Christopher Horvat, MD, MHA
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania
Disclosure information not submitted.
Anthony Fabio, MPH, PhD
Associate Professor of Epidemiology
University of Pittsburgh, United States
Disclosure information not submitted.
Daniel Nagin, PhD
Professor
Carnegie Mellon University, United States
Disclosure information not submitted.
Collaborative Pediatric Critical Care Research Network, n/a
.
National Institute of Child Health and Human Development
Ethnicity, United States
Disclosure information not submitted.
Robert Berg, MD, MCCM (he/him/his)
Division Chief, Pediatric Critical Care Medicine
Children's Hospital of Philadelphia
Merion Station, Pennsylvania, United States
Disclosure information not submitted.
David Wessel, MD
Executive Vice President, Chief Medical Officer, Physician-In-Chief
Childrens National Health Systems, United States
Disclosure information not submitted.
Murray Pollack, MBA, MD, MCCM
M.D.
Childrens National Health Systems, United States
Disclosure information not submitted.
Kathleen Meert, MD, FCCM (she/her/hers)
Professor and Chairman of Pediatrics
Children's Hospital of Michigan
Detroit, Michigan, United States
Disclosure information not submitted.
Mark Hall, MD, FCCM
Chief Division Pediatric Critical Care Medicine
Nationwide Children's Hospital At Ohio State University
Columbus, Ohio, United States
Disclosure information not submitted.
Christopher Newth, MD, ChB
Professor
Children's Hospital of Los Angeles, United States
Disclosure information not submitted.
John Lin, MD
Program Director, PCCM Fellowship
Washington University School of Medicine
Saint Louis, MO
Disclosure information not submitted.
Allan Doctor, MD
Professor
University of Maryland School of Medicine, United States
Disclosure information not submitted.
Tom Shanley, MD
Professor
Ann and Robert H Lurie Childrens Hospital of Chicago, United States
Disclosure information not submitted.
Timothy Cornell, MD
Chambers-Okamura Endowed Professor of Pediatric Critical Care Medicine
Stanford University - Lucille Packard Children's Hosptal Stanford, United States
Disclosure information not submitted.
Joseph Carcillo, MD
Professor
Children's Hospital of Pittsburgh of UPMC, United States
Disclosure information not submitted.
Title: Group-based multi-trajectory analysis of C-reactive protein and ferritin levels in pediatric sepsis
Introduction: Interest in using bedside C-reactive protein and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies piqued with the COVID-19 pandemic experience. These widely available, low-cost biomarkers might be similarly useful for assessing inflammatory profiles of all critically ill children with sepsis and septic shock and eventually guiding the use of precision anti-inflammatory therapies. We hypothesized group-based trajectories of CRP and ferritin among critically ill children with sepsis would be associated with mortality and distinct inflammatory cytokine profiles.
Methods: Children with sepsis and organ failure from 9 pediatric intensive care units were enrolled in a prospective, observational cohort. Plasma CRP (mg/dL), ferritin (ng/mL), and 29 cytokine levels were measured at two samplings 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.
Results: Two hundred and fifty-five children had at least 2 CRP and ferritin measurements. Five distinct clinical multi-trajectory groups were identified with significantly different median maximum organ failures (MOF) and mortality. Group 1 had normal CRP and ferritin levels (n = 8; median MOF 2.0 [interquartile range 1.0, 2.0] and 0 % mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout (n = 80; median MOF 2.0 [1.0, 2.0] and 5% mortality); Group 3 had high ferritin levels alone (n=16; median MOF 2.5 [2.0, 3.0] and 6.3% mortality); Group 4 had very high CRP levels, and increased ferritin levels (n = 121; median MOF 2.0 [2.0, 4.0] and 10.7% mortality); and, Group 5 had very high CRP and very high ferritin levels (n = 30; median MOF 3.0 [2.0, 4.0] and 40% mortality). Cytokine responses differed across the 5 groups, with ferritin levels associated with macrophage inflammatory protein 1 a , and CRP levels reflective of many cytokines.
Conclusions: Bedside CRP and ferritin levels can be used together to compute distinct groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks potentially targetable in clinical trials evaluating specific anti-inflammatory therapies.