BRAIN DEATH - ITS DIAGNOSIS, MANAGEMENT , LEGAL ISSUES AND PREPARATION OF ORGAN DONOR FOR HARVESTING

1. Dr.VAIDYANATHAN R
VICE PRESIDENT, ISA MYSORE
CHIEF INTENSIVIST & HEAD OF DEPT
DEPT OF ANAESTHESIA ,INTENSIVE CARE & PAIN
CAUVERY HEART & MULTISPECIALTY
HOSPITAL,MYSORE
BRAIN DEATH
- Enigma of death & life in death

2. MY ALMA MATER..

3. GREETINGS FROM CAUVERY……

4. BRAIN DEATH
 Historical Perspective
 Legal status
 Prerquisites – Differential diagnosis
 Brain stem reflexes
 Apnea test
 Certification and formalities
 Management of brain death for organ donation

5. HISTORICAL PERSPECTIVE
 1950s saw an unusual challenge for clinicians
 ACLS and ventilators saved lot of lives…….
 But there were also unanticipated outcomes
 Physicians saw things they never saw before
 Clinicians saw patients in a state “Beyond Coma”
Neuroophysiologists saw Electrocerebral silence &
Pathologists saw the “Respirator Brain”
 Guy Alexandre in 1963,first retrieved kidneys for transplant
from such patients.
 1968: Harvard Medical SchoolAd Hoc Committee,a
special committee formed to look into aspects of brain death.
 Harvard Criteria for brain death
 Loss of animation, brainstem reflexes and respiration
 Electrocerebral silence
 Persistence of the condition for 24 hours

6.  In 1980, President's Commission for the Study of Ethical
Problems in Medicine and Biomedical Research published
a landmark report on the ethical and legal implications of defining
death and presented conceptual basis for whole-brain-death.
 The report 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”.
 Consistency is maintained with the fact that after brain-death,
cardiopulmonary death quickly follows despite continued
intensive care.This is known as the somatic disintegration
hypothesis.
 Uniform Determination of DeathAct 1981 gets passed in US
 An individual who has sustained either
(1) irreversible cessation of circulatory and respiratory
functions or (2) irreversible cessation of all functions of the entire
brain, including the brain-stem is dead.
 TheTransplantation of Human Organs Act 1994-THOA DOI.10.4103/0972-5229.140151
(Ammended in 2011)

7. Relationship of Organ Function
 Heart
 Needs O2 to survive and w/o O2 will stop beating
 Not controlled by the brain but it is autonomous
 Breathing
 Controlled by vagus nerve, located in the brain stem.
 Main stimulant for vagus nerve is  CO2 in the blood.
 Causes the diaphragm & chest muscles to expand
 Spontaneous breathing can not occur after brain stem death
 With artificial ventilation,the heart may continue to beat for a period of
time after brain stem death.
 Time lag between brain death and circulatory death is ~2-10 days.
(A case report has demonstrated a woman's heart beating for 63 days after a
brain death)
ENIGMA OF LIFE
& DEATH

8. Brain Death Current Consensus
 Absent Cerebral Function – Patient in Coma
 Absent Brainstem Function – Absent brain stem reflexes
 Apnea - Not triggering ventilator and Apnea test
positive

9. Normal Brain Anatomy

10. Normal Brain Anatomy
Cerebral Cortex
Brain Stem
Reticular
Activating
System

11. Cerebral Cortex
 Cognition
 Voluntary Movement
 Sensation
 Consciousness
 Consciousness is wakefulness and
awareness of oneself or surroundings
for which normal functioning of RF
and cerebral cortex is necessary.
 Hence in the lesions of cortex and
RF,consciouness will be altered.

12. Reticular Activating System
• The reticular activating system (RAS),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 behaviour

13. Brain Stem

14. Brain Stem -MIDBRAIN
Midbrain
Cranial Nerve III
 Pupillary function
 Eye movement

15. Brain Stem- PONS
Pons
Cranial Nerves IV,V,VI
 conjugate eye movement
 corneal reflex

16. Brain Stem - MEDULLA
Medulla
1.Cranial Nerves IX, X
 Pharyngeal (Gag) Reflex
 Tracheal (Cough) Reflex
2.Respiration

17. Parts of Brainstem with functions and lesion effects

18. Brain Death & Brain Stem Death
 To assess the function of the entire brain diagnostic tests of cerebral cortex
function and brain-stem function are done.
 Cerebral cortical function can be assessed by testing for electrical activity with
an electroencephalogram (EEG)
 Absence of cerebral circulation is the gold standard indicative of
cortical death -The 4 vessel angiogram.
 Absence of cerebral cortical function can also be determined by a
lack of verbal response and lack of spontaneous or coordinated
eye movements.

