Moderate hypothermia in traumatic brain injury: results of clinical trials [Ipotermia moderata nel danno cerebrale traumatico: I risultati dei trial clinici]

The concept of 'neuroprotection' by hypothermia dates back to ancient times. This paper reviews the results of clinical trials using mild hypothermia (32-35°C) in patients with severe traumatic brain injury over the past decade. Induced hypothermia has been used in experimental models mostly to prevent or attenuate secondary neurological injury and has been used to provide neuroprotection in traumatic brain injury, both in animal models and clinical trials. Results from animal experiments largely confirm that hypothermia can provide protection for the injured brain; however, the results from clinical trials and from a number of meta-analyses have been conflicting. This paper reviews the evidence and explores possible reasons for the mixed results from clinical trials. Hypothermia is clearly effective in controlling intracranial hypertension. Early favourable results on neurological outcome and mortality were not confirmed in a subsequent multi-center trial. Subsequently, single-centre studies, with quicker induction of hypothermia and longer duration of cooling, again reported benefits on outcome. These differences may be explained by differences in study protocols (i.e. speed and duration of cooling, speed of re-warming), prevention of side effects and various supportive measures in the ICU. Although induced hypothermia appears to be a highly promising treatment in various forms of neurological injury including traumatic brain injury, the difficulties in realising its therapeutic potential are underscored by the negative results from a large multi-center trial. Routine usage of hypothermia in traumatic brain injury can not currently be recommended.