Association Of Neuroinflammatory Biomarkers With Postoperative Delirium In Elderly Patients With Hip Replacement

ObjectiveThe purpose of this study was to predict and detect postoperative delirium(POD)in elderly hip replacement patients by using Olink proteomic analysis to detect the relationship between neuroinflammatory biomarkers in preoperative cerebrospinal fluid and preoperative and postoperative plasma with postoperative delirium.BackgroundHip replacement is one of the effective treatments for elderly patients affected by hip fracture and femoral head necrosis,which reduce their mobility and quality of life.At present,the number of elderly patients undergoing hip replacement is increasing,and POD is a more frequent complication in the perioperative period of elderly patients with hip disease.The occurrence of POD is closely related to other complications in the perioperative period and poor prognosis after surgery.At present,the potential pathophysiological mechanism of POD has not been fully elaborated,including the neuroinflammation theory that surgery and trauma promote the release of inflammatory factors,enter the central nervous system through the damaged blood-brain barrier,aggravate the nervous system inflammatory response,and promote the occurrence of POD.The study of POD biomarkers is beneficial to explore its pathophysiological mechanism,so more and more studies focus on the role of neuroinflammatory biomarkers in POD.Plasma samples are readily available and readily accepted by patients,while cerebrospinal fluid is the body fluid most likely to accurately reflect the brain and vasculature response to a damaged blood-brain barrier in the central nervous system.Most of the previous detection methods can only detect one or several biomarkers,which has disadvantages such as poor accuracy,low sensitivity,and large sample size required,and the lag of detection methods is easy to affect timely intervention treatment.Olink proteomic analysis can not only detect a large number of biomarkers at the same time,but also has the advantages of high sensitivity,high specificity,and only small samples are required for detection.In this study,Olink proteomics was used to analyze the relationship between neuroinflammatory biomarkers in cerebrospinal fluid and plasma and POD in elderly patients with hip replacement,so as to provide reference for predicting and detecting perioperative POD.MethodsThis prospective cohort study included 91 patients ≥65 years of age,ASA grade II-III,who underwent elective hip replacement surgery at our hospital between July 2022 and February 2023 under combined epidural anesthesia.Informed consent was signed before surgery,and 5ml of peripheral blood from the elbow was reserved before anesthesia,and patients were given combined epidural and lumbar anesthesia in lateral position.1ml of preoperative cerebrospinal fluid was extracted after successful puncture.And 5ml of elbow peripheral blood was extracted at 24 h and 48 h,respectively.We used Olink proteomic analysis to detect inflammatory marker concentrations in cerebrospinal fluid and plasma.Before surgery,Mini-Mental State Examination(MMSE)was used to assess patients’ cognitive function and status,and modified frailty scale was used to assess patients’ activity ability.After surgery,The Confusion Assessment Method(CAM)was used to assess whether patients had POD.If patients had POD,the Delirium Rating Scalerevised 98(DRS-R-98)was used.The DRS-R-98 scale assessed the severity of postoperative delirium after POD,calculated the incidence of POD,and counted perioperative adverse events.Patients were divided into POD group(DP group)and non-POD group(NDP group)according to the presence of POD.Preoperative cerebrospinal fluid,preoperative and postoperative plasma were compared according to the groups,and differential protein information was obtained by screening according to P< 0.05.According to this,differential protein expression was analyzed,and volcano map and box diagram were drawn.ROC curve was used for statistical analysis of biomarkers.The predictors of POD in cerebrospinal fluid and plasma and the factors for diagnosis and staging of POD in plasma were obtained.ResultsA total of 91 patients were included in this study,including 20 patients in DP group and 71 patients in NDP group,with POD incidence of 22.0%.Cerebrospinal fluid and plasma of 22 patients with similar general conditions were selected for Olink proteomic analysis,including 6 cases in DP group and 16 cases in NDP group.Compared with NDP group,the concentrations of CCL3,CCL23,ADA,4EBP-1,STAMBP,TNF,TNF-β and CD5 in cerebrospinal fluid of DP group were increased before surgery,with statistical differences(P<0.05).According to the concentration of CCL3,CCL23,ADA,4EBP-1,STAMBP,TNF,TNF-β and CD5 in cerebrospinal fluid,Receiver Operating Characteristic Curve(ROC)analysis showed that CCL3,CCL23,ADA,4EBP-1,STAMBP,TNF,TNF-β,CD5 in preoperative cerebrospinal fluid had predictive value(P<0.05).Compared with NDP group,the preoperative plasma IL-10 RB concentration in DP group was increased(P<0.05).However,ROC curve analysis of IL-10 RB concentration in plasma before surgery showed that IL-10 RB concentration in plasma before surgery had no predictive value(P>0.05).There was no significant difference in plasma levels of inflammatory factors between 24 h and48h after surgery(P>0.05).Conclusion1.The concentration of neuroinflammatory biomarkers in the cerebrospinal fluid of POD patients was significantly increased before operation,and had a predictive effect on POD in elderly patients with hip replacement;2.Neuroinflammatory biomarkers in cerebrospinal fluid and plasma are associated with POD occurrence in elderly patients with hip replacement.