What is the management approach for patients with refractory ascites?

Management of Refractory Ascites

For patients with refractory ascites, therapeutic paracentesis is the first-line treatment, followed by consideration of transjugular intrahepatic portasystemic shunt (TIPS) for suitable candidates, with liver transplantation being the ultimate definitive therapy. 1

Definition of Refractory Ascites

Refractory ascites is defined as:

• Ascites that is unresponsive to sodium-restricted diet and high-dose diuretic treatment (400 mg/day spironolactone and 160 mg/day furosemide) OR
• Ascites that recurs rapidly after therapeutic paracentesis OR
• Development of diuretic-related complications that prevent effective diuretic dosing 1

Diagnostic Approach

Before confirming refractory ascites:

• Perform diagnostic paracentesis to rule out spontaneous bacterial peritonitis (SBP)
• Ensure proper medication compliance
• Exclude use of medications that impair sodium excretion (especially NSAIDs)
• Verify adequate sodium restriction by checking urinary sodium excretion 1

Management Algorithm

1. First-Line Treatment: Large Volume Paracentesis (LVP)

• Perform total paracentesis in a single session
• Administer volume expansion once paracentesis is complete:
  • For <5 liters: Use synthetic plasma expander (150-200 ml of gelofusine or haemaccel)
  • For >5 liters: Use albumin at 8g/L of ascites removed (approximately 100 ml of 20% albumin per 3L ascites) 1
• Continue sodium restriction (<90 mmol/day or 2000 mg/day)
• Reintroduce diuretics 1-2 days after paracentesis if tolerated 1

2. Second-Line Treatment: TIPS

Consider TIPS for patients who:

• Require frequent therapeutic paracentesis
• Have preserved liver function
• Do not have severe hepatic encephalopathy
• Do not have severe cardiac dysfunction 1, 2

3. Liver Transplantation

• All patients with refractory ascites should be evaluated for liver transplantation
• Development of ascites is an important landmark in cirrhosis progression and indicates poor prognosis 1

Pharmacological Management

Diuretic Therapy

Even in refractory ascites, attempt to maintain diuretic therapy if tolerated:

• Maximum doses: spironolactone 400 mg/day and furosemide 160 mg/day 1, 3
• Monitor for complications:
  • Hyponatremia (serum sodium <120-125 mmol/L)
  • Hyperkalemia (>6.0 mmol/L)
  • Renal impairment (creatinine >2.0 mg/dL)
  • Hepatic encephalopathy 1

Management of Electrolyte Abnormalities

• Serum sodium 126-130 mmol/L with normal creatinine: Continue diuretics with close monitoring
• Serum sodium 121-125 mmol/L with normal creatinine: Consider stopping diuretics or reduce dose
• Serum sodium 121-125 mmol/L with elevated creatinine: Stop diuretics and give volume expansion
• Serum sodium <120 mmol/L: Stop diuretics and consider volume expansion with colloid or saline
• Avoid increasing serum sodium by >12 mmol/L per 24 hours 1

Special Considerations

Spontaneous Bacterial Peritonitis (SBP)

• All patients with SBP should be considered for liver transplantation
• Patients recovering from SBP should receive prophylaxis with norfloxacin 400 mg/day or ciprofloxacin 500 mg/day 1

Pitfalls to Avoid

1. Excessive diuresis: Can lead to intravascular volume depletion, renal impairment, and hepatic encephalopathy
2. NSAIDs: Can convert diuretic-sensitive patients to refractory and should be strictly avoided 1
3. Inadequate albumin replacement: After large volume paracentesis can lead to post-paracentesis circulatory dysfunction 1
4. Delay in transplant evaluation: Given poor prognosis, early referral is essential 1, 2
5. Inappropriate TIPS placement: In patients with severe hepatic encephalopathy or cardiac dysfunction 1

Prognosis

Refractory ascites indicates advanced liver disease with poor prognosis. The development of ascites is associated with 50% 2-year survival, which worsens significantly when ascites becomes refractory 4. This underscores the importance of early transplant evaluation.