Outcome	Definition
Brain death	irreversible cessation of cerebral and brainstem function
Persistent vegetative state	severe anoxic brain injury progressing to a state of wakefulness without awareness. No purposeful responses, but sleep wake cycles intact
Minimal conscious state	Limited interaction with the environment with visual tracking +/- simple commands. Intelligible verbalization or sometimes yes/no but not always appropriate
Locked in	retained alertness, cognitive abilities, can move eyes and blink voluntarily, but with paralysis of the limbs and oral structures.

Relevant guidelines:

1. Shemie SD, Wilson LC, Hornby L, Basmaji J, Baker AJ, Bensimon CM, et al. A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline. Can J Anesth/J Can Anesth. 2023 Apr 1;70(4):483–557.
2. Shemie CMAJ 2006

Unified Brain-Based Definition of Death

Based on the 2023 joint Canadian guidelines as referenced above. The definition of brain-based death should apply to all patients in all circumstances.

Death is defined as the permanent cessation of brain function (function is lost, will not resume spontaneously, and will not be restored through intervention) characterized by the complete absence of consciousness, brainstem reflexes, ability to breath independently. Residual brain cell activity (ADH release, thermoregulation, etc) does not preclude death determination.

Death cannot be declared if there is any level of consciousness remaining and/or residual brainstem function exists.

Determination of Death

Death Determination by Circulatory Criteria (DCC)

1. DCC is based on the absence of extra-cranial circulation (i.e. systemic) that leads to the permanent cessation of intracranial (brain) circulation.
2. Invasive arterial BP monitoring is recommended in potential organ donors undergoing DCC. If not possible, then use cECG monitoring. An arterial pulse pressure < 5 mmHg and within the error of measurement is used to confirm this.
   1. Minimum 5 minutes of observation for controlled donation after DCC
   2. Minimum 10 minutes of observation for uncontrolled donation after DCC. Evidence shows that in this situation, for example, after failed CPR, there may be false positives if the observation period is less than 10 minutes.
   3. The patient should not be moved or transported during this period, and should be monitored by at least two clinicians determining death. The observation period should be restarted, if any signs of returning or returning circulation are observed.

The legal time of death is noted to be after the full observation period.

Death Determination by Neurologic Criteria (DNC)

DNC requires there be an established causes of devastating brain injury severe enough to cause death and supported by neuroimaging evidence, and potential confounders must be considered and excluded. The duty of the clinician determining DNC is to never conclude that the patient is dead if they are not. When there is clinical doubt, the patient cannot, and should not be declared deceased.

DNC is a clinical assessment that requires all three:

1. Absence of consciousness shown by lack of wakefulness and awareness in response to stimuli
2. Absence of brainstem function through cranial nerve testing
3. Absence of capacity to breath through a formal apnea test

Ancillary tests are not alone sufficient to confirm death and do not override a clinical assessment incompatible with death. However, in isolated infratentorial injury, these tests are required to determine death.

Confounders for DNC

• Hypothermia (req core temp > 36 C)
• Severe facial/ocular trauma (may interfered with cranial nerve testing)
• Decompressive craniectomy
• Spinal cord injury (can confound apnea test)
• Severe metabolic, endocrine, electrolyte abnormalities such as sodium, phosphate, glucose, magnesium, potassium, thyroid, liver, renal
• Unresuscitated shock (SBP > 100, MAP > 60 for adults)
• Neuromuscular blockade accounting for motor unresponsiveness (can use TOF or DTRs)
• Neuromuscular disorders (severe ALS, GBS, sensory neuropathy, etc)
• Pharmacologic confounders (alcohol <80 mg/dL, sedatives, drugs of abuse. Allow at least 5 elimination half lives for the drugs to clear from the body)
• Infratentorial brain injury without supratentorial involvement

Clinical Assessment for DNC

Cranial Nerve Testing

1. Quantitative or clinical pupil assessment are acceptable.
2. Oculocephalic reflex (OCR) is NOT recommended anymore due to low specificity, and only the cold caloric vestibulo-ocular reflex (VOR) is recommended.

Apnea Testing

1. Pre-oxygenate the patient and obtain an ABG (baseline per TGLN should be PaCO2 35-45, pH 7.35 to 0.45).
2. Disconnect from ventilator but provide either CPAP or passive low-flow oxygenation
3. Monitor for respiratory efforts
4. Serial ABGs q5 minutes
5. Threshold for completion: PaCO2 > 60 mmHg and >20 mmHg from pre-apnea baseline and pH < 7.28

Nuances of DNC

1. Clinical assessment for DNC should wait at least 48 hours after ROSC for patients with HIE without clear imaging evidence of devastating brain injury.
2. Core body temperature should be ≥36℃
3. One clinical assessment is sufficient for patients 1+ years of age undergoing DNC. However, legal requirements for organ donation someones mandate 2 clinicians.

Ancillary Testing

If ancillary investigations show the presence of brain blood flow/perfusion, death cannot be determined at that time.

Ancillary test	Notes
CT perfusion	Newer technology and variable expertise
CT angiography	Widespread availability and expertise
Transcranial Doppler (TCD)	Requires adequate bone windows and formal neuroultrasonography expertise
Radionuclide brain perfusion study	Widespread historical use and expertise

EEG, radionuclide flow studies, brainstem auditory evoked potentials, MRA are not suggested due to false positive rates or poor false negative rates.