Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Yongzheng Han; Wenchao Zhang; Jiao Liu; Yanan Song; Taotao Liu; Zhengqian Li; Xiaoxiao Wang; Ning Yang; Yue Li; Dengyang Han; Xinning Mi; Yang Zhou; Min Li; Xiangyang Guo; Lijun Zhong; Geng Wang; Yi Yuan

doi:10.3389/fnagi.2020.570210

Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Front Aging Neurosci. 2020 Oct 22:12:570210. doi: 10.3389/fnagi.2020.570210. eCollection 2020.

Authors

Yongzheng Han¹, Wenchao Zhang², Jiao Liu³, Yanan Song¹, Taotao Liu¹, Zhengqian Li¹, Xiaoxiao Wang⁴, Ning Yang¹, Yue Li¹, Dengyang Han¹, Xinning Mi¹, Yang Zhou¹, Min Li¹, Xiangyang Guo¹, Lijun Zhong³, Geng Wang², Yi Yuan²

Affiliations

¹ Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
² Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing, China.
³ Center of Medical and Health Analysis, Peking University Health Science Center, Beijing, China.
⁴ Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.

Abstract

Objective: To investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD.

Materials and methods: This nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (n = 40) who developed POD undergone hip fracture surgery (n = 10) and those who did not (n = 30). Thirty Non-POD patients were matched to 10 POD patients by age (± 2 years) and Mini Mental State Examination score (± 2 points). CSF was collected after successful spinal anesthesia and banked for subsequent analysis. On the first two postoperative days, patients were assessed twice daily using the Confusion Assessment Method-Chinese Revision. CSF samples from the two groups were analyzed to investigate possible relevant pathological mechanisms and identify candidate biomarkers.

Results: Demographic characteristics of the groups were matched. Eighteen metabolites and thirty-three lipids were dysregulated in the preoperative CSF of POD patients. Pathway enrichment analysis revealed perturbations in D-glutamine and D-glutamate metabolism; glycerophospholipid metabolism; alanine, aspartate and glutamate metabolism; sphingolipid metabolism; histidine metabolism; and arginine biosynthesis at the pre-delirium stage. Receiver operating characteristic curve analysis indicated that phosphatidylethanolamine (PE, 40:7e), with an area under the curve value of 0.92, is a potential biomarker for POD.

Conclusion: Multiple pathological mechanisms in the POD group were involved before surgery, including neuroinflammation, oxidative stress, and energy metabolism disorders induced by hypoxia, as well as neurotransmitter imbalances such as increased dopamine and glutamate, and decreased glutamine. These metabolic abnormalities potentially increase the fragility of the brain, thus contributing to POD. PE (40:7e) might be a potential biomarker for POD. Not only do our results provide potential biomarkers for POD, but also provide information for deep pathological research.

Clinical trial registration: www.ClinicalTrials.gov, identifier ChiCTR1900021533.

Keywords: cerebrospinal fluid; hip fracture; lipidomics; metabolomics; postoperative delirium.