REVIEW ARTICLE
Brain Death/Death by
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C O N T I N UU M A UD I O
I NT E R V I E W A V AI L A B L E
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CONTINUUM (MINNEAP MINN)
2021;27(5, NEUROCRITICAL CARE):
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Address correspondence to
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Neurocritical Care, Departments
of Neurology and Neurosurgery,
NYU Langone Medical Center,
530 First Ave, HCC-5A, New York,
NY 10016, ariane.kansas.lewis@
gmail.com.
RELATIONSHIP DISCLOSURE:
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editor for Neurology and
Seminars in Neurology.
Dr Kirschen has received
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the Neurocritical Care Society.
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© 2021 American Academy
of Neurology.
1444
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Neurologic Criteria
Determination
By Ariane Lewis, MD; Matthew P. Kirschen, MD, PhD
ABSTRACT
PURPOSE OF REVIEW: This article describes the prerequisites for brain
death/death by neurologic criteria (BD/DNC), clinical evaluation for
BD/DNC (including apnea testing), use of ancillary testing, and challenges
associated with BD/DNC determination in adult and pediatric patients.
RECENT FINDINGS: Although death determination should be consistent among
physicians and across hospitals, states, and countries to ensure that
someone who is declared dead in one place would not be considered
alive elsewhere, variability exists in the prerequisites, clinical evaluation,
apnea testing, and use of ancillary testing to evaluate for BD/DNC.
Confusion also exists about performance of an evaluation for BD/DNC in
challenging clinical scenarios, such as for a patient who is on
extracorporeal membrane oxygenation or a patient who was treated with
therapeutic hypothermia. This prompted the creation of the World Brain
Death Project, which published an international consensus statement on
BD/DNC that has been endorsed by five world federations and 27 medical
societies from across the globe.
SUMMARY: The World Brain Death Project consensus statement is intended
to provide guidance for professional societies and countries to revise or
develop their own protocols on BD/DNC, taking into consideration local
laws, culture, and resource availability; however, it does not replace local
medical standards. To that end, pending publication of an updated
guideline on determination of BD/DNC across the lifespan, the currently
accepted medical standards for BD/DNC in the United States are the 2010
American Academy of Neurology standard for determination of BD/DNC in
adults and the 2011 Society of Critical Care Medicine/American Academy
of Pediatrics/Child Neurology Society standard for determination of
BD/DNC in infants and children.
INTRODUCTION
eath can be declared using cardiopulmonary or neurologic criteria
(traditionally termed brain death). Brain death/death by neurologic
criteria (BD/DNC) is accepted as death throughout much of the
world.1,2 The incidence of BD/DNC declaration worldwide is
unknown, but epidemiologic studies have found that 2% to 12% of
OCTOBER 2021
adult deaths in the United States and Europe and 20% of pediatric deaths in the KEY POINTS
United States are declared using neurologic criteria.2-4 Although BD/DNC is
● The incidence of brain
declared less frequently than death by cardiopulmonary criteria, it is imperative death/death by neurologic
(1) for neurologists to be adept at BD/DNC determination to prevent criteria declaration
false-positive declarations in which a person who is alive is declared dead and (2) worldwide is unknown, but
for the process to be consistent across hospitals, states, and countries to ensure epidemiologic studies have
found that 2% to 12% of adult
that someone who is declared dead in one place would not be considered alive
deaths in the United States
elsewhere. This article reviews the history of BD/DNC, the medical standards for and Europe and 20% of
BD/DNC determination, and some challenges associated with BD/DNC pediatric deaths in the
determination. United States are declared
using neurologic criteria.

HISTORY OF BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA ● The World Brain Death

The concept of BD/DNC was introduced in Europe in the 1950s when Mollaret Project standard is not
and Goulon5 noticed that some patients with catastrophic brain injuries who were intended to replace local
being maintained on ventilators were comatose, had no brainstem reflexes, medical standards; rather, it
aims to provide guidance for
and were unable to breathe spontaneously. In 1968, a multidisciplinary professional societies and
committee at Harvard Medical School introduced the first medical standard countries to revise or
for BD/DNC.6 The ensuing years led to the creation of additional medical develop their own protocols
standards for BD/DNC and the realization that BD/DNC needed to be on brain death/death by
neurologic criteria, taking
incorporated into law in order for society to accept it as death. In response, the into consideration local
President’s Commission for the Study of Ethical Problems in Medicine and laws, culture, and resource
Biomedical and Behavioral Research drafted a model statute on death availability.
determination, the Uniform Determination of Death Act.7 BD/DNC was
● Pending publication of an
subsequently accepted as death throughout the United States.8 The American
updated guideline on
Academy of Neurology (AAN) published a standard for BD/DNC in adults in determination of brain
1995 and updated it in 2010.9,10 The Task Force for Determination of Brain Death death/death by neurologic
in Children published a standard for BD/DNC in infants and children in 1987; criteria across all age groups
this was updated in 2011 by the Society of Critical Care Medicine (SCCM), beginning at birth, the 2010
American Academy of
American Academy of Pediatrics (AAP), and Child Neurology Society Neurology and 2011 Society
(CNS).11,12 of Critical Care Medicine/
Despite the existence of these standards and the fact that no aspects of the American Academy of
standards themselves are believed to inherently pose challenges to widespread Pediatrics/Child Neurology
Society standards remain
adoption, variability exists in the process of evaluation for BD/DNC between the current accepted
institutions within the United States13; further, determination of BD/DNC medical standards for brain
around the world is inconsistent.1 This prompted the creation of the World Brain death/death by neurologic
Death Project (WBDP), which published an international consensus statement criteria in the United States.
on BD/DNC that has been endorsed by five world federations and 27 medical
societies from across the globe.2 The WBDP standard is not intended to replace
local medical standards; rather, it aims to provide guidance for professional
societies and countries to revise or develop their own protocols on BD/DNC,
taking into consideration local laws, culture, and resource availability. Thus,
pending publication of an updated guideline on determination of BD/DNC across
all age groups beginning at birth, the 2010 AAN and 2011 SCCM/AAP/CNS
standards remain the current accepted medical standards for BD/DNC in the
United States.14,15

GENERAL PRINCIPLES
BD/DNC evaluations should only be performed by licensed practitioners who are
experienced in caring for patients with devastating brain injuries and have been
trained in determination of BD/DNC and in counseling families at the end of

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

life.2 Although no formal credentialing is required for determination of BD/DNC

at present, residency and fellowship programs should ensure trainees are
appropriately educated about this topic via didactics, simulations, and direct
observation of and participation in the evaluation of patients with catastrophic
brain injuries. Additional training is also available online through the Neurocritical
Care Society.16 To prevent false-positive declarations of death, practitioners must
take a conservative approach and be scrupulous and attentive to details. A
BD/DNC evaluation should never be rushed. Further, practitioners must be
familiar with local guidelines and laws regarding determination of BD/DNC.2

