Can spironolactone (Aldactone) be used for portal‑hypertension‑related ascites in patients with liver dysfunction, and what initial dose and monitoring are recommended?

Spironolactone (Aldactone) in Liver Dysfunction

Spironolactone is the drug of choice for treating ascites in patients with liver dysfunction and should be initiated at 100 mg daily, with or without furosemide 40 mg daily depending on ascites severity, while monitoring electrolytes at day 3, week 1, and monthly thereafter. 1, 2

Initial Dosing Strategy

First-Presentation Moderate Ascites

• Start spironolactone monotherapy at 100 mg once daily in the morning for patients presenting with their first episode of moderate ascites 1, 3
• Add furosemide only after spironolactone reaches 400 mg/day without adequate response 3

Recurrent or Severe Ascites

• Initiate combination therapy immediately with spironolactone 100 mg plus furosemide 40 mg once daily (maintaining a 100:40 ratio) for patients with recurrent or severe ascites, or when hospitalized and faster diuresis is needed 1, 2
• This combination approach provides faster ascites resolution and lower treatment failure rates compared to sequential monotherapy 3

Dose Escalation Protocol

• Increase both medications every 3–5 days while maintaining the 100:40 ratio if weight loss is inadequate 1, 2
• Maximum doses: spironolactone 400 mg/day and furosemide 160 mg/day 1, 2

Current Dose	Next Step	Maximum
100/40 mg	150/60 mg	400/160 mg
150/60 mg	200/80 mg
200/80 mg	300/120 mg
300/120 mg	400/160 mg

2

Administration Guidelines

• Give as a single morning oral dose to maximize adherence and minimize nocturia 2
• Avoid intravenous furosemide as it can cause acute falls in glomerular filtration rate in cirrhotic patients 2, 4

Monitoring Schedule

Timing

• Check electrolytes and renal function at day 3, week 1, then monthly for 3 months 2, 3
• Monitor serum sodium weekly during the first month 2
• Assess daily body weight 2

Target Weight Loss

• 0.5 kg/day when peripheral edema is absent 2, 3
• Up to 1 kg/day when peripheral edema is present 2, 3

Absolute Contraindications

Stop or do not initiate spironolactone if any of the following are present: 2, 3

• Serum creatinine >2.5 mg/dL 2
• Serum sodium <120–125 mmol/L 2, 5
• Baseline serum potassium >5.0 mEq/L 2, 3
• Overt hepatic encephalopathy without another precipitating factor 2
• Acute kidney injury (creatinine rise >0.3 mg/dL within 48 hours) 2
• Concurrent NSAID or COX-2 inhibitor use 2, 3

Electrolyte Management

Hyperkalemia (K+ >5.5 mmol/L)

• Immediately stop spironolactone 2, 5
• Continue furosemide alone temporarily 2, 3

Hypokalemia (K+ <3.0 mmol/L)

• Reduce or temporarily hold furosemide 2
• Continue spironolactone 2

Severe Hyponatremia (Na <120–125 mmol/L)

• Stop both diuretics immediately (absolute contraindication) 2, 5
• Consider fluid restriction to 1–1.5 L/day only if patient is clinically hypervolemic 1
• Expand plasma volume with normal saline if hypovolemic 1

Dietary Recommendations

• Sodium restriction: limit to 2 g/day (88 mmol, equivalent to 5–6.5 g salt) with no added salt and avoidance of precooked meals 1, 2, 6
• Protein intake: 1.2–1.5 g/kg/day to prevent malnutrition 2, 3
• Fluid restriction: not required when serum sodium is within normal range 2, 3

Special Considerations in Hepatic Impairment

• Initiate spironolactone in the hospital for patients with hepatic disease, cirrhosis, and ascites due to risk of sudden electrolyte alterations that may precipitate hepatic encephalopathy and coma 4
• Start with the lowest initial dose and titrate slowly as clearance of spironolactone and its metabolites is reduced in cirrhosis 4
• Spironolactone is the most effective single agent for ascites in cirrhosis, achieving better natriuresis than loop diuretics alone 1

Refractory Ascites

Definition

• Ascites persisting despite maximum tolerated doses (spironolactone 400 mg + furosemide 160 mg daily for ≥1 week) with sodium restriction <5 g/day 2, 5, 3
• OR development of complications (hyperkalemia, hyponatremia, renal dysfunction) preventing effective diuretic dosing 5

Management

• Perform large-volume paracentesis with albumin replacement (8 g albumin per liter of ascites removed) 1, 2, 5
• Restart diuretics 1–2 days after paracentesis to prevent rapid reaccumulation 2, 3
• Refer promptly for liver transplantation evaluation irrespective of MELD score 2

Common Pitfalls

• Over-diuresis leads to intravascular volume depletion (25%), renal impairment, hepatic encephalopathy (26%), and hyponatremia (28%) 1
• Spironolactone has a lag of 3–5 days between treatment initiation and onset of natriuretic effect; avoid premature dose escalation 1
• Antiandrogenic side effects (gynaecomastia, decreased libido, impotence) occur frequently but can be managed with tamoxifen 20 mg twice daily if needed 1
• Approximately 10% of patients develop refractory ascites despite optimal medical therapy 1