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Metabolic Profiling of Serum Samples by 1H Nuclear Magnetic Resonance Spectroscopy as a Potential Diagnostic Approach for Septic Shock*

Mickiewicz, Beata PhD1; Duggan, Gavin E. PhD1; Winston, Brent W. MD2; Doig, Christopher MD3; Kubes, Paul PhD4; Vogel, Hans J. PhD1; for the Alberta Sepsis Network

doi: 10.1097/CCM.0000000000000142
Clinical Investigations

Objectives: To determine whether a nuclear magnetic resonance–based metabolomics approach can be useful for the early diagnosis and prognosis of septic shock in ICUs.

Design: Laboratory-based study.

Setting: University research laboratory.

Subjects: Serum samples from septic shock patients and ICU controls (ICU patients with systemic inflammatory response syndrome but not suspected of having an infection) were collected within 24 hours of admittance to the ICU.

Interventions: None.

Measurements and Main Results: 1H nuclear magnetic resonance spectra of septic shock and ICU control samples were analyzed and quantified using a targeted profiling approach. By applying multivariate statistical analysis (e.g., orthogonal partial least squares discriminant analysis), we were able to distinguish the patient groups and detect specific metabolic patterns. Some of the metabolites were found to have a significant impact on the separation between septic shock and control samples. These metabolites could be interpreted in terms of a biological human response to septic shock and they might serve as a biomarker pattern for septic shock in ICUs. Additionally, nuclear magnetic resonance–based metabolomics was evaluated in order to detect metabolic variation between septic shock survivors and nonsurvivors and to predict patient outcome. The area under the receiver operating characteristic curve indicated an excellent predictive ability for the constructed orthogonal partial least squares discriminant analysis models (septic shock vs ICU controls: area under the receiver operating characteristic curve = 0.98; nonsurvivors vs survivors: area under the receiver operating characteristic curve = 1).

Conclusions: Our results indicate that nuclear magnetic resonance–based metabolic profiling could be used for diagnosis and mortality prediction of septic shock in the ICU.

1Bio-NMR-Centre, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.

2Critical Care Epidemiologic and Biologic Tissue Resource (CCEPTR), Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.

3Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.

4Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada.

* See also p. 1300.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by Alberta Innovates-Health Solutions. Critical Care Epidemiologic and Biologic Tissue Resource also receives funding from the Alberta Sepsis Network and from the Canada Foundation for Innovation. Drs. Kubes and Vogel hold Scientist awards from the AI-HS. Dr. Winston received grant support from AI-HS (Team Grant “Alberta Sepsis Network”). The remaining authors have disclosed that they do not have any potential conflicts of interest

For information regarding this article, E-mail: vogel@ucalgary.ca

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins