The document discusses the diagnosis of brain death through neurological criteria. It begins by describing the main parts of the brain and their functions. It then discusses the concepts, laws, and types of brain death in India. The key components of determining brain death are described, including establishing the cause of coma, achieving normal temperature and blood pressure, performing neurological examinations to check for absence of brainstem reflexes and response to stimuli, and conducting an apnea test. Potential mimics of brain death and pitfalls in the clinical evaluation are outlined. Confirmatory ancillary tests like cerebral angiography and EEG are also discussed.

1. DIAGNOSIS BY NEUROLOGICAL CRITERIA
Dr. RAM NAIK. M (MD2)
IACC & MMC

2. Cerebral hemispheres:
 Conscious part of the brain
 Controls thought and memory
 Feels sensations
 Directs conscious movements
Thalamus
 Relay station for sensory informa
to go to the brain
Hypothalamus
 Temperature control, controls
hormone systems, food intake,
emotions
Cerebellum:
• Balance
• Coordination
Brain stem: Midbrain + Pons + Medulla
 Attention, arousal & consciousness
 Cranial nerve reflexes
 Control of breathing
 Control of blood pressure, heart function

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121917/

6. 1959, Brain Death Recognition in ICU, Paris
Le coma de passe= Beyond coma
Some patients with head injury or intracranial bleed never recovered
1968, Ad Hoc Committee from Harvard Medical School
Consensus on brain death- Hopelessly unconscious patient
‘Irreversible coma= Brain death’: - Totally unresponsive, no cranial reflexes, no respiratory efforts
1981, Uniform Determination of Death Act / US President’s Commission
Individual who sustained either
(i) irreversible cessation of circulatory and respiratory functions or
(ii) irreversible cessation of all functions of the entire brain, including the brain stem, is DEAD
2010, American Academy of Neurology
“cessation of all functions of the entire brain, including the brain stem,” = Irreversible coma + absent brain stem reflexes + positive apnea testing
1976, The UK criteria: Diagnosis By Neurological Criteria were published
and subsequently clarified in Codes of Practice
CONCEPT OF BRAIN DEATH
1971, Britain, Mohandas& Chow
claimed that Brainstem damage was the crucial component of severe brain damage leading to
profound coma

7. LAWS DETERMINING DEATH IN INDIA
The Registration of Births and Deaths Act (RBDA), 1969
Death = “The permanent disappearance of all evidence of life at any time after livebirth has
taken place”
Section 46, IPC-1860
The word death = “death of a human unless the contrary appears from the context”
The Transplantation of Human Organs Act, 1994
Death = “Permanent disappearance of all evidence of life, by reason of brain stem death or in a
cardio-pulmonary sense at any time after live birth has taken place”
Brain death= Stage at which all functions of the brain stem have permanently & irreversibly
ceased. Sub-section (6) of section 3
The Transplantation of Human Organs& Tissues Act, 2014

10. TYPES OF BRAIN DEATH
CORTICAL
• Cessation of cerebral
functions-
IRREVERSIBLE,
PERMANENT
• Brainstem is preserved
BRAINSTEM
• Intact cerebrum(EEG+)
• Brainstem functions
lost
• Irreversible coma
• No spontaneous
respiration
• Intracranial circulation
maybe preserved.
• In India & UK.
WHOLE BRAIN
• Little practical significance
• Death is not a single
event, BUT a
progressive process
of failure of all body
functions.
• With a threshold of
irreversibility, need
not wait for the
death of whole
organism
• In USA

11. MIMICS BRAIN STEM DEATH
BRAIN STEM
DEATH
COMA VEGETATIVE STATE MINIMALLY
RESPONSIVE STATE
LOCKED IN
SYNDROME
No arousal
No eye opening
No awareness
Apnea +ve
No reflexes
No arousal
No eye opening
No awareness
Impaired
breathing
Impaired reflexes
No vocalization
>1hr
Arousal
Eye opening
(spontaneousstimulus induced)
No awareness
Spontaneous breathing
Preserved reflexes
No purposeful behavior
Preserved hypothalamic
and brainstem
autonomic functions
> 1month: Persistent
Vegetative state
Grimace to pain.
Localizes sound
Arousal
Eye opening (spontaneous)
Aware (fluctuating, but
reproducible)
Spontaneous breathing
Verbalizations
Visual fixation
-sustained, Pursuit+
Object localization
Smiling/crying
Communication –
intentional, but
unreliable
Arousal
Eye opening
(spontaneous)
Aware
Preserved
cognition
Eye gaze
communication
Anarthria
Tetraplegia

