How should albumin be dosed in an adult patient with hypotension refractory to an initial crystalloid bolus (approximately 30 mL kg⁻¹ isotonic saline)?

Albumin Dosing in Hypotension After Initial Crystalloid Resuscitation

Albumin is NOT recommended as first-line therapy for hypotension refractory to initial crystalloid bolus in general critically ill adults; instead, continue crystalloid boluses (250-1000 mL) with dynamic reassessment, and reserve albumin only for cirrhotic patients with sepsis-induced hypotension at 0.5-1.0 g/kg over 3 hours using 5% albumin solution. 1, 2, 3

Primary Recommendation: Continue Crystalloids, Not Albumin

• After the initial 30 mL/kg crystalloid bolus, administer additional crystalloid boluses of 250-1000 mL and reassess hemodynamic response after each bolus rather than switching to albumin. 4, 3

• Albumin shows no mortality benefit compared to crystalloids in general critically ill populations (RR 0.98; 95% CI 0.92-1.06), making it inappropriate as a second-line agent after crystalloid failure. 1, 2

• Use dynamic measures like passive leg raise (PLR) testing after the initial crystalloid bolus to determine if additional fluid is warranted; a ≥10-15% increase in stroke volume or cardiac output indicates fluid responsiveness and justifies further crystalloid boluses. 4

• Balanced crystalloids (lactated Ringer's or Plasma-Lyte) are preferred over normal saline for ongoing resuscitation to reduce hyperchloremic acidosis and acute kidney injury risk. 4, 3

The Single Exception: Cirrhotic Patients with Sepsis-Induced Hypotension

• In patients with underlying cirrhosis and sepsis-related hypotension, administer 5% albumin at 0.5-1.0 g/kg over 3 hours as the preferred resuscitation fluid, as it more effectively reverses hypotension and improves short-term survival compared to crystalloids. 2, 5

• Use 5% albumin rather than 20% albumin in cirrhotic patients because 20% albumin, while achieving faster MAP >65 mmHg, required discontinuation in 22% of patients due to pulmonary complications without improving 28-day mortality. 2, 5

• The dose for cirrhotic patients translates to approximately 35-70 grams of albumin for a 70 kg patient (0.5-1.0 g/kg), administered as 5% solution over 3 hours. 2, 5

Why Albumin Should Be Avoided in General Hypotension

• Multiple high-quality trials (SAFE, ALBIOS, EARSS) demonstrated no mortality benefit when albumin was compared to crystalloids in septic shock and general critical illness. 2

• Albumin carries significant risks including fluid overload, pulmonary edema, paradoxical hypotension, tachycardia, and hemodilution requiring red-cell transfusion, particularly in patients with compromised cardiac or pulmonary function. 2, 6

• The cost of albumin is prohibitively high at approximately $130 per 25 g vial in the United States, compared to $1.50 per liter for isotonic saline, without demonstrating superior outcomes. 2, 3

• In pediatric populations, the FEAST trial showed excess mortality with albumin bolus in children with febrile illness and hypoperfusion, leading to recommendations against its use in pediatric critical care. 1, 2

Practical Algorithm for Hypotension After Initial Crystalloid

Step 1: Reassess After Initial 30 mL/kg Crystalloid Bolus

• Evaluate hemodynamic parameters: heart rate, blood pressure, capillary refill time (<2 seconds target), skin temperature, mental status, urine output (>0.5 mL/kg/hr target), and lactate clearance (aim for 20% reduction). 4, 3

• Perform passive leg raise test to determine fluid responsiveness; if positive (≥10-15% increase in stroke volume or pulse pressure), proceed with additional crystalloid. 4

Step 2: Continue Crystalloid Boluses if Fluid-Responsive

• Administer 250-1000 mL crystalloid boluses (preferably balanced crystalloids like lactated Ringer's or Plasma-Lyte) over 15-30 minutes. 4, 3

• Reassess after each bolus using both clinical endpoints and dynamic measures; continue as long as objective perfusion parameters improve. 4, 3

• Stop fluid administration immediately if signs of volume overload appear: rising jugular venous pressure, new/worsening pulmonary crackles, decreasing SpO₂, or peripheral edema. 4

Step 3: Initiate Vasopressors if Fluid-Refractory

• If mean arterial pressure remains <65 mmHg after adequate crystalloid challenge and PLR is negative, start norepinephrine rather than adding albumin. 2

• The total crystalloid volume may exceed 4 liters in the first 24 hours for septic patients without requiring albumin, as long as fluid responsiveness persists and overload signs are absent. 1, 4

Step 4: Consider Albumin ONLY in Cirrhotic Patients

• Identify if the patient has underlying cirrhosis through history, physical examination (stigmata of chronic liver disease), or laboratory findings (thrombocytopenia, coagulopathy, hypoalbuminemia). 2

• If cirrhosis is present with sepsis-induced hypotension, switch to 5% albumin at 0.5-1.0 g/kg over 3 hours instead of continuing crystalloids. 2, 5

• Monitor closely for pulmonary complications (increased work of breathing, declining SpO₂, new crackles) and discontinue albumin immediately if these develop. 2, 5

Common Pitfalls and Caveats

• Do not use static measures like central venous pressure (CVP) alone to guide fluid therapy, as CVP has <50% positive predictive value for fluid responsiveness and can lead to under-resuscitation. 4

• Avoid albumin in patients with pre-existing heart failure or pulmonary edema, as it increases the risk of worsening fluid overload despite theoretical oncotic benefits. 2, 7

• Do not administer albumin to correct hypoalbuminemia alone in critically ill patients, as serum albumin levels do not correlate with volume status and albumin infusion does not improve outcomes when used for this indication. 1, 2

• Hydroxyethyl starches are absolutely contraindicated in septic shock due to increased mortality and acute kidney injury; they should never be considered as an alternative to albumin. 4, 3

• In elderly patients with known hypertension presenting with "normal" systolic blood pressure <100 mmHg, use smaller bolus volumes (250-500 mL) with more frequent reassessment to avoid fluid overload. 1, 4

• Paradoxical hypotension can occur with rapid albumin infusion, particularly in patients taking ACE inhibitors preoperatively, due to bradykinin generation through pre-kallikrein activator presence. 6

Specific Dosing When Albumin IS Indicated (Cirrhosis Only)

• Calculate dose based on actual body weight: 0.5-1.0 g/kg of 5% albumin solution. 2, 5

• For a 70 kg patient: administer 35-70 grams of albumin, which equals 700-1400 mL of 5% albumin solution. 2, 5

• Infusion rate: deliver over 3 hours to minimize risk of pulmonary complications. 2, 5

• Do not exceed 100 grams per day as the total dose should not surpass the level of albumin found in normal individuals (approximately 2 g/kg body weight). 8

• Monitor for treatment failure: if MAP does not improve to >65 mmHg within 3 hours, initiate vasopressor support rather than administering additional albumin. 2, 5