Metabolomic derangements are associated with mortality in critically ill adult patients.
Abstract
OBJECTIVE: To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU)
mortality in adults. RATIONALE: Comprehensive metabolomic profiling of plasma at ICU
admission to identify biomarkers associated with mortality has recently become feasible.
METHODS: We performed metabolomic profiling of plasma from 90 ICU subjects enrolled
in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and
a Bayesian Network of metabolites for association with 28-day mortality, using logistic
regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites
and the network were tested for replication in an independent cohort of 149 adults
enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD)
study. RESULTS: We tested variable metabolites for association with 28-day mortality.
In RoCI, nearly one third of metabolites differed among ICU survivors versus those
who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality
replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating
metabolites included lipids (N = 14), amino acids or amino acid breakdown products
(N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated
metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that
are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic
network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine,
1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose,
kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI,
and 74% of the AUC in CAPSOD (p<.001 in both populations). CONCLUSION: Both individual
metabolites and a metabolomic network were associated with 28-day mortality in two
independent cohorts. Metabolomic profiling represents a valuable new approach for
identifying novel biomarkers in critically ill patients.
Type
Journal articleSubject
AgedBayes Theorem
Biomarkers
Community-Acquired Infections
Critical Illness
Female
Hospital Mortality
Humans
Intensive Care Units
Male
Metabolomics
Middle Aged
Prognosis
Sepsis
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https://hdl.handle.net/10161/13313Published Version (Please cite this version)
10.1371/journal.pone.0087538Publication Info
Rogers, Angela J; McGeachie, Michael; Baron, Rebecca M; Gazourian, Lee; Haspel, Jeffrey
A; Nakahira, Kiichi; ... Choi, Augustine MK (2014). Metabolomic derangements are associated with mortality in critically ill adult patients.
PLoS One, 9(1). pp. e87538. 10.1371/journal.pone.0087538. Retrieved from https://hdl.handle.net/10161/13313.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Christopher Wildrick Woods
Wolfgang Joklik Distinguished Professor of Global Health
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance
for communicable diseases 7. Antimicrobial resistance
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