This document discusses brain death, including its definition, criteria, and controversies. It begins by explaining how advances in medicine led to the development of neurological criteria for determining death. It then covers the anatomical and physiological basis of brain death, focusing on damage to the brainstem and reticular formation. The document outlines the clinical criteria for diagnosing brain death, including the absence of brainstem reflexes and apnea testing. It notes complicating factors and observation periods. The history and acceptance of brain death criteria internationally is reviewed. Some bioethical controversies are also presented, such as debates around the definition of death and higher brain formulations.

1. Brain Death- D r H i m a n s h u S on i

2. Introduction
• Death is both legal and medical question.
• Traditionally, death means simply documentation of loss
of vital signs. This is simpler to understand and is
accepted by relatives.
• Beginning of 20th century, medical science advanced to
the point that it was possible to sustain more and more
patients who had sustained irreversible brain damage.
• Then where were those whose cardiopulmonary
functions had been restored but who remained
profoundly and persistently unconscious and
unresponsive.
• This led to the development of guidelines for making
neurological based determinations of death.

3. Anatomical and Physiological Basis
• The brain-stem consists of the midbrain, pons and medulla.
• It contains the nuclei of last ten cranial nerves and ascending and
descending tracts.
• The reticular formation (RF) is a complex network of nuclei and
interconnecting fibers.
• The reticular activating system (RAS), which occupies the core of the brain-
stem, provides the anatomical and physiological basis for wakeful
consciousness.
• The medullary RF contains the vital centers controlling the heartbeat,
breathing and circulation.
• The pontine RF contains centers for coordination of acoustic, vestibular,
respiratory and cardiovascular processes.
• The midbrain RF contains centers for visuospatial orientation and eating
behavior.
• As brain-stem is structurally and functionally very compact, even small
lesions can destroy vital cardiac and respiratory centers; disconnect cerebral
cortex from brain-stem; damage sensory fibers from higher centers of
consciousness, perception and cognition.
• Damage to RF may lead to loss of cognition, persistent unconsciousness
and coma.

4. Role of Cerebral Cortex in
Consciousness
• Consciousness consists of
• Wakefulness – a function of RF
• Awareness of oneself and surroundings – a function of
cerebral cortex.
• Cerebral cortical function can be assessed by
EEG.
• Absence of CC function can also be determined
by a lack of verbal response and lack of
spontaneous or coordinated eye movements.
• Absence of cerebral circulation is also indicative
of cortical death.

5. Causes and Pathophysiology
• Most common causes
• Head injury
• SAH
• Ischemic stroke
• Others
• ICH
• Hypoxic ischemic encephalopathy
• They cause neuronal damage, leading ot edema and
increase in ICP.
• Raised ICP reduced CPP and CBF.
• The decreasing cerebral perfusion and increasing ICP
form a vicious cycle until blood no longer enters the
cranial cavity and transtentorial herniation and coning at
foramen magnum occurs.
• This herniation crushes the brain stem.

6. Criteria
• Patient should be deeply comatose (due to
irreversible brain damage of known etiology)
• Exclude reversible causes of coma
• Patient should be on a ventilator because of the
cessation of spontaneous respiration
• Exclude neuromuscular blocking agents as a cause of
respiratory failure

7. • All brain-stem reflexes should be absent
– Pupillary light reflex
– Pupils are dilated, fixed and donot react to light
– Doll’s head eye movements (oculocephalic reflex)
– Absence of conjugate deviation of eyes when head is fully
rotated to one side. Performed only when there is no fracture or
instability of the cervical spine.
– Corneal reflex is absent.
– No motor response to stimulation within any cranial
nerve distribution (eg. No response to supraorbital
pressure)

8. – No Gag (pharyngeal) reflex
– To stimulation of pharynx
– No Cough reflex
– To suction catheter in the trachea
– Vestibulo-occular reflex (oculovestibular or Caloric
testing) is absent
– No eye movements after installation of 50ml of ice cold water into
each EAM for 1 min, done after ruling out TM perforation
– Apnea test
– Absence of respiratory movements after disconnection from the
ventilator for sufficient duration to have PCO2 risen above
threshold (60mmHg) for stimulating respiration

