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Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies

Doctor, Allan MD; Zimmerman, Jerry MD; Agus, Michael MD; Rajasekaran, Surender MD; Bubeck Wardenburg, Juliane MD, PhD; Fortenberry, James MD; Zajicek, Anne PhD; Mairson, Emma; Typpo, Katri MD

doi: 10.1097/PCC.0000000000001053
MODS Supplement

Objective: To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26–27, 2015).

Data Sources: Literature review, research data, and expert opinion.

Study Selection: Not applicable.

Data Extraction: Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities.

Data Synthesis: Summary of presentations and discussion supported and supplemented by relevant literature.

Conclusions: Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

1Departments of Pediatrics (Critical Care Medicine) and Biochemistry, Washington University in St. Louis, St. Louis, MO.

2Department of Pediatrics (Critical Care Medicine), University of Washington, Seattle, WA.

3Department of Pediatrics (Critical Care Medicine), Harvard University, Boston, MA.

4Department of Pediatrics (Critical Care Medicine), Michigan State University, Grand Rapids, MI.

5Departments of Pediatrics (Critical Care Medicine) and Microbiology, University of Chicago, Chicago, IL.

6Department of Pediatrics (Critical Care Medicine), Emory University, Atlanta, GA.

7Obstetric and Pediatric Pharmacology and Therapeutics Branch, NICHD, Bethesda, MD.

8Department of Pediatrics (Critical Care Medicine), University of Arizona, Phoenix, AZ.

This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. government.

This article is funded in part by R01GM113838 (Dr. Doctor), R01AI097434 (Dr. Wardenburg), and the Burroughs Welcome Foundation Investigators in the Pathogenesis of Infectious Disease (Dr. Wardenburg).

Dr. Doctor’s institution received funding from the National Institutes of Health (NIH), the Department of Defense, and Children’s Discovery Institutes, and he received support for article research from the NIH. Dr. Zimmerman’s institution received funding from NIH, Immunexpress, and Seattle Children’s Research Institute, Seattle, WA; he received support for article research from the NIH; he received funding from Elsevier Publishing (coediting the textbook Pediatric Critical Care); he disclosed other support in the form of travel reimbursement from the Society of Critical Care Medicine to attend board meeting; and he disclosed off-label product use of various steroid class medications as adjunctive therapy for sepsis. Dr. Agus received support for article research from the NIH. Dr. Wardenburg received support for article research from the NIH and Burroughs Wellcome Foundation, and she received funding from Novartis Vaccines. Dr. Fortenberry received funding from the National Institute of Child Health and Human Development. Dr. Zajicek disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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