脑脊液神经损伤相关蛋白水平预测患者术后谵妄的价值

Value of cerebrospinal fluid nerve injury-related proteins levels in predicting postoperative delirium

目的评价脑脊液神经损伤相关蛋白水平预测患者术后谵妄(POD)的价值。方法选取拟在脊椎-硬膜外麻醉下行膝/髋关节置换术的患者1000例,性别不限,年龄40~90岁,ASA分级Ⅰ或Ⅱ级,术前1 d时的MMSE评分>24分。麻醉前抽取患者肘静脉血样,检测血浆总胆固醇、高密度脂蛋白、低密度脂蛋白和甘油三酯浓度。脊椎-硬膜外麻醉穿刺成功后,取脑脊液2 ml,采用ELISA法测定α-突触核蛋白(α-syn)、β淀粉样蛋白1-40(Aβ1-40)、A_(β1-42)、总Tau蛋白(t-Tau)、磷酸化Tau蛋白(p-Tau)、颗粒蛋白前体(PGRN)和髓样细胞触发受体2(sTREM2)的浓度。分别于术后1、3和7 d时,采用意识模糊评估法评估POD发生情况。依据是否发生POD分为POD组与非POD组。将组间比较差异有统计学意义的因素进行logistic回归分析,筛选POD的危险因素。绘制受试者工作特性曲线(ROC曲线),计算曲线下面积(AUC),评估相关危险因素预测POD的准确性。结果共纳入964例患者,其中108例发生POD,发生率为11.2%。logistic回归分析结果表明,高龄和脑脊液α-syn浓度升高是POD的危险因素,脑脊液PGRN浓度和A_(β1-42)/p-Tau降低是POD的保护因素(P<0.05)。ROC曲线分析结果显示,脑脊液α-syn浓度(AUC 0.693,95%CI 0.634~0.748,灵敏度57.41%,特异度82.10%,约登指数0.3951)、PGRN浓度(AUC 0.695,95%CI 0.637~0.750,灵敏度59.26%,特异度80.86%,约登指数0.4012)和A_(β1-42)/p-Tau(AUC 0.635,95%CI 0.574~0.692,灵敏度93.52%,特异度30.25%,约登指数0.2377)均可预测POD的发生。结论脑脊液PGRN、α-syn浓度和A_(β1-42)/p-Tau均可预测患者POD的发生。

Objective To evaluate the value of cerebrospinal fluid(CSF)nerve injury-related proteins levels in predicting postoperative delirium(POD)in patients.Methods A total of 1000 patients of both sexes,aged 40-90 yr,of American Society of Anesthesiologists physical statusⅠorⅡ,with Mini-Mental State Examination score>24 at 1 day before operation,undergoing elective knee/hip arthroplasty under spinal-epidural anesthesia,were enrolled in this study.Cubital venous blood samples were drawn before anesthesia for detection of the concentrations of plasma total cholesterol,high-density lipoprotein,low-density lipoprotein and triglyceride.CSF 2ml was extracted after successful spinal-epidural anesthesia puncture for measurement of concentrations ofα-synuclein(α-syn),β-amyloid protein1-40(Aβ1-40),A_(β1-42),total-Tau(t-Tau),phosphorylated Tau(p-Tau),progranulin(PGRN)and soluble myeloid cell triggering receptor 2(sTREM2)(by enzyme-linked immunosorbent assay).The Confusion Assessment Method was used at 1,3 and 7 days after surgery to evaluate the occurrence of POD.The patients were divided into POD group and non-POD group according to whether POD occurred after operation.Logistic regression analysis was used to analyze the variables of which P values were less than 0.05 to analyze the risk factors for POD.The receiver operating characteristic(ROC)curve was drawn and area(AUC)under the curve was calculated to evaluate the accuracy of the related risk factors in predicting POD.Results A total of 964 patients were enrolled in the study,and 108 patients were diagnosed with POD,and the incidence was 11.2%.The results of logistic regression analysis found that age and and increasedα-syn in CSF concentration were risk factors for POD,and decreased PGRN in CSF concentration and A_(β1-42)/p-Tau in CSF were the protective factors for POD(P<0.05).ROC curve analysis showed thatα-syn(AUC 0.69,95%confidence interval(CI)0.634-0.748,sensitivity 57.41%,specificity 82.10%,Youden Index 0.3951),PGRN in CSF concentration(AUC 0.695,95%CI 0.637-0.750,sensitivity 59.26%,specificity 80.86%,Youden Index 0.4012)and A_(β1-42)/p-Tau in CSF(AUC 0.635,95%CI 0.574-0.692,sensitivity 93.52%,specificity 30.25%,Youden Index 0.2377)could predict the occurrence of POD.Conclusion PGRN,α-syn concentration and A_(β1-42)/p-Tau in CSF can predict the occurrence of POD in patients.