When is albumin replacement indicated in patients with hypoalbuminemia?

When to Replace Albumin in Hypoalbuminemia

Albumin replacement should NOT be used routinely to correct hypoalbuminemia in most clinical settings, with specific exceptions limited to cirrhosis-related complications (large-volume paracentesis >5L and spontaneous bacterial peritonitis). 1

General Principle: Treat the Underlying Cause, Not the Number

• The primary approach to hypoalbuminemia is treating the underlying disease process and providing adequate nutritional support, rather than administering exogenous albumin. 2
• Hypoalbuminemia in acute and chronic illness results from suppressed hepatic synthesis due to inflammatory cytokines and transcapillary loss, not simply from nutritional deficiency. 1
• Each 10 g/L decline in serum albumin increases mortality odds by 137% and morbidity by 89%, but this association does not prove that albumin replacement improves outcomes. 3

Specific Indications Where Albumin IS Recommended

Cirrhosis-Related Conditions (Strong Evidence)

Large-Volume Paracentesis:

• Administer 8 grams of albumin per liter of ascitic fluid removed when removing >5L of ascites to prevent post-paracentesis circulatory dysfunction. 2, 4
• For patients with acute-on-chronic liver failure, use 6-8 g/L regardless of volume removed. 2

Spontaneous Bacterial Peritonitis:

• Give 1.5 g/kg body weight on day 1 and 1.0 g/kg on day 3, which reduces acute kidney injury and mortality. 2, 5
• Patients with serum bilirubin >4 mg/dL or baseline creatinine >1.0 mg/dL benefit most. 2

Hepatorenal Syndrome (Type 1):

• Albumin is indicated as part of treatment for type 1 hepatorenal syndrome. 5
• For Stage 2-3 acute kidney injury in cirrhosis with ascites, withdraw diuretics and administer 1 g/kg body weight albumin daily for 2 consecutive days. 2

Clinical Settings Where Albumin Is NOT Recommended

Critical Care Patients (Excluding Specific Exceptions)

• Intravenous albumin is NOT suggested for first-line volume replacement or to increase serum albumin levels in critically ill adult patients (excluding thermal injuries and ARDS). 1
• This includes patients with sepsis, hypovolemia, and general critical illness. 1
• Albumin administration in critically ill patients showed no benefit in mortality (39% vs 27%), major complications, length of stay, or ventilator dependence despite successfully raising albumin levels. 6

Other Specific Populations Where Albumin Is NOT Recommended

Burn Patients:

• Routine albumin supplementation to maintain albumin ≥20 g/L provides no benefit in mortality, organ failure scores, wound healing, or ventilator duration. 7
• The practice is expensive (>4 times the cost) without clinical benefit. 7

Chronic Kidney Disease/Dialysis:

• Albumin is NOT recommended for routine prevention or treatment of intradialytic hypotension. 1, 2
• Infused albumin in chronic nephrosis is promptly excreted with no relief of edema or effect on underlying renal lesion. 4

Pediatric Cardiac Surgery:

• Albumin infusion is NOT recommended for pediatric patients undergoing cardiovascular surgery. 2

Preterm Neonates:

• Albumin is NOT recommended for preterm neonates with respiratory distress and low serum albumin. 2

Chronic Conditions:

• In chronic cirrhosis (without acute complications), malabsorption, protein-losing enteropathies, and undernutrition, albumin infusion as protein nutrition is NOT justified. 4

Diuretic Therapy:

• Albumin is NOT recommended in conjunction with diuretics for removal of extravascular fluid. 2

Hospitalized Cirrhosis Patients:

• In hospitalized patients with decompensated cirrhosis, hyperoncotic albumin targeting levels >30 g/L showed no improvement in infections, kidney dysfunction, or death. 2

Alternative Management Approach

Nutritional Support:

• Ensure protein intake of 1.2-1.3 g/kg body weight/day with adequate calories (30-35 kcal/kg/day). 2
• Hemodialysis patients require ≥1.2 g protein/kg/day; peritoneal dialysis patients require ≥1.3 g protein/kg/day. 2

Address Underlying Causes:

• Treat active inflammation, which directly downregulates hepatic albumin synthesis even with adequate nutrition. 2
• Correct fluid overload, as hemodilution decreases serum albumin concentration. 2
• Minimize external protein losses by treating proteinuria or reducing dialysate losses. 2
• Measure C-reactive protein to distinguish inflammation-driven hypoalbuminemia from pure malnutrition. 2

Important Safety Considerations

Potential Adverse Effects of Albumin Administration:

• Fluid overload and pulmonary edema, especially in patients with cardiac or pulmonary compromise. 1, 8
• Hypotension and tachycardia despite intended use for hypovolemia. 8
• Hemodilution requiring RBC transfusion. 1, 8
• Anaphylactic/allergic reactions including rash, pruritus, rigors, and pyrexia. 8
• Peripheral gangrene from dilution of natural anticoagulants. 1
• Cost: approximately $130 per 25g. 1

Patients with cirrhosis are at particularly high risk for pulmonary edema and circulatory overload due to increased capillary permeability and compromised lymphatic drainage. 8

Common Pitfalls to Avoid

• Do not assume hypoalbuminemia is solely due to nutritional deficiency when inflammation is often the primary driver. 2
• Recognize that serum albumin <3.0 g/dL reflects disease-associated catabolism and disease severity, not just malnutrition. 2
• Avoid using albumin as a marker of nutritional status in acute inflammatory conditions—it is primarily a marker of inflammation. 2
• Do not routinely supplement albumin in surgical patients with hypoalbuminemia; instead, optimize nutrition preoperatively when feasible. 2