血管外肺水指数和血管生成素-2动态变化对严重多发伤合并ARDS患者预后的预测价值

Prognostic value of the dynamic changes in extra vascular lung water index and angiopoietin-2 in severe multiple trauma patients with acute respiratory distress syndrome

目的观察严重多发伤合并急性呼吸窘迫综合征(ARDS)患者血管外肺水指数(EVLWI)和血管生成素-2(Ang-2)的动态变化,分析影响短期病死率的危险因素,并评价其对预后的预测价值。方法选择2014年6月至2018年12月贵州医科大学附属医院急诊重症医学科(ICU)收治的115例严重多发伤合并ARDS患者。记录所有患者的急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、创伤严重度评分(ISS)以及入ICU 0(即刻)、24、48、72 h氧合指数(PaO2/FiO2)、EVLWI〔脉搏指示连续心排血量(PiCCO)监测〕、血浆Ang-2水平〔酶联免疫吸附试验(ELISA)〕,计算PaO2/FiO2、EVLWI和Ang-2在0 h与72 h的差值(ΔPaO2/FiO2、ΔEVLWI、ΔAng-2)。记录患者28 d生存情况,并将患者分为存活组和死亡组。比较两组患者上述指标间的差异;采用多因素Logistic回归分析筛选影响预后的危险因素;绘制受试者工作特征曲线(ROC),分析ΔEVLWI、ΔAng-2对预后的预测价值,并构建Kaplan-Meier生存曲线。结果115例患者均纳入最终分析,其中28 d存活72例,死亡43例,病死率为37.4%。死亡组患者APACHEⅡ、ISS评分均明显高于存活组〔APACHEⅡ(分):25.7±2.7比20.6±2.2,ISS(分):22.1±3.1比18.1±2.1,均P<0.05〕。EVLWI和Ang-2在存活组随入ICU时间延长呈逐渐下降趋势,而在死亡组随时间推移无明显变化;经平行轮廓检验,均P<0.05,说明两组间曲线变化趋势不同,且不平行。死亡组EVLWI、Ang-2、PaO2/FiO2水平在0~24 h与存活组比较差异无统计学意义,而于48 h起EVLWI、Ang-2明显高于存活组〔EVLWI(mL/kg):15.5±4.2比10.8±3.2,Ang-2(ng/L):352.7±51.2比237.9±42.8,均P<0.05〕,PaO2/FiO2明显低于存活组〔mmHg(1 mmHg=0.133 kPa):126.1±43.7比211.2±33.8,P<0.05〕;死亡组患者ΔEVLWI和ΔAng-2均明显低于存活组〔ΔEVLWI(mL/kg):-0.9±6.1比3.1±6.4,ΔAng-2(ng/L):-45.3±32.1比79.8±58.2,均P<0.05〕,但ΔPaO2/FiO2与存活组比较差异无统计学意义(mmHg:23.2±24.2比-22.1±22.8,P>0.05)。多因素Logistic回归分析显示,ΔEVLWI〔优势比(OR)=2.811,95%可信区间(95%CI)=1.232~3.161,P=0.001〕、ΔAng-2(OR=2.204,95%CI=1.012~3.179,P=0.001)和APACHEⅡ评分(OR=1.206,95%CI=1.102~1.683,P=0.002)为严重多发伤合并ARDS患者28 d死亡的独立危险因素。ROC曲线分析显示,ΔEVLWI预测严重多发伤合并ARDS患者28 d预后的ROC曲线下面积(AUC)为0.832,大于ΔAng-2(AUC=0.790)和APACHEⅡ评分(AUC=0.735);当ΔEVLWI的最佳截断值为2.3 mL/kg时,其敏感度为79.1%,特异度为81.9%。Kaplan-Meier生存曲线分析显示,ΔEVLWI>2.3 mL/kg患者28 d累积生存率显著高于ΔEVLWI≤2.3 mL/kg者(log-rank检验:χ^2=23.385,P=0.000)。结论ΔEVLWI与ΔAng-2可作为预测严重多发伤合并ARDS患者28 d死亡的独立危险因素,且ΔEVLWI预测价值优于ΔAng-2和APACHEⅡ评分;动态监测EVLWI可提高预测死亡的准确性。

