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.