@article{93120730c4c84becbbc68a5f0dddcdb9,
title = "A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure",
abstract = "Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. Design: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. Setting: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Patients: Children with severe sepsis and indwelling arterial or central venous catheters. Interventions: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. Measurements and Main Results: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08). Conclusions: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.",
keywords = "immune paralysis, macrophage activation syndrome, sequential liver failure associated multiple organ failure, thrombocytopenia associated multiple organ failure",
author = "Carcillo, {Joseph A.} and Berg, {Robert A.} and David Wessel and Murray Pollack 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 Russell Banks and Kellum, {John A.} and Richard Holubkov and Notterman, {Daniel A.} and Dean, {J. Michael}",
note = "Funding Information: 1Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children{\textquoteright}s Hospital of Pittsburgh, Center for Critical Care Nephrology and Clinical Research Investigation and Systems Modeling of Acute Illness Center, University of Pittsburgh, Pittsburgh, PA. 2Division of Pediatric Critical Care Medicine, Department of Anesthesiology, Children{\textquoteright}s Hospital of Philadelphia, Philadelphia, PA. 3Division of Critical Care Medicine, Department of Pediatrics, Children{\textquoteright}s National Medical Center, Washington, DC. 4Division of Critical Care Medicine, Department of Pediatrics, Children{\textquoteright}s Hospital of Michigan, Detroit, MI. 5Division of Critical Care Medicine, Department of Pediatrics, The Research Institute at Nationwide Children{\textquoteright}s Hospital Immune Surveillance Laboratory, and Nationwide Children{\textquoteright}s Hospital, Columbus, OH. 6Division of Pediatric Critical Care Medicine, Department of Anesthesiology and Pediatrics, Children{\textquoteright}s Hospital Los Angeles, Los Angeles, CA. 7Division of Critical Care Medicine, Department of Pediatrics, St. Louis Children{\textquoteright}s Hospital, St. Louis, MO. 8Division of Critical Care Medicine, Department of Pediatrics, C. S. Mott Children{\textquoteright}s Hospital, Ann Arbor, MI. 9Division of Critical Care Medicine, Department of Pediatrics, Mattel Children{\textquoteright}s Hospital at University of California Los Angeles, Los Angeles, CA. 10University of Utah, Salt Lake City, UT. 11Princeton University, Princeton, NJ. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal{\textquoteright}s website (http://journals.lww.com/ pccmjournal). Supported, in part, by grant R01GM108618 (to Dr. Carcillo) from the National Institutes of General Medical Sciences, by 5U01HD049934-10S1 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. Publisher Copyright: {\textcopyright} 2019 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.",
year = "2019",
month = dec,
day = "1",
doi = "10.1097/PCC.0000000000002105",
language = "English (US)",
volume = "20",
pages = "1137--1146",
journal = "Pediatric Critical Care Medicine",
issn = "1529-7535",
publisher = "Lippincott Williams and Wilkins",
number = "12",
}
