• Joseph A Carcillo, E Scott Halstead, Mark W Hall, Trung C Nguyen, Ron Reeder, Rajesh Aneja, Bita Shakoory, Dennis Simon, and Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigators.
• 1Department of Critical Care Medicine, Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA. 2Department of Pediatrics, Nationwide Children's Hospital and Ohio State University, Columbus, OH. 3Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX. 4Department of Pediatrics, University of Utah, Salt Lake City, UT. 5Department of Medicine, George Washington University Hospital, Washington, DC.
• Pediatr Crit Care Me. 2017 Jun 1; 18 (6): 513-523.

ObjectivesWe hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis.DesignProspective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes.SettingTertiary children's hospital PICU.PatientsOne hundred consecutive severe sepsis admissions.InterventionsClinical data were recorded daily, and blood was collected twice weekly.Measurements And Main ResultsMultiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002).ConclusionsOur approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

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