What is the role and evidence for using albumin in the management of hypotension, and in which clinical situations is it indicated?

Role and Evidence for Albumin in Hypotension

Albumin is NOT recommended as first-line therapy for hypotension in most critically ill patients, with the important exception of cirrhotic patients with sepsis-induced hypotension, where 5% albumin is superior to crystalloids for reversing hypotension and improving short-term survival. 1, 2

General Critically Ill Patients with Hypotension

Albumin should not be used for first-line volume replacement in general critical care settings. The most recent international guidelines (2024) provide a conditional recommendation against albumin use in critically ill adults for volume replacement or to increase serum albumin levels, based on moderate certainty evidence. 1

Key Evidence Against Routine Use:

• Meta-analyses show no mortality benefit when albumin is compared to crystalloids (RR 0.98; 95% CI 0.92-1.06) in general critically ill populations 2
• Balanced crystalloids (lactated Ringer's, Plasma-Lyte) are associated with reduced mortality compared to saline in general critically ill populations 2
• The 2022 French guidelines similarly recommend against albumin as first-line treatment in sepsis or septic shock to reduce mortality or renal replacement therapy requirement 1

Why the Evidence is Against Routine Use:

The SAFE study (nearly 7,000 patients) comparing 4% albumin to 0.9% saline showed no overall mortality difference. 1 The ALBIOS and EARSS trials using 20% albumin in septic patients also showed no mortality benefit, even in septic shock subgroups. 1 Multiple meta-analyses consistently demonstrate no beneficial effect on mortality in general critical care populations. 1

Cirrhotic Patients with Sepsis-Induced Hypotension: THE EXCEPTION

This is the primary evidence-based indication for albumin in hypotension. 2, 3

Specific Recommendations:

• Use 5% albumin as the resuscitation fluid of choice in cirrhotic patients with sepsis-induced hypotension 2, 3
• The FRISC trial (2021) demonstrated that 5% albumin was superior to normal saline for reversing hypotension at 1 hour (25.3% vs 11.7%, p=0.03) and 3 hours (11.7% vs 3.2%, p=0.008) 3
• One-week survival was higher with albumin (43.5% vs 38.3%, p=0.03) 3
• Sustained reduction in heart rate and hyperlactatemia was better with albumin 3

Important Caveat with 20% Albumin:

The ALPS trial (2022) compared 20% albumin to plasmalyte in cirrhotic patients with sepsis-induced hypotension. While 20% albumin achieved faster hemodynamic improvement (62% vs 22% reaching MAP >65 mmHg at 3 hours, p<0.001), treatment had to be discontinued in 22% of albumin patients due to adverse effects, primarily pulmonary complications. 4 The 28-day mortality was similar between groups (58% vs 62%, p=0.57). 4 This suggests that 5% albumin is preferable to 20% albumin due to better safety profile with comparable efficacy. 2, 3, 4

Other Specific Cirrhosis Indications (Not General Hypotension)

While not primarily for hypotension management, albumin has established roles in cirrhosis:

• Large-volume paracentesis (>5L): 8g albumin per liter of ascites removed 2
• Spontaneous bacterial peritonitis: 1.5 g/kg on day 1 and 1.0 g/kg on day 3 2
• Hepatorenal syndrome: Part of standard management 2

Intradialytic Hypotension

Albumin is NOT recommended for routine use in intradialytic hypotension. 1, 2 The 2024 guidelines suggest against routine albumin use due to high costs (approximately $20,000 per patient annually for thrice-weekly dialysis) and limited evidence of benefit. 1, 2 Alternative strategies including higher dialysate calcium, lower dialysate temperature, and individualized ultrafiltration rates are recommended instead. 1, 2

Limited evidence suggests 25% albumin may improve hypotension and ultrafiltration in hospitalized hemodialysis patients with serum albumin <30 g/L, but the cost-benefit ratio is unfavorable. 1, 5

Cardiovascular Surgery

Albumin is not recommended in cardiovascular surgery. 2 A meta-analysis of 43 randomized trials (N=3,862) found albumin did not reduce mortality, kidney failure, blood loss, or ICU length of stay compared to other fluids. 2 The largest trial (1,386 patients) comparing 4% albumin with Ringer's lactate showed higher rates of bleeding, resternotomy, and infection with albumin. 2

Critical Safety Considerations

Albumin carries significant risks that can paradoxically worsen hypotension and clinical status: 1, 6

Major Adverse Effects:

• Fluid overload and pulmonary edema, especially in patients with compromised cardiac or pulmonary function 6
• Hypotension and tachycardia can occur despite albumin being used to treat hypovolemia 6
• Hemodilution requiring RBC transfusion 6
• Anaphylactic/allergic reactions including rash, pruritus, rigors, and pyrexia 6

Highest Risk Populations:

Patients with cirrhosis are at particularly high risk due to increased capillary permeability and compromised lymphatic drainage capacity. 6 Higher rates of pulmonary edema are observed in cirrhotic patients receiving albumin, especially with 20% formulations. 6, 4

Practical Algorithm for Albumin Use in Hypotension

Step 1: Identify the Underlying Cause

Use bedside transthoracic echocardiography to assess preload, cardiac function, and fluid status. 2

Step 2: Determine Patient Population

• If cirrhosis with sepsis-induced hypotension: Use 5% albumin as resuscitation fluid 2, 3
• If general critically ill (no cirrhosis): Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) as first-line 2
• If intradialytic hypotension: Use alternative strategies (dialysate adjustments) rather than albumin 1, 2
• If cardiovascular surgery: Use crystalloids or other colloids, not albumin 2

Step 3: Monitor Closely if Albumin is Used

• Watch for respiratory distress, pulmonary rales, and peripheral edema (fluid overload) 6
• Monitor for hypotension and tachycardia during infusion 6
• Be vigilant for allergic reactions (skin changes, fever, rigors) 6
• Consider discontinuation if adverse effects develop, particularly pulmonary complications 4

Cost Considerations

Albumin is expensive (approximately $130/25g in the United States), and the acquisition cost is likely a fraction of total healthcare expenditure. 1 Given the lack of superiority over less costly alternatives in most settings, crystalloids should be the default choice except in cirrhotic patients with sepsis-induced hypotension. 2

Common Pitfalls to Avoid

• Do not use albumin to "correct" hypoalbuminemia in critical illness. Hypoalbuminemia in acute illness results from transcapillary leak, decreased synthesis, and dilution—addressing the underlying disorder is essential, not albumin infusion. 1, 7
• Do not assume albumin is a superior volume expander in general populations. Clinical trials demonstrate albumin is not as effective a volume expander as theoretical oncotic properties would suggest. 5
• Do not use 20% albumin in cirrhotic patients with sepsis-induced hypotension due to high rates of pulmonary complications requiring treatment discontinuation. 4
• Avoid albumin in pediatric critical care with severe infections, as the FEAST trial showed excess mortality with albumin bolus strategies in children with febrile illness and hypoperfusion. 1