12. • Time of death
• Fill up the check list
• Date and signature
• Contact organ
procurement organization
• Cerebral angiography
• EEG
• Nuclear scan
• TCD
• CTA
• MRI/MRA
• Coma
• Absence of brainstem
reflexes
• Apnea
• Establish irreversible and
proximate cause of coma
• Achieve normal core temperature
• Achieve normal systolic blood
pressure
• Perform one neurological
examination.
PREREQUISITES
NEUROLOGIC
ASSESSMENT
DOCUMENTATION
ANCILLARY
TESTS
THE DETERMINATION OF BRAIN DEATH

13. 1) ESTABLISH IRREVERSIBLE & PROXIMATE CAUSE OF COMA:
History, Examination, Neuro-imaging & Laboratory tests
Exclude CNS-depressant drug effect by history, drug screen, calculation of clearance using 5 times the
drug’s half-life, or drug plasma levels below the therapeutic range
Prior use of hypothermia may delay drug metabolism
Prior use of NMBs: ongoing or continued infusion
No severe electrolyte, acid-base, or endocrine disturbance
The legal alcohol limit for driving (blood alcohol content 0.08%) is a practical threshold below which an
examination to determine brain death could reasonably proceed
2) ACHIEVE NORMAL CORE TEMPERATURE:
 A warm blanket may be needed for normal or near-normal temperature.
 Avoids any delay in the rise of PaCO2 during apnea testing.
3) ACHIEVE NORMAL SYSTOLIC BLOOD PRESSURE:
 Neurological examination is usually reliable with SBP ≥100 mm Hg
 Hypotension: Loss of peripheral vascular tone, hypovolemia(Diabetes Insipidus)
 Vasopressors or Vasopressin are often required
4) PERFORM ONE NEUROLGICAL EXAMINATION
PREREQUISITES (Clinical examination)

14. NEUROLOGICAL ASSESSMENT (Clinical examination)
COMA.
PATIENTS MUST LACK ALL EVIDENCE OF RESPONSIVENESS.
• Eye opening or eye movement to noxious stimuli is absent.
• Noxious stimuli should not produce a motor response.
•Supraorbital Pressure/ Nail Bed Pressure/ Pinch trapezius/ TMJ
• Differentiation of spinal responses from retained motor responses
ABSENCE OF BRAINSTEM REFLEXES
Absence of PUPILLARY REFLEX to a bright light {CN- 2,3} . Size >4mm.
Absence of CORNEAL REFLEX. {CN- 5,7}
Absence of ocular movements-OCULOCEPHALIC TESTING( Doll’s eyes) {CN- 3,4,6,8,11}
Absence of ocular movements- OCULOVESTIBULAR TESTING(Cold caloric test) {CN-3,6,8}
Absence of facial muscle(Trigeminal) movement to a noxious stimulus. {CN- 5,7}
Absence of the pharyngeal reflexes (GAG REFLEX) {CN- 9,10}
Absence of the tracheal reflexes (COUGH REFLEX) {CN- 10}
Testing for APNEA

17. MANDATORY POINTS TO BE NOTED:
Consultant Physician and/or Neurologist/Neurosurgeon should conduct
a thorough and methodological clinical examination of the neurological
status & functioning of the patient
Examination should remain consistent with prescribed brain stem death
guidelines throughout the observation and testing period
Two tests are necessary, separated by no less than 6 hours in adults
Once a time interval has been set for the second test, it must be
carried out within that interval, either by the examining physician or by
suitable designated medical practitioner
 In children,
 1 week to 2 months : 48hours
 2 months to 1 year: 24 hours
 >1 year: 12 hours

