Criteria and Practical Guidance for Determination of Brain Death in Adults (2nd Edition)

Brain death—the irreversible loss of all brain function, including the brainstem—is one of medicine’s most critical distinctions. It affects end-of-life care, organ donation, and legal decisions, yet it remains widely misunderstood. In 2013, China released its first national guidelines for brain death determination. Five years later, in 2018, experts updated these guidelines to reflect real-world clinical experience, quality control data, and feedback from neurologists, neurosurgeons, and critical care teams. The 2nd edition of Criteria and Practical Guidance for Determination of Brain Death in Adults aims to standardize evaluations, reduce errors, and ensure consistency across China’s healthcare system. Here’s a clear, evidence-based breakdown of how brain death is diagnosed.

What Is Brain Death?

Brain death is not a coma or a vegetative state. It means the entire brain—including the brainstem (which controls breathing, heart rate, and reflexes)—has permanently stopped working. Unlike a coma, there is no chance of recovery. The body can only be kept alive with mechanical ventilation and life support.

Key Prerequisites for Brain Death Determination

Before evaluating a patient for brain death, two critical conditions must be met:

1. The Cause of Coma Is Known

Coma must stem from a confirmed brain injury (e.g., trauma, stroke) or secondary injury (e.g., cardiac arrest, drowning, anesthesia accident). Brain death cannot be declared if the cause of coma is unknown.

2. Reversible Coma Is Excluded

Some conditions mimic brain death but are treatable. These include:

Acute intoxication: Carbon monoxide, alcohol, sedatives, or muscle relaxants.
Shock or hypothermia (body temperature <32°C).
Severe metabolic/electrolyte imbalances: Liver/kidney failure, low blood sugar, or extreme acidosis.

Reversible causes must be ruled out before proceeding.

Clinical Evaluation: The First Step in Brain Death Diagnosis

To confirm brain death, three clinical criteria must be met: deep coma, absence of all brainstem reflexes, and no spontaneous respiration (complete reliance on a ventilator).

A. Deep Coma

The patient must show no motor response to painful stimulation of the face (e.g., pressing the supraorbital ridge or pricking the skin). The Glasgow Coma Scale (GCS)—a tool to measure consciousness—must be 3 (the lowest possible score, meaning no eye, verbal, or motor response).

Critical Pitfalls:

Stimulate only the head/face—neck or body stimulation can trigger spinal reflexes (e.g., limb movement), which do not indicate brain activity (the spinal cord can survive brain death).
Do not diagnose deep coma if the trigeminal (face sensation) or facial (facial movement) nerves are damaged.

B. Absence of All Brainstem Reflexes

The brainstem controls basic reflexes. All five of these must be absent:

Pupillary Light Reflex: No constriction of either pupil when a bright light is shined into the eyes. (Note: Pupil size alone doesn’t matter—some brain-dead patients have small or medium pupils.)
Corneal Reflex: No blink when the edge of the cornea (eye surface) is touched with a cotton swab.
Oculocephalogyric Reflex (“Doll’s Eyes”): No eye movement when the head is quickly turned side to side (do not test if the neck is injured).
Oculovestibular Reflex: No eye twitching (nystagmus) after flushing cold saline (0–4°C) into the ear canal (skip if the eardrum is damaged).
Cough Reflex: No cough when the trachea is stimulated with a suction tube.

Important Notes:

If any reflex cannot be tested (e.g., eye injury), repeat other reflexes and add ancillary tests (see below).
Weak eyelid or muscle movements do not count as a reflex—only clear, purposeful responses matter.

C. Apnea: No Spontaneous Breathing

Brain-dead patients cannot breathe on their own. To confirm this, a formal apnea test is required:

Preconditions for Safety:

Core body temperature ≥36.5°C.
Systolic blood pressure ≥90 mmHg (or mean arterial pressure ≥60 mmHg).
Preoxygenate with 100% oxygen for 10–15 minutes to ensure high blood oxygen levels (PaO₂ ≥200 mmHg).
Adjust ventilation to normalize carbon dioxide (PaCO₂ 35–45 mmHg).

