This document discusses brain death, including its historical definition, current diagnostic criteria, pathophysiology, and management of organ donors. Key points include: - Brain death is defined as irreversible cessation of all functions of the entire brain, including the brain stem. - Diagnosis requires two examinations at least 6 hours apart showing coma, absence of brainstem reflexes, and apnea during a standardized test. Ancillary tests like EEG can be used if clinical criteria are inconclusive. - After brain death, pathophysiological changes occur like hypotension, diabetes insipidus, and coagulopathies due to loss of autonomic and endocrine functions regulated by the brain.

1. Moderator: Prof. Dr R. N. Khadgaray
Presenter: Dr Kundan Kishor Ghimire
UCMS-TH
BRAIN DEATH

2. Objectives
•Will be able to know when to, how to, and
why to declare a patient as brain dead.

3. Historical Perspective
•Historically death defined as “permanent cessation of
circulatory and respiratory function.”
•However, in 1968 a committee at Harvard Medical School
decided to redefine death by using “irreversible coma” as
a new criterion.

4. • advancements in CPR techniques and widespread
mechanical ventilators use, number of patients could be
kept temporarily ‘alive.
• Consequently, Harvard criteria was developed and formed
the basis for all brain death guidelines.

5. BRAIN DEATH
Uniform Determination of Death
Act(UDDA) 1981
•An individual who has sustained either
•Irreversible cessation of circulatory and
respiratory functions, or
•Irreversible cessation of all functions of the entire
brain, including the brain stem

6. American Academy of
Neurology(1995)
Published practice parameter to
describe medical standards for
the determination of brain death
•essential findings necessary to
confirm irreversible cessation
of all functions of the entire
brain, including brain stem.

7. Pathophysiology of brain
death

8. cerebral hypoxia, traumatic head
injury, subarachnoid or intracerebral
hemorrhage and bacterial meningitis.
primary brainstem pathology
or conditions causing cerebral
edema. E.g DKA, HE, Water
intoxication, eclampsia,
Aspirin overdose, Malignant
hypertension.
irreversible rise
in ICP
increased ICP compresses the
entire brain including the
brainstem
total brain infract

9. •Rise in ICP ➡️ massive release of catecholamine stores
➡️ increased systemic arterial blood pressure, sometimes
associated with reflex bradycardia, bradyarrhythmia, or
both.
•Decreased cardiac output, pulmonary edema, and cardiac
ischemia may be encountered.

10. •Once total brain infarction has occurred ➡️ catecholamines
depletion ➡️ loss of sympathetic output ➡️ peripheral
vasodilation and systemic hypotension.
•Other common problems after brain death include diabetes
insipidus, hypothermia, metabolic acidosis and cardiac
arrest.

11. Physiological change after brain
death
Neurological Changes:-
• temperature regulation center in hypothalamus is impaired.
• patient becomes poikilothermic and hypothermic.
Cardiovascular Changes:-
• Raised ICP may cause rise in catecholamines, leading to
'sympathetic storm', responsible for the increased blood pressure,
cardiac dysrhythmias, ECG abnormalities, myocardial damage
and renal impairment.

12. Pulmonary Changes:-
• During the sympathetic storm, rapid rise in left atrial pressure
exceeds pulmonary artery pressure may result in capillary
disruption, protein-rich pulmonary edema and interstitial
hemorrhage.
Endocrine Changes:-
• Neurogenic diabetes insipidus.
• Electrolyte disturbances: hypernatremia, hypokalemia,
hypocalcaemia, hypophosphatemia and hypomagnesemia occur
rapidly without treatment.

13. •Interrupt hypothalamic-pituitary axis leading to
serum hormone depletion.
• Hypothyroidism & adrenal insufficiency
•Fall in insulin levels
Leads to systemic hyperglycemia with severe
osmotic diuresis and profound hypovolemia.

14. Hematological:-
•Release of fibrinolytic agents and plasminogen activators
into the circulation can cause coagulation defects, DIC.

15. Incidence of pathophysiological changes following
brain death:
•- Hypotension 81%
•- Diabetes Insipidus 65%
•- DIC 28%
•- Cardiac arrhythmias 25%
•- Pulmonary edema 18%
•- Metabolic acidosis 11%

16. DIAGNOSTIC CRITERIA
•Two examinations, separated by at least 6
hours
•Done by 2 or 3 physicians independent of the
transplant team
•At least one physician should be a specialist
in neurology/neurosurgery/neuroanesthesia

17. •Prerequisites
•Inclusion criteria
•Exclusion criteria
•Demonstration of clinical signs of brain death
•Ancillary tests for brain death

18. PREREQUISITES:
Inclusion criteria
•patient must be totally unresponsive and ventilator
dependent.
•Irreversible cause of brain death of known etiology:
evidence of brain injury-clinical, radiological.

