1. Brain death is defined as the irreversible loss of all brain function, including the brainstem. The three essential findings are coma, absence of brainstem reflexes, and apnea on testing. 2. Common causes of brain death include traumatic brain injury, intracerebral hemorrhage, hypoxic-ischemic injury from cardiopulmonary arrest. A thorough exam is required to determine the cause and rule out potential confounders. 3. Evaluation of brain death involves assessing for coma, absence of brainstem reflexes on exam, and a positive apnea test showing lack of respiratory drive and rising CO2 levels. Ancillary tests like angiography or EEG can also be

1. MR. ASHISH YADAV
MASTERS(RESPIRATORY THERAPY)
BRAIN DEATH

2. Altered state of Consciousness
Consciousness - The quality or state of being aware especially of something within oneself.
Sleep - Normal state of unconsciousness with prompt reversibility on threshold sensory
stimulus and maintain wakefulness following recovery.
Stuporous - a chiefly mental condition marked by absence of spontaneous movement,
greatly diminished responsiveness to stimulation, and usually impaired consciousness (
unresponsiveness from which a person can be aroused only by vigorous, physical
stimulation).
Coma - is a deep state of unconsciousness in which patient cannot be aroused even to
the stimulation pressure on supraorbital nerve, sternum , nail bed or temporo -
mandibular angle of the mandible.
Locked in state - Locked-in syndrome is a rare neurological disorder in which there is
complete paralysis of all voluntary muscles except for the ones that control the
movements of the eyes.

3. Altered state of Consciousness
Persistent vegeatative state -
● Also know cerebral state.
● Normal sleep- wake cycles.
● No response to environmental stimuli
● Diffuse brain injury with brain stem
function.

4. Definition.
Brain death is defined as the irreversible loss of all functions of the
brain, including the brainstem.
● The three essential findings in brain death are -
❖ Coma.
❖ Absence of brainstem reflexes,
❖ Apnoea.
An evaluation for brain death should be considered in patients who
have suffered a massive, irreversible brain injury of identifiable cause.
A patient determined to be brain dead is legally and clinically dead.

5. Etiology
● Brain death occurs after the destruction of enough neuronal cells in the brain that
there is both an irreversible loss of consciousness (coma) and the absence of
brainstem reflexes, including the inability of the lungs to inhale and exhale without
external positive pressure support (apnea).
In adults and children, the precipitant of brain death is either from an intracranial or
extracranial cause.
● First, we have to establish an acute and irreversible cause.
➔ Extracranial brain injury- as seen in patients post cardiopulmonary arrest with
delayed resuscitation causing prolonged cessation of brain blood flow. cerebral
oxygenation is still severely impaired by the catastrophic injury at the cellular level
leading to brain death.
➔ Intracranial brain injury -as seen in traumatic brain injury and intracerebral
hemorrhage, can cause an elevation in intracranial pressure and impairment of brain
oxygenation, as mentioned above.

6. Etiology
● Identification of history or physical examination findings that
provide a clear etiology of brain dysfunction.
The determination of brain death requires the identification of the
proximate cause and irreversibility of coma.
❖ Severe head injury,
❖ Hypertensive intracerebral hemorrhage,
❖ Aneurysmal subarachnoid hemorrhage,
❖ Hypoxic-ischemic brain insults and
❖ Fulminant hepatic failure are potential causes of irreversible
loss of brain function.
The evaluation of a potentially irreversible coma should include, as
may be appropriate to the particular case; clinical or neuro-imaging
evidence of an acute CNS catastrophe that is compatible with the
clinical diagnosis of brain death;

7. Etiology
● However, in children, the most common cause is non-
accidental trauma.
● The extracranial cause of brain death is most commonly
cardiopulmonary arrest with inadequate cardiopulmonary
resuscitation.
● One has to exclude the presence of any drugs or poisoning
in the system.
● This can be accomplished by history, drug screen, etc.
● A thorough lab testing is to be done to exclude severe
endocrine, acid-base, and electrolyte disturbances

8. Irreversible coma
Exclusion of any condition that might confound the subsequent
examination of cortical or brain stem function. The conditions that may
confound clinical diagnosis of brain death are:
1. Shock/ hypotension.
2. Hypothermia -temperature < 32°C.
3. Drugs known to alter neurologic, neuromuscular function and
electroencephalographic testing, like-
❖ anaesthetic agents, barbiturates
❖ neuroparalytic drugs, benzodiazepines
❖ Methaqualone
❖ High dose bretylium, amitryptiline, meprobamate,
trichloroethylene, alcohols.

9. Irreversible coma
4. Brain stem encephalitis.
5. Guillain-Barre syndrome
6. Encephalopathy associated with hepatic
failure, uraemia and hyperosmolar coma
7. Severe hypophosphatemia.

