for the Diagnosis of Brain Death
Neurocritical Care Group*
J. Neurol. Sci. 1999; 26: 64-66
death is defined as the irreversible loss of the capacity
for consciousness combined with the irreversible loss of all
brainstem functions including the capacity to breathe.(1,2)
Brain death is equivalent to death of the individual, even
though the heart continues to beat and spinal cord functions
for organ transplantation and the removal of organs from brain-dead
donors is a separate issue that is not addressed in this document.
Such procedures must respect provincial and institutional
guidelines. As a general rule, those individuals who assess
patients for brain death should not be part of the transplant
death must be determined clinically by an experienced physician
and in accord with the accepted medical standards.1 Thus the
guidelines described below are recommendations based on current
medical information and experience. As knowledge advances,
it can be anticipated that further revisions will be necessary.
Because of the major consequences of the diagnosis of brain
death, consultation with other physicians experienced in the
relevant clinical examinations and diagnostic procedures is
death can usually be diagnosed reliably by clinical criteria
alone. However, there are special circumstances when these
are not suitable and cannot be applied. These are discussed
below under "Special Circumstances" and "Laboratory Tests".
etiology has been established that is capable of causing
brain death and potentially reversible causes have been
excluded (see Comment 2 below.)
patient is in deep coma and shows no response within cranial
nerve distribution to stimulation of any part of the body.
No movements such as cerebral seizures, dyskinetic movements,
decorticate or decerebrate movements arising from the brain
should be present (see 1a below.)
stem reflexes are absent (see 1b, below.)
patient is apneic when taken off the respirator for an appropriate
time (see 1c below.)
conditions listed above persist when the patient is reassessed
after a suitable interval (see 2 below.)
should be no confounding factors for the application of
clinical criteria (see 1c, 2 and Special Circumstances below.)
Cessation of brain function
clinical absence of brain function is defined as the profound
coma, apnea and the absence of brain stem reflexes.
Coma The patient should be observed for spontaneous
behaviour and response to noxious stimuli. In particular,
there should be no motor response within cranial nerve distribution
to stimuli applied to any body regions. There should be no
spontaneous or elicited movements (dyskinesias, decorticate
or decerebrate posturing or epileptic seizures arising from
the brain). However, various spinal reflexes may persist in
Brain-stem reflexes Pupillary light, corneal, vestibulo-ocular
and pharyngeal reflexes must be absent. The pupils should
be midsize or larger and must be unreactive to light. Care
should be taken that atropine or related drugs that could
block the pupillary light reflex have not been given to the
patient. The vestibulo-ocular reflexes should be tested with
caloric stimulation while the head is 30° above the horizontal.
In adults a minimum of 50 ml of ice water should be used.
A minimum of 5 minutes should be allowed between testing on
each side. Grimacing or other motor response to corneal stimulation
or pharyngeal or tracheal suctioning is incompatible with
Apnea Apnea testing requires the availability of blood
gas measurement. It is recommended that a PaCO2 of
60 mm Hg be achieved to ensure that an adequate stimulus is
presented to the respiratory centre.(5) It is also suggested
that the arterial or capillary blood should be acidemic (pH
< 7.28) by the end of the apnea test. The following prerequisites
are recommended: i) core temperature should be at least 32.2°C,
preferably > 36.5°C, to allow an adequate rate of
rise of PaCO2. (Great caution must be exercised in patients
with subnormal body temperatures. Further, in chronic retainers
of carbon dioxide, the apnea test may not be valid.); ii)
systolic blood pressure should be
90 mm Hg in adults and within normal limits for age in infants
and children; iii) the patient should be euvolemic; iv) an
initially normal PaCO2 before apnea testing is begun (40 ±
5 mm Hg); v) pre-oxygenation with 100 oxygen allowing a PaO2
> 200 mm Hg. In performing the apnea test, it is suggested
that 100% oxygen is delivered via a cannula placed in the
trachea, or at the level of the carina, while the ventilator
is stopped. The arterial PaO2, PaCO2 and pH should be checked
at 8-10 minutes. The apnea test is positive if no respirations
are observed over the 8-10 minutes of observation, provided
that the PaCO2 rises to greater than 60 mm Hg.(1,3,6)
of brain function is determined to be irreversible when: the
proximate cause of the coma is known and is capable of causing
neuronal death; the loss of brain stem function is total and
constant over time; reversible causes of brain dysfunction
have been excluded. Drug intoxication (particularly barbiturates,
sedatives and hypnotics), treatable metabolic disorders, hypothermia
(temperature less than 32.2°C), shock and peripheral
nerve or muscle dysfunction due to disease or neuromuscular
blocking agents must be excluded. Neuro-imaging, in selected
cases, may be useful in documenting a structural cause and
determining the extent of anatomical damage.