19. PREREQUISITES:
Exclusion criteria
•No drug intoxication or poisoning
•Recent administration or continued presence of
neuromuscular blockers.
•Guillain-Barré or the locked-in syndrome

20. PREREQUISITES:
Exclusion criteria
•Metabolic or endocrine factors:
• Hypothermia(<32ºC)
• Hypoglycemia/ Hyperglycemia/ ketoacidosis
• Hepatic failure/ Reye’s syndrome
• Uremia
• Hyponatremia
• Hypercalcemia
• Panhypopituitarism
• Myxedema
• Adrenal cortical failure

21. Demonstration of clinical signs of brain death
1. Coma or unresponsiveness
•GCS of 3
•No cerebral motor response in all extremities or
facial muscles to painful nail-bed pressure or
supraorbital ridge pressure.

22. 2. Absence of brainstem reflexes
A. Pupils
a) No response to bright light
b) Size: midposition (4 mm) to dilated (9 mm)
B. Facial sensation and facial motor response
a) No corneal reflex to touch with a cotton swab
b) No jaw reflex
c) No grimacing to deep pressure on nail bed,
supraorbital ridge, or temporomandibular joint

23. C . Pharyngeal(gag) and tracheal(cough) reflexes
a) No response after stimulation of the posterior
pharynx with tongue blade
b) No cough response to tracheal suctioning
D. Ocular movement
a) No oculocephalic reflex (testing only when no
fracture or instability of the cervical spine is
apparent)
b) No occulo-vestibular reflex

24. Oculocephalic reflex

25. Oculo-Vestibular Reflex
“ Caloric Testing”

26. 3. Apnea test:
considered as most important test.
• main components
• Prevent hypoxemia
• Ensure an adequate PaCO2
• Observe that spontaneous respiratory effort is
absent

27. Prerequisites
•Normothermia (Core temperature>35ºC or
97ºF).
•Normotension (SBP >=100 mm Hg or MAP>60
mm of Hg)
•Euvolemia.
• Eucapnia(PaCO2 35-45 mm Hg)
• no prior evidence of CO2 retention

28. Procedure
•Adjust vasopressors to a systolic blood pressure 100
mm Hg
•Pre-oxygenate with 100% oxygen for at least 10
minutes to PaO2 of 200 mm Hg.
•Reduce ventilation frequency to 10 breath to eucapnia
•Reduce PEEP to 5 cm H2O.
•If oxygen saturation remains 95%, obtain baseline
ABG

29. •Disconnect the patient from the ventilator.
•Deliver 100% O2
•4-6 L/m via a insufflation catheter inserted at the
level of carina.
•6 L/m by T piece attached to the ETT tube
•Look closely for the respiratory effort for 8-10 mins.
•If no respiratory drive observed after 8 min draw
blood for blood gas analysis and reconnect ventilator

30. Apnea test- Positive
•respiratory movements- absent
•and arterial PaCO2 is ≥ 60 mm Hg or 20 mm Hg
increase in PaCO2 over a baseline
Apnea test- Indeterminate
•Respiratory movement-absent
•PaCO2<60 mm Hg.
Apnea test- Negative
•respiratory movements-present.

31. Criteria to abort test
•Presence of respiratory movements
•systolic blood pressure becomes < 90 mm Hg.
•significant oxygen desaturation.
•New cardiac arrhythmias.

32. Factors that can interfere the clinical
diagnosis of brain death
•Severe facial or cervical spine trauma
•Preexisting pupillary abnormalities
•Toxic levels of any sedative drugs, aminoglycosides,
TCA, anticholinergics, antiepileptic drugs,
chemotherapeutic agents, or neuromuscular blocking
agents
•Sleep apnea or severe pulmonary disease resulting in
chronic retention of CO2

33. Ancillary Testing
Recommended when
•cause of coma is not known
•Apnea testing inconclusive or aborted
•confounding clinical conditions limit the
clinical examination.
•Skull or cervical injuries
•Cardiovascular instability
•To reassure family member and medical staff

