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

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

doi:10.1097/PCC.0000000000003074

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

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. ZuppaRon W. Reeder, Kathy Sward, Richard Holubkov, Daniel A. Notterman, J. Michael Dean, Joseph A. Carcillo^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

OBJECTIVES: 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. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

Original language	English (US)
Pages (from-to)	968-979
Number of pages	12
Journal	Pediatric Critical Care Medicine
Volume	23
Issue number	12
DOIs	https://doi.org/10.1097/PCC.0000000000003074
State	Published - Dec 1 2022

Funding

Supported, in part, by grant R01GM108618 (to Drs. Carcillo principal investigator, Park, and Canna) from the National Institutes of General Medical Sciences, and by 5U01HD049934-10S1 (to Dr. Carcillo), 1K23HD099331-01A1 (to Dr. Horvat) and K12HD047349 (to Dr. Kernan) from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services and the following cooperative agreements: U10HD049983, U10HD050096, U10HD049981, U10HD063108, U10HD63106, U10HD063114, U10HD050012, and U01HD049934.

Keywords

C-reactive protein
children
ferritin
immunomodulation
multiple organ failure
sepsis

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Critical Care and Intensive Care Medicine

Access to Document

10.1097/PCC.0000000000003074

Cite this

Horvat, C. M., Fabio, A., Nagin, D. S., Banks, R. K., Qin, Y., Park, H. J., Kernan, K. F., Canna, S. W., Berg, R. A., Wessel, D., Pollack, M. M., Meert, K., Hall, M., Newth, C., Lin, J. C., Doctor, A., Shanley, T., Cornell, T., Harrison, R. E., ... Carcillo, J. A. (2022). Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels. Pediatric Critical Care Medicine, 23(12), 968-979. https://doi.org/10.1097/PCC.0000000000003074

@article{6e99e026ea924ab7932a894cc6713734,

title = "Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels",

abstract = "OBJECTIVES: 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. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.",

keywords = "C-reactive protein, children, ferritin, immunomodulation, multiple organ failure, sepsis",

author = "Horvat, \{Christopher M.\} and Anthony Fabio and Nagin, \{Daniel S.\} and Banks, \{Russell K.\} and Yidi Qin and Park, \{Hyun Jung\} and Kernan, \{Kate F.\} and Canna, \{Scott W.\} and Berg, \{Robert A.\} and David Wessel and Pollack, \{Murray M.\} and Kathleen Meert and Mark Hall and Christopher Newth and Lin, \{John C.\} and Allan Doctor and Tom Shanley and Tim Cornell and Harrison, \{Rick E.\} and Zuppa, \{Athena F.\} and Reeder, \{Ron W.\} and Kathy Sward and Richard Holubkov and Notterman, \{Daniel A.\} and Dean, \{J. Michael\} and Carcillo, \{Joseph A.\}",

note = "Publisher Copyright: {\textcopyright} 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.",

year = "2022",

month = dec,

day = "1",

doi = "10.1097/PCC.0000000000003074",

language = "English (US)",

volume = "23",

pages = "968--979",

journal = "Pediatric Critical Care Medicine",

issn = "1529-7535",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "12",

}

Horvat, CM, Fabio, A, Nagin, DS, Banks, RK, Qin, Y, Park, HJ, Kernan, KF, Canna, SW, Berg, RA, Wessel, D, Pollack, MM, Meert, K, Hall, M, Newth, C, Lin, JC, Doctor, A, Shanley, T, Cornell, T, Harrison, RE, Zuppa, AF, Reeder, RW, Sward, K, Holubkov, R, Notterman, DA, Dean, JM & Carcillo, JA 2022, 'Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels', Pediatric Critical Care Medicine, vol. 23, no. 12, pp. 968-979. https://doi.org/10.1097/PCC.0000000000003074

TY - JOUR

T1 - Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels

AU - Horvat, Christopher M.

AU - Fabio, Anthony

AU - Nagin, Daniel S.

AU - Banks, Russell K.

AU - Qin, Yidi

AU - Park, Hyun Jung

AU - Kernan, Kate F.

AU - Canna, Scott W.

AU - Berg, Robert A.

AU - Wessel, David

AU - Pollack, Murray M.

AU - Meert, Kathleen

AU - Hall, Mark

AU - Newth, Christopher

AU - Lin, John C.

AU - Doctor, Allan

AU - Shanley, Tom

AU - Cornell, Tim

AU - Harrison, Rick E.

AU - Zuppa, Athena F.

AU - Reeder, Ron W.

AU - Sward, Kathy

AU - Holubkov, Richard

AU - Notterman, Daniel A.

AU - Dean, J. Michael

AU - Carcillo, Joseph A.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - OBJECTIVES: 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. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

AB - OBJECTIVES: 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. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

KW - C-reactive protein

KW - children

KW - ferritin

KW - immunomodulation

KW - multiple organ failure

KW - sepsis

UR - https://www.scopus.com/pages/publications/85143197771

UR - https://www.scopus.com/inward/citedby.url?scp=85143197771&partnerID=8YFLogxK

U2 - 10.1097/PCC.0000000000003074

DO - 10.1097/PCC.0000000000003074

M3 - Article

C2 - 36178701

AN - SCOPUS:85143197771

SN - 1529-7535

VL - 23

SP - 968

EP - 979

JO - Pediatric Critical Care Medicine

JF - Pediatric Critical Care Medicine

IS - 12

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this