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脓毒症及其并发症的病死率较高[1],严重威胁患者生命。研究显示,脓毒症的发生可致血管内皮细胞损伤,增加毛细血管通透性,造成微循环障碍,从而导致组织缺血缺氧[2]。中枢神经系统对于缺血缺氧最为敏感,因此脓毒症多诱发脑部功能损伤,即出现脓毒症相关性脑病(sepsis associated encephalopathy,SAE)[3]。对于SAE的病理机制,多认为是由炎症介质、氧化应激反应等导致脑血流减慢、血脑屏障破坏、脑细胞水肿,从而使神经元受损。SAE的发病率为9%~71%,但有研究表明SAE患者的预后较差[4]。目前,对于SAE的诊断仍是采用排除性诊断,通过其临床表现、格拉斯哥昏迷评分(GCS)、电生理生化检测及影像学辅助检查进行综合判断,但临床诊断标准尚未确定。本研究通过对比分析脓毒症和SAE患者的CT灌注成像参数、血脑屏障损伤标志物,以期评价CT灌注成像联合血脑屏障损伤标志物对SAE的诊断价值。
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由表1所见,观察组和对照组患者第3天的rCBF、rCBV显著低于第1天,差异有统计学意义(观察组:t=2.923、2.165,P=0.005、0.034;对照组:t=2.155,2.167,P=0.034,0.033);第3天rMTT分别高于第1天,差异有统计学意义(观察组:t=3.507,P=0.000;对照组:t=2.278,P=0.025);组间比较,观察组患者第1、3天的rCBF均较对照组显著降低,差异有统计学意义(t=4.945、8.003,均P=0.000);观察组患者第1、3天的rCBV均较对照组显著降低,差异有统计学意义(t=2.234、2.240,P=0.028),而第1天观察组rMTT与对照组比较,差异无统计学意义(t=1.022,P=0.310),第3天观察组rMTT较对照组显著升高,差异有统计学意义(t=2.254,P=0.027)。
组别 例数 rCBF(mL·100 g-1·min-1) rCBV (mL/100 g) rMTT(s) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 45.63±16.56 34.83±15.64a 2.04±0.95 1.59±0.86a 3.21±1.01 3.92±0.93a 对照组 46 63.61±16.61 56.34±15.74a 2.53±1.04 2.06±1.04a 3.03±0.58 3.43±1.04a t 值 4.945 8.003 2.234 2.240 1.022 2.254 P 值 0.000 0.000 0.028 0.028 0.310 0.027 注:表中,a:与第1天比较,差异均有统计学意义(t=2.155~2.923,均P<0.05)。CT:计算机体层摄影术;rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;rMTT:感兴趣区的平均通过时间。 表 1 2组脓毒症患者入院后第1和第3天CT灌注成像结果的比较(
)$\scriptstyle \bar x \pm s $ Table 1. Comparison of CT perfusion imaging parameters on 1 day and 3 day in two groups of sepsis patients (
)$\scriptstyle\bar x \pm s $ -
由表2可见,入院后第1天,两组患者血清Occludin、NOS、NSE、S100β、GFAP、EAA水平差异均无统计学意义;第3天观察组患者血清Occludin、NOS、NSE、S100β、GFAP、EAA水平均较对照组显著升高,差异有统计学意义。入院后第3天,两组组内比较,上述指标均较第1天升高,差异有统计学意义(观察组:t=5.106、2.562、3.731、7.199、6.506、3.092,P=0.000、0.012、0.000、0.000、0.000、0.003;对照组:t=2.371、2.572、7.839、12.540、2.073、2.858,P=0.020、0.012、0.000、0.000、0.041、0.005)。
组别 例数 Occludin(ng/L) NOS(U/mL) NSE(mg/L) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 112.45±12.33 128.37±15.61a 47.76±18.62 56.04±10.54a 17.28±5.47 23.03±4.96a 对照组 46 109.21±11.70 115.21±12.56a 43.04±19.75 51.67±11.30a 16.87±4.46 20.43±3.34a t值 1.233 4.282 1.119 2.379 0.379 2.858 P值 0.221 0.000 0.267 0.020 0.706 0.005 组别 例数 S100β(μg/L) GFAP(ng/L) EAA(μmol/L) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 0.33±0.12 0.39±0.05a 78.91±24.76 125.39±37.83a 4.48±1.02 5.88±2.63a 对照组 46 0.32±0.09 0.35±0.06a 72.54±28.72 82.67±16.55a 4.27±0.97 4.73±1.05a t值 0.436 5.732 1.093 10.351 0.965 2.718 P值 0.664 0.000 0.278 0.000 0.337 0.008 注:表中,a:与第1天比较,差异均有统计学意义(t=2.073~12.540,均P<0.05)。Occludin:闭锁蛋白;NOS:一氧化氮合酶;NSE:神经元特异性烯醇化酶;S100β:中枢神经特异蛋白;GFAP:胶质纤维酸性蛋白;EAA:兴奋性氨基酸。 表 2 2组脓毒症患者第1和第3天血清学指标的比较(
