Definition of Refractory Ascites
Refractory ascites is fluid overload in cirrhotic patients that either fails to respond to sodium restriction (<5 g/day) and maximum-dose diuretic therapy (spironolactone 400 mg/day plus furosemide 160 mg/day) for at least one week, or recurs rapidly (within 4 weeks) after therapeutic paracentesis. 1
Diagnostic Criteria
Refractory ascites is established when patients meet one of two conditions:
Diuretic-Resistant Ascites
- Inadequate response despite intensive treatment with spironolactone 400 mg/day and furosemide 160 mg/day for at least one week 2, 1
- Sodium restriction to less than 5 g/day (ideally 2 g or 90 mmol/day) 1
- Mean weight loss less than 0.8 kg over four days 1
- Urinary sodium excretion less than 78 mmol/day despite maximum diuretics 2
- Urinary sodium output remains less than sodium intake 1
Diuretic-Intractable Ascites
Patients develop clinically significant complications that prevent reaching maximum diuretic doses 2:
- Hepatic encephalopathy developing without other precipitating factors 1
- Renal impairment: serum creatinine ≥2.0 mg/dL or increase >0.3 mg/dL within 48 hours 2, 1
- Severe hyponatremia: serum sodium <120-125 mmol/L or decrease >10 mEq/L to <125 mEq/L 2, 1
- Electrolyte disorders: serum potassium <3 mmol/L or >6 mmol/L despite appropriate measures 2, 1
- Severe muscle cramps preventing effective diuretic dosing 1
Early Recurrence
- Reappearance of grade 2-3 ascites within four weeks of initial mobilization 1
Clinical Significance
Refractory ascites carries a grave prognosis with median survival of approximately 6 months. 1 This represents a critical turning point in cirrhosis progression, occurring in 5-10% of patients with cirrhotic ascites. 2, 3, 4
Important Caveats
Exclude Pseudo-Refractoriness Before Diagnosis
- Check spot urine sodium-to-potassium ratio: ratio >1 suggests dietary non-compliance rather than true refractoriness 1
- Verify medication compliance: confirm patients are actually taking maximum doses for at least one week 1
- Identify offending medications: NSAIDs and prostaglandin inhibitors can convert diuretic-sensitive ascites to refractory ascites and must be discontinued 2, 1
Management Implications Once Diagnosed
- Discontinue diuretics in most cases once refractoriness is established 1
- Diuretics may only be maintained if renal sodium excretion exceeds 30 mmol/day 1
- Immediate referral to liver transplant center is mandatory, as transplantation is the only definitive therapy that improves survival 1, 5, 6
- Large-volume paracentesis with albumin (6-8 g per liter removed) becomes first-line treatment 1