术前血清胱抑素C浓度与患者术后谵妄的关系

Relationship between preoperative serum cystatin C concentration and postoperative delirium

目的:评价术前血清胱抑素C(Cys C)浓度与患者术后谵妄(POD)的关系。方法:择期在脊髓-硬膜外麻醉下行膝和髋关节置换术患者390例,年龄>50岁,ASA分级Ⅰ或Ⅱ级,术前1 d时MMSE评分>23分。术前抽取外周血标本,采取胶乳增强免疫比浊法检测血清Cys C浓度。脊髓-硬膜外麻醉穿刺成功后抽取2 ml脑脊液(CSF),采用ELISA法检测β淀粉样蛋白42(Aβ42)、总tau蛋白(T-tau)及磷酸化tau蛋白(P-tau)浓度。根据是否发生POD将患者分为POD组和未发生POD组。采用logistic回归筛选POD的危险因素和保护因素,并分析CSF生物标志物的中介效应;绘制受试者工作特征曲线,评价血清Cys C浓度及其联合CSF生物标志物浓度预测POD的准确性。结果:最终纳入327例患者,POD发生率为13.5%。logistic回归在校正年龄、性别、受教育年限、MMSE评分、吸烟史、饮酒史、高血压和糖尿病病史等多项混杂因素后的结果表明,血清Cys C浓度升高、CSF P-tau和T-tau的浓度升高是POD的危险因素,CSF Aβ42浓度、Aβ42/P-tau比值和Aβ42/T-tau比值升高是POD的保护因素( P<0.05)。中介效应分析显示,血清Cys C浓度和POD的关系由CSF T-tau浓度(11.1%)和CSF Aβ42/T-tau比值(18.0%)介导。血清Cys C浓度联合CSF生物标志物浓度预测POD的受试者工作特征曲线下面积为0.807( P<0.001)。 结论:术前血清Cys C浓度升高是患者POD的危险因素;CSF T-tau浓度和Aβ42/T-tau比值在血清Cys C浓度与患者POD的关系中发挥中介效应。

Objective To evaluate the relationship between preoperative serum cystatin C(Cys C)concentration and postoperative delirium(POD)in the patients.Methods Three hundred and ninety patients,aged>50 yr,of American Society of Anesthesiologists Physical Status classificationⅠorⅡ,scheduled for elective knee and hip replacement under combined spinal-epidural anesthesia,with Mini-Mental State Examination scores>23 at 1 day before operation,were included in the study.Peripheral blood samples were collected before operation,and the serum Cys C concentration was measured by the latex-enhanced immunoturbidimetric assay.The cerebrospinal fluid(CSF)2 ml was collected after successful spinal-epidural puncture for determination of amyloid-β42(Aβ42),total tau(T-tau)and phosphorylated tau(P-tau)concentrations by enzyme-linked immunosorbent assay.The patients were divided into POD group and non-POD group according to whether POD occurred.The logistic regression analysis was used to identify the risk and protective factors for POD,and the mediating effect of CSF biomarkers was analyzed.The receiver operating characteristic curve was drawn to evaluate the accuracy of serum Cys C concentration and combination of serum Cys C conceatration and CSF biomarker concentration in predicting POD.Results Three hundred and twenty-seven patients were finally enrolled,and the incidence of POD was 13.5%.The results of logistic regression showed that increased serum Cys C concentration and increased concentrations of P-tau and T-tau in CSF were risk factors for POD,while increased concentration of Aβ42 and increased Aβ42/P-tau ratio and Aβ42/T-tau ratio in CSF were protective factors for POD(P<0.05)after adjusting for multiple confounding variables such as age,sex,years of education,Mini-Mental State Examination score,smoking history,drinking history,hypertension and diabetes history.The mediation analysis showed that the relationship between serum Cys C concentration and POD was mediated by T-tau concentration in CSF(11.1%)and by Aβ42/T-tau ratio in CSF(18.0%).The area under the receiver operating characteristic curve of serum Cys C and CSF biomarker concentrations in predicting POD was 0.807(P<0.001).Conclusions Increase in preoperative serum Cys C concentration is a risk factor for POD.T-tau concentration and Aβ42/T-tau ratio in CSF serve as the key mediators in the relationship between preoperative serum Cys C concentration and POD.