Metabolic profiling of children undergoing surgery for congenital heart disease

G.D.S. Correia, Keng Wooi Ng, A. Wijeyesekera, S. Gala-Peralta, Rachel Williams, Sarah Bacon, David Inwald, Duncan Macrae, Gary Frost, Elaine Holmes, Nazima Pathan, B. Jiménez

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Inflammation and metabolism are closely interlinked. Both undergo significant dysregulation following surgery for congenital heart disease, contributing to the development of organ failure and morbidity. We combined cytokine and metabolic profiling to examine the effect of post-operative tight glycemic control compared to conventional blood glucose management on metabolic and inflammatory outcomes in children undergoing congenital heart surgery. We explored the potential of metabolic profiling for stratifying patients according to clinical outcomes and evaluated changes in key metabolites. DESIGN: Laboratory and clinical study SETTING: University Hospital and Laboratory. PATIENTS: 28 Children undergoing surgery for congenital heart disease. 15 underwent tight glycaemic control post-operatively, 13 were treated conventionally. INTERVENTIONS: Metabolic profiling of blood plasma was undertaken using proton nuclear magnetic resonance (NMR) spectroscopy. A panel of metabolites were measured using a curve-fitting algorithm. Inflammatory cytokines were measured by ELISA. The data were assessed with respect to clinical markers of disease severity (RACHS-1, PELOD, inotrope score, duration of ventilation and PICU free days). MEASUREMENTS AND MAIN RESULTS: Changes in metabolic and inflammatory profiles were seen over the timecourse following congenital heart surgery through to recovery, compared to the pre-operative state. Tight glycaemic control did not significantly alter the response profile. We identified eight metabolites (3-D-hydroxybutyrate, acetone, acetoacetate, citrate, lactate, creatine, creatinine and alanine) associated with surgical and disease severity. The strength of proinflammatory response, particularly IL-8 and IL-6 levels, inversely correlated with PICU free days. The ratio of IL-6 to IL-10 was directly correlated with plasma lactate. CONCLUSIONS: This is the first study to profile the metabolic response to cardiac surgery in children. Using NMR to monitor the patient journey we identified metabolites whose levels and trajectory appeared to be associated with clinical outcome, indicating that metabolic profiling could be used to augment patient stratification with respect to post-surgical intervention.
Original languageEnglish
Pages (from-to)1467-1476
Number of pages10
JournalCritical Care Medicine
Volume43
Issue number7
DOIs
Publication statusPublished - 1 Jan 2015

Bibliographical note

Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • bioinformatics
  • biomarkers
  • congenital heart disease
  • critical illness
  • metabolic profiling

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  • Cite this

    Correia, G. D. S., Ng, K. W., Wijeyesekera, A., Gala-Peralta, S., Williams, R., Bacon, S., Inwald, D., Macrae, D., Frost, G., Holmes, E., Pathan, N., & Jiménez, B. (2015). Metabolic profiling of children undergoing surgery for congenital heart disease. Critical Care Medicine, 43(7), 1467-1476. https://doi.org/10.1097/CCM.0000000000000982