John Bro-Jeppesen1, Pär I Johansson2, Jesper Kjaergaard3, Michael Wanscher4, Sisse R Ostrowski5, Mette Bjerre6, Christian Hassager3. 1. Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Denmark. Electronic address: jbj@dadlnet.dk. 2. Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery, Division of Acute Care Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School at Houston, TX, USA. 3. Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Denmark. 4. Department of Cardiothoracic Anesthesiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Denmark. 5. Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark. 6. The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Denmark.
Abstract
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 24h. 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 72h 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 24h: (r=0.19, p=0.02) 48h: (r=0.31, p=0.0001) and 72h: (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 48h. All inflammatory markers excerpt IL-10 and all endothelial markers correlated with CVI at 72h. 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 48h. At 72h 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 72h 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.
RCT Entities:
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 comatosepatients included at a single center in the Target Temperature Management (TTM) trial, randomly assigned to TTM at 33°C or 36°C for 24h. 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 72h 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 24h: (r=0.19, p=0.02) 48h: (r=0.31, p=0.0001) and 72h: (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 48h. All inflammatory markers excerpt IL-10 and all endothelial markers correlated with CVI at 72h. 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 48h. At 72h 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 72h 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.
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