1. Brain Death
Shawn Ng

2. • ANZICs Statement on death and organ
donation Edition 3.2 (2013)

3. CICM Fellowship exam /2012
With regards to the determination of brain death:
1. Apart from identifying evidence of sufficient intracranial pathology, list the
preconditions that must be met prior to the determination of brain death by clinical
criteria:
2. What is the recommended minimum time for observation in cases of hypoxic-
ischaemic brain injury, prior to performing clinical testing of brain-stem function?
3. For each of the following brainstem reflexes, list the cranial nerves that are tested:
a. Cough reflex
b. Vestibulo-ocular reflex
c. Pupilary light reflex
d. Corneal reflex
e. Gag reflex
4. List three contraindications to performing apnoea testing:
5. List the acceptable imaging techniques that may be used to demonstrate brain
death as an alternative to clinical testing as recommended by the ANZICS Statement
on Death and Organ Donation

4. Which of the following precludes
certification of death by clinical brain
death testing?
• A) Flexion of the right elbow on painful
stimulus within the cranial nerve distribution
• B) Unilateral hemotympanum
• C) No family consent
• D) Isolated Brainstem infarction without
cerebral injury
• E) Avulsion of one eye

5. Brain Death
• Brain death occurs in the setting of a severe brain
injury associated with marked elevation of
intracranial pressure.
• Inadequate perfusion pressure results in a cycle
of cerebral ischaemia and oedema and further
increases in intracranial pressure.
• When intracranial pressure reaches or exceeds
systemic blood pressure, intracranial blood flow
ceases and the whole brain, including the brain-
stem dies.

6. • Determination of brain death requires that
there is unresponsive coma, the absence of
brain-stem reflexes and the absence of
respiratory centre function.
• These findings are irreversible.
• In particular, there must be definite clinical or
neuro-imaging evidence of acute brain
pathology consistent with the irreversible loss
of neurological function.

7. • Brain death cannot be determined without evidence of
sufficient intracranial pathology.
• Cases in which brain-stem has been the primary site of
injury and death of the brain-stem has occurred
without death of the cerebral hemispheres.
• Thus brain death cannot be determined when the
condition causing coma, and loss of all brain stem
functions has affected only the brain stem, and there is
still blood flow to the supratentorial part of the brain.
• Whole brain death is required for the legal
determination of death in Australia and NZ. (cf to the
UK.)

8. • The 3 essential findings in brain death are
– Coma(unresponsiveness)
– Absence of brainstem reflexes
– Apnoea

9. Brain death determination
• Clinical testing if preconditions are met
• Imaging that demonstrates the absence of
intracranial blood flow.
• There is no documented case of a person who fulfills the preconditions
and criteria for brain death ever subsequently developing any return of
brain function.

10. Determination of Brain death by
clinical examination
• Preconditions
– Evidence of sufficient intracranial pathology
• ALL the following preconditions must be met if brain
death is to be determined by clinical examination.
– cause for coma consistent with brain death
– at least 4 hours of observation during which preconditions
must be met (GCS 3, pupil non-reactive, no cough, apnoea)
– neuro-imaging consistent with acute brain pathology that
could cause brain death
– normothermia (T>35C)

11. Brain death preconditions
• normotension (SBP>90 or MAP>60mmHg in an adult)
• no sedation or analgesia (dependent on types of drugs
used, renal and hepatic function; use antagonists if
concerned)
• absence of severe electrolyte, metabolic and endocrine
disturbances (glucose, Na+, PO43-, Mg2+, renal and hepatic
function)
• no paralysis (use NMJ monitor or electromyography if
concerned)
• ability to assess brain stem reflexes (at least one eye and
ear)
• ability to perform apnoea test (doesn’t have severe hypoxic
respiratory failure or have a high cervical spine injury)

12. • In cases of acute hypoxic ischaemic brain injury, clinical
testing for brain death be delayed for at least 24 hours
subsequent to ROSC.
• Therapeutic hypothermia may modify outcome
prediction after cardiac arrest.
• It is therefore recommended when induced
hypothermia has been used after resuscitation from
cardiorespiratory arrest that clinical testing for brain
death be delayed for at least 24 hours AFTER
rewarming.
• Brain death may be determined PRIOR to 24 hours by
demonstration of absent cerebral blood flow.