PREREQUISITES FOR BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

Performance of an evaluation for BD/DNC should only be considered if a patient
is comatose, has absent brainstem reflexes, and is not breathing spontaneously
because of a known etiology that can cause catastrophic irreversible brain injury.
Examples of etiologies that can lead to BD/DNC include hypoxic-ischemic brain
injury, hemorrhagic stroke, ischemic stroke, traumatic brain injury, bacterial
meningitis, viral encephalitis, hepatic encephalopathy, and obstructive
hydrocephalus.2 Mimics of BD/DNC include fulminant Guillain-Barré
syndrome, botulism, high cervical cord injuries, snake bites, and rabies.2 Even
when a mechanism that is known to potentially lead to catastrophic irreversible
brain injury is identified, it is necessary to ensure the assessment is not
confounded by circumstances that could falsely suggest BD/DNC, such as
hypotension, hypothermia, or hypoglycemia.2,10,12
The minimum acceptable blood pressure for a BD/DNC evaluation in adults is
a systolic pressure ≥100 mm Hg or a mean arterial pressure ≥60 mm Hg.2,10
In pediatric patients, the systolic or mean arterial blood pressure should not be
less than 2 standard deviations below age-appropriate norms.2,12

TABLE 12-1 Medications That Could Lead to False-positive Declaration of Brain

Death/Death by Neurologic Criteriaa

◆ Antibiotics (aminoglycosides, ethambutol, isoniazid, tetracyclines)

◆ Antiepileptic drugs
◆ Baclofen
◆ Barbiturates
◆ Benzodiazepines
◆ Dexmedetomidine
◆ IV/inhaled anesthetics
◆ Narcotics
◆ Propofol
◆ Tricyclic antidepressants
◆ Zolpidem

IV = intravenous.
a
Practitioners must be aware of medications that could lead to false-positive declaration of brain
death/death by neurologic criteria. Examples are provided here, but this list is not exhaustive.

1446 OCTOBER 2021

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 The minimum acceptable temperature for a BD/DNC evaluation is ≥36 °C KEY POINTS
(≥96.8 °F) according to the 2010 AAN and WBDP standards and >35 °C (>95 °F)
● To prevent false-positive
according to the 2011 SCCM/AAP/CNS standard.2,10,12 Additional guidance declarations of death,
regarding BD/DNC evaluation after treatment with therapeutic hypothermia is practitioners must take a
discussed later in this article. conservative approach and
Although some countries provide clear guidance on the lower and upper limits be scrupulous and attentive
to details.
for electrolytes, pH, and hormones before BD/DNC evaluation, no scientific
rationale exists for the selection of values; as a result, the 2010 AAN, 2011 ● Examples of etiologies
SCCM/AAP/CNS, and WBDP standards recommend the need to exclude that can lead to brain
“severe” derangements.1,2,10,12 death/death by neurologic
Finally, it is necessary to ensure that medications or drugs that can depress criteria include
hypoxic-ischemic brain
the central nervous system or yield pharmacologic paralysis have been injury, hemorrhagic stroke,
metabolized or cleared before BD/DNC evaluation (TABLE 12-1).2,10,12 A ischemic stroke, traumatic
BD/DNC evaluation should not be performed until at least 5 half-lives have brain injury, bacterial
passed following administration of medications that depress the central meningitis, viral
encephalitis, hepatic
nervous system (CASE 12-1).2,10,12 Additional time may be warranted to ensure encephalopathy, and
clearance of medications that depress the central nervous system in the presence obstructive hydrocephalus.
of renal or hepatic dysfunction, recent hypothermia, or obesity. When
evaluating neonatal and pediatric patients, it should also be noted that ● Mimics of brain
death/death by neurologic
pharmacokinetics of medications vary by age. To evaluate for the residual
criteria include fulminant
presence of drugs, serum or urine toxicology screens can be employed, but it Guillain-Barré syndrome,
should be noted that the utility of these tests is limited as they do not evaluate for botulism, high cervical cord
all agents or provide quantified drug levels. injuries, snake bites, and
rabies.
No finite observation period before evaluation for BD/DNC has been
established.2,10,12 Rather, it is necessary for practitioners to err on the side of
caution when determining the appropriate time to perform a BD/DNC
evaluation, taking the mechanism of injury (particularly in the setting of
hypoxic-ischemic brain injury, in which recovery can be delayed), neuroimaging
findings, intracranial pressure, blood pressure, temperature, laboratory values,
medication or drug effects, social factors, and the patient’s age into
consideration. Infants with open fontanelles and unfused sutures may not have
the characteristic rise in intracranial pressure and subsequent brain herniation
due to cerebral edema as older children and adults with a rigid skull.
Additionally, the infant’s brainstem is more resistant to hypoxic-ischemic brain
injury than other brain structures. This may lead to the emergence of brainstem
reflexes or spontaneous respirations several days after the injury when the
cerebral edema subsides. Thus, longer observation periods, particularly after
hypoxic-ischemic brain injury, should be considered in infants and young
children.12 TABLE 12-2 provides a summary of the prerequisites for BD/DNC
included in the 2010 AAN, 2011 SCCM/AAP/CNS, and WBDP standards.2,10,12

CLINICAL EXAMINATION FOR BRAIN DEATH/DEATH BY

NEUROLOGIC CRITERIA
Once the prerequisites for BD/DNC have been met, a clinical evaluation is
performed to assess for coma, absence of motor response of the face and extremities,
and brainstem areflexia (TABLE 12-3). Of note, a number of conditions can
preclude completion of the clinical evaluation and necessitate ancillary testing. In
these situations, it is essential to perform all parts of the clinical examination that can
be completed, and they must be consistent with BD/DNC to declare BD/DNC
(ie, ancillary testing augments, but does not replace, the clinical evaluation). These

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

CASE 12-1 A 45-year-old woman with a history of hypertension was found

unresponsive on the sidewalk. She was intubated by emergency medical
services. Head CT revealed a large left basal ganglia hemorrhage with
intraventricular extension leading to moderate hydrocephalus and 1 cm
of midline shift (FIGURE 12-1). On a fentanyl drip, she had no response
to voice or pain, her pupils were 4 mm and unreactive bilaterally, and
corneal and oculovestibular reflexes were absent. However, cough and
gag reflexes were present, she was overbreathing the ventilator, and she
extended her right arm and leg but was
plegic on the left. She was given
hypertonic saline and mannitol and
started on nicardipine.
The following day, she no longer
had cough and gag reflexes, was not
overbreathing the ventilator, and did
not move any extremities in response
to pain. Fentanyl was stopped, and
no further hypertonic saline or
mannitol was administered.
Twenty-four hours later, she continued
to show no clinical evidence of
neurologic activity. Renal and hepatic
function were normal. Her blood
pressure was 130/80 mm Hg, and
FIGURE 12-1
her temperature was 36.5 °C Imaging of the patient in CASE 12-1. Axial
(97.7 °F). An evaluation for brain noncontrast head CT shows a large left
death/death by neurologic criteria basal ganglia hemorrhage extending to
(BD/DNC), including an apnea test, the bilateral thalami (as well as to the
midbrain and pons [not shown]).
was performed. She was Intraventricular extension, 1 cm of
subsequently declared dead by left-to-right midline shift, and
neurologic criteria. moderate hydrocephalus are seen.

