Epidemiology of Cause of Death in Pediatric Acute Respiratory Distress Syndrome

Objectives: Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia. Design: Retrospective, decedent-only analysis. Setting: Two large, academic PICUs. Patients: Nonsurvivors with pediatric acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3–13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a neurologic cause, including brain death. Patients dying greater than or equal to 7 days after pediatric acute respiratory distress syndrome onset were more commonly immunocompromised. Multisystem organ failure predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was the most common mode of death at all timepoints, accounting for 66% of all deaths. Organ dysfunction was common at time of death, irrespective of cause of death. Refractory hypoxemia accounted for only a minority of pediatric acute respiratory distress syndrome deaths (20%). Conclusions: In pediatric acute respiratory distress syndrome, early deaths were due primarily to neurologic failure, whereas later deaths were more commonly due to multisystem organ failure. Deaths from neurologic causes accounted for a substantial portion of nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our study highlights limitations associated with using death as an endpoint in therapeutic pediatric acute respiratory distress syndrome trials. This work was performed at Children's Hospital of Philadelphia. 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 (https://ift.tt/29S62lw). Supported, in part, by grants K23-HL136688 (to Dr. Yehya). Dr. Thomas' institution received funding from Gene Fluidics, and he received funding from Therabron and CareFusion. Dr. Yehya's institution received funding from the National Institutes of Health (NIH), and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: yehyan@email.chop.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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