SAFE: A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit

The SAFE Study Investigators. N Engl J Med 2004; 351:1905-1908.

Clinical Question

• Does fluid resuscitation with albumin, compared to saline, affect mortality for patients in the ICU?

Design

• Randomised controlled trial
• Stratified by centre and according to whether there was a diagnosis of trauma
• Double Blinded

Setting

• 16 ICUs in Australasia
• November 2001 – June 2003

Population

• Adult patients admitted to academic tertiary ICUs who were judged to require fluid administration to maintain or increase intravascular volume
• Excluded post-op cardiac surgery, liver transplantation, burns
• 6997 patients randomised

Intervention

• Resuscitation with 4% albumin

Control

• Resuscitation with 0.9% sodium chloride

Outcome

• Comparing 4% albumin to 0.9% sodium chloride
  • Primary outcome: all cause mortality at 28-days
    • 20.9% vs. 21.1%, Relative risk of death 0.99 (95% C.I. 0.91-1.09, P=0.87)
  • Secondary outcomes
    • There was no difference in length of ICU stay, duration of mechanical ventilation or renal replacement therapy
    • Mortality at 28 days in patients with severe sepsis
      • 30.7% vs 35.3% (RR 0.87, 95% C.I. 0.74 – 1.02), P=0.09
    • Mortality at 28 days in patients with trauma
      • 13.6% vs. 10% (RR 1.36, 95% C.I 0.99 – 1.86), P=0.06
  • Post-hoc analysis: mortality at 28 days in patients with brain injury
    • 24.5% vs. 15.1% (RR 1.62, 95% C.I 1.12-2.34), P=0.009

Authors’ Conclusion

• Use of 4% albumin or 0.9% sodium chloride for fluid resuscitation results in similar  outcomes at 28 days

Strengths

• Multi-centre
• Large number of patients included – a huge trial which demonstrates the importance of collaborative research
• Double blinded – specifically designed fluid containers and administration sets were used
• Robustly defended the short term safety profile of 4% albumin after concerns were raised by the Cochrane Injuries Group Albumin Reviewers

Weaknesses

• Minimal weaknesses. This was a great trial. The authors note that the sub-group analyses had insufficient power.