Abstract:

Objective　To analyze the relationships between serum lactate (Lac), D-dimer (D-D), soluble thrombomodulin (sTM), and endothelium-specific molecule-1 (ESM-1) levels and 28-day mortality in patients with sepsis associated acute respiratory distress syndrome (SAARDS). Methods　This was a cohort study. A total of 375 SAARDS patients treated in Tianjin First Central Hospital and Special Medical Center of Armed Police from January 2018 to January 2023 were selected as the study objects, including 198 males and 177 females, aged (65.26±11.35) years. According to the oxygenation index (OI) at admission, the patients were divided into a mild group [96 cases, OI >200 mmHg (1 mmHg=0.133 kPa)], a moderate group (152 cases, OI >100 - 200 mmHg), and a severe group (127 cases, OI ≤100 mmHg). They were divided into a survival group (238 cases) and a death group (137 cases) according to the survival conditions within 28 days. Spearman correlation coefficient was used to analyze the correlations between OI and serum Lac, D-D, sTM, and ESM-1 levels in SAARDS patients. Multivariate logistic regression analysis was used to analyze the independent risk factors affecting the prognosis in SAARDS patients, and the predictive value of the risk factors was analyzed using the receiver operating characteristic curve (ROC). For the measurement data conforming to normal distribution, t test was used for comparison between two groups, F test was used for comparison among multiple groups, and SNK method was used for pairwise comparison. Kruskal-Wallis test was used for the measurement data conforming to non-normal distribution, and Bonferroni correction was used for pairwise comparison. The count data were measured using χ² test. Results　Serum Lac, D-D, sTM, and ESM-1 levels were increased sequentially in the mild group, moderate group, and severe group (all P<0.001). Serum Lac, D-D, sTM, and ESM-1 levels were negatively correlated with OI (r=-0.663, -0.664, -0.690, and -0.682, all P<0.001). The proportions of septic shock, ICU time ≥10 days, and mechanical ventilation time ≥3 days, the levels of age, D-D, sTM, Lac, and ESM-1, and the Sepsis-Related Organ Failure Assessment (SOFA) score of the death group were higher than those of the survival group [65.69% (90/137) vs. 52.10% (124/238), 63.50% (87/137) vs. 52.10% (124/238), 58.39% (80/137) vs. 47.06% (112/238), (66.24±4.73) years old vs. (64.87±6.07) years old, (3.59±0.84) mg/L vs. (2.87±0.70) mg/L, (125.77±19.25) μg/L vs. (102.29±20.94) μg/L, 8.39 (7.31, 8.84) mmol/L vs. 5.62 (4.11, 8.04) mmol/L, 3.91 (3.20, 4.48) μg/L vs. 2.92 (2.31, 3.47) μg/L, 14.00 (12.00, 17.00) points vs. 12.00 (10.00, 13.00) points], but the OI was significantly lower than that of the survival group [92.74 (82.83, 156.64) mmHg vs. 183.87 (137.68, 254.56) mmHg], with statistically significant differences (χ²=5.675, 4.594, and 4.471, t=2.439, 9.232, and 10.767, Z=9.199, 9.319, 7.270, and 8.723; all P<0.05). Multivariate logistic regression analysis showed that septic shock, SOFA score, Lac, D-D, sTM, and ESM-1 were independent risk factors for poor prognosis in SAARDS patients (OR=2.625, 3.410, 1.461, 2.231, 1.048, 1.316, all P<0.05), while OI was an independent protective factor (OR=0.978, P<0.05). ROC analysis showed that serum Lac [area under the curve (AUC) = 0.786], D-D (AUC=0.748), sTM (AUC=0.797), and ESM-1 (AUC=0.788) in SAARDS patients had certain predictive value for death within 28 days. The AUC of combined prediction of the four was 0.908, which was higher than that of any single index (P<0.001). Conclusion　Serum Lac, D-D, sTM, and ESM-1 levels are independent risk factors for 28-day death in SAARDS patients, and have certain predictive value for 28-day death.