18. APNEA TESTING PREREQUISITES:
Normotension
Normothermia
Euvolemia
Eucapnia
Absence of hypoxia
No prior evidence of
CO2 retention
Adjust Vasopressors to a SBP ≥100 mm Hg.
Preoxygenate: 10 minutes. 100% O2, PaO2 >200 mm Hg.
Eucapnia: Ventilation@Rate-10 bpm, PEEP- 5cm H2O
Baseline ABG, If SpO2 remains >95%
Disconnect the patient from the ventilator.
Keep Oxygenating( Insufflation catheter through ETT, close to
the carina, 100% O2 @ 6L/min
Watch for respiratory movements for 8–10min
(Brief gasp, abdominal or chest excursions)
ABORT:
SBP : <90 mm Hg
SpO2 <85% for > 30sec
Respiratory drive +
Arrhythmias
Retry with T-piece, CPAP 10cm
H2O, 100% O2 @ 12 L/min
Repeat ABG, If no respiratory drive is observed for 8min
Apnea test POSITIVE
•No respiratory
movements
•PaCO2 ≥60 mm Hg
•∆PaCO2 > 20mm Hg
INCONCLUSIVE Apnea Test
Repeat after 10-15min after
adequate preoxygenation

19. PITFALLS IN CLINICAL EVALUATION
•Interfere with the clinical diagnosis of brain death.
•Confirmatory tests are recommended for the diagnosis..
Severe facial trauma
Pre existing pupillary abnormalities
Sleep apnea
Toxic levels of sedatives
Amino glycosides
Tricyclic antidepressants
Anticholinergics
Neuromuscular blockers
Chemotherapeutic agents
Antiepileptics
Severe pulmonary diseases
Lazarus sign
Sweating
Blushing
Tachycardia
Normal BP without supports
Absence of diabetes insipidus
Occasional deep tendon reflexes
Superficial abdominal reflexes
Triple flexion response
Babinski response

20. The most common movements:
• Finger jerks
• Undulating toe flexion sign (initial plantar flexion of great toe followed by sequential brief plantar
flexion of the 2nd, 3rd, 4th & 5th toes)
• Triple flexion response (flexion of thigh, leg and dorsiflexion of foot)
• Lazarus sign
• Pronation-extension reflex
• Facial myokymia (bag of worms appearance= continuous twitching of small bands/strips of muscles
giving an undulating/rippling appearance to overlying skin)

21. LAZARUS SIGN
Spontaneous body movements may be observed during the apnea test, while the body is
being prepared for transport, at the time of a skin incision for the retrieval of organs, or in
synchrony with the respiration produced by mechanical ventilation.
BIZARRE, SEEMINGLY PURPOSEFUL movements of the upper extremities, in which the arms
flexed quickly to the chest from the patient’s side, the shoulders adducted, and in some
patients, the hands crossed or opposed just below the chin.
Remember that a patient may move in response to noxious stimulation and that full curarization
is required for surgical procedures involving brain death.

23. STEPS TO BE FOLLOWED WHEN DIAGNOSIS OF BRAIN DEATH IS BEING CONSIDERED
TIME OF DEATH = TIME OF SECOND POSITIVE APNEA TEST
TESTING
INVESTIGATIONS
INFORM TRANSPLANT COORDINATOR
• 1st test done by consultant of ICU unit
• 2nd test done by two consultants (one from the nominated panel)
• Second series of tests done 6 hours after the first
Available / at least sent to the laboratory (by the end of 1st series of tests)
HIV/HCV/ HbsAg
Blood Grouping & Typing
LFTs, WBC, TC/DC
PT, PTT, Platelets
• ONLY After 1st positive apnea test
• ABORT if transplant team examines/enquires/
talks to the candidate’s relatives before
informing them
• Interact with the family & Keep the ICU informed at all times
• Informs other personnel of the transplant team
• Obtain all drugs & fluids necessary, after the first positive apnea test
• Complete all legal formalities except Form-8

24. Neurological examination &
Apnea testing
Inconsistent Incomplete/ Unreliable Consistent
BRAINSTEMDEATHDETERMINATIONPROCESS
FLOWCHART
COMPLETECHECKLIST
INITIATEORGANPROCUREMENTPROCESS
Confirmatory tests
Negative/
Not consistent
Positive/
Consistent
Repeat clinical exam
CANNOT BE DONE
RELIABLE & complete
clinical exam DONE
Repeat confirmatory
tests within 24hrs
NO FURTHER TESTING

