Hypothermia for Traumatic Brain Injury

Source: Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med. 2008;358(23):2447–2456; doi:10.1056/NEJMoa0706930Canadian investigators performed a randomized trial between 1999 and 2004 to determine if elective hypothermia is better than normothermia (37.0° C) at preventing adverse outcomes in children with severe traumatic brain injury (TBI).Children aged 1–17 years with a Glasgow Coma Scale (GCS) of ≤ 8 were enrolled. Patients randomized to hypothermia were cooled with surface cooling techniques until they had esophageal temperatures of 32.5° ± 0.5°C for 24 hours.After rewarming those in the hypothermia group (at a rate of 0.5°C every two hours), and beginning immediately for the normothermia group, core temperature was maintained at 37.0° ± 0.5°C until intracranial hypertension resolved.The primary outcome was an unfavorable outcome defined as severe disability, a persistent vegetative state, or death within six months. The six-point Pediatric Cerebral Performance Category Scale was utilized to assess the level of neurologic function.1A total of 225 children were enrolled; mean age was 10 years and 70% were male. The mean time to initiation of cooling was 6.3 hours after injury and the mean time to attainment of target temperature was 3.9 hours after cooling began. Patients in the treatment groups were similar in age, GCS score, presence of hypotension or hypoxia at the time of intensive care unit (ICU) admission, cranial computed tomography finding, and other organ injuries.During the following three days after the injury, the hypothermia group had significantly lower cerebral perfusion pressure (61 vs 66 mmHg), increased need for vasoactive infusions (85% vs 56%), and more episodes of hypotension (45% vs 32%). Hospital mortality was 21% in the hypothermia group and 22% in the normothermia group. Length of hospital stay was similar in both groups. At six months, there was no statistically significant difference in unfavorable outcomes (31% in the hypothermia group vs 22% in the normothermic group, P=.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (P=.06). The authors concluded that moderate hypothermia for 24 hours was not effective in treating children with severe TBI.Dr. Zebrack has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.In animal models TBI hypothermia has been beneficial,2,3 but results in human studies have been equivocal. Four recent systematic reviews of therapeutic hypothermia in adults illustrate the complexity of the issue, with two reporting no benefit4,5 and two suggesting some benefit.6,7One of the reviews, a 2008 evidence report performed to update guidelines from the Brain Trauma Foundation/American Association of Neurological Surgeons Task Force, led to a recommendation for optional and cautious use of hypothermia in adults with severe TBI.7Given the differing conclusions regarding the use of therapeutic hypothermia in adults, the current study on pediatric patients is timely. The trial was well designed and extraordinary in its scope – involving 17 centers in three countries. Therapeutic hypothermia initiated within eight hours of injury and maintained for 24 hours did not improve functional outcome at six months. It is important to note that some brain-injured children were excluded, such as patients with refractory shock, suspected brain death, nonaccidental injury, or high cervical spinal cord injury.The authors point out that hypothermia initiated earlier and/or maintained for a longer period may be more effective. It is unclear whether hypotension, increased need for vasoactive infusion, and lower cerebral perfusion pressure noted after 24 hours in the hypothermia group could be diminished by slower rewarming or less extreme hypothermia. Further research is underway.For asphyxiated neonates hypothermia appears to be beneficial (see AAP Grand Rounds, January 2008;19:3–48) so it seems premature to give a cold shoulder to hypothermia for older children with TBI, although we do not yet know which patients are most likely to benefit nor how best to use the technique.

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