Circulating metabolite profiles may reflect the physiological status before cardiac surgery and could contribute to predicting clinical outcome. Accordingly, metabolite levels may improve risk models as clinical models alone using known, or suspected, risk factors may have limited applicability to subtler organ‐specific injury. Hence, the aim of this study was to comprehensively describe perioperative changes in metabolic profiles in cardiac surgical patients requiring cardiopulmonary bypass to find association with outcomes.

In this work, a sequential extraction strategy using two SPME devices with different selectivity (C18/PAN- and C8-SCX/PAN-coated fibers) next to dual-mode separation (hydrophilic

interaction – reversed-phase) was proposed for improving plasma metabolome coverage and data quality, and consequently facilitating discriminative biomarker discovery. This complementary methodology enhanced metabolome coverage demonstrating that patients undergoing complex open cardiac surgery (n = 22) could be efficiently distinguished from low-risk surgery patients (n = 27) based on their metabolic profiles. Metabolite profiles belonging to the high-risk patients showed higher levels of accumulation of incomplete products of fatty acid (FA) β-oxidation, bile acids, glucuronides, and lipid mediators derived from polyunsaturated FAs, along with perturbations in essential amino acid metabolism that potentially might be linked with multiple poor clinical outcomes (i.e. postoperative seizure, ischemic-thrombotic complications, death).

The analytical workflow, presented in this study, greatly expanded the capacity for comprehensive metabolite profiling in demanding biological matrices. With more patients undergoing complex cardiac surgery at the advanced age, this work adds to improving perioperative care through implementing metabolic solutions that may streamline recovery.