Moderate systemic
hypothermia has been shown to improve neurologic outcomes in both fluid-percussion and
cortical contusion models of experimental
brain injury. Based upon initial clinical work, it was concluded that at temperatures < 32 degrees C, patients with severe
brain injury were at increased risk of ventricular arrhythmias, and that rapid
rewarming immediately postinjury predisposed to intracranial pressure increases. Subsequent clinical studies of moderate
hypothermia (32 degrees C) for 24- to 48-hr duration with slow
rewarming in human
brain injury showed indications of neurologic improvement and a low incidence of
hypothermia-related complications. Based upon the strengths of both laboratory and clinical data, a multicenter (nine centers), randomized, prospective trial testing moderate systemic
hypothermia in patients with severe
brain injury has been organized. This trial, funded by National Institutes of Health, National Institute of Neurological Disorders and Stroke, began on October 20, 1994. Five hundred patients are to be treated in an intent-to-treat protocol using standard management at normothermia versus standard management at
hypothermia. The trial is designed to detect an absolute shift of 12% in the percentage of patients achieving satisfactory outcome (good recovery/moderate disability) at a power of 85% at 6 months postinjury. The efficacy of hyperbaric
oxygen administered every 8 hrs for 1-hr duration for a 2-wk period has also been tested in patients after severe
brain injury. While the mortality rate was reduced in the treated group, the percentage of favorable outcomes was unchanged. Further studies are in progress.