Plasma metabolomics reveals systemic alterations associated with cardiac surgery and identifies candidate predictors of postoperative outcomes: a prospective cohort study

Abstract Cardiac surgery with cardiopulmonary bypass (CPB) is associated with systemic metabolic alterations related to stress and immune responses. We aimed to map these dynamics through perioperative metabolomics. Furthermore, we assessed whether baseline metabolites predict postoperative outcomes. Plasma was sampled pre- and post-surgery in a discovery (n = 98) and validation cohort (n = 24). Targeted metabolomics was performed with the Biocrates MxP Quant 500XL kit. Statistical analysis involved principal component analysis, linear mixed effects models, and machine learning-based approaches. The plasma metabolome exhibited marked pre- to post-surgery alterations, primarily driven by postoperative lipid reduction. Baseline metabolic profiles showed no global separation between outcome groups. Individual preoperative metabolites however demonstrated exploratory evidence of higher discriminative performance than established biomarkers (CRP, urea) and clinical risk scores for prolonged ICU stay (> 3 days) in the discovery cohort (n = 22 events). External validation showed discrimination comparable to conventional parameters, although precision was limited by only five outcome events. Our findings highlight substantial metabolic alterations following CPB and suggest baseline metabolites as candidate predictors of postoperative outcomes, supporting further evaluation as prognostic markers in larger cohorts. Trial registration: The study was registered in the German Clinical Trials Register (DRKS00016493, https://drks.de/search/en/trial/DRKS00016493 ) on 15 March 2019.