Title

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response.

Document Type

Article

Publication Date

3-2018

Identifier

DOI: 10.1097/CCM.0000000000002932; PMCID: PMC5825261

Abstract

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.

Journal Title

Critical care medicine

Volume

46

Issue

3

First Page

242

Last Page

242

MeSH Keywords

Acute Disease; Adrenal Cortex Hormones; Age Factors; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Male; Risk Factors; Severity of Illness Index; Shock, Septic; Transcriptome

Keywords

Acute Disease; Adrenal Cortex Hormones; Age Factors; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Male; Risk Factors; Severity of Illness Index; Shock, Septic; Transcriptome

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