Sympathoadrenal activation and endothelial damage are inter correlated and predict increased mortality in patients resuscitated after out-of-hospital cardiac arrest. a post Hoc sub-study of patients from the TTM-trial

Pär I Johansson, John Bro-Jeppesen, Jesper Kjaergaard, Michael Wanscher, Christian Hassager, Sisse R Ostrowski, Pär I Johansson, John Bro-Jeppesen, Jesper Kjaergaard, Michael Wanscher, Christian Hassager, Sisse R Ostrowski

Abstract

Objective: Sympathoadrenal activation and endothelial damage are hallmarks of acute critical illness. This study investigated their association and predictive value in patients resuscitated from out-of-hospital cardiac arrest (OHCA).

Methods: Post-hoc analysis of patients included at a single site in The Targeted Temperature Management at 33 degrees versus 36 degrees after Cardiac Arrest (TTM) trial. The main study reported similar outcomes with targeting 33 versus 36 degrees. TTM main study ClinicalTrials.gov: NCT01020916. One hundred sixty three patients resuscitated from OHCA were included at a single site ICU. Blood was sampled a median 135 min (Inter Quartile Range (IQR) 103-169) after OHCA. Plasma catecholamines (adrenaline, noradrenaline) and serum endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) were measured at admission (immediately after randomization). We had access to data on demography, medical history, characteristics of the OHCA, patients and 180-day outcome.

Results: Adrenaline and noradrenaline correlated positively with syndecan-1 and thrombomodulin i.e., biomarkers reflecting endothelial damage (both p<0.05). Overall 180-day mortality was 35%. By Cox analyses, plasma adrenaline, serum sE-selectin, reflecting endothelial cell activation, and thrombomodulin levels predicted mortality. However, thrombomodulin was the only biomarker independently associated with mortality after adjusting for gender, age, rhythm (shockable vs. non-shockable), OHCA to return of spontaneous circulation (ROSC) time, shock at admission and ST elevation myocardial infarction (30-day Hazards Ratio 1.71 (IQR 1.05-2.77), p=0.031 and 180-day Hazards Ratio 1.65 (IQR 1.03-2.65), p=0.037 for 2-fold higher thrombomodulin levels).

Conclusions: Circulating catecholamines and endothelial damage were intercorrelated and predicted increased mortality. Interventions aiming at protecting and/or restoring the endothelium may be beneficial in OHCA patients.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Correlations between admission levels of…
Fig 1. Correlations between admission levels of syndecan-1 or thrombomodulin, reflecting endothelial glycocalyx and cell damage, respectively, and plasma (p)-adrenaline (pg/ml) (A and D), administered adrenaline (mg) (B and E) and pH (C and F) in 163 OHCA patients
P- and rho-values for Spearman´s correlations are displayed.
Fig 2. Kaplan-Meier plots displaying 180-day mortality…
Fig 2. Kaplan-Meier plots displaying 180-day mortality in 163 OHCA patients stratified according to median levels (high vs. low) of A) plasma (p)-adrenaline and B) Serum thrombomodulin at hospital admission.
Chi-square and p-values for log-rank tests are shown.

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