• Christopher M Horvat, Anthony Fabio, Daniel S Nagin, Russell K Banks, Yidi Qin, Hyun-Jung Park, Kate F Kernan, Scott W Canna, Robert A Berg, David Wessel, Murray M Pollack, Kathleen Meert, Mark Hall, Christopher Newth, John C Lin, Allan Doctor, Tom Shanley, Tim Cornell, Rick E Harrison, Athena F Zuppa, Ron W Reeder, Kathy Sward, Richard Holubkov, Daniel A Notterman, J Michael Dean, Joseph A Carcillo, and on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
• Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA.
• Pediatr Crit Care Me. 2022 Dec 1; 23 (12): 968979968-979.

ObjectivesInterest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.Data SourcesA prospective, observational cohort study.Study SelectionChildren with sepsis and organ failure in nine pediatric intensive care units in the United States.Data ExtractionTwo hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin.Data SynthesisGroup 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines.ConclusionsBedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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