Spironolactone for Ascites
Spironolactone is the primary diuretic for cirrhotic ascites, started at 50-100 mg/day and typically combined with furosemide 40 mg in a 100:40 ratio as first-line therapy, with doses increased simultaneously every 3-5 days up to maximum 400 mg/day spironolactone and 160 mg/day furosemide if weight loss remains inadequate. 1
Initial Dosing Strategy
Start spironolactone 50-100 mg/day as a single morning dose, preferably combined with furosemide 40 mg from the outset rather than sequential monotherapy. 1, 2
The 100:40 ratio (spironolactone:furosemide) maintains adequate serum potassium balance and prevents both hyperkalemia and hypokalemia. 1, 2
Combination therapy from the start is superior to spironolactone monotherapy for recurrent ascites, providing faster control with lower hyperkalemia risk. 2, 3
Spironolactone directly antagonizes the secondary hyperaldosteronism that drives sodium and water retention in cirrhosis, making it physiologically superior to loop diuretics alone. 4, 5, 6
Dose Titration Algorithm
Increase both medications simultaneously every 3-5 days if weight loss remains inadequate (<0.5 kg/day without peripheral edema, or <1 kg/day with peripheral edema). 1, 2
Maximum doses are spironolactone 400 mg/day and furosemide 160 mg/day. 1, 2
In the absence of peripheral edema, target weight loss of 0.5 kg/day; with peripheral edema, weight loss can exceed this but should be carefully monitored. 1
Always maintain the 100:40 ratio during dose escalation to preserve potassium balance. 2
Critical Monitoring Requirements
Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months. 2, 4
Monitor daily weight to ensure adequate diuresis without excessive fluid loss. 1
Assess serum sodium weekly for the first month, watching for hyponatremia. 7
Measure 24-hour urinary sodium excretion to verify dietary compliance (target <88 mmol/day) and exclude confounding factors if response is inadequate. 2, 4
Absolute Contraindications
Do not initiate spironolactone when creatinine clearance <30 mL/min, baseline potassium >5.0 mEq/L, anuria, marked hypovolemia, or severe hyponatremia (sodium <120-125 mmol/L). 2, 4
Avoid concomitant NSAIDs or COX-2 inhibitors, which increase hyperkalemia risk and inhibit diuretic response. 2, 5
When to Reduce or Stop Diuretics
Immediately reduce or discontinue spironolactone if any of the following develop: 1, 4
- Hepatic encephalopathy in the absence of other precipitating factors
- Severe hyponatremia (sodium <120-125 mmol/L despite water restriction)
- Acute kidney injury (creatinine increase >0.3 mg/dL within 48 hours or 1.5-fold increase within 1 week)
- Hyperkalemia >5.5 mEq/L
- Severe muscle spasms
Management of Hyperkalemia
When hyperkalemia develops (>5.5 mEq/L), reduce spironolactone dose or switch to every-other-day dosing. 2, 4
Temporarily increase or add furosemide to enhance potassium excretion. 1
If hyperkalemia persists despite these measures, substitute amiloride 10-40 mg/day (1/10 the spironolactone dose). 4
Discontinue or significantly reduce potassium supplements when initiating therapy. 2, 4
High-Risk Populations for Hyperkalemia
Monitor more closely in patients with: 2, 4
- Baseline creatinine >1.6 mg/dL
- Baseline potassium >5.0 mEq/L
- Concomitant ACE inhibitors or ARBs
- Diabetes mellitus
- Elderly patients
- Dehydration
Management of Refractory Ascites
Refractory ascites is defined as failure to respond to maximum diuretic doses (spironolactone 400 mg/day + furosemide 160 mg/day) for at least 1 week on a salt-restricted diet (<5 g/day), with mean weight loss <800 g over 4 days and urinary sodium output less than sodium intake. 1
Before declaring ascites refractory, verify dietary sodium compliance (target 5-6.5 g/day or 87-113 mmol/day) and measure 24-hour urinary sodium excretion. 2, 4
Large-volume paracentesis with albumin replacement (6-8 g per liter of ascites removed) is the treatment of choice for refractory ascites. 1, 2
Reinstitute diuretics 1-2 days post-paracentesis to prevent recurrence. 2, 4
Refer for liver transplantation evaluation, as it is the only treatment associated with improved survival in cirrhotic patients with ascites. 7
Essential Supportive Measures
Restrict dietary sodium to ≤5 g/day (sodium 2 g/day, 88 mmol/day), as diuretics alone are often insufficient. 1, 4
Fluid restriction is not necessary if serum sodium concentration is in the normal range. 1
Supplement protein at 1.2-1.5 g/kg/day to prevent malnutrition. 1
Treat the underlying liver disease, as this is fundamental to managing cirrhotic ascites. 1
Practical Administration Tips
Give both spironolactone and furosemide as a single morning dose to maximize compliance and minimize nocturia. 2, 4
Always use oral spironolactone—never intravenous diuretics—to avoid acute GFR reduction and kidney damage from sudden fluid loss. 2, 4
Food increases spironolactone bioavailability by approximately 95%; patients should establish a routine pattern for taking spironolactone with regard to meals. 5
In patients with cirrhosis, initiate spironolactone in the hospital due to risk of sudden alterations in fluid and electrolyte balance that may precipitate hepatic encephalopathy and coma. 5
Start with the lowest initial dose and titrate slowly in cirrhotic patients, as clearance of spironolactone and its metabolites is reduced. 5
Common Pitfalls to Avoid
Do not use loop diuretics alone as monotherapy for cirrhotic ascites—they are physiologically inferior to aldosterone antagonists and cause severe hypokalemia requiring massive potassium supplementation. 2, 8, 6
Do not continue escalating diuretics beyond maximum doses without first verifying dietary sodium compliance and considering large-volume paracentesis. 2, 4
Do not abruptly discontinue diuretics once ascites is controlled; use the lowest effective dose to prevent complications while maintaining control. 7, 4
Be aware that spironolactone has antiandrogenic effects (gynecomastia, mastalgia, sexual dysfunction); if these become intolerable, substitute amiloride 10-40 mg/day. 4