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Morbidity and Mortality in Critically Ill Children. I. Pathophysiologies and Potential Therapeutic Solutions
Murray M Pollack1, Russell Banks2, Richard Holubkov2
1Department of Pediatrics, Children's National Health System and the- George Washington University School of Medicine and Health Sciences, Washington, DC.
Insights
Identifying key pathophysiologies and therapeutic needs in pediatric critical care is crucial for reducing mortality. This study found impaired substrate delivery and inflammation were common, with needs for new drugs and cell regeneration therapies.
Area of Science:
- Pediatric Critical Care Medicine
- Pathophysiology
- Therapeutic Development
Background:
- Effective therapies for pediatric critical care require understanding underlying pathophysiologies.
- Identifying impactful therapeutic advances is essential for reducing morbidity and mortality in critically ill children.
Purpose of the Study:
- To determine patient-level pathophysiological processes contributing to poor outcomes in pediatric intensive care unit (PICU) survivors.
- To identify needed therapeutic additions and advances to prevent or ameliorate morbidity and mortality in critically ill children.
Main Methods:
- A structured chart review was conducted by pediatric intensivists.
- The study analyzed data from 292 randomly selected PICU patients discharged with significant new morbidity or mortality.
- Data were collected from general and cardiac PICUs across eight sites within the Collaborative Pediatric Critical Care Research Network.
Main Results:
- Impaired substrate delivery (54.1%) and inflammation (35.6%) were the most common pathophysiologies associated with poor outcomes.
- Therapeutic needs included new drugs (51.0%), cell regeneration (39.4%), and immune/inflammatory modulation (27.1%).
- No dominant pathophysiology or therapeutic need clusters were identified.
Conclusions:
- Poor outcomes in pediatric critical care are not attributable to a single dominant pathophysiology or cluster.
- Therapeutic needs often involve advanced, not-yet-implemented strategies like cell regeneration and artificial organs.
- Further research into novel drugs and regenerative therapies is warranted for pediatric critical care.
Objectives:
Developing 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.
Design:
Structured 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.
Setting:
Multicenter study (eight sites) from the Collaborative Pediatric Critical Care Research Network of general and cardiac PICUs.
Patients:
First PICU admission of patients from December 2011 to April 2013.
Interventions:
None.
Measurements And Main Results:
Two-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.
Conclusions:
There 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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