What is the role of human albumin (HA) 25% in managing medical diseases characterized by significant hypoalbuminemia, such as liver cirrhosis, nephrotic syndrome, and severe burns?

Role of Human Albumin 25% in Medical Diseases

Human albumin 25% has well-defined, evidence-based indications primarily in liver cirrhosis complications, severe burns, and shock states, but should NOT be used to simply correct low serum albumin levels in chronic conditions like nephrotic syndrome, malnutrition, or stable cirrhosis without acute complications. 1, 2

Established Indications with Strong Evidence

Liver Cirrhosis Complications (Highest Quality Evidence)

Large-Volume Paracentesis (>5L)

• Administer 8 g of albumin per liter of ascites removed after the procedure is completed 1
• This prevents paracentesis-induced circulatory dysfunction and reduces hyponatremia 1
• In patients with acute-on-chronic liver failure, use 6-8 g/L regardless of volume removed 1

Spontaneous Bacterial Peritonitis (SBP)

• Give 1.5 g/kg within 6 hours of diagnosis, followed by 1.0 g/kg on day 3 1
• This reduces acute kidney injury from 33% to 10% and mortality from 29% to 10% 1
• Patients with serum bilirubin >4 mg/dL or creatinine >1.0 mg/dL benefit most 1

Hepatorenal Syndrome (HRS-AKI)

• Administer 1 g/kg on day 1, then 20-40 g daily in combination with vasoconstrictors 1
• Continue until serum creatinine returns to within 0.3 mg/dL of baseline for 2 consecutive days, or maximum 14 days 3

Severe Burns (>30% Total Body Surface Area)

• Administer albumin after the first 6 hours of management 1
• Target plasma albumin concentration of 2.5 ±0.5 g/100 mL or plasma oncotic pressure of 20 mmHg 2
• Typical doses are 1-2 g/kg/day to maintain albumin >30 g/L 1
• Critical caveat: During the first 24 hours, prioritize large volumes of crystalloids with lesser amounts of albumin; after 24 hours, increase albumin and decrease crystalloid 2

Shock States (Limited Evidence)

Septic Shock in Cirrhosis

• One RCT showed albumin improved 1-week survival (43.5% vs 38.3%, p=0.03) compared to normal saline in cirrhotic patients with sepsis-induced hypotension 1
• However, another trial showed higher rates of shock reversal but no survival benefit and increased pulmonary complications 1
• Use cautiously: Albumin may be considered as second-line after crystalloids, but evidence is mixed 1

Indications Where Albumin Should NOT Be Used

Chronic Hypoalbuminemia (Strong Contraindication)

The FDA label explicitly states albumin is NOT justified for: 2

• Stabilized hypoproteinemia accompanying chronic cirrhosis
• Chronic nephrosis
• Protein-losing enteropathy
• Malabsorption and pancreatic insufficiency
• Intravenous nutrition

The 2024 AASLD guidelines confirm: 1

• Targeting albumin >30 g/L in hospitalized cirrhotic patients showed NO difference in infections, renal failure, or death
• This approach was associated with significantly higher rates of pulmonary edema and fluid overload

Other Contraindications

• NOT for first-line volume replacement in critically ill adults (excluding burns/ARDS) 3, 4
• NOT for routine use in cardiovascular surgery 3, 4
• NOT for intradialytic hypotension as routine therapy 3, 4
• NOT for correcting hypoalbuminemia alone without specific complications 3, 4

Critical Safety Considerations

Risk of Pulmonary Edema

Doses exceeding 87.5 g (>4×100 mL of 20% albumin) may worsen outcomes due to fluid overload 1, 4

High-risk scenarios for pulmonary complications: 5

• Patients with cirrhosis receiving albumin infusions (demonstrated in ATTIRE trial)
• Traumatic brain injury patients (increased mortality with albumin)
• ARDS patients with increased capillary permeability

Monitor carefully for: 4, 2

• Circulatory overload (FDA-mandated monitoring)
• Hypotension
• Hemodilution requiring RBC transfusion
• Anaphylaxis
• Peripheral gangrene from dilution of natural anticoagulants

Dosing and Administration Specifics

Concentration Selection

• 25% albumin is hyperoncotic and draws fluid from interstitial space into circulation 2
• Use 25% when treating oncotic deficit with fluid overload
• Use 5% when treating volume deficit without significant edema

Duration of Effect

• Albumin has a transient effect lasting hours to days, not weeks 4
• This is why SBP protocols require dosing on day 1 AND day 3 1, 4
• Long-term administration requires weekly or twice-weekly dosing to maintain benefit 4

Common Clinical Pitfalls to Avoid

1. Administering albumin to "correct" a low albumin number without addressing the underlying cause (inflammation, malnutrition, protein loss) 3, 6

2. Assuming hypoalbuminemia equals malnutrition when inflammation is often the primary driver 3

3. Using albumin for chronic conditions like nephrotic syndrome or stable cirrhosis without acute complications 2

4. Rapid or excessive administration leading to fluid overload, especially in cirrhotic patients 1

5. Ignoring the high cost (~$130 per 25g) when crystalloids would be equally effective 3, 4

When Acute Complications Arise in Chronic Hypoalbuminemia

The FDA label provides important guidance: 2 If a patient with chronic hypoproteinemia (cirrhosis, nephrosis, malabsorption) faces a superimposed acute stress (anesthesia, surgery, major infections), carefully assess:

• Hemodynamic state
• Oncotic deficit
• Fluid balance

Then take appropriate steps based on individual circumstances, potentially including albumin for the acute complication—but NOT for the chronic condition itself 2

Practical Algorithm for Decision-Making

Step 1: Identify the clinical scenario

• Liver cirrhosis with specific complication (LVP >5L, SBP, HRS)? → Use albumin per protocols above
• Severe burns >30% TBSA after 6 hours? → Use albumin per protocols above
• Chronic hypoalbuminemia without acute complication? → Do NOT use albumin

Step 2: Assess for contraindications

• Signs of fluid overload or pulmonary edema? → Avoid or use extreme caution
• Stable chronic condition without acute decompensation? → Do NOT use albumin

Step 3: Monitor during administration

• Watch for circulatory overload (mandatory FDA monitoring) 4
• Assess fluid balance carefully, especially in cirrhotic patients 1
• Consider stopping if doses exceed 87.5 g without clear benefit 1, 4

Human albumin 25% is a powerful therapeutic tool with specific, evidence-based indications primarily in acute complications of liver disease and severe burns, but its use must be restricted to these scenarios to avoid harm and unnecessary cost 1, 3, 2.