What are the guidelines for managing ascites?

Guidelines on Management of Ascites in Cirrhosis: AASLD, EASL, and INASL Comparison

The management of ascites in cirrhosis should begin with dietary sodium restriction (5-6.5g salt/day), followed by diuretic therapy starting with spironolactone 100mg/day (increasing to 400mg/day as needed), with addition of furosemide 40mg/day (up to 160mg/day) for suboptimal response or recurrent ascites. 1, 2

Pathophysiology and Initial Assessment

• Ascites occurs in >50% of patients with cirrhosis and marks hepatic decompensation

• Pathophysiological mechanisms include:

  • Portal hypertension
  • Splanchnic vasodilation
  • Activation of renin-angiotensin-aldosterone system
  • Sodium and water retention

• Initial assessment should include:

  • SAAG (serum-ascites albumin gradient) measurement
  • Ascitic fluid neutrophil count and culture
  • Consider ultrasound guidance for paracentesis 2

Comparative Table of Management Options

Treatment	Dosage	Efficacy	Complications	Level of Evidence
Medical Management
Spironolactone monotherapy	100-400 mg/day	94% response rate	Hyperkalemia, gynecomastia, cramps	High (Grade A) [1,2,3,4]
Combination therapy (Spironolactone + Furosemide)	Spironolactone 100-400 mg/day + Furosemide 40-160 mg/day (ratio 100:40)	98% response rate	Higher rate of dose adjustments (68% vs 34%), electrolyte imbalances	High (Grade A) [1,2,4]
Interventional Management
Large Volume Paracentesis (LVP)	Remove ascites with albumin infusion (8g/L of ascites removed)	Rapid relief of symptoms	Circulatory dysfunction, hyponatremia	High (Grade A) [2]
Transjugular Intrahepatic Portosystemic Shunt (TIPS)	N/A	Effective for refractory ascites	Hepatic encephalopathy, liver failure	Moderate (Grade B) [2,5,6]
Alfapump system	N/A	Promising for refractory ascites	Safety concerns, limited data	Low (Grade C) [5]
Adjunctive Therapies
Midodrine	Case-by-case basis	Limited data	Hypertension	Low (Grade C) [2,5]
Liver transplantation	Definitive treatment	Curative	Surgical complications, rejection	High (Grade A) [2,5,7]

Stepwise Management Algorithm for Ascites

Step 1: First Presentation of Moderate Ascites

1. Dietary sodium restriction: 5-6.5g salt/day (90 mmol/day) 1, 2
2. Protein supplementation: 1.2-1.5 g/kg/day 2
3. Diuretic therapy:
   • Start with spironolactone 100 mg/day
   • Titrate up to maximum 400 mg/day as needed 1, 2, 3
4. Monitoring:
   • Target weight loss: 0.5 kg/day without peripheral edema
   • No limit to weight loss with peripheral edema (but use caution)
   • Monitor serum electrolytes, creatinine within 1 week of initiation/titration 2, 3
   • Consider spot urine Na/K ratio to assess natriuresis 1, 2

Step 2: Suboptimal Response to Initial Therapy

1. Add furosemide: 40 mg/day, increasing to maximum 160 mg/day 1, 2
2. Maintain spironolactone:furosemide ratio of 100:40 mg 2
3. Reassess salt intake and adherence to dietary restrictions 1

Step 3: Management of Complications

1. Temporarily discontinue diuretics if:

   • Serum sodium <125 mmol/L
   • Worsening hypokalemia or hyperkalemia
   • Rising serum creatinine
   • Hepatic encephalopathy
   • Severe muscle cramps 1, 2, 3, 8

2. Hyponatremia management:

   • Serum Na 126-135 mmol/L: Continue diuretics with monitoring
   • Serum Na 121-125 mmol/L with normal creatinine: Consider reducing/stopping diuretics
   • Serum Na 121-125 mmol/L with elevated creatinine: Stop diuretics, volume expansion
   • Serum Na <120 mmol/L: Stop diuretics, consider volume expansion
   • Fluid restriction (1-1.5 L/day) only for severe hyponatremia (<125 mmol/L) 1, 2

Step 4: Recurrent Ascites

1. Combination therapy: Start with spironolactone 100 mg/day + furosemide 40 mg/day
2. Titrate doses up to maximum (spironolactone 400 mg/day, furosemide 160 mg/day) 1, 2

Step 5: Refractory Ascites

1. Large Volume Paracentesis (LVP):

   • For paracentesis >5L: Infuse albumin (8 g/L of ascites removed)
   • Consider albumin even for <5L in acute-on-chronic liver failure 2

2. Consider TIPS for truly refractory ascites, with caution in:

   • Age >70 years
   • Serum bilirubin >50 μmol/L
   • Platelet count <75×10^9/L
   • MELD score ≥18
   • Current hepatic encephalopathy
   • Active infection
   • Hepatorenal syndrome 2, 6

3. Consider midodrine on case-by-case basis (limited evidence) 2, 5

4. Evaluate for liver transplantation as definitive treatment 2, 5, 7

Special Considerations

• Spontaneous bacterial peritonitis (SBP): Infuse albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3 2
• Gastrointestinal bleeding with ascites: Consider prophylactic antibiotics 2
• Avoid: NSAIDs, ACE inhibitors, angiotensin receptor blockers 2, 3, 8

Pitfalls and Caveats

1. Overly aggressive diuresis can lead to:

   • Hypovolemia
   • Hepatorenal syndrome
   • Hepatic encephalopathy
   • Electrolyte imbalances 3, 8

2. Hyperkalemia risk is increased with:

   • Impaired renal function
   • Concomitant potassium supplements
   • ACE inhibitors/ARBs 3

3. Spironolactone-related gynecomastia occurs in approximately 9% of male patients and is dose-dependent 3

4. Furosemide ototoxicity risk increases with:

   • Rapid injection
   • Severe renal impairment
   • Higher than recommended doses
   • Hypoproteinemia
   • Concomitant ototoxic drugs 8

5. Refractory ascites (occurs in ~10% of patients) has poor prognosis and should prompt evaluation for liver transplantation 5, 6