What is the recommended use of albumin (human albumin) for a patient with pleural effusions, likely due to underlying conditions such as liver disease, nephrotic syndrome, or heart failure, and hypoalbuminemia?

Albumin Use for Pleural Effusions

Albumin is NOT routinely indicated for pleural effusions due to hypoalbuminemia alone; however, it has a specific, evidence-based role in cirrhotic patients with spontaneous bacterial empyema (SBE) when pleural fluid PMN count >250/mm³, particularly in those with renal dysfunction or severe hepatic decompensation. 1

Key Clinical Context: Albumin Does Not Treat Hypoalbuminemia or Pleural Effusions Directly

• Albumin should NOT be administered simply to correct low serum albumin levels or to treat pleural effusions from hypoalbuminemia. 2, 3
• Treatment should primarily target the underlying cause (heart failure, nephrotic syndrome, cirrhosis) rather than the hypoalbuminemia itself. 4
• Hypoalbuminemia from nephrotic syndrome, heart failure, or malnutrition causes transudative pleural effusions through altered oncotic pressure, but albumin infusion is not the appropriate management. 4, 5, 6

Evidence-Based Indication: Cirrhosis with Infected Pleural Effusion (SBE)

The only well-established indication for albumin in pleural effusion management is in cirrhotic patients with spontaneous bacterial empyema (SBE). 1

Specific Criteria for Albumin Administration:

• Pleural fluid PMN count >250/mm³ (diagnostic of SBE) 1
• Presence of renal dysfunction (BUN >30 mg/dL or creatinine >1.0 mg/dL) OR severe hepatic decompensation (bilirubin >5 mg/dL) 1
• These patients benefit most from albumin because it improves survival by preventing progression of acute kidney injury (AKI), not just by volume expansion. 1

Dosing Protocol:

• 1.5 g/kg IV on day 1 1
• 1.0 g/kg IV on day 3 1
• This dosing regimen, though arbitrarily determined in the original trial, remains the standard recommendation. 1

Mechanism of Benefit:

• In cirrhotic patients with infection, albumin functions beyond simple volume expansion—it reduces systemic inflammation, prevents circulatory dysfunction, and most importantly, prevents AKI progression, which is the main predictor of in-hospital mortality. 1

Management of Non-Cirrhotic Pleural Effusions with Hypoalbuminemia

Hepatic Hydrothorax (Cirrhosis without Infection):

• First-line therapy: Dietary sodium restriction and diuretics, plus therapeutic thoracentesis as needed. 4
• Albumin is NOT indicated unless there is concurrent SBE or large-volume thoracentesis (>1.5 L). 1, 4

Nephrotic Syndrome:

• Focus on managing fluid overload and the underlying nephrotic syndrome, not albumin replacement. 4
• Albumin administration for nephrotic syndrome-related effusions is not supported by widely accepted guidelines and does not represent first-choice treatment. 3

Heart Failure:

• Treat the underlying heart failure with standard therapies (diuretics, afterload reduction). 4, 5
• Hypoalbuminemia in heart failure results from malnutrition, inflammation, hemodilution, and liver dysfunction—albumin infusion does not address these mechanisms. 5
• There is no evidence that albumin administration confers benefits to hypoalbuminemic patients with heart failure. 5

Critical Pitfalls to Avoid

Do Not Target Serum Albumin Levels:

• A 2024 trial (Albumin to Prevent Infection in Chronic Liver Failure) showed that targeting serum albumin levels of 3 g/dL in hospitalized cirrhotic patients resulted in significantly higher rates of pulmonary edema and fluid overload without benefit. 1
• This reinforces that albumin should only be used for specific indications, not to "normalize" albumin levels. 1

Do Not Use Albumin as Routine Resuscitation in Pleural Effusions:

• While albumin has a role in septic shock resuscitation in cirrhotic patients, its broader use as a resuscitation agent in critically ill patients with cirrhosis and/or ACLF is not well defined. 1
• Recent evidence shows albumin may increase pulmonary complications when used broadly. 1

Recognize Transudative vs. Exudative Effusions:

• Hypoalbuminemia typically causes transudative effusions (serum-effusion albumin gradient >1.2 g/dL). 4
• Light's criteria should be applied to classify the effusion; if transudate is confirmed, the focus is on treating the underlying condition, not administering albumin. 4

Summary Algorithm for Albumin Use in Pleural Effusions

1. Identify the underlying cause of pleural effusion (cirrhosis, heart failure, nephrotic syndrome). 4
2. Perform thoracentesis and analyze pleural fluid (PMN count, protein, LDH, albumin gradient). 1, 4
3. If cirrhosis with pleural fluid PMN >250/mm³ (SBE):
   • Start empirical IV antibiotics (third-generation cephalosporin). 1
   • Administer albumin (1.5 g/kg day 1.0 g/kg day 3) if renal dysfunction or severe hepatic decompensation present. 1
4. If non-cirrhotic or cirrhotic without infection:
   • Treat underlying condition (diuretics for heart failure, sodium restriction for hepatic hydrothorax, manage nephrotic syndrome). 4
   • Do NOT administer albumin to correct hypoalbuminemia or treat the effusion. 2, 3