COMMENT This patient was comatose because of a known etiology (intracerebral

hemorrhage). Although hypertonic saline and mannitol were initially
administered when they were felt to potentially provide therapeutic
benefit, they were discontinued once the injury progressed as it is not
necessary to perform interventions to decrease intracranial pressure if
they are not felt to be beneficial simply for the purpose of demonstrating
irreversibility of the clinical state. As the half-life of fentanyl is about
4 hours and the patient had no renal or hepatic dysfunction, an evaluation
for BD/DNC was delayed 24 hours (over 5 half-lives) from the time that
fentanyl was discontinued.2 Her blood pressure and temperature were
above the minimum threshold for BD/DNC evaluation. Thus, all
prerequisites were met.

1448 OCTOBER 2021

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conditions include, but are not limited to, severe neuromuscular disorders/sensory KEY POINTS
neuropathies, spinal cord injuries, orbital/facial trauma/swelling/chemosis,
● Conditions that can
ophthalmic surgery, anophthalmia, and a ruptured tympanic membrane.2,10,12 preclude completion of the
To deem patients comatose with absent motor response of the face or clinical evaluation for brain
extremities, it is necessary to demonstrate that they are unresponsive to tactile, death/death by neurologic
auditory, and visual stimulation and make no cerebrally mediated movements criteria and thus necessitate
ancillary testing include, but
following application of painful tactile stimulation to the face and two locations
are not limited to, severe
on each extremity (or on the side of the body if an extremity is missing).2,10,12 neuromuscular
Numerous spinally mediated reflexes have been observed in patients who meet disorders/sensory
clinical criteria for BD/DNC, including myoclonus, spontaneous extensor neuropathies, spinal cord
injuries, orbital/facial
posturing, intermittent head turning, slow flexion then extension of the toes
trauma/swelling/chemosis,
(undulating toe), and isolated thumb extension (thumbs-up sign). These ophthalmic surgery,
responses have been confirmed to originate below the level of the brainstem via anophthalmia, and a
ancillary testing.2 If it is unclear whether a finding is cerebrally mediated, it is ruptured tympanic
necessary to consult with another practitioner or perform ancillary testing membrane.

following completion of the clinical examination and apnea test.2 ● Numerous spinally
The brainstem reflexes included in the 2010 AAN and WBDP standards are mediated reflexes have
the pupillary, corneal, oculocephalic, oculovestibular, gag, and cough reflexes.2,10 been observed in patients
The 2011 SCCM/AAP/CNS standard includes all of these reflexes except the who meet clinical criteria for
brain death/death by
oculocephalic reflex. The 2011 SCCM/AAP/CNS standard, like the WBDP neurologic criteria, including
standard, also notes the need to confirm absence of the sucking and rooting myoclonus, spontaneous
reflexes in neonates and infants.2,12 To be compatible with BD/DNC, the extensor posturing,
pupillary reflex assessment should demonstrate fixed midsize or dilated pupils intermittent head turning,
slow flexion then extension
bilaterally that are unresponsive to direct or consensual stimulation.2,10,12 A
of the toes (undulating toe),
magnifying glass can help facilitate assessment for a pupillary response. Use of and isolated thumb
a pupillometer may also be considered, but this has not been validated. The extension (thumbs-up sign).
corneal reflex is assessed by applying light pressure to the cornea at the external
border of the iris with a cotton swab on a stick to evaluate for eyelid movement,
which is absent in BD/DNC.2,10,12 The oculocephalic reflex is tested by briskly
rotating the head horizontally and evaluating for eye movements, the presence of
which is not compatible with BD/DNC.2,10,12 This should not be done if
evidence or suspicion of cervical injury exists.2,10 The oculovestibular reflex tests
the same nerves as the oculocephalic reflex and is, in fact, more sensitive. Thus,
in the setting of known or suspected cervical trauma when the oculocephalic
reflex cannot be performed, BD/DNC can still be declared clinically if the
oculovestibular reflex is absent.2 Before testing the oculovestibular reflex, the
auditory canal should be inspected to confirm it is patent and that the tympanic
membrane is intact (note that a ruptured membrane would lead to a stronger
response, if present, but could increase the risk of meningitis, which could be
harmful if the examination is not consistent with BD/DNC). With the head of
bed elevated to 30 degrees, 50 mL to 60 mL of cold water should be injected into
the ear while the eyes are monitored for movement for at least 1 minute. This
should be repeated on the other side following a 5-minute interval that facilitates
equilibration of the endolymph temperature.2,10,12 The gag and cough reflexes are
assessed by stimulating both sides of the posterior pharynx and the
tracheobronchial wall.2,10,12 In neonates and infants, the sucking reflex is assessed
by placing a gloved finger in the baby’s mouth to see if sucking occurs (ie, if the
lips close around the finger) and the rooting reflex is assessed by stroking the
cheeks bilaterally to see if the baby’s head moves (which indicates a
positive response).2,12

