Nuclear magnetic resonance-based serum metabolomic analysis reveals different disease evolution profiles between septic shock survivors and non-survivors.


Journal

Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902

Informations de publication

Date de publication:
14 05 2019
Historique:
received: 29 11 2018
accepted: 25 04 2019
entrez: 16 5 2019
pubmed: 16 5 2019
medline: 20 12 2019
Statut: epublish

Résumé

Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality. Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (Δ Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes. All human serum samples were collected and stored, provided by the "center of biologic resources for liver disease", in Jean Verdier Hospital, Bondy, France (BB-0033-00027).

Sections du résumé

BACKGROUND
Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis.
METHODS
Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality.
RESULTS
Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (Δ
CONCLUSIONS
Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes.
TRIAL REGISTRATION
All human serum samples were collected and stored, provided by the "center of biologic resources for liver disease", in Jean Verdier Hospital, Bondy, France (BB-0033-00027).

Identifiants

pubmed: 31088568
doi: 10.1186/s13054-019-2456-z
pii: 10.1186/s13054-019-2456-z
pmc: PMC6518644
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

169

Subventions

Organisme : Funding of Anhui Medical University
ID : XJ201729
Pays : International

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Auteurs

Zhicheng Liu (Z)

School of Pharmacy, Anhui Medical University, Hefei, China.
Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.

Mohamed N Triba (MN)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.

Roland Amathieu (R)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.
Intensive Care Unit, Diaconesse-Croix Saint-Simon Hospital, 125 rue d'Avron, 75020, Paris, France.

Xiangping Lin (X)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.

Nadia Bouchemal (N)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.

Edith Hantz (E)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France.

Laurence Le Moyec (L)

Université Paris Saclay, University Evry, UBIAE EA 7362, 91025, Evry, France.

Philippe Savarin (P)

Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, UMR 7244, University Paris 13, F-93017, Bobigny, France. philippe.savarin@univ-paris13.fr.

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