Objective To observe the dynamic changes in extra vascular lung water index(EVLWI)and angiopoietin-2(Ang-2)in severe multiple trauma patients with acute respiratory distress syndrome(ARDS),analyze the risk factor for short-term mortality,and to evaluate their prognostic values for prognosis.Methods A total of 54 severe multiple trauma patients with ARDS admitted to emergency intensive care unit(ICU)of the Affiliated Hospital of Guizhou Medical University from June 2014 to December 2018 were enrolled.The acute physiology and chronic health evaluationⅡ(APACHEⅡ),injury severity score(ISS)and oxygenation index(PaO2/FiO2),EVLWI[pulse-induced contour cardiac output(PiCCO)monitor]and plasma Ang-2 level[enzyme-linked immunosorbent assay(ELISA)]at 0(immediately),24,48 and 72 hours after ICU admission,and the differences in PaO2/FiO2,EVLWI and Ang-2 between 0 hour and 72 hours(ΔPaO2/FiO2,ΔEVLWI,ΔAng-2)were calculated.The 28-day survival of patients was recorded,and the patients were divided into survival group and non-survival group.The differences in above mentioned parameters between the two groups were compared.Multivariate Logistic regression was used to analyze the independent risk factors associated with the prognosis.Receiver operating characteristic(ROC)curve was drawn to evaluate the prognostic values ofΔEVLWI andΔAng-2 on the prognosis,and the Kaplan-Meier survival curve was plotted.Results 115 patients were enrolled in the final analysis,72 survived in 28 days,43 died,and the mortality rate was 37.4%.The APACHEⅡand ISS scores of the non-survival group were significantly higher than those of the survival group[APACHEⅡscore:25.7±2.7 vs.20.6±2.2,ISS score:22.1±3.1 vs.18.1±2.1,both P<0.05].EVLWI and Ang-2 showed a gradual downwards tendency with the prolongation of the length of ICU stay in the survival group,but no significant change was found in the non-survival group.Parallel contour test showed that both P<0.05,indicating that the curves between the two groups had different tendencies and were not parallel.The levels of EVLWI,Ang-2 and PaO2/FiO2 showed no statistical differences from 0 hour to 24 hours between the two groups,but EVLWI and Ang-2 in the non-survival group were significantly higher than those in the survival group from 48 hours on[EVLWI(mL/kg):15.5±4.2 vs.10.8±3.2,Ang-2(ng/L):352.7±51.2 vs.237.9±42.8,both P<0.05],and PaO2/FiO2 was significantly decreased[mmHg(1 mmHg=0.133 kPa):126.1±43.7 vs.211.2±33.8,P<0.05].TheΔEVLWI andΔAng-2 in the non-survival group were significantly lower than those in the survival group[ΔEVLWI(mL/kg):-0.9±6.1 vs.3.1±6.4,ΔAng-2(ng/L):-45.3±32.1 vs.79.8±58.2,both P<0.05],butΔPaO2/FiO2 showed no significant difference as compared with the survival group(mmHg:23.2±24.2 vs.-22.1±22.8,P>0.05).Multivariate Logistic regression analysis demonstrated thatΔEVLWI[odds ratio(OR)=2.811,95%confidence interval(95%CI)=1.232-3.161,P=0.001],ΔAng-2(OR=2.204,95%CI=1.012-3.179,P=0.001)and APACHEⅡ(OR=1.206,95%CI=1.102-1.683,P=0.002)were independent risk factors for 28-day mortality of severe multiple trauma patients with ARDS.ROC curve analysis showed that the area under ROC curve(AUC)ofΔEVLWI for predicting 28-day prognosis of severe multiple trauma patients with ARDS was 0.832,which was higher thanΔAng-2(AUC=0.790)and APACHEⅡ(AUC=0.735).When the cut-off value ofΔEVLWI was 2.3 mL/kg,the sensitivity was 79.1%,and the specificity was 81.9%.Kaplan-Meier survival curve showed that the patients withΔEVLWI>2.3 mL/kg had a significantly higher 28-day cumulative survival rate as compared with the patients withΔEVLWI≤2.3 mL/kg(log-rank test:χ^2=23.385,P=0.000).ConclusionsΔEVLWI andΔAng-2 can be used as independent risk factors for 28-day mortality of severe multiple trauma patients with ARDS,and the predictive value ofΔEVLWI was better than Ang-2 and APACHEⅡ.Dynamic observation of EVLWI could improve the accuracy of death forecasting for severe multiple trauma patients with ARDS.