19. Normal Electrocerebral Silence
Electroencephaolgram (EEG)

20. 4 VESSEL CEREBRAL ANGIOGRAM
CerebralAngiography
Normal No Intracranial Flow

21. Diagnosis of Brain-Stem Death In India
 Brain-stem death is medically and legally de ned as the total
fi
and irreversible cessation of all brain-stem functions.
 Diagnosis of brain-stem death is required to discontinue
artificial ventilation and to ask legal consent for organ
donation from relatives.
Role of investigations
 The diagnosis is based only on the clinical examination.
 A neurophysiological or imaging study neither form part of the
diagnostic requirements nor are legally required.
 Con rmatory tests / ancillary tests may however be carried out if the
fi
panel of doctors is in doubt or disagreement of the diagnosis.

22. THO Act 1994 and the THO Rules, 1995
 Team of four medical experts including
• MedicalAdministrator / In charge of the hospital.
• Authorized Specialist
• Authorized Neurologist/Neuro-Surgeon
• Medical Officer treating the patient.
 Amendments in theTHO Act (2011) have allowed selection of a
surgeon/physician and an anesthetist/intensivist, in the event of the
non-availability of approved neurosurgeon/ neurologist.
Who will declare brain dead ?

23. Ancilliary Tests
 Cerebral angiography particularly a four-vessel angiogram demonstrating absent cerebral
circulation remains the gold-standard supplementary test for brain-death.
 EEG - most commonly applied supplementary test for brain-death worldwide,Signi cantly
fi
affected by hypothermia, drug administration and metabolic disturbances, diminishing
its clinical utility.
 Transcranial Doppler (TCD) is a noninvasive technique can be used.
 Radionuclide imaging techniques likeTechnetium-99 m scan has been widely performed.
There is no uptake of isotope in brain parenchyma (“hollow the skull phenomenon”) in brain-
death.
 Multimodal evoked potentials are useful in the diagnosis of brain-death
 A combination of median nerve somatosensory, brain-stem auditory and visual
evoked potentials is used in the evaluation of brain-death.

24. CAUSES OF BRAIN DEATH
 HYPOXIA ( PostArrest, Ischemic Stroke,etc)
 BLEEDING ( IVH, Extenive ICH,etc)
 TRAUMA (contusions, bleed , any lesions eventually sec brain stem dysfunction)
 SAH ( Aneurysmal rupture,severe spasm,etc )
 TUMOURS
 ENCEPHALITIS
 ENCEPHALOPATHY
 REFRACTORY STATUS EPILEPTICUS

25. Mechanism of Cerebral Death
Increased ICP
ICP >MAP is
incompatible
with life

26. Conditions Distinct From Brain Death
 PersistentVegetative State
 Locked-in Syndrome
 Minimally Responsive State
(MCS)

27. Locked-in Syndrome
Ventral Pontine Infarct
 Complete Paralysis
 Preserved Consciousness
 Preserved Eye Movement

28. Minimally Responsive State (MCS)
- Static Encephalopathy
Distinguished from coma and
Vegetative state by documenting
the presence of specific behavioral
features not found in either of these
conditions
“A condition of severely altered
consciousness in which minimal, but
definite, behavioral evidence of self or
environmental awareness is
demonstrated.”

