The SAFE trial: Normal saline vs. albumin for fluid resuscitation [Classics Series]

1. There was no significant difference in 28-day mortality when comparing albumin and normal saline for fluid resuscitation in the intensive care setting.

2. Compared to normal saline, fluid resuscitation with albumin did not yield any significant benefits in terms of secondary outcomes (i.e., length of ICU/hospital stay, duration of supportive treatment measures).

Original Date of Publication: May 27, 2004

Study Rundown: In various types of shock, resuscitation with intravenous fluids helps to maintain circulating pressure and tissue perfusion. A myriad of options are available for fluid resuscitation, including blood products, non-blood products, or combinations of these. Crystalloid and colloid solutions are two classes of fluids that may be used. Crystalloid solutions are composed of sterile water and electrolytes, in concentrations that are similar to human serum. Colloids contain an additional colloidal substance (e.g., albumin, dextran) that does not cross semipermeable membranes. As a result, colloids are better at maintaining intravascular volume. While studies have demonstrated that crystalloids and colloids have different effects on physiological measures, it remains uncertain whether one is more beneficial in reducing mortality. It is an important consideration because colloid solutions are far more expensive than crystalloids. Moreover, previous systematic reviews have reached conflicting conclusions, with one suggesting albumin-containing solutions were linked with increased mortality and another suggesting there was no significant difference when compared to crystalloids.

The Saline versus Albumin Fluid Evaluation (SAFE) trial was a randomized, controlled trial designed to explore whether the use of 4 percent albumin led to any significant difference in mortality when compared with 0.9% sodium chloride (i.e., normal saline) in intensive care settings. In summary, there was no difference between the two groups in 28-day mortality (RR 0.99; 95%CI 0.91-1.09). Moreover, there were no differences between the two groups in length of ICU/hospital stay, duration of mechanical ventilation, or duration of renal replacement therapy.

Click to read the study in NEJM

In-Depth [randomized, controlled study]: The study was conducted in 16 tertiary intensive care units in Australia and New Zealand. Patients were eligible if they were ≥18 years of age, were admitted to intensive care, and required fluid administration. Patients were excluded if they were admitted after cardiac surgery, liver transplantation, or for burns treatment. A total of 6,997 patients were randomized to receive either 4 percent albumin or normal saline. Study fluids were provided in identical 500 mL bottles. The primary outcome measure was death from any cause in the first 28 days after randomization, while secondary outcomes included the duration of mechanical ventilation, the duration of renal replacement therapy, and the duration of ICU/hospital stay.

There was no significant difference between the albumin and saline groups in 28-day mortality (RR 0.99; 95%CI 0.91-1.09). Moreover, there were no significant differences between the two groups in terms of length of ICU stay (p=0.44), length of hospital stay (p=0.30), duration of mechanical ventilation (p=0.74), or duration of renal replacement therapy (p=0.41).

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