Abstract: We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification. Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta-analysis. We considered duration of hypothermia therapy and the length of follow-up in collected data for these subgroups; differences in study data remained such that we did not perform meta-analysis. Studies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low. Despite a large number studies, there remains no high-quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.

Plain-language summary: We included 37 studies with 3110 participants. In each trial, patients were randomly divided into two groups: one group remained at normal body temperature of 36.5 to 38 °C, and the other group was cooled to a maximum of 35 °C for at least 12 hours. We did not combine results of these studies to assess whether hypothermia improves patient outcome. This was because the results had large differences which we could not explain. We identified some differences in the ways in which the studies were carried out and the participants that study authors had recruited, but we did not assess whether this could explain the differences in results. We did not have enough good quality evidence that was sufficiently similar to be confident that treating people who have had a severe brain injury with hypothermia will reduce the incidence of death or severe disability, or increase the incidence of pneumonia. Many of the studies were not well reported and we were unable to assess whether differences between the quality of the studies may also have affected our results. We used the GRADE approach to judge the quality of evidence. We judged the evidence for death or severe disability to be very low quality, and the evidence for pneumonia to be low quality.