29. Brain Death Neurological Examination
Prerequisites:
• Irreversible Coma with Causes listed earlier
• Exclusion of Potentially Reversible Conditions
• Core Body temperature > 32° C
• Absence of Confounding clinical conditoion for examination of cortical or
brain stem function
• Brain stem encephalitis
• Guillain- Barre' syndrome
• Drug Intoxication or Poisoning
• Shock
• Electrolyte or Acid-Base Imbalance
• Endocrine Disturbances
• Encephalopathy – hepatic/uraemia/metabolic
• Residual anaesthetic / neuroparalysing effects

30. Irreversible Coma
No Response to Noxious Stimuli
 Nail Bed Pressure
 Sternal Rub
 Supra-Orbital Ridge Pressure

31. Absence of Brain Stem Reflexes
 Pupillary Reflex
 Eye Movements
 Facial Sensation and Motor Response
 Pharyngeal (Gag) Reflex
 Tracheal (Cough) Reflex

32. Pupillary Reflex
Pupils dilated with no constriction to bright light

33. Eye Movements
“Doll’s Eyes Maneuver”
- Occulo-Cephalic Response

34. Eye Movements
Oculo-vestibular reflex is tested with 50 to
100 ml of ice water irrigated into an
external auditory canal clear of cerumen,
and after elevating the patients head 30'
• No deviation of the eyes to irrigation in each
ear with 50 ml of cold water (tympanic
membranes intact)
• No deviation is a +ve test
• Allow 1 minute after injection and at least 5
minutes between testing on each side
“Cold CaloricTesting”
- Oculo-Vestibular Response

35. CORNEAL REFLEX AND GAG REFLEX
 Corneal Reflex
• Gag reflex can be evaluated by stimulating the posterior pharynx
with a tongue blade, but the results can be difficult to evaluate in
orally intubated patients
• Stroking each side of the mucous membrane of the uvula tests the palatal
reflex; the side that is touched will rise
• Cough reflex can be tested by using ETT suctioning, past end of ETT
•Gag And Cough Reflexes

36. • Grimace to Supraorbital orTemporo-Mandibular Pressure is normally seen
• Absence of such response is suggestive of brain stem death

37. Apnea Testing
Prerequisites
- Normotensive,Normothermia,Eucapnia,Normoxia
 Core BodyTemperature > 36.5° C
 Systolic Blood Pressure ≥ 90 mm Hg,titrate vasopressors
 Euvolemia - positive fluid balance in the previous 6 hours
 Normal Electrolytes
 Normal PCO2:Ventialte to achieve PCO2 35- 40 mm Hg
 Normal PO2 : pre-oxygenate for 10 mins with 100% FiO2 to
arterial PO2 ≥ 200 mm Hg

38. Apnea Testing
• Connect a pulse oximeter and disconnect the ventilator.
• Deliver 100% O2 @ 6 l/min into the trachea OR place a
cannula at the level of the carina.
• Can use aT-piece / CPAP
• Look closely for any respiratory movements (abdominal or
chest excursions that produce adequate tidal volumes).
• DrawABG after approximately 8 minutes and reconnect the
ventilator.

39. Results
 TEST POSITIVE If respiratory movements are absent and
arterial PCO2 is ≥ 60 mm Hg OR if there is 20 mm Hg
increase in PCO2 over a baseline normal PCO2
• TEST NEGATIVE If respiratory movements are observed.
• DiscontinueTesting if i.BP < 90,
ii.SPO2/ saturation decreases,
or iii. Presence of arrhythmias
• Inconclusive tests can be repeated after 2 hours

40. Apnea test challenges
 Hypotension (SBP<90 mmHg), hypoxemia (SaO2<85 percent for >30 seconds), or
cardiac arrhythmia may occur during the apnea and lead to abortion of the apnea
test.
 These events may suggest inadequate oxygenation or preoxygenation, or baseline
cardiopulmonary disease.
 Reconnect the ventilator,Immediately draw an ABG and analyse.
 If PCO2 is ≥ 60 mm Hg or increase ≥ 20 mm Hg- the apnoea test result is positive
 If PCO2 is < 60 mm Hg , the result is indeterminate and a confirmatory test can be
considered.
 When appropriate a 10 min. apnoea test can be done after preoxygenation for 10
mins with Fi02 of 1.0 and normalization of PaCO2 to 40 mmHG

41. STEPS TO BE FOLLOWED WHEN BRAIN
DEATH IS BEING CONSIDERED
 Testing
 The first series of tests to be done by the intensivist or ICU consultant
or Neurologist or neuro-surgeon of the hospital
 The second series of tests to be done by two senior consultants of the
department, one of whom should be on the officially nominated panel.
 The second series to be done 6 hours after the first.
 Ensure that the following results are available (or at least have
been sent) at the conclusion of the first series of tests:
 HIV,HB S AgHCV,blood group analysis,CBC,LFT

