Neuroprotection in pediatric cardiac surgery: What is on the horizon?

Neurological injury still occurs in association with pediatric cardiac surgery, despite major progress in reducing mortality. Forty to 50% of 5 year olds who underwent complex open cardiac surgery as neonates and young infants have impaired neurodevelopmental outcomes. In order to apply neuroprotective strategies, it is necessary to develop markers for acute neurological injury, and surrogates that predict later abnormal neurodevelopmental outcomes. Near infrared spectroscopy holds promise as a marker of acute brain injury, with several pediatric cardiac surgery studies indicating a relationship between prolonged low cerebral oxygen saturation and clinical or MRI change. EEG seizures have not been found to have a relationship with acute or longer term neurological injury in recent studies. Brain MRI indicates that approximately 30% of neonates have MRI injury before cardiac surgery, and 40% have new injury postoperatively, predominately white matter injury. Serum or urine biomarkers, such as S100β protein, neuron–specific enolase, or creatine kinase brain band, lack specificity for nervous system injury. Newer biomarkers, such as glial fibrillary acidic protein, ubiquitin C-terminal hydrolase 1, and phosphorylated axonal neurofilament heavy chain, have potential for much greater specificity. Neuroprotective strategies include cardiopulmonary bypass techniques which avoid circulatory arrest and low flows. Certain anesthetic regimens such as halogenated anesthetic agents, ketamine, and dexmedetomidine may be neuroprotective in pediatric cardiac surgery. Therapeutic hypothermia, and remote ischemic preconditioning are two simple techniques that may prove to have neuroprotective properties. Erythropoietin pretreatment, and treatment with neurotrophic factors such as brain-derived neurotrophic factor, glial cell line derived neurotrophic growth factor, vascular endothelial growth factor, and nerve growth factor also have potential to prevent and treat neuronal loss in the perioperative period. Finally, neural stem cells derived from the patient’s own umbilical cord blood could potentially be utilized for neuroprotection in neonates with a prenatal diagnosis of congenital heart disease.