2. HISTORICAL GLIMPSE
• Before 1960, death was defined as the complete and irreversible cessation
of spontaneous cardiac and respiratory functions
• Refinement of CPR techniques and the advent of ICUs with mechanical
ventilators enabled temporary support of cardiopulmonary function in the
absence of brain function.
• Hence, the cardiopulmonary definition of death lost relevance in such
cases and brain-stem death concept evolved
3. • 1959- Mollaret and Goulon coined the term “coma de' passe'” (a state
beyond the coma) for an irreversible state of apneic coma with absent
brain-stem reflexes and EEG activity, but with preserved cardiac and
metabolic activities
• In 1968, an Ad Hoc Committee of Harvard Medical School on Brain Death
published a landmark report, “the definition of irreversible coma.” It
defined the criteria for determining brain death as apneic coma and
absence of elicitable brain-stem reflexes for a period of 24 h as confirmed
by an electroencephalogram
4. • In 1971, Mohandas and Chou emphasized the importance of irreversible
loss of brain-stem function in brain death (Minnesota criteria)
• Focusing on the brain-stem function, the Conference of Medical Royal
Colleges in the UK published a breakthrough code for the determination of
“brain death” (brain-stem death) in 1976
• In 1981, the US President’s Commission published a landmark report on
the ethical and legal implications of defining death and presented
conceptual basis for whole-brain-death. “The permanent cessation of
functioning of the entire brain.”
5. • In 1995, American Academy of Neurology (AAN) published practice
parameters for diagnosis of brain-death
– The parameter emphasizes on irreversible coma (with a known cause),
absence of brain-stem reflexes and irreversible apnea.
– Fifteen years after its first report, the AAN issued an evidence-based
guideline update in 2010
– It concluded that there are no published reports of recovery of
neurologic function after a diagnosis of brain-death using the 1995
AAN criteria
6. THE CONCEPT OF BRAIN DEATH
• Brain-oriented death can have three forms, defined by the structures
– Whole-brain death
– Brainstem death
– Neocortical death
• Brainstem is
– The through-station for almost all hemispheric input and output
– The center that generates arousal (which is essential for
consciousness)
– The center of respiration
7. • The brainstem is often the last structure to be injured in brain damage
• Therefore, the term brainstem death came into practice, which is
diagnosed with irreversible
– Loss of consciousness
– Loss of brainstem reflexes
– Apnea
8. Indian Context
• India follows the UK concept of brain-stem death and the transplantation of
human organs (THO) act was passed by Indian parliament in 1994 which
legalized the brain-stem death
• Brain-stem death is medically and legally defined as the total and irreversible
cessation of all brain-stem functions
• It is mandatory now for all NTORCs and authorized transplant centers in the
state to certify and notify the brain-death cases to zonal transplantation co-
ordination committee
9. • Who should diagnose: Team of four medical experts including
– Medical Administrator In charge of the hospital.
– Authorized Specialist
– Authorized Neurologist / Neurosurgeon
– Medical Officer treating the patient
• Amendments in the THO Act (2011) have allowed selection of a
surgeon/physician and an Anaesthetist/ Intensivist, in the event of the
nonavailability of approved neurosurgeon/ neurologist
10. BRAIN STEM
Pons
• Cranial nerves IV, V, VI
• Conjugate eye movement
• Corneal reflex
Medulla
• Cranial nerves IX, X
• Pharyngeal (gag) reflex
• Tracheal (cough) reflex
• Respiration
Midbrain
• Cranial nerve III
• Pupillary function
• Eye movement
12. Cerebral edema
Vasogenic
edema
• Increase in cerebrovasvular
permeability
• Destruction of blood brain barrier
Increase in ICP
• Hypoxic & ischemic conditions
• Disturbance in cellular
osmoregulation(depends on ATP
dependent ionic pumps)
Cytotoxic
edema
>ABP Brainstem compression
Brainstem infarct
Aseptic necrosis
Respirator brain
13. CRITERIA AND TESTS FOR DETERMINING
BRAIN DEATH
• Determination of brain death confirms the irreversible cessation of all
functions of the entire brain, including the brainstem
• Although testing all functions of the brain is conceptually impossible, the
cessation of all functions of the brain is practically determined by
– Loss of consciousness
– Loss of brainstem responses
– Apnea
– Confirmatory tests, including the lack of electroencephalographic
activity
14. • Loss of consciousness and unresponsiveness
– The patient should be in coma and scored as 3 on the GCS
– Motor responses of the limbs or facial muscles to painful supraorbital
pressure should be absent
– Reflex: afferent nerve V and efferent nerve VII.