9. Apnea test
– Elevating PaCO2 increases ICP which could precipitate
herniation and vasomotor instability, this test should be
reserved for last and only used when the diagnosis is
reasonably certain.
1. apnea for > 2 minutes with PaC02 > 60 mm Hg or PaC02 > 20 mm Hg
over baseline or pH< 7.3 (C02 is the most potent stimulus for
respirations). If patient does not breathe by this point, they won't
breathe at a higher PaC02 ( Not valid with
severe COPD or CHF)
2. to prevent hypoxemia during the test (with the danger of cardiac
arrhythmia or myocardial infarction):
• precede the test with 15 minutes of ventilation with 100% F10 2
(pre-oxygenation)
• prior to the test, adjust the ventilator to bring the PaC02 ... 40 mm Hg
(to shorten the test time and thus reduce the risk of hypoxemia)
• during the test, have passive 0 2 flow administered at 6 Umin
through either a pediatric oxygen cannula or a No. 14 French tracheal
suction catheter (with the side port covered with adhesive tape) passed
to the estimated level
ofthe carina

10. 1. starting from normocapnea, the average time to reach PaC02 = 60 mm Hg is 6
minutes (classic teaching is that PaC02 rises 3 mm Hg/min, but in actuality this
varies widely, with an average 3.7 ± 2.34; or 5.1 mm Hg/min if starting at
normocarbia5). Sometimes as long as 12 minutes may be necessary
2. the test is aborted prematurely if:
• the patient breathes: incompatible with brain death
• significant hypotension occurs
• if O2 saturation drops below 80% (on pulse oximeter)
• significant cardiac arrhythmias occur
3. if patient does not breathe, send ABG at regular intervals and at the completion
oftest regardless of reason for termination. Ifthe patient does not breathe for at
least 2 minutes after PaC02 > 60 mm Hg is documented, then the test is valid
and is compatible with brain death
4. ifthe patient is stable and ABGs results are available within a few minutes, the apnea
challenge may be continued while waiting for results in case the PaC02 is< 60)
5. ifPaC02 stabilizes below 60 mm Hg and the p02 remains adequate, try reducing
the passive 0 2 flow rate slightly (02 flow may be washing out C02)

11. Complicating conditions
• Hypothermia : core temp should be >32.2 (90 F).
• Below this, pupils may dilate and get fixed, respiration is
difficult to detect and recovery is possible.
• Remedial exogenous or endogenous intoxication,
incl. Drugs or metabolic
• Barbiturates, benzodiazepines, meprobamate, methaqualone,
trichloroethylene, paralytics, hepatic enceph, hyperosmolar
coma ... )
• If doubt exist, lab tests incl drug levels (serum and urine) may
be sent.
• Pseudocholinesterase deficiency is present in 1/3000 patients
which cause succinylcholine to last upto 8 hours (instead of 5
min).
• A twitch monitor can rule-out NMB ( place electrodes
immediately behind the eye or across the zygomatic arch)

12. • Shock and anoxia
• SBP should be >= 90 mmHg
• Loss of >45% of circulating blood volume can produce
lethargy.
• Immediately post-resusciation
• Shock and anoxia fixes and dilated pupils
• Atropine cause slight dilatation but NOT unreactivity.
• NM blockage for intubation does NOT affect pupils coz they
lack nicotinic receptors.
• Patients coming out of pentobarbital coma (wait
until level <=10mcg/ml)
• Confirmatory tests are not required, but may be
used as determined by the physician or in case of
discrepancy between the physicians.

