What is the role of albumin with diuretics in cirrhosis?

Role of Albumin with Diuretics in Cirrhosis

Albumin should not be used routinely with diuretics in patients with cirrhosis and uncomplicated ascites as it does not improve control of ascites or enhance the diuretic effect of furosemide. 1, 2

Evidence on Albumin with Diuretics in Cirrhosis

The use of albumin with diuretics for managing ascites in cirrhosis remains controversial with conflicting evidence:

• Early studies (1962) with 16 patients showed no improvement in control of ascites with albumin 1
• A crossover randomized study demonstrated that albumin failed to enhance the diuretic effect of furosemide 1, 3
• However, one unblinded RCT with 126 patients not responsive to salt restriction alone showed faster resolution of ascites and lower recurrence with albumin, though without survival benefit and not cost-effective 1

Indications for Albumin in Cirrhosis

While albumin is not recommended with diuretics for uncomplicated ascites, it has established benefits in specific scenarios:

1. Large volume paracentesis (>5L): Recommended at 8g per liter of ascites removed to prevent post-paracentesis circulatory dysfunction 2

2. Spontaneous bacterial peritonitis (SBP): Recommended with antibiotics (1.5g/kg on day 1 and 1g/kg on day 3) to reduce incidence of hepatorenal syndrome and mortality, particularly in patients with:

   • Serum bilirubin >4 mg/dL
   • Creatinine >1.0 mg/dL 1, 2

3. Acute kidney injury (AKI): IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI 1, 2

   • Recommended dose: 1g/kg daily for 2 consecutive days (maximum 100g/day)
   • Lack of response to albumin is a diagnostic criterion for hepatorenal syndrome 1

4. Hepatorenal syndrome: Used in conjunction with vasoconstrictors like terlipressin 1, 2

Management of Ascites in Cirrhosis

The standard therapy for cirrhotic ascites remains:

• Sodium restriction
• Diuretics (spironolactone with or without furosemide) 1, 2

Potential Risks of Albumin Administration

• Pulmonary edema and fluid overload, particularly in patients receiving high doses 1, 2
• Not cost-effective for routine management of uncomplicated ascites 1
• Higher rate of pulmonary edema observed in the ATTIRE trial where albumin was given to maintain serum albumin levels >3.0 g/L 1

Long-term Albumin Administration

Evidence regarding long-term weekly albumin administration is mixed:

• The ANSWER trial (431 patients with persistent ascites) showed significantly lower 18-month mortality, less need for paracentesis, and fewer complications with weekly albumin infusions 1, 2
• However, the MACHT trial, a better-designed placebo-controlled study, found no differences in mortality or other complications 1
• The ATTIRE trial with 777 inpatients showed no effect on preventing bacterial infection, AKI, or death 1

Clinical Approach to Ascites Management

1. Begin with sodium restriction and diuretics (spironolactone 100-400 mg/day with or without furosemide 20-160 mg/day)
2. Reserve albumin for specific indications (large volume paracentesis, SBP, AKI)
3. Monitor for response to diuretics (continue only if urinary sodium excretion >30 mmol/day)
4. Consider liver transplantation evaluation for patients with refractory ascites (median survival approximately 6 months) 2

In conclusion, while albumin has important therapeutic roles in specific complications of cirrhosis, current evidence does not support its routine use with diuretics for uncomplicated ascites management.