25. ANCILLARY TESTS
•Tests that confirm the loss of bioelectrical activity of the brain or the cerebral
circulatory arrest.
• NOT ALWAYS MANDATORY FOR ADULTS.
• Can reduce the time of observation and are strongly recommended when
uncertainties exist about the reliability of certain aspects of the clinical
examinations and in situations in which the apnea testing cannot be
completed.
•Young and associates proposed criteria for ideal confirmatory ancillary tests
i. No instances of false positive findings should occur
ii. should be independently sufficient to establish that brain death is or
is not present
iii. should not be susceptible to confounders
iv. should be standardized in technology, technique, and classification of
results
v. should be available, safe, and readily applied. Testing should not be
restricted to only a few research centers

26. ANCILLARY TESTS (….contd)
CEREBRAL ANGIOGRAPHY (S4VA) , that demonstrates an absent cerebral circulation
remains the GOLD-STANDARD supplementary test for the diagnosis of brain-death
• The contrast medium should be injected in the aortic arch under high pressure and
reach both anterior and posterior circulations.
• No intra-cerebral filling should be detected at the level of entry of the carotid or
vertebral artery to the skull.
• The external carotid circulation should be patent.
• The filling of the superior longitudinal sinus may be delayed.

27. ANCILLARY TESTS (….contd)
ELECTROENCEPHALOGRAM:
• Loss of bioelectric brain activity for at least 30 minutes of recording, is a reliable test.
• EEG may also not show electrical activity in barbiturate coma.
• Devices in the ICU may cause artifacts, leading to spurious results.
• Affected by hypothermia, drug administration and metabolic disturbances.
• A minimum of 8 scalp electrodes should be used.
• Inter-electrode impedance should be between 100 and 10,000 Ω .
• The integrity of the entire recording system should be tested.
• The distance between electrodes should be at least 10 cm.
• The sensitivity should be increased to at least 2 V for 30 minutes.
• The high-frequency filter setting should not be set below 30 Hz & the low-frequency setting should not be above 1 Hz.
• Electroencephalography should demonstrate a lack of reactivity to intense somato-
sensory or audiovisual stimuli.

28. ANCILLARY TESTS (….contd)
TRANSCRANIAL DOPPLER ULTRASONOGRAPHY:
 Subject to technical problems
 Noninvasive & found to be highly sensitive to determine absent cerebral perfusion
• The abnormalities should include either reverberating flow or small systolic peaks in
early systole.
• A finding of a complete absence of flow may not be reliable owing to inadequate trans-
temporal windows for insonation.
• There should be bilateral insonation and anterior and posterior insonation.
• The probe should be placed at the temporal bone, above the zygomatic arch and the
vertebro-basilar arteries, through the sub-occipital trans-cranial window.
• Insonation through the orbital window can be considered to obtain a reliable signal.
• TCD may be less reliable in patients with a prior craniotomy.

29. ANCILLARY TESTS (….contd)
CEREBRAL SCINTIGRAPHY (technetium Tc 99m hexametazime(HMPAO), have been widely
performed. There is no uptake of isotope in the brain (“hollow skull phenomenon”) in brain-
dead patients
• The isotope should be injected within 30 minutes after its reconstitution.
• Anterior and both lateral planar image counts (500,000) of the head should be obtained at
several time points: immediately, between 30 and 60 minutes later, and at 2 hours.
• A correct IV injection may be confirmed with additional images of the liver demonstrating
uptake (optional).
• No radionuclide localization in the middle cerebral artery, anterior cerebral artery, or basilar
artery territories of the cerebral hemispheres (hollow skull phenomenon).
• No tracer in superior sagittal sinus (minimal tracer can come from the scalp).

30. •Most of these tests have been validated against the gold standard of bedside diagnosis and
are not 100% specific or sensitive.
•May have a place in patients in whom the results of specific components of clinical testing
cannot be reliably evaluated
•Currently do not form part of the mandatory diagnostic requirements in most
countries, including India.
Multimodal Evoked Potentials. (SSEP/BERA)
Computed tomographic Angiography(CTA) – 7 point, 10 point scoring and Perfusion(CTP)
Positron Emission Tomography(PET)
Magnetic resonance Angiography(MRA) and Perfusion(MRP)
ANCILLARY TESTS (….contd)

