What is the definition of refractory ascites?

Definition of Refractory Ascites

Refractory ascites is defined as fluid overload which 1) fails to respond to a restriction of salt intake and the maximum dose of diuretic treatment (spironolactone at 400 mg/day and furosemide at 160 mg/day) for at least one week, or 2) reappears rapidly after therapeutic paracentesis. 1

Types of Refractory Ascites

Refractory ascites is classified into two distinct forms:

• Diuretic-resistant ascites: Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment 1
• Diuretic-intractable ascites: Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage 1

Diagnostic Criteria for Refractory Ascites

Treatment Requirements

• Intensive diuretic therapy with spironolactone 400 mg/day and furosemide 160 mg/day for at least one week 1
• Salt-restricted diet of less than 5 g/day (sodium 2 g/day, 88 mmol/day) 1

Criteria for Lack of Response

• Mean weight loss of less than 0.8 kg over four days 1
• Urinary sodium output less than the sodium intake 1

Early Ascites Recurrence

• Reappearance of grade 2-3 ascites within four weeks of initial mobilization 1

Diuretic-Induced Complications (for Diuretic-Intractable Ascites)

• Hepatic encephalopathy: Development of encephalopathy in the absence of any other precipitating factor 1
• Renal impairment: >0.3 mg/dL increase of serum creatinine within 48 hours of baseline or 1.5-fold increase within 1 week 1
• Hyponatremia: Decrease of serum sodium by >10 mEq/L to a serum sodium of <125 mEq/L 1
• Electrolyte disorders: Change in serum potassium to <3 mmol/L or >6 mmol/L despite appropriate measures 1
• Muscle cramps: Invalidating muscle cramps that prevent effective diuretic dosing 1

Clinical Significance

• Refractoriness of ascites is associated with a poor prognosis, with a median survival of about six months 1
• Patients with refractory ascites should be immediately referred to a liver transplant center for evaluation 1, 2
• The diagnosis should be made in stable patients without associated complications such as bleeding or infection, after confirming patient compliance to treatment 1

Management Considerations

• Once refractoriness is established, diuretics should generally be discontinued 1, 2
• Diuretics may be maintained only when renal sodium excretion on diuretics exceeds 30 mmol/day 1
• Large-volume paracentesis with albumin administration (6-8 g per liter of ascites drained) is the initial treatment of choice 1, 2
• Transjugular intrahepatic portosystemic shunt (TIPS) may be superior to repeated paracentesis in reducing the need for repeated procedures 2
• Liver transplantation remains the only definitive therapy for refractory ascites 2, 3