What is spironolactone given for in portal hypertension?

Role of Spironolactone in Portal Hypertension

Spironolactone is primarily used in portal hypertension to manage ascites through its aldosterone-antagonist action, which increases natriuresis and reduces fluid retention, and secondarily to reduce portal pressure directly. 1

Mechanism of Action in Portal Hypertension

Spironolactone works through several mechanisms in portal hypertension:

1. Primary mechanism: Acts as an aldosterone antagonist in the distal tubules to increase natriuresis and conserve potassium, counteracting the secondary aldosteronism that contributes to sodium retention in cirrhosis 1

2. Secondary effects:

   • Reduces plasma volume, which can decrease portal venous pressure 2
   • May have direct vasoactive effects on the splanchnic circulation independent of its diuretic action 3
   • Helps manage the edema associated with hepatic cirrhosis, especially when edema is not responsive to fluid and sodium restriction 4

Dosing and Administration

• Initial dose: 100 mg daily, which may need to be progressively increased up to 400 mg to achieve adequate natriuresis 1
• Onset of action: There is typically a lag of 3-5 days between starting spironolactone and the onset of natriuretic effect 1
• Stepped approach: Treatment typically starts with modest dietary salt restriction plus spironolactone, with furosemide added only when spironolactone alone at maximum doses proves ineffective 1

Evidence for Portal Pressure Reduction

Research demonstrates that spironolactone can directly reduce portal pressure:

• In patients with cirrhosis without ascites, a 4-week regimen of spironolactone (100 mg/day) significantly reduced hepatic venous pressure gradient (HVPG) from 16.5 to 12.9 mmHg 2
• In patients with propranolol-resistant portal hypertension, spironolactone alone or in combination with propranolol achieved adequate reduction in HVPG 5

Combination Therapy

• With beta-blockers: While the combination of spironolactone with non-selective beta-blockers has been studied for prevention of first variceal hemorrhage, current evidence does not support this combination over beta-blockers alone 1, 6
• With loop diuretics: Spironolactone is often combined with furosemide when higher doses of spironolactone alone are ineffective, as simultaneous administration increases the natriuretic effect 1

Adverse Effects and Monitoring

Common side effects include:

• Endocrine effects: Gynecomastia, decreased libido, and impotence in men; menstrual irregularities in women 1
• Electrolyte disturbances: Hyperkalemia is a significant complication that can limit spironolactone use 1
• Renal effects: Risk of renal impairment, especially with aggressive diuresis 1

Clinical Pitfalls to Avoid

1. Overly aggressive diuresis: Can lead to intravascular volume depletion (25%), renal impairment (14-20%), hepatic encephalopathy (26%), and hyponatremia (28%) 1

2. Inadequate monitoring: Serum electrolytes and renal function should be regularly monitored, especially when initiating therapy

3. Inappropriate salt restriction: Extremely salt-restricted diets (<5g salt/day) are difficult to comply with and don't improve ascites control. A moderately salt-restricted diet (5-6.5g salt/day) is recommended 1

4. Ignoring hyperkalemia risk: Particularly important when combining with ACE inhibitors or ARBs 7

In summary, spironolactone plays a dual role in portal hypertension: managing ascites through its diuretic effect and potentially reducing portal pressure directly through effects on plasma volume and splanchnic circulation.