Abstract 18190: Associations Between Endothelial Injury, Severity of Post-cardiac Arrest Syndrome and Mortality After Out-of-hospital Cardiac Arrest

Abstract

Background: Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation and endothelial dysfunction, which may exacerbate organ failure and may be related to adverse outcome. We sought to investigate the associations between trombomodulin (TM), a marker of endothelial cell injury, and severity of PCAS and the possible prognostic importance in comatose survivors of out-of-hospital cardiac arrest treated with targeted temperature management (TTM). Methods: We included 163 patients, randomly assigned to TTM at 33°C or 36°C for 24 h in the TTM-trial at a single center. Serum TM was analyzed at 0, 24, 48 and 72 hours after cardiac arrest and stratified in median value of TM for outcome analysis at each time point to a high or low TM group. Severity of PCAS was assessed daily by the Sequential Organ Failure Assessment score. Survival status was recorded at 180 days. Results: Corresponding values of TM and severity of PCAS correlated at each time point, baseline (r=0.31, p=0.0001), 24 h (r=0.52, p<0.0001), 48 h (r=0.50, p<0.0001) and 72 h (r=0.36, p<0.0001). Levels of TM changed significantly within the first 3 days (p<0.0001) with no significant difference between temperature groups, p interaction =0.32. At 24 h, the 180-day mortality rate in patients with high TM levels (> 6.9 ng·ml -1 = median) was 42% compared to 18% in patients with low TM levels, p=0.002 (Figure), corresponding to an unadjusted hazard ratio of 2.6 (95%CI: 1.4-4.9), p=0.003. When adjusting for pre-hospital prognostic factors the hazard ratio for high TM levels at 24 h was 1.5 (95%CI: 0.7-3.1), p=0.31, with no significant interaction between level of TM and TTM-group, p=0.74. Analysis of TM at 48 and 72 hours showed similar results. Conclusions: Levels of TM are significantly elevated and associated with severity of PCAS with no effect of target temperature at 33°C or 36°C. High TM levels were associated with increased mortality, but the association was explained by confounding factors.