不同炎症因子对细菌性血流感染所致脓毒症患者的早期诊断价值

The diagnostic value of different pro-inflammatory factor in early diagnosis of sepsis in patients with bloodstream infection

目的 比较降钙素原（PCT）、C-反应蛋白（CRP）、内毒素等炎症因子在细菌性血流感染所致脓毒症患者中的水平差异及其早期诊断价值.方法 回顾性分析2012年2月至2013年5月入住首都医科大学附属北京世纪坛医院重症监护病房（ICU）确诊为脓毒症且血培养阳性的132例患者的临床资料,根据血培养结果将脓毒症患者分为革兰阴性（G-）杆菌血流感染组（98例）和革兰阳性（G＋）球菌血流感染组（34例）,比较两组患者6h内的炎症因子,如白细胞计数（WBC）、中性粒细胞比例（N）、CRP、PCT、内毒素水平等的差异及其之间的相关性；绘制各炎症因子对血流感染所致脓毒症诊断的受试者工作特征曲线（ROC曲线）,根据曲线下面积（AUC）来评价其对血流感染所致脓毒症的诊断价值,根据最佳诊断临界值评估各数值对血流感染诊断的敏感性和特异性.结果 ①G-菌组PCT、CRP、内毒素水平明显高于G＋菌组[PCT（μg/L）：5.11（0.99,18.00）比1.00（0.36,2.73）,Z=49.647,P=0.000; CRP（mg/L）：111.5±57.4比75.9±56.6,t=9.947,P=0.000；内毒素（ng/L）：18.00（8.75,28.00）比5.00（5.00,6.25）,Z=52.333,P=0.000],而WBC、N差异无统计学意义.②相关性分析显示：G菌组患者PCT与CRP（r=0.671,P=0.000）、PCT与内毒素（r=0.916,P=0.000）、CRP与内毒素（r=0.687,P=0.004）均呈正相关；G＋菌组患者PCT与CRP（r=0.620,P=0.000）、PCT与内毒素（r=0.487,P=0.010）、PCT与WBC（r=0.537,P=0.001）、PCT与N（r=0.432,P=0.011）、CRP与内毒素（r=0.674,P=0.000）、内毒素与WBC（r=0.197,P=0.024）均呈正相关；而所有细菌性血流感染患者PCT与CRP（r=0.538,P=0.000）、PCT与内毒素（r=0.740,P=0.000）、PCT与WBC （r=0.259,P=0.003）、CRP与内毒素（r=0.579,P=0.000）、内毒素与WBC（r=0.197,P=0.024）均呈正相关.③ROC曲线分析显示：在G-菌血流感染所致脓毒症患者,PCT的AUC为0.825,最佳诊断临界值＞2.455 μg/L时敏感度71.4％、特异度96.2％; CRP的AUC为0.761,最佳诊断临界值＞79.45 mg/L时敏感度64.3％、特异度80.8％；内毒素的AUC为0.797,最佳诊断临界值＞ 15.5 ng/L时敏感度61.2％、特异度94.2％.在G＋菌血流感染所致脓毒症患者,PCT的AUC为0.619,最佳诊断临界值＞ 1.585 μg/L时敏感度41.2％、特异度82.7％；CRP的AUC为0.533,最佳诊断临界值＞95.25 mg/L时敏感度32.4％、特异度82.7％.结论 G-菌血流感染所致脓毒症患者PCT、CRP、内毒素水平高于G＋菌血流感染者,三者联合检测有望成为早期判断血流感染所致脓毒症及其病情严重程度的指标.

Objective To investigate the expression of different inflammatory variables, such as procalcitonin （PCT）, C-reactive protein （CRP）, and endotoxin in septic patients with bacterial bloodstream infection, in order to assess the value of these variables in early diagnosis. Methods The clinical data of 132 bacterial bloodstream infection patients with clinical diagnosis of sepsis in intensive care unit （ICU） of Beijing Shijitan Hospital of Capital Medical University from February 2012 to May 2013 were analyzed retrospectively. Patients were divided into Gram-negative （ G- ） bacterial bloodstream infection group （n = 98 ） and Gram-positive （ G ± ） bacterial bloodstream infection group （n = 34） according to the result of blood culture. The inflammatory variables including white blood cell （WBC） count, percentage of neutrophils （N）, CRP, PCT mad level of endotoxin in blood of both groups within 6 hours of bloodstream infection were compared, and their correlation was analyzed. The receiver operating characteristic （ROC） curve of inflammatory variables for the diagnosis of bloodstream infection was plotted, and their diagnostic value for bloodstream infection was evaluated according to area under ROC curve （AUC）, and finally the sensitivity and specificity of inflammatory variables for bloodstream infection were assessed based on the best diagnostic cut-off points. Results （1） The levels of the variables, including PCT, CRP, and endotoxin content in the G- bacterial bloodstream infection group were significantly higher than that of G ± bacterial bloodstream infection group [ PCT （ug/L） ： 5.11 （0.99, 18.00） vs. 1.00 （0.36, 2.73）, Z=49.647, P=0.000; CRP （mg/L）： 111.5 ± 57.4 vs. 75.9 ± 56.6, t=9.947, P=0.000; endotoxin （ng/L）： 18.00 （8.75, 28.00） vs. 5.00 （5.00, 6.25）, Z=52.333, P=0.000]. There was no significant difference in WBC and N between two groups. （2） The results of the correlation coefficient of the inflammatory variables showed： in G- bacterial bloodstream infection group positive correlation was found between PCT and CRP （r=0.671, P=0.000）, PCT and endotoxin （r=0.916, P=0.000）, CRP and endotoxin （r=0.687, P=0.004）. On the other hand, in G± bacterial bloodstream infection group, correlation was shown between PCT and CRP （r=0.620, P= 0.000）, PCT and endotoxin （r=0.487, P=0.010）, PCT and WBC （r=0.537, P=0.001）, PCT and N （r=0.432, P=0.011）, CRP and endotoxin （r=0.674, P=0.000）, endotoxin and WBC （r=0.197, P=0.024）. In all of bloodstream infection patients positive correlation was found between PCT and CRP （r=0.538, P=0.000）, PCT and endotoxin （r=0.740, P=0.000）, PCT and WBC （r=0.259, P=0.003）, CRP and endotoxin （r=0.579, P=0.000）, endotoxin and WBC （r =0.197, P =0.024）. （3） The ROE curve in patients with the diagnosis of sepsis due to bloodstream infection showed that： in the G- bacterial bloodstream infection group, AUC for PCT was 0.825, sensitivity of 71.4% and specificity of 96.2% with the best cut-off value 〉2.455 ug/L; AUC for CRP was 0.761, sensitivity of 64.3% and specificity of 80.8% with the best cut-off value 〉79.45 mg/L; AUC for endotoxin was 0.797, sensitivity of 61.2% and specificity of 94.2% with the best cut-off value 〉 15.5 ng/L. In the G± bacterial bloodstream infection group, AUC for PCT was 0.619, sensitivity of 41.2% and specificity of 82.7% with the best cut-off value 〉 1.585 ug/L; AUC for CRP was 0.533, sensitivity of 32.4% and specificity of 82.7% with the best cut-off value 〉95.25 mg/L. Conclusions The concentrations of PCT, CRP, and endotoxin in patients with G- bacterial bloodstream infection were significantly higher than those of G ＋ bacterial bloodstream infection group. They are valuable for the early diagnosis of bloodstream infection, and judgment of its severity, and it is more valuable with the combination of PCT, CRP, and endotoxin concentration determinations.