%0 Journal Article
%T Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury
%J Journal of trauma and acute care surgery
%D 2017
%A Feng, Jin-Zhou
%A Wang, Wen-Yuan
%A Zeng, Jun
%A Zhou, Zhi-Yuan
%A Peng, Jin
%A Yang, Hao
%A Deng, Peng-Chi
%A Li, Shi-Jun
%A Lu, Charles D.
%A Jiang, Hua
%V 83
%N 2
%P 296-304
%X BACKGROUND: Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target as optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. <br><br>METHODS: Severe TBI patients (Glasgow Coma Scale, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group: 50-60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group: hypothermia therapy target of 32-35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using HNMR technology, we tracked and located the disturbances of metabolic networks. <br><br>RESULTS: 88 severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% males; mean Glasgow Coma Scale 6.17±1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%, p=0.049). From these, 8 cases of MTHT and 6 cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through HNMR metabolomics. <br><br>CONCLUSIONS: MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50-60% should be set as the hypothermia therapy target. STUDY TYPE: Randomized Controlled Trial LEVEL OF EVIDENCE: I.<p /> <p>Language: en</p>
%G en
%I Lippincott Williams and Wilkins
%@ 2163-0755
%U http://dx.doi.org/10.1097/TA.0000000000001522