13. Observation periods
• In presence of overwhelming brain damage from an
irreversible condition, some experts pronounce death
following a single valid examination in cunjunction with a
clinical confirmatory test.
• If an irreversible condition is well established + clinical
confirmatory tests are used : 6 hours
• If an irreversible condition is well established, but NO
tests are used : 12 hours
• If diagnosis is uncertain and NO tests are used : 12-24
hours
• If anoxic injury is the cause of brain death : 24 hours
(may be shortened if cessation of CBF is demonstrated )

14. Clinical confirmatory tests
• Cerebral angiongraphy
• Absence of intracranial flow at the level of carotid
bifurcation or circle of Willis.
• Filling of the Superior Sagittal Sinus may occur in a
delayed fashion.
• Not routinely used in the diagnosis of brain death.
• EEG
• Can be done bedside
• Requires expert interpreter.
• Doesnot detect brainstem activity and electrocerebral
silence (ECS) doesnot exclude possibility of reversible
coma.
• Atleast 6 hours observation is recommended in conjuction
with ECS.

15. • Cerebral Radionuclide Angiogram (CRAG)
• Performed bedside with general purpose scintillation
camera with low energy collimator.
• May not detect minimal blood flow to the brain, especially
brain stem
• Therefore 6 hours observation with CRAG is
recommended, unless there is a clear etiology of
overwhelming brain injury (eg massive h’hage )
• Transcranial Doppler
• Small peaks in early systole without diastolic flow or
reverbrating flow (indicative of significantly increased ICP)
• Initial absence cannot be used as criteria since 10%
patients donot have temporal insonation windows.

16. • SSEPs
• Bilateral absence of N20-P22 response with median
nerve stimulation
• Atropine
• 1mg atropine should not affect the heart rate due to
absence of vagal tone.
• However, not useful in some conditions such as GBS

17. Brain death in children
• Assumption (not proven clinically) that a child’s
brain is more resilient makes the determination
of brain death more difficult.
• Following guidelines for patients <5 years age.
– Not applicable to a premature infant
– Determination of proximate cause of coma should
be made to ensure absence of remedial condiitons;
especially toxic and metabolic disorders, sedatives,
paralytics, hypothermia, hypotension and surgically
treatable conditions.

18. Criteria
• Coma and apnea must coexist
• Complete loss of consciousness
• Vocalization and
• Volitional activity
• Absence of brainstem function
• Midposition or fully dilated pupils, unresponsive to light (R/O
drug effects )
• EOM : absence of spontaneous, doll’s eyes and caloric
movements
• Absence of bulbar musculature movement; incl.
Oropharyngeal and facial muscles; absence of corneal, gag,
cough, suck and rooting reflex.
• Absence of respiratory movement (tested after other criteria
met)
• Flaccid tone and absence of spontaneous or induced
movements (spinal myoclonus and spinal cord movements eg
reflex withdrawl are not included)

19. • Observation periods
– Newborns at or after term : 7 days
– 7days to 2 months : 2 examinations and 2 EEG 48
hours apart (repeat not necessary if CRAG
negative)
– 2-12 months : 24 hours apart
– >12 months : if irreveresible condition exists, lab
testing not necessary and 12 hours sufficient
– Unclear condition like HIE are difficult to assess and 24 hours
required unless ECS + or CRAG –ve.
• Confirmatory tests
– EEG or CRAG (>2mo)

20. History
• 1959, Mollaret and Guolon, coined the term “coma de’ passe’” (a
state beyond the coma) for an irreversibel state of apneic coma with
absent brain stem reflexex and EEG activity but with preserved
cardiac and metabolic activities. If the ventilation were stopped, the
cardiac arrest would follow.
• 1963, Guy Alexender used theis criteria, for procuring kidney for
transplant.
• In 1968, an Ad Hoc Committee of Harvard Medical School on
Brain Death published a landmark report, “the definition of
irreversible coma.” It defined the criteria for determining brain death
as apneic coma and absence of elicitable brain-stem reflexes for a
period of 24 h as confirmed by an electroencephalogram.
• The committee proposed a whole-brain formulation to define death. A
major aim of Harvard criteria was claimed to be the avoidance of
prolonged futile life-support and promoting death with dignity. After
this report, brain death was widely accepted.

