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New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality*

Lin, John C. MD; Spinella, Philip C. MD, FCCM; Fitzgerald, Julie C. MD, PhD; Tucci, Marisa MD; Bush, Jenny L. RN, BSN; Nadkarni, Vinay M. MD; Thomas, Neal J. MD, MSc; Weiss, Scott L. MD, MSCEfor the Sepsis Prevalence, Outcomes, and Therapy Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators Network

Pediatric Critical Care Medicine: January 2017 - Volume 18 - Issue 1 - p 8–16
doi: 10.1097/PCC.0000000000000978
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Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis.

Design: Secondary analysis of a prospective, cross-sectional, point prevalence study.

Setting: International, multicenter PICUs.

Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period.

Interventions: None.

Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis–associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001).

Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

Supplemental Digital Content is available in the text.

1Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

2Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

3Division of Critical Care Medicine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.

4Pediatric Critical Care Medicine, Departments of Pediatrics and Public Health Sciences, Penn State University College of Medicine, Hershey, PA.

*See also p. 82.

A list of all Sepsis Prevalence, Outcomes, and Therapy Study Investigators are given in Appendix 1.

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’s website (http://journals.lww.com/pccmjournal).

Supported, in part, by the Endowed Chair, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine and the Center for Pediatric Clinical Effectiveness at The Children’s Hospital of Philadelphia. Financial support for data collection in all U.K. centers was provided by the U.K. National Institute of Health (NIHR) Clinical Research Network and in Southampton by the Southampton NIHR Wellcome Trust Clinical Research Facility.

Dr. Fitzgerald’s institution received funding from the Children's Hospital of Philadelphia Center for Pediatric Clinical Effectiveness. Dr. Thomas received funding from Therabron and CareFusion; his institution received funding from the U.S. Food and Drug Administration. Dr. Weiss’ institution received funding from the Center for Pediatric Clinical Effectiveness at The Children's Hospital of Philadelphia, NIGMS K23GM110496, and Thermo-Fisher Scientific (honorarium for lecture). The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: John C. Lin, MD, 1 Children’s Place, Campus Box 8116, St. Louis, MO 63110. E-mail: lin_jo@kids.wustl.edu

©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies