Prediction of postoperative delirium by blood metabolome analysis

Abstract

No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively. Higher preoperative levels of amino acid (tryptophan) catabolites, via the indoleamine 2,3-dioxygenase pathway, were observed in the delirium group and identified as potential predictors of postoperative delirium in this study. The delirium group had preoperatively elevated levels of tryptophan catabolites and only a limited increase postoperatively, suggesting that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk of delirium. Non-targeted metabolomic analysis found a set of preoperatively elevated γ-glutamyl dipeptides as potential predictors of postoperative delirium. In vitro experiments showed that T-cell-receptor stimulation increases tryptophan metabolism and specific γ-glutamyl dipeptide secretion, offering a possible explanation for the increased levels of metabolites in postoperative delirium. This study showed that levels of amino acid metabolites associated with blood immune activity may have the potential to predict postoperative delirium.

Keywords: Delirium; Kynurenine; Metabolomics; Tryptophan; γ-glutamyl dipeptide.