The Journal of clinical endocrinology and metabolism · 2026
The dynamic adrenal response of children to cardiac surgery and cardiac catheterization.
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Fudulu Daniel Paul, Marinelli Isabella, Galvis Daniel, Zavala Eder, Walker-Smith Terrie, Evans Jonathan, Papadopoulou Fanoula, Upton Thomas, Ramesh Aravind, Rapetto Filippo, Kershaw Yvonne, Fox Jan, Aramburo Angela, Stoica Serban Constantin, Caputo Massimo, Parry Andrew, Macrae Duncan, Michielon Guido, Hoschtitzky Johann Andreas, Sheehan Karen, van Faassen Martijn, Kema Ido, Angelini Gianni Davide, Lightman Stafford, Gibbison Ben
Аннотация
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.
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.