31. NEONATES,INFANTS&CHILDREN PREREQUISITES:
a) Correct hypothermia, hypotension, metabolic disturbances
b) Discontinue sedatives, analgesics, NMBs, anticonvulsants (based on t ½)
i. Supra therapeutic/ High therapeutic range: No diagnosis based on
Neurological examination alone.
ii. Mid and low therapeutic range: unlikely to affect diagnosis
a) Defer neurological examination for 24-48hrs: Immediately after CPR, severe cute brain
injuries
NUMBER OF EXAMINATIONS, EXAMINERS:
2 examinations separated by an observation period (1st = determines if criteria are
met for BD, 2nd =confirms that the child fulfilled BD criteria)
Examinations by 2 different attending physicians.
Apnea test by Physician in charge of the ventilator
OBSERVATION PERIODS:
A. Neonates(37wk gestation to 30days age): 24hrs
B. Infants(>30days) and Children(<18yrs): 12hrs
APNEA TESTING:
PaCO2 >60mm Hg or ∆PaCO2 >20mm Hg.
Desaturation <85%, or inability to reach PaCO2 60mm Hg: Perform Ancillary tests.
ANCILLARY TESTS:
Never a substitute for clinical examination
If tests are unreliable, waiting period= 24hrs. Supportive care must be continued
during this period.

32. DOCUMENTATION: THOTA, 2014

34. WHOCERTIFIES?“THEPANEL” RMP in charge of hospital
Head of the Institute, RMO, ARMO, Duty RMO
No clearance from Appropriate authority
RMP (Physician/ Surgeon/ Intensivist)
Clearance from Appropriate authority
Neurologist or Neuro-surgeon
Intensivists & Anaesthesiologists
Clearance from Appropriate authority
RMP treating the aforesaid patient
No clearance from Appropriate authority4
2
3
1
1st & 2nd medical examinations of Form-8 of THO rules: Category 2&3 doctors
No category 3 doctor? Request from any panel member from another hospital
Appropriate authority = Director of Medical & Rural Health Services

35. Need for Declaration of Brain Death
Once an unequivocal diagnosis of brain death has been made,
 Most medical and legal authorities agree that continuing treatment is
not in the interest of the patient or is ethically permissible.
 This is not related to withdrawing support to allow a patient to die, but
rather to ceasing a futile intervention in a patient who is already dead.
Acceptance of this approach would
 Reduce human distress
 Lead to the rational use of the limited ICU facilities
 Increase the availability of organs.
Solid organs can be donated only after confirmation of brain death.
Unless medical personnel provide family members with information that
all cognitive and life support functions have irreversibly stopped, the
family may harbor false hopes for the loved one's recovery.

36. Ethical Issues in Declaring Brain Death
•The DDR (Dead Donor Rule) is the formalization of the widely held belief that it
is wrong to kill one person to save the life of another, leading to the conclusion
that people should already be dead before vital organs are removed, an act that
would certainly kill them.
•The DDR is neither a law nor a regulation — it is a description of an ethical
norm: an organ donor must be dead before vital organs are removed.

37. OFFENSES & PENALITIES
CHAPTER VI, THOA,1994
PUNISHMENT FOR REMOVAL OF HUMAN ORGANS WITHOUT AUTHORITY:
 Any person who
 Renders his service to or at any hospital
 Conducts, associates with, or helps in any manner for removal of any organ
5 years Imprisonment + up to Rs.10,000
 If he/she is a RMP
 Reported to the appropriate authority, state medical council
Cancel registration for 2 years for the first offence
Permanent cancellation for subsequent offence.

38. OFFENSES & PENALITIES
CHAPTER VI, THOA,1994
PUNISHMENT FOR REMOVAL OF HUMAN ORGANS WITHOUT AUTHORITY:
 Any person who
 Makes or receives payment for the supply of, or offers to supply any human organ
 Seeks to find a person who is willing to supply any organ for payment
 Offers to supply any organ for payment
 Initiates or negotiates any arrangement for payment
 Takes part in management/control of a body of persons(society/firm/company)
 Advertisements – publishes/ distributes/ causes to be published/distributed
 Inviting persons to supply organs for payment
 Offering to supply organs for payment
Term not less than 2 years (up to 7 years) +
Fine not less than Rs.10000 (up to Rs.20,000)

