Preoperative Serum Metabolites Are Associated With Postoperative Delirium in Elderly Hip-Fracture Patients.

Background: Hypotheses on the development of postoperative delirium (PD) include "neuroinflammatory," "neuronal aging," " oxidative stress," "neurotransmitter deficiency," and "neuroendocrine." Here, we employed metabolomics to determine the serum metabolites in the baseline associated with an increased risk of PD. Methods: Two hundred and nine elderly hip-fracture patients who had undergone hemiarthroplasty and had completed our assessments were selected. Fasting venous blood was collected at 7:00 on the morning of surgery and a serum sample bank was created for analysis. On the first 3 postoperative days, the patients were assessed twice daily using the Confusion Assessment Method - Chinese Revision. Ultimately, 43 patients were diagnosed with PD, who comprised the PD group. Meanwhile, 43 matched non-PD patients were selected based on age, sex, and body mass index. Serum samples from the two groups were analyzed by gas chromatography-time-of-flight mass spectrometry and Acquity ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results: The demographic characteristics of the groups were matched. Four metabolites associated with an increased risk of PD were identified, including S-methylcysteine, linolenic acid, eicosapentaenoic acid, and linoleic acid. Conclusions: Multiple metabolic pathways in the PD group altered before surgery, including deficiency of omega 3 and omega 6 fatty acids, energy metabolism and oxidative stress with interactions between hypoxia and mitochondrial dysfunction, in addition to glutamate-glutamine cycle dysfunction. These metabolic abnormalities could possibly increase the fragility of the brain and then contribute to PD.