Feng Jin-Zhou, Wang Wen-Yuan, Zeng Jun, Zhou Zhi-Yuan, Peng Jin, Yang Hao, Deng Peng-Chi, Li Shi-Jun, Lu Charles D, Jiang Hua
From the Department of Trauma Surgery (J.F., W.W., J.Z., S.L., H.J.), Department of Computational Mathematics and Biostatistics (W.W., J.Z., Z.Z., J.P., H.Y., C.D.L., H.J.), Metabolomics and Multidisciplinary Laboratory for Trauma Research, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu; North Sichuan Medical College (W.W.), Nanchong, China; Department of Biochemistry (Z.Z.), Southwest Medical University, Luzhou; and Analytical and Testing Center (P.D.), Sichuan University, Chengdu, China.
J Trauma Acute Care Surg. 2017 Aug;83(2):296-304. doi: 10.1097/TA.0000000000001522.
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 because 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.
Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 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 H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks.
Eighty-eight 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% men; mean Glasgow Coma Scale score, 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, eight cases of MTHT and six 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 H nuclear magnetic resonance metabolomics.
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% to 60% should be set as the hypothermia therapy target.
Therapeutic study, Level I.
治疗性低温广泛用于治疗创伤性脑损伤（TBI）。然而，确定最佳的低温治疗策略仍然是一项挑战。我们假设降低代谢率而非达到固定体温将是一个合适的目标，因为优化代谢条件尤其是脑代谢环境可能会增强神经保护作用。设计了一项初步单盲随机对照试验来检验这一假设，并进行了一项嵌套代谢组学研究以探索其机制。
将重度TBI患者（格拉斯哥昏迷量表评分3 - 8分）随机分为代谢靶向低温治疗（MTHT）组，以静息代谢率的50%至60%作为低温治疗目标，以及体温靶向低温治疗（BTHT）对照组，体温32°C至35°C作为低温治疗目标。在低温治疗期间的基线以及第1、3和7天收集脑和循环代谢池血样，这些样本从MTHT和BTHT组的一个亚组中随机选取。主要结局是死亡率。使用氢核磁共振技术，我们追踪并定位了代谢网络的紊乱情况。
2013年12月至2014年12月招募并分析了88例重度TBI患者，MTHT组和BTHT组各44例（中位年龄42岁；69.32%为男性；格拉斯哥昏迷量表平均评分6.17 ± 1.02）。MTHT组的死亡率显著低于BTHT组（15.91%对34.09%；p = 0.049）。从中选取MTHT组8例和BTHT组6例进行代谢组学分析，基于模型参数和得分图显示MTHT组在第7天脑和循环代谢模式存在显著差异。最后，通过氢核磁共振代谢组学确定了代表低温治疗潜在神经保护监测参数的代谢物。
MTHT可显著降低重度TBI患者的死亡率。代谢组学研究表明该策略可有效改善脑代谢，提示应将代谢率降低至50%至60%设定为低温治疗目标。
治疗性研究，I级。
