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Trauma therapy on ice Cooling the body after brain is beneficial in animal models of . But such ‘hypothermia therapy’ does not work in children, according to the results of a clinical trial of 225 subjects with brain injury. James Hutchison et al.1 found that, six months after injury, 31 percent of the children who received hypothermia therapy suffered from unfavorable outcomes, compared with 22 percent who did not receive the therapy; children receiving the therapy were also more likely to die. We asked three experts their views on this unexpected outcome.

The fundamental biology underlying hypothermic therapy for preventing neuronal “injury is sound. —EHL Tadeusz Wieloch: The main problem in the new study is the delay—a mean of “ about six hours—before treatment. All available experimental data show that the therapeutic time window of hypothermia treatment after experimental traumatic brain injury is less than one hour. Hypothermia may depress and repair, thereby aggravating damage, particularly in children with mul- tiple body traumas. Faster cooling to 34 °C for a shorter period,

http://www.nature.com/naturemedicine 6–12 hours, should be considered in future trials, though more preclinical research is needed. A similar lesson also applies to impending hypothermia trials in stroke patients: initiate hypo- thermia fast, in the pre-hospital setting. Professor of Neurobiology, Wallenberg Neuroscience Center, Lund, Sweden

Eng H. Lo: The fundamental cell biology underlying hypothermic therapy Nature Publishing Group Group Nature Publishing

8 for preventing neuronal injury is sound. But this trial reminds us how difficult it is to translate promising experimental ideas 200 into meaningful clinical results. As the authors point out, several ©

questions remain. Would initiating hypothermia more quickly LIBRARY PHOTO SCIENCE / KULYK MEHAU help? Would outcomes be improved if brain temperature were kept down for longer periods of time? An emerging notion from animal models is that the rate of rewarming is critical, but find- Costantino Iadecola: ing the optimal rewarming protocol for people will not be easy. The study suggests that hypothermia was effective in reducing More broadly, this study may point to mechanistic differences brain swelling and maintaining flow of into the brain between brain trauma and -, wherein hypo- during the cooling phase. This benefit, however, was lost dur- thermia appears to be beneficial (it protects patients with car- ing rewarming, when lowered blood pressure reduced cere- diac arrest, for instance, from brain injury). As new hypothermia bral and, presumably, exacerbated brain damage, trials may be planned, it should also be useful to keep in mind leading to a worse outcome. Hypothermia could be effective that the response to brain injury in adult versus younger brains in reducing brain swelling in traumatic brain injury, but the might be extremely different. complications associated with rewarming need to be better Professor, Neuroprotection Research Laboratory, Massachusetts understood and more effectively managed. General Hospital, Harvard Medical School, Charlestown, Chief, Division of Neurobiology, Weill Cornell Medical College, Massachusetts, USA New York, USA

1Hutchison, J. et al. Hypothermia therapy after traumatic brain injury in children. N. Engl. J. Med. 258, 2447–2456, 2008.

nature medicine volume 14 | number 7 | july 2008 717