Derivation and Validation of Novel Phenotypes of Multiple Organ Dysfunction Syndrome in Critically Ill Children

Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity and mortality in critically ill children. To determine whether data-driven phenotypes of MODS based on the trajectories of 6 organ dysfunctions have prognostic and therapeutic relevance i...

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Bibliographic Details
Published in:JAMA network open 2020-08, Vol.3 (8), p.e209271-e209271
Main Authors: Sanchez-Pinto, L Nelson, Stroup, Emily K, Pendergrast, Tricia, Pinto, Neethi, Luo, Yuan
Format: Article
Language:English
Subjects:
Child
Child, Preschool
Critical Care Medicine
Critical Illness - epidemiology
Critical Illness - mortality
Female
Genotype & phenotype
Humans
Infant
Intensive care
Intensive Care Units, Pediatric
Male
Multiple organ dysfunction syndrome
Multiple Organ Failure - classification
Multiple Organ Failure - diagnosis
Multiple Organ Failure - epidemiology
Multiple Organ Failure - mortality
Online Only
Organ Dysfunction Scores
Original Investigation
Pediatrics
Phenotype
Prognosis
Retrospective Studies
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Summary:Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity and mortality in critically ill children. To determine whether data-driven phenotypes of MODS based on the trajectories of 6 organ dysfunctions have prognostic and therapeutic relevance in critically ill children. This cohort study included 20 827 pediatric intensive care encounters among 14 285 children admitted to 2 large academic pediatric intensive care units (PICUs) between January 2010 and August 2016. Patients were excluded if they were older than 21 years or had undergone cardiac surgery. The 6 subscores of the pediatric Sequential Organ Failure Assessment (pSOFA) score were calculated for the first 3 days, including the subscores for respiratory, cardiovascular, coagulation, hepatic, neurologic, and renal dysfunctions. MODS was defined as a pSOFA subscore of at least 2 in at least 2 organs. Encounters were split in a 80:20 ratio for derivation and validation, respectively. The trajectories of the 6 subscores were used to derive a set of data-driven phenotypes of MODS using subgraph-augmented nonnegative matrix factorization in the derivation set. Data analysis was conducted from March to October 2019. The primary exposure was phenotype membership. In the subset of patients with vasoactive-dependent shock, the interaction between hydrocortisone and phenotype membership and its association with outcomes were examined in a matched cohort. The primary outcome was in-hospital mortality. Secondary outcomes included persistent MODS on day 7, and vasoactive-free, ventilator-free, and hospital-free days. Regression analysis was used to adjust for age, severity of illness, immunocompromised status, and study site. There were 14 285 patients with 20 827 encounters (median [interquartile range] age 5.2 years [1.5-12.7] years; 11 409 [54.8%; 95% CI, 54.1%-55.5%] male patients). Of these, 5297 encounters (25.4%; 95% CI, 24.8%-26.0%) were with patients who had MODS, of which 5054 (95.4%) met the subgraph count threshold and were included in the analysis. Subgraph augmented nonnegative matrix factorization uncovered 4 data-driven phenotypes of MODS, characterized by a combination of neurologic, respiratory, coagulation, and cardiovascular dysfunction, as follows: phenotype 1, severe, persistent encephalopathy (1019 patients [19.2%]); phenotype 2, moderate, resolving hypoxemia (1828 patients [34.5%]); phenotype 3, severe, persistent hypoxemia and shock
ISSN:2574-3805
2574-3805
DOI:10.1001/jamanetworkopen.2020.9271