Credit: MEHAU KULYK / SCIENCE PHOTO LIBRARY

Cooling the body after brain injury is beneficial in animal models of traumatic brain injury. 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.

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 wound healing and repair, thereby aggravating damage, particularly in children with multiple body traumas. Faster cooling to 34 °C for a shorter period, 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 hypothermia fast, in the pre-hospital setting.

Professor of Neurobiology, Wallenberg Neuroscience Center, Lund, Sweden

Eng H. Lo:

The fundamental cell biology underlying hypothermic therapy for preventing neuronal injury is sound. But this trial reminds us how difficult it is to translate promising experimental ideas into meaningful clinical results. As the authors point out, several questions remain. Would initiating hypothermia more quickly 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 finding the optimal rewarming protocol for people will not be easy. More broadly, this study may point to mechanistic differences between brain trauma and hypoxia-ischemia, wherein hypothermia appears to be beneficial (it protects patients with cardiac arrest, for instance, from brain injury). As new hypothermia trials may be planned, it should also be useful to keep in mind that the response to brain injury in adult versus younger brains might be extremely different.

Professor, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

Costantino Iadecola:

The study suggests that hypothermia was effective in reducing brain swelling and maintaining flow of blood into the brain during the cooling phase. This benefit, however, was lost during rewarming, when lowered blood pressure reduced cerebral perfusion and, presumably, exacerbated brain damage, leading to a worse outcome. Hypothermia could be effective in reducing brain swelling in traumatic brain injury, but the complications associated with rewarming need to be better understood and more effectively managed.

Chief, Division of Neurobiology, Weill Cornell Medical College, New York, USA