13. Brain death examination

14. “It’s about testing connections”
• GCS 3 – no response in CN distribution (supraorbital
compression) and deep nail bed pain in all four limbs
• !!Spinal reflexes may be present in patients with brain
death
• Observations that are incompatible with brain death
– Decerebrate/decorticate posturing
– True extensor or flexor motor responses to painful stimuli
– Seizures

15. Brain Stem Reflexes testing
ALL MUST BE ABSENT
• pupils fixed, no reaction to light (CN II, III) –
must be > 4mm
• !! Anticholinergic drugs such as atropine can
cause pupillary dilatation
• Cataract or iris surgery is not a CI for clinical
testing

16. • no corneal reflex (CN V, VII)
• !! Touching the sclera is not sufficient

17. • Reflex response to pain in the trigeminal nn
distribution- CN V-VII

18. • no oculo-vestibular reflexes (CN III, IV, VI, VIII)
• !! Ruptured eardrums does not invalidate test
• # to BOS or petrous temporal bone may
obliterate the response on the side of the #
• Testing for the oculocephalic reflex – submaximal
stimulus/aggravate spinal injury

20. • no gag (CN IX, X)

21. • no cough (CN X)
• !! Efferent nerves are the phrenic/innovation
of the thoracic and abdominal musculature.
Therefore it cannot be assessed in patients
with high cervical cord injury.

22. • positive apnoea test (after preoxygenation,
and pH 7.3, no breath taken after
disconnection from ventilator with a PaCO2 >
60mmHg; or increase in PCO2 by 20 mmHg if
COPD/ CO2 retainer)
Apnoea test

23. • independent examination by 2 suitably trained
and experienced doctors
• can be sequential (don’t have to wait 2 hours
between testing)
• time of death is the time of completion of the
second examination

24. Brain Death Investigations
• the indication for cerebral perfusion imaging is
when clinical brain death can not be
determined (any of the preconditions can not
be met)
• an investigation showing absent cerebral
parenchymal blood flow is required

25. • Problematic in
– Infants
– Massive skull fractures
– Craniotomy with extensive bone removal

26. Imaging
• 4 vessel angiogram
• Tc-99 HMPAO SPECT radionuclide
• CT angiography
• Transcranial doppler (TCD)

27. Other ancillary tests
• Cerebral Perfusion Scintigraphy
• XeCT
• MRAngiography
• MR perfusion

28. ANZICS recommendation
• 4 vessel angiography
• Radionuclide imaging
• CT A may be acceptible, although experience
in the technique is limited.
• MRI and TCD are not recommended.

29. 4 vessel cerebral angiography
• Gold standard of confirmatory tests.
• No false positives reported.
• False negative examinations may occur if
– No significant elevation of the ICP
– Contrast is injected too vigorously into the
downstream circulation, thereby artifactually
opacifying the intracranial vasculature. (?screen
with TCD)

30. 4 vessel angiography
• Advantages
– Able to visualise cerebral and posterior fossa
blood flow
– Gold standard
• Disadvantages
– Invasive
– Expensive
– Exposed donor to toxic contrast material
– False negatives

31. 4 vessel angiography

32. Tc-99 HMPAO SPECT radionuclide
• Absence of intracranial perfusion.
• IV bolus of radioactive material Crosses BBB to
be retained in the parenchyma
• There are occasional technical failures due to
inadequate bolus injection of the
radiopharmaceutical.
• Single Photon Emission CT(SPECT) provides
superior imaging in adults and in children Vs
2-planar imaging

33. • Advantages:
– ?Ability to detect blood flow patients who are in a
coma due to drug intoxication.
• Disadvantages:
– Posterior fossa circulation not evaluated
– Occasional technical failure- inadequate bolus
injection of the radiopharmaceutical.

34. Empty skull sign

35. CT angiography
• Small studies have shown absent enhancement
bilaterally of peripheral intracranial arteries and central
veins on CTA at 60 secs. There should be absent
enhancement bilaterally on ALL these
– MCA cortical branches- that is beyond the sylvian branches
– P2 segment of the posterior cerebral arteries
– Pericallosal arteries
– Internal cerebral veins
• to perform this examination, the potential risk of
contrast-mediated tissue injury is still present

36. CT angiography
• No large studies with matched controls
• When compared to clinical testing for brain
death, the CTA test had a sensitivity of 0.85
• (Cochrane systematic review -The use of
computed tomography angiography (CTA) to
confirm the clinical diagnosis of brain death
Taylor et al 31.3.2014

