Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease
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Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2015-07-01
Date Acceptance
2015-07-01
Citation
Critical Care Medicine, 2015, 43 (7), pp.1467-1476
ISSN
1530-0293
Publisher
Lippincott, Williams & Wilkins
Start Page
1467
End Page
1476
Journal / Book Title
Critical Care Medicine
Volume
43
Issue
7
Copyright Statement
© 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.
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.
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
General & Internal Medicine
bioinformatics
biomarkers
congenital heart disease
critical illness
metabolic profiling
PEDIATRIC SEPTIC SHOCK
CARDIOPULMONARY BYPASS
CARDIAC-SURGERY
INTENSIVE-CARE
SPECTROSCOPY
INFANTS
LACTATE
PLASMA
SERUM
INTERLEUKIN-10
Publication Status
Published