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

Abstract

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.

A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round

“…LVEF increased when concentration decreased to approximately 1100 mcg/L; however, the authors presented only the sum of V + ODV, the number of concentrations was low, and there was no comparison of concentrations with a normalized LVEF. In the publication by Magny et al 17 they stopped ECLS when V + ODV was around 1400 mcg/L, coinciding with a clinical improvement (no data about LVEF were provided). They also indicated a negative correlation between V and glutamic acid, suggesting that toxicity could be attributed to inhibiting excitatory amino acids and dysregulation of amino acid homeostasis.…”