BRAIN DEATH
Pediatric Critical Care Medicine
Emory University
Children’s Healthcare of Atlanta
Background
• Before the 1960’s, donation after cardiac death (DCD) was
the general approach to organ donation
• 1968, an ad hoc committee at Harvard Medical School
proposed a neurologic based death definition, which
replaced DCD
2
Background
• 1980, with modifications, by the President’s Commission for
the Study of Ethical Problems in Medicine & Biomedical
Research, as a recommendation for state legislature & court
• The “brain death” standard was also employed in the model
legislation known as the Uniform Determination of Death
Act, which has been enacted by a large number of
jurisdictions & the standard has been endorsed by the
influential American Bar Association
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Background
• Even though there has been legal acceptance of the concept
of brain death, there is a lack of a standardized approach
• No national brain death law exists
• State law & statutes may restrict the determination of brain
death
• Reasons for revising guidelines
– Allow physicians to pronounce brain death in pediatric patients in a
more precise and orderly manner
– Appropriate documentation
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Brain Death
• An individual who has sustained either
– Irreversible cessation of circulatory & respiratory functions
– Irreversible cessation of all functions of the entire brain, including
the brainstem, is dead
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The Examination – human brain
• Cerebrum: memory, consciousness & higher mental function
• Cerebellum: controls various muscle functions
• Brain stem consisting of the midbrain, pons & medulla,
which extends downwards to become the spinal cord
– Controls respiration & various basic reflexes (e.g., swallow & gag)
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Coma
• Deep coma
– Non responsive to most external stimuli
– At most, such patients may have a dysfunctional cerebrum but, by
virtue of the brain stem remaining intact, are capable of
spontaneous breathing & heartbeat
• PVS: persistent vegetative state
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Organ function
• Heart
– Needs O2 to survive & w/o O2 will stop beating
– Not controlled by the brain but it is autonomous
• Breathing
– Controlled by vagus nerve, located in the brain stem
– Main stimulant is increase in CO2 in the blood
» Causes the diaphragm & chest muscles to expand
» Spontaneous breathing can not occur after brain stem death
• With artificial ventilation, the heart may continue to beat
for a period of time after brain stem death
• Time lag between brain death & circulatory death is ~2-10
days
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Initial requirements
• Clinical or radiographic evidence of an acute catastrophic
cerebral event c/w dx of brain death
• Exclusion of conditions that confound clinical evidence (i.e.
metabolic)
• Confirmation of absence of drug intoxication or poisoning
– Including barbituratds, NMB;s
• Core body temp > 35oC
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Term – 18 yrs of age
• Determination of brain death by neurologic examination
should be performed in the setting of normal ageappropriate physiological parameters
– Corrected hypotension, metabolic disturbances, recent
administration of neuromuscular blockaded, or any drug
intoxication
• Placement of an arterial line is recommended for close
monitoring of BP & PaCO2
10
Hypothermia & Brain Death
• An adjunctive therapy for acute brain injury
– Reduces cerebral metabolic activity
• Hypothermia is known to depress cerebral activity
– May lead to a false diagnosis of brain death
– Adequately re-warm with rec. 12 hrs of normal temperature prior to
performing brain death exam
• A core body temperature of >35oC should be achieved prior
to doing brain death exam
– Previous guidelines stated that the patient should not be
significantly hypothermic but no definition was provided
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Drugs
• Long acting or continuous infusions of sedative agents
should be discontinued
• When available levels should be obtained & documented to
be in a low to mid therapeutic range
• If a neuromuscular blocking agent has been used,
confirmation of it’s clearance should be established
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Observation Period
• General consensus was the younger the child the longer the
waiting period
– If ancillary studies supported the diagnosis of brain death, the
observation period could be shortened
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Observation Period
• 2011 Guidelines
– Examinations should be performed by 2 separate attendings
– Both apnea tests may be performed by the same physician
– Recommends:
» 37 weeks up to 30 days: 24 hours
» >30 days – 18 yrs: 12 hours
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• It is reasonable to defer neurologic examination to
determine brain death for >24 hrs if dictated by clinical
judgment
– After cardiopulmonary arrest
– If apnea testing cannot be performed
• If patient is not stable enough to perform certain parts of
the exam, ancillary testing may be used to assist in the
diagnosis
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Ancillary Studies
• Four vessel cerebral angiography is the gold standard for
determining the absence of CBF
• EEG & radionuclide CBF are the most widely used methods
• Radionuclide CBF can be used in patients with high dose
barbiturate therapy
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Ancillary Studies
• Ancillary studies are not required and should not be used as
a substitute to the clinical exam
• They must be used when
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–
–
–
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Components of the exam or apnea test cannot be completed safely
Uncertainty about the results
Medication effect may be present
Reduce the inter-examination observation period
Basic exam 1 - Pain
• Cerebral motor response to pain
– Supra-orbital ridge, the nail beds, trapezius
– Motor responses may occur spontaneously during apnea testing
(spinal reflexes)
– Spinal reflex responses occur more often in young
– If patient had NMB, then confirm clearance with train-of-four
• Spinal arcs are intact!
