The pioneering work of Safar et al. in 1958 (1) on airway methods of artificial respiration and of Kouwenhoven et al. in the early 1960s (2,3) on the closed cardiac massage with external defibrillation led to the development of modern basic and advanced cardiac life support for patients in cardiopulmonary arrest. Since these early works, several large clinical trials have been undertaken to improve survival and functional outcome in this patient population.

With advances in critical care, cardiopulmonary resuscitation led to increased survival, but the functional outcome continued to be poor. Many patients who were successfully resuscitated remained in persistent coma or suffered significant cognitive deficits. Realizing the importance of neurologic injury from global cerebral ischemia of cardiac arrests (CA), the American Heart Association focused on brain injury and introduced the term "cardiopulmonary-cerebral resuscitation" in the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care of 2000 (4). The same guidelines further provide that, "The cerebral cortex, the tissue most susceptible to hypoxia, is irreversibly damaged, resulting in death or severe neurological damage. The need to preserve cerebral viability must be stressed in research endeavors and in practical interventions." (4).

Several advances have been added in the practice of resuscitation, but neurologic functional outcome, especially in comatose patients following CA, continues to be poor. Examples of these advancements include faster response time to patients with out-of-hospital CA, the use of early cardiac defibrillation, and increased public awareness of basic life-support skills (5,6). Consequently, the number of CA victims who survive with severe neurologic injury has increased (7).

However, recently, survival and functional neurologic outcomes have been significantly improved by therapeutic intervention. Two studies reported that induced hypothermia from 32 to 34°C for 12 to 24 hours resulted in improved survival and functional outcome (8,9), and these findings led the International Liaison Committee on Resuscitation (ILCOR) to recommend hypothermia in patients who are unconscious after resuscitation from CA (10) . This chapter discusses the development of controlled clinical trials and management of brain injury after CA.

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