– Motor responses (i.e., the Lazarus sign) may occur spontaneously
during apnea testing and are considered to have a spinal origin
– This sign is often observed during hypoxic or hypotensive episodes
15. • Pupils
– The shape of the pupils can be round, oval, or irregular.
– The size of the pupils may vary from 4 to 9 mm, but in most cases is 4
to 6 mm
– Sympathetic cervical pathways can be intact in the state of brain
death, connect with the radially arranged fibers of the dilator muscle,
and dilate the pupils
– Reflex: afferent nerve II and efferent nerve III
16. • Brainstem responses
– The tests for brainstem responses vary in different countries
– The criteria of the American academy of neurology include
• Light reflex
• Oculocephalic reflex
• Caloric (vestibular) test
• Corneal reflex
• Facial muscle movement to a
noxious stimulus
• Pharyngeal (gag) reflex
• Tracheal (cough) reflex
17. • Corneal reflex
– Test the corneal reflex by touching the cornea with a wisp of cotton wool
– Blinking of the eyelids is the normal response and both eyelids must be
observed
– Reflex: afferent nerve V and efferent nerve VII
18. • Pharyngeal (gag) reflex
– A tongue depressor is used to stimulate each side of the oropharynx
and the patient observed for any pharyngeal or palatal movement.
– Reflex: afferent nerve IX and efferent nerve X.
• Laryngeal (cough) reflex
– A suction catheter is introduced into the endotracheal or
tracheostomy tube to deliberately stimulate the carina
– The patient is observed for any cough response or movement of the
chest or diaphragm
– Reflex: Afferent nerve IX and efferent nerve X.
19. • Oculovestibular reflex (caloric testing):
– Patency of external auditory canal to be checked before doing
– Tested by irrigating each ear with ice water(caloric testing)
– Head is elevated to 30 degrees, each external auditory canal is irrigated
(1 ear at a time) with approximately 50 ml of ice water. Allow 1 minute
after injection and at least 5 minutes between testing on each side.
– Normal response is nystagmus with FAST component opposite to the
ear irrigated(COWS)
– NO movement indicates brain stem death
– Reflex: afferent nerve VIII and efferent nerves III and VI.
20.
21. • Apnea test
– The apnea test should be performed as the last test after the other
tests fulfill the criteria of brain death
– Prerequisites are
• Normotension (systolic blood pressure ≥100 mm hg)
• Normothermia (core temperature >36° C)
• Euvolemia
• Eucapnia (paco2 35 to 45 mm hg)
• No prior evidence of carbon dioxide retention
22. – Preoxygenation with 100% O2 for at least 10 minutes is required
before apnea testing to PaO2 greater than 200 mm Hg
– Ventilator requirements should be evaluated, and the patient should
be well-oxygenated with low PEEP (5 cm H2O)
– During apnea testing, 100% O2 is delivered at 6 L/min through a
catheter placed at the level of the carina
– Look closely for respiratory movements for 8-10 min.
– Respiration is defined as abdominal or chest excursions
23. – Apnea testing should be aborted if systolic blood pressure decreases to
less than 90 mm Hg or O2 saturation (SpO2) decreases to less than 85%
for longer than 30 seconds
– A bolus of intravenous phenylephrine 100 μg is recommended in the
case of hypotension
– If respiratory movements are absent and arterial PCO2 is 60 mmHg or
more (or 20 mmHg above baseline), the apnea test result is positive
24. PREREQUISITES FOR DIAGNOSING
BRAIN DEATH
• The absence of these conditions must be confirmed and the following
factors considered before the criteria for brain death are applied
25. • Deep coma
– Drug intoxication, severe electrolyte, acid-base or endocrine
disturbance, hypothermia, and other common treatable disorders
should be ruled out.
