A prospective pilot study using metabolomics discloses specific fatty acid, catecholamine and tryptophan metabolic pathways as possible predictors for a negative outcome after severe trauma

Abstract

Background We wanted to define metabolomic patterns in plasma to predict a negative outcome in severe trauma patients. Methods A prospective pilot study was designed to evaluate plasma metabolomic patterns, established by liquid chromatography coupled to mass spectrometry, in patients allocated to an intensive care unit (in the University Hospital Arnau de Vilanova, Lleida, Spain) in the first hours after a severe trauma ( n = 48). Univariate and multivariate statistics were employed to establish potential predictors of mortality. Results Plasma of patients non surviving to trauma ( n = 5) exhibited a discriminating metabolomic pattern, involving basically metabolites belonging to fatty acid and catecholamine synthesis as well as tryptophan degradation pathways. Thus, concentration of several metabolites exhibited an area under the receiver operating curve (ROC) higher than 0.84, including 3-indolelactic acid, hydroxyisovaleric acid, phenylethanolamine, cortisol, epinephrine and myristic acid. Multivariate binary regression logistic revealed that patients with higher myristic acid concentrations had a non-survival odds ratio of 2.1 (CI 95% 1.1–3.9). Conclusions Specific fatty acids, catecholamine synthesis and tryptophan degradation pathways could be implicated in a negative outcome after trauma. The metabolomic study of severe trauma patients could be helpful for biomarker proposal. Electronic supplementary material The online version of this article (10.1186/s13049-019-0631-5) contains supplementary material, which is available to authorized users.

Myristic Acid Serum Levels and Their Significance for Diagnosis of Systemic Inflammatory Response, Sepsis, and Bacteraemia

“…In the light of Fong et al (1990) [40], it is possible to admit that alterations in lipid metabolism that are related to changes in cellular energy production during inflammatory response activation may be responsible for the elevated levels of myristic acid in the early stages of septic episode [7]. The question still to be answered is, however, 'why only this fatty acid, and not other shorter or longer chain fatty acid correlate with mortality', as already pointed out by Servià et al (2019) [13].…”

“…Cambiaghi et al (2017) have observed a significant decrease of myristic acid in the plasma of non-responders to the septic shock treatment after 48 h [12]. Servià et al (2019) observed a significant correlation of increased myristic acid levels and mortality from severe trauma in a prospective metabolomic study including 48 trauma patients [13].…”

Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury

“…Our current understanding of the metabolic response to traumatic injury is based almost entirely upon the results of studies that have analysed serum samples acquired from patients at either a single post-injury time-point [20][21][22]24,43] or at multiple timepoints during the acute injury phase (days 1-7) [23,25,26,28,44,45]. Thus, via the analysis of blood samples obtained in the acute (days 0-4), intermediate (days [5][6][7][8][9][10][11][12][13][14] and late (days 15-112) post-injury phases, our study has provided novel insights into both the kinetics of the metabolic response to injury as well as the long-term metabolomic profiles of major trauma patients.…”

“…Metabolomics is a systems-based approach for analysing low molecular weight metabolites present in cells, tissues or biofluids. Applying this analytical technique to serum or plasma samples acquired in the minutes [20], hour [21][22][23] and days [23][24][25][26] following combat injury, TBI or blunt/penetrative trauma has revealed significant traumainduced metabolic perturbations, with changes reported in glucose, fatty acid, amino acid and lipid metabolism. Showing promise as a diagnostic tool for mild TBI [27] and stratifying patients according to injury severity [22,23], metabolic profiling of the circulating metabolome has revealed unique signatures for patients with distinct clinical outcomes.…”

Metabolome of the Brain

“…Повышенные уровни производных сахара отражают нарушенный после ЧМТ церебральный метаболизм глюкозы, другие специфические метаболиты могут транспортироваться в поврежденный мозг для поддержания нормального метаболизма [3]. В качестве предикторов неблагоприятных исходов были предложены свободные жирные кислоты: декановая и октановая, вызывающие митохондриальную дисфункцию и окислительное повреждение липидов и белков [54], и мирамистиновая кислота, способная ингибировать выработку противовоспалительного интерлейкина-10 и повреждать клеточные мембраны, а также метаболиты катехоламинов и триптофана [55].…”