Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review

This systematic review delineates the effect of primary therapeutic hypothermia (PTH) (initiated on presentation of the patient) on both mortality and neurological outcome in patients with traumatic brain injury. The safety profile of the therapy is also assessed. A systematic search of the following databases was performed: MEDLINE, EMBASE, Zetoc database of conference proceedings, the Cochrane Database of Systematic Reviews, and the clinicaltrials.gov website, up to July 28, 2011. Relevant journals were hand-searched for further articles and reference lists were checked against the retrieved results for additional resources. The retrieved results were filtered for randomized controlled trials in English where systemic hypothermia was applied for ≥ 12 h in the treatment arm and outcome was assessed at a minimum of 3 months. Randomized controlled trials were assessed for quality of evidence using the GRADE system. Eighteen randomized controlled trials (1851 patients) were identified. The overall relative risk of mortality with PTH when compared with controls was 0.84 [95% confidence interval (CI)=0.72-0.98] and of poor neurological outcome was 0.81 (95% CI=0.73-0.89). However, when only high-quality trials were analysed, the relative risks were 1.28 (95% CI=0.89-1.83) and 1.07 (95% CI=0.92-1.24), respectively. Hypothermia was associated with cerebrovascular disturbances on rewarming and possibly with pneumonia in adult patients. Given the quality of the data currently available, no benefit of PTH on mortality or neurological morbidity could be identified. The therapy should therefore only be used within the confines of well-designed clinical trials.