39. http://www.ijtonline.in/article.asp?issn=2212-0017;year=2018;volume=12;issue=2;spage=84;epage=89;aulast=Sahay
https://www.notto.gov.in/act-end-rules-of-thoa.htm
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2018;volume=66;issue=2;spage=308;epage=315;aulast=Ganapathy
https://www.mohanfoundation.org/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121917/

40. “So Uncertain Is The Man’s
Judgment, That They Cannot
Determine Even Death
Itself”
Pliny, The Elder
“Historia Naturalis”

41. BEATING HEART DONOR
PATHOPHYSIOLOGY
RAM NAIK. M (MD2)
IACC & MMC

42. Demand for organs- much higher than organs which are being available
With demand, the responsibility to caring for potential organ donors is also rising
Appropriate multidisciplinary team approach for successful organ transplantation
WHY…..???
For graft survival after donation, all available organs in the donor need to be
maintained at their normal physiological condition until the time of organ retrieval
Early identification of a potential donor is critical in starting early medical
management for successful organ transplantation

43. WHO CERTIFIES…??
A panel of four doctors:
(I) Hospital administrator
(II) Resident doctor of the hospital
(III) Neurologist/Neurosurgeon/Physician, Intensivist, and Anesthetist
(IV) Treating doctor.
In the recent 2014 rules apart from neurologist or neurosurgeons,
anesthetists, critical care specialists, intensivists, physicians, or
surgeons have been included to facilitate brain death declaration
In MLC cases, Role of Forensic medicine..????
Police clearance is MUST. (Superintendent of Police or Deputy Inspector General)

44. POTENTIAL ORGAN DONOR
• An individual who has suffered a fatal injury to the brain (with impending or
actual brain death), yet has intact cardiovascular function.
•Cause of death:
• Severe traumatic head injury
•Others: Primary Brain tumors, CVAs, drug overdose.
i. Meet age and Brain dead criteria. {Newborn to 65years. Ideally 10-50 years}
ii. Infection free. Antibiotic coverage and negative cultures are necessary
iii. STD screening. HIV, HTLV, Syphilis, Viral hepatitis
iv. No history of carcinoma, except primary brain or low-grade skin caner
v. Free of severe systemic disease
vi. Relatively normal organ functions
vii. Hemo-dynamically salvageable
viii.At least one organ that has a reasonable likelihood of functioning well
(post transplantation)

45. DEAD DONOR RULE

46. ABSOLUTE CONTRAINDICATIONS
•Active visceral or hematologic neoplasm
•Clinical signs that indicate organ is unlikely to function well
•Transmissible infections that will adversely affect recipient
•HIV
•Active HBV
•Encephalitis of unknown cause
•CJD
•Disseminated TB
Organ donation exclusion criteria related to HIV risk:
•Drugs( iv, im, sc) for nonmedical reasons in past 5 years
•Persons with hemophilia, who received human derived clotting factors
•Persons engaged in sex in exchange for money, drugs or with another man in the past 5
years
•Persons exposed to known/suspected HIV infected blood in past 12 months
•Inmates of correctional systems.
If the risk to the recipient of not performing the transplant is deemed to be greater than the
risk of transmitting disease, then it is carried out & the recipient is informed the potential risk

47. DIAGNOSIS
DNC
PREREQUISITES
CLINICAL
EXAMINATION
ANCILLARY
TESTS
DOCUMENTATION
NORMAL TEMPERATURE
CAUSE OF COMA NORMOTENSIVE
CLINICAL EXAMINATION
COMA APNEA
BRAINSTEM REFLEXES

48. PATHOPHYSIOLOGY OF BRAIN DEATH
Severe damage to neuronal tissue
Intra-cranial edema
Raised ICP
Reduces cerebral perfusion
Reduces cerebral blood flow
Trans-tentoral herniation
Coning of the foramen magnum
Crushing of the brain stem
Permanent dysfunction
VISCIOUS
Late neuronal injury
Hypoxic ischemic
brain injury
MUNRO-KELLY
DOCTRINE
1. VASOGENIC EDEMA(↑ vascular permeability)
2. CYTOGENIC EDEMA (altered cellular osmoregulation)
CUSHING’S
REFLEX

49.  Death is an ONGOING PROCESS, rather than isolated event.
 Total loss of neuro-physiological functions for >8 minutes confirms
total &irreversible loss of brain function.
 Complete cardiovascular and autonomic uncoupling occurs.
 Hypernatremia and diabetes insipidus are more often the effect
rather than the cause of brain death.
 Even with maximal support, cardio-respiratory deterioration
leading to somatic death will occur within days.
 Damage to the RF may lead to loss of cognition, persistent
unconsciousness and coma.