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Basic exam 2 - Pupils
• Round, oval or irregularly shaped
• Midsize 94-6 mm0, but may be totally dilated
• Absent pupillary light reflex
– Although drugs can influence pupillary size, the light reflex remains
intact only in the absence of brain death
– IV atropine does not markedly affect response
– Paralytics do not affect pupillary size
– Topical administration of drugs and eye trauma may influence
pupillary size and reactivity
– Pre-existing ocular anatomic abnormalities may also confound
pupillary assessment in brain death
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Basic exam 3 – Eye movement
• Oculocephalic reflex = doll’s eyes
• Vestibulo-ocular = cold caloric test
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Doll’s eyes
• Oculocephalic reflex
– Rapidly turn the head 90° on both sides
– Normal response = deviation of the eyes to the opposite side of head
turning
– Brain death = oculocephalic reflexes are absent (no Doll’s eyes) = no
eye movement in response to head movement
• Not Barbie, but old fashioned type dolls
– Painted vs. wooden eyes in porcelain heads
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Doll’s eyes
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Cold calorics
• Elevate the HOB 30°
• Irrigate both tympanic membranes with iced water
– Observed pt for 1 min after each ear irrigation, with a 5 min wait
between testing of the other ear
– Facial trauma involving the auditory canal & petrous bone can also
inhibit these reflexes
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Cold calorics
• Nystagmus both eyes slow toward cold, fast to midline
– Not comatose
• Both eyes tonically deviate toward cold water
– Coma with intact brainstem
• Movement only of eye on side of stimulus
– Internuclear ophthalmoplegia
– Suggests brainstem structural lesion
• No eye movement
– Brainstem injury/death
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Basic exam 4 –
Facial sensory & motor responses
• Corneal reflexes are absent in brain death
– Corneal reflexes – tested by using a cotton-tipped swab
– Grimacing in response to pain can be tested by applying deep
pressure to the nail beds, supra-orbital ridge, TMJ, or swab in nose
– Severe facial trauma can inhibit interpretation of facial brain stem
reflexes
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Basic exam 5 –
Pharyngeal & tracheal responses
• Both gag & cough reflexes are absent in pts w/brain death
– Gag reflex can be evaluated by stimulating the posterior pharynx
w/a tongue blade, but the results can be difficult to evaluate in
orally intubated patients
– Cough reflex can be tested by using ETT suctioning, past end of
ETT
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Apnea Testing
• Should be performed with each test unless there is a clinical
contraindication
– If cannot be performed an ancillary test should be performed to
assist
• PaCO2 >60 mmHg has been used as the threshold to
stimulate ventilatory efforts
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Apnea Testing
• Technique:
–
–
–
–
Normalization of pH & PaCO2
Maintenance of core temperature > 35oC degrees
Normalization of BP – age appropriate
Pre-oxygenation for 5-10 min with 100% oxygen via connectin to tpiece or self-inflating bag
– Apneic oxygenation for ~6 min
• PaCO2 should rise >20 mmHg above baseline & >60 mmHg
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Ancillary Studies
• Four vessel cerebral angiography is the gold standard for
determining the absence of CBF
• EEG & radionuclide CBF are the most widely used methods
– Cerebral blood flow = perfusion scan
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Cerebral perfusion scan
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Common misconceptions
• Since there is a heartbeat, he is alive
– Brain dead pts have permanently lost the capacity to think, be
aware of self or surroundings, experience, or communicate w/others
• He’s in a coma
– Reinforce that they are dead
• With rehab/time he’ll get better
– Irreversible, dead brain cells do not regrow
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How to make it clear
• Say “dead”, not “brain dead”
• Say “artificial or mechanical ventilation”, not “life support”
• Time of death = neurologic determination
– NOT when ventilator removed
– NOT when heart beat ceases
• Do not say “kept alive” for organ donation
• Do not talk to the pt as if he’s still alive
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Ancillary Studies
• If EEG shows electrical activity or CBF study shows
evidence of flow, patient cannot be pronounced dead
• Patient should be medically treated until brain death can be
established solely on clinical examination & apnea testing
• If repeat ancillary testing is performed, a waiting period fo
