What are the criteria for diagnosing brain death in a patient with a severe brain injury and underlying neurological or medical conditions?

Brain Death Criteria

Brain death is diagnosed clinically based on irreversible cessation of all brain function with a known cause, requiring coma, absent brainstem reflexes, and apnea, confirmed by two separate examinations by different attending physicians separated by an observation period. 1, 2

Prerequisites That Must Be Corrected Before Any Examination

Before initiating brain death evaluation, the following confounding factors must be normalized to avoid false-positive diagnosis:

• Core body temperature ≥35°C (95°F) must be achieved and maintained throughout the evaluation period 1, 3
• Systolic blood pressure must be within 2 standard deviations of age-appropriate norms (or mean arterial pressure in acceptable range for age) 1
• All metabolic disturbances corrected, including electrolyte abnormalities and glucose derangements that could cause reversible coma 1, 2
• Sedatives, analgesics, neuromuscular blockers, and anticonvulsants discontinued with adequate clearance time based on elimination half-life and total cumulative dose administered 1
• Blood levels of sedating medications must be in low-to-mid therapeutic range (not supratherapeutic or high therapeutic) before proceeding with clinical examination alone 1
• Neuromuscular blockade reversed with nerve stimulator documentation of twitch response if these agents were used 1

Critical Timing Consideration

Defer brain death evaluation for 24-48 hours (or longer) following cardiopulmonary resuscitation or severe acute brain injury if there are concerns about examination validity or inconsistencies 1, 3. This waiting period allows for stabilization and ensures the neurologic examination accurately reflects irreversible brain injury rather than acute stunning. 1

Required Neuroimaging

CT or MRI must demonstrate acute CNS catastrophe consistent with profound loss of brain function before proceeding with brain death determination 1. Early imaging may not show significant injury; repeat studies help document that severe acute brain injury has occurred. 1 Note that neuroimaging is NOT an ancillary test and cannot substitute for clinical examination. 1

Clinical Examination Components

The neurologic examination must document:

• Coma (complete unresponsiveness to all stimuli) 1, 2
• Absent brainstem reflexes, including:
  • Pupillary light reflex (pupils mid-position or dilated, 4-9mm, no response to bright light)
  • Corneal reflexes
  • Oculocephalic reflex (doll's eyes)
  • Oculovestibular reflex (cold caloric testing)
  • Gag and cough reflexes 1, 2
• Apnea confirmed by formal apnea testing 1

Apnea Testing Protocol

The apnea test confirms loss of brainstem respiratory drive and requires PaCO₂ ≥60 mmHg AND ≥20 mmHg above baseline with no respiratory effort observed. 2, 4

Technique:

• Preoxygenate with 100% FiO₂ for 5-10 minutes 4
• Normalize baseline pH and PaCO₂ before starting 4
• Disconnect ventilator while providing passive oxygenation (oxygen insufflation via catheter in endotracheal tube) 4
• Observe continuously for any respiratory movements 4
• Obtain serial arterial blood gases to document PaCO₂ rise 4
• Abort test if oxygen saturation drops below 85% or hemodynamic instability occurs 4

If apnea testing cannot be safely completed due to hypoxemia, hemodynamic instability, or severe lung injury, an ancillary study must be performed. 1, 2, 4

Number of Examinations and Observation Periods

Two complete examinations by different attending physicians are mandatory, regardless of ancillary study results 1, 3. The apnea test may be performed by the same physician (preferably the attending managing ventilator care). 1

Age-Specific Observation Periods:

• Term newborns (37 weeks gestation to 30 days): 24 hours between examinations 1, 3
• Infants and children (>30 days to 18 years): 12 hours between examinations 1, 3
• Adults: Variable (typically 6-12 hours, though not explicitly stated in pediatric guidelines) 3

The observation period can be shortened if an ancillary study supports brain death, but all components of the second clinical examination that can be safely completed must still be performed, including a second apnea test (unless contraindicated). 1, 3

Ancillary Studies (When Needed)

Ancillary studies are NOT required for brain death determination and are NOT substitutes for clinical examination. 1, 2, 3 They should be used when:

• Components of examination or apnea testing cannot be safely completed 1, 2
• Uncertainty exists about examination results 1, 2
• Medication effects cannot be excluded despite adequate waiting periods 1, 3
• To reduce the inter-examination observation period 1

Recommended Ancillary Tests:

• Electroencephalogram (EEG) demonstrating electrocerebral silence 2, 5
• Cerebral blood flow studies: catheter cerebral angiography (gold standard), nuclear scintigraphy (99mTc-HMPAO or ECD showing no intracranial uptake), or transcranial Doppler 2, 6, 5

CT angiography, MR angiography, and perfusion studies are frequently used but not currently recommended by the American Academy of Neurology, though they show promise as future diagnostic tools. 6, 5

Declaration of Death

Death is declared when all clinical criteria are fulfilled after the second examination, with documentation that the condition remains unchanged and irreversible. 1, 2, 3 The time of death is the time when the second examination and apnea test confirm brain death criteria are met. 3

Common Pitfalls to Avoid

• Never proceed if medication effects cannot be excluded through adequate clearance time or blood level documentation 1, 3
• Do not diagnose brain death with supratherapeutic or high therapeutic sedative levels present 1
• Avoid apnea testing in hemodynamically unstable patients without first stabilizing or planning for ancillary testing 2
• Do not rush evaluation immediately post-resuscitation; wait the recommended 24-48 hours 1, 3
• Beware of spinal reflexes (spontaneous movements, deep tendon reflexes) which can persist and do not preclude brain death diagnosis 1
• Consider confounders: hypothermia, locked-in syndrome, and drug intoxication are the three most common mimics of brain death 5
• In patients with high spinal cord injury or severe neuromuscular disease, examination validity may be compromised; defer evaluation or use ancillary studies 1

Special Populations

These guidelines apply to term newborns, infants, and children; insufficient data exists for preterm infants <37 weeks gestational age. 1 For adults, the American Academy of Neurology provides separate criteria that emphasize the same core principles. 2, 7