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Published on: June 25, 2010
Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease
Goncalo D S Correia1, Keng Wooi Ng, Anisha Wijeyesekera
11Computational 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.
Insights
Metabolic profiling in children after heart surgery identified key metabolites linked to disease severity. This approach may help stratify patients and guide clinical interventions for better outcomes.
Area of Science:
- Biochemistry and clinical medicine
- Pediatric cardiology and critical care
- Metabolomics and inflammation research
Background:
- Inflammation and metabolism are intricately linked, with dysregulation common after congenital heart disease surgery.
- Postoperative organ failure and morbidity are significant concerns in pediatric cardiac surgery.
- Understanding metabolic and inflammatory changes is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the impact of tight glycemic control versus conventional management on metabolic and inflammatory profiles in children undergoing congenital heart surgery.
- To identify key metabolites associated with surgical outcomes and disease severity.
- To explore the utility of metabolic profiling for patient stratification.
Main Methods:
- A laboratory and clinical study involving 28 children undergoing congenital heart surgery.
- Postoperative management included either tight glycemic control (15 children) or conventional blood glucose management (13 children).
- Metabolic profiling using proton nuclear magnetic resonance spectroscopy and cytokine analysis via ELISA, correlated with clinical severity markers.
Main Results:
- Metabolic and inflammatory profiles changed significantly from pre-surgery to recovery.
- Tight glycemic control did not substantially alter the overall response profile.
- Eight metabolites (e.g., 3-D-hydroxybutyrate, lactate, citrate) were associated with surgical and disease severity.
- Pro-inflammatory cytokines (IL-8, IL-6) inversely correlated with pediatric intensive care unit (PICU)-free days.
Conclusions:
- This study is the first to report on the metabolic response to cardiac surgery in children.
- Nuclear magnetic resonance-based metabolic profiling identified metabolites associated with clinical outcomes.
- Metabolic profiling shows promise for stratifying pediatric patients and guiding clinical interventions.
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.
Design:
Laboratory and clinical study.
Setting:
University Hospital and Laboratory.
Patients:
Of 28 children undergoing surgery for congenital heart disease, 15 underwent tight glycemic control postoperatively and 13 were treated conventionally.
Interventions:
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).
Measurements And Main 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.
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