34. Choice of test
•Ideal ancillary test should meet all of the
following criteria:
• no false positives results
• sufficient on its own to establish is or is not present.
• not susceptible to ”confounders” such as drug effect
or metabolic disturbances.
•standardized in technology, technique and
classification of results
•available, safe and readily applied in all medical
centers with ICUs,

35. Ancillary test for brain death
•Electroencephalography
•Cerebral Angiography
•Nuclear brain scanning
•Transcranial doppler ultrasonography
•CT Scan
•MRI/ MRI-angiography
•SSEP

37. Spinal reflex
•Movements originating from the spinal cord or
peripheral nerve.
•Common(33-75%), triggered by tactile stimuli or
spontaneously.
•Examples include:
• Undulating toe flexion response- planter tactile
stimulation
• Triple flexion response with flexion at the hip, knee and
ankle.
• Pronator extensor reflex- head turning.
• Facial myokymia, repetitive twitching of facial muscles.
• Lazarus sign
• truncal movements including asymmetrical opisthotonic
posturing of the trunk and preservation of superficial and
deep abdominal reflexes.

38. Brain death in child
•Most commonly occurs as a result of trauma and
anoxic encephalopathy.
•Anatomic neurodevelopment continues by 2 years of
age or beyond the first dacade of life.
•Presence of open fontanelles and open sutures makes
the skull an expandable chamber.
•ICP may not exceed MAP and cerebral blood flow
continues.

39. History: determination of the proximate cause of
coma to ensure absence of remediable or reversible
conditions.
Physical examination criteria:
1. coma and apnea
2. absence of brainstem function
• Midposition or fully dilated pupils
• Absence of spontaneous eye movements.
• Absence of movement of bulbar musculature and
corneal, gag, cough, sucking and rooting reflexes.
• Absence of respiratory movements with standardized
testing for apnea.

40. 3. patient must not be hypothermic or hypotensive for
age.
4. Flaccid tone and absence of spontaneous or induced
movements, excluding spinal cord events.
5. Examination results should remain consistent with
brain death throughout the observation and testing
period.

41. •Exclusion of preterm infants younger than 37 weeks
of gestational age.
•Observational period:
•24 hours: neonates (37 weeks of gestation to term
infants 30 days of age)
•12 hours: Infants and children (>30 days to 18 years)

42. Management of organ Donors
•Consent from family for organ donation can be
obtained after the diagnosis of brain death is
established.
•primary goal:
•preserve organ viability.
•best achieved by ensuring oxygenation and
ventilation, maintaining homodynamic stability, and
correcting electrolyte problems and acid-base
abnormalities.

43. •“Rules of 100’s”
•- Maintain SBP > 100 mmHg
•- HR < 100 BPM
•- UOP > 100 ml/hr
•- PaO2 > 100 mmHg

44. •Methylprednisolone 15mg/kg bolus
•Triiodothyronine (T3) 4mcg bolus, 3mcg/hr.
•Arginine vasopressin 1 unit bolus, 0.5-4 units/hr
•Insulin infusion 1 unit/hr minimum

45. •Donor organ preservation ( cold ischemic time):
• Heart & Lungs 3-4 hrs
• Pancreas 6 hrs
• Liver 8 hrs
• Kidneys 36 hrs

46. Conditions Distinct From Brain Death
•Deep coma
•Persistent Vegetative State
•Minimally Responsive State
•Locked in syndrome

47. Deep coma
•Non-responsive to external stimuli
•Dysfunctional cerebrum
• Brain stem intact spontaneous breathing and
heartbeat

48. Vegetative state
•Appears to be wakeful with cycles of eyes
closure and opening.
•Normal Sleep-Wake Cycles
•No Response to Environmental Stimuli
•Can ventilate themselves
•Lack of higher brain function to control
emotions, consciousness and cognition.
•Hypoxic brain injury.

49. Minimally Responsive State
•Unlike vegetative state, patients with MCS have
partial preservation of conscious awareness.
•Diffuse or Multi-Focal Brain Injury

50. Locked in syndrome
• Lesion to the brainstem, most frequently an ischemic
pontine lesion.
•complete disruption of the motor pathways
• face, trunk and limb movements, including
breathing, swallowing and phonation.
• Consciousness and cortical functions are preserved.

51. References
• Miller’s Anesthesia, 8th Edition
• ICU book.
• American Academy of Neurology guidelines for brain death
determination.
• Textbook of Neuroanaesthesia and Critical Care.

52. Thank you