Elevated soluble thrombomodulin is associated with organ failure and mortality in children with acute respiratory distress syndrome (ARDS): A prospective observational cohort study

Introduction: The significance of endothelial injury in children with the acute respiratory distress syndrome (ARDS) has not been well studied. Plasma levels of soluble thrombomodulin (sTM), an endothelial surface protein involved in coagulation, have been associated with endothelial injury. We hypothesized that elevated plasma sTM would correlate with mortality and organ failure in children with ARDS. Methods: We conducted a multicenter prospective observational study of pediatric patients with ARDS between 2008 and 2014. sTM was measured in plasma collected less than 24hours from ARDS diagnosis. Outcomes were intensive care unit mortality and organ dysfunction by pediatric logistic organ dysfunction scores. Logistic regression was used to adjust for clinically relevant covariates. Results: Plasma sTM was higher in patients with indirect lung injury compared to direct lung injury (100ng/mL vs. 86ng/mL, p=0.02). Increased sTM levels were correlated with more organ dysfunction in the entire study population (Spearman's rho=0.37, p<0.01). Overall mortality was 16%. sTM levels were associated with increased mortality in patients with indirect lung injury (OR 2.7 per log(sTM), p=0.02). These relationships were independent of age, oxygenation defect, or presence of acute kidney injury. Conclusion: Elevated plasma sTM levels are associated with organ dysfunction in children with ARDS and with higher mortality in children with indirect lung injury. These findings highlight the importance of endothelial injury in children with ARDS and may guide the development of future therapies targeted toward endothelial stabilization, repair, or functional replacement in this population.