Brain Death

The neurological syndrome of brain death has been accepted by the medical profession as a distinct clinical entity that experienced clinicians can diagnose with an extremely high degree of certainty and usually can distinguish easily from other neurological syndromes. Brain death is defined as the irreversible cessation of all the functions of the entire brain, including the brainstem. If the brain can be viewed simplis-tically as consisting of two parts—the cerebral hemispheres (higher centers) and the brainstem (lower centers)—brain death is defined as the destruction of the entire brain, both the cerebral hemispheres and the brainstem. In contrast, in the permanent vegetative state the cerebral hemispheres are damaged extensively and permanently but the brainstem is relatively intact (Cranford, 1988).

An understanding of the pathological sequence of events that leads to brain death is essential if one is to appreciate fully why brain death is a unique syndrome and why it can be differentiated readily from other neurological syndromes with a high degree of certainty. Although a variety of insults can cause the brain to die, head trauma, cardiorespiratory failure, and intracerebral hemorrhage are the most common causes. Regardless of the underlying cause, the pathological sequence is essentially the same in almost all cases. The acute massive insult to the brain causes brain swelling (cerebral edema). Because the brain is contained in an enclosed cavity, brain swelling gives rise to a massive increase in intracranial pressure. In brain death the increased intracranial pressure becomes so great that it exceeds the systolic blood pressure, thus causing a loss of blood flow to both the cerebral hemispheres and the brainstem. Whatever the primary cause of brain death, this end result of loss of blood flow results in the destruction of the entire brain. This sequence of events usually occurs within a matter of hours after the primary event, and so brain death can be diagnosed within a short period of time with an extraordinarily high degree of certainty.

The loss of both cerebral hemisphere and brainstem functions is usually clearly evident to an experienced clinician from the clinical bedside examination. The patient is in a coma, the deepest possible coma, a sleeplike state associated with a loss of all brainstem functions, such as pupillary reaction to light; gag, swallowing, and cough reflexes; eye movements in response to passive head turning (the oculocephalic response) and in response to cold caloric stimulation (oculovestibular response); and spontaneous respiratory efforts.

However, whereas respirations are completely dependent on the functioning of the brainstem, cardiac function can continue independent of brain destruction because the heart has an independent mechanism for spontaneously firing (semiautonomous functioning). With modern lifesupport systems continued cardiac and blood pressure functions can persist for hours, days, or even longer. Extremely rare cases of continued cardiovascular functions for over a year in the presence of the loss of all brain functions have been reported. The first cases of prolonged somatic survival in brain death usually occurred in the context of brain-dead pregnant women who were maintained on lifesupport systems for several months so that a viable fetus could be delivered (Wijdicks). However, the most extraordinary case of prolonged somatic survival of a patient with well-documented brain death involved a young adult age twenty-two who for eighteen years has been without any brain functions (Shewmon, 1998; Cranford, 1998; Shewmon, 2000).

In the 1970s and 1980s numerous medical organizations in the United States and around the world developed specific medical criteria for the diagnosis of brain death (Bernat). In the United States major criteria were published by Harvard University, the University of Minnesota, the National Institutes of Health, Cornell University, and the President's Commission. Major international criteria emerged from Sweden, Japan, the United Kingdom, and Canada. All those standards essentially agreed on three clinical findings: coma, apnea (loss of spontaneous respirations), and absence of brainstem reflexes.

The critical issue distinguishing these international criteria was not the clinical findings but how best to establish irreversibility. The United Kingdom, deemphasizing the use of laboratory studies such as electroencephalography, focused on the basic diagnosis as clinical and asserted that the best way to establish irreversibility was to preclude any reversible processes before making a final determination of brain death (Conference of Royal Colleges). Reversible processes that could mimic brain death include a variety of sedative medications and hypothermia (low body temperature, below 32.2° Centigrade). The British also recommended a period of observation of at least twelve hours. In contrast, the Swedish criteria focused less on the period of observation and more on the need for definitive laboratory studies to document a loss of blood flow to the brain, such as intracranial angiography.

In the United States the earlier standards emphasized the use of electroencephalography to establish electrocerebral silence (a loss of all electrical activity of the brain); more recent standards focused on establishing a loss of intracranial circulation by means of radioisotope angiography. The 1981 report of the medical consultants to the President's Commission, which became the definitive medical standard in the United States, recommended a period of observation of at least six hours combined with a confirmatory study, such as tests measuring intracranial circulation ("Guidelines for the Determination of Death"). If no confirmatory laboratory studies were performed, an observation period of at least twelve hours was suggested, assuming that all reversible causes of loss of brain functions had been excluded. In cases of damage to the brain caused by the lack of blood or oxygen (hypoxic-ischemic encephalopathy) the consultants recommended an observation period of at least twenty-four hours if confirmatory studies were not performed.

The diagnosis of brain death in newborns, infants, and children is often more difficult than is the diagnosis in adults. A major reason for this difficulty is that the usual pathological sequence of events in adults that leads to increased intracranial pressure and loss of all blood flow to the brain does not apply to newborns and infants because the cranial cavity in those patients has not yet closed completely. Thus, the mechanism for brain death in newborns and infants may be different from what it is in older children and adults.

To address this question a task force for the determination of brain death in children representing several neurological and pediatric specialty organizations in the United States developed specific diagnostic criteria for the younger age groups (Task Force for the Determination of Brain Death in Children). That task force stated that it would be extremely difficult to establish brain death in newborns less than seven days old. It recommended that in infants seven days to two months of age there should be two separate clinical examinations and two electroencephalograms separated by at least forty-eight hours; for infants two months to one year of age, two clinical examinations and two electroencephalograms separated by at least twenty-four hours; and for children over one year of age, criteria similar to those established for adults.

Beginning in the early 1990s, the University of Pittsburgh and a few other large transplants centers developed protocols for removing organs from patients whose hearts had stopped beating but who were not brain-dead (non-heartbeating organ donors, or NHBOD) (DeVita et al.). In cases of brain death and organ donation the patient is first pronounced dead after the medical diagnosis of brain death has been established, including a period of time to establish irreversibility. The patient then is transferred to the operating room for organ removal while life-support systems are continued. After the transplantable organs are removed, lifesupport systems are discontinued, but the cessation of heartbeat at this time has no clinical or legal significance. In cases of non-heartbeating organ donors, patients who are terminally ill or have sustained severe irreversible brain damage and are ventilator-dependent are transferred to the operating room, where the respirator is removed, with the resultant loss of heartbeat, usually within minutes. After two minutes of pulselessness, apnea, and unresponsiveness the patient is pronounced dead on the basis of cardiorespiratory criteria. Organ removal then occurs as expeditiously as possible before the organs incur ischemic damage from lack of perfusion. The entire process is carried out in the most humane and caring way possible, including full disclosure to the appropriate surrogate decision makers and the obtaining of their consent (Ethics Committee, American College of Critical Care Medicine). The success and limitations of this controversial procedure have been reported by some of the pioneering transplant centers.

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