10. Pathophysiology
● The physiology of brain death is similar regardless of the etiology.
● Inadequate tissue oxygenation leads to a progressive cascade of further edema, increasing intracranial
pressure, a further decrease in cerebral perfusion and eventual herniation, or complete cessation of blood
flow and aseptic necrosis of brain tissue.
● In anoxic brain injuries, mainly inadequate cardiopulmonary resuscitation following a cardiopulmonary
arrest, tissue hypoxia leads to the release of cytotoxic material that leads to progressive cerebral edema,
and eventually, the cascade described above.
● For traumatic brain injuries or other intracranial injuries, the presence of increasing intracranial pressure
as a result of injury beyond the mean arterial pressure will prevent adequate oxygenation of neuronal
tissues.
● This situation will result in further injury, edema, and, eventually, the process

12. Evaluation
Before deciding to proceed with the diagnosis of brain death, several
conditions must be evaluated and met:
● Ensure no recent neuromuscular blocking agents have been
administered.
● There must be a waiting period of five times the drug half-life, or drug
plasma levels should be below the therapeutic range.
● Drug screen to ensure no central nervous system (CNS) depressants are
present.
● Normal core temperature must be present greater than 36 C.
● Normal systolic blood pressure must be greater than 100 mmHg.
Vasopressors may be administered if necessary.
● No severe electrolyte, acid-base, or endocrine disturbance must be
present.

13. Performance of a complete neurological examination.
Examination of the patient-absence of -
○ Spontaneous movement,
○ Decerebrate or decorticate posturing,
○ Seizures.
○ Shivering
○ Response to verbal stimuli,
○ Response to noxious stimuli administered through a cranial
nerve path way.

14. Brain stem reflexes - Pupils Response.
● Loss of pupillary reflex (light reflex): Pupils
should be fixed in mid-size or dilated (4 to 9
mm) and not reactive to light; a magnifying
glass can be used to evaluate further.
● Absent pupillary reflex to direct and
consensual light; pupils need not be equal or
dilated. The pupillary reflex may be
selectively altered by eye trauma,
cataracts, high dose dopamine,
glutethamide, scopolamine, atropine,
bretilium or monoamine oxidase
inhibitors.

15. Brain stem reflexes - Doll's eye
Eye motion is lost in reaction to head movement "doll's eye").

16. Brain stem reflexes - Loss of corneal reflex
Loss of corneal reflex determined by
using a cotton swab or drops of
water/normal saline.
The corneal reflex is tested by closure of the
eyelids in response to irritation of the
cornea by touching with a sterile cotton
applicator. It involves afferent impulses
transmitted by the trigeminal nerve and
efferent motor impulses via the facial nerve.
Look for blinking of the eyes for the
normal stimulus response.

17. Brain stem reflexes - Oculovestibular reflex (Caloric test).
● Loss of oculovestibular reflex
(Caloric test). The test requires a
cervical spine integrity check and
head elevation at 30 degrees.
● Irrigation of each ear by 50 to 60
ml of ice water won't move the
eyes towards the irrigated side
within 1 minute of the test
performed.
● Each ear should be irrigated after a
pause of a couple of minutes.

18. Brain stem reflexes - Gag reflex
● Loss of gag reflex confirmed
after stimulation of bilateral
posterior pharyngeal
membranes.

19. Brain stem reflexes - Cough
reflex
● Loss of cough reflex confirmed
after tracheal suctioning.

20. APNEA TEST
● Vasopressors should be adjusted to maintain a systolic blood pressure
≥100 mm Hg.
● Preoxygenate is given for at least 10 minutes with 100% fraction of
inspired oxygen (FiO2) to a partial pressure of oxygen, arterial (PaO2)
greater than 200 mmHg.
● Reduce ventilator frequency to 10 breaths per minute.
● Reduce positive end-expiratory pressure to 5 cm H2O.
● If the peripheral capillary oxygen saturation (SPO2) remains greater
than 95%, obtain baseline blood gas.
● Disconnect the patient from the ventilator, preserve oxygenation with
oxygen delivered through insufflation tubing given at 100% FiO2 at 6
L/min near the level of the carina through the endotracheal tube.

21. APNEA TEST
● Look for respiratory movements for 8 to 10 minutes.
● If no respiratory drive is observed, repeat blood gas at approximately 8
minutes.
● If no respiratory movements are observed and partial pressure of carbon
dioxide (PCO2) is greater than 60 mmHg or 20 mm Hg increase in PCO2
over a baseline normal PCO2, the apnea test result is positive.
● For patients on extracorporeal membrane oxygenation (ECMO) machines,
oxygenation can be maintained while performing the apnea test by
decreasing the gas sweep flow rate to 0.5 to 1.0 L/min and using an
oxygenation source through the endotracheal (ET) tube
If the above list is completed, and coma, the absence of brainstem
reflexes, and a positive apnea test are present, the diagnosis of brain
death can be made.