37. CT angiography
• Advantages
– Cheap, easily accessible
– Only needs IV access
• Disadvantages
– Low overall sensitivity-0.85
– Contrast mediated toxicity to donor organs

38. Transcranial Duplex US
• Classical findings in a patient who is brain
dead are short systolic spikes or peaks,
oscillating movement of blood within the
assessed arteries, and disappearance of
systolic flow on subsequent testing when
previously documented as present
• TCD is not considered an accurate and reliable
ancillary test in the confirmation of brain

39. • Advantages
– Easily accessible, portable
– Relatively inexpensive
– No contrast agents
• Disadvantages
– Lack of validation. Many false positives and
negatives
– 20%- thick cranium
• Used as a screening tool

40. Brain Death Controversy
• Controversial
• ?non acceptance of brain death as death.
• The idea that irreversible loss of brain function is
a sufficient condition for the certification of
death?
• Ariel Sharon? 8 years- vegetative state.
– fMRI – response to stimuli from family?
• Jahi McMath?

42. One case study of reversible brain
death.
• One case study
• “reversible brain death after cardiopulmonary
arrest and induced hypothermia”
• Webb Adam C. MD, Samuels, OwenB MD
• Critical care Medicine June 2011 Vol 39- issue
6 pp 1538-1542
• ICU of an academic tertiary care hospital

43. Reversible brain death?
• 55 yo M
• This patient had a PEA arrest from asthma with time to ROSC of 20mins.
His sats were 60% even before the arrest.
• Cardiac arrest preceded by respiratory arrest.
• Therapeutic hypothermia for neuroprotection. ?not indication to be
cooled
• After rewarming to 36’5, sluggishly reactive pupils, spontaneous
myoclonic movements, absent corneal reflexes, and intact gag and
spontaneous respirations.
• Over 24 hours, remaining cranial nn function was lost. Clinical examination
consistent with brain death. Apnea test and repeat clinical examination
after 6 hours confirms brain death.
• Family consented for organ donation
• 24 hours after brain death pronouncement, in OT, patient regained corneal
and cough reflex, and spontaneous respirations.

44. DBD,DNDD
• Problems with terminology. “brain death”, “cardiac
death” and “circulatory death” is that they are
inaccurate and potentially misleading.
• “Donation after Neurological Determination of Death”
DNDD

45. • Failure to distinguish between patients who
are “dead,” “brain-dead,” “in a chronic
vegetative state,” “minimally conscious,”
“comatose,” or “terminally ill but conscious” is
a source of endless confusion.

46. 1. Apart from identifying evidence of sufficient intracranial pathology, list the
preconditions that must be met prior to the determination of brain death by
clinical criteria.
Minimum period of 4 hours in which the patient is observed to have
unresponsive coma, unreactive pupils, absent cough/tracheal reflex and no
spontaneous respiratory effort
• Normothermia (temp >35oC)
• Normotension (SBP >90 mmHg, MAP >60 mmHg in adult)
• Exclusion of sedative drugs
• Absence of severe electrolyte, metabolic or endocrine disturbance
• Intact neuromuscular function
• Ability to examine the brainstem reflexes including at least one ear and
one eye
• Ability to perform apnoea testing
2. What is the recommended minimum time for observation in cases of
hypoxic- ischaemic brain injury, prior to performing clinical testing of brain-
stem function?
24hours
Answers to CICM exam question

47. 3. For each of the following brainstem reflexes, list the
cranial nerves that are tested
a. Cough reflex - cranial nerve X
b. Vestibulo-ocular reflex - cranial nerve III,IV,VI,VIII
c. Pupilary light reflex - cranial nerve II & III
d. Corneal reflex - cranial nerve V & VII
e. Gag reflex - cranial nerve IX & X
(for each part of this question ALL cranial nerves are
required in order to receive the 5 marks, no marks should
be given for an incomplete response)

48. 4. List three contraindications to performing apnoea testing
a. Concomitant high cervical cord injury
b. Severe hypoxaemia
c. Haemodynamic instability
5. List the acceptable imaging techniques that may be used to
demonstrate brain death as an alternative to clinical testing as
recommended by the ANZICS Statement on Death and Organ
Donation
• Four vessel intra-arterial catheter angiography with digital
subtraction (preferred)
• Radionuclide imaging with Tc-99mHMPAO and single
photon emission computerised tomography (SPECT)
(preferred)
• CT angiography (limited experience to date) (acceptable)