Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels.

Interest 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. A prospective, observational cohort study. Children with sepsis and organ failure in nine pediatric intensive care units in the United States. Two 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. Group 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. Bedside 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.

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Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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Drs. Horvat’s, Banks’, Newth’s, Shanley’s, Zuppa’s, Sward’s, Dean’s, and Carcillo’s and institutions received funding from the National Institutes of Child Health and Human Development (NICHD). Drs. Banks’s, Berg’s, Wessel’s, Pollack’s, Meert’s, Hall’s, Newth’s, Doctor’s, Shanley’s, Cornell’s, Harrison’s, Zuppa’s, Reeder’s, Holubkov’s, Dean’s, and Carcillo’s institutions received funding from the National Institutes of Health (NIH). Drs. Horvat, Banks, Park, Kernan, Canna, Berg, Wessel, Pollack, Meert, Hall, Newth, Doctor, Shanley, Harrison, Zuppa, Reeder, Sward, Holubkov, Dean, and Carcillo received support for article research from the NIH. Drs. Horvat and Carcillo disclosed the off-label product use of Tumor Necrosis Factor Receptor Apoptosis Inducing Ligand Interleukin Receptor Antagonist Protein. Dr. Kernan’s institution received funding from the NICHD (K12HD047349). Dr. Canna’s institution received funding from InnVention Therapeutix; he received funding from Simcha Therapeutics. Dr. Pollack disclosed that his research is supported by philanthropy from Mallinckrodt Pharmaceuticals. Dr. Hall received funding from La Jolla Pharmaceuticals, Abbvie, and Kiadis. Dr. Hall received funding from Bristol Myers-Squibb (for service on an advisory board) and LaJolla Pharmaceuticals (service as a consultant), both unrelated to the current submission. Dr. Newth received funding from Philips Research North America, Hamilton Medical AG, and Nihon Kohden Orange Med. Dr. Doctor’s institution received funding from the Department of Defense and KaloCyte. Dr. Shanley received funding from Springer publishing, International Pediatric Research Foundation, and Pediatric Academic Societies. Dr. Cornell disclosed he is co-founder of Pre-Dixon Bio. Dr. Holubkov’s institution received funding from AltaThera Pharmaceuticals; he received funding from Pfizer (Data Safety Monitoring Board [DSMB] member), Medimmune (DSMB member), the Physicians Committee for Responsible Medicine (biostatistical consulting), DURECT corporation (biostatistical consulting), Armaron Bio (DSMB past member), and St Jude Medical (DSMB past member). Dr. Carcillo’s institution received funding from the National Institutes of General Medical Sciences. The remaining authors have disclosed that they do not have any potential conflicts of interest.