正五聚蛋白3联合血管外肺水指数评估脓毒症患者病情严重程度及预后的价值研究

Value of detection of pentraxins 3 value combined with measurement of vascular lung water index in prognosis of patients with sepsis

目的评价正五聚蛋白3（PTX3）联合血管外肺水指数（EVLWI）对脓毒症患者病情及预后的评估价值。方法回顾性分析2013年2月至2014年2月入住郑州大学第一附属医院重症医学科脓毒症患者的临床资料，按28d预后分为存活组及死亡组。所有患者均于入重症加强治疗病房（ICU）1、2、3d时采用脉搏指示连续心排血量仪（PiCCO）监测EVLWI，用酶联免疫吸附试验（ELISA）检测血浆PTX3水平；并计算急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分和序贯器官衰竭评分（SOFA）；对PTX3和EVLWI进行相关性分析；绘制受试者工作特征曲线（ROC），评价各指标对预后的价值。结果共入选74例脓毒症患者，28d存活41例，死亡33例。死亡组除人ICU时血乳酸及APACHEⅡ、SOFA评分均明显高于存活组，ICU住院时间明显短于存活组外，其他基线资料与存活组比较差异均无统计学意义。随治疗时间延长，两组血浆PTX3水平均逐渐下降，死亡组入ICU1、2、3d时血浆PTX3水平均明显高于存活组[PTX3（μg/L）1d：46．3±10．5比19．4±6．5，t=-13．486，P=0．000；2d：34．8±10．7比17．7±8．4，t=-8．284，P=0.000；3d：23．9±11．2比15．6±7．9,t=-5．036，P=0.000]。存活组EVLWI逐渐下降，死亡组逐渐升高；死亡组入ICU1、2、3d时EVLWI均明显高于存活组[EVLWI（mL／kg）1d：12．12±4．31比10．02±2．87，t=-2．502，P=0．023；2d：13．67±4．95比9．08±2．89，t=-5．188，P=0．000；3d：14．51±5．06比8．09±2．50，t=-7．126，P=0．000]。入ICU1、2、3d时PTX3与EVLwI均呈显著正相关（r1=0．747、r2=0．719、r3=0．705，均P=0．000）。ROC曲线分析显示，人ICU 1d时PTX3的ROC曲线下面积（AUC）为0．845±0．045，截断值为23．0μg/L时，评估预后的敏感度为84．8％，特异度为74．1％，阴性预测值为85．81％，阳性预测值为72．42％；人ICU 3d时EVLWI的AUC为0．838±0．048，截断值为10．5mL／kg时，评估预后的敏感度为83．9％，特异度为82．9％，阴性预测值86．45％，阳性预测值79．79％；二者的预后评估价值均优于同时间点APACHEⅡ、SOFA评分。1d时PTX3联合EVLWI的AUC为0．886±0．038，截断值为0．312时，评估预后的敏感度为86．8％，特异度为85．4％，阴性预测值为88．93％，阳性预测值为82．72％；人ICU 3d时PTX3联合EVLWI的AUC为0．856±0．046，截断值为0．471时，评估预后的敏感度为85．8％，特异度为85．4％，阴性预测值为87．97％，阳性预测值82．50％，二者均较其他单独评价指标具有更好的预后评估价值。结论PTX3可作为脓毒症的一个新标志物，与EVLWI联合可为临床早期评估脓毒症患者的病情及预测预后、并针对高危患者积极进行干预治疗提供参考。

Objective To evaluate prognostic value of pentraxin3 （PTX3） content combining with extravascular lung water index （EVLWI） in patients with sepsis. Methods A retrospective analysis of complete clinical data of septic patients admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Zhengzhou University from February 2013 to February 2014 was conducted. These patients were divided into two groups, survival group and death group, according to the outcome on the 28th day. Pulse index continuous cardiac output （PiCCO） was used to record the levels of EVLWI on the 1st, 2nd and 3rd day of intensive care unit （ICU） admission. The plasma level of PTX3 was measured simultaneously by enzyme-linked immunosorbent assay （ELISA）. At the same time, acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score and sequential organ failure assessment （SOFA） were calculated. Correlation analysis between plasma PTX3 and EVLWI values was performed, receiver operating characteristic curve （ROC） was drawn, and the prognostic value of each parameter was assessed finally. Results A total of 74 septic patients were enrolled, with 41 cases in the survival group and 33 cases in the non-survival group. Blood lactate, APACHE Ⅱ,SOFA scores in the non-survival group were significantly higher than those of the survival group at ICU admission, and the length of ICU stay was significantly shorter than that of the survival group, while differences of the other clinical characteristics between two groups were not statistically significant. The plasma PTX3 level gradually declined with time in both groups, and plasma PTX3 at 1, 2, 3 days after ICU admission in non-survival group were significantly higher than those in survival group [ PTX3 （μg/L） at 1 day： 46.3 ± 10.5 vs. 19.4±6.5, t = -13.486, P = 0.000; 2 days： 34.8±10.7 vs. 17.7±8.4, t = -8.284, P = 0.000; 3 days： 23.9±11.2 vs. 15.6 ± 7.9, t = -5.036, P = 0.000 ]. EVLWI gradually declined in survival group, but increased in death group. EVLWI at 1, 2, 3 days after ICU admission in non-survival group were significantly higher than those in survival group [EVLWI （mL/kg） at 1 day： 12.12 ± 4.31 vs. 10.02 ± 2.87, t = -2.502, P = 0.023; 2 days： 13.67 ±4.95 vs. 9.08 ±2.89, t = -5.188, P = 0.000; 3 days： 14.51 ±5.06 vs. 8.09±2.50, t = -7.126, P = 0.000]. PTX3 at 1, 2, 3 days after ICU admission showed a significant positive correlation with EVLWI （r1= 0.747, r2 = 0.719, r3 = 0.705, all P = 0.000）. ROC curve analysis showed that the area under the ROC （AUC） of PTX3 at 1 day was 0.845 ± 0.045, at the cut-off point of 23.0 μg/L, PTX3 showed a sensitivity of 84.8%, a specificity of 74.1%, a negative predictive value of 85.81%, and a positive predictive value of 72.42%. AUC of EVLWI at 3 days was 0.838 ± 0.048, at the cut-off point of 10.5 mL/kg, EVLWI showed a sensitivity of 83.9%, a specificity of 82.9%, a negative predictive value of 86.45%, and a positive predictive value of 79.79%. Their sensitivities and specificities were found to be better than APACHE Ⅱ, SOFA score. AUC of PTX3 combined with EVLWI at 1 day was 0.886 ± 0.038. On the 1st day after ICU admission, with combination of the two indicators, cut-off point was found to be 0.312, a sensitivity of 86.8%, a specificity of 85.4%, a negative predictive value of 88.93%, and a positive predictive value of 82.72%. On the 3rd day after ICU admission, AUC of PTX3 combined with EVLW! was 0.856 ± 0.046, and showed a cut-off of 0.471 for the prognosis of sepsis, a sensitivity of 85.8%, a specificity of 85.4%, a negative predictive value of 87.97%, and a positive predictive value of 82.50%. Compared with other single index, a combination of above mentioned two indexes showed a better sensitivity and specificity. Conclusions PTX3 can serve as a novel prognostic indicator at early stage in septic patients. Combined with EVLWI, it shows important value in predicting prognosis of septic patients, and it also provides guidance in treatment of high-risk patients.