24 hours should be observed
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Ancillary Studies
• If an ancillary study, in conjunction with the first
neurologic examination, supports the diagnosis of brain
death, the inter-examination observation period can be
shortened
• The second test can be performed at any time thereafter for
children of all ages
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2011 Strong Evidence
• High – further research is very unlikely to change our
confidence in the estimate of effect
• When an ancillary study is used because there are inherent
examination limitations, then components of the
examination done initially should be completed &
documented
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2011 Strong Evidence
• High – further research is very unlikely to change our
confidence in the estimate of effect
• When an ancillary study is used because there are inherent
examination limitations, then components of the
examination done initially should be completed &
documented
• Determination of brain death in neonates, infants &
children relies on a clinical diagnosis that is based on the
absence of neurologic function with a known irreversible
cause of coma. Coma & apnea must coexist to diagnose
brain death.
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2011 Strong Evidence
• Prerequisites for initiating a brain death evaluation:
– Hypotension, hypothermia, & metabolic disturbances that could
affect the neurologic examination must be corrected before the
examination for brain death
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2011 Strong Evidence
• Declaration of death:
– Death is declared after confirmation & completion of the second
clinical examination & apnea test
– When ancillary studies are used, documentation of components from
the second clinical examination that can be completed must remain
consistent with brain death. All aspects of the clinical examination
including the apnea test, or ancillary studies must be appropriately
documented
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2011 Strong Evidence
• The clinical examination should be carried out by
experienced clinicians who are familiar with infants &
children & have specific training in neuro-critical care
• The examination should be performed by different
attending physicians involved in the care of the child
• The apnea test may be performed by the same physician,
preferably the attending physician who is managing
ventilator care of the child – low evidence but strong
recommendation
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2011 Moderate Evidence
• Prerequisites for initiating a brain death examination
– Sedatives, analgesics, NMB & anti-convulsant agents should be
discontinued for a reasonable time period based on elimination halflife of the pharmacologic agent to ensure they do not affect the
neurologic examination
» Knowledge of the total amount of each agent (mg/kg) administered
since hospital admission may provide useful information concerning the
risk of continued medication effects
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2011 Moderate Evidence
• Prerequisites for initiating a brain death examination
– Sedatives, analgesics, NMB & anti-convulsant agents should be
discontinued for a reasonable time period based on elimination halflife of the pharmacologic agent to ensure they do not affect the
neurologic examination
» Knowledge of the total amount of each agent (mg/kg) administered
since hospital admission may provide useful information concerning the
risk of continued medication effects
– Blood or plasma levels to confirm high or supra-therapeutic levels of
anti-convulsant with sedative effects should be obtained (if
available) & repeated as needed or until the levels are in the low to
mid-therapeutic range
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2011 Moderate Evidence
• The diagnosis of brain death based on neurologic exam
alone should not be made if supra-therapeutic or high
therapeutic levels of sedative agents are present
– When levels are in the low or in the min-therapeutic range,
medication effects sufficient to affect the result of the neurologic
exam are unlikely
– If uncertainty remains, an ancillary study should be performed
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2011 Moderate Evidence
• Assessment of neurologic function may be unreliable
immediately after cardiopulmonary resuscitation or other
severe acute brain injuries & evaluation for brain death
should be deferred for 24-48 hrs if there are concerns or
inconsistencies in the exam
• Number of exams, examiners & observation periods
– 2 exams including apnea testing with each exam separated by an
observation period are required
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