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The dynamic adrenal response of children to cardiac surgery and cardiac catheterization
Daniel Paul Fudulu1,2, Isabella Marinelli3, Daniel Galvis4
1Bristol Medical School, University of Bristol, Bristol BS8 1TH, UK.
Insights
Neonates undergoing cardiac surgery exhibit distinct hypothalamic-pituitary-adrenal (HPA) axis hormone profiles. Higher free cortisol levels in neonates impact perioperative management strategies for pediatric cardiac surgery patients.
Area of Science:
- Pediatric Endocrinology
- Cardiovascular Surgery
- Stress Physiology
Background:
- The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to surgical stress.
- HPA axis hormone imbalances increase morbidity and mortality in pediatric cardiac surgery.
- The HPA axis physiology in children undergoing cardiac surgery remains poorly understood.
Purpose of the Study:
- To characterize dynamic HPA axis responses in children undergoing cardiac surgery.
- To determine age- and procedure-related differences in cortisol and cortisone physiology.
Main Methods:
- Recruited children (0-18 years) undergoing cardiac surgery or catheterisation.
- Collected tissue-free cortisol/cortisone via microdialysis (24h), serum ACTH, cortisol, CBG, and inflammatory markers.
- Developed dynamic markers and a mathematical model to analyze age- and procedure-dependent hormonal responses.
Main Results:
- Neonates showed higher free cortisol and cortisone AUC and peak concentrations than catheterisation patients and older children.
- Elevated cortisone in neonates is linked to enzymatic interconversion (persistent high 11-βHSD2, reduced 11-βHSD1 activity).
- Low post-operative blood cortisol and CBG in neonates led to high interstitial free cortisol peaks.
Conclusions:
- Neonates exhibit distinct physiology with higher free cortisol levels.
- Higher free cortisol readily diffuses into interstitial tissues in neonates.
- Findings have significant implications for perioperative management in neonates undergoing cardiac surgery.
Context:
The hypothalamic-pituitary-adrenal (HPA) axis is the key homeostatic system regulating the response to surgical stress. Imbalances in HPA axis hormones increase morbidity and mortality in children after cardiac surgery. Despite this, the physiology of the HPA axis in children undergoing cardiac surgery is poorly understood, leading to controversies in clinical practice.
Objective:
To characterize dynamic HPA axis responses in children undergoing cardiac surgery and to determine age- and procedure-related differences in cortisol and cortisone physiology.
Methods:
We recruited children (0-18 years) undergoing cardiac surgery with cardiopulmonary bypass or cardiac catheterization. Tissue-free cortisol and cortisone were sampled every 20 minutes for up to 24 hours via microdialysis, alongside serum adrenocorticotropic hormone (ACTH), cortisol, cortisol-binding globulin (CBG), and inflammatory markers. We developed dynamic markers to quantify age- and procedure-dependent differences in hormonal responses and built a mathematical model to explain them.
Results:
Neonates undergoing surgery showed higher free cortisol and cortisone AUC and peak concentrations than catheterization patients. Neonates had higher peaks of cortisol and cortisone than older children undergoing surgery. The much higher tissue cortisone levels observed in neonates can be explained by enzymatic interconversion between cortisol and cortisone, likely due to persistent fetal high 11-βHSD2 activity and reduced 11-βHSD1 activity. Low postoperative blood cortisol and CBG values in neonates resulted in high free cortisol peaks in interstitial fluid during and after surgery.
Conclusion:
Neonates differ physiologically, with higher free cortisol levels that more readily diffuse into interstitial tissues, with implications for perioperative management.
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