What are the criteria for diagnosing brain death?

Brain Death Criteria

Brain death is diagnosed clinically based on the irreversible cessation of all brain function including the brainstem, requiring coma and apnea to coexist with a known irreversible cause, confirmed by two complete neurological examinations separated by an age-appropriate observation period. 1

Prerequisites Before Testing

Before initiating any brain death evaluation, you must correct all confounding factors that could interfere with the neurological examination:

• Normalize hemodynamics and temperature: Correct hypotension, hypothermia (core temperature must be normalized), and all metabolic disturbances (electrolyte abnormalities, acid-base disorders, endocrine dysfunction) before proceeding 1, 2

• Eliminate medication effects: Discontinue sedatives, analgesics, neuromuscular blockers, and anticonvulsants for a time period based on their elimination half-lives 1. Blood or plasma levels should confirm low to mid-therapeutic range for anticonvulsants; do not diagnose brain death if supratherapeutic or high therapeutic sedative levels are present 1

• Verify neuromuscular blockade reversal: If neuromuscular blocking agents were used, confirm train-of-four stimulation shows 4/4 twitches on peripheral nerve stimulation 3

• Defer testing after resuscitation: Assessment should be deferred for 24-48 hours or longer following cardiopulmonary resuscitation or severe acute brain injury if there are concerns or inconsistencies 1

Clinical Examination Requirements

The neurological examination must demonstrate:

• Coma: Complete unresponsiveness to all stimuli 2, 3

• Absence of all brainstem reflexes: This includes pupillary (pupils mid-position or dilated, no response to light), corneal, oculocephalic (doll's eyes), oculovestibular (cold caloric), gag, and cough reflexes 2, 3

• Apnea: Confirmed by formal apnea testing 1

Apnea Testing Protocol

Apnea testing must demonstrate PaCO₂ ≥60 mmHg or ≥20 mmHg above baseline with no respiratory effort observed 1, 2:

• Pre-oxygenate with 100% oxygen for 5-10 minutes 4
• Disconnect from ventilator while providing oxygen via catheter or T-piece 4
• Monitor continuously for any respiratory effort while allowing PaCO₂ to rise 4
• Abort the test if hemodynamic instability occurs; if apnea testing cannot be safely completed, proceed to ancillary studies 1

Number of Examinations and Observation Periods

Two complete examinations including apnea testing are required, performed by different attending physicians 1:

Age-Based Observation Periods:

• Term newborns (37 weeks gestation to 30 days): 24-hour observation period between examinations 1

• Infants and children (31 days to 18 years): 12-hour observation period between examinations 1

• Adults: Variable observation periods based on institutional protocols 2

Note: The first examination determines the patient meets brain death criteria; the second examination confirms an unchanged and irreversible condition 1

Ancillary Testing

Ancillary studies (EEG, radionuclide cerebral blood flow, transcranial Doppler, cerebral angiography) are NOT required to establish brain death and are NOT substitutes for the clinical examination 1. However, they may be used in specific circumstances:

Indications for Ancillary Testing:

• Components of the examination or apnea testing cannot be completed safely due to the patient's underlying medical condition 1
• Uncertainty exists about neurologic examination results 1
• Medication effects may be present 1
• To reduce the inter-examination observation period 1

Validated Ancillary Tests:

The American Academy of Neurology has validated only three imaging studies for brain death diagnosis 5, 6:

• Cerebral angiography (four-vessel): Gold standard showing absence of cerebral blood flow 5, 6
• Transcranial Doppler: Shows characteristic flow patterns (oscillating flow, systolic spikes, or absent signal) 6, 7
• Cerebral scintigraphy (nuclear medicine): Demonstrates no intracranial radiotracer uptake 5, 6
• EEG: Shows electrocerebral silence 2, 4

When ancillary studies are used, a second clinical examination must still be performed with all completable components remaining consistent with brain death 1

Declaration of Death

Death is declared when all clinical criteria are fulfilled: two complete examinations by different physicians, successful apnea testing (or ancillary studies if apnea test cannot be completed), and appropriate observation periods met 1, 2

Critical Pitfalls to Avoid

• Never attempt brain death determination while neuromuscular blocking agents are active, as this prevents adequate examination and could lead to false diagnosis 3

• Do not diagnose brain death in hypothermic patients without first normalizing core temperature 3

• Avoid testing in the presence of high or supratherapeutic sedative levels; if uncertainty remains about medication effects, perform ancillary studies 1

• Do not rush the diagnosis; ensure adequate observation periods are met based on patient age 1, 2

• Be aware that residual spinal reflexes can persist after brain death and should not be confused with brainstem function 6

• In patients with decompressive craniectomy, ventricular drainage, or skull fractures, residual brain perfusion may occur despite brain death, potentially causing false-negative ancillary test results 6