Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients

TY - JOUR

T1 - Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients

AU - Bro-Jeppesen, John

AU - Johansson, Pär I

AU - Kjaergaard, Jesper

AU - Wanscher, Michael

AU - Ostrowski, Sisse R

AU - Bjerre, Mette

AU - Hassager, Christian

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/12

Y1 - 2017/12

N2 - 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 °C or 36 °C for 24 h. Inflammatory biomarkers (interleukin (IL)-6, IL-10, procalcitonin and Tumor Necrosis Factor-α (TNF-α)) 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 (β = 0.2 (95% CI: 0.06–0.3), p = 0.004) and TTM-group (TTM36: β = −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 (β = 0.3 (95% CI: 0.03–0.6), p < 0.0001), TNF-α (β = −0.4 (95% CI:− 0.5 to 0.2), p < 0.0001) and TTM-group (TTM36: β = −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 (β = 0.2 (95% CI: 0.1–0.3), p < 0.0001) and IL-10 (β = −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 (pinteraction= 0.008), but not with IL-10 (pinteraction= 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.

AB - 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 °C or 36 °C for 24 h. Inflammatory biomarkers (interleukin (IL)-6, IL-10, procalcitonin and Tumor Necrosis Factor-α (TNF-α)) 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 (β = 0.2 (95% CI: 0.06–0.3), p = 0.004) and TTM-group (TTM36: β = −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 (β = 0.3 (95% CI: 0.03–0.6), p < 0.0001), TNF-α (β = −0.4 (95% CI:− 0.5 to 0.2), p < 0.0001) and TTM-group (TTM36: β = −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 (β = 0.2 (95% CI: 0.1–0.3), p < 0.0001) and IL-10 (β = −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 (pinteraction= 0.008), but not with IL-10 (pinteraction= 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.

KW - Journal Article

U2 - 10.1016/j.resuscitation.2017.09.019

DO - 10.1016/j.resuscitation.2017.09.019

M3 - Journal article

C2 - 28947390

SN - 0300-9572

VL - 121

SP - 179

EP - 186

JO - Resuscitation

JF - Resuscitation

ER -