"Albumin Replacement in Patients with Severe Sepsis or Septic Shock". The New England Journal of Medicine. 2014.

Clinical Question

Does albumin replacement improve survival compared with crystalloid solutions alone in patients with severe sepsis or septic shock?

Bottom Line

In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, does not improve the rate of survival at 28 and 90 days.

Major Points

Albumin has been used for decades to maintain oncotic pressure and intravascular volume. While albumin administration was suggested to potentially offer benefits over crystalloids, this study demonstrated no survival benefit at 28 or 90 days for albumin replacement to achieve hypoalbuminemia correction. Beneficial effects such as increased mean arterial pressure and decreased net fluid balance were observed in the albumin group.

Guidelines

As of the last update, current clinical guidelines do not provide specific recommendations regarding the preference for albumin over crystalloids for fluid resuscitation in patients with severe sepsis or septic shock.

Design

Multicenter, open-label, randomized, controlled trial comparing 20% albumin and crystalloid solution vs. crystalloid solution alone.
N=1,818 patients with severe sepsis in ICU.
Randomization: Albumin + crystalloid group (n=908) vs. Crystalloid group (n=910).

Population

Inclusion Criteria: Patients ≥18 years with severe sepsis within the past 24 hours at ICU.
Exclusion Criteria: N/A; details provided in the Supplementary Appendix.

Interventions

Albumin group received 20% albumin to maintain serum albumin ≥30 g/L until ICU discharge or day 28.
Crystalloid group received crystalloid solutions as clinically indicated.
Synthetic colloids were not allowed.

Outcomes

Primary Outcome: Death from any cause at 28 days.
Secondary Outcomes: Death from any cause at 90 days, organ dysfunction, and length of stay in ICU and hospital.

Major Points

No significant difference in 28-day mortality (Albumin 31.8% vs. Crystalloid 32.0%; RR 1.00).
No significant difference in 90-day mortality (Albumin 41.1% vs. Crystalloid 43.6%; RR 0.94).
No significant differences in secondary outcomes.
Post hoc analysis indicated potential benefit for the subset of patients with septic shock.

Criticisms

Variations in albumin doses (20% vs. 4% in previous studies) may have influenced fluid administration volume and outcomes.
Lower than expected mortality rate may have resulted in underpowered study.
One-third of the population was enrolled during the early phase of severe sepsis.

Funding

Italian Medicines Agency.

Further Reading

Additional details about the study, including participating ICU sites and secondary outcome measures, can be found at ClinicalTrials.gov number, NCT00707122, and the Supplementary Appendix available with the full text of the article at NEJM.org.