Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning-A Case Report with Metabolomic Approach

Metabolomics in clinical toxicology aim at reliably identifying and semi-quantifying a broad array of endogenous and exogenous metabolites using dedicated analytical methods. Here, we developed a three-step-based workflow to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient who developed life-threatening cardiac failure managed with extracorporeal membrane oxygenation. Both targeted quantitative and untargeted semi-quantitative metabolomic analyses using liquid chromatography hyphenated to high-resolution tandem mass spectrometry were performed to determine the plasma kinetics of venlafaxine, O-desmethyl-venlafaxine, and N-desmethyl-venlafaxine and to identify sixteen different venlafaxine-derived metabolites including one unknown (i.e., venlafaxine conjugated to a hexosyl-radical), respectively. Correlations between the quantitative metabolomic data and annotated endogenous metabolites suggested impaired amino acid and lipid metabolism, Krebs cycle, and kynurenine pathway. This preliminary study represents a first step towards a more extensive application of toxicometabolomics in clinical toxicology and a useful workflow to identify the biomarkers of toxicity.

Automated summary

Metabolomics in clinical toxicology aims to identify and semi-quantify a wide range of endogenous and exogenous metabolites. In this study, a three-step workflow was developed to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient. Targeted quantitative and untargeted semi-quantitative metabolomic analyses were performed to determine the plasma kinetics of venlafaxine and its metabolites, and correlations between the metabolomic data and endogenous metabolites were explored. This preliminary study is a first step towards the application of toxicometabolomics in clinical toxicology and provides a useful workflow for identifying toxicity biomarkers.