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

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.