Objective
We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of Macrophage Activation Syndrome (MAS), and Multiple Organ Failure (MOF) related death in pediatric severe sepsis.
Design
Prospective cohort study comparing children with severe sepsis and any of three phenotypes; 1) Immune paralysis Associated MOF (whole blood ex vivo TNF response to endotoxin < 200 pg/mL), 2) Thrombocytopenia Associated MOF (new onset thrombocytopenia with acute kidney injury and ADAMTS13 activity < 57%), and / or 3) Sequential MOF with Hepatobiliary Dysfunction (respiratory distress followed by liver dysfunction with sFASL > 200 pg/mL), to those without any of these phenotypes.
Setting
Tertiary children's hospital pediatric intensive care unit.
Patients
One hundred consecutive severe sepsis admissions.
Interventions
Clinical data was recorded daily and blood was collected twice weekly.
Measurements and Main Results
Seventy five cases developed MOF and 8 died. MOF cases with any of the three inflammation phenotype(s) (n = 37) had higher inflammation (C-reactive protein p=0.009 and ferritin p<0.001) than MOF cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of MAS and death were more common among MOF cases with any of the phenotypes (MAS 10/37, 27%; death 8/37, 22%) compared to MOF cases without any phenotype (MAS 1/38, 3%, p=0.003, death 0/38, 0%, p=0.002).
Conclusion
Our approach to phenotype categorization remains hypothetical and the phenotypes identified need to be confirmed in multicenter studies of pediatric MODS.