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In addition to developing mouth-to-mouth resuscitation, Dr. Peter Safar introduced the concept of cardiopulmonary cerebral resuscitation to save lives and promote research that focused on therapies to treat brains that “were too good to die.”1 The concept of brain-directed therapy has since expanded to include all causes of acute brain injury and led to the field of reanimatology, commonly referred to as cerebral resuscitation.


Acute brain injury is a leading cause of morbidity and mortality in both adults and children. Hundreds of thousands of patients worldwide suffer permanent neurologic deficits and death every year after acute brain injuries from cardiac arrest, stroke, near drowning, anesthesia mishaps, traumatic brain injury, and other acute injuries.2 In addition to personal tragedy and impaired functional capacity to individuals, the financial strain on the health care system is enormous. Estimates indicate that >3% of every health care dollar is spent on care for patients who sustain acute brain injury, totaling over $60 billion dollars a year.3 Cerebral resuscitation research provides hope for patients with acute brain injuries.


Although there is minimal pathologic evidence of irreversible brain injury after nearly 2 hours of complete disruption of blood flow to the brain,4 as little as 5 minutes of transient ischemia prime the brain for a cascade of vascular, cellular, biochemical, and molecular events that result in irreversible brain damage during reperfusion. This cascade of events are collectively referred to as reperfusion disease or the postresuscitation syndrome.5


Postresuscitation syndrome occurs after both focal and global cerebral ischemia. Stroke and traumatic brain injury cause disruption of local blood brain flow (focal ischemia), whereas cardiac arrest and severe asphyxia result in global brain ischemia. The chapters on stroke (see Chapter 161, Stroke, Transient Ischemic Attack, and Cervical Artery Dissection) and traumatic brain injury (see Chapter 254, Head Trauma in Adults and Children) provide information on the pathophysiology of focal cerebral ischemia. This chapter provides information on the pathophysiology of the postresuscitation syndrome specific to transient global brain ischemia.


Primary cardiac arrest from ventricular fibrillation/tachycardia is the most common cause of global brain ischemia in adults, whereas asphyxia is the leading cause of global brain ischemia in children.6 The differences in postresuscitation syndrome from primary cardiac versus asphyxial cardiac arrest are not well studied. There is likely overlap in the mechanisms that lead to irreversible brain injury, as brain injury occurs in the same selectively vulnerable regions of the hippocampus, thalamus, and cerebellum independent of the etiology of the cardiac arrest.7 In addition, brain injury occurs in a similar “delayed neuronal death pattern” of hours after the transient global brain ischemia, suggesting that there is a window of opportunity to treat all forms of acute brain injury.8


After cardiac arrest, there is an initial period of no cerebral blood flow even if normal blood pressure is restored. This no reflow phenomenon is ...

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