Intraoperative plasma proteomic changes in cardiac surgery: In search of biomarkers of post-operative delirium

PurposeDelirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse outcomes, longer hospital stays and higher cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking. ObjectiveTo identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms. Experimental DesignComparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery. Validation by targeted proteomics was performed in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy. ResultsForty-seven percent of subjects demonstrated delirium. Of 3803 proteins identified from patient samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B. Conclusions and Clinical RelevanceThe interplay of systemic and central inflammatory markers sheds new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using panels of biomarkers.