Serum Metabolomics Analysis Identifies Acetyl-N-formyl-5-methoxykynurenamine as a Promising Dynamic Predictive Biomarker for Postoperative Delirium in Patients With Acute Type A Aortic Dissection

INTRODUCTION: Postoperative delirium (POD) is a common neurological complication following acute type A aortic dissection surgery and is associated with poor clinical outcomes. Identifying reliable biomarkers, particularly those reflecting dynamic perioperative changes, may improve risk stratification and provide insights into POD pathophysiology. METHODS: This was a prospective observational study with a secondary analysis of perioperative serum samples from a registered clinical cohort (ChiCTR2200055980). A total of 128 acute type A aortic dissection patients undergoing open thoracotomy aortic surgery were enrolled, with 52 (40.6%) developing POD. For metabolomic analysis, 30 POD and 30 non-POD patients were matched for age, sex, and body mass index. Serum samples were collected at three time points: preoperatively, on intensive care unit admission, and on postoperative day 3. Untargeted metabolomics using liquid chromatography-mass spectrometry was performed. Differential metabolites were identified using multivariate and univariate analyses with false discovery rate correction. Receiver operating characteristic analysis was used to evaluate exploratory discriminative performance. RESULTS: After false discovery rate correction, no metabolites remained significant in preoperative samples, and only one metabolite, Acetyl-N-formyl-5-methoxykynurenamine, remained significant in postoperative comparisons. In contrast, several metabolites remained significant during the recovery stage. Notably, Acetyl-N-formyl-5-methoxykynurenamine exhibited a consistent temporal pattern, with increased levels in POD patients after surgery and a decline during recovery. Receiver operating characteristic analysis showed promising discriminative ability in postoperative (area under the curve: 0.833) and recovery-stage comparisons (area under the curve: 0.938), while preoperative performance was limited. CONCLUSIONS: Under stringent statistical correction, acetyl-N-formyl-5-methoxykynurenamine emerged as the most robust candidate dynamic biomarker associated with both POD occurrence and recovery. Its temporal pattern highlights the value of longitudinal metabolomic analysis and provides a basis for future validation studies.