Mortality Advantage for Saline Resuscitation After Brain Trauma

SYDNEY, Australia, Aug. 29 -- Acute restoration of fluid volume for patients with severe traumatic brain injury should be done with saline rather than albumin, researchers said.

The mortality rate at two years was 63% lower among head trauma patients resuscitated with saline rather than albumin (P=0.003), revealed an analysis of the Saline versus Albumin Fluid Evaluation (SAFE) study

The advantage was even greater for those with severe brain trauma (relative risk 1.88, P<0.001), reported John Myburgh, M.D., Ph.D., of the George Institute for International Health, and colleagues, in the Aug. 30 issue of the New England Journal of Medicine.

Saline and other crystalloid-based fluids have been favored in trauma-resuscitation protocols, but evidence to guide selection of a resuscitation fluid for brain injury patients has been limited, they wrote. The SAFE study compared 4% albumin and normal saline in a heterogeneous population of patients in 16 intensive care units. Overall, the study showed no difference in the risk of death.

But because there did appear to be a substantial mortality difference among trauma patients, the researchers decided to look further into the subgroup that was powering this difference--traumatic brain injury patients.

Their post hoc study included all patients with head trauma evidence on CT and a score of less than 13 on the Glasgow Coma Scale from the main SAFE study as well as other eligible head injury patients admitted to the participating hospitals.

Researchers blinded to treatment collected data from case-report forms, clinical records, and CT scans and determined vital status and functional neurologic outcomes for the 24 months after randomization. Most of the data were collected prospectively.

Of the 460 patients, 50.2% were randomized to receive albumin and 49.8% to receive saline. The groups had similar baseline characteristics, injury-severity scores, and pre-randomization hypotension and intracranial hypertension rates.

At 24 months, mortality rates significantly favored saline over albumin (20.4% versus 33.2%). The overall relative risk of death was 63% higher in the albumin group (95% confidence interval 1.17 to 2.26, P=0.003).

Most of the deaths were early (within 28 days), caused by traumatic brain injury, and occurred in the ICU.

A larger advantage for saline resuscitation was seen among patients with severe traumatic brain injury. The 24-month mortality rate was 41.8% in the albumin group compared with 22.2% in the saline group (RR 1.88, 95% CI 1.31 to 2.70, P<0.001). There was no difference for those with only moderate traumatic brain injury (P=0.50).

Controlling for baseline factors increased the 24-month mortality advantage for saline slightly overall (odds ratio 1.70, 95% CI 1.03 to 2.83, P=0.04) and more substantially for severe traumatic brain injury patients (OR 2.38, 95% CI 1.33 to 4.26, P=0.003).

As expected from the mortality rate, favorable neurologic outcomes were less frequent in the albumin group at 24 months compared with the saline group (47.3% versus 60.6%, P=0.007). Functional outcomes among survivors were similar between groups (RR 0.95, 95% CI 0.83 to 1.08, P=0.41).

Although the study provides evidence to guide physicians in choosing a resuscitation fluid for traumatic brain injury patients, "the biologic mechanisms for the observed differences in mortality are unclear," the investigators said.

No differences in hemodynamic-resuscitation end points or cause or time of death were seen to explain the results.

The researchers suggested that a mechanism might be that albumin exacerbates vasogenic or cytotoxic cerebral edema. But, further study is needed to analyze this possible mechanism, they said.