老年下肢骨折手术患者术后谵妄与巨噬细胞迁移抑制因子的相关性

Correlation between postoperative delirium and macrophage migration inhibitory factor in elderly patients after lower limb fracture surgery

【摘要】目的 探讨巨噬细胞迁移抑制因子(MIF)与术后谵妄的相关性。方法 选取2022年6月至2023年6月南京医科大学第二附属医院收治、在脊椎-硬膜外联合阻滞下进行下肢骨折手术的109例老年患者为研究对象(年龄≥65岁)。术前采用简易智能精神状态检查量表(MMSE)对每位患者进行认知评估,收集患者术前血液和脑脊液,以酶联免疫吸附试验检测MIF水平；术后采用谵妄评定方法中文修订版(CAM-CR)进行谵妄评估。根据是否发生谵妄将患者分为谵妄组(13例)和非谵妄组(96例)。采用SPSS 26.0统计软件进行数据分析。根据数据类型,分别采用t检验或Mann-Whitney U检验进行组间比较。采用多因素logistic回归分析评估老年患者下肢手术的危险因素。采用受试者工作特征(ROC)曲线计算ROC曲线下面积(AUC),评估MIF的诊断价值。采用Spearman相关性分析评估MIF与MMSE的相关性。结果 109例老年患者中,谵妄发生率为11.93%(13/109)。与非谵妄组比较,谵妄组术前脑脊液和血液中MIF浓度明显升高,差异有统计学意义(P<0.05)。多因素logistic回归分析显示,术前脑脊液MIF水平(OR=1.273,95%CI 1.120~1.446；P<0.001)和血液MIF水平(OR=1.016,95%CI 1.001~1.031；P=0.032)是老年下肢骨折手术患者术后谵妄发生的独立危险因素。脑脊液和血液MIF预测术后谵妄的AUC分别为0.877(95%CI 0.799~0.956)、0.884(95%CI 0.819~0.949),灵敏度分别分81.50%、76.84%,特异度分别为84.62%、100.00%,约登指数分别为0.66、0.77,差异均有统计学意义(P<0.001)。Spearman相关性分析结果显示,脑脊液和血液MIF水平与MMSE评分呈负相关(r=-0.335,-0.286；P<0.05)。结论 术前MIF水平与老年患者术后发生谵妄密切相关,有作为预测POD生物标志物的潜能。MIF可以反映认知水平,与MMSE评分呈负相关,脑脊液和血液MIF浓度越高,MMSE评分越低。

基金项目:江苏省科技厅省级重点研发计划(社会发展)面上项目(BE2021748)

【Abstract】Objective To explore the correlation of macrophage migration inhibitory factor (MIF) and postoperative delirium. Methods A total of 109 elderly patients (≥65 years) undergoing lower extremity fracture surgery under combined spinal-epidural block in our hospital from June 2022 to June 2023 were prospectively enrolled. Before operation, mini-mental state examination (MMSE) was used to evaluate the cognitive function of each participants, and their blood and cerebrospinal fluid (CSF) samples were harvested to detect MIF level by enzyme linked immunosorbent assay (ELISA). After operation, confusion assessment method Chinese reversion (CAM-CR) was used to assess delirium, and according to the results, they were divided into delirium group (POD group, n=13) and non-delirium group (NPOD group, n=96). SPSS statistics 26.0 was used for data analysis. Depending on data type, student′s t test or Mann-Whitney U test was used for comparison between groups. Multivariate logistic regression model was used to analyze the risk factors of lower limb surgery in elderly patients. Receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC) to evaluate the diagnostic value of MIF. Spearman correlation analysis was employed to analyze the correlation between MIF and MMSE score. Results Among the 109 elderly patients, the incidence of delirium was 11.93% (13/109). Before operation, the MIF levels in the CSF and blood were significantly higher in the POD group than the NPOD group (P<0.05). Multivariate logistic regression analysis showed that preoperative MIF levels in CSF (OR=1.273,95%CI 1.120-1.446; P<0.001) and blood (OR=1.016,95%CI 1.001-1.031; P=0.032) were independent risk factors for postoperative delirium in elderly patients after lower limb fracture surgery. The AUC value of CSF and blood MIF levels in predicting POD was 0.877 (95%CI 0.799-0.956) and 0.884 (95%CI 0.819-0.949), the sensitivity was 81.50% and 76.84%, and the specificity was 84.62% and 100.00%, respectively. The Youden index was 0.66 and 0.77, which were statistically significant (P<0.0001). Spearman correlation analysis showed that CSF and blood MIF levels were negatively correlated with MMSE score (r=-0.335, -0.286; P<0.05). Conclusion Preoperative MIF level is closely associated with the occurrence of POD in elderly patients after surgery, and has the potential to be used as a biomarker to predict POD. MIF can reflect cognitive level, and is negatively correlated with MMSE score. The higher the CSF and blood MIF levels, the lower the MMSE score.

This work was supported by the General Project of Key R&D Plan (Social Development) of Jiangsu Provincial Department of Science and Technology (BE2021748).