Is spironolactone (aldosterone antagonist) preferred over intravenous (IV) furosemide (loop diuretic) in patients with liver cirrhosis?

Spironolactone is Superior to IV Furosemide for Patients with Liver Cirrhosis and Ascites

Spironolactone should be used as the primary diuretic for managing ascites in patients with liver cirrhosis rather than IV furosemide. 1

Pathophysiological Rationale

Liver cirrhosis leads to secondary hyperaldosteronism, which is a key mechanism in ascites formation:

• Spironolactone directly antagonizes aldosterone, addressing the underlying pathophysiology
• Aldosterone antagonists inhibit sodium reabsorption in the distal tubule, which is the primary site of sodium retention in cirrhosis
• Spironolactone has been shown to be more effective than furosemide in cirrhotic patients with ascites 2

Evidence-Based Recommendations

First-Line Therapy

• Spironolactone is recommended as the primary diuretic for cirrhotic ascites by multiple guidelines 1
• Starting dose: 50-100 mg/day, can be increased up to 400 mg/day 1
• Spironolactone monotherapy has a response rate of up to 95% in non-azotemic cirrhotic patients 2, 3

Role of Furosemide

• Loop diuretics like furosemide should not be used as monotherapy 1
• Furosemide should be added only when:
  • There is insufficient response to spironolactone monotherapy
  • Hyperkalemia develops from spironolactone
  • Faster diuresis is needed in hospitalized patients 1

Combination Therapy vs. Monotherapy

When combination therapy is needed:

• Recommended ratio: 100 mg spironolactone to 40 mg furosemide to maintain normokalemia 1
• Maximum doses: spironolactone 400 mg/day and furosemide 160 mg/day 1

A randomized study showed that 3:

• Spironolactone monotherapy was as effective as combination therapy (94% vs 98% response)
• Monotherapy required fewer dose adjustments (34% vs 68%)
• Complication rates were similar between both approaches

Safety Considerations

Spironolactone

• Slower onset of action (3-4 days to reach stable concentration) 1
• Main side effects: hyperkalemia, gynecomastia, mastalgia, sexual dysfunction 1
• Better suited for outpatient management due to fewer dose adjustments 3

IV Furosemide

• Rapid onset but can cause:
  • Acute reduction in renal perfusion
  • Azotemia
  • Hypokalemia
  • Worsening of neurohormonal activation 1

Special Situations

Tense Ascites

• Large volume paracentesis (LVP) with albumin (8 g/L of ascites removed) is preferred for initial management 1
• After LVP, spironolactone-based diuretic therapy should be initiated to prevent reaccumulation 4

Refractory Ascites

• Defined as ascites that fails to respond to sodium restriction and maximum diuretic doses (spironolactone 400 mg/day and furosemide 160 mg/day) 1
• Serial LVP with albumin is the treatment of choice 1

Monitoring Parameters

• Weight loss should not exceed 0.5 kg/day without peripheral edema
• Monitor serum potassium, sodium, and creatinine
• Spot urine Na/K ratio >1 indicates adequate sodium excretion 1, 5
• Diuretics should be reduced or stopped if:
  • Hepatic encephalopathy develops
  • Serum sodium <125 mmol/L
  • Acute kidney injury occurs
  • Severe hypokalemia or hyperkalemia develops 1

In conclusion, spironolactone is the cornerstone of diuretic therapy for cirrhotic ascites due to its superior efficacy in addressing the underlying pathophysiology. IV furosemide should be reserved for specific situations requiring rapid diuresis or as an adjunct to spironolactone when needed.