Abstract

Background Inflammation and endothelial damage accelerate cleavage of endothelium bound Thrombomodulin (TM). Elevated soluble TM (sTM) in plasma is associated with adverse outcomes in sepsis and DIC in adults, but this has not been studied among children with ARDS. Objective Test the relationship of plasma sTM with clinical outcomes in paediatric ARDS. Design/methods We measured sTM in plasma collected within 24 h of onset of ARDS (diagnosed by Berlin criteria) in an ongoing multi-centre observational cohort. We used non-parametric Mann-Whitney and trend tests, and regression models. Results Baseline characteristics of study population are shown in Table. Among children with indirect lung injury, mean sTM levels were higher in non-survivors [241 ng/mL (102–134)] compared to survivors [118 ng/mL (107–374)] (p = 0.004). Mortality and Paediatric Logistic Organ Dysfunction (PELOD) score increased stepwise by tertile of plasma sTM (figure). On logistic regression, the odds of death increased by 4.5 for every log increase in plasma sTM and the association was independent of age, race, gender and severity of illness. No such relationship existed for direct ARDS. Conclusions Higher plasma sTM is associated with increased mortality and organ failure in children with indirect ARDS. This supports the importance of endothelial injury and TM in pathobiology of indirect ARDS and suggests that early elevation in plasma sTM is an independent risk factor for mortality.

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