The brain consumes a significant amount of energy compared to its weight and size.
Anoxia is a complete lack of oxygen delivery to an organ. Hypoxia represents decreased oxygen delivery to an organ with some continuous blood flow remaining. Thus, an anoxic brain injury represents a complete lack of oxygen to the brain.
Anoxic and hypoxic brain injury is most often the result of cardiac arrest, vascular injury, near drowning, strangulation, smoke inhalation, shock, poisoning from a drug overdose such as opiates, intoxication from carbon monoxide intoxication or head trauma. Cardiac arrest is the most common cause of anoxic brain injury.
Cognitive symptoms secondary to cardiac arrest affect up to 50–83% of survivors after discharge from the hospital. The incidence rates are approximately 50 per 100,000 population and survival-to-discharge rates of roughly 8% which represents over 10,000 patients per year in the United States alone.
The brain depends on a constant energy supply provided by glucose and oxygen but is unable to store energy. Anaerobic glycolysis may generate lactate and provide neurons with lactate that the mitochondria can use. However, this is not sufficient to meet the needs of the brain. The brain cannot use fatty acids as a direct source of energy, but it can use ketone bodies that derive from fat. In the ketogenic diet used for the treatment of drug-resistant epilepsy, ketone bodies become the primary energy source. Decreased oxygen will decrease the energy that can be produced by the cell and in turn, lead to cell death.
The mechanisms that lead to delayed cell death following hypoxic-ischemic injury in the developing brain remain unclear. What is, however, more clear is that ischemic cell death occurs via two different modes: necrosis and apoptosis. During hypoxia-ischemia of the brain, acute energy failure leads to loss of ion homeostasis where intracellular sodium and calcium accumulate creating osmotic swelling which, can lead to cell lysis. This process releases glutamate and free radicals which are cytotoxic and exacerbate the injury. A secondary phase of neuronal death can occur hours later.
Moderate global ischemia leads to infarcts in watershed areas (e.g., the area lying between regions fed by the anterior and middle cerebral artery). These infarcts can damage the highly vulnerable areas such as pyramidal neurons of the hippocampus (CA1 region), pyramidal neurons of the cerebral cortex (layers 3, 5, and 6) which leads to laminar necrosis, the death of neurons in the basal ganglia (caudate nucleus and putamen), and the Purkinje cell layer of the cerebellum.
The cells of these areas are high in metabolic demand and contain a high concentration of excitatory neurotransmitter receptors. Other histologic findings include a shrunken eosinophilic neuron (anoxic neuron) and a red neuron which represents neuronal cells that die because of hypoxia.
The patient found to have a severe brain anoxic brain injury will often be unconscious and unable to answer questions that would be part of the regular interaction during history taking. It is then vital to obtain as complete as possible history from the family. Obtain information such as a history of drug consumption, length of time of resuscitation, and the length of time of the suspected brain anoxia.
Performing a thorough neurological exam is a crucial component of assessing a patient with an anoxic brain injury. Findings such as response to painful stimuli, light touch, or voice should be noted, plus the presence of spontaneous movement and pupillary size and its response to light. Reflexes such as corneal and oculovestibular reflexes should also undergo assessment.
Some studies have found serum neuron-specific enolase (NSE) to be a specific factor for poor outcomes. Others have found NSE and S-100 protein to be reliable predictors only when used in combination with the Glasgow Coma Scale. Blood markers remain controversial.
The literature describes magnetic resonance imaging (MRI) findings in anoxic brain injury in four phases: an acute phase which lasts 24 hours after anoxia or hypoxia; an early subacute phase lasting from one to thirteen days, a late subacute phase lasting from fourteen to twenty days; and a chronic phase, starting at day twenty-one. MRI will show swelling, a hyper signal of basal ganglia, delayed white matter degeneration, cortical laminar necrosis, and atrophy occurring in succession.
Somatosensory evoked potentials are of use in the setting of anoxic brain injury and are helpful in predicting the prognosis.
In the setting of brain anoxia due to cardiac arrest, resuscitation efforts, optimizing blood pressure, and maintaining systemic perfusion are the critical component of treatment. There is evidence that artificially lowering body and brain temperature can significantly improve the outcomes in anoxia or hypoxia to the brain. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Suspicions are that induction of therapeutic hypothermia may dampen the molecular cascade that results in neuronal damage, and that hypothermia may attenuate the toxicity produced by the initial injury that typically produces reactive oxygen species, apoptosis, neurotransmitters such as glutamate, and inflammatory mediators. In some animal studies, melatonin has also been shown to be protective against hypoxic as it attenuates the damage in different areas of the brain.
Patients with anoxic brain injury have a dismal prognosis despite our understanding of the complex of pathways leading to anoxic brain injury. More clinical and basic science research are necessary to determine ways to slow down the anoxic and hypoxic brain injury. Overall, the best treatment solution is prevention.
Anoxic brain injury can be devastating after prolonged cerebral hypoxia; further, it is often challenging to predict the prognosis based on clinical findings. Evaluation with somatosensory evoked potentials showing an absent bilateral cortical response, and status epilepticus during active cooling period represent a poor prognosis. A Glasgow Coma Scale (GCS) of 4 or less within the first 48 hours correlates with poor outcomes. Poor neurological outcomes are the rule in patients who sustained a cardiac arrest and those who have an absent pupillary light response or corneal reflex, absent motor response, or myoclonus status epilepticus.
Anoxic brain injury often results in a prolonged coma, but the pattern of recovery ranges from recovery to mild cognitive deficits to coma and possibly death. Trials show that 27% of patients with post-hypoxic coma regained consciousness within 28 days, Nearly 9% remained comatose or in a vegetative state, and unfortunately, 64% died. Common sequelae can occur after sustaining an anoxic brain injury and may vary from persistent vegetative states, seizures, myoclonus, movement disorder, cognitive dysfunction, and other neurological abnormalities.
The patient and family should receive education and counseling about the prognosis and sequelae of an anoxic brain injury. Patients with anoxic brain injury secondary to drug overdose should receive extensive use disorder counseling. Patients with anoxic brain injury secondary to a cardiac arrest should receive education about lifestyle modification such as diet, exercise, and adherence to medications.
It is crucial for the critical care team and the primary care team to discuss the patient's prognosis and chances of recovery; this will help provide accurate information to the family of the patient regarding prognosis. This type of communication allows for important discussions between physicians, patients, and family members concerning the level of care needed and whether they should escalate medical care.
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