Abstract
Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics.Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini–Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms.Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development.Conclusion: We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium.Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).
Highlights
Postoperative delirium (POD) is an acute neuropsychiatric syndrome characterized by cognitive dysfunction and decreased attention after anesthesia and surgery [1]
Dementia was defined as a Mini–Mental State Examination (MMSE) score of ≤17 for illiterate patients, ≤20 for patients with 1–6 years of education, and ≤24 for patients with 7 or more years of education [8]; [2] were unable to read or had severe visual or auditory deficits; [3] had a history of alcohol abuse and drug dependence; or [4] were unwilling to comply with the study protocol or procedures
There were no differences in age, MMSE score, sex, height, weight, body mass index (BMI), American Society of Anesthesiologists (ASA) class, education years, length of anesthesia and surgery, Charlson comorbidity score and preoperative visual analog scale (VAS) between the POD and No-POD groups
Summary
Postoperative delirium (POD) is an acute neuropsychiatric syndrome characterized by cognitive dysfunction and decreased attention after anesthesia and surgery [1]. Preoperative brain function reserve is often low in patients at high risk of POD. POD is a common complication following surgery for hip fracture induced by traumatic stimulation in older patients, with an incidence of 4.0–53.3% [2]. With an aging population and an increase in older patients undergoing surgery, the incidence of POD has increased significantly [3]. Epidemiological investigation has revealed that POD occurs mainly 24–72 h after surgery, increases mortality by 10–20%, and has a serious adverse effect on patient prognosis, including an increased risk of cognitive impairment and the development of Alzheimer’s disease [4, 5]. With the acceleration of aging in the global population, POD incidence has become one of the main indicators of medical quality [6]
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