Sepsis is associated with morbidity and mortality.The presense of hypoalbuminemia is associated with poor outcomes in septic patients. Could administration of albumin be beneficial? Results from trials have not shown any mortality benefits (1-3)
The aims of this study were:
- To assess the feasibility of identifying ED patients with suspected sepsis and hypoperfusion and intervening early
- To determine whether treatment with concentrated albumin affected clinical outcomes.
The Study
Williams J M. Intervention With Concentrated Albumin for Undifferentiated Sepsis in the Emergency Department (ICARUS-ED): A Pilot Randomized Controlled Trial. Ann of Emerg Med. Volume 86, no. 1 : July 2025.
What They Did
This was an investigator-initiated, parallel-group, open-label, randomized controlled, pilot study in a single urban tertiary hospital Emergency Department.
Inclusion criteria were suspected infection and hypoperfusion(SBP < 90mmHg or lactate > 4mmol/L).
Patients were randomized 1:1. All patients were treated with crystalloids, antibiotics and vasopressors. Those patients in the intervention arm received 400 mL IV of 20% albumin over 4 hours (100mL/h). For patients in the control group, treating clinicians were encouraged to avoid albumin use.
20% albumin solution was used in this study. Previous studies have also used 4% and 5% Albumin.
Primary outcome was SBP at 24 hours.
Secondary outcomes included:
- SBP at 6 hours,
- Total fluid therapy (6, 24, and 72 hours),
- Organ dysfunction (24 and 72 hours),
- Organ support requirements (24 and 72 hours, including vasopressor use, invasive ventilation, renal replacement therapy),
- ICU admission,
- Length of stay, and mortality.
N= 464
What They Found
- Median SBP was significantly higher in the intervention group at 6 hours but not at 24 hours
- Those patients in the Intervention arm received less total fluid that was significant at 72 hours;
- The amount of crystalloid used was similar in both study arms,
- Fewer patients in the intervention arm required vasopressor therapies at all timepoints
- Organ dysfunction scores (median total SOFA) were significantly lower in albumin-treated patients at 24 and 72 hours.
- There was no significant difference in mortality
A subgroup analysis on 440 patients found results similar to the primary analysis.
Discussion
This was a single center, open label trial. It tried to answer a very relevant question. It was limited by a small sample size and being conducted in a single medium-sized department. It looked at undifferentiated sepsis
The results don't change our current clinical management. They add to the literature already present, that finds no greater benefit from using albumin above other fluids.
The results although in some cases significant, do not translate to a change in clinical outcome or approach. For example, at 6 hours the SBP in the albumin arm was 108mm Hg(98-122), and 104 mmHg (96-118) in the standard care group. A 4 mm Hg difference in blood pressure, would not trigger a change of management. Less fluid was given at 72 hours in the intervention group, but this was a median of 4275 mL vs 5000mL in the standard group.
The use of vasopressors was found to be reduced in the albumin group, as were the SOFA Sores. but its clinical significance is uncertain, given the short followup time of 72 hours. There was no difference in mortality in this time frame.
It is important to say that it was safe to give with no hypersensitivity reactions to albumin.
References
- Finfer S, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-2256.
- Charpentier J, et al. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study. Intensive Care Med. 2011;37:S115.
- Caironi P, et al; ALBIOS study investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-1421.
