Is albumin indicated in septic patients?

Albumin Use in Septic Patients

Albumin is probably not recommended as a first-line fluid treatment in septic patients to reduce mortality or renal replacement therapy requirements. 1

Evidence-Based Approach to Albumin in Sepsis

First-Line Fluid Therapy

• Crystalloids are the preferred initial fluid choice for septic patients
• Balanced/buffered crystalloids should be administered at 30 mL/kg within the first 3 hours of resuscitation 2
• Continue fluid challenge as long as hemodynamic improvement occurs, with careful monitoring for fluid overload 2

Current Evidence Against First-Line Albumin Use

The recommendation against first-line albumin use is based on several key findings:

• Multiple randomized controlled trials have failed to demonstrate a mortality benefit for albumin as first-line therapy in sepsis 1
• The SAFE study (largest randomized trial with nearly 7000 patients) comparing 4% albumin to 0.9% NaCl showed no overall mortality benefit 1
• The ALBIOS trial comparing 20% albumin to crystalloids showed no effect on mortality in the overall septic patient population (OR 1.00,95% CI 0.87-1.14) 1
• The EARSS trial similarly found no mortality benefit (OR 0.92,95% CI 0.72-1.17) 1
• Meta-analyses have consistently found no beneficial effect on mortality with either 4-5% or 20% albumin 1

Potential Considerations for Albumin Use

While not recommended as first-line therapy, albumin may be considered in specific circumstances:

1. After large volumes of crystalloids:

   • The International Collaboration for Transfusion Medicine Guidelines (ICTMG) notes that albumin may be considered in patients who have received large volumes of crystalloids 1
   • However, this is based on low-quality evidence 1

2. Patients with septic shock:

   • A subgroup analysis of the ALBIOS study suggested a potential benefit in patients with septic shock (OR 0.87,95% CI 0.77-0.99) 1
   • However, this finding should be interpreted cautiously as it was a post-hoc analysis

3. Patients with hypoalbuminemia:

   • Despite the theoretical rationale that correcting hypoalbuminemia might be beneficial, recent evidence does not support this approach
   • A 2024 study found no difference in vasopressor-free days at day 14 in hypoalbuminemic septic shock patients who received albumin versus those who did not 3

Physiological Considerations

Albumin has several theoretical advantages:

• Remains in the intravascular space longer than crystalloids 4
• Has antioxidant effects and positive effects on vessel wall integrity 4
• May help achieve negative fluid balance in hypoalbuminemia 4
• Less likely to cause nephrotoxicity than artificial colloids 4

However, these theoretical benefits have not translated to improved mortality outcomes in clinical trials.

Practical Algorithm for Fluid Management in Sepsis

1. Initial resuscitation: Use balanced crystalloids at 30 mL/kg within first 3 hours 2
2. Ongoing fluid needs: Continue crystalloids based on hemodynamic response
3. Consider albumin only if:
   • Patient has received large volumes of crystalloids AND
   • Patient remains hemodynamically unstable OR
   • Patient has septic shock with persistent hypotension despite adequate crystalloid resuscitation

Monitoring Response to Fluid Therapy

• Reassess patients every 30-60 minutes based on risk level 2
• Monitor mean arterial pressure (target ≥65 mmHg) 2
• Measure serum lactate and repeat within 6 hours if initially elevated 2
• Watch for signs of fluid overload

Caveats and Pitfalls

• Concentration matters: Studies have used different concentrations (4-5% iso-oncotic or 20% hyper-oncotic) with varying protocols, making definitive conclusions challenging 1
• Cost considerations: Albumin is significantly more expensive than crystalloids without proven mortality benefit
• Albumin retention: Septic patients have increased capillary leak, with studies showing that albumin concentration decreases significantly faster in septic patients than in healthy controls 5
• Practice variation: Substantial variation exists in albumin use across institutions, with factors like gastrointestinal focus of infection and higher doses of norepinephrine being associated with increased albumin use 6

In conclusion, while albumin has theoretical benefits in sepsis, the current evidence does not support its use as a first-line fluid therapy for improving mortality outcomes in septic patients.