脑脊液炎症因子对颅脑损伤术后继发颅内感染的诊断价值

Analysis of the diagnostic value of cerebrospinal fluid inflammatory factors in the patients with craniocerebral injury suffered from intracranial infection after craniocerebral surgery:a prospective study

目的 探讨脑脊液炎症因子对颅脑损伤术后继发颅内感染的诊断价值。方法 前瞻性选择郑州大学附属郑州中心医院高新区医院重症医学科(ICU)2018年6月1日至2020年12月31日连续收治的228例接受颅脑手术并在术中放置脑室引流管的颅脑损伤患者为研究对象,并按照术后是否继发颅内感染分为非感染组和感染组。所有患者均记录一般临床资料及术后3 d连续监测脑脊液(CSF)中白细胞介素(IL)-2、IL-4、IL-6、IL-10、肿瘤坏死因子-α(TNF-α)和γ-干扰素(γ-IFN)水平,比较两组间上述指标差异,绘制受试者工作特征(ROC)曲线,探讨上述指标对诊断颅脑损伤术后继发颅内感染的诊断价值。结果 228例患者中非感染组206例(90.4%),感染组22例(9.6%),术后感染平均时间为术后5.0 d。感染组急性生理和慢性健康状况评分Ⅱ[APACHEⅡ,分:19.9(16.0,32.5)vs.15.0(14.0,17.0)]、入院心率(HR,次/min:98.8±22.1 vs.75.1±15.5)、手术持续时间[min:166.0(143.3,176.3)vs.120.0(109.0,142.0)]、脑室引流管留置时间(d:4.9±0.9 vs.4.4±0.7)、ICU停留时间[d:11.0(9.0,12.3) vs.6.0(5.0,7.0)]及机械通气时间[d:8.0(7.0,9.0)vs.5.0(4.0,5.0)]均明显大于非感染组,而患者发病至就诊时间[min:55.0(50.0,59.3)vs.61.0(54.0,65.0)]、格拉斯哥昏迷评分(GCS,分:4.9±0.9 vs.7.8±1.7)、入院血红蛋白[HGB,g/L:121.5(98.7,133.5)vs.127.0(120.7,134.0)]及血清白蛋白(ALB,g/L:30.5±4.5 vs.36.0±6.5)均明显小于非感染组,非感染组患者预后结局明显优于感染组,差异均有统计学意义(均P<0.05)。非感染组患者术后CSF中IL-2、IL-4和TNF-α均呈升高趋势,IL-6逐渐下降,而感染组患者升高趋势更为明显,IL-6也逐渐升高,γ-IFN呈下降趋势。感染组患者术后第1天(IL-2)、术后第2天(IL-2、IL-4和IL-6)和术后第3天(IL-4、IL-6和TNF-α)均明显大于非感染组,而术后第3天γ-IFN明显小于非感染组,差异均有统计学意义(均P<0.05)。ROC结果发现,术后第3天CSF中IL-6(IL-6-D3)诊断颅内感染的临床价值最高,其曲线下面积(AUC)为0.958[95%CI(0.933~0.984),P=0.000],最佳截断点为4349 pg/mL时,其敏感度、特异度和约登指数分别为0.909、0.893和0.802;其次为IL-6-D2(AUC=0.951,95%CI 0.917~0.984,P=0.000)、TNF-α-D3(AUC=0.845,95%CI 0.795~0.845,P=0.000)、IL-6-D1(AUC=0.684,95%CI 0.608~0.761,P=0.005)、IL-4-D2(AUC=0.754,95%CI 0.680~0.828,P=0.000)、γ-IFN-D3(AUC=0.804,95%CI 0.723~0.886,P=0.000)、IL-2-D1(AUC=0.717,95%CI 0.585~0.849,P=0.001)、IL-4-D3(AUC=0.659,95%CI 0.533~0.785,P=0.014)和IL-2-D2(AUC=0.640,95%CI 0.530~0.750,P=0.031)。结论 颅脑损伤术后患者CSF中IL-2、IL-4、IL-6和TNF-α水平的升高对诊断颅内感染具有极高的临床价值,其中术后第3天IL-6的诊断价值最高,而γ-IFN水平的降低也具有明显的诊断价值。