is essential to ensure that the nonfunctioning state of the
brain is persistent and to reduce the possibility of error.
Depending on the etiology, the interval between such examinations
may be as short as 2 hours or as long as 24 hours; observation
for 24 hours is usually recommended to confirm brain death
due to anoxic-ischemic insults (e.g., post-cardiac arrest).
In situations where brain death is declared for purposes of
organ transplantation, local regulations may stipulate specific
intervals for reassessment.
and young children
children with a conceptional age of 52 weeks or older (more
than 2 months post-term) the adult clinical criteria can be
applied. Clinical criteria alone are not sufficient in the
determination of brain death in infants under this age.(7-9)
The basic tenets accepted in adults that apply to children
include: (i) the importance of excluding remediable or reversible
conditions, specially toxic and metabolic derangement and
the effects of sedative drugs, paralytic agents, hypothermia
and hypotension, (ii) physical examination criteria must be
satisfied (outlined under "comments" above) and (iii) irreversibility
must be ensured by re-evaluation at specified intervals. It
is recommended that: (a) for term newborns (greater than 38
weeks gestation) and young infants, aged 7 days to 2 months,
that the clinical examination and a radionuclide brain flow
study be done, (b) for those 2 months to 1 year, two examinations
and EEGs separated by at least 24 hours was suggested; a repeat
examination and EEG would not be necessary if a concomitant
radionuclide angiographic study failed to visualize cerebral
arteries, and (c) in those over 1 year of age, an observation
period of at least 12 hours is recommended. However, in those
comatose due to hypoxic-ischemic encephalopathy, at least
24 hours of observation is suggested. The validity of the
application of clinical criteria to preterm infants is still
uncertain. Further guidelines are needed. Clearly additional
supportive investigative tests, e.g., those of brain perfusion,
are needed to substantiate the diagnosis of brain death in
To Apply The Clinical Criteria
clinical situations may preclude the valid application of
the listed clinical criteria, e.g., trauma to the eyes, middle
or inner ear injuries, cranial neuropathies, severe pulmonary
disease and some cases of profound metabolic and endocrine
disturbances. In these situations, the most reliable means
of determining brain death is the demonstration of the absence
of brain perfusion. Some conditions may mimic brain death,
e.g., hypothermia, drug intoxication, the use of neuromuscular
blocking and anticholinergic agents and shock. These should
be excluded or reversed before applying the clinical criteria.
In some situations, the use of reliable laboratory tests for
brain perfusion, providing the blood pressure is normal, are
utilized to confirm the diagnosis of brain death.
brain death can be established reliably by clinical criteria
alone, special tests can be used to support the clinical diagnosis.
