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Surrogate Markers for Neurological Outcome in Children After Deep Hypothermic Circulatory Arrest

Department of Anesthesiology and Critical Care Medicine, Suite 9329, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104; markowitzs{at}email.chop.edu

Rebecca N. Ichord, MD

Gil Wernovsky, MD

J. William Gaynor, MD

Susan C. Nicolson, MD

The Children's Hospital of Philadelphia, The University of Pennsylvania, PA

Improved survival for infants with congenital heart disease (CHD) has led to increased focus on the most significant morbidities that are neurodevelopmental. Neurologic injury in neurodevelopmental outcome may have many causes in children with complex CHD undergoing cardiopulmonary bypass and deep hypothermic circulatory arrest, including genetic syndromes, abnormal blood flow patterns, prenatal insults, and hemodynamic instability. Although gross neurological injury can be detected in the perinatal and postoperative period, more subtle injury may not be identified until much later. Disabilities in speech and language, motor skills, and attention deficit disorder are present by school age in up to 50% of the complex CHD population. It is imperative that the mechanisms of these injuries be identified to enable the application of neuroprotective interventions. To facilitate clinical investigation, evaluation of surrogate markers for these longer term "real" outcomes continues. Because some abnormalities may not be detected for years, the evaluation of a surrogate marker takes a long time. Thus, identification of surrogate markers is in its infancy. Serologic proteins, seizures, magnetic resonance findings, cerebral oxygenation, and the neurologic examination have all been studied. Continuing innovation in the use of magnetic resonance imaging techniques and the application of physiologic measures including near-infrared spectroscopy currently pose the greatest potential for advances. This article summarizes the state of the art and an admission about how far we have yet to travel as we strive to make the neurodevelopmental outcomes of patients with CHD comparable to their healthy peers.

Key Words: congenital heart disease • deep hypothermic circulatory arrest • neurodevelopmental outcome • surrogate markers • near infrared spectroscopy • serological markers • electroencephalography • magnetic resonance imaging • magnetic resonance spectroscopy

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