)$\scriptstyle \bar x \pm s $ Table 2. Comparison of serological indicators on 1 day and 3 day in two sepsis patients (
)$\scriptstyle \bar x \pm s $ -
以是否发生SAE为因变量,以上述差异有统计学意义的各项指标为自变量,行Logistic回归分析发现,SAE发生与第3天rCBF、rCBV呈负相关(r=−0.624,−0.709,P=0.037,0.040),与第3天Occludin、GFAP水平呈正相关(r=0.722,0.688,P=0.039,0.035)(表3)。
自变量 B SE Wald P值 Exp 95%CI 第1天rCBF −0.107 0.073 2.130 0.144 0.898 0.778~1.037 第3天rCBF −0.229 0.120 3.637 0.037 0.796 0.629~1.006 第1天rCBV −0.262 0.778 0.113 0.736 0.770 0.167~3.538 第3天rCBV −2.202 1.205 3.338 0.040 0.111 0.010~1.174 第3天rMTT 1.619 1.142 2.011 0.156 5.049 0.539~47.330 第3天Occludin 0.226 0.109 4.255 0.039 1.253 1.011~1.553 第3天NOS −0.022 0.031 0.509 0.476 0.978 0.920~1.040 第3天NES 0.222 0.239 0.863 0.353 1.249 0.781~1.996 第3天S100β 8.712 21.409 0.166 0.684 6075.067 3.631e-15~1.016e22 第3天GFAP 0.074 0.035 4.466 0.035 1.077 1.005~1.154 第3天EAA 0.263 0.531 0.246 0.620 1.301 0.459~3.685 注:表中,rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;rMTT:感兴趣区的平均通过时间;Occludin:闭锁蛋白;NOS:一氧化氮合酶;NSE:神经元特异性烯醇化酶;S100β:中枢神经特异蛋白;GFAP:胶质纤维酸性蛋白;EAA:兴奋性氨基酸;CI:可信区间。 表 3 2组患者各项指标诊断脓毒症相关性脑病的Logistic回归分析
Table 3. Logistic regression analysis of indicators in diagnosis of sepsis associated encephalopathy of two groups
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由表4可见,单项指标检测SAE患者以入院后第3天GFAP水平诊断的曲线下面积最大(0.849),其次为第3天的Occludin、rCBF,rCBV最小(0.625);联合检测中,rCBF+rCBV+Occludin+GFAP的曲线下面积最大,为0.939。
指标 AUC 标准误 P值 95%CI rCBF 0.783 0.050 0.000 0.685~0.881 rCBV 0.625 0.061 0.000 0.505~0.744 Occludin 0.792 0.049 0.000 0.696~0.888 GFAP 0.849 0.043 0.000 0.765~0.933 rCBF+rCBV 0.788 0.049 0.000 0.693~0.884 Occludin+GFAP 0.856 0.042 0.000 0.772~0.936 rCBF+rCBV+Occludin+GFAP 0.939 0.023 0.000 0.894~0.985 注:表中,SAE:脓毒症相关性脑病;ROC:受试者工作特征;rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;Occludin:闭锁蛋白;GFAP:胶质纤维酸性蛋白;AUC:曲线下面积;CI:可信区间。 表 4 38例SAE患者入院后第3天不同指标及联合诊断的ROC曲线分析结果
Table 4. ROC curve analysis results of different indicators and combined diagnosis in 38 patients after admission
CT灌注成像联合血脑屏障损伤标志物对脓毒症相关性脑病的诊断价值
Diagnostic value of CT perfusion imaging combined with markers of blood-brain barrier injuryin of sepsis associated encephalopathy
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摘要:
