1. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit The SAFE Study Investigators
N Engl J Med 2004: 350:

2. Background
Conflicting results from meta-analyses comparing saline to albumin on survival of critically ill patients exist.
Cochrane Injuries Group Albumin Reviewers’ meta-analysis of 24 studies and 1419 patients suggested albumin increased the absolute risk of death by 6 percent compared to crystalloid.
No adequately powered randomized, controlled trials have examined the effects of fluid choice on the survival of patients in the ICU.
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3. Hypothesis
When 4% albumin is compared to 0.9% sodium chloride for intravascular resuscitation in the ICU there will be no difference in 28 day rate of death from any cause.
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4. Methods 16 ICUs in Australia and New Zealand 6997 patients
3497 received albumin, 3500 received saline
Randomized, blinded
Inclusion criteria
Fluid replacement needed and 4% albumin or 0.9% sodium chloride acceptable
At least one clinical sign of hypovolemia
Exclusion criteria
A/E human albumin, religion, plasmapheresis, cardiac surgery, burns, liver transplantation, < 18 years, brain death, moribund, previous enrollment, previous fluid resuscitation.
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5. Outcome Measures Primary outcome measures Secondary outcome measures
28 day all cause mortality
Secondary outcome measures
28 day survival time
Number of new organ failures
Duration of mechanical ventilation
Duration of renal replacement therapy
Duration of ICU and hospital LOS
Subgroup comparison
Trauma, sepsis, ARDS
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6. Results- Primary and Secondary Outcomes
Outcome Albumin(3473) Saline(3460) RR (95% CI) P value
Status at 28 days: No.(%)
Death (20.9) (21.1) 0.99 (0.91 to 1.09)
Alive in ICU (3.2) (2.5) 1.27 (0.96 to 1.68)
Alive in HOS (22.8) (24.5) 0.93 (0.86 to 1.01)
Outcome Albumin(3473) Saline(3460) AD (95% CI) P value
ICU LOS (d)   (-0.06 to 0.54) 0.44
HOS LOS (d) 15.3  (-0.70 to 0.21) 0.30
Vent days 4.5 ± (-0.08 to 0.47) 0.74
RRT days 0.48  (-0.0 to 0.19)
No difference in 0-5 new organ failures (p=0.85)
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7. Results- New Organ Failures
New organ failure-no. (%) p=0.85*
No (%) Albumin Saline
1 organ (52.7) 1424 (53.3)
2 organs (30.0) 796(29.8)
3 organs (13.9) (13.5)
4 organs (2.6) (2.8)
5 organs (0.1)
*The P value pertains to the comparison between the albumin and saline groups
In the numbers of patients who had no new organ failure of new failure of one,
Two, three, four, or five organs.
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8. Probability of Survival Results
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9. Results- Mortality by Subgroup
Death within 28 days by subgroup: No./total (%)
Albumin Saline RR (95% CI) P value
Trauma 81/596 (13.6) /590 (10.0) (0.99 to 1.86)
Severe Sepsis 185/603 (30.7) /615 (35.3) 0.87 (0.74 to 1.02)
ARDS 24/61 (39.3) /66 (42.4) 0.93 (0.61 to 1.41)
Study had insufficient power to detect small differences in mortality among subgroups.
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10. Relative Risk of Death
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11. Summary
4 percent albumin or normal saline for intravascular volume resuscitation in a heterogeneous population resulted in equivalent rates of death at 28 days.
Mechanical ventilation, ICU and hospital days and renal replacement therapy needs were equivalent.
Findings do not support Cochrane Injuries Group Albumin Reviewers meta-analysis.
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12. Conclusion
“ Our study provides evidence that albumin and saline should be considered clinically equivalent treatments for intravascular volume resuscitation in a heterogeneous population of patients in the ICU. Whether albumin or saline confers benefit in highly select populations of critically ill patients requires further study.”
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