50. PATHOPHYSIOLOGICAL CHANGES
CARDIOVASCULAR RESPIRATORY
TEMPERATURE FLUIDS & BLOOD
RENAL ENDOCRINE
BRAINDEATH

51. CARDIOVASCULAR
• Physiological, histological, biochemical and electrocardiographic evidence of "damage" to
the heart at the time of brain death.
• Induced by the vascular regulatory injury and the diffuse metabolic injury.
• The autonomic storm results from a sudden increase in ICP and cerebral ischemia (Cushing's
reflex), a last-ditch effort by the brain to maintain its perfusion.
• The magnitude of the rise in catecholamines and the sequelae thereof depend on the rate
of rise in intracranial pressurel5

52. Brain stem death
(acute ischemia)
Parasympathetic predominance
(Bradycardia, idioventricular rhythms, asystole)
CATECHOLAMINE
STORM
Malignant Tachyarrhythmia
Myocardial
ischemia
Transient
Severe HTN
Severe
Vasoconstriction
↑cardiac filling pressures
Myocardial O2 consumption
↑LV wall tension & Afterload
Coronary
spasm
↓O2 supply
LVF
Neurogenic pulmonary edema
ESTABLISHED
BRAIN DEATH
Rapid ↓in catecholamine, sympathetic tone, ↓SVR, HYPOTENSION
CARDIOVASCULAR
↑ICT
CUSHING’S

54. RESPIRATORY
•LUNGS- most often assumed to be unsuitable for transplantation.
•Only 10-20% of lungs are eligible for transplantation
• 2 factors: Neurogenic pulmonary edema (NPE) and inflammatory acute lung injury
Catecholamine
storm
Systemic VC
↑Afterload
↑ LA & LV pressures
↑ Pulmonary blood volume
↑ Pulmonary artery pressure
Massive pulmonary capillary pressure
Pulmonary edema
↑ Hydrostatic pressure
Endothelial damage
Capillary leakage
Respiratory arrhythmias
Other factors:
Pro-inflammatory mediators
Chest wall trauma
Atelectasis
Aspiration
Long term Mechanical ventilation

55. TEMPERATURE
 Loss of thermoregulatory control
 Exposure to cold ambient temperature
 Massive infusion of cold IvF & Blood
 Loss of protective mechanisms ( Vasoconstriction, Shivering)
 ↓ BMR
 Preventive Hypothermia is attempted rather than treating hypothermia.
 Once hypothermia sets in, it is difficult to warm the patient.
 Hypothermia
Induces Arrhythmias
Alters coagulation cascade
Interferes with O2 delivery to tissues
Affects cardiac function
POIKILOTHERMIC

56. RENAL
 Biomarkers for renal tubular injury increases as early as 30 minutes after onset .
 Both pro-inflammatory and pro-coagulant effects are contributing factors
 Pre-transplant workup (of Brain-Dead Donors) showed more T-Lymphocytes and
Macrophages than the live donors.
 The Na/K ATPase mechanism requires ATP produced from mitochondria to
maintain Na/K ratio. ( ionic gradient)
• Levels of ATP in human cadaver kidneys correlate well with post-transplantation
function
Aggravating factors
Marked vasoconstriction (Autonomic Storm)
Hypovolemia
Diabetes Insipidus
Marked histological changes associated with
renal dysfunction have been described in the
kidneys of brain dead organ donors maintained
for prolonged periods on Vasopressin and
adrenaline

57. HEMATOLOGICAL
Necrotic brain
tissue
Thromboplastin
Plasminogen activators
DIC
Passage of cerebral tissue into the circulation may also initiate the clotting cascade,
with a consumptive coagulopathy ensuing
Brain Death → Catecholamines →Stress Response → Tendency to coagulate↑
Anemia and coagulopathy are common
Deranged coagulation profile (PT & aPTT)
Thrombocytopenia
↑Total Cell counts

58. ENDOCRINE
HYPOTHALAMO-PITUTORY-NEUROENDOCRINE AXIS
• Posterior pituitary function is clinically lost in 80% BDDs
•Anterior pituitary: relatively preserved because of pituitary blood flow
•Normal ACTH, GH, TSH
•SICK-EUTHYROID SYNDROME
•Diabetes Insipidus
•Hyperglycemia
•↓ insulin secretion
•↑ insulin resistance
•Hyperosmolarity.
Untreated Hyperglycemia: pancreatic cell damage & alters Renal Transplant outcome.