Key words:

Sepsis, Acute respiratory distress syndrome, Lactate, D-dimer, Soluble thrombomodulin, Endothelium-specific molecule-1, Prognosis

摘要：

目的　分析脓毒症相关急性呼吸窘迫综合征（ARDS）患者血清乳酸（Lac）、D-二聚体（D-D）、可溶性血栓调节蛋白（sTM）、内皮细胞特异性分子-1（ESM-1）水平与患者28 d死亡的关系。方法　采用队列研究选取2018年1月至2023年1月天津市第一中心医院和武警特色医学中心救治的375例脓毒症相关ARDS患者作为研究对象，其中男198例、女177例，年龄（65.26±11.35）岁。根据入院氧合指数（OI）分为轻度组［96例，OI>200 mmHg（1 mmHg=0.133 kPa）］、中度组（152例，OI>100～200 mmHg）和重度组（127例，OI≤100 mmHg），根据28 d内生存情况分为存活组（238例）和死亡组（137例）。Spearman相关系数分析脓毒症相关ARDS患者OI与血清Lac、D-D、sTM、ESM-1水平的相关性；多因素logistic回归分析影响脓毒症相关ARDS患者预后的危险影响因素，并使用受试者操作特征曲线（ROC）构建危险因素预测其发生的价值。符合正态分布的计量资料两组间比较采用t检验，多组间比较使用F检验，两两比较使用SNK法；非正态分布使用Kruskal-Wallis检验，两两比较使用Bonferroni校正；计数资料使用χ²检验。结果　3组脓毒症相关ARDS患者血清Lac、D-D、sTM和ESM-1水平比较，轻度组<中度组<重度组（均P<0.001）。血清Lac、D-D、sTM、ESM-1水平与OI均呈负相关（r=-0.663、-0.664、-0.690、-0.682，均P<0.001）。死亡组脓毒性休克比例、ICU时间≥10 d、机械通气时间≥3 d、年龄、D-D、sTM、Lac、ESM-1水平及脓毒症相关器官衰竭评估（SOFA）评分均高于存活组［65.69%（90/137）比52.10%（124/238）、63.50%（87/137）比52.10%（124/238）、58.39%（80/137）比47.06%（112/238）、（66.24±4.73）岁比（64.87±6.07）岁、（3.59±0.84）mg/L比（2.87±0.70）mg/L、（125.77±19.25）μg/L比（102.29±20.94）μg/L、8.39（7.31，8.84）mmol/L比5.62（4.11，8.04）mmol/L、3.91（3.20，4.48）μg/L比2.92（2.31，3.47）μg/L、14.00（12.00，17.00）分比12.00（10.00，13.00）分］，OI低于存活组［92.74（82.83，156.64）mmHg比183.87（137.68，254.56）mmHg］，差异均有统计学意义（χ²=5.675、4.594、4.471，t=2.439、9.232、10.767，Z=9.199、9.319、7.270、8.723；均P<0.05）。多因素logistic回归分析显示，脓毒性休克、SOFA评分、Lac、D-D、sTM和ESM-1为脓毒症相关ARDS患者预后不良的独立危险因素（OR=2.625、3.410、1.461、2.231、1.048、1.316，均P<0.05），OI为独立保护因素（OR=0.978，P<0.05）。ROC分析显示，脓毒症相关ARDS患者血清Lac［曲线下面积（AUC）=0.786］、D-D（AUC=0.748）、sTM（AUC=0.797）和ESM-1（AUC=0.788）对28 d死亡具有一定预测价值，而四者联合预测的AUC为0.908，大于任一单项指标（P<0.001）。结论　血清Lac、D-D、sTM和ESM-1水平是脓毒症相关ARDS患者28 d死亡的独立危险因素，对28 d死亡具有一定预测价值。

关键词:

脓毒症, 急性呼吸窘迫综合征, 乳酸, D-二聚体, 可溶性血栓调节蛋白, 内皮细胞特异性分子-1, 预后