Abstract

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.

Highlights

  • There is a clear difference between severe brain damage and brain death

  • It can be concluded that, despite the seriousness of the problem, this theme is a kind of terra incognita in medicine, scientific reports dedicated to this subject are practically nonexistent, and the search for new methods of brain death diagnosis seems to be an absolute necessity

  • The discrimination potential between groups was confirmed for specific metabolites with high receiver operating characteristic curve (ROC) area under the curve value (AUC)

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Summary

Introduction

There is a clear difference between severe brain damage and brain death. in clinical practice, the differentiation of these states can be challenging. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). The concept of metabolomic studies is based on the observation that with the development of pathological processes, both local and systemic, the first symptoms appearing at the cellular level are directly reflected in the chemical composition of tissues subject to these processes and in body fluids These processes may be minor changes involving the disruption of the quantitative ratio between different chemical compounds as well as changes that are easier to detect, such as the appearance of entirely new chemical compounds (biomarkers of disease) or the disappearance of specific molecules present in homeostasis. Metabolomics research is primarily based on gas or liquid chromatography–mass spectrometry (GC–MS/LC–MS) and nuclear magnetic resonance (NMR) p­ latforms[12,13,14,15]

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