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA
TABLE 12-2 Prerequisites for Brain Death/Death by Neurologic Criteria
2011 Society of Critical Care
Medicine, American
Academy of Pediatrics, and
2010 American Academy of Child Neurology Society
Neurology Medical Standards for Standards for BD/DNC in
Component BD/DNC in Adults10 Infants and Children12
Etiology Establish cause of coma through Establish that patient has a
history, examination, neuroimaging, known diagnosis that has
and laboratory tests resulted in irreversible coma
Exclude mimicking conditions Exclude mimicking conditions
Observation period Insufficient evidence to determine Assessment of neurologic
before the (first) the minimally acceptable function may be unreliable
neurologic observation period to ensure immediately following
examination irreversible loss of function of the cardiopulmonary
brain resuscitation or other severe
acute brain injuries, and
evaluation for brain death
should be deferred for 24 to
48 hours or longer if concerns
or inconsistencies in the
examination exist
First examination may be
performed 24 hours after birth
Irreversibility Establish that brain injury is Establish that brain injury is
irreversible irreversible
Neuroimaging should
demonstrate evidence of an
acute central nervous system
injury consistent with the
profound loss of brain
function
Temperature >36 °C (96.8 °F) >35 °C (95 °F)
Blood pressure Systolic blood pressure Systolic or mean arterial blood
≥100 mm Hg pressure should not be less
than 2 standard deviations
below age-appropriate norms
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World Brain Death Project2
Establish cause of coma
Exclude mimicking conditions
Ensure an adequate
observation period (erring on
the side of caution) before
evaluation
Minimum of 24 hours after
resuscitated cardiac arrest,
rewarming after therapeutic
hypothermia or birth asphyxia
Establish that brain injury is
irreversible
Suggested to ensure
neuroimaging evidence of
intracranial hypertension is
present or intracranial
pressure measurements equal
or exceed mean arterial
pressure
It is not necessary to perform
interventions to decrease
intracranial pressure simply for
the purpose of demonstrating
irreversibility of the clinical
state
≥36 °C (96.8 °F)
Systolic blood pressure
≥100 mm Hg or mean arterial
pressure ≥60 mm Hg in adults
and age-appropriate in
pediatric patients
CONTINUED ON PAGE 1451
OCTOBER 2021
CONTINUED FROM PAGE 1450
2010 American Academy of
Neurology Medical Standards for
Component BD/DNC in Adults10
Exclude intoxication Exclude intoxication by any
substance that can depress the
central nervous system by history,
drug screen, ensuring serum level is
below the therapeutic range, and
waiting at least 5 half-lives, taking
hepatic or renal dysfunction into
consideration
Ensure blood alcohol level is below
0.08%
Exclude Ensure presence of four twitches
pharmacologic with maximum ulnar stimulation
paralysis
Laboratory Exclude severe electrolyte, acid-
parameters base, and endocrine disturbance
BD/DNC = brain death/death by neurologic criteria.
a
A peripheral nerve stimulator/train-of-four delivers a small electric current to the ulnar nerve to evaluate for the presence of muscle twitches to
confirm absence of pharmacologic neuromuscular blockade (four twitches). This can be performed at the bedside by any clinician/nurse.
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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
2011 Society of Critical Care
Medicine, American
Academy of Pediatrics, and
Child Neurology Society
Standards for BD/DNC in
Infants and Children12
Exclude intoxication by any
substance that can depress
the central nervous system
(alcohol, antiepileptic drugs,
barbiturates, IV/inhaled
anesthetics, opioids,
sedatives) by ensuring serum
level is in the low to
midtherapeutic range and
waiting several half-lives
Exclude alcohol intoxication
by checking levels
Evaluate nerve function with a
nerve stimulator
Identify and treat reversible
causes of coma that interfere
with the clinical evaluation,
including severe electrolyte
derangements,
hyperglycemia or
hypoglycemia, severe pH
disturbances, severe hepatic
or renal dysfunction, and
inborn errors of metabolism
World Brain Death Project2
Exclude intoxication by any
substance that can depress
the central nervous system by
drug screen, ensuring serum
level does not exceed the
therapeutic range, and waiting
at least 5 half-lives, taking
hepatic or renal dysfunction
into consideration
Ensure blood alcohol level is
≤80 mg/dL
Exclude pharmacologic
paralysis with a peripheral
nerve stimulator/train-of-
foura or by demonstrating
presence of deep tendon
reflexes
Correct severe metabolic,
acid-base, and endocrine
derangements that could
impact the examination
1451
BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

TABLE 12-3 Clinical Examination/Examiner Specifications for Brain Death/Death by

Neurologic Criteria

2011 Society of Critical Care

2010 American Academy of Medicine, American Academy of
Neurology Medical Pediatrics, and Child Neurology
Standards for BD/DNC in Society Standards for BD/DNC in
Component Adults10 Infants and Children12 World Brain Death Project2
Number of One Two One
examiners

Qualifications of Not stated Attending physicians who are
examiners qualified and competent to
perform the brain death
examination
Specialty of pediatric critical care,
pediatric neurology, neonatology,
pediatric anesthesiology with
critical care training, pediatric
neurosurgery, or pediatric trauma
surgery
Adult specialists should have
appropriate neurologic and critical
care training to diagnose brain
death when caring for the pediatric
patient from birth to 18 years of age
Practitioners who have completed
training, are licensed to
independently practice medicine,
and are trained in determination of
BD/DNC, counseling families at
end of life, and managing
devastating brain injuries
Pediatric patients should be
evaluated by experienced
pediatric clinicians with specialty
in neonatology, neurosurgery,
pediatric critical care, pediatric
neurointensive care, pediatric
neurology, or trauma surgery

Number of One Two One in adults and two in pediatric

examinations patients

Observation Not stated 12 hours (>30 days-18 years of age) If two examinations are
period between performed, an observation period
24 hours (37 weeks estimated
examinations between examinations is
gestational age to 30 days)
unnecessary

Components of Assessment for Assessment for unresponsiveness Assessment for unresponsiveness

clinical unresponsiveness
examination
Assessment for absence of
motor response of face/
extremities
Assessment for absence of
pupillary light reflex
Assessment for absence of
oculocephalic and
oculovestibular reflexes
Assessment for absence of
corneal reflex
Assessment for absence of
gag and cough reflexes
Assessment for absence of motor
response of face/extremities
Assessment for absence of
pupillary light reflex
Assessment for absence of
oculovestibular reflex
Assessment for absence of corneal
reflex
Assessment for absence of gag and
cough reflexes
Assessment for absence of sucking
and rooting reflexes (neonates and
infants)
Assessment of absence of motor
response of face/extremities
Assessment for absence of
pupillary light reflex
Assessment for absence of
oculocephalic and oculovestibular
reflexes
Assessment for absence of
corneal reflex
Assessment for absence of gag
and cough reflexes
Assessment for absence of
sucking and rooting reflexes
(neonates)

BD/DNC = brain death/death by neurologic criteria.

1452 OCTOBER 2021

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 Concordant with the 2010 AAN and 2011 SCCM/AAP/CNS standards,
the WBDP standard indicates that the minimum number of clinical
examinations for BD/DNC is one for adults and two for pediatric patients.2,10,12
However, around the world, the minimum number of clinical examinations
for BD/DNC varies.1 The rationale for conducting more than one
examination is that it decreases the potential for diagnostic error and may
increase familial confidence in a declaration of BD/DNC.2 However, no
physiologic reason exists for why more than one examination is needed or for
the number of examinations to differ by age. The 2011 SCCM/AAP/CNS
standard notes that the observation period between the first and second
clinical examination should be 24 hours for neonates between 37 weeks
estimated gestational age and 30 days of age and 12 hours for infants and
children older than 30 days of age to 18 years of age.12 Again, no data support
any particular length of an observation period. As a result, the WBDP
standard emphasizes that an adequate observation period should be allowed
before evaluation for BD/DNC, but that no scientific rationale exists for an
interexamination observation period if more than one examination
is performed.2

