Refractory Ascites

Background

• Ascites is refractory when optimal medical management is ineffective, intolerable due to side effects, or is successful but ascites recurs in less than one month.
• Refractory ascites may be classified by etiology (portal hypertensive etiology versus not) and responsiveness to therapy (diuretic failure versus intolerance).
• Optimal medical management is usually defined as at least one week of adherence to a diet of < 5.2 grams of salt per day with at least one week of furosemide at 160 mg/day plus spironolactone at 400 mg/day.
• Ineffective response is defined as < 0.8 kg weight loss over 4 days while measured sodium output in urine is less than input or re-accumulation of fluid and weight within 4 weeks despite continued therapy.
• Intolerance is defined as doubling of creatinine and increase > 2 mg/dL, encephalopathy, serum sodium dropping by > 10 mmol/L to < 125 mmol/L or a change in serum potassium to < 3 or > 6 mmol/L despite appropriate countermeasures.
• Refractory ascites develops in up to 10% of patients with cirrhosis and ascites within 1 year of recognition of onset of this complication.
• Often, the only approach is that of sequential paracenteses with all of the associated risks and complications.

Evaluation

• Assess for adherence and response to salt restriction and diuretic therapy as well as secondary etiologies (Strong Recommendation).
• Evaluate for transient treatment resistance due to altered renal function or secondary etiology such as infection.
• Recognize that patients with a serum-ascites albumin gradient (SAAG) of < 1.1 g/dL are less likely to respond to diuretics.

Management

• Discontinue angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) and NSAIDs if not already done (Strong Recommendation).
• Weigh risks and benefits of nonselective beta-blockers (NSBBs) carefully in patients with refractory ascites. Systemic hypotension may complicate NSBB usage, but do not consider refractory ascites an absolute contraindication.
  • Avoid high doses (> 160 mg/day) of propranolol or (> 80 mg/day) of nadolol (Strong Recommendation).
  • Discontinue NSBB's in patients with systemic hypotension (Strong Recommendation), and not initiating this class of drugs.
  • Monitor serum creatinine, sodium and blood pressure closely.
  • For patients with circulatory dysfunction (serum sodium < 130 meq/L, hepatorenal syndrome, acute kidney injury, or systolic BP < 90 mmHg).
    • Consider decreasing NSBB dose and/or temporarily suspending NSBB treatment
    • Consider cautious reintroduction of NSBB treatment if circulation improves and precipitating events (peritonitis or hemorrhage) resolves, but retitrate dose starting at lowest dose
• Perform large-volume paracentesis (LVP) performed along with administration of albumin IV to prevent paracentesis-induced circulatory dysfunction (PICD) for refractory ascites (Strong Recommendation).
• Evaluate patients with refractory ascites for liver transplantation (Strong Recommendation).
• Discontinue diuretics if sodium excretion ≤ 30 mmol/day due to lack of effectiveness or for complications such as symptomatic hyponatremia (Strong Recommendation).
• Evaluate patients for transjugular intrahepatic portosystemic shunt (TIPS) procedure as a substitute for repeated LVP, particularly in those with loculated ascites (Strong Recommendation).
• Use small-diameter polytetrafluoroethylene (PTFE)-covered stents for TIPS, which may enhance shunt functionality long term and improve survival (Strong Recommendation).
• Follow-up frequently for monitoring and management.