Serum Levels of Acylcarnitines and Amino Acids Are Associated with Liberation from Organ Support in Patients with Septic Shock

Theodore S. Jennaro, Elizabeth M. Viglianti, Nicholas E. Ingraham, Alan E. Jones, Kathleen A. Stringer, Michael A. Puskarich

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sepsis-induced metabolic dysfunction is associated with mortality, but the signatures that differentiate variable clinical outcomes among survivors are unknown. Our aim was to determine the relationship between host metabolism and chronic critical illness (CCI) in patients with septic shock. We analyzed metabolomics data from mechanically ventilated patients with vasopressor-dependent septic shock from the placebo arm of a recently completed clinical trial. Baseline serum metabolites were measured by liquid chromatography-mass spectrometry and1H-nuclear magnetic resonance. We conducted a time-to-event analysis censored at 28 days. Specifically, we determined the relationship between metabolites and time to extubation and freedom from vasopressors using a competing risk survival model, with death as a competing risk. We also compared metabolite concentrations between CCI patients, defined as intensive care unit level of care ≥ 14 days, and those with rapid recovery. Elevations in two acylcarnitines and four amino acids were related to the freedom from organ support (subdistributional hazard ratio < 1 and false discovery rate < 0.05). Proline, glycine, glutamine, and methionine were also elevated in patients who developed CCI. Our work highlights the need for further testing of metabolomics to identify patients at risk of CCI and to elucidate potential mechanisms that contribute to its etiology.

Original languageEnglish (US)
Article number627
JournalJournal of Clinical Medicine
Volume11
Issue number3
DOIs
StatePublished - Feb 1 2022

Bibliographical note

Funding Information:
Funding: This study was supported by the National Institute of General Medical Sciences (NIGMS) via R01GM103799 (A.E.J.), K23GM113041 (M.A.P.) and R01GM111400 (K.A.S.) and R35GM136312 (K.A.S.). T.S.J.’s contributions were supported by the Michigan Institute for Data Science “Propelling Original Data Science” grant from the University of Michigan and from the American Foundation of Pharmaceutical Education. N.E.I.’s contributions were supported by the National Heart, Lung, and Blood Institute (NHLBI) via T32HL07741. E.M.V. was supported by an NHLBI K23 HL157364. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS, NHLBI, or the NIH.

Funding Information:
This study was supported by the National Institute of General Medical Sciences (NIGMS) via R01GM103799 (A.E.J.), K23GM113041 (M.A.P.) and R01GM111400 (K.A.S.) and R35GM136312 (K.A.S.). T.S.J.?s contributions were supported by the Michigan Institute for Data Science ?Propelling Original Data Science? grant from the University of Michigan and from the American Foundation of Pharmaceutical Education. N.E.I.?s contributions were supported by the National Heart, Lung, and Blood Institute (NHLBI) via T32HL07741. E.M.V. was supported by an NHLBI K23 HL157364. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS, NHLBI, or the NIH.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Acetylcarnitine
  • Acylcarnitines
  • Liquid chromatography-mass spectrometry
  • Metabolomics
  • Nuclear magnetic resonance spectroscopy
  • Organ failure
  • Sepsis

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'Serum Levels of Acylcarnitines and Amino Acids Are Associated with Liberation from Organ Support in Patients with Septic Shock'. Together they form a unique fingerprint.

Cite this