What is the recommended diuretic regimen for a patient with liver cirrhosis?

Diuretic Regimen for Liver Cirrhosis with Ascites

Start with spironolactone 50-100 mg/day as the primary diuretic, and add furosemide 20-40 mg/day simultaneously in a 100:40 ratio to maintain normokalemia, titrating both upward together every 3-5 days to maximum doses of 400 mg/day and 160 mg/day respectively if response is inadequate. 1, 2

Initial Diuretic Strategy

Spironolactone is the cornerstone drug because it directly antagonizes aldosterone, which is the primary driver of sodium retention in cirrhotic ascites. 1 Loop diuretics like furosemide alone are insufficient as monotherapy because hyperaldosteronism causes the distal tubule to reabsorb any sodium that escapes proximal reabsorption. 3, 4

Starting Doses and Titration

• Begin with spironolactone 50-100 mg once daily in the morning, which can be increased to a maximum of 400 mg/day. 1
• Add furosemide 20-40 mg once daily simultaneously, maintaining the 100:40 mg ratio to prevent both hyperkalemia and hypokalemia, with maximum doses up to 160 mg/day. 1, 2
• Increase both medications together every 3-5 days if weight loss is inadequate (less than 0.5 kg/day without peripheral edema, or insufficient mobilization with edema). 2, 5
• Single morning dosing maximizes compliance and mimics physiologic diurnal patterns. 2, 5

The combination approach is superior to sequential monotherapy because it provides faster ascites control while maintaining electrolyte balance. 5

Essential Adjunctive Measures

• Restrict dietary sodium to ≤5 g/day (88 mmol/day or 2 g sodium), which is critical for diuretic efficacy. 1
• Protein supplementation of 1.2-1.5 g/kg/day should be maintained to prevent malnutrition. 1
• Fluid restriction is unnecessary unless serum sodium falls below 125 mmol/L. 1, 2

Critical Monitoring Requirements

Monitor the following parameters closely to prevent life-threatening complications:

• Daily body weight with target loss of 0.5 kg/day without peripheral edema, or more aggressive loss if edema is present. 1, 2
• Serum electrolytes (sodium and potassium) at baseline, 3 days, 1 week, then monthly for 3 months. 2, 5
• Serum creatinine to detect acute kidney injury (defined as >0.3 mg/dL increase within 48 hours or 1.5-fold increase within 1 week). 1, 6
• Vital signs to detect hypotension. 2, 6

Dose Adjustments for Electrolyte Abnormalities

When hypokalemia (K+ <3 mmol/L) develops:

• Reduce or stop furosemide immediately. 1, 5

When hyperkalemia (K+ >6 mmol/L) develops:

• Reduce or stop spironolactone immediately. 1, 5

When severe hyponatremia (Na+ <125 mmol/L or drop >10 mEq/L) occurs:

• Reduce or discontinue both diuretics and initiate fluid restriction. 1, 2

When to Stop or Reduce Diuretics

Immediately reduce or discontinue diuretics if any of the following develop:

• Acute kidney injury (creatinine increase as defined above). 1, 7
• Overt hepatic encephalopathy in the absence of other precipitating factors. 1, 6
• Severe muscle cramps that impair function. 1, 2
• Severe hyponatremia (Na+ <120-125 mmol/L). 1, 5

The FDA label specifically warns that spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate hepatic encephalopathy and coma in cirrhotic patients, and therapy should be initiated in the hospital for these patients. 7

Special Consideration: Tense Ascites

If the patient presents with tense ascites causing respiratory compromise or severe discomfort:

• Perform large-volume paracentesis first (removing >5 L), which is faster and more effective than diuretics alone. 1, 2
• Administer 6-8 g of albumin per liter of ascites removed to prevent post-paracentesis circulatory dysfunction. 1
• Follow with maintenance diuretic therapy using the regimen above to prevent reaccumulation. 2, 6

Large-volume paracentesis with albumin reduces hospital stay and has lower rates of hyponatremia, acute kidney injury, and hepatic encephalopathy compared to diuretics alone for tense ascites. 1, 8

Defining Refractory Ascites

Ascites is considered refractory when:

• Diuretic-resistant: No response after at least 1 week of maximum doses (spironolactone 400 mg/day + furosemide 160 mg/day) with sodium restriction <5 g/day, defined as weight loss <800 g over 4 days and urinary sodium less than intake. 1
• Diuretic-intractable: Development of complications (encephalopathy, renal impairment, severe hyponatremia, or severe electrolyte disturbances) that prevent effective diuretic dosing. 1

When refractory ascites develops, consider discontinuing diuretics (especially if urinary sodium <30 mmol/day) and transition to serial large-volume paracentesis. 1

Critical Safety Warning for Cirrhotic Patients

Never use intravenous diuretics in cirrhotic ascites as they cause rapid fluid shifts that can precipitate acute kidney injury. 6 The furosemide FDA label specifically warns that therapy is best initiated in the hospital for patients with hepatic cirrhosis and ascites, and sudden alterations may precipitate hepatic coma. 9