title: Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease.
abstract: OBJECTIVE
  Inflammation and metabolism are closely interlinked. Both undergo significant dysregulation following surgery for congenital heart disease, contributing to organ failure and morbidity. In this study, we combined cytokine and metabolic profiling to examine the effect of postoperative tight glycemic control compared with conventional blood glucose management on metabolic and inflammatory outcomes in children undergoing congenital heart surgery. The aim was to evaluate changes in key metabolites following congenital heart surgery and to examine the potential of metabolic profiling for stratifying patients in terms of expected clinical outcomes.
  
  
  METHODS
  Laboratory and clinical study.
  
  
  METHODS
  University Hospital and Laboratory.
  
  
  METHODS
  Of 28 children undergoing surgery for congenital heart disease, 15 underwent tight glycemic control postoperatively and 13 were treated conventionally.
  
  
  METHODS
  Metabolic profiling of blood plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A panel of metabolites was measured using a curve-fitting algorithm. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The data were assessed with respect to clinical markers of disease severity (Risk Adjusted Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope score, duration of ventilation and pediatric ICU-free days).
  
  
  RESULTS
  Changes in metabolic and inflammatory profiles were seen over the time course from surgery to recovery, compared with the preoperative state. Tight glycemic 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 interleukin-8 and interleukin-6 concentrations, inversely correlated with PICU-free days at 28 days. The interleukin-6/interleukin-10 ratio directly correlated with plasma lactate.
  
  
  CONCLUSIONS
  This is the first report on the metabolic response to cardiac surgery in children. Using nuclear magnetic resonance to monitor the patient journey, we identified metabolites whose concentrations and trajectory appeared to be associated with clinical outcome. Metabolic profiling could be useful for patient stratification and directing investigations of clinical interventions.
authors.affiliation: 1Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom. 2School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom. 3Paediatric Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom. 4Department of Intensive Care, Southampton General University Hospital, Southampton, United Kingdom. 5Paediatric Intensive Care Unit, Imperial College London NHS Foundation Trust, London, United Kingdom. 6Department of Nutrition and Dietetics, Faculty of Medicine, Imperial College London, United Kingdom. 7University Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Goncalo D S
authors.initials: GD
authors.lastname: Correia
authors.forename: Keng
authors.initials: K
authors.lastname: Wooi Ng
authors.forename: Anisha
authors.initials: A
authors.lastname: Wijeyesekera
authors.forename: Sandra
authors.initials: S
authors.lastname: Gala-Peralta
authors.forename: Rachel
authors.initials: R
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: MacCarthy-Morrogh
authors.forename: Beatriz
authors.initials: B
authors.lastname: Jiménez
authors.forename: David
authors.initials: D
authors.lastname: Inwald
authors.forename: Duncan
authors.initials: D
authors.lastname: Macrae
authors.forename: Gary
authors.initials: G
authors.lastname: Frost
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Nazima
authors.initials: N
authors.lastname: Pathan
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000601:surgery*; D006801:Humans; D007223:Infant; D055442:Metabolome
chemical_list: D001786:Blood Glucose
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