Journal
CRITICAL CARE MEDICINE
Volume 46, Issue 3, Pages e242-e249Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0000000000002932
Keywords
adaptive immunity; endotypes; gene expression; glucocorticoids; sepsis
Categories
Funding
- National Institutes of Health [RO1GM099773, R01GM108025]
- National Institutes of Health (NIH)
- NIH
- Cincinnati Children's Hospital Medical Center
- Boston Children's Hospital
- NIH grant
- University of Cincinnati through an NIH
- Therabron
- CareFusion
- GeneFluidics
- ThermoFisher Scientific
- Bristol-Meyers Squibb Company
- Cincinnati Children's Medical Center
- University of Michigan Medical School
- Bristol-Myers Squibb
- NIH through Cincinnati Children Hospital Medical Center
- NIH/National Institute of General Medical Sciences
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Objective: We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes. Design: Observational cohort study including existing and newly enrolled participants. Setting: Multiple PICUs. Patients: Children with septic shock. Interventions: None. Measurements and Main Results: We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype A by day 3. Assignment to endotype A on day 1 was associated with increased odds of mortality. This risk was modified by the subsequent day 3 endotype assignment. Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A. Conclusions: A substantial proportion of children with septic shock transition endotypes during the acute phase of illness. The risk of poor outcome and the response to corticosteroids change with changes in endotype assignment. Patients persisting as endotype A are at highest risk of poor outcomes.
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