alone, as they will likely develop a satisfactory response with few side effects 1.

A randomized controlled trial demonstrated that spironolactone alone was as effective as combination therapy with furosemide (94% vs 98% response rate) for moderate ascites, but required fewer dose adjustments, making it more suitable for outpatient management 2.

Monitoring Requirements

During diuretic therapy, particularly in the first month, patients should undergo:

• Frequent clinical assessment
• Regular monitoring of serum electrolytes (sodium, potassium)
• Renal function tests
• Body weight measurement (target weight loss: 0.5 kg/day without edema, 1 kg/day with edema) 1

Complications to Watch For

1. Hyperkalemia: Most common complication with spironolactone monotherapy
2. Gynecomastia: May occur with prolonged spironolactone use (consider amiloride 10-40 mg/day as alternative if severe) 1
3. Hyponatremia: Discontinue diuretics if serum sodium <120-125 mmol/L 1
4. Renal failure: Stop diuretics if progressive renal dysfunction occurs
5. Hepatic encephalopathy: Diuretics may precipitate or worsen encephalopathy

Special Considerations

• For recurrent ascites (not first episode), combination therapy with spironolactone plus furosemide from the beginning is preferred 1
• Patients with long-standing, recurrent ascites should receive combination therapy from the start, as it shortens time to achieve natriuresis and lowers hyperkalemia incidence 1
• Single morning dosing maximizes compliance 1
• Dietary sodium restriction (≤2 g or 90 mmol/day) should be implemented alongside diuretic therapy 1, 3

Clinical Pitfalls to Avoid

1. Overly aggressive diuresis: Can lead to intravascular volume depletion, renal failure, and hepatic encephalopathy
2. Inadequate monitoring: Electrolyte disturbances can develop rapidly, especially during the first weeks of treatment
3. Using loop diuretics alone: Monotherapy with furosemide is not recommended as it is less effective and requires massive potassium supplementation 4
4. Continuing diuretics despite complications: Promptly discontinue diuretics if severe hyponatremia, progressive renal failure, or worsening hepatic encephalopathy develops

Following this evidence-based approach will optimize outcomes while minimizing complications in patients with grade 2 ascites due to cirrhosis.