Hypoxic-Ischemic Encephalopathy

Brain injury after cardiac arrest has been referred to as hypoxic-ischemic encephalopathy, global cerebral ischemia, anoxic encephalopathy, and postcardiac arrest syndrome. Whatever term we use, this injury has dramatic consequences for patients and their families. The importance of brain injury in survivors of cardiac arrest has been known for a long time, but its recognition peaked with the development of modern cardiopulmonary resuscitation.

Advances in the understanding and practice of cardiopulmonary resuscitation and critical care medicine have led to increasing success in patient survival; however, functional outcome due to neurologic injury remains a significant concern. Numerous clinical trials with neuroprotective agents undertaken over the past 30 years have failed to show functional benefit in survivors. The impact of neurologic injury postresuscitation refocused the practice to become cardio-pulmonary-cerebral resuscitation. Despite this realization, the continued lack of effective neurologic intervention resulted in unmitigated neurologic injury, which resulted in poor quality of life in the vast majority of survivors. With the predominance of poor outcome in survivors and the absence of effective therapies, neurologic care in these patients was limited to supportive care and prognostication of functional outcome.

The recent success of therapeutic hypothermia leading to improved survival and neurologic outcomes in survivors showed that this brain injury could be ameliorated. The American Heart Association (AHA) in its 2005 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care and the International Liaison Committee on Resuscitation (ILCOR) acknowledged the effectiveness of this therapy and recommends its use for appropriate patients. Therapeutic hypothermia is currently being incorporated in the resuscitation practices in many medical institutions in the United States and across the world. In these institutions, consultation and co-management with practicing neurologists are requested for cardiac arrest survivors. It is recognized that the involvement of the neurologist in the care of these patients is extending beyond prognostication to actual neuroprotective strategies, which at this time focuses on therapeutic hypothermia. The change of neurologic care from supportive to injury reversal and prevention necessitates the evolution of the traditional role of the neurologist solely as a diagnostician to one who works directly with the multidisciplinary resuscitation team and critical care physicians to provide acute interventions that will ameliorate acute brain injury.

This issue of Seminars in Neurology provides a comprehensive and multidisciplinary review of the current research and clinical practices related to hypoxic-ischemic encephalopathy. The first article, written by Dr. Greer focuses not only on the mechanisms of brain injury in global ischemia, but also provides potential therapeutic interventions related to the injury mechanisms. The following article by Dr. Little, Dr. Paradis, and Dr. Heard provides an authoritative review on the emergency and prehospital interventions undertaken to improve neurologic outcome. After successful resuscitation, therapeutic hypothermia has to be considered for all appropriate comatose survivors. Dr. Rincon and Dr. Mayer provide an evidence-based review on therapeutic hypothermia. As the potential for more neurologic injury exist, Dr. Wright and I discuss neuroprotective strategies in the intensive care unit in cardiac arrest survivors.

The next series of articles provide key updates on the care provided by neurologists for these patients. Dr. Kaplan provides a review on the state of the art of electrophysiologic prognostication. Recent advances in the use of biomarkers and neuroimaging is provided in the article by Dr. Kandiah, Dr. Ortega, and Dr. Torbey. Dr. Khot and Dr. Tirschwell provide an update on the management of long-term neurological complications after hypoxic-ischemic encephalopathy.

The last three articles deal with important specialized topics that are closely related to hypoxic-ischemic encephalopathy. As a form of incomplete global cerebral ischemia, neurologic injury related to cardiac bypass procedures has been an important clinical problem. Dr. Gottesman and Dr. Wityk provide a review on brain injury and cardiac bypass. While this issue focuses on hypoxic-ischemic encephalopathy, recent research indicates a high prevalence of metabolic encephalopathy causing delirium and coma among patients in the intensive care unit. The article by Dr. Stevens and Dr. Pronovost reviews the spectrum of encephalopathy in critical illness. Despite the recent advances in this field many problems still persist and new ones are identified. The ongoing need for more rigorous research is recognized to be able to benefit patients, their families, and society. The last article by Mr. Donatelli, Dr. Williams, and myself deals with the difficult but important issue of ethics in clinical research, brain death, and organ donation in the context of cardiac arrest and critical care.

This issue of Seminars in Neurology is a product of the hard work and dedication of many people. I would like to recognize the contributing authors, their expertise, and clinical interest in helping redefine and enhance the role of neurologists in the care of these patients. I would also like to express my gratitude to those who have supported my research interest: Nitish Thakor, Dan Hanley, Tracey Hartmann, Steve Schulman, Nisha Chandra, Peter Kaplan, and numerous colleagues within and outside of Johns Hopkins. To Dr. Karen Roos, the Editor in Chief of Seminars in Neurology, her assistant Linda Hagan, and the production staff at Thieme Publishers, I thank you for recognizing the importance of this topic and dedicating an issue of Seminars in Neurology to it. To my wife Effie, and our children, Ginno and Sofia, I thank you for the unwavering support and for allowing me to work during nights and weekends on this project. And lastly, I would like to dedicate this to my father, Romeo, Sr., whose untimely death from cardiac arrest made me appreciate not only the medical challenges, but also the social and personal ramification of this problem.