Intervention With Concentrated Albumin for Undifferentiated Sepsis in the Emergency Department (ICARUS-ED): A Pilot Randomized Controlled Trial.

Summary

In a 464-patient pilot RCT of ED patients with suspected sepsis and hypoperfusion, early 20% albumin (400 mL over 4 hours) was feasible and safe but did not improve 24-hour SBP versus standard care. Albumin reduced total fluids, vasopressor requirements at 24/72 hours, and improved organ dysfunction, without a mortality difference.

Key Findings

• 24-hour systolic blood pressure was similar between albumin and standard care arms (110.5 vs 110 mmHg).
• At 6 hours, SBP was higher with albumin; total infused fluid at 72 hours was lower.
• Fewer patients required vasopressors at 24 and 72 hours in the albumin arm; organ dysfunction improved.
• No significant difference in mortality between groups.
• Protocol compliance exceeded 95%, and infection was confirmed in 95% of enrolled patients.

Clinical Implications

Early concentrated albumin may reduce fluid burden and vasopressor exposure while not worsening hemodynamics, supporting consideration of albumin in selected ED sepsis patients and the need for stratified, multicenter trials.

Limitations

• Primary endpoint (24-hour SBP) negative; mortality unchanged.
• Likely unblinded and single health system; co-interventions at clinician discretion may introduce variability.

Future Directions

Conduct adequately powered multicenter RCTs with patient-centered outcomes (mortality, ventilator/vasopressor-free days), stratifying by shock severity, baseline albumin, and fluid responsiveness.