Abstract
ObjectiveTo 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 MethodsThis 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.ResultsDemographic 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.ConclusionMultiple 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 Registrationwww.ClinicalTrials.gov, identifier ChiCTR1900021533.
Highlights
Patients over 65 years of age are the largest consumers of procedural care, and postoperative delirium (POD) is one of the most common complications experienced by elderly patients during the postoperative period (Daiello et al, 2019)
10 cerebrospinal fluid (CSF) samples were collected from patients with Confusion Assessment Method (CAM)-confirmed POD, while 30 matched CSF samples were collected from patients without POD
After processing the raw MS data, Principal component analysis (PCA) analysis was used to create an overview of metabolomic expression profiles of all samples in positive and negative ion modes
Summary
MATERIALS AND METHODSPatients over 65 years of age are the largest consumers of procedural care, and postoperative delirium (POD) is one of the most common complications experienced by elderly patients during the postoperative period (Daiello et al, 2019). POD is an acute neuropsychiatric syndrome occurring in the hours to days after anesthesia and surgery (Vutskits and Xie, 2016), which can elicit durable deficits in executive function, memory, attention, and other cognitive domains (Eckenhoff et al, 2020). The incidence of POD is 20–45% among elderly adult surgery patients (Rudolph and Marcantonio, 2011; Inouye et al, 2014). POD primarily occurs 24–72 h after surgery, and most symptoms disappear in 1 week. It is linked with persistent impairments in brain function, including cognitive decline (Inouye et al, 2016), increased risk for Alzheimer’s disease (AD) (Olofsson et al, 2018), and serious negative outcomes on patient prognosis such as longer hospitalization, decline in physical function, and even death (Schmitt et al, 2012). Considering the aggravation of an aging global population, the incidence of POD has become a major evaluation index of medical quality and safety (Berian et al, 2018)
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