22. The apnea test has to be aborted if:
● There is any respiratory movement (abdominal or chest
excursions or brief gasp)
● Systolic blood pressure decreases to <90 mm Hg
● Oxygen saturation is less than 85% for more than 30 seconds. If
so, the procedure has to be retried with T-piece, maintaining a
continuous positive airway pressure (CPAP) 10 cm H2O, and
administration of 100% O2 at 12 L/min

23. Ancillary Tests
Cerebral angiography: Four vessel angiography is considered the gold standard for tests that evaluate cerebral
blood flow. It can confirm brain death when it shows cessation of blood flow to the brain. Limitations include
invasiveness of the test and transferring the patient to the radiology suite. Also, the contrast may induce
nephrotoxicity affecting the donor's kidney. False-negative tests can occur when ICP becomes lowered by
surgery, trauma, or ventricular shunts.
Transcranial ultrasound: Can be used to assess pulsations of middle cerebral arteries, vertebral and basilar
arteries bilaterally, also anterior cerebral arteries or ophthalmic arteries if possible. The transcranial US can
confirm brain death by showing small peaked systolic pulsations or the absence of diastolic pulsations. Test
limitations include the examiner's expertise, the presence of unsuitable windows due to thick temporal bones,
as well as lowered ICP by surgery or ventricular shunts giving false-negative tests.

24. Ancillary Tests
Computed tomogram (CT) brain angiography and MR angiography show cessation of cerebral blood flow.
Radionuclide brain imaging: This can be done using a 99mTc-labeled hexamethyl propylene amine oxime
(HMPAO) isotope tracer then imaging by single-photon emission computed tomography (SPECT) brain
scintigraphy. The absence of a tracer in the brain circulation (the hollow skull phenomenon) is consistent with brain
death. The test may show false-positive results if imaging is done in one plane only instead of two planes (anterior
and lateral).
Electroencephalography: Brain death confirmed by documenting the absence of electrical activity during at least
30 minutes of recording that adheres to the minimal technical criteria for EEG recording in suspected brain death as
adopted by the American Electroencephalographic Society, including 16-channel EEG instruments. The ICU setting
may result in false readings due to electronic background noise creating innumerable artifacts.

25. Management.
Angle head of the bed ≥ 30 degrees
This facilitates easier displacement of venous cerebral blood into the systemic
system and cerebral CSF into the spinal region via gravity drainage
It is important to ensure that the head of the patient does not tilt to one side, thereby
blocking effective drainage of venous blood
Cause rectification
● There are many causes that can result in increased ICP including:
○ Oedema and swelling that requires time to decrease
○ Intracranial haemorrhage that requires immediate surgical evacuation if it is
large or time to reabsorb if it is smaller
○ Brain tumour that requires surgical intervention to remove, if possible
Temperature control
Maintain temperature between 35 – 37 degrees to reduce cerebral metabolic
demands

26. Seizure prophylaxis
● Increased ICP can lead to an increased risk of seizures
● Seizures further increase ICP and cerebral metabolic demands and therefore should be actively prevented, if
possible.
Fluid status and electrolytes
● Maintain even balance for the patient and ensure that electrolytes are within their normal ranges
● If intravascular filling is required, colloids should be avoided due to studies showing an increased mortality
when used in patients with neurological pathophysiology
● Cerebral oedema can be reduced by utilising Mannitol to shift fluid from the intracellular cerebral tissue
into the intravascular space, which can then be removed from the body by utilising a diuretic such as
Frusemide.
Perfusion and pressures
● Maintain the following pressures within the body:
○ MAP ≥ 60
○ ICP ≤ 20
○ CPP ≥ 60

27. Sedation and analgesia
This reduces the increased ICP and cerebral metabolic demands associated with increased levels of
consciousness/anxiety/pain/endotracheal tube intolerance etc
Ensure the patient is disturbed as little as possible and that all interventions potentially increasing cerebral metabolic
demands are grouped together
Breathing
● Maintain carbon dioxide levels between 35 – 40 mmHg in order to reduce the cerebral vasodilation associated
with hypercapnia
● By avoiding excessive cerebral vasodilation, cerebral venous blood will be more easily displaced as it will not
pool within the brain vault
● Maintain partial pressures of oxygen (PaO2) ≥ 60 to ensure adequate oxygenation to aid with cerebral perfusion
Decompressive therapy
● If the pathophysiological process of the secondary brain injury is too severe, additional interventions may be
required to help with compensation:
● The insertion of an external ventricular drain (EVD) via a ventriculostomy to help drain excess CSF from the
brain vault and additionally monitor ICP
● A craniotomy to remove a portion of the skull to allow for excessive swelling of brain tissue

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