Plasma cortisol response to ACTH challenge in hypoxic newborn piglets resuscitated with 21% and 100% oxygen

Although the use of supplemental oxygen to resuscitate asphyxiated neonates remains controversial, the effects of hypoxia and reoxygenation (room air versus pure oxygen) on the hypothalamo-pituitary-adrenal axis are unknown. We aimed to evaluate the effect of hypoxia and reoxygenation with either 21% or 100% oxygen on plasma cortisol before and after an adrenocorticotrophin (ACTH) challenge in newborn piglets. Thirty-five piglets (aged 1-3 days, weighing 1.5-2.4 kg) were instrumented to measure heart rate, MAP, and cardiac output. After 2 h of normocapnic hypoxia (PaO2, 20-30 mmHg; pH, <6.95), piglets were resuscitated with 21% or 100% oxygen for 1 h and then 21% oxygen for 3 h. Sham-operated piglets had no hypoxia-reoxygenation (H-R). Serial plasma cortisol levels were determined after a blinded randomized administration of ACTH (4 microg/kg, i.v.) or saline at 2 h reoxygenation. The expression of steroidogenic factor 1 in the adrenals was studied. Cardiac output decreased with hypoxia and recovered with resuscitation. Piglets developed hypotension similarly in 21% and 100% H-R groups during reoxygenation (versus sham-operated group, P < 0.05). Both H-R groups had increased plasma cortisol levels (versus sham-operated group, P < 0.05) at 2 h of reoxygenation after hypoxia, with a further increase in levels in 21% H-R piglets at 4 h reoxygenation (versus 100% H-R piglets, P < 0.05). The response to ACTH was delayed in H-R groups, with the maximum increase at 120 min post-ACTH administration (versus 30-60 min post-ACTH for sham-operated piglets). Plasma cortisol levels increased significantly post-ACTH administration in 21% H-R and sham-operated piglets (115% +/-50% and 126% +/- 25% at 120 min, respectively, P < 0.05 vs. pre-ACTH baselines) but not in 100% H-R piglets (51% +/-14%), which had a lower expression of steroidogenic factor 1 than the other groups. Although the clinical significance of high cortisol levels and cortisol response to ACTH in H-R newborn piglets is uncertain, a preserved cortisol response may support using room air in neonatal resuscitation.