APNEA TESTING
Upon completion of the clinical evaluation, if a patient is found to be comatose
and have absent brainstem reflexes, barring a contraindication, the next
step is apnea testing (TABLE 12-4). Contraindications to apnea testing described
in the 2010 AAN, 2011 SCCM/AAP/CNS, and WBDP standards include severe
obesity or chronic obstructive pulmonary disease (2010 AAN standard), high
cervical spine injury (2011 SCCM/AAP/CNS and WBDP standards), chronic
hypoxemia due to cyanotic heart disease (WBDP standard), or any safety
concerns (2011 SCCM/AAP/CNS standard).2,10,12
The purpose of apnea testing is to determine if the medullary chemoreceptors,
which should stimulate respiration in the setting of hypercarbia and acidosis, are
functional.2,10,12,17 Following preoxygenation, the apnea test is performed by
removing intermittent mechanical ventilation and observing for spontaneous
respirations. In adults, hypoxia is avoided by placing an insufflation catheter that
is less than 70% of the endotracheal tube diameter down the endotracheal tube
and delivering up to 6 L/min of oxygen (these limits are in place to decrease the
risk of a pneumothorax); continuous positive airway pressure (CPAP) can also
be used if needed.2,10,17 In infants and children, tracheal insufflation generally is
not performed because of a heightened concern that their lower lung capacity
can put them at higher risk for washout of carbon dioxide, which can delay or
prevent completion of the test, or barotrauma to the lungs.2,17 Thus, in this age
group, oxygenation is provided via a T-piece circuit connected to the
endotracheal tube with a functioning positive end-expiratory pressure valve or
CPAP with a flow-inflating anesthesia bag or ventilator.2,12,18
Although the carbon dioxide level and pH at which the medullary
chemoreceptors would definitively stimulate respiration if they were functional
is unknown, the 2010 AAN standard indicates that the target PaCO2 is ≥60 mm
Hg or ≥20 mm Hg above baseline and the 2011 SCCM/AAP/CNS standard
indicates that the target PaCO2 is ≥60 mm Hg and ≥20 mm Hg above
baseline.10,12,17 However, the meaning of “baseline” is unclear in both of these
standards and, similar to the majority of standards for BD/DNC around the

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA
TABLE 12-4 Apnea Testing for Brain Death/Death by Neurologic Criteria
2010 American Academy of
Neurology Medical Standards
Component for BD/DNC in Adults10
Number of apnea One
tests
Contraindications Prior evidence of carbon
dioxide retention (severe
obesity or chronic obstructive
pulmonary disease)
Technique Preoxygenate for at least
10 minutes with 100% oxygen to
PaO2 >200 mm Hg
Ensure PaCO2 35-45 mm Hg
Reduce ventilator frequency to
10 breaths per minute
Reduce positive end-expiratory
pressure to 5 cm H2O
Disconnect the ventilator
Preserve oxygenation with an
insufflation catheter placed
through the endotracheal tube
delivering 100% oxygen at 6 L/min
Use T-piece circuit or
continuous positive airway
pressure (CPAP), if needed
Apnea testing PaCO2 ≥60 mm Hg or ≥20 mm Hg
target above baseline
Reasons to abort Systolic blood
testing pressure <90 mm Hg
Oxygen saturation <85% for
>30 seconds
BD/DNC = brain death/death by neurologic criteria.
1454
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2011 Society of Critical Care
Medicine, American
Academy of Pediatrics, and
Child Neurology Society
Standards for BD/DNC in
Infants and Children12
Two
High cervical spine injury
Safety concerns for the
patient (eg, high oxygen
requirement or ventilator
settings)
Preoxygenate for 5-10 minutes
with 100% oxygen
Ensure normalization of the
pH and PaCO2, measured by
arterial blood gas analysis
Discontinue intermittent
mandatory ventilation
Attach a T-piece circuit or a
self-inflating bag valve
system such as a Mapleson
circuit to the endotracheal
tube or use CPAP if needed
PaCO2 ≥60 mm Hg
and ≥20 mm Hg above
baseline
Hemodynamic instability
Oxygen saturation <85%
PaCO2 level of ≥60 mm Hg
cannot be achieved
World Brain Death Project2
One in adults and two in pediatric
patients
High cervical spine injury
Chronic hypoxemia due to
cyanotic heart disease
Preoxygenate for at least
10 minutes with 100% oxygen
Ensure PaCO2 35-45 mm Hg
Preserve oxygenation with an
insufflation catheter placed
through the endotracheal tube
(except in neonates, infants, or
young children)
Consider use of CPAP on the
ventilator or via resuscitation bag
pH <7.3 and PaCO2 ≥60 mm Hg
unless the patient has preexisting
hypercapnia, in which case target
should be ≥20 mm Hg above
baseline, if known
Spontaneous respirations
witnessed
Systolic blood pressure
<100 mm Hg or mean arterial
pressure <60 mm Hg
Sustained oxygen desaturation <85%
Unstable arrhythmia
OCTOBER 2021
world, these standards do not emphasize the impact of acidosis on the medullary KEY POINTS
chemoreceptors by providing a pH target.1,2,10,12 This has been remedied in
● If the complete clinical
the WBDP standard, which indicates the target for apnea testing should assessment is performed
be pH <7.3 and PaCO2 ≥60 mm, unless the patient has preexisting hypercapnia, and found to be consistent
in which case the target should be ≥20 mm Hg above their baseline, if with brain death/death by
known.2 The rate of CO2 rise is approximately 3 mm Hg to 5 mm Hg neurologic criteria, the pH
and PaCO2 thresholds are
per minute.17
reached during the apnea
In line with the recommendations on the number of clinical evaluations test, and the patient does
needed to declare BD/DNC, the 2010 AAN and WBDP standards state that only not take any breaths, the
one apnea test is needed to declare BD/DNC in adults, whereas the 2011 patient is declared dead at
the time the arterial blood
SCCM/AAP/CNS and WBDP standards recommend performance of two apnea
gas results are reported.
tests for pediatric patients.2,10,12 Around the world, the number of apnea tests
required to declare BD/DNC ranges from one to three.1 Again, no data support ● Although EEG was
the performance of more than one apnea test. included in the 1968 Harvard
If the complete clinical assessment is performed and found to be consistent standard and is considered
an acceptable ancillary test
with BD/DNC, the pH and PaCO2 thresholds are reached during the apnea test, in the 2010 AAN and 2011
and the patient does not take any breaths, the patient is declared dead at the time SCCM/AAP/CNS standards,
the arterial blood gas results are reported.2 If two clinical examinations the World Brain Death
and apnea tests are performed and are consistent with BD/DNC, death is Project standard suggests it
only be used if mandated by
declared at the time the arterial blood gas results are reported after the second regional policy or law or if
apnea test.2 craniovascular impedance is
affected by an opening in
ANCILLARY TESTING the skull (such as a skull
fracture or open fontanelle),
If a portion of the clinical evaluation or the apnea test cannot be completed or
leading to concerns about
uncertainty exists about the interpretation of findings on the clinical the accuracy of a blood flow
evaluation, the 2010 AAN, the 2011 SCCM/AAP/CNS, and the WBDP study.
standard all note that ancillary testing is needed.2,10,12 The 2011
SCCM/AAP/CNS standard states that ancillary testing can also be used to ● Clearance of carbon
dioxide on extracorporeal
reduce the interexamination observation period. It further specifies that membrane oxygenation is
ancillary testing can be performed if medication effect may be present or if it influenced by the rate of
is felt that this would be helpful for family members to understand the sweep gas flow through the
diagnosis of BD/DNC.12 Similarly, the WBDP standard notes that ancillary oxygenator, so the sweep
gas flow rate is reduced to
testing is needed in the setting of uncertainty about drug elimination or severe 0.5 L/min to 1 L/min during
laboratory derangements that cannot be corrected and are felt to potentially apnea testing to facilitate
be contributing to loss of brain function.2 Although the 2010 AAN and 2011 accumulation of carbon
SCCM/AAP/CNS standards, like the WBDP standard, promote the dioxide in the arterial blood.
whole-brain formulation of death by neurologic criteria (as opposed to the
● When a patient is on
brainstem formulation that is used in some other parts of the world, most venoarterial extracorporeal
notably the United Kingdom), only the WBDP standard specifies that membrane oxygenation,
ancillary testing is needed in the setting of isolated brainstem pathology if the arterial blood should be
sampled simultaneously
whole-brain formulation is being followed (TABLE 12-5).1,2,10,12
from both the patient’s
The purpose of ancillary testing is to evaluate for loss of intracranial blood flow arterial catheter and the
or loss of electrical activity in the brain. A number of tests are currently used extracorporeal membrane
around the world for this purpose, including EEG, evoked potentials, four-vessel oxygenation circuit
catheter angiography, radionuclide cerebral perfusion scan, transcranial postoxygenator to ensure
the pH and carbon dioxide in
Doppler, CT, and magnetic resonance angiography (MRA).2,19 However, pitfalls the cerebral circulation
are associated with all these tests, and, as BD/DNC is first and foremost a clinical exceed the brain
evaluation, none are 100% sensitive or specific.2,19,20 The 2010 AAN, 2011 death/death by neurologic
SCCM/AAP/CNS, and WBDP standards all consider four-vessel catheter criteria thresholds.
angiography and radionuclide cerebral blood flow scan to be acceptable ancillary

