Preoperative cerebrospinal fluid biomarkers may be associated with postoperative delirium in patients undergoing knee/hip arthroplasty: the PNDABLE study

Abstract

Background: In the global aging population, the incidence of postoperative delirium (POD) is increasing. Therefore, finding its effective predictive tools becomes crucial. We aimed to identify potential Cerebrospinal fluid (CSF)biomarkers for POD.

Methods: A total of 825 patients undergoing knee/hip arthroplasty under combined spinal-epidural anesthesia were selected. The patients were aged 40 to 90 years with American Society of Anesthesiologists physical status I~II. The Mini-Mental State Examination was completed 1 day before the operation. CSF was extracted after successful spinal-epidural combined puncture, and α-synuclein (α-syn), amyloid beta₄₀ (Aβ₄₀), amyloid beta₄₂ (Aβ₄₂), t-Tau, phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). The patient's operation time, anesthesia time, intraoperative blood loss and fluid input were also recorded. After the operation, the occurrence rate and severity of POD were determined by the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and non-POD group. Logistic regression analysis was performed on the indicators with statistically significant differences, and the area under the ROC curve (AUC) was used to estimate the predictive accuracy of the biomarkers for POD.

Results: A total of 92 patients developed POD and the incidence of POD was 11.15%. The results of the multivariable logistic regression showed that CSF t-Tau (P = 0.004, OR = 1.006, 95%CI 1.002~1.009) and α-syn (P = 0.004, OR = 1.001, 95%CI 1.000~1.001) were positively associated with the occurrence rate of POD, while Aβ₄₂ (P < 0.001, OR = 0.989, 95%CI 0.986~0.993), CSF PGRN (P = 0.002, OR = 0.999, 95%CI 0.999~1.000), Aβ₄₂/ t-Tau (P < 0.001, OR = 0.181, 95%CI 0.102~0.319) and Aβ₄₂/p-Tau (P < 0.001, OR = 0.617, 95%CI 0.526~0.725) were inversely proportional to the occurrence of POD. ROC curve analysis indicated that Aβ₄₂/t-Tau (AUC = 0.823), CSF Aβ₄₂ (AUC = 0.813), Aβ₄₂/p-Tau (AUC = 0.810), α-syn (AUC = 0.644) and PGRN (AUC = 0.638) could predict the occurrence rate of POD. The combination of all these biomarkers showed a greater AUC(0.896) than using any of them alone.

Conclusions: CSF Aβ₄₂, PGRN, α-syn, Aβ₄₂/t-Tau and Aβ₄₂/p-Tau might be associated with the occurrence rate of POD in patients undergoing knee/hip arthroplasty.

Trial registration: Clinical Registration No. ChiCTR2000033439.

Keywords: Aged; Biomarkers; Delirium; Predictive factors, cerebrospinal fluid.