目的 探讨CT灌注成像联合血脑屏障损伤标志物对脓毒症相关性脑病(SAE)的诊断价值。 方法 选取2015年7月至2017年10月收治的脓毒症患者84例[男性46例、女性38例,年龄19~76(54.05±13.70)岁]。将发生SAE作为观察组(38例),不发生SAE作为对照组(46例),分别于入院后第1、3天检测血清闭锁蛋白(Occludin)、一氧化氮合酶(NOS)、神经元特异性烯醇化酶(NSE)、中枢神经特异蛋白(S100β)、胶质纤维酸性蛋白(GFAP)和兴奋性氨基酸(EAA)的水平,并行脑部CT灌注成像,计算感兴趣区(ROI)的脑血流量(rCBF)、血容量(rCBV)、平均通过时间(rMTT),比较两组患者血清学指标及CT灌注成像结果。组间、组内比较均行t检验,Logistic回归分析SAE发生与各指标的相关性。采用受试者工作特征(ROC)曲线分析各变量单独及联合检测诊断脓毒症脑病的临床价值。 结果 观察组患者第1、3天rCBF分别为(45.63±16.56)、(34.83±15.64) mL·100 g−1·min−1,分别低于对照组的(63.61±16.61)、(56.34±15.74) mL·100 g−1·min−1,且差异有统计学意义(t=4.945、8.003,均P=0.000);第1、3天rCBV分别为(2.04±0.95)、(1.59±0.86) mL/100 g,分别低于对照组的(2.53±1.04)、(2.06±1.04) mL/100 g,差异有统计学意义(t=2.234、2.240,均P=0.028);第3天rMTT为(3.92±0.93) s,高于对照组的(3.43±1.04) s,且差异有统计学意义(t=2.254,P=0.027)。入院后第3天,观察组患者血清Occludin、NOS、NSE、S100β、GFAP、EAA水平分别为(128.37±15.61) ng/L、(56.04±10.54) U/mL、(23.03±4.96) mg/L、(0.39±0.05) μg/L、(125.39±37.83) ng/L、(5.88±2.63) μmol/L,分别高于对照组的(115.21±12.56) ng/L、(51.67±11.30) U/mL、(20.43±3.34) mg/L、(0.35±0.06) μg/L、(82.67±16.55) ng/L、(4.73±1.05) μmol/L,且差异均有统计学意义(t=4.282、2.379、2.858、5.732、10.351、2.718,P=0.000、0.020、0.005、0.000、0.000、0.008)。Logistic回归分析发现,SAE的发生与入院后第3天的rCBF(95%CI: 0.629~1.006,r=−0.624,P=0.037)、rCBV(95%CI: 0.010~1.174,r=−0.709,P=0.040)呈负相关;与第3天的Occludin(95%CI: 1.011~1.553,r=0.722,P=0.039)、GFAP(95%CI: 1.005~1.154,r=0.688,P=0.035)水平呈正相关。ROC曲线分析结果发现,入院后第3天rCBF+rCBV+Occludin+GFAP 联合检测时ROC曲线下面积最大,为0.939。 结论 脓毒症患者早期均表现出一定程度的神经元损伤,CT灌注成像联合血脑屏障损伤标志物检测对SAE具有较高的诊断价值。 -
关键词:
- 脓毒症 /
- 脓毒症相关性脑病 /
- 体层摄影术,X线计算机 /
- 灌注成像 /
- 血脑屏障
Abstract:Objective To explore the diagnostic value of CT perfusion imaging combined with markers of blood-brain barrier injury in sepsis-associated encephalopathy. Methods A total of 84 patients with sepsis were selected in the intensive medicine department from July 2015 to October 2017 and divided into observation and control groups according to the presence of sepsis-associated encephalopathy, there were 46 males and 38 females, aged 19−76(54.05±13.7). The serum levels of Occludin, nitric oxide synthase(NOS), neuron specific enolase(NSE), central nerve specific protein(S100β), glial fibrillary acidic protein(GFAP), and excitatory amino acids(EAA) were measured on the first and third day after admission. Brain CT perfusion imaging was performed to calculate regional cerebral blood flow(rCBF), relative cerebral blood volume(rCBV), and regional mean transit time(rMTT) in the region of interest(ROI). Serological and CT perfusion imaging parameters of the two groups were compared. T-test was performed for comparison between groups and within groups. The correlation between sepsis associated encephalopathy(SAE) and each indicator was analyzed by logistic regression analysis. The receiver operating characteristic(ROC) curve was used to analyze the clinical value of various variables in diagnosis of septic encephalopathy. Results The rCBF of patients in the observation group