Metabolic profiling of children undergoing surgery for congenital heart disease

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.