What is the evidence for using albumin (human albumin) in a patient with hypotension, considering their volume status, cardiac function, and underlying cause of hypotension?

Evidence for Albumin in Hypotension

Albumin should NOT be used routinely for hypotension in general critically ill patients, as it provides no mortality benefit over crystalloids and significantly increases costs; however, albumin IS indicated specifically for cirrhotic patients with sepsis-induced hypotension, where 5% albumin is superior to crystalloids for reversing hypotension and improving short-term survival. 1

General Critically Ill Hypotensive Patients

Crystalloids are the first-line fluid for volume resuscitation in hypotension without cirrhosis. 1, 2

• The Society of Critical Care Medicine explicitly states albumin is NOT recommended as first-line volume replacement in general critically ill hypotensive patients, showing no mortality benefit compared to crystalloids (RR 0.98; 95% CI 0.92-1.06) 1
• The Surviving Sepsis Campaign guidelines recommend initial resuscitation with crystalloids in septic shock, as albumin offers no survival advantage and increases complications 2
• Balanced crystalloids (lactated Ringer's, Plasma-Lyte) are associated with reduced mortality compared to saline in general critically ill populations 1
• Initial crystalloid boluses of 20-30 mL/kg should be administered before considering alternative fluids 2

Cirrhotic Patients with Hypotension

For cirrhotic patients with sepsis-induced hypotension, 5% albumin is the preferred resuscitation fluid. 1

• The American Association for the Study of Liver Diseases recommends 5% albumin for sepsis-induced hypotension in cirrhotic patients, as it is superior to crystalloids for reversing hypotension and improving short-term survival 1
• The European Association for the Study of the Liver indicates albumin reduces systemic inflammation and circulatory dysfunction in decompensated cirrhosis 1
• Critical warning: 20% albumin in cirrhosis with extraperitoneal infections increases pulmonary edema 5-fold (OR 5.17,95% CI 1.62-16.47) 2

Specific Cirrhosis-Related Indications Beyond General Hypotension

While not primary hypotension management, these cirrhosis scenarios have strong albumin evidence:

• Large-volume paracentesis (>5L): 8g of 20% albumin per liter of ascites removed to prevent paracentesis-induced circulatory dysfunction 1, 3
• Spontaneous bacterial peritonitis: 1.5 g/kg on day 1 and 1.0 g/kg on day 3 1, 3
• Hepatorenal syndrome: Albumin combined with vasoconstrictors (terlipressin) as standard management 1, 3

Intradialytic Hypotension

Albumin should NOT be used routinely for intradialytic hypotension. 4

• A 2024 international guideline from the International Collaboration for Transfusion Medicine Guidelines suggests against routine albumin use for intradialytic hypotension 4
• Limited evidence shows 25% albumin may improve hypotension and ultrafiltration in hospitalized hemodialysis patients with serum albumin <30 g/L, but the annual cost is approximately $20,000 per patient 4
• Preferred alternative: Midodrine 5-10 mg orally 30 minutes before dialysis is safer and more cost-effective 2
• Other strategies include higher dialysate calcium, lower dialysate temperature, and individualized ultrafiltration rates 4

Cardiovascular Surgery

Albumin should NOT be used routinely in cardiovascular surgery. 4, 3

• 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 4
• The largest trial (1,386 patients) comparing 4% albumin with Ringer's lactate showed higher rates of bleeding, resternotomy, and infection with albumin 4, 3

Septic Shock Subgroup Analysis

In septic shock specifically, 20% albumin may provide mortality benefit when used to maintain elevated serum albumin levels, but this remains controversial. 3

• The ALBIOS trial showed mortality benefit in the septic shock subgroup (OR 0.87,95% CI 0.77-0.99) when 20% albumin was used 3
• One meta-analysis found 90-day mortality benefit in septic shock (OR 0.81,95% CI 0.67-0.97) with 20% albumin 3
• However, the overall ALBIOS trial showed no mortality difference in general septic shock 2
• Current recommendation: Consider 20% albumin only when large volumes of crystalloids are needed and serum albumin is low 3

Hypoalbuminemia as Effect Moderator

The volume effectiveness of albumin appears greater when serum albumin levels are low (<25 g/L). 5

• In the SAFE study, the saline-to-albumin ratio of study fluids was significantly higher in patients with baseline serum albumin ≤25 g/L compared to >25 g/L 5
• In patients receiving renal replacement therapy, 20-25% albumin reduces intradialytic hypotension better than saline when serum albumin levels are similarly reduced 5
• Hypoalbuminemia acts as an effect moderator in volume resuscitation and plasma expansion with albumin 5

Critical Safety Considerations

Monitor closely for fluid overload, particularly in cirrhotic patients with compromised cardiac or pulmonary function. 1

• Albumin carries significant risks of fluid overload, with pulmonary edema being a dose-dependent adverse effect 1
• Patients with cirrhosis have increased capillary permeability and compromised lymphatic drainage, increasing fluid overload risk 1
• Stop albumin immediately if hepatomegaly or rales develop and switch to inotropes 2
• Other adverse effects include hypotension, hemodilution requiring RBC transfusion, anaphylaxis, and peripheral gangrene from dilution of natural anticoagulants 3

Practical Algorithm for Hypotension Management

1. Identify underlying cause: Use bedside transthoracic echocardiography to assess preload, cardiac function, and fluid status 1

2. Determine if cirrhosis is present:

   • No cirrhosis: Use crystalloid boluses 20-30 mL/kg, NOT albumin 2
   • Cirrhosis with sepsis-induced hypotension: Use 5% albumin as resuscitation fluid 1

3. Initiate vasopressors if MAP remains <65 mmHg after initial fluid resuscitation 2

4. For specific cirrhosis complications: Use albumin per established protocols (large-volume paracentesis, spontaneous bacterial peritonitis, hepatorenal syndrome) 1

Common Pitfalls to Avoid

• Do not use albumin as first-line for general septic shock without cirrhosis, as it offers no mortality benefit over crystalloids and costs significantly more 2
• Do not use albumin to correct hypoalbuminemia alone without specific indications, as serum concentration does not reflect albumin function 3
• Do not use albumin routinely in cardiovascular surgery, as the largest trial showed increased morbidity 4, 3
• Do not continue albumin if signs of fluid overload develop (rales, hepatomegaly) 2

Cost Considerations

• 20% albumin costs approximately $130 per 25g, significantly more expensive than crystalloids 3
• Thrice-weekly albumin for hemodialysis patients would cost approximately $20,000 per patient per year 4, 3
• The 2024 international guidelines emphasize that given albumin's high costs and lack of superiority over less costly alternatives in most settings, alternative fluids should be considered 4