Faculty Collaboration Database

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response. Crit Care Med 2018 Mar;46(3):e242-e249

Date

12/19/2017

Pubmed ID

29252929

Pubmed Central ID

PMC5825261

DOI

10.1097/CCM.0000000000002932

Scopus ID

2-s2.0-85051091373 (requires institutional sign-in at Scopus site)   40 Citations

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.

Author List

Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald JC, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Lutfi R, Gertz S, Grunwell JR, Lindsell CJ

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

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