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

tests.2,10,12 The 2010 AAN and WBDP standards consider transcranial Doppler to
be an acceptable ancillary test in adults. Given that transcranial Doppler has not
been validated as an ancillary test in pediatrics, it is not included in the 2011
SCCM/AAP/CNS standard, and the WBDP standard recommends it not be used
in pediatrics until more studies determine its utility in this population.2,10,12
Although EEG was included in the 1968 Harvard standard and is considered an
acceptable ancillary test in the 2010 AAN and 2011 SCCM/AAP/CNS standards,
the WBDP standard suggests it only be used if mandated by regional policy or
law or if craniovascular impedance is affected by an opening in the skull (such as

TABLE 12-5 Ancillary Testing for Brain Death/Death by Neurologic Criteria

2011 Society of Critical Care

2010 American Academy of Medicine, American Academy of
Neurology Medical Pediatrics, and Child Neurology
Standards for BD/DNC in Society Standards for BD/DNC in
Component Adults10 Infants and Children12 World Brain Death Project2

Indications Components of the Components of the examination Components of the examination

examination cannot be
completed because of the
underlying medical condition
Uncertainty about the
reliability of parts of the
neurologic examination
Apnea test cannot be
performed
cannot be completed because of the
underlying medical condition
Uncertainty about the reliability of
parts of the neurologic examination
Apnea test cannot be performed
Medication effect may be present
Reduce interexamination observation
period
May be helpful for social reasons,
allowing family members to better
comprehend the diagnosis of BD/DNC
cannot be completed because of the
underlying medical condition
Uncertainty regarding interpretation
of spinal-mediated motor reflexes
High cervical spine injury
Uncertainty about drug elimination
Severe metabolic, acid-base, or
endocrine derangements that cannot
be corrected and are judged to
potentially be contributing to loss of
brain function
The whole-brain death formulation is
being followed and there is isolated
brainstem pathology
Law/regional guidance mandates
ancillary testing

Acceptable Four-vessel catheter Four-vessel catheter angiography Four-vessel catheter angiography

tests angiography
EEG Radionuclide cerebral blood flow
EEG scan
Radionuclide cerebral blood flow
Radionuclide cerebral blood scan Transcranial Doppler (adults only)
flow scan
EEG only if mandated by regional law
Transcranial Doppler or policy or if craniovascular
impedance has been affected by
open skull fracture, decompressive
craniectomy, or an open fontanelle/
sutures, in which case it should be
performed in conjunction with
somatosensory and brainstem
auditory evoked potentials

BD/DNC = brain death/death by neurologic criteria; EEG = electroencephalography.

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 A 5-year-old previously healthy boy with a recent viral upper respiratory CASE 12-2
infection presented to the emergency department with fever, decreased
oral intake, and altered mental status. In the emergency department, he
was tachycardic and hypotensive, so he was given crystalloid fluid. He
subsequently became pulseless and unresponsive. He was intubated and
cardiopulmonary resuscitation was initiated. Cardiopulmonary
resuscitation was performed for 75 minutes with return of circulation
after cannulation onto venoarterial extracorporeal membrane
oxygenation (ECMO). He was diagnosed with viral myocarditis. His
cardiac, renal, and hepatic function improved over the next few days.
On ECMO day 3, he was noted to be hypertensive and bradycardic and
had unreactive pupils. Head CT demonstrated severe hypoxic-ischemic
injury with loss of gray-white differentiation and extensive cerebral
edema with herniation. His family was updated about the imaging and his
clinical examination and was told that the team was concerned he may
have lost all function of the brain and may meet criteria for brain death/
death by neurologic criteria (BD/DNC). Sedatives and neuromuscular
blockade were stopped. Forty-eight hours later, he showed no evidence
of neurologic recovery. Deep tendon reflexes were present. After
ensuring confounders were excluded and the prerequisites were met, a
clinical evaluation for BD/DNC was performed. He was found to be
comatose with brainstem areflexia. Following preoxygenation through
the ventilator and the ECMO circuit, an arterial blood gas revealed pH of
7.4, PaCO2 of 40 mm Hg, and PaO2 of 210 mm Hg. The sweep gas flow was
reduced to 0.5 L/min, and the patient was placed on continuous positive
airway pressure (CPAP) with a flow-inflating anesthesia bag with a
positive end-expiratory pressure equivalent to the ventilator positive
end-expiratory pressure. Serial blood gases were sent from the patient’s
radial arterial line and the ECMO circuit postoxygenator to measure pH
and PaCO2. After 12 minutes, both blood gases showed pH <7.3 and
PaCO2 ≥60 mm Hg. The clinical examination and apnea test were repeated
the following day, and death was declared.

This patient had severe hypoxic-ischemic brain injury after a prolonged COMMENT
cardiac arrest due to myocarditis and was cannulated onto venoarterial
ECMO. BD/DNC evaluation was appropriately initiated after waiting a
sufficient time to allow for clearance of sedating medications and after
meeting all prerequisites. Following completion of the clinical examination,
the apnea test was performed on ECMO. The patient was taken off
mechanical ventilation, and the sweep gas flow was reduced to allow
carbon dioxide to accumulate in the blood. The practitioners ensured that
the PaCO2 levels from both the arterial catheter and the ECMO circuit
postoxygenator were above the BD/DNC thresholds. If the patient had
been too hemodynamically unstable to undergo apnea testing or the test
could not be completed because of hypotension or hypoxemia, ancillary
testing could have been performed.

