Cerebral resuscitation after cardiac arrest

Introduction

Out-of-hospital cardiac arrest is a common cause of death in developed countries. Prolonged cardiac arrest may lead to neurological injury as a result of global cerebral ischaemia, and most patients who are initially successfully resuscitated from out-of-hospital cardiac arrest and transported to an emergency department (ED) remain comatose and require admission to an intensive care unit (ICU). Subsequently many of these patients die as a consequence of severe anoxic neurological injury. Current international recommendations for care after resuscitation from cardiac arrest outline goals for oxygenation, ventilation, blood pressure control and targeted temperature management (TTM).

This chapter details the pathophysiology of the neurological injury and presents recent data on current treatment strategies that may decrease this injury and improve outcomes after resuscitation from cardiac arrest.

Pathophysiology of cerebral ischaemia and reperfusion injury

The brain is highly dependent on an adequate supply of oxygen and glucose for metabolism. When cerebral oxygen delivery falls below 20 mL/100 g, brain tissue/minute aerobic metabolism changes to anaerobic glycolysis, with a marked decrease in the generation of adenosine triphosphate (ATP). After several minutes of cerebral ischaemia, the supply of ATP is exhausted and cellular metabolism ceases. The failure of the sodium/potassium trans-membrane pump leads to a shift of sodium into the cell, with cell swelling. In addition, hydrogen ions are generated, and the resulting intracellular metabolic acidosis is toxic to intracellular enzyme systems.

Additional injury may occur following return of a spontaneous circulation (ROSC) and reperfusion of the brain with oxygenated blood. The intracellular levels of glutamate, an excitatory neurotransmitter released from pre-synaptic terminals, increase dramatically during reperfusion. Glutamate activates calcium ion channel complexes, and these shift calcium from the extracellular fluid to the intracellular fluid. The calcium influx into cells initiates multiple biochemical cascades, leading to the production of ‘free radicals’ and the activation of degradative enzymes.

Finally, some neurones that survive the initial anoxic insult proceed to ‘programmed cell death’, also known as apoptosis. This delayed neuronal death may occur at different rates, varying from 6 hours for neurons in the striatum to 7 days for hippocampal CA1 neurones. Apoptosis is characterized by cellular and nuclear shrinkage, chromatin condensation and DNA fragmentation.