Objective To discuss the diagnostic value of cerebrospinal fluid inflammatory factors in the patients with craniocerebral injury suffered from intracranial infection after craniocerebral surgery.Methods A prospective study was conducted on 228 patients with craniocerebral injury admitted to intensive care unit(ICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 1 st,2018 to December 31 th,2020 who received craniocerebral surgery,and ventricular drainage tubes were placed during the operation.All the patients were divided into non-infection group and infection group according to whether they had secondary intracranial infection after surgery.General clinical data were recorded for all the patients.The levels of interleukin(IL)-2,IL-4,IL-6,IL-10,tumor necrosis factor-α(TNF-α) and γ-interferon(γ-IFN) in cerebrospinal fluid(CSF) were monitored continuously for 3 days after surgery.The differences of above indicators were compared between the two groups and the receiver operating characteristic curves(ROC) were drawn to explore the diagnostic value of above indicators in the diagnosis of secondary intracranial infection after craniocerebral surgery.Results Among the 228 patients,206 cases(90.4%) were non-infected and 22 cases(9.6%) were infected and the mean time of postoperative infection was 5.0 d.The acute physiology and chronic health evaluationⅡ(APACHEⅡ) [scores:19.9(16.0,32.5)vs.15.0(14.0,17.0)],admission heart rate(HR)(bpm:98.8±22.1 vs.75.1±15.5),the duration of surgery[min:166.0(143.3,176.3) vs.120.0(109.0,142.0)],ventricle drainage tube indwelling time(d:4.9±0.9 vs.4.4±0.7),ICU stay time[d:11.0(9.0,12.3) vs.6.0(5.0,7.0)] and mechanical ventilation[d:8.0(7.0,9.0) vs.5.0(4.0,5.0)] of the infected group were significantly greater than those of non-infection group,while the time from onset to visit to hospital[min:55.0(50.0,59.3) vs.61.0(54.0,65.0)],Glasgow coma scale(GCS scores)(scores:4.9±0.9 vs.7.8±1.7),hemoglobin(HGB) on admission[g/L:121.5(98.7,133.5)vs.127.0(120.7,134.0)] and serum albumin(ALB)(g/L:30.5±4.5 vs.36.0±6.5)were significantly less in the infected group than in the non-infection group,the outcome of the non-infected group was significantly better than that of the infected group,differences were statistically significant(all P<0.05).Postoperative IL-2,IL-4 and TNF-α of CSF in the non-infected group showed a trend of increase,while IL-6 gradually decreased,while those in the infected group showed a more obvious trend of increase,IL-6 gradually increased and γ-IFN decreased.The indexes of patients in the infected group were significantly higher than those in the non-infected group on 1 d(IL-2),2 d(IL-2,IL-4 and IL-6) and 3 d(IL-4,IL-6 and TNF-α),while γ-IFN were significantly lower than that of the non-infected group on 3 d,the differences were statistically significant(all P<0.05).ROC results showed that the IL-6 of CSF on the third day after operation(IL-6-D3)had the highest clinical value in the diagnosis of intracranial infection,the AUC was 0.958 [95%CI 0.933-0.984,P=0.000];When the best cut-off point was 4349 pg/mL,its sensitivity,specificity and Youden index were 0.909,0.893 and 0.802 respectively and it was followed by IL-6-D2(AUC=0.951,95%CI 0.917-0.984,P=0.000),TNF-α-D3(AUC=0.845,95%CI 0.795-0.845,P=0.000),IL-6-D1(AUC=0.684,95%CI 0.608-0.761,P=0.005),IL-4-D2(AUC=0.754,95%CI 0.680-0.828,P=0.000),γ-IFN-D3(AUC=0.804,95%CI 0.723-0.886,P=0.000),IL-2-D1(AUC=0.717,95%CI 0.585-0.849,P=0.001),IL-4-D3(AUC=0.659,95%CI 0.533-0.785,P=0.014)and IL-2-D2(AUC=0.640,95%CI 0.530-0.750,P=0.031).Conclusions The increased levels of IL-2,IL-4,IL-6 and TNF-α in CSF of the patients with craniocerebral injury after craniocerebral surgery have a very high clinical value in the diagnosis of intracranial infection.Among them,IL-6 on the 3 rd day after surgery shows the highest diagnostic value,while the decreased levels of γ-IFN also have significant diagnostic value,which is worth promoting in clinical practice.