Associations between serum cortisol, cardiovascular function and neurological outcome following acute global hypoxia in the newborn piglet

Perinatal asphyxia is a significant contributor to neonatal brain injury. However, there is significant variability in neurological outcome in neonates after global hypoxia-ischemia. The aims of this study were to identify which physiological response/s during global hypoxia-ischemia influence the severity of brain injury and to assess their relative importance. Hypoxia/hypercapnia was induced in 20 anaesthetized piglets by reducing the inspired oxygen fraction to 10% and the ventilation rate from 30 to 10 breaths per minute for 45 min. Neurological outcome was assessed using functional markers including cerebral function amplitude (via electroencephalography) and cerebral impedance, and the structural marker microtubule associated protein-2 by immunohistochemistry at 6 h post hypoxia. Significant variability in neurological outcome was observed following the constant hypoxia/hypercapnia insult. There was a high degree of variability in cardiovascular function (mean arterial blood pressure and heart rate) and serum cortisol concentrations in response to hypoxia. More effective maintenance of cardiovascular function and higher serum cortisol concentrations were associated with a better outcome. These two variables were strongly associated with neurological outcome, and together explained 68% of the variation in the severity of neurological outcome. The variability in the cardiovascular and cortisol responses to hypoxia may be a more important determinant of neurological outcome then previously recognized.