We studied patients from the Protocolized Care in Early Septic Shock (ProCESS) trial to determine: the effects of alternative resuscitation strategies on circulating markers of endothelial cell permeability and hemostasis, and; the association between biomarkers and mortality.
Prospective study of biomarkers of endothelial cell permeability (vegf, sflt-1, ang-2) and hemostasis (vwf, thrombomodulin, tpa) in 605 of the 1341 ProCESS participants in a derivation cohort and 305 in validation. Analyses assess: 1) impact of varying resuscitation strategies on biomarker profiles; and, 2) association of endothelial biomarkers with 60-day in-hospital mortality. The study was conducted in 31 United States EDs in adult septic shock patients. Patients were randomly assigned to one of three resuscitation strategies. Blood samples were collected at enrollment, 6, and 24 hours.
There were 116 (19.2%) and 52 (17.0%) deaths in the derivation and validation cohorts. There was no significant association between treatment strategy and any biomarker levels. Permeability (Ang-2 and SFLT-1) and hemostasis (vwf, thrombomodulin, tpa) biomarkers were higher and VEGF levels were lower in non-survivors (P<0.05 for all). At baseline, sFLT-1 had the highest point estimate for mortality discrimination (derivation AUC=0.74; validation=0.70), similar to lactate (AUC=0.74) and SOFA score (AUC=0.73). In an analysis including all time points and adjusted for age, cancer, and Charlson, sFLT-1 adjusted AUC was 0.80.
We found no relationship between different resuscitation strategies and biomarker profiles in sepsis, but we did identify that elevated levels of Endothelial Cell biomarkers of permeability and hemostasis were associated with increased mortality.