• Murray M Pollack, Russell Banks, Richard Holubkov, Kathleen L Meert, and Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
• Department of Pediatrics, Children's National Health System and the- George Washington University School of Medicine and Health Sciences, Washington, DC.
• Crit. Care Med. 2020 Jun 1; 48 (6): 790-798.

ObjectivesDeveloping effective therapies to reduce morbidity and mortality requires knowing the responsible pathophysiologies and the therapeutic advances that are likely to be impactful. Our objective was to determine at the individual patient level the important pathophysiological processes and needed therapeutic additions and advances that could prevent or ameliorate morbidities and mortalities.DesignStructured chart review by pediatric intensivists of PICU children discharged with significant new morbidity or mortality to determine the pathophysiologies responsible for poor outcomes and needed therapeutic advances.SettingMulticenter study (eight sites) from the Collaborative Pediatric Critical Care Research Network of general and cardiac PICUs.PatientsFirst PICU admission of patients from December 2011 to April 2013.InterventionsNone.Measurements And Main ResultsTwo-hundred ninety-two patients were randomly selected from 681 patients discharged with significant new morbidity or mortality. The median age was 2.4 years, 233 (79.8%) were in medical/surgical ICUs, 59 (20.2%) were in cardiac ICUs. Sixty-five (22.3%) were surgical admissions. The outcomes included 117 deaths and 175 significant new morbidities. The most common pathophysiologies contributing to the poor outcomes were impaired substrate delivery (n = 158, 54.1%) and inflammation (n = 104, 35.6%). There were no strong correlations between the pathophysiologies and no remarkable clusters among them. The most common therapeutic needs involved new drugs (n = 149, 51.0%), cell regeneration (n = 115, 39.4%), and immune and inflammatory modulation (n = 79, 27.1%). As with the pathophysiologies, there was a lack of strong correlations or meaningful clusters in the suggested therapeutic needs.ConclusionsThere was no single dominant pathophysiology or cluster of pathophysiologies responsible for poor pediatric critical care outcomes. Therapeutic needs often involved therapies that are not close to implementation such as cell regeneration, improved organ transplant, improved extracorporeal support and artificial organs, and improved drugs.

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