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 characterise 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 catheterisation. 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 catheterisation 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 foetal high 11-βHSD2 activity and reduced 11-βHSD1 activity.Low post-operative 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.
Fudulu et al. (2026) studied this question.