Relationship Between Alternative Resuscitation Strategies, Host Response and Injury Biomarkers, and Outcome in Septic Shock: Analysis of the Protocol-Based Care for Early Septic Shock Study.
Relationship Between Alternative Resuscitation Strategies, Host Response and Injury Biomarkers, and Outcome in Septic Shock: Analysis of the Protocol-Based Care for Early Septic Shock Study.
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DOI：
10.1097/ccm.0000000000002206
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发表时间：
2017-03
影响因子：
8.8
通讯作者：
and the Protocol-based Care for Early Septic Shock Investigators (ProCESS) Investigators
中科院分区：
文献类型：
--
作者：
Kellum JA;Pike F;Yealy DM;Huang DT;Shapiro NI;Angus DC;and the Protocol-based Care for Early Septic Shock Investigators (ProCESS) Investigators
基于方案的早期感染性休克护理 (ProCESS) 试验发现，替代复苏策略在全因死亡率方面没有差异。另一个目的是确定复苏策略的差异是否影响与脓毒症下游临床结果相关的关键途径的生物标志物轨迹，以及具有不同基线生物标志物特征的患者在不同治疗组的生存率是否存在差异。大型随机临床试验的二次分析。 31家美国医院。 628 名感染性休克患者。两种复苏方案与常规护理的对比。我们测量了一组代表四个病理生理学领域的生物标志物：炎症（肿瘤坏死因子、白介素-6 和 -10）；凝血（D-二聚体，凝血酶-抗凝血酶复合物）；治疗后0、6、24和72小时的氧化应激（尿液异前列烷）和组织缺氧（乳酸）。我们分析了替代复苏策略是否会影响 72 小时内的生物标志物轨迹，以及对 90 天住院死亡率的影响是否因基线（时间 0）生物标志物概况而异，两者均使用具有治疗组交互项的回归模型。对于所有基线生物标志物，较高浓度与 90 天死亡风险增加相关。然而，治疗分配对随后的生物标志物轨迹没有显着影响。我们确实发现了基于方案的护理对具有不同基线 [IL-6] 和 [IL-6]·[IL-10] 特征的患者的死亡率的治疗效果存在异质性的证据，其中最低四分位的患者在基于方案的护理中表现更好（比值比分别为 0.32 [0.13, 075] p=0.01 和 0.32 [0.14, 0.73] p=0.01）。在感染性休克患者中，炎症、凝血、氧化应激和组织缺氧的改变很常见，并且与不良结局相关，但与常规护理相比，不受基于方案的复苏的影响。然而，与预期相反，基于方案的复苏似乎对于炎症生物标志物浓度较低的患者更有效。造成这种效应的机制尚不清楚。
The Protocol-based Care for Early Septic Shock (ProCESS) trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. Secondary analysis of a large randomized clinical trial. 31 US hospitals. 628 patients with septic shock. Two resuscitation protocols versus usual care. We measured a panel of biomarkers representing four pathophysiologic domains: inflammation (tumor necrosis factor, interleukin-6, and -10); coagulation (D-dimers, thrombin-anti-thrombin complex); oxidative stress (urine isoprostane) and tissue hypoxia (lactate) at 0, 6, 24 and 72 hours after treatment. We analyzed whether alternative resuscitation strategies affected biomarker trajectories over 72 hours and whether effects on 90-day hospital mortality varied by baseline (time 0) biomarker profiles—both using regression models with interaction terms for treatment arms. For all baseline biomarkers, higher concentrations were associated with increased risk of death by 90 days. However, there was no significant effect of treatment assignment on subsequent biomarker trajectories. We did find evidence for heterogeneity of treatment effect of protocol-based care on mortality for patients with different baseline [IL-6] and [IL-6]•[IL-10] profiles wherein patients with the lowest quartiles fared better with protocol-based care (Odds Ratios 0.32 [0.13, 075] p=0.01 and 0.32 [0.14, 0.73] p=0.01 respectively). In patients with septic shock, alterations in inflammation, coagulation, oxidative stress and tissue hypoxia are common and associated with adverse outcomes but are not influenced by protocol-based resuscitation compared to usual care. However, contrary to expectation, protocol-based resuscitation appeared to be superior in patients with lower concentrations of inflammatory biomarkers. The mechanisms responsible for this effect are unclear.