What are the steps to diagnose brain death in an adult patient with no significant underlying medical conditions?

How to Diagnose Brain Death in Adults

Brain death determination requires two complete neurological examinations by different attending physicians, separated by an observation period, after establishing an irreversible cause of coma and excluding all confounding factors. 1

Prerequisites Before Any Examination

Before initiating brain death evaluation, you must systematically address these mandatory prerequisites:

Establish Irreversible Cause

• Neuroimaging (CT or MRI) must demonstrate acute CNS catastrophe consistent with complete loss of brain function (e.g., massive intracerebral hemorrhage, severe traumatic brain injury, anoxic injury, large territory infarction). 2, 3
• The structural injury must explain the clinical presentation—imaging findings may evolve, so repeat studies may be needed if initial scans are inconclusive. 2

Correct Physiological Confounders

• Core temperature must be ≥36°C (96.8°F) before examination. 2, 1
• Systolic blood pressure must be ≥100 mmHg (or mean arterial pressure ≥60 mmHg). 2, 1
• Correct severe metabolic derangements including sodium abnormalities, severe acidosis, hypoglycemia, and uremia that could impair neurological function. 2, 1

Eliminate Drug Effects

• Discontinue all sedatives, analgesics, neuromuscular blockers, and anticonvulsants for a duration based on elimination half-life (typically 5 half-lives). 2, 1
• If neuromuscular blockers were used, confirm clearance with nerve stimulator showing adequate twitch response. 2
• Obtain serum drug levels when available—levels should be in low-to-mid therapeutic range or undetectable for sedating medications. 2
• If supratherapeutic sedative levels persist, defer examination or use ancillary testing. 2

Timing Considerations

• Defer examination for 24-48 hours following cardiopulmonary resuscitation or other acute severe brain injuries to allow stabilization and ensure confounders are resolved. 2

The Clinical Neurological Examination

The examination requires assessment of approximately 25 individual components: 4, 5

Coma Assessment

• Patient must be completely unresponsive to all stimuli, including noxious stimulation (supraorbital pressure, nail bed pressure, sternal rub). 1, 3
• No purposeful or localizing movements to painful stimuli. 3

Brainstem Reflex Testing

Pupillary reflex:

• Pupils must be fixed and unreactive to bright light (may be mid-position, dilated, or unequal). 1, 3

Corneal reflex:

• No blink response to direct corneal stimulation with cotton swab or tissue. 1, 3

Oculocephalic reflex (doll's eyes):

• No eye movement when head is turned rapidly side-to-side (only if cervical spine cleared). 3, 6

Oculovestibular reflex (cold caloric):

• Elevate head 30 degrees, confirm intact tympanic membranes, irrigate each ear with 50mL ice-cold water over 1 minute, observe for 1 minute—no eye movement should occur. 3, 6

Facial movement and grimacing:

• No facial muscle response to deep pressure on supraorbital ridge, temporomandibular joint, or nail beds. 3

Gag and cough reflexes:

• No gag with posterior pharyngeal stimulation, no cough with deep tracheal suctioning. 3, 6

Motor Response Assessment

• No motor response to noxious stimuli in cranial nerve distribution. 3
• Spinal reflexes may persist (e.g., triple flexion response, Lazarus sign) and do not preclude brain death. 6, 5

Apnea Testing Protocol

This is the definitive test for brainstem function and must be performed carefully: 1, 3

Pre-test Requirements

• Core temperature ≥36.5°C. 1
• Systolic BP ≥100 mmHg. 1
• Euvolemia established. 1
• Pre-oxygenate with 100% FiO₂ for 5-10 minutes to achieve PaO₂ ≥200 mmHg. 1
• Baseline arterial blood gas showing PaCO₂ 35-45 mmHg (normalize if needed with ventilator adjustments). 1, 3

Procedure

• Disconnect ventilator while providing passive oxygenation via tracheal catheter at 6 L/min or T-piece with 100% O₂. 1, 3
• Observe closely for any respiratory effort (chest or abdominal excursion). 1
• Continue for 8-10 minutes or until PaCO₂ ≥60 mmHg (or ≥20 mmHg above baseline). 1, 3
• Obtain arterial blood gas to confirm PaCO₂ target reached. 1

Interpretation

• Brain death confirmed if no respiratory effort occurs despite PaCO₂ ≥60 mmHg. 1, 3
• Abort test if: oxygen saturation <85% for >30 seconds, systolic BP <90 mmHg, or cardiac arrhythmias develop—proceed to ancillary testing. 3, 6

Number of Examinations Required

• Two complete examinations (including apnea testing) by different attending physicians. 2, 1
• Observation period between examinations: No specific duration mandated for adults, but typically several hours to ensure consistency. 2, 4
• The same physician may perform both apnea tests. 2

Ancillary Testing (When Clinical Exam Cannot Be Completed)

Ancillary tests are NOT required if clinical examination and apnea testing are completed successfully. 1, 3 Use ancillary testing when:

• Apnea testing cannot be safely performed (severe lung injury, hemodynamic instability). 2, 1
• Components of clinical exam cannot be assessed (severe facial trauma, pre-existing blindness). 1, 5
• Uncertainty remains despite clinical examination. 7

Accepted Ancillary Tests

Electroencephalogram (EEG):

• Must show electrocerebral silence (no activity >2 microvolts) for 30 minutes using standardized technique. 1, 3
• Prone to electrical interference—requires experienced interpretation. 7

Cerebral blood flow studies (gold standard):

• Four-vessel cerebral angiography showing no intracranial filling at carotid bifurcation or circle of Willis. 1, 3
• Nuclear scintigraphy (99mTc-HMPAO or 99mTc-ECD) showing no intracranial radiotracer uptake ("hollow skull sign"). 1, 3
• Transcranial Doppler showing reverberating flow, systolic spikes, or absent signals. 3, 6

Note: CT angiography and MR angiography show promise but are not yet endorsed by American Academy of Neurology guidelines. 3

Critical Pitfalls to Avoid

• Never diagnose brain death with residual sedative effects—wait for adequate drug clearance or obtain confirmatory levels. 2, 7
• Do not rely solely on ancillary tests without attempting clinical examination—the clinical exam remains the cornerstone. 7, 3
• Spinal reflexes do not exclude brain death—distinguish these from brainstem-mediated responses. 6, 5
• Hypothermia, locked-in syndrome, and drug intoxication are the three most common mimics—systematically exclude these. 3
• Do not perform examination immediately post-resuscitation—allow 24-48 hours for stabilization. 2
• Ensure adequate PaCO₂ rise during apnea testing—inadequate hypercarbic stimulus yields false results. 3, 6

Documentation Requirements

Record comprehensively: 1

• All prerequisites verified (temperature, blood pressure, drug clearance, metabolic status)
• Detailed findings of both neurological examinations with specific reflex testing results
• Complete apnea test procedure with pre- and post-test blood gas values
• Names and credentials of examining physicians
• Time of death declaration (typically after second examination confirms brain death)

The diagnosis of brain death aids end-of-life communication and facilitates organ donation discussions, which should be routine considerations. 2