Test Steps:

Draw blood to measure baseline PaCO₂.
Disconnect the ventilator.
Insert an oxygen tube to the carina (windpipe split) and deliver 100% oxygen at 6L/min.
Watch closely for chest/abdominal breathing for 8–10 minutes.
Draw blood again to measure PaCO₂.
Reconnect the ventilator.

Results:

Apnea is confirmed if:

PaCO₂ rises to ≥60 mmHg (or 20 mmHg above baseline).
No breathing movements are observed.

Safety First:

Abort the test if the patient’s heart rate, blood pressure, or oxygen levels drop dangerously. At least two clinicians must monitor the test.

Ancillary Tests: Confirming Brain Death When Clinical Signs Are Unclear

If clinical evaluation is incomplete (e.g., eye injury limits reflex testing) or requires confirmation, two of three ancillary tests must support brain death:

1. Electroencephalogram (EEG)

EEG measures brain electrical activity. For brain death, it must show electrical silence—no activity over 2 microvolts (μV) for at least 30 minutes.

Key Requirements:

Use 8+ electrodes placed per the international 10–20 system.
Test for reactivity (no response to sound or touch).
Sedatives/anesthesia can affect results—rely on other tests if these drugs were used.

2. Short-Latency Somatosensory Evoked Potential (SLSEP)

SLSEP tracks nerve signals from the median nerve (wrist) to the brain. For brain death:

N9/N13 waves (from the arm/neck) are present.
P14/N18/N20 waves (from the brain) are absent bilaterally.

Pitfalls:

Hypothermia or median nerve damage can distort results—use other tests if these apply.

3. Transcranial Doppler (TCD)

TCD uses ultrasound to check blood flow in brain arteries (middle cerebral, vertebral, basilar). Brain death is supported if:

Reverberating flow: Forward (systole) and reverse (diastole) flow in the same heartbeat (directional flow index <0.8).
Small systolic spikes: Brief forward flow (≤200ms, <50cm/s) in early systole.
No blood flow signal.

Critical Rules:

Test twice, 30 minutes apart.
Check both anterior (middle cerebral artery) and posterior (basilar artery) circulation.

Alternative Tests:

If TCD is unavailable, CT angiography (CTA) or digital subtraction angiography (DSA) can show absent brain blood flow.

Step-by-Step Procedure for Brain Death Declaration

Clinical Evaluation: Confirm deep coma, no brainstem reflexes, and ventilator dependence.
Ancillary Tests: Perform at least two tests (e.g., EEG + SLSEP, or EEG + TCD).
Apnea Test: Confirm no spontaneous breathing (must be done at least once).

If all criteria are met, brain death is declared. If clinical evaluation is incomplete, repeat testing in 6 hours and add more ancillary tests.

Who Can Determine Brain Death?

At least two physicians must participate. They must:

Have ≥5 years of clinical experience.
Complete standardized training in brain death determination.

Why This Guideline Matters

Standardizing brain death criteria is critical for:

Patient Safety: Avoiding misdiagnosis of reversible conditions.
Ethical Care: Ensuring end-of-life decisions are based on clear evidence.
Organ Donation: Facilitating timely,legal donation when families consent.

This 2nd edition builds on China’s growing experience with brain death evaluation, incorporating feedback from hundreds of experts to reduce errors and improve consistency.

Brain Injury Evaluation Quality Control Center of National Health Commission; Neurocritical Care Committee of the Chinese Society of Neurology (NCC/CSN); Neurocritical Care Committee of China Neurologist Association (NCC/CNA). Criteria and practical guidance for determination of brain death in adults (2nd edition). Chinese Medical Journal 2019;132(3):329–335. doi: 10.1097/CM9.0000000000000014

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