Albumin resuscitation for traumatic brain injury: is intracranial hypertension the cause of increased mortality?

Abstract

Mortality is higher in patients with traumatic brain injury (TBI) resuscitated with albumin compared with saline, but the mechanism for increased mortality is unknown. In patients from the Saline vs. Albumin Fluid Evaluation (SAFE) study with TBI who underwent intracranial pressure (ICP) monitoring, interventional data were collected from randomization to day 14 to determine changes in ICP (primary outcome) and in therapies used to treat increased ICP. Pattern mixture modelling, designed to address informative dropouts, was used to compare temporal changes between the albumin and saline groups, and 321 patients were identified, of whom 164 (51.1%) received albumin and 157 (48.9%) received saline. There was a significant linear increase in mean ICP and significantly more deaths in the albumin group compared with saline when ICP monitoring was discontinued during the first week (1.30±0.33 vs. -0.37±0.36, p=0.0006; and 34.4% vs. 17.4%; p=0.006 respectively), but not when monitoring ceased during the second week (-0.08±0.44 vs. -0.23±0.38, p=0.79; and 18.6% vs. 12.1%; p=0.36 respectively). There were statistically significant differences in the mean total daily doses of morphine (-0.42±0.07 vs. -0.66±0.0, p=0.0009), propofol (-0.45±0.11 vs. -0.76±0.11; p=0.034) and norepinephrine (-0.50±0.07 vs. -0.74±0.07) and in temperature (0.03±0.03 vs. 0.16±0.03; p=0.0014) between the albumin and saline groups when ICP monitoring ceased during the first week. The use of albumin for resuscitation in patients with severe TBI is associated with increased ICP during the first week. This is the most likely mechanism of increased mortality in these patients.

FIG. 1.

Changes in mean±standard error of intracranial pressure from randomization to 14 days post-randomization for entire cohort, without correction for dropouts. Table below study day is number of patients per group for that day.

FIG. 2.

Individual profile plots of patients are presented in light lines, with solid lines for those who died and dashed lines for those who were alive after ICP monitoring was discontinued during the 1st week (top panel) and 2nd week (bottom panel). Pattern-mixture analysis showing temporal changes in unadjusted mean intracranial pressure (ICP) for each group and time period are presented by the heavy line; p value relate to the difference in slopes of mean ICP between albumin and saline groups.