What are the indications for albumin infusion in patients with hypoalbuminemia?

Indications for Albumin Infusion

Albumin infusion should NOT be used routinely to correct hypoalbuminemia or for nutritional purposes in critically ill patients, but is specifically indicated for cirrhosis complications (large-volume paracentesis >5L, spontaneous bacterial peritonitis, hepatorenal syndrome) and may be considered as second-line therapy in specific shock states when crystalloids are insufficient. 1, 2

Evidence-Based Indications for Albumin Administration

Strong Indications (High-Quality Evidence)

Liver Disease Complications:

• Large-volume paracentesis (>5L): Administer 8 grams of albumin per liter of ascitic fluid removed to prevent post-paracentesis circulatory dysfunction 2, 3, 4

  • In 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, 3, 4

  • Patients with serum bilirubin >4 mg/dL or baseline creatinine >1.0 mg/dL benefit most 2

• Hepatorenal syndrome-AKI: Administer 1 g/kg on day 1 followed by 20-40 g daily along with vasoactive agents, continuing until serum creatinine returns to within 0.3 mg/dL of baseline for 2 consecutive days or maximum 14 days 2

• Stage 2-3 acute kidney injury in cirrhosis with ascites: Withdraw diuretics immediately and administer 1 g/kg body weight albumin daily for 2 consecutive days 2

Plasmapheresis: Fluid replacement during therapeutic plasma exchange 4

Conditional/Second-Line Indications (Moderate-Quality Evidence)

Hypovolemic Shock:

• Albumin 25% is hyperoncotic and expands plasma volume by 3-4 times the volume administered by withdrawing fluid from interstitial spaces 3
• Total dose should not exceed 2 g per kg body weight in the absence of active bleeding 3
• Consider only when crystalloid resuscitation is insufficient 4

Burn Therapy:

• Beyond 24 hours post-thermal injury, albumin 25% can maintain plasma colloid osmotic pressure 3
• Aim to maintain plasma albumin concentration around 2.5 ± 0.5 g per 100 mL 3

Severe and Refractory Edema with Hypoalbuminemia:

• When combined with diuretics in patients not responding to other treatments, particularly with effective arterial volume depletion 5
• Based on pathophysiological concept of increasing intravascular oncotic pressure to mobilize extravascular fluid 5

Neonatal Hemolytic Disease:

• Administer 1 g/kg body weight approximately 1 hour prior to exchange transfusion to bind free bilirubin and reduce kernicterus risk 3

Specific Clinical Scenarios (Weak Evidence)

• Cardiopulmonary bypass: Adjust albumin and crystalloid pump prime to achieve hematocrit of 20% and plasma albumin concentration of 2.5 g per 100 mL 3
• Adult Respiratory Distress Syndrome (ARDS): When clinical signs show hypoproteinemia with fluid volume overload, albumin 25% together with a diuretic may play a role 3
• Sequestration of protein-rich fluids: In acute peritonitis, pancreatitis, mediastinitis, and extensive cellulitis when magnitude of third-space loss requires treatment 3

When Albumin Infusion is NOT Recommended

The 2024 International Collaboration for Transfusion Medicine Guidelines explicitly recommend AGAINST albumin in the following situations:

• First-line volume replacement in critically ill adults (excluding thermal injuries and ARDS) - conditional recommendation with moderate certainty of evidence 1
• To increase serum albumin levels in critically ill patients - this does not improve mortality, morbidity, or quality of life 1, 6, 7
• Nutritional supplementation - albumin should never be used as a protein or nutritional source 2, 4
• In conjunction with diuretics for removal of extravascular fluid (except in specific refractory cases) 2
• Preterm neonates with respiratory distress and low serum albumin 2
• Intradialytic hypotension in kidney replacement therapy 2
• Pediatric patients undergoing cardiovascular surgery 2
• Extraperitoneal infections in cirrhosis - increases pulmonary edema without benefit 2
• Modest volume paracentesis (<5L) - weak recommendation against 4

Critical Pitfalls to Avoid

Understanding Hypoalbuminemia Pathophysiology:

• Hypoalbuminemia in acute illness is primarily a marker of inflammation and disease severity, NOT nutritional deficiency 2, 7
• Inflammatory cytokines directly downregulate hepatic albumin synthesis even with adequate protein intake 2
• Simply correcting the albumin number does not improve outcomes - treat the underlying disease 2, 7, 8

Clinical Studies Show No Benefit:

• A prospective randomized trial in critically ill hypoalbuminemic patients showed no difference in mortality (39% vs 27%), major complications, length of stay, or ICU outcomes despite achieving higher albumin levels 6
• Simple albumin infusion or hyperalimentation for hypoalbuminemia did not improve survival in acute surgical patients 7

Proper Treatment Approach for Hypoalbuminemia

Primary Strategy (NOT albumin infusion):

• Treat the underlying cause: Address inflammation, infection, protein losses, or liver dysfunction 2, 7
• Provide adequate nutrition: 1.2-1.3 g/kg body weight/day protein intake with 30-35 kcal/kg/day calories 2
• Correct fluid overload: Hemodilution from excess fluid decreases serum albumin concentration 2
• Minimize external protein losses: Treat proteinuria or reduce dialysate losses 2
• Measure inflammatory markers: C-reactive protein helps distinguish inflammation-driven hypoalbuminemia from pure malnutrition 2

Adverse Effects to Monitor

Albumin administration carries significant risks:

• Fluid overload and pulmonary edema - especially in patients with compromised cardiac or pulmonary function 9
• Hypotension and tachycardia - paradoxically can occur despite treating hypovolemia 9
• Hemodilution requiring RBC transfusion 1, 9
• Anaphylactic/allergic reactions - rash, pruritus, rigors, pyrexia 9
• Peripheral gangrene - from dilution of natural anticoagulants 1
• High cost - approximately $130/25g with questionable benefit in most situations 1, 9

Administration Guidelines When Indicated

Dosing and Rate:

• For hypoproteinemia: Usual adult dose 50-75 g, pediatric 25 g daily 3
• Rate should not exceed 2 mL per minute in hypoproteinemic patients to avoid circulatory embarrassment and pulmonary edema 3
• May be administered undiluted or diluted in 0.9% sodium chloride or 5% dextrose in water 3
• If sodium restriction required, use only undiluted or with 5% dextrose in water 3