60. CARDIOVASCULAR SUPPORT
Maintain tissue perfusion ( adequate Cardiac output& Tissue perfusion pressure)
Correct intravascular fluid depletion : aggressive fluid resuscitation.
Invasive BP, CVP. (if unstable, Pulmonary artery catheter to monitor Q, PAOP, SVR)
Choice of fluid? { Hb, Albumin, Electrolytes, coagulation profile, ongoing losses }
Vasopressor(s) support. Prefer agents with both Ionotropic and Vasopressor properties
DOPAMINE (2-5 mcg/kg/min)- improves perfusion of transplantable abdominal organs
DOBUTAMINE/ NORADRENALINE
Arrhythmias found to occur in 27-56% in any form.
Diuretics, Diabetes Insipidus, Acidosis: further worsen arrhythmias
Correct the coexisting conditions first & then arrhythmias can be managed.
MAP >60mm Hg
CVP up to 15mm HgULTIMATE GOAL= NORMOTENSIVE, EUVOLEMIC STATE

61. VENTILATORY SUPPORT
Lung protective mechanisms.
TV(6-9ml/kg) with optimal PEEP to maintain PaO2 > 70-80mm Hg
Optimal PEEP may reduce high FiO2 requirements. ( FiO2 to maintain SpO2 >90%)
Avoid PEEP > 15cm H2O
HOB 30-40 degrees
Tracheal cuff pressure 25cm H2O
Maintain normocarbia. (if not possible, moderate hypercarbia is permitted)
Recruitment maneuvers initially, repeat after apnea testing and tracheal suction.
 If hyperventilation is employed, discontinue after diagnosis of Brain Death
Avoid administration of excess IVF. (Consider Diuretics, if marked fluid overload)
ABG every 4 hours, After 30min of change in settings
Paw< 40 m H2O
Pplat <35 cm H2O
FiO2- [ SpO2>92% and PaO2 > 70-80mm Hg]
Rate- To maintain normocarbia and pH
Auto PEEP < 5 cm H2O
TV- 6-9ml/kg

62. FLUIDS & ELECTROLYTES
s. Na Fluid
> 150 mEq/L 0.2% NS
<133 mEq/L 0.9% NS
< 128mEq/L 3% NS
s. K Correction
>5.8 mEq/L 50cc 5%D, 15U Insulin, 50mEq NaHCO3
<3.4 mEq/L 20mEq KCl, 2 doses over 1 hour
<3.1 mEq/L 20mEq KCl, 3 doses over 1 hour
< 2.9 mEq/L 20mEq KCl, 4 doses over 1 hour
↓ Mg <1.5mg/dl: 4gm MgSO4 over 2 hours
↓ P <2.2mg/dl: 30 mmol Potassium/ Sodium phosphate over 2 hours and repeat
↓ Ionized Ca <2.1 mEq/L: 10cc of 10% Ca.Gluconate, slow iv and repeat if needed

63. RENAL SUPPORT
Polyuria:
Adjust intake to 100ml/hr
S.Na > 145 mEq/L.
Vasopressin/ Desmopressin(DDAVP)

64. BLOOD & COAGULATION
Coagulopathy:
 PLC< 65,000/CC: 1 Platelet pack transfusion (5-6 units of platelets)
 PT>15sec, aPTT >38s seconds: 4 units of FFP, repeat after 30min& 1 hour
 Fibrinogen <100mg/dl, 6 units of cryoprecipitate. Repeat after 1 and 2 hours.
Anemia:
 Reserve 2-4 units of PRBC.
 Maintain Hct 28-30% with transfusion
 Insert NGT, if UGI bleed is suspected

65. TEMPERATURE