Moderate hypothermia in the management of severe traumatic brain injury: a good idea proved ineffective?
Many drugs with proven efficacy in the preclinical stage have failed to show any benefit in improving the outcome of severe traumatic brain injury (TBI) when tested in controlled clinical trials. Hypothermia is still the most powerful neuroprotective method in experimental models of TBI. Its ability to influence the multiple biochemical cascades that are set in motion after TBI is quite unique. In experimental models hypothermia protects against mechanical neuronal and axonal injury and improves behavioral outcome. Encouraging results from phase II and III clinical trials of hypothermia in TBI reported in the 1990s generated great enthusiasm. However, enthusiasm faded in 2001 after the final report of the multicenter phase III trial in which the neuroprotective effects of moderate hypothermia in TBI were formally tested. This study found no significant effect on outcome in the hypothermia group, leading many clinicians to lose interest in this therapy. The present article reviews the historical background of the use of hypothermia, presents the rationale for using both immediate and deferred hypothermia, and summarizes both experimental and clinical evidence supporting its potential benefits in the management of severe TBI. New technologies using intravascular methods to induce fast hypothermia have recently become available. Cooling either through the intravenous or intra-arterial route is an exciting alternative with great potential. We argue that moderate hypothermia is still the most powerful neuroprotective candidate for severe TBI and that it merits further research and discussion. We also defend the need for further clinical trials to prove or refute its potential for treating high intracranial pressure refractory to first level therapeutic measures. The premature abandonment of hypothermia could close new avenues for improving the devastating effects of TBI.
Departmrnt of Neurosurgery, Vall d'Hebron University Hospital, 08023 Barcelona, Spain. sahuquillo@homemail.com
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Sahuquillo
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Mena
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Vilalta
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Poca
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019468:Disease Management; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods* / Q000639:trends; D013997:Time Factors