In an adult with sepsis who remains hypotensive after receiving at least 30 mL/kg of balanced crystalloid, when and how should 20% human albumin be used to maintain mean arterial pressure?

Albumin Use to Maintain MAP in Septic Shock

Add 20% human albumin only after the patient has received at least 30 mL/kg of balanced crystalloid and remains hypotensive (MAP < 65 mmHg), using it as an adjunct to ongoing crystalloid resuscitation rather than as first-line therapy or as a treatment for low albumin levels. 1

Initial Crystalloid Resuscitation Must Come First

• Administer at least 30 mL/kg of balanced crystalloid (or normal saline) within the first 3 hours as the primary resuscitation fluid for all adult patients with sepsis-induced hypotension 2, 1
• Continue 250–500 mL crystalloid boluses while monitoring hemodynamic parameters (MAP, heart rate, mental status, urine output, peripheral perfusion) and stop when no further improvement is observed 1
• Crystalloids remain the fluid of choice; albumin should never be used as first-line resuscitation 1, 3

When to Add Albumin

Consider adding 20% albumin only when large volumes of crystalloid are required to maintain an adequate MAP (this is a weak recommendation, 2C evidence). 2, 1

The Surviving Sepsis Campaign positions albumin as an adjunct to high-volume crystalloid resuscitation, not as a treatment for hypoalbuminemia itself. 1 A meta-analysis of 7 trials (n=1441) showed reduced mortality when albumin was added to crystalloids (OR 0.78,95% CI 0.62–0.99), but this benefit emerged only in the context of substantial crystalloid administration. 2

Practical Dosing Protocol

• Use 20% albumin at 20 g every 8 hours for 3 days when indicated for persistent hypotension despite adequate crystalloid resuscitation 2
• Alternatively, use 4–5% albumin solution for volume expansion, as this concentration provides volume expansion without excessive oncotic pull 3
• The typical approach involves adding albumin when crystalloid requirements exceed 30–50 mL/kg and hemodynamic instability persists 3

Critical Contraindications and Warnings

An isolated serum albumin concentration of ≈2.3 g/dL is NOT an indication for albumin infusion in septic patients. 1 Low albumin reflects the severity of systemic inflammation (negative acute-phase reactant) rather than a correctable deficiency. 3

The German Society of Hematology and Oncology explicitly states that human albumin should not be used in sepsis because meta-analyses showed no favorable outcome even in patients with hypoalbuminemia. 3 Routine administration to "correct" low serum levels does not improve outcomes and may increase the risk of pulmonary edema and fluid overload (OR 5.17,95% CI 1.62–16.47) in cirrhotic patients with infection. 3

Vasopressor Initiation Takes Priority

If MAP remains < 65 mmHg after adequate fluid resuscitation, initiate norepinephrine as the first-line vasopressor (strong recommendation, 1B evidence) rather than continuing to escalate fluid administration. 2, 1 The titration of norepinephrine to a MAP of 65 mmHg has been shown to preserve tissue perfusion. 2

• Add vasopressin (0.03 U/min) to norepinephrine when additional MAP support is needed or to allow a lower norepinephrine dose 1
• Epinephrine may be used as a second-line agent if further pressor support is required 1

Special Population: Cirrhosis with Septic Shock

In cirrhotic patients with sepsis-induced hypotension, 5% albumin is preferred for initial resuscitation because it more effectively reverses hypotension (22% vs 62% requiring vasopressors at 3 hours; P < 0.001). 3

Recommended dosing for this subgroup is 0.5–1.0 g/kg administered over 3 hours. 3

Hemodynamic Monitoring to Guide Therapy

• Use dynamic variables such as pulse pressure variation or stroke volume variation to assess fluid responsiveness and guide ongoing therapy (diagnostic OR 59.86,95% CI 23.88–150.05 for pulse pressure variation) 2, 1
• Continue fluid administration as long as there is hemodynamic improvement based on either dynamic or static variables (arterial pressure, heart rate) 2, 1
• These dynamic techniques generally require sedation and are limited in the presence of atrial fibrillation or spontaneous breathing 2

Critical Pitfalls to Avoid

• Do not delay crystalloid resuscitation to give albumin first; crystalloids should always precede albumin 1
• Do not use albumin level as a transfusion trigger; albumin is indicated only when large crystalloid volumes fail to maintain MAP 1
• Avoid hydroxyethyl starch solutions completely, as they increase the risk of acute kidney injury (RR 1.60,95% CI 1.26–2.04) and mortality 2, 3
• Do not treat uncorrected total calcium values in hypoalbuminemic patients; obtain ionized calcium when symptomatic hypocalcemia is suspected 1

Clinical Context from Recent Data

Recent observational data from the CLASSIC trial showed that gastrointestinal focus of infection and higher doses of norepinephrine at baseline were most strongly associated with albumin use (HR 2.58,95% CI 1.89–3.53 for highest quartile of norepinephrine doses), suggesting clinicians reserve albumin for patients with more severe shock. 4