Brain death is a condition characterized by cessation of spontaneous respiration, loss of all brainstem reflexes and coma. All the functions performed by the cerebrum and the brainstem are lost. However, spinal reflexes such as plantar flexion, withdrawal reflex and deep tendon reflex may persist. Brain death is an irreversible condition.
Neurological examination is considered as the gold standard to diagnose brain death and therefore must be performed accurately  . It is essential to document presence of apnea, absence of brainstem reflexes and coma. The brainstem reflexes are lost in a rostral-to-caudal direction, with the medulla oblongata to be the last one to cease functioning in the event of brain death. Medullary function usually lasts for several hours as other functions of the brainstem are being lost . If the medulla oblongata does not cease functioning, administration of 1 mg atropine will cause tachycardia, tracheal suctioning will lead to cough reflex and the blood pressure will be normal. The depth of coma can be assessed based upon the motor response to a standardized pain stimulation, done by pressing on temporomandibular joint, supraorbital nerve or finger nail bed. Next step is the evaluation of brainstem reflexes, which if absent, should show mid dilated non reactive round/oval pupils on ocular exam with absence of oculocephalic reflex. Presence of a spinal injury makes the interpretation of oculocephalic reflex challenging.
In order to diagnose a patient with brain death, the first step is to rule out potential influence of paralyzing or sedating agents. The possibility of self administration of such agents should also be considered. In case status epilepticus is suspected, an electroencephalogram (EEG) must be performed. Hypothermia, defined by a core body temperature of < 35°C should be increased gradually to > 36°C. The patient should be routinely evaluated for 6-24 hours. Ocular examination, with emphasis on brainstem reflexes and apnea testing must be performed with every examination. If the absence of brainstem reflexes is noted, apnea test must be performed.
To reduce the chances of misdiagnosing an individual with brain death, several countries have made a second clinical examination as a mandatory requirement, despite the absence of any evidence suggesting a possible benefit with this practice. On the contrary, it has been demonstrated that this practice, in fact delays the diagnosis of brain death. To determine the cause of brain death, a computed tomography (CT) scan of the head may be performed to look for pathologies such as hemispheric lesions, edema, mass, or herniation of the brain. Evaluation of the cerebrospinal fluid (CSF) is diagnostic where a central nervous system (CNS) infection is suspected.
The following tests are indicated when only one clinical examination is desired (in a scenario where organ procurement needs to be done for transplantation) or if the apnea test is not tolerable hemodynamically:
The current recommendations state that confirmatory testing must be performed in all children less than one year of age . Several countries across the world have made confirmatory testing compulsory. However, it is for the physician to decide the battery of tests to be performed in the United States, where most physicians prefer bedside testing. Cerebral angiography is the only required confirmatory test in Sweden.
Determination of brain death
Prerequisites (all prerequisites should be met)
Examination (all findings must be present)
Apnea testing (all findings must be present)
There are several alternative methods to support a diagnosis of brain death, in case if the apnea test is not conclusive or there are limitations due to patient factors that will not allow a complete clinical examination. These include:
The criteria for diagnosing brain death are firm. Using the practice parameters published in 1995 by the AAN as a criteria for diagnosis, there is no data since 1995 that shows recovery of neurological deficits after a diagnosis of brain death was made .
The state of brain death is equivalent to the death of the person since it is irreversible. Once brain death is confirmed, all life support is withdrawn. It must be noted that as the whithdrawl of ventilatory support after brain death will result in terminal arrythmias and terminal apnea may provoke spinal reflexes, which should not be interpreted as signs of life.
The epidemiology of brain death is in direct association with the epidemiology of the two main causes for brain death. namely traumatic brain injury and subarachnoid hemorrhage. Traumatic brain injury leads to almost 52,000 deaths every year in United States alone. Mortality rate is significantly lower in the patients that are hospitalized (6/100,000 persons) versus those who do not receive hospitalization (17/100,000 persons).
In order to maintain cerebral perfusion pressure, the arterial blood pressure increases in response to an elevated intracranial pressure. If the cerebral perfusion remains inadequate, pontine ischemia may develop leading to Cushing's reflex, consisting of bradycardia and hypertension. Ischemic injury rapidly progresses to involve other parts of the brain leading to an autonomic storm that is characterized by peripheral vasoconstriction, hypertension and tachycardia. It is frequently associated with an elevated amount of catecholamines in circulation and myocardial dysfunction (due to increased oxygen demand and arrythmias). During the hypertensive phase, the vasomotor nuclei in the brainstem suffer irreversible damage which leads to loss of sympathetic outflow and as a consequence, hypotension ensues.
Brain death is the complete cessation of integrated functions of the cerebrum and brainstem and constitutes the death of person. This concept is accepted in both legal and cultural aspects throughout the world. The need to develop this concept arose because certain drugs and medical equipment like a ventilator could maintain basic functions of the body such as cardio-pulmonary activity for an indefinite period of time even after cessation of all brain activity.
The Uniform Determination of Death Act (UDDA) was formed based off a report on "guidelines for determination of death" by the president's commission . The act states:
"An individual who has sustained either 1. Irreversible cessation of circulatory and respiratory functions or 2. Irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made with accepted medical standards" .
In the year 1995, the American Academy of Neurology (AAN) put forth a practice parameter in order to outline the medically acceptable standards to determine brain death . They stated that for diagnosing brain death, the patient must have absence of brainstem reflexes, apnea and in a state of coma for which the cause is known.
Inspite of the practice parameter made available by the AAN, there is significant variation in practice at different medical institutions. A study conducted in US hospitals identified the points of variations . The most important points of variation were:
Brain activity is lost permanently in brain death. The patient loses the ability to breathe and perform other important functions, along with complete loss of capacity to think and be aware of surroundings. The patient will not respond to any stimulus. Once a diagnosis of brain death is made, no further treatment can be of any help and the patient is legally dead.
Various advances in medical science can help maintain some vital functions like beating of the heart and breathing even after the brain stops working completely. However, even with the use of such devices and drugs, the organs will stop working eventually.
Brain death is diagnosed based on a strict criteria. Some of these criteria are:
The doctors will also check certain reflexes elsewhere in the body to confirm brain death. The doctors will notify the next of kin about the diagnosis.
Doctors will not confirm a diagnosis of brain death until they check for and treat all problems that can possibly affect the brain function. These problems include, but are not limited to low blood pressure, low body temperature, abnormal levels of normally found substances in the blood, ingestion of toxic drugs and sedative overdose.
The above criteria are checked for at least one more time in 6-24 hours to confirm the presence of these criteria. Once the criteria have been confirmed two times, no further testing is needed and a diagnosis of brain death can be confirmed. In case if the diagnosis needs to be performed in a shorter time, the doctors may run certain tests to do so, thus eliminating the need to recheck the patient 6-24 hours later.
Individuals who have been diagnosed with brain death do not recover. Once the diagnosis is confirmed, all life supporting treatment is withdrawn. Family members may be allowed to be with the patient at the time of withdrawing life support. It is important to note that the patient might move his/her limbs or may even sit up when the device that assists in breathing is withdrawn.