42.  If permission for harvesting organs is not granted,
discontinue ventilation and certify death RATHERTHAN
WAITING FOR CARDIAC DEATH…
 The time of death in all cases will be recorded as the time of
the second positive test.
• InformTransplant Coordinator about possible candidate
after first positive test.
• The coordinator will
• Interact with family & keep the ICU informed at all times.
• Inform all other personnel of the transplant team (it is not the
responsibility of the ICU to contact anyone other than the
coordinator.)
• Complete all legal formalities except for filling Form 8

43. FORM 8 - DECLARATION CUM CONSENT FORM
(To be filled by near relative or lawful possessor of brain-stem dead person)

44. FORM 10
FOR CERTIFICATION OF BRAIN STEM DEATH
(To be filled by the board of medical experts certifying brain-stem death)

45. BRAIN CERTIFICATION APP- MOHAN FOUNDATION

47. ORGAN DONOR CARD

48. NOTTO AND SOTTO
https://notto.mohfw.gov.in/index.htm

49. https://www.jeevasarthakathe.karnataka.gov.in/
website/English/Home.aspx

50. JEEVASARTHAKATE DONOR CARD

51. CHALLENGES
 HYPOTENSION
 DIABETES INSIPIDUS
 HYPERGLYCEMIA
 HYPOTHERMIA
 INFECTIONS
 ANEMIA
 COAGULOPATHY
 MAIN AIM IS TO MAINTAIN HEMODYNAMIC STABILITY
FOR ORGAN PERFUSIONTILL ORGANS ARE HARVESTED
FROM BRAIN DEAD PATIENTS
MEDICAL MANAGEMENT OFTHE POTENTIAL DONOR
AIM

53. RULE OF 100 FOR MANAGEMENT OF DONOR

54. Hypotension
 Blood pressure:Aggressive management combination of Volume,Inotropes &
Pressors to maintain MAP between 70-80 mmHg (VIP)
 Vasopressin, Noradrenaline and adrenaline are the choice of drugs
 Dopamine preferred in many centres as pressors worsen ischemia.(+/-Dobut)
 Start Hydrocortisone at 50mg q6h
 Add levothyroxine bolus of 20 mcg followed by an infusion of 10
mcg/hr if dose of dopamine crosses 10 mcg/kg/min
 Frequently before final brain death there is a surge in blood pressure; the MAP
must be kept below 100 mmHg at this time by reducing dose of dopamine /
noradrenaline

55. Diabetes Insipidus (DI)
 Recognize DI early do not wait for formal fulfillment of output or serum sodium
criteria as applicable for suprasellar lesions.
 Target sodium <150 mEq/L and potassium >3 mEq/L
 A triple lumen line and a large bore peripheral line for volume & Keep CVP over 10 cm H20
 Check electrolytes every 4 hours,If patient develops DI ,
• StartVasopressin IV at a dose of 0.5–2.0 U/hour IF donor is in hypotension
refractory to fluid resuscitation; it acts equally at all three vasopressin receptors, so has
pressor effects in addition to antidiuretic actions.
• Aim to maintain sodium level between 135–145 mEq/L but < 155 mEq/L
• For DI with hypernatremia without hypotension ,desmopressin ,a vasopressin
analogue with greater affinity for theV2 receptor can be used.
• Dosage:An initial IV dose of desmopressin of 1–4 g
μ is used and subsequntly
titrated as per urine volume, serum sodium concentration and urine osmolality.

56. Hypothermia,Ventilation & Supportive measures
 Ventilation: Once the patient is suspected to be brain dead andsedation has
been stopped change ventilator settings to a tidal volumeof 6 ml/kg
predicted body weight
• Aim is to maintain a temperature over 35.8°C before and
during the retrieval operation.
• Active warming can be achieved using warm blankets, fluid
warmers, and heated humidifiers in ventilator circuits,
administration of warm IV fluids and by adjusting the ambient
temperature.
• Consider broad spectrum antibiotics and follow FASTHUG

57. NOTHING CAN BE MORE NOBLE
ENCOURAGE ORGAN DONATION

58. TAKE CARE OF POTENTIAL DONORS AS WELL

59. R .Vaidyanathan
vaidyanathandr@gmail.com
9886031067