The brain after cardiac arrest

Jonathan Elmer, MD, MS; Clifton W. Callaway, MD, PhD . The Brain After Cardiac Arrest. Semin Neurol. 2017;37(1):019-024.

Abstract

Cardiac arrest is common and deadly. Most patients who are treated in the hospital after achieving return of spontaneous circulation still go on to die from the sequelae of anoxic brain injury. In this review, the authors provide an overview of the mechanisms and consequences of postarrest brain injury. Special attention is paid to potentially modifiable mechanisms of secondary brain injury including seizures, hyperpyrexia, cerebral hypoxia and hypoperfusion, oxidative injury, and the development of cerebral edema. Finally, the authors discuss the outcomes of cardiac arrest survivors with a focus on commonly observed patterns of injury as well as the scales used to measure patient outcome and their limitations.

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From the article

Despite advances in care, the majority of patients who are treated after the return of spontaneous circulation (ROSC) will succumb to the sequelae of hypoxic-ischemic brain injury before hospital discharge. Similar to traumatic brain injury, hypoxic-ischemic brain injury after CA results in both primary and secondary injuries, with distinct mechanisms and treatment strategies…

 High-quality cardiopulmonary resuscitation (CPR) initiated as soon as possible after collapse, and early defibrillation to rapidly restore normal perfusion, are the most important interventions to reduce the severity of primary brain injury.  It remains unclear whether care provided after ROSC can reduce the severity of primary brain injury or if therapies after CPR improve outcomes only by reducing the risk of secondary brain injury. Evidence-based therapies in the hours to days after ROSC that improve neurologic outcomes include targeted temperature management; early coronary revascularization; delayed, multimodal neurologic prognostication; and postacute care rehabilitation…

Substantial current research focuses on understanding the fact that histological signs of post-CA neuronal death are delayed for hours or days after ischemia-reperfusion. This observation has prompted an analogy to other types of delayed, programmed cell death such as apoptosis, autophagy, necroptosis, and ferroptosis…

Potentially modifiable mechanisms of secondary brain injury include seizures, hyperpyrexia, cerebral hypoxia, oxidative stress, the development of cerebral edema, microcirculatory dysfunction, impaired autoregulation of cerebral blood flow, and increased cerebral vascular resistance…

Seizures occur in 10 to 20% of comatose patients after CA, may worsen excitotoxicity, and are associated with worse outcomes.  It remains unknown whether seizures are simply an epiphenomenon of more severe injury or by themselves produce secondary injury…

Thus, the brain is particularly sensitive to hypotension and may require higher than normal arterial pressure to maintain normal blood flow. Combined with the fact that systemic hypotension and shock after CA are also common, and microvascular dysfunction can lead to areas of no-reflow despite return of a perfusing rhythm, significant cerebral hypoperfusion is a real risk. Aggressive early resuscitation, coronary revascularization, and vasopressor use to increase mean arterial pressure may reduce this risk…

Hyperventilation-associated hypocapnia may lead to cerebral vasoconstriction and exacerbate hypoperfusion, whereas normocapnia or even mild permissive hypercapnia are associated with improved neurologic outcomes…

The timing of early cerebral edema and mechanistic studies suggest a vasogenic rather than cytotoxic mechanism for early edema and indeed hyperosmolar therapy may reduce radiographic signs of edema and intracranial hypertension. Reducing gross edema theoretically will improve microvascular blood flow to vulnerable brain regions, but it is unknown whether treating postanoxic cerebral edema improves patient outcomes…

Guidelines recommend delaying withdrawal of life-sustaining therapy based on neurologic prognosis until at least 72 hours after ROSC because the accuracy of prognostic information available prior to this time is limited. Even patients who remain comatose 72 hours after ROSC may go on to awaken and have favorable recoveries. Unfortunately, the withdrawal of life-sustaining therapy in the first 24 hours after ROSC based on perceived neurologic prognosis remains common…

Several neuronal subtypes and brain regions are particularly sensitive to the physiological and cellular effects of anoxic injury and circulatory arrest. This results in distinct phenotypes among survivors of CA. For example, vulnerable cell populations include the hippocampal CA1 pyramidal neurons in the mesial temporal lobe,  As a consequence, memory impairments, particularly the ability to consolidate short-term memory, are common after CA even among patients with otherwise favorable functional outcomes. Cerebellar Purkinje cell and basal ganglia injury with cortical sparing may lead to postanoxic myoclonus and a range of other movement disorders in patients who are cognitively intact. Cortical pyramidal neuron injury can cause impaired attention, processing speed, and/or executive function depending on the region of injury…

Regardless, many patients experience substantial improvement in symptom severity in the months after CA, and rehabilitation improves recovery. Randomized trials have demonstrated that focused rehabilitation can improve social engagement, quality of life, and emotional outcomes as well as reduce medical complications in those discharged after CA…

Despite their limitations, short-term measures of functional recovery at hospital discharge do predict long-term survival. Those discharged with moderate or severe disability as measured by CPC are at substantially higher hazard of death compared with those with mild or no disability…

Post-CA brain injury results in multiple molecular and physiological changes over the hours to days after CPR. In practice, monitoring the status of the brain after CA and the prevention of secondary injury are central organizing principles for postarrest care. Reducing the deleterious effects of impaired homeostasis guides blood pressure and ventilator, fluid, and temperature management, as well as neurophysiological monitoring during postarrest intensive care. Proper multimodal assessment of coma is critical to avoid premature withdrawal of life support resulting in death. The pattern of brain injury that remains after intensive care varies from mild to severe, with some brain regions being particularly susceptible. Proper evaluation of cognition and other functions after emergence from coma is critical for guiding postacute rehabilitation and support services. Traditional outcome scales (MRS, CPC) may be too coarse to detect cognitive issues that affect patients' quality of life.

Courtesy of:  http://www.medscape.com/viewarticle/876559