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. Hypothermia < 32° C must be corrected, and if status epilepticus is suspected, EEG should be done. Sequential testing over 6 to 24 h is necessary (see Table 6: Coma and Impaired Consciousness: Guidelines for Determining Brain Death (in Patients > 1 Yr)). Examination includes assessment of pupil reactivity, oculovestibular and oculocephalic reflexes, corneal reflexes, and 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).

Table 6
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Guidelines for Determining Brain Death (in Patients > 1 Yr) All 9 items must be confirmed to declare brain death: 1. Reasonable efforts were made to notify the patient's next of kin or another person close to the patient. 2. Cause of coma is known and sufficient to account for irreversible loss of all brain function. 3. CNS depressant drugs, hypothermia (< 32° C), and hypotension (MAP < 55 mm Hg) have been excluded. No neuromuscular blockers contribute to the neurologic findings. 4. Any observed movements can be attributed entirely to spinal cord function. 5. The cough reflex, pharyngeal reflexes, or both are tested and shown to be absent. 6. Corneal and pupillary light responses are absent. 7. No caloric responses follow ice water siphoned against the tympanic membrane. 8. 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. O2 (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 > 55 mm Hg or has increased by > 20 mm Hg. This finding validates the clinical diagnosis of brain death. 9. At least one of the following 4 criteria has been established: a. Items 2–8 have been confirmed by 2 examinations separated by at least 6 h. b. Items 2–8 have been confirmed AND An EEG shows electrocortical silence. A 2nd examination at least 2 h after the 1st confirms items 2–8. c. Items 2–8 have been confirmed AND Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow. A 2nd examination at least 2 h after the first confirms items 2–8. 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. A 2nd examination 6 h after the first confirms all assessable items. MAP = mean arterial pressure. Adapted from the American Academy of Neurology Guidelines (1995). Guidelines for Determining Brain Death (in Patients > 1 Yr) All 9 items must be confirmed to declare brain death: 1. Reasonable efforts were made to notify the patient's next of kin or another person close to the patient. 2. Cause of coma is known and sufficient to account for irreversible loss of all brain function. 3. CNS depressant drugs, hypothermia (< 32° C), and hypotension (MAP < 55 mm Hg) have been excluded. No neuromuscular blockers contribute to the neurologic findings. 4. Any observed movements can be attributed entirely to spinal cord function. 5. The cough reflex, pharyngeal reflexes, or both are tested and shown to be absent. 6. Corneal and pupillary light responses are absent. 7. No caloric responses follow ice water siphoned against the tympanic membrane. 8. 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. O2 (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 > 55 mm Hg or has increased by > 20 mm Hg. This finding validates the clinical diagnosis of brain death. 9. At least one of the following 4 criteria has been established: a. Items 2–8 have been confirmed by 2 examinations separated by at least 6 h. b. Items 2–8 have been confirmed AND An EEG shows electrocortical silence. A 2nd examination at least 2 h after the 1st confirms items 2–8. c. Items 2–8 have been confirmed AND Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow. A 2nd examination at least 2 h after the first confirms items 2–8. 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. A 2nd examination 6 h after the first confirms all assessable items. MAP = mean arterial pressure. Adapted from the American Academy of Neurology Guidelines (1995).

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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.

Last full review/revision September 2012 by Kenneth Maiese, MD