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Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care

A New Paradigm for Outcomes Assessment*

Pollack, Murray M. MD1,2; Holubkov, Richard PhD3; Funai, Tomohiko MS3; Berger, John T. MD4; Clark, Amy E. MS3; Meert, Kathleen MD5; Berg, Robert A. MD6; Carcillo, Joseph MD7; Wessel, David L. MD8; Moler, Frank MD9; Dalton, Heidi MD10; Newth, Christopher J. L. MD, FRCPC11; Shanley, Thomas MD9; Harrison, Rick E. MD12; Doctor, Allan MD13,14; Jenkins, Tammara L. MSN, RN15; Tamburro, Robert MD, MSc15; Dean, J. Michael MD3 for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network

doi: 10.1097/CCM.0000000000001081
Pediatric Critical Care
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Objectives: Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality.

Design: Prospective cohort study from December 4, 2011, to April 7, 2013.

Setting: General and cardiac/cardiovascular PICUs at seven sites.

Patients: Randomly selected PICU patients from their first PICU admission.

Interventions None.

Measurements and Main Results: Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6–7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3–5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios.

Conclusions: New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

1Department of Pediatrics, Children’s National Medical Center and the George Washington University School of Medicine and Health Sciences, Washington, DC.

2Department of Child Health, Phoenix Children’s Hospital and the University of Arizona School of Medicine, Phoenix, AZ.

3Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT.

4Department of Pediatrics, Children’s National Medical Center, Washington, DC.

5Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI.

6Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA.

7Department of Critical Care Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA.

8Department of Pediatrics, Children’s National Medical Center, Washington, DC.

9Department of Pediatrics, University of Michigan, Ann Arbor, MI.

10Department of Child Health, Phoenix Children’s Hospital and University of Arizona College of Medicine-Phoenix, Phoenix, AZ.

11Department of Anesthesiology and Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles, CA.

12Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA.

13Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

14Department of Biochemistry, Washington University School of Medicine, St. Louis, MO.

15Pediatric Trauma and Critical Illness Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, MD.

*See also p. 1781.

Drs. Pollack and Holubkov had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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/ccmjournal).

Supported, in part, by the following cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services: U10HD050096, U10HD049981, U10HD049983, U10HD050012, U10HD063108, U10HD063106, U10HD063114, and U01HD049934.

Results were presented, in part, at the Annual Society of Critical Care meeting in January 2015 and have been submitted to the Academic Pediatric Societies Meeting for April 2015.

Dr. Pollack received grant support from the National Institute of Child Health and Human Development (NICHD), has planned patents through Children’s National Medical Center (his not-for-profit employer), and received support for article research from the National Institutes of Health (NIH). Dr. Holubkov served as a board member for Pfizer, the National Burn Association, and Fibrocell (Data Safety Board Membership); consulted for St. Jude Medical, Physicians Committee for Responsible Medicine, and Covidien (Biostatistical Consulting); received support for article research from the NIH. Dr. Holubkov and his institution received grant support (Salary support [biostatistician]) and support for travel (Steering Committee Meeting Travel) from the NIH. Dr. Funai received support for article research from the NIH. Dr. Funai and his institution received grant support from the NIH (salaries support Biostatistician). Dr. Berger received support for article research from the NIH. His institution received grant support from the NIH and the Association for Pediatric Pulmonary Hypertension. Dr. Clark received support for article research from the NIH. Her institution received grant support from the NIH. Dr. Meert received support for article research from the NIH. Her institution received grant support from the NIH. Dr. Berg received grant support from the NICHD and received support for article research from the NIH. Dr. Carcillo received support for article research from the NIH. His institution received grant support and support for travel. Dr. Wessel received support for article research from the NIH. His institution received grant support from the NIH (ongoing). Dr. Moler received support for article research from the NIH. His institution received grant support and support for travel from the NICHD. Dr. Dalton lectured for rEVO Biologics, received royalties from the Society of Critical Care Medicine (SCCM) for Pediatric Multidisciplinary Board Review Book, and received support for article research from the NIH. Her institution received grant support from the NIH. Dr. Newth received support for article research from the NIH. His institution received grant support from the NIH/NICHD (Collaborative Pediatric Critical Care Research Network). Dr. Shanley received support for article research from the NIH and served as a board member for International Pediatric Research Foundation (Society for Pediatric Research Representative on Executive Committee). His institution received grant support from the NICHD (Collaborative Pediatric Critical Care Research Network [CPCCRN] grant) and the NIH (Clinical and Translational Science Award grant) and received support for travel from the NICHD (CPCCRN grant). Dr. Harrison lectured for the SCCM (board review lectures for my professional society) and received support for article research from the NIH. His institution received grant support from the NIH (CPCCRN funding and Therapeutic Hypothermia for Pediatric Cardiac Arrest trial funding via NIH). Dr. Doctor consulted for the NICHD/CPCCRN (honorarium to serve as Steering Committee chairperson), Terumo, BCT, iNO Therapeutics, Novartis, and Galleon Pharmaceuticals; received support for travel from the NICHD/CPCCRN; and lectured for Terumo, BCT. His institution received grant support from the NIH, the American Hospital Association, and the Children’s Discovery Institute. Dr. Jenkins received support for article research from the NIH and disclosed government work. Dr. Tamburro received grant support from the U.S. Food and Drug Administration Office of Orphan Product Development Grant to study calfactant in pediatric stem cell transplant patients (No longer co-principal investigator on the trial secondary to accepting a new position), received royalties from Springer Publisher (received royalties for serving as an associate editor on a pediatric critical care textbook and study guide), received support for article research from the NIH, and disclosed government work. Dr. Dean received support for article research from the NIH. His institution received grant support from the NIH and Health Services and Resources Administration.

For information regarding this article, E-mail: mpollack@childrensnational.org

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