Endothelial Permeability and Hemostasis in Septic Shock Results From the ProCESS Trial
Endothelial Permeability and Hemostasis in Septic Shock Results From the ProCESS Trial
复制标题
DOI：
10.1016/j.chest.2017.01.010
复制
发表时间：
2017-07-01
期刊：
影响因子：
9.6
通讯作者：
Shapiro, Nathan I.
中科院分区：
文献类型：
--
作者：
Hou, Peter C.;Filbin, Michael R.;Shapiro, Nathan I.
背景：我们对早期感染性休克的规范化治疗（ProCESS）试验中的患者进行了研究，以确定不同复苏策略对内皮细胞通透性和止血的循环标志物的影响，以及生物标志物与死亡率之间的关联。
方法：这是一项对内皮细胞通透性生物标志物（血管内皮生长因子[VEGF]、可溶性类fms酪氨酸激酶1[sFLT - 1]、血管生成素2[Ang - 2]）和止血生物标志物（血管性血友病因子[vWF]、血栓调节蛋白[TM]、组织型纤溶酶原激活物[tPA]）的前瞻性研究，研究对象包括推导队列中1341名ProCESS参与者中的605名以及验证队列中的305名参与者。分析评估了（1）不同复苏策略对生物标志物谱的影响，以及（2）内皮生物标志物与60天住院死亡率的关联。该研究在美国31个急诊科的成年感染性休克患者中进行。患者被随机分配到三种复苏策略中的一种。在入组时、6小时和24小时采集血液样本。
结果：推导队列和验证队列中分别有116例（19.2%）和52例（17.0%）死亡。治疗策略与任何生物标志物水平之间均无显著关联。在未存活者中，通透性（Ang - 2和sFLT - 1）和止血（vWF、TM、tPA）生物标志物水平较高，而VEGF水平较低（所有指标P <.05）。在基线时，sFLT - 1对死亡率区分的点估计值最高（推导曲线下面积[AUC]为0.74；验证为0.70），与乳酸（AUC为0.74）和序贯器官衰竭评估评分（AUC为0.73）相似。在一项包括所有时间点并对年龄、癌症存在情况和查尔森合并症评分进行调整的分析中，sFLT - 1调整后的AUC为0.80。
结论：我们发现脓毒症中不同复苏策略与生物标志物谱之间没有关系，但我们确实发现内皮细胞通透性和止血生物标志物水平升高与死亡率增加有关。
BACKGROUND: We studied patients from the Protocolized Care in Early Septic Shock (ProCESS) trial to determine the effects of alternative resuscitation strategies on circulating markers of endothelial cell permeability and hemostasis and the association between biomarkers and mortality.METHODS: This was a prospective study of biomarkers of endothelial cell permeability (vascular endothelial growth factor [VEGF], soluble fms-like tyrosine kinase 1 [sFLT-1], angiopoietin 2 [Ang-2]) and biomarkers of hemostasis (von Willebrand factor [vWF], thrombomodulin [TM], tissue plasminogen activator [tPA] in 605 of the 1,341 ProCESS participants in a derivation cohort and 305 participants in a validation cohort. Analyses assessed (1) the impact of varying resuscitation strategies on biomarker profiles and (2) the association of endothelial biomarkers with 60-day in-hospital mortality. The study was conducted in 31 US EDs in adult patients with septic shock. Patients were randomly assigned to one of three resuscitation strategies. Blood samples were collected at enrollment, at 6 h, and at 24 h.RESULTS: There were 116 (19.2%) and 52 (17.0%) deaths in the derivation and validation cohorts, respectively. There was no significant association between treatment strategy and any biomarker levels. Permeability (Ang-2 and sFLT-1) and hemostasis (vWF, TM, tPA) biomarkers were higher and VEGF levels were lower in nonsurvivors (P < .05 for all). At baseline, sFLT-1 had the highest point estimate for mortality discrimination (derivation area under the curve [AUC], 0.74; validation, 0.70), similar to lactate (AUC, 0.74) and Sequential Organ Failure Assessment score (AUC, 0.73). In an analysis including all time points and adjusted for age, presence of cancer, and Charlson comorbidity score, the adjusted AUC for sFLT-1 was 0.80.CONCLUSIONS: We found no relationship between different resuscitation strategies and biomarker profiles in sepsis, but we did find that elevated levels of endothelial cell biomarkers of permeability and hemostasis were associated with increased mortality.