Brain death, also known as brain death/death by neurologic criteria, refers to a permanent loss of brain function that cannot resume spontaneously and cannot be restored by medical interventions. Function of the entire cerebrum and brain stem is lost, 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.
The concept of brain death developed because ventilators and medications can perpetuate cardiopulmonary and other body functions despite complete cessation of all cerebral activity. The determination that brain death/death by neurologic criteria (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.
Brain death/death by neurologic criteria cannot be determined in infants < 37 weeks old.
Diagnosis of Brain Death/Death by Neurologic Criteria
Serial determination of clinical criteria to demonstrate permanent loss of brain function, including that of the brain stem
Apnea testing
Sometimes electroencephalography (EEG), brain vascular imaging, or both
For a clinician to declare brain death (see table Guidelines for Determining Brain Death (in Patients ≥ 37 Weeks Old) (1), the following requirements must be met:
A known catastrophic and permanent brain injury must have occurred.
A structural or metabolic cause of brain damage must be present.
Use of potentially anesthetizing (including nervous system depressants and alcohol) or paralyzing medications and illicit drugs, especially self-administered, must be excluded.
Potentially reversible metabolic abnormalities, including hypoglycemia and acid-base and electrolyte abnormalities, must be excluded.
Brain death should not be declared or considered and brain death assessment should not be done if any of the following is present:
The patient is breathing spontaneously.
The patient can be aroused.
The patient is not in coma.
The patient has intact brain stem reflexes.
Clinicians who evaluate brain death (eg, neurologists, neurosurgeons, intensivists) need sufficient training and must be credentialed. Brain death assessment should not begin until at least 24 hours after a brain injury capable of causing brain death.
If hypothermia is present, a core temperature < 36° C must be increased slowly to > 36° C for ≥ 24 hours. Systolic blood pressure should be ≥ 100 mm Hg, and arterial pressure should be maintained at ≥ 75 mm Hg. 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. At least 1 complete brain death assessment by a clinician must be done for an adult, but doing at least 1 additional brain death examination subsequently by the same or another independent clinician is recommended to reduce the risk of a false-positive assessment. For children, some states advise clinicians to do 2 separate examinations by independent clinicians separated by at least 48 hours (1).
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 1 neurologic examination is desirable (eg, to expedite organ procurement for transplantation).
Guidelines for Determining Brain Death/Death by Neurologic Criteria in Patients ≥ 37 Weeks Old*†
All 8 items must be confirmed to declare brain death: |
1. Cause of coma is known, catastrophic, and sufficient to account for irreversible and permanent loss of all brain function. |
2. CNS depressant medications and illicit drugs; metabolic, acid-base, and electrolyte disorders; hypothermia (< 36° C); and hypotension (mean arterial pressure < 75 mm Hg) have been excluded. No neuromuscular blockers contribute to the neurologic findings. |
3. The patient is comatose and not responsive to visual, auditory, and tactile stimulation. Any observed movements can be attributed entirely to spinal cord reflexes. |
4. The cough reflex, pharyngeal (gag) reflex, or both are tested and shown to be absent. |
5. Corneal and pupillary light responses are absent bilaterally. |
6. Bilateral oculocephalic reflex testing that shows fixed eye movement with rotation of the head and caloric vestibulo-ocular reflex testing and that shows no caloric response after ice water is applied to the tympanic membrane must be demonstrated. |
7. An apnea test is done. PROCEDURE: Before the apnea test, 100% oxygen is given for ≥ 10 minutes. Arterial blood gas testing is done to document a PaCO2 of 35–45 mm Hg and a pH of 7.35–7.45. If the patient is known to have chronic hypercarbia, the PaCO2 level used should be the patient's baseline. Apnea testing is then done by disconnecting the ventilator from the endotracheal tube. Oxygen (4–6 L/min) can be supplied by diffusion from a cannula placed through the endotracheal tube. Despite the ventilatory stimulus of the passively rising PaCO2, brain death requires the absence of spontaneous respirations, a pH of < 7.30, and a PaCO2 of ≥ 60 mm Hg and ≥ 20 mm Hg above the patient's baseline. NOTE: The apnea test should be done with extreme caution to minimize risks of hypoxia and hypotension, particularly in potential organ donors. The test should be stopped and arterial blood samples drawn if any of the following occurs during the test:
The apnea testing procedures can be used in patients receiving extracorporeal membrane oxygenation. |
8. At least 1 of the following 4 criteria has been established: |
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* Based on Greer DM, Kirschen MP, Lewis A, et al: Pediatric and adult brain death/death by neurologic criteria consensus guideline: Report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM. Neurology 101 (24):1112–1132, 2023. doi: 10.1212/WNL.0000000000207740 Epub 2023 Oct 11. |
† Before the examination for brain death, the patient's family or caregivers should be informed of the process and be offered the opportunity to witness the brain death evaluation process, which may help them accept that brain death has occurred. |
BP = blood pressure; CNS = central nervous system; EEG = electroencephalography; PaCO2 = arterial carbon dioxide partial pressure. |
Diagnosis reference
1. Greer DM, Kirschen MP, Lewis A, et al: Pediatric and adult brain death/death by neurologic criteria consensus guideline: Report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM. Neurology 101 (24):1112–1132, 2023. doi: 10.1212/WNL.0000000000207740 Epub 2023 Oct 11.
Prognosis for Brain Death/Death by Neurologic Criteria
The diagnosis of brain death is equivalent to the person’s death. No further treatment can prevent death.
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.