21. • Focusing on the brain-stem function, the Conference of Medical
Royal Colleges in the UK published a breakthrough code for the
determination of “brain death” (brain-stem death) in 1976.[21] In a
subsequent memorandum, it equated brain-stem death with death of
the whole person.[22] The code requires confirmation of the
“irreversible loss of the capacity for consciousness combined with the
irreversible loss of the capacity to breathe.”
• In 1981, the US President’s Commission published a lanrmark report
on the ethical and legal implications of defining death and presented
conceptual basis for whole brain death
• It defined death as “ the permanent cessation of functioning of
the organism as a whole” and the criterion as “the permanent
cessation of functioning of the entire brain”.
• It is known as the somatic disintegration hypothesis – that after the
brain death, cardiopulmonary death quickly follows despite continued
intensive care.

22. • Most nations adopted either whole brain death or
brainstem death criteria.
• In 1995, AAN published parameters for diagnosis
of brain death.
• Irreveresible coma , with known cause
• Absence of brain stem reflexes
• Irreversible apnea.
– The diagnosis is clinical and supplementary tests to be
used in presence of confounding factors.
• 15 years later, AAN issued an evidence based
guideline updated in 2010, concluding no
published reports of recovery of neurologic
function after the diagnosis based on the above
criteria.

23. Bioethics and controversies
• Shewmon and others point out that certain areas are
intact and rudimentary EEG activity is retained in brain
death criteria.
• US President’s Commission, argued that isolated
metabolic or electrical activity in dispersed cells
cannot be a sign that a patient is still alive.
• However, cessation of pituitary function is inconsistent
with the above definition, arguments have been that
pituitary blood flow arises from extracranial sources,
which is preserved in raised ICP.
• Bernat revised both
• Organismic definition to “permanent cessation of the critical functions
of the organism as a whole” and
• Corresponding standard to permanent cessation of critical functions
of the whole brain.

24. • Gray areas are
– Integrative role of brain, counter arguments are that
integration is an emergent function of the organism and
brain functions only as a modulator.
– Inner drive to breathe, is absent also in lower brain stem
lesions and hence cannot be considered a necessary
feature of organismic wholeness.
– Self development and self maintainence as a
fundamental vital work of a living organism, is counter
argued as that an embryo fulfills definition of death, yet
it is unquestionably alive.

25. Higher brain formulation
• Bernat point out “profound locked in syndrome”
where awereness might be retained in absence of
brain stem activity.
• A third formulation, “higher brain formulation” is
proposed by Veatch. It is based on another
definition as “ irreversible loss of personhood”.
• Argue as permanent unconsciousness and loss of
cognition negated personhood and that law should
equate death with loss of Higher brain functions.
• The problem with this is that persistent vegetative
state and anencephalic neonates are dead by this
definition.

26. Indian context
• 1994, Transplantation of Human Organs (THO) Act was
passed which legalizes brain stem death.
• 1995, rules were laid down describing brain stem death
certification procedure.
• Underlines responsibilities of hospitals registered under THO
Act, i.e. Authorized transplant centers.
• Since most brain stem death occurs in non-transplant
hospitals, it makes Director of Health Services, authorize to
register all hospitals in the state that have an operation
theatre and ICU as Non Transplant Organ Retrieval Centers
(NTORCs).
• These hospitals are permitted to certify brain death as per
procedure and conduct organ retrieval.
• Its mantatory for all NTORCs and ATCs to certify and notify
the brain death cases to the Zonal Transplantation Co-
ordination Committee.

27. Diagnosis of Brain Stem Death in
India
• THO 94 and THO rules 95 are the only laws
where in brain death certification procedures
are laid down.
• Form 8 of THO Act and Rules prescribed as
Brain Death Certification Format is to be utilised
to certify brain stem death.

28. • Who should diagnose ??
• Team of four medical experts including
• Medical administrator in charge of the hospital
• Authorized specialist
• Authorized Neurologist/NeuroSurgeon
• Medical Officer treating the patient.
• Amendments in the THO Act (2011) allowed
selection of a surgeon/physician and an
anesthetist/intensivists, in the event of the
nonavailability of approved
neurosurgeon/neurologist.

29. Time of Death
• The time of the completion of the last
confirmatory test.

30. Thank you
“concern for man and his fate must always form
the chief interest of all technical endeavours.
Never forget this in the midst of your diagrams
and equations.”
- Albert Einstein