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

a skull fracture or open fontanelle), leading to concerns about the accuracy of a

blood flow study.2,10,12 This is attributed to the fact that EEG primarily assesses
the cortex and can be confounded by drugs/medications, hypothermia, and
metabolic derangements.2
After performance of as much of the clinical assessment and apnea test as can
be completed, if the findings are consistent with BD/DNC and ancillary testing is
consistent with BD/DNC, the time of death is the time that the ancillary test
results are formally interpreted and documented.2

DETERMINATION OF BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

IN PATIENTS ON EXTRACORPOREAL MEMBRANE OXYGENATION
Although adults and children who are being supported by extracorporeal
membrane oxygenation (ECMO) may require evaluation for BD/DNC, only the
WBDP standard provides guidance about how to do so.2 The prerequisites for the
BD/DNC evaluation do not change for patients on ECMO. The ECMO circuit can
be used to help control temperature and blood pressure before and during the
BD/DNC evaluation. For patients on venoarterial ECMO with limited native
cardiac output, only the mean arterial pressure threshold is targeted. Similarly,

FIGURE 12-2
Examples of what to say when talking to families about brain death/death by neurologic
criteria. Communication about brain death/death by neurologic criteria can be challenging.
These examples can help to educate families while empathizing with them about their family
member’s catastrophic brain injury.

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 A 60-year-old woman was admitted to the intensive care unit with a CASE 12-3
catastrophic intracerebral hemorrhage. On hospital day 1, the neurologist
explained to the patient’s daughter that the patient had sustained a
very serious injury to her brain. The neurologist explained that the patient
still showed subtle signs of brain function but that it was possible the
injury to the brain would worsen and she would lose these functions. The
neurologist further noted that loss of all functions of the brain would
mean that the patient was legally dead, just as if her heart and lungs had
stopped working.
On hospital day 2, the neurologist explained to the patient’s daughter
that her mother was still comatose, had shown no signs of neurologic
recovery, and no longer had evidence of brain function. The neurologist
told the daughter that the next step would be to conduct a formal
evaluation to assess for brain death/death by neurologic criteria (BD/
DNC). The daughter objected to this evaluation, noting that she was not
ready to lose her mother, that her mother did not look like she was dead,
and that she wanted to give her mother more time to recover. The
neurologist explained that nothing could be done to improve her
mother’s condition and that neurologic recovery was impossible. The
neurologist showed the daughter her mother’s imaging and performed a
complete neurologic examination for her, explaining the findings as she
went. She reviewed that the purpose of a formal BD/DNC evaluation was
to follow a strict detailed protocol to determine if her mother showed
any signs of neurologic function. The neurologist noted that if even a
single brainstem reflex was present, it would mean her mother was alive.
However, if her mother were unresponsive, had no brainstem reflexes,
and could not take any breaths when she was taken off the ventilator and
the carbon dioxide level reached the appropriate threshold that should
stimulate the base of the brain leading to a breath if it were functional, it
would mean her mother was legally dead and that organ support would
be discontinued. After further discussions that included a social worker
and a spiritual counselor, the daughter and neurologist agreed that the
examination would be performed the following day. The next morning,
the evaluation was completed with the patient’s daughter at the bedside.
The patient’s daughter was tearful throughout but accepted the
declaration of death and subsequent discontinuation of organ support.

Patience and empathy are needed when discussing BD/DNC with a COMMENT
patient’s family. Education, including a review of imaging and
demonstration of the neurologic examination, helps families come to terms
with the severity and irreversibility of a patient’s catastrophic brain injury.
Although consent is not needed to conduct a BD/DNC evaluation, it is
appropriate to allow a family a brief period of time to process the situation.
Multidisciplinary support for a patient’s family from both hospital staff and
the family’s community can be beneficial.

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

the clinical examination is unchanged for patients on ECMO. Care should be

taken to avoid displacing ECMO cannulas during procedures such as testing for
the oculocephalic reflex.
The physiologic principles of apnea testing are the same for patients who
require extracorporeal support as for those who do not. Patients must
demonstrate absence of spontaneous respirations in the setting of hypercarbia
and acidosis. Apnea testing can often safely be conducted in patients
supported on both venoarterial and venovenous ECMO, although it must be
recognized that the potential for hemodynamic instability requiring the test to
be aborted is higher in this patient population.2,21 Patients should be

TABLE 12-6 Communication About Brain Death/Death by Neurologic Criteria

2011 Society of Critical Care

2010 American Academy of
Neurology Medical Standards
Component for BD/DNC in Adults10
Communication Inform patient’s surrogate about
before testing the intent to perform an
evaluation for BD/DNC
Medicine, American Academy
of Pediatrics and Child
Neurology Society Standards
for BD/DNC in Infants and
Children12
Physicians are obligated to
provide support and guidance
for families as they face difficult
end-of-life decisions and
attempt to understand what has
happened to their child
Permitting families to be present
during the evaluation can help
them understand that their child
has died
World Brain Death Project2
Health care teams should be
trained in cultural sensitivity and
communication and treat all
persons and families with respect
Families should be provided with
support and education before
BD/DNC evaluation, during the
evaluation, and after
discontinuation of organ support
A multidisciplinary support team
should be included in discussions
about BD/DNC
Families should be invited to
observe the evaluation
Reasonable efforts should be
made to notify the patient’s next
of kin before a BD/DNC
evaluation

Need for consent No obligation to obtain consent Not discussed No obligation to obtain consent
before the clinical evaluation,
apnea testing, or ancillary testing

CONTINUED ON PAGE 1461

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preoxygenated through both the ventilator and the ECMO circuit. As with
conventional apnea testing, patients are removed from intermittent
mechanical ventilation and provided apneic oxygenation, typically either by
tracheal insufflation or CPAP via a flow-inflating anesthesia bag or the
ventilator. Clearance of carbon dioxide on ECMO is influenced by the rate of
sweep gas flow through the oxygenator, so the sweep gas flow rate is reduced
to 0.5 L/min to 1 L/min during apnea testing to facilitate accumulation of
carbon dioxide in the arterial blood.2
Unique to apnea testing on venoarterial ECMO as compared with apnea
testing on venovenous ECMO or off ECMO, it is necessary to ensure that the

