Key Point:

A large, randomized, double-blind clinical trial has shown that albumin and saline have the same safety and efficacy for fluid resuscitation in most critically ill patients. Only those with traumatic brain injury fared worse with albumin.

ORLANDO, FLA—Whether albumin or saline is the preferred resuscitation fluid for critically ill patients has long been debated. Advocates of albumin point to saline’s tendency to extravasate across the endothelium as a potential danger; saline proponents have argued, among other things, that the colloid’s cost is too high.

Even meta-analyses have been unable to resolve the debate. In 1998, a Cochrane analysis compared albumin with other fluid resuscitation methods.[1] After analyzing 24 randomized controlled trials, the authors concluded that albumin does not reduce mortality and, in some cases, may increase it. They therefore recommended that albumin not be used outside of clinical trials.

In response to these findings, Wilkes and Navickis performed a meta-analysis of 55 trials.[2] Although their data set included many of the same trials that the Cochrane group used, Wilkes and Navickis found that albumin had no significant effect on mortality. They stated that their findings supported albumin’s safety but added the caveat that well-designed clinical trials were needed.

Recently, a group of Australian and New Zealand researchers decided to take on the challenge of the colloid/crystalloid debate by conducting a randomized, controlled, double-blind trial comparing albumin and saline in almost 7,000 critically ill patients. At the 33rd Annual Congress of the Society of Critical Care Medicine (SCCM), Simon Finfer, MD, Senior Staff Specialist in Intensive Care at Royal North Shore Hospital in Sydney, Australia, and Chair of the Australian and New Zealand Intensive Care Society (ANZIC) Clinical Trials Group, presented preliminary findings from this trial—the Saline versus Albumin Fluid Evaluation (SAFE) study—which may finally resolve the debate over the safety of albumin.[3] The SAFE study found that:
•Albumin and saline are clinically equivalent.
•The only increase in mortality with albumin occurred in patients with traumatic brain injury.

SAFE

The SAFE study was undertaken by ANZIC in collaboration with the Institute for International Health of the University of Sydney and the Australian Red Cross Blood Service, which provides albumin free of charge to hospitals in Australia. The study took place at 16 ICUs in Australia and New Zealand over a period of 18 months. All study patients needed intravascular fluid resuscitation at the time of ICU admission. At enrollment, three subgroups were identified: patients admitted to the ICU with trauma, patients with sepsis, and those with ARDS.

The patients were randomized to receive fluid resuscitation with 4% albumin or 0.9% saline solution. The amount and rate of fluid administration was left to the discretion of the treating clinician; however, the study equipment was carefully designed so that the ICU staff could not tell which fluid was being given. Study treatments were continued until patient discharge or death, or until 28 days after initial randomization.

The primary end point was 28-day all-cause mortality. Secondary outcomes included survival time, proportion of new organ failures, duration of mechanical ventilation or renal replacement therapy, and length of hospital and ICU stay.

There were 3,473 evaluable patients in the albumin group and 3,460 in the saline group. Both groups were well matched for baseline characteristics and APACHE II scores.

NO SIGNIFICANT DIFFERENCES

During the first four days of treatment, patients in the albumin group received less fluid than did patients in the saline group; however, the difference was not as great as had been expected: The ratio of albumin to saline was 1:1.38 liters. Also during the first four days, patients in the albumin group received more packed red blood cells (a mean of 79 mL more per patient) than did those in the saline group. The net daily positive fluid balance for this period was greater in the saline group than in the albumin group by about 1 liter.

Mean arterial pressure, heart rate, and central venous pressure did not differ significantly between groups throughout the study.

There were 726 deaths in the albumin group and 729 deaths in the saline group. Thus, the 28-day mortality rate was almost identical: 20.9% versus 21.1%.

No significant differences in outcome were noted when the three subgroups of patients were analyzed separately. However, when patients with traumatic brain injury were separated from the rest of the trauma group, there were 21 more deaths in patients given albumin than in those given saline. There was no treatment difference in trauma patients without brain injury.

Furthermore, there were no between-group differences in any of the secondary outcomes.

“We conducted a randomized controlled trial to compare the effects of two resuscitation fluids on 28-day all-cause mortality in critically ill patients requiring intravascular volume resuscitation,” reported Dr. Finfer at the SCCM meeting. “This is the question that our study was designed to answer and powered to answer. Our conclusion is that in this population of patients, in this setting, albumin and saline are clinically equivalent treatments.”

—Gale Jurasek

References
1. Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ. 1998;317:235-240.
2. Wilkes MM, Navickis RJ. Patient survival after human albumin administration: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2001;135:149-164.
3. Finfer S. Does albumin kill? Results of a randomized control of 7,000 patients. Presented at: 33rd Critical Care Congress; February 22, 2004; Orlando, Fla.

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