Citation

Feng JZ, Wang WY, Zeng J, Zhou ZY, Peng J, Yang H, Deng PC, Li SJ, Lu CD, Jiang H. J. Trauma Acute Care Surg. 2017; 83(2): 296-304.

Affiliation

From Department of Trauma Surgery (J.F., W.W., J.Z., S.L., H.J.), Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, China; 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, China; North Sichuan Medical College (W.W.), Nanchong, China; Department of Biochemistry (Z.Z.), Southwest Medical University, Luzhou, China; Analytical & Testing Center (P.D.), Sichuan University, Chengdu, China.

Copyright

(Copyright © 2017, Lippincott Williams and Wilkins)

DOI

10.1097/TA.0000000000001522

PMID

28452885

Abstract

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.

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.

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.

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.

Language: en