CONTINUED FROM PAGE 1460

2011 Society of Critical Care

2010 American Academy of
Neurology Medical Standards
Component for BD/DNC in Adults10
Management of No ethical obligation to provide
objections to organ support to a deceased
BD/DNC person
No legal obligation to provide
indefinite accommodation in the
United States outside of New
Jersey
Involve mediators (spiritual
counselor, mental health
professionals, palliative care
specialists, ethicists)
Attempt to transfer a patient to
another facility as a last resort
Unilateral withdrawal of organ
support is acceptable as a last
resort when supported by law
and institutional policy and the
patient is not pregnant
Medicine, American Academy
of Pediatrics and Child
Neurology Society Standards
for BD/DNC in Infants and
Children12
Communication with families
must be clear and concise using
simple terminology so that
parents and family members
understand that their child has
died
It should be made clear that
once death has occurred,
continuation of medical
therapies, including ventilator
support, is no longer an option
unless organ donation is planned
Appropriate emotional support
for the family should be
provided, including adequate
time to grieve with the child
after death is declared
World Brain Death Project2
Seek guidance from local ethical
team, legal team, and
administration
Attempt to handle requests to
forgo a BD/DNC evaluation or
continue organ support after
BD/DNC within a hospital
system before turning to the legal
system
It is reasonable to continue
support after BD/DNC for a finite
period, assuming the period is
brief and uniform and the family is
informed of the time frame in
advance, but this period should
not ordinarily exceed 48 hours
Families should be informed that
there will be no escalation of
treatment, including
cardiopulmonary resuscitation
Invite a second physician to
provide a second opinion
Provide a finite time for the family
to arrange transfer to another
facility
Organ support should be
discontinued if a hospital bed is
required for a living patient and
no other bed is available

BD/DNC = brain death/death by neurologic criteria.

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BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

measured arterial pH and carbon dioxide represent the values in the cerebral
circulation.2 Oxygenated blood can arise from native cardiac output (after gas
exchange in the native lungs) and mix with oxygenated blood from the ECMO
circuit. Therefore, when a patient is on venoarterial ECMO, arterial blood should
be sampled simultaneously from both the patient’s arterial catheter and the
ECMO circuit postoxygenator to ensure the pH and carbon dioxide in the
cerebral circulation exceed the BD/DNC thresholds.2 CASE 12-2 illustrates apnea
testing for a patient on venoarterial ECMO. The WBDP standard does not
address ancillary testing for patients on ECMO, but a 2020 review of the
literature noted that all the ancillary tests used in patients who are not on ECMO
have been used in patients on ECMO.21

DETERMINATION OF BRAIN DEATH/DEATH BY NEUROLOGIC CRITERIA

AFTER TREATMENT WITH THERAPEUTIC HYPOTHERMIA
Hypothermia can lead to reversible brainstem areflexia and coma, particularly
when it is used in conjunction with drugs or medications that depress the central
nervous system.2 In two cases in the literature, a declaration of BD/DNC was
made prematurely following treatment with therapeutic hypothermia.22,23
Despite this, aside from denoting a minimum temperature at which it is
acceptable to perform a BD/DNC evaluation, the 2010 AAN and 2011
SCCM/AAP/CNS standards, like most standards around the world, do not
provide guidance on the length of time necessary to delay performance of a
BD/DNC evaluation in a patient who was previously treated with therapeutic
hypothermia.1,2,10,12 To prevent false-positive declarations of BD/DNC after
treatment with therapeutic hypothermia, the WBDP standard delineates the
timetable to delay evaluation for BD/DNC in this setting.2 If the clinical
examination appears consistent with BD/DNC, neuroimaging is recommended
to assess for severe cerebral edema and brainstem herniation. It is
recommended to delay the evaluation for a minimum of 24 hours after
rewarming is complete or longer, depending on when the most recent
medication that could depress the central nervous system was administered.
As with all patients undergoing evaluation for BD/DNC, it is recommended to
wait at least 5 half-lives to ensure adequate clearance of medications that
depress the central nervous system, but a longer duration may be needed as
hypothermia can affect pharmacokinetics and pharmacodynamics. Clearance
can also be reduced because of concomitant hepatic or renal dysfunction. If
uncertainty exists regarding the residual effects of medications or effects due
to hypothermia, an ancillary study should be performed to assess for absence
of intracranial blood flow in addition to the complete clinical evaluation
and apnea test.2

COMMUNICATION ABOUT BRAIN DEATH/DEATH BY

NEUROLOGIC CRITERIA
Family education about BD/DNC should begin as soon as a practitioner believes a
patient might meet criteria for BD/DNC.24 In addition to being timely,
communication must be clear and consistent. Practitioners should be empathetic,
patient, and culturally sensitive during discussions about BD/DNC and recognize
that public understanding of BD/DNC is poor because of misinformation
promulgated by the media, television, and movies.25,26 The fact that BD/DNC is
legal death, equivalent to loss of function of the heart and lungs, should be

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explained. Examples of phrases to use during these discussions are included in KEY POINTS
FIGURE 12-2. Although practitioners should make reasonable efforts to inform a
● Hypothermia can lead to
patient’s surrogate/health care proxy about the intent to perform an evaluation reversible brainstem
for BD/DNC, the WBDP standard and guidance published by the AAN in areflexia and coma,
2019 note that consent is not required to complete a BD/DNC evaluation, particularly when it is used in
including apnea testing or ancillary testing.2,15 However, practitioners should be conjunction with drugs or
medications that depress
aware that families sometimes object to performance of an evaluation for
the central nervous system.
BD/DNC or discontinuation of organ support after BD/DNC for a number of
reasons, including distrust, hope that the patient will regain neurologic function, ● Practitioners should be
grief, guilt, and religious or moral belief that death does not occur until the heart empathetic, patient, and
stops beating.24,27 Objections should be handled in a consistent manner by culturally sensitive during
discussions about brain
practitioners in conjunction with a multidisciplinary team that includes social death/death by neurologic
workers, spiritual counselors, ethicists, palliative care specialists, hospital criteria and recognize that
administrators, and hospital lawyers, as appropriate (CASE 12-3). TABLE 12-6 public understanding of
reviews recommendations on communication about BD/DNC and strategies to brain death/death by
neurologic criteria is poor
employ if families object to BD/DNC evaluation.2,10,12 because of misinformation
promulgated by the media,
television, and movies.
CONCLUSION
● Although practitioners
BD/DNC determination is a nuanced process that must be performed
should make reasonable
thoughtfully and carefully to prevent false-positive declarations of death. efforts to inform a patient’s
Neurologists in the United States should be familiar with the 2010 AAN and 2011 surrogate/health care proxy
SCCM/AAP/CNS standards, which are the currently accepted standards for about the intent to perform
an evaluation for brain
BD/DNC determination pending publication of a uniform standard for the entire
death/death by neurologic
lifespan. They should also be aware of the content of the WBDP standard, criteria, the World Brain
which provides updated consensus-based guidance endorsed by five world Death Project standard and
federations and 27 medical societies from across the globe on numerous facets of guidance published by the
BD/DNC, including the science behind BD/DNC, the minimum accepted criteria American Academy of
Neurology in 2019 note that
for BD/DNC, BD/DNC evaluation for a patient on ECMO, BD/DNC evaluation consent is not required to
after treatment with therapeutic hypothermia, and management of requests to complete a brain
forgo a BD/DNC evaluation or continue organ support after BD/DNC.2 death/death by neurologic
criteria evaluation, including
apnea testing or ancillary
testing.
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OCTOBER 2021