Pathologic metabolism: an exploratory study of the plasma metabolome of critical injury

Abstract

Background: Severe trauma is associated with massive alterations in metabolism. Thus far, investigations have relied on traditional bioanalytic approaches including calorimetry or nuclear magnetic resonance. However, recent strides in mass spectrometry (MS)-based metabolomics present enhanced analytic opportunities to characterize a wide range of metabolites in the critical care setting.

Methods: MS-based metabolomics analyses were performed on plasma samples from severely injured patients' trauma activation field blood and plasma samples obtained during emergency department thoracotomy. These were compared against the metabolic profiles of healthy controls.

Results: Few significant alterations were observed between trauma activation field blood and emergency department thoracotomy patients. In contrast, we identified trauma-dependent metabolic signatures, which support a state of hypercatabolism, driven by sugar consumption, lipolysis and fatty acid use, accumulation of ketone bodies, proteolysis and nucleoside breakdown, which provides carbon and nitrogen sources to compensate for trauma-induced energy consumption and negative nitrogen balance. Unexpectedly, metabolites of bacterial origin (including tricarballylate and citramalate) were detected in plasma from trauma patients.

Conclusion: In the future, the correlation between metabolomics adaptation and recovery outcomes could be studied by MS-based approaches, and this work can provide a method for assessing the efficacy of alternative resuscitation strategies.

Figure 1

An overview of heme metabolism and antioxidant compounds in plasma samples from controls, emergency department thoracotomies (EDT) and trauma-activated field blood (TAFB) patients. Results are graphed as box-plots indicating median values (line), mean values (+) and upper/lower quartile distributions for each group.

Figure 2

An overview of glycolysis and the TCA cycle in plasma samples from controls, emergency department thoracotomies (EDT) and trauma-activated field blood (TAFB) patients. Results are graphed as box-plots indicating median values (line), mean values (+) and upper/lower quartile distributions for each group.

Figure 3

An overview of protein and lipid metabolism in plasma samples from controls, emergency department thoracotomies (EDT) and trauma-activated field blood (TAFB) patients. Results are graphed as box-plots indicating median values (line), mean values (+) and upper/lower quartile distributions for each group.

Figure 4

An overview of purine and pyrimidine metabolism in plasma samples from controls, emergency department thoracotomies (EDT) and trauma-activated field blood (TAFB) patients. Results are graphed as box-plots indicating median values (line), mean values (+) and upper/lower quartile distributions for each group.

Figure 5

A summary of the main metabolic pathways assayed in this study. Mean metabolite quantitative fluctuations were Z-score normalized and graphed as heat maps in GENE-E. For each metabolite, three values are given, indicating values detected, from top to bottom, in TAFB, EDT or control samples, respectively. Quantitative values progressively increase from blue (minimum) to red (maximum), while white indicates normalized values close to 1.