Early Serum Metabolism Profile of Post-operative Delirium in Elderly Patients Following Cardiac Surgery With Cardiopulmonary Bypass

Abstract

BackgroundCardiac surgery with cardiopulmonary bypass (CPB) is considered to be one of the surgical types with the highest incidence of post-operative delirium (POD). POD has been associated with a prolonged intensive care and hospital stay, long-term neurocognitive deterioration, and increased mortality. However, the specific pathogenesis of POD is still unclear. Untargeted metabolomics techniques can be used to understand the changes of serum metabolites in early POD to discover the relationship between serum metabolites and disease.Materials and MethodsThe present study recruited 58 elderly patients undergoing cardiac surgery with CPB. Serum was collected within the first 24 h after surgery. The Confusion Assessment Method (CAM) and ICU-CAM assessments were used to identify patients who experienced POD. All patients with normal post-operative cognitive assessment were included in the non-POD groups. Moreover, we collected serum from 20 healthy adult volunteers. We performed untargeted analyses of post-operative serum metabolites in all surgical groups, as well as serum metabolites in healthy non-surgical adults by using liquid chromatography mass spectrometry (LC/MS) and analyzed metabolic profiles and related metabolites.ResultsThe probability of POD after cardiac surgery were 31%. There were statistically significant differences in post-operative mechanical ventilation time, ICU stay time and post-operative hospital stay between POD and non-POD group (P < 0.05). And ICU stay time was an independent risk factor for POD. The analysis revealed that a total of 51 differentially expressed metabolites (DEMs) were identified by comparing the POD and non-POD group, mostly lipids and lipid-like molecules. Three phosphatidylinositol (PI) were down-regulated in POD group, i.e., PI [18:0/18:2 (9Z, 12Z)], PI [20:4 (8Z, 11Z, 14Z, 17Z)/18:0], and PI [18:1 (9Z)/20:3 (8Z, 11Z, 14Z)]. The receiver operating characteristic (ROC) curve analysis showed that three kinds of PI metabolites had the highest area under the curve (AUC), which were 0.789, 0.781, and 0.715, respectively. Correlation analysis showed that the expression of three PIs was negatively correlated with the incidence of POD.ConclusionOur findings suggest that lipid metabolism plays an important role in the serum metabolic profile of elderly patients with POD in the early post-operative period. Low serum lipid metabolic PI was associated with incidence of POD in elderly following cardiac bypass surgery, which may provide new insights into the pathogenesis of POD.

Discovery of Delirium Biomarkers through Minimally Invasive Serum Molecular Fingerprinting

“…The bands at 2912 and 1149 cm −1 are associated with lipids and carbohydrates, respectively, aligning with the known link between delirium and disruptions in the lipid metabolism and the energetic metabolism [39][40][41]43,59]. Indeed, these metabolic alterations serve as recognized indicators for post-operative delirium [39,43]. The bands at 942 and 1546 cm −1 , associated with proteins, and the band at 1041 cm −1 , linked to phosphate esters, along with those at 1268 and 987 cm −1 , related to phosphate groups (which can also be attributed to phosphorylated proteins and lipids), can be associated with the neuroinflammation, metabolic imbalances and oxidative stress in delirium [20,84].…”

“…Among these, bands at 2853, 2926 and 2961 cm −1 are associated with lipids, while the band at 1470 cm −1 is associated with both lipids and proteins. This association highlights the disruptive role of lipids in similar neurodegenerative diseases [43,[53][54][55][56][57][58]. For instance, Huang et al [43] observed significant changes in the lipid profiles of patients with post-operative delirium, hypothesizing that lipid dysregulation might contribute to the pathogenesis of the condition.…”

“…Non Huang et al [43] observed significant changes in the lipid profiles of patients wit operative delirium, hypothesizing that lipid dysregulation might contribute pathogenesis of the condition. Similarly, Guo et al [59] found that deficiencies in ω6 fatty acids and disruptions in the energy metabolism may diminish the brain's in protective capacity, potentially contributing to the development of post-op delirium.…”

Postoperative delirium in geriatric patients with hip fractures

“…These metabolic abnormalities most likely reduce the ability of the brain to provide neuroprotection and take part in neuroinflammatory responses. Another study applied untargeted metabolomics techniques to investigate the change of serum metabolites in POD patients undergoing cardiopulmonary bypass, and found that low serum lipid metabolic phosphatidylinositol was linked to an increased risk of POD in the geriatric patient, which may shed fresh light on the pathophysiology of POD ( Huang et al, 2022 ).…”

AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

“…A compilation of 45 genes that were cited as POD markers and their role in the pathogenesis of POD extensively deliberated, were selected for analysis. Many of these genetic markers of POD are inflammatory factors, and their escalated levels have been documented in the plasma of POD patients in the preoperative and/or early postoperative period 55,56 . For instance, elevated plasma concentrations of interleukin 6 (IL6), tumor necrosis factor alpha (TNFA), and vascular endothelial growth factor (VEGF) have been detected in the early postoperative period in elderly patients who exhibited POD 57 .…”