measured(45.63±16.56) and(34.83±15.64) mL·100 g−1·min−1 on the first and third day, respectively, which were lower than those of the control group at(63.61±16.61) and(56.34±15.74) mL·100 g−1·min−1. Statistically significant difference was observed(t=4.945, 8.003, both P=0.000). The rCBV on the first and third day reached(2.04±0.95) and(1.59±0.86) mL/100 g, respectively, which were lower than those of the control group(2.53±1.04) and (2.06±1.04) mL/100 g, presenting a statistically significant difference(t=2.234, 2.240, both P=0.028). The rMTT on the third day amounted to(3.92±0.93) s, which is higher than the(3.43±1.04) s of the control group, and the difference was statistically significant(t=2.254, P=0.027) . Three days after admission, the levels of occludin, NOS, NSE, S100β, GFAP, and EAA of the observation group reached (128.37±15.61) ng/L, (56.04±10.54) U/mL, (23.03±4.96) mg/L, (0.29±0.05) µg/L, (125.39±37.83) ng/L, and(5.88±2.63) µmol/L, respectively, which were higher than those of the control group, which yielded values of (115.21±12.56) ng/L, (51.67±11.30) U/mL, (20.43±3.34) mg/L, (0.35±0.06) µg/L, (82.67±16.55) ng/L, and (4.73±1.05) µmol/L. Significant differences were observed between the two groups(t=4.282, 2.379, 2.858, 5.732, 10.351, 2.718, P=0.000, 0.020, 0.005, 0.000, 0.000, 0.008). Logistic regression analysis showed that the incidence of sepsis-associated encephalopathy was negatively correlated with rCBF(95%CI: 0.629−1.006, r=−0.624, P=0.037) and rCBV(95%CI: 0.010−1.174, r=−0.709, P=0.040) and positively correlated with occludin(95%CI: 1.011−1.553, r=0.722, P=0.039) and GFAP(95%CI: 1.005–1.154, r=0.688, P=0.035) levels on the third day. ROC curve analysis revealed that the area under the curve, with combined detection of rCBF + rCBV + occludin + GFAP, reached 0.939 on the third day. Conclusion The patients with sepsis showed a certain degree of neuronal injury in the early stage, and the combined detection of CT perfusion imaging and markers of blood-brain barrier injury presented a high diagnostic value for sepsis-associated encephalopathy. -
表 1 2组脓毒症患者入院后第1和第3天CT灌注成像结果的比较(
)$\scriptstyle \bar x \pm s $ Table 1. Comparison of CT perfusion imaging parameters on 1 day and 3 day in two groups of sepsis patients (
)$\scriptstyle\bar x \pm s $ 组别 例数 rCBF(mL·100 g-1·min-1) rCBV (mL/100 g) rMTT(s) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 45.63±16.56 34.83±15.64a 2.04±0.95 1.59±0.86a 3.21±1.01 3.92±0.93a 对照组 46 63.61±16.61 56.34±15.74a 2.53±1.04 2.06±1.04a 3.03±0.58 3.43±1.04a t 值 4.945 8.003 2.234 2.240 1.022 2.254 P 值 0.000 0.000 0.028 0.028 0.310 0.027 注:表中,a:与第1天比较,差异均有统计学意义(t=2.155~2.923,均P<0.05)。CT:计算机体层摄影术;rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;rMTT:感兴趣区的平均通过时间。 表 2 2组脓毒症患者第1和第3天血清学指标的比较(