These are discussed below.
selective 4-vessel angiogram is done with the iodinated contrast
medium injected under high pressure in both the anterior and
posterior circulations. It should be assured that the mean
arterial pressure is at least 80 mm Hg. In brain death no
intracranial perfusion other than an occasional filling of
the superior sagittal sinus is seen. The lack of intracranial
perfusion other than filling of the superior sagittal sinus
is strongly confirmatory of brain death.(10,11)
is being increasingly used as an alternative to cerebral angiography
as a test of cerebral perfusion. Two&endash;planar imaging
using a radioactively-labeled substance that readily crosses
the blood-brain barrier (such as Technetium-99m hexamthylproplyeneamineoxme
[99mTc-HMPAO] is recommended.(12) In brain
death no uptake is seen in the brain parenchyma. Alternatively,
the rapid bolus injection of serum albumin labeled with technetium
99m is given, followed by imaging with a gamma camera. In
brain death there is lack of penetration of 99mTc
HMPAO into the brain parenchyma or no intracranial perfusion
seen in the arterial phase following the bolus injection of
radio-labeled albumin. Late filling of the superior sagittal
sinus may occur, however.
a 2 MHz pulsed Doppler instrument, the intracranial arteries
are insonated bilaterally, including the middle and/or anterior
cerebral arteries and the vertebral or basilar artery.(13)
The finding of absent diastolic or reverberating flow or small
systolic peaks have been reported in brain death. The absence
of transcranial Doppler signals cannot be taken as evidence
of brain death, as 10% of people do not have temporal insonation
windows.(5) The test should be performed and interpreted by
qualified individuals with considerable experience.
magnetic resonance imaging (MRI) techniques hold promise,
they have not been sufficiently studied or validated to be
used as the sole confirmatory test at this time. Neuro-imaging,
e.g., with MRI or computed axial tomography, may help to confirm
the structural nature and extent of damage in selected cases.
electroencephalogram (EEG) is of some confirmatory value and
may have a place in selecting certain individuals, e.g., very
young children, for apnea testing. The EEG does not, however,
adequately assess brainstem function and should not be used
as the sole confirmatory test for brain death. The use of
evoked potentials, including brainstem auditory and somatosensory
evoked potential testing, has promise, but these have not
been sufficiently validated. Furthermore, they are highly
dependent on technical quality and require considerable expertise
and experience for reliable performance and interpretation.
absence of an increase in heart rate after the intravenous
injection of 2 mg of atropine, is confirmatory of the absence
of vagal tone and is helpful in confirming dysfunction of
the caudal brainstem.(14,15) Although helpful, the atropine
test is not sufficient as the sole confirmatory test of brain
death. Because of the anticholinergic effects on pupillary
reactivity and EEG, the test should be performed after completion
of clinical and electroencephalographic testing. Further,
the test is not valid in cases of autonomic neuropathy or
following cardiac transplantation with denervation of the
autonomic fibres to the heart.
guidelines were prepared by a subcommittee of the Canadian
Neurocritical Care Group at the request of the Canadian Neurological
Society, the Canadian Neurosurgical Society, the Canadian
Association of Child Neurology and the Canadian Society of
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Group of Conference of Medical Colleges and their Faculties
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Consultants on the Diagnosis of Death to the President's
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JAMA 1981; 246: 2184-2185.
C, Harley DH: ABC of Brainstem Death, 2nd Edition. London:
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EFM. Determining brain death in adults. Neurology 1995;
Standards Subcommittee of the American Academy of Neurology:
Practice parameters for determining brain death in adults.
Neurology 1995; 45: 1012-1014.
Force for the Determination of Brain Death in Children:
Guidelines for the determination of brain death in children.
Arch Neurol 1998; 44: 587-588.
K, Sugimoto T. Return of spontaneous respiration in
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brain death. Pediatrics 1995; 96: 518-520.
MA. Validity of brain death in infants. Paediatrics
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GB, Simon RS. Angiography in brain death. Neuroradiology
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A, Schonfeld S, Hiatt M, Hegyi T. Digital subtraction
angiography &endash; a new approach to brain death determination
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A, Mercatello A, Coronel B, et al. 99mTc-HMPAO cerebral
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AH, Kehne SM, Weschler L. Transcranial Doppler in brain
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Y, Ouaknine G, Kosary IZ, Kellermann JJ. Electrocardiographic
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of Canadian Neurocritical Care Group: Drs. Marc-André
Beaulieu, Shashikant Seshia, Jeanne Teitelbaum and Bryan
J. Neurol. Sci. 1999; 26: 64-66