Our hypothesis is that high dose EPO will have neuroprotective effects in neonatal cardiac surgery, reducing both early and late neurological and neurodevelopmental injury. Early primary outcome improvement is defined by reduction in postoperative MRI severity of injury score by 25%. Late outcome improvement is defined by increase in Bayley Scales of Infant Development score by 18% at age 3 years.
1. To determine the effect of high-dose perioperative EPO on short and long term neurological outcomes in neonates undergoing cardiac surgery with an optimized cardiopulmonary bypass strategy, using MRI as primary early outcome modality.
2. To determine EPO tolerability and safety with short term high dose administration.
3. To determine EPO pharmacokinetics in this population.
4. To determine the relationship of neurological monitoring, specifically near-infrared spectrscopy (NIRS), to neurological outcomes with an optimized cardiopulmonary bypass technique in neonates that avoides deep hypothermic circulatory arrest, and to determine if EPO affects this relationship
We will randomize newborns scheduled for cardiac surgery for the arterial switch operation, Norwood Stage I palliation, or aortic arch reconstruction. Each patient will undergo NIRS monitoring pre-, intra-, and postoperatively for a total of 96 hours; pre- and postoperative EEG monitoring during the same period; and a brain MRI immediately prior to surgery, and 7 days after surgery. Patients will be randomized to receive EPO, 1000 units/kg per dose IV, or placebo, administered 12-24 hours before surgery, the day of surgery, and the day after surgery. Patients will also have a third brain MRI at 3-6 months; and a complete neurodevelopmental assessment at age 1, 3, and 5 years. The early primary outcome variable will be MRI severity of injury score; and the later primary outcome will be Bayley Scales of Infant Development scores. MRI parameters include T1 and T2 weighted imaging, diffusion tensor imaging, volumetrics, MR spectroscopy, and severity of hypoxic ischemic injury score for infarction, hemorrhage, periventicular leukomalacia, thrombosis, and other injuries. Early MRI findings will be correlated with later MRI changes, and with long term neurodevelopmental outcomes.