Therapeutic Moderate Hypothermia for Severe Traumatic Brain Injury

Use of therapeutic hypothermia to treat patients with severe traumatic brain injury was described more than 50 years ago. Unexpected improvement in some of these patients was attributed to hypothermia, but none of the early studies systematically evaluated the efficacy of hypothermia, and many patients were thought to have been harmed by the treatment, particularly when cooled below 30°C or when cooled for longer than 48 hours. Recent investigations have found that therapeutic moderate hypothermia (32–34°C) for relatively brief durations can improve histological and behavioral outcome following experimental brain injury. Cooling to this degree and duration has not been implicated as a cause for the cardiac arrhythmias, coagulation abnormalities, or infections attributed to hypothermia in the earlier studies. These laboratory investigations also defined several neurochemical mechanisms through which hypothermia may limit secondary brain injury and brain swelling. Four clinical trials of therapeutic moderate hypothermia were completed during the past three years; each detected a beneficial effect from cooling patients with severe traumatic brain injury to 32 to 34°C for up to 48 hours. In the largest of these studies, therapeutic moderate hypothermia was shown to cause a significant improvement in neurological outcomes 3, 6, and 12 months after injury for those patients with an initial Glasgow Coma Scale score of 5 to 7. The improvement in outcome for these patients was associated with a hypothermia-induced reduction of intracranial pressure and cerebrospinal fluid levels of interleukln-1β and glutamate.