The efficacy of therapeutic hypothermia in adult patients with traumatic brain injury: a systematic review and meta-analysis

Therapeutic hypothermia (TH) has been one amazing treatment option for patients with traumatic brain injury (TBI), but its effect is still controversial. This systematic review is to assess the effectiveness of the application of therapeutic hypothermia to reduce mortality, and poor neurological outcome of adult patients admitted to hospital following TBI. A systematic review of 21 randomized controlled trials was conducted to investigate the effects of therapeutic hypothermia on the mortality and poor neurological outcomes after TBI. Review Manager (RevMan, Cochrane Collaboration, version 5.3) and Comprehensive Meta-Analysis (CMA version 2.0, Biostat) were used to perform the meta-analysis. Pooled effects were estimated for each outcome using a random-effects meta-analysis model. Twenty-one randomized controlled trials are included in the review. Nineteen studies with 2, 245 patients reported mortality at final follow-up. Therapeutic hypothermia was associated with a significant reduction in mortality (relative risk (RR) = 0.78, 95% CI = 0.64-0.96, P = 0.02). However, the pooled data from five recent studies after 2010 showed that this treatment increased the mortality (RR = 0.67, 95% CI = 0.53-0.84, P = 0.0005). Twenty-one trials involving 2, 302 patients reported death, vegetative state, and long-term disability and therapeutic hypothermia was associated with a significant reduction in poor outcomes (RR = 0.71, 95% CI = 0.60-0.84, P<0.00001). Although the studies before 2010 showed that therapeutic hypothermia improved the neurological outcomes, the ones after 2010 did not get this conclusion (RR = 1.02, 95% CI = 0.82-1.27, P = 0.880). In conclusion, therapeutic hypothermia may be beneficial in the treatment of TBI. Further large-scale, multi-center studies with careful matching and enough follow-up periods needed for more persuasive analysis.