)$\scriptstyle \bar x \pm s $ Table 2. Comparison of serological indicators on 1 day and 3 day in two sepsis patients (
)$\scriptstyle \bar x \pm s $ 组别 例数 Occludin(ng/L) NOS(U/mL) NSE(mg/L) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 112.45±12.33 128.37±15.61a 47.76±18.62 56.04±10.54a 17.28±5.47 23.03±4.96a 对照组 46 109.21±11.70 115.21±12.56a 43.04±19.75 51.67±11.30a 16.87±4.46 20.43±3.34a t值 1.233 4.282 1.119 2.379 0.379 2.858 P值 0.221 0.000 0.267 0.020 0.706 0.005 组别 例数 S100β(μg/L) GFAP(ng/L) EAA(μmol/L) 第1天 第3天 第1天 第3天 第1天 第3天 观察组 38 0.33±0.12 0.39±0.05a 78.91±24.76 125.39±37.83a 4.48±1.02 5.88±2.63a 对照组 46 0.32±0.09 0.35±0.06a 72.54±28.72 82.67±16.55a 4.27±0.97 4.73±1.05a t值 0.436 5.732 1.093 10.351 0.965 2.718 P值 0.664 0.000 0.278 0.000 0.337 0.008 注:表中,a:与第1天比较,差异均有统计学意义(t=2.073~12.540,均P<0.05)。Occludin:闭锁蛋白;NOS:一氧化氮合酶;NSE:神经元特异性烯醇化酶;S100β:中枢神经特异蛋白;GFAP:胶质纤维酸性蛋白;EAA:兴奋性氨基酸。 表 3 2组患者各项指标诊断脓毒症相关性脑病的Logistic回归分析
Table 3. Logistic regression analysis of indicators in diagnosis of sepsis associated encephalopathy of two groups
自变量 B SE Wald P值 Exp 95%CI 第1天rCBF −0.107 0.073 2.130 0.144 0.898 0.778~1.037 第3天rCBF −0.229 0.120 3.637 0.037 0.796 0.629~1.006 第1天rCBV −0.262 0.778 0.113 0.736 0.770 0.167~3.538 第3天rCBV −2.202 1.205 3.338 0.040 0.111 0.010~1.174 第3天rMTT 1.619 1.142 2.011 0.156 5.049 0.539~47.330 第3天Occludin 0.226 0.109 4.255 0.039 1.253 1.011~1.553 第3天NOS −0.022 0.031 0.509 0.476 0.978 0.920~1.040 第3天NES 0.222 0.239 0.863 0.353 1.249 0.781~1.996 第3天S100β 8.712 21.409 0.166 0.684 6075.067 3.631e-15~1.016e22 第3天GFAP 0.074 0.035 4.466 0.035 1.077 1.005~1.154 第3天EAA 0.263 0.531 0.246 0.620 1.301 0.459~3.685 注:表中,rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;rMTT:感兴趣区的平均通过时间;Occludin:闭锁蛋白;NOS:一氧化氮合酶;NSE:神经元特异性烯醇化酶;S100β:中枢神经特异蛋白;GFAP:胶质纤维酸性蛋白;EAA:兴奋性氨基酸;CI:可信区间。 表 4 38例SAE患者入院后第3天不同指标及联合诊断的ROC曲线分析结果
Table 4. ROC curve analysis results of different indicators and combined diagnosis in 38 patients after admission
指标 AUC 标准误 P值 95%CI rCBF 0.783 0.050 0.000 0.685~0.881 rCBV 0.625 0.061 0.000 0.505~0.744 Occludin 0.792 0.049 0.000 0.696~0.888 GFAP 0.849 0.043 0.000 0.765~0.933 rCBF+rCBV 0.788 0.049 0.000 0.693~0.884 Occludin+GFAP 0.856 0.042 0.000 0.772~0.936 rCBF+rCBV+Occludin+GFAP 0.939 0.023 0.000 0.894~0.985 注:表中,SAE:脓毒症相关性脑病;ROC:受试者工作特征;rCBF:感兴趣区的脑血流量;rCBV:感兴趣区的血容量;Occludin:闭锁蛋白;GFAP:胶质纤维酸性蛋白;AUC:曲线下面积;CI:可信区间。 -
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