What are the definitions of resistant and refractory ascites?

Definition of Resistant and Refractory Ascites

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

Types of Refractory Ascites

There are two main types of refractory ascites:

• 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 2

• 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 2

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 2, 1
• Salt-restricted diet of less than 5 g/day (90 mmol/day) 2, 1

Lack of Response Criteria

• Mean weight loss of less than 0.8 kg over four days 2, 1
• Urinary sodium output less than the sodium intake 2, 1

Early Recurrence Criteria

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

Diuretic-Induced Complications That Define Intractable Ascites

• Hepatic encephalopathy: Development of encephalopathy in the absence of any other precipitating factor 2, 1

• Renal impairment:

  • 0.3 mg/dL increase of serum creatinine within 48 hours of baseline or 1.5-fold increase within 1 week 2

  • Increase of serum creatinine by >100% to a value >2 mg/dl (177 μmol/L) in patients with ascites responding to treatment 2

• Hyponatremia: Decrease of serum sodium by >10 mmol/L to a serum sodium of <125 mmol/L 2, 1

• Electrolyte disorders: Change in serum potassium to <3 mmol/L or >6 mmol/L despite appropriate measures 2, 1

• Muscle cramps: Invalidating muscle cramps that prevent effective diuretic dosing 2, 1

Clinical Significance

• Refractory ascites is associated with poor prognosis, with a median survival of approximately 6 months 1, 3
• Once refractoriness is established, diuretics should generally be discontinued 1
• Diuretics may be maintained only when renal sodium excretion on diuretics exceeds 30 mmol/day 2, 1

Management Options for Refractory Ascites

• Large-volume paracentesis with albumin administration (6-8 g of albumin per liter of ascites drained) is the initial treatment of choice 2, 1
• Transjugular intrahepatic portosystemic shunt (TIPS) should be considered in patients who repeatedly fail large-volume paracentesis and have relatively preserved liver function 4
• Liver transplantation is the only definitive therapy for refractory ascites and should be considered early in the treatment plan 1, 3, 4