Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

The ultimate goal of the present study, is to describe a new approach of more personalized and safe care to infants with birth asphyxia and hemodynamic instability.

Asphyxiated infants often present with multiorgan failure and low blood pressure. Therapeutic hypothermia, the standard of care, could worsen hemodynamic instability; therefore, treatment of cardiovascular impairment represents a major challenge in this clinical setting. An association was previously described between hypotension and low serum cortisol values in this patient population, and it was suggested that relative adrenal insufficiency (RAI) is an important factor in the circulatory compromise of these patients. In the "CORTISoL" clinical trial, it was also demonstrated that low-dose hydrocortisone therapy was effective in the treatment of cardiovascular impairment in asphyxiated neonates; however, some gaps remain in the knowledge on optimal dosing. Importantly, steroid therapy should be administered at the lowest effective dose and for the shortest possible duration in this vulnerable population.

In the current pharmacokinetic study, the investigators propose a stepwise approach to more detailed understanding of RAI and hydrocortisone pharmacokinetics in asphyxiated neonates. The findings would certainly aid clinical decision-making and allow for more personalized therapeutic interventions for the treatment of hemodynamic instability.

Inclusion criteria

• gestational age ≥ 36 weeks
• provision of whole-body hypothermia treatment (as described by Azzopardi et al.)
• presence of systemic hypotension (defined as a mean arterial pressure less than the gestational age in weeks)
• indication for hydrocortisone treatment during hypothermia by the attending physician
• indwelling arterial catheter to take blood samples without additional painful punctures: umbilical arterial catheter or peripheral arterial catheter
• written informed parental consent

Exclusion criteria

• infants who are expected to be > 6 hours of age (not suitable for cooling)
• critical congenital abnormalities
• genetic disease
• signed informed consent is unavailable