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Brain Death

By Kenneth Maiese, MD, Member and Advisor, Biotechnology and Venture Capital Development, Office of Translational Alliances and Coordination;Past Professor, Chair, and Chief of Service, Department of Neurology and Neurosciences, National Heart, Lung, and Blood Institute;Rutgers University

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Brain death is loss of function of the entire cerebrum and brain stem, resulting in coma, no spontaneous respiration, and loss of all brain stem reflexes. Spinal reflexes, including deep tendon, plantar flexion, and withdrawal reflexes, may remain. Recovery does not occur.

The concept of brain death developed because ventilators and drugs can perpetuate cardiopulmonary and other body functions despite complete cessation of all cerebral activity. The concept that brain death (ie, total cessation of integrated brain function, especially that of the brain stem) constitutes a person’s death has been accepted legally and culturally in most of the world.

Diagnosis

  • Serial determination of clinical criteria

  • Apnea testing

  • Sometimes EEG, brain vascular imaging, or both

For a physician to declare brain death, a known structural or metabolic cause of brain damage must be present, and use of potentially anesthetizing or paralyzing drugs, especially self-administered, must be ruled out.

If hypothermia is present, a core temperature < 35° C must be increased slowly to > 36° C, and if status epilepticus is suspected, EEG should be done. In adults, after all complicating medical conditions have been excluded and a comprehensive neurologic examination with the required testing has been done, brain death can be confirmed. Some states advise clinicians to do two separate examinations separated by at least 48 h in children; this approach is not consistently recommended or required for adult patients (see Table: Guidelines for Determining Brain Death (in Patients > 1 Yr)*).

Examination includes

  • Assessment of pupil reactivity

  • Assessment of oculovestibular, oculocephalic, and corneal reflexes

  • Apnea testing

Sometimes EEG or tests of brain perfusion are used to confirm absence of brain activity or brain blood flow and thus provide additional evidence to family members, but these tests are not usually required. They are indicated when apnea testing is not hemodynamically tolerated and when only one neurologic examination is desirable (eg, to expedite organ procurement for transplantation).

Guidelines for Determining Brain Death (in Patients > 1 Yr)*

All 9 items must be confirmed to declare brain death:

1. Cause of coma is known and sufficient to account for irreversible loss of all brain function.

2. CNS depressant drugs, hypothermia (< 35° C), and hypotension (MAP < 55 mm Hg) have been excluded. No neuromuscular blockers contribute to the neurologic findings.

3. Any observed movements can be attributed entirely to spinal cord function.

4. The cough reflex, pharyngeal reflexes, or both are tested and shown to be absent.

5. Corneal and pupillary light responses are absent.

6. Oculocephalic reflex testing that observes fixed eye movement with rotation of the head and caloric vestibulo-ocular reflexes that show no caloric response after ice water is siphoned against the tympanic membrane must be demonstrated.

7. An apnea test of a minimum of 8 min shows no respiratory movements with a documented increase in Paco2 of > 20 mm Hg from pretest baseline.

PROCEDURE: Apnea testing is done by disconnecting the ventilator from the endotracheal tube. Oxygen (6 L/min) can be supplied by diffusion from a cannula placed through the endotracheal tube. Despite the ventilatory stimulus of the passively rising Paco2, no spontaneous respirations are seen over an 8- to 12-min period.

Note: The apnea test should be done with extreme caution to minimize risks of hypoxia and hypotension, particularly in potential organ donors. If arterial BP falls significantly during the test, the test should be stopped, and an arterial blood sample drawn to determine whether Paco2 has risen either to > 60 mm Hg or has increased by > 20 mm Hg. This finding validates the clinical diagnosis of brain death.

8. At least one of the following 4 criteria has been established:

a. Items 2–8 have been confirmed.

b. Items 2–8 have been confirmed AND (done when components of the examination or apnea testing cannot be completed or when results of the examination are uncertain)

  • An EEG shows electrocortical silence.

c. Items 2–8 have been confirmed AND (done when components of the examination or apnea testing cannot be completed or when results of the examination are uncertain)

  • Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow.

d. If any of items 2–8 cannot be determined because the injury or condition prohibits evaluation (eg, extensive facial injury precludes caloric testing), the following criteria apply:

  • Items that are assessable are confirmed.

  • Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow or an EEG shows no cortical activity.

*Before the examination for brain death, the patient's family or caregivers should be informed of the process.

MAP = mean arterial pressure.

Adapted from the American Academy of Neurology Guidelines (2010).

Prognosis

The diagnosis of brain death is equivalent to the person’s death. No one who meets the criteria for brain death recovers.

After brain death is confirmed, all supporting cardiac and respiratory treatments are ended. Cessation of ventilatory support results in terminal arrhythmias. Spinal motor reflexes may occur during terminal apnea; they include arching of the back, neck turning, stiffening of the legs, and upper extremity flexion (the so-called Lazarus sign). Family members who wish to be present when the ventilator is shut off need to be warned of such reflex movements.

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