Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients
Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients
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DOI：
10.1016/j.resuscitation.2017.09.019
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发表时间：
2017-12-01
期刊：
影响因子：
6.5
通讯作者：
Hassager, Christian
中科院分区：
文献类型：
--
作者：
Bro-Jeppesen, John;Johansson, Par I.;Hassager, Christian
目的：心脏骤停后综合征（PCAS）以脓毒症样炎症反应和血流动力学不稳定为特征。我们调查了全身炎症，内皮损伤和血流动力学参数之间的关联，包括血管加压素支持患者院外心脏骤停（OHCA）：在这个事后研究中，我们分析了163昏迷患者的数据，包括在一个单一的中心在目标温度管理（TTM）试验，随机分配到TTM在33摄氏度或36摄氏度24小时。在随机分组和OHCA后24、48和72 h测量炎症生物标志物（白细胞介素（IL）-6，IL-10，降钙素原和肿瘤坏死因子-α（TNF-α））和内皮生物标志物（血栓调节蛋白，sE-选择素，syndecan-1和VE-钙粘蛋白）。结果：随机分组时，IL-6水平与MAP呈负相关（r =-0.19，p = 0.03），与HR呈正相关（r = 0.29，p = 0.0002）。连续IL-6水平与24 h的CVI一致相关：（r = 0.19，p = 0.02），48 h：（r = 0.31，p = 0.0001）和72 h：（r = 0.39，p < 0.0001）。血栓调节蛋白（r = 0.23，p = 0.004）和多配体蛋白聚糖-1（r = 0.27，p = 0.001）与48小时的CVI相关。所有炎症标志物均与IL-10和所有内皮标志物在72小时时与CVI相关。（β = 0.2（95% CI：0.06-0.3），p = 0.004）和TTM组（TTM 36：β = -0.5（95% CI：-0.9至0.1），p = 0.01）与48小时的CVI相关。OHCA后72 h，IL-6（β = 0.3（95% CI：0.03-0.6），p < 0.0001），TNF-α（β = -0.4（95% CI：-0.5至0.2），p < 0.0001）和TTM组（TTM 36：β = -0.4（95%CI：-0.8至0.1），p = 0.008）与CVI相关。OHCA后72小时内的IL-10（β = 0.2（95%CI：0.1-0.3），p < 0.0001）和IL-10（β = -0.2（95%CI：-0.3至0.06），p = 0.005）与CVI显著相关。TTM组改变了CVI和IL-6之间的相互作用（p（相互作用）= 0.008），但不改变与IL-10之间的相互作用（p（相互作用）= 0.23）。结论：在OHCA后昏迷的幸存者中，全身炎症和内皮损伤的增加与血管加压素支持需求的增加有关。全身性炎症，特别是IL-6，始终与血管加压素支持相关，然而内皮损伤也可能在OHCA后PCAS相关的心血管功能障碍中发挥作用。(C)2017爱思唯尔B. V.保留所有权利。
Aim: Post-cardiac arrest syndrome (PCAS) is characterized by a sepsis-like inflammatory response and hemodynamic instability. We investigated the associations between systemic inflammation, endothelial damage and hemodynamic parameters including vasopressor support in patients with out-of-hospital cardiac arrest (OHCA).Methods: In this post-hoc study, we analysed data from 163 comatose patients included at a single center in the Target Temperature Management (TTM) trial, randomly assigned to TTM at 33 degrees C or 36 degrees C for 24 h. Inflammatory biomarkers (interleukin (IL)-6, IL-10, procalcitonin and Tumor Necrosis Factor-alpha (TNF-alpha)) and endothelial biomarkers (thrombomodulin, sE-selectin, syndecan-1 and VE-cadherin) were measured at randomization and 24, 48 and 72 h after OHCA. Corresponding hemodynamic status, heart rate (HR), mean arterial pressure (MAP) and Cumulative Vasopressor Index (CVI) was reported.Results: At randomization, level of IL-6 correlated negatively with MAP (r = -0.19, p = 0.03) and positively with HR (r = 0.29, p = 0.0002). Serial IL-6 levels correlated consistently with CVI at 24 h: (r = 0.19, p = 0.02) 48 h: (r = 0.31, p = 0.0001) and 72 h: (r = 0.39, p < 0.0001). Thrombomodulin (r = 0.23, p = 0.004) and syndecan-1 (r = 0.27, p = 0.001) correlated with CVI at 48 h. All inflammatory markers excerpt IL-10 and all endothelial markers correlated with CVI at 72 h.Multivariable regression models adjusting for potential confounders confirmed that IL-6 (beta = 0.2 (95% CI: 0.06-0.3), p = 0.004) and TTM-group (TTM36: beta = -0.5 (95% CI: -0.9 to 0.1), p = 0.01) were associated with CVI at 48 h. At 72 h after OHCA, IL-6 (beta = 0.3 (95% CI: 0.03-0.6), p < 0.0001), TNF-alpha (beta = -0.4 (95% CI:-0.5 to 0.2), p < 0.0001) and TTM-group (TTM36: beta = -0.4 (95% CI: -0.8 to 0.1), p = 0.008) were associated with CVI.An overall two-fold increase in levels of IL-6 (beta = 0.2 (95% CI: 0.1-0.3), p < 0.0001) and IL-10 (beta = -0.2 (95% CI: -0.3 to 0.06), p = 0.005) within 72 h after OHCA were significantly associated with CVI. TTM-group modified the interaction between CVI and IL-6 (p(interaction) = 0.008), but not with IL-10 (p(interaction) = 0.23).Conclusions: In comatose survivors after OHCA, increasing systemic inflammation and endothelial injury was associated with increased need of vasopressor support. Systemic inflammation, in particular IL-6, was consistently associated with vasopressor support, however endothelial injury may also play a role in PCAS associated cardiovascular dysfunction after OHCA. (C) 2017 Elsevier B.V. All rights reserved.