Selective Hypothermia in the Management of Traumatic Brain Injury

Eisha Christian, B.A.; Gabriel Zada, M.D.; Gene Sung, M.D.; Steven L. Giannotta, M.D.


Neurosurg Focus. 2008;25(4):E9 

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Although a large multicenter RCT by Clifton et al.[8] did not demonstrate an overall benefit of hypothermia in severe TBI, subsequent clinical trial data have suggested that systemic methods of inducing hypothermia provide effective control of ICP and cerebral perfusion pressure, as well as improvements in neurological outcome.[15] Several meta-analyses have attempted to reconcile the results from more than 25 clinical studies in which systemic hypothermia was assessed over the past 2 decades.[24,28,31] McIntyre and colleagues[28] published a systematic review of 12 trials on therapeutic hypothermia with results demonstrating an overall beneficial effect of moderate hypothermia (32-33°C) in severe TBI. They reported a 19% relative reduction in deaths and a 22% relative reduction in poor neurological outcomes in comparison with normothermia. The review indicated that therapy should be conducted for at least 24 hours, with temperatures ranging between 32° and 33°C and a rewarming period of < 24 hours. Peterson and associates[31] conducted a systematic review and meta-analysis and concluded that there was a significant reduction in deaths in the hypothermia group, although outcomes were influenced by variations in the induction method. It is likely that systemic hypothermia confers some neuroprotective effect, yet its benefits are potentially offset by the added risks incurred in patients with polytrauma. For instance, the relative risk of pneumonia associated with hypothermia according to one meta-analysis was 2.37 (95% confidence interval 1.37-4.10).[20] In another study, authors reported an increased rate of thrombocytopenia following hypothermic management, with associated unfavorable neurological outcomes.[34]

In response to the systemic risks revealed by these studies, investigators have recently pursued more selective methods of brain cooling. The same principles that have been shown to increase the efficacy of systemic hypothermia are maintained for regional methods as well. For instance, authors of prior studies have determined that hypothermic interventions following longer delays are less efficacious.[5,9,11,27] Moreover, prolonged treatment with hypothermia (12-48 hours) showed longer lasting neuroprotective benefits than shorter periods of therapy.[10,11,12] Another important principle established by previous authors is that brain temperature should be maintained at ≤ 34°C for the duration of therapy.[18,37] These guidelines suggest that the extent and duration of cooling, as well as the induction time, are likely to affect outcomes and should play a central role in guiding the development and research of regional hypothermic methods. Furthermore, in the case of selective hypothermia, maintaining the brain-body gradient is of paramount importance.

Proponents of the cooling helmet point to the feasibility of its use by emergency personnel in the field, yet outcome benefits and costs associated with this therapy still need to be analyzed.[41] Based on the limited studies available, the intranasal method can be used to reach the target hypothermic zone in less time than the helmet (15 minutes vs 3.4 hours).[41,44] Potential concerns regarding the uneven distribution of cooling of various brain regions have been reported in association with some regional methods, including surface, epidural, and intranasal cooling.[6,23] On the other hand, endovascular cooling and extraluminal cuffs have been shown to provide uniform cooling of the brain.[42]


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