• Body temperature
– Because hypothermia suppresses CNS function and can lead to
misdiagnosis of brain death, body temperature must be within normal
range (i.e., Hypothermia must be corrected) before the criteria for
brain death are applied.
26. • Absence of cardiovascular collapse
– Hypotension may result in compromised cerebral perfusion leading to
loss of electroencephalographic activity, thus causing a spurious
diagnosis
– Therefore, administration of a vasopressor to achieve relative
normotension should be considered; vasopressor therapy will
occasionally restore electroencephalographic activity in the
determination of brain death
27. SPINAL CORD REFLEXES AND SURGERY
• The CNS structures essential to the definition of brain death do not
include the spinal cord
• Spontaneous and reflex movements are found in brain-dead patients
• 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 respirations
produced by mechanical ventilation
28. • Not always mandatory for adults
• 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
ANCILLARY TESTS FOR BRAIN DEATH
29. • Cerebral angiography
– The contrast medium should be injected in the aortic arch under high
pressure and reach both anterior and posterior circulations
– No intracerebral 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
30. • Electroencephalography
– A minimum of eight scalp electrodes should be used
– Interelectrode 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 μV for 30 minutes with
inclusion of appropriate calibrations
– The high-frequency setting should not be set below 30 Hz, and the low-
frequency setting should not be above 1 Hz
– Electroencephalography should demonstrate a lack of reactivity to
intense somatosensory or audiovisual stimuli
32. • Transcranial Doppler (TCD) ultrasonography
– TCD is useful only if a reliable signal is found
– The abnormalities should include either
reverberating flow or small systolic peaks in early
systole
– The probe should be placed at the temporal bone, above the
zygomatic arch and the vertebrobasilar arteries, through the
suboccipital transcranial 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
33. • Cerebral scintigraphy (technetium-99m hexamethylpropyleneamine-oxime [HMPAO])
– 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 intravenous 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)
35. INTRODUCTION
• Prior to proceeding to organ procurement, the anesthesiologist should
ensure that diagnosis of brain death has been made in accordance with
the American Academy of Neurology guidelines
• The Anaesthesiologist plays a pivotal role in organ procurement from the
brain dead patient, as hemodynamics, thermoregulation, intravascular
volume status, and skeletal muscle paralysis require active management
and are vital to the procurement of healthy organs
36. • Effective anesthetic management of donation requires an understanding
of the effects of brain death on each organ system
38. • Cardiovascular responses to brain death
– The cardiovascular system is closely regulated by the central neural
system
– Cardiovascular responses to brain death usually consist of two phases
– Failure to correct these cardiovascular derangements results in poor
organ perfusion and inadequate tissue oxygenation, which will
threaten the viability of the donated organs
39. Cardiovascular responses
to brain death
First phase
Loss of sympathetic tone
Sympathetic discharge
(catecholamine storm)
Second phase
Profound and sustained
• ↓CO
• Severe peripheral vasodilatation
(vasoplegia)
• Intense vasoconstriction
(↑SVR) (hypertensive crisis)
• Tachycardia / Bradycardia
• Redistribution of blood volume
with visceral ischemia
Transient period
Due to brain ischemia
related ↑ICP
Due to cerebral herniation and
spinal cord ischemia
40. • Respiratory responses to brain death
– Sympathetic activity triggers a sterile systemic inflammatory response,
initiating infiltration of neutrophils and increasing pulmonary
endothelial permeability, which further contributes to lung injury
– Proinflammatory cytokines are released at the alveoli and are
associated with early graft failure and mortality after lung
transplantation
– The inflammatory response in brain-dead donors is associated with the
deterioration in cardiac function and a shift to anaerobic metabolism
41. ↑SVR after brain death
Blood shift from the systemic
circulation into the more compliant
pulmonary circulation
↑ in hydrostatic pressure in the
pulmonary circulation
Pulmonary capillary leakage and
pulmonary edema
42. • Endocrine, metabolic, and stress responses to brain death
– Posterior pituitary function in brain dead donors is frequently lost
• The development of central diabetes insipidus results in severe
fluid and electrolyte derangements and can be observed in up to
90% of brain dead donors
– Anterior pituitary function in brain death can also be affected,
resulting in a deficiency in T3 &T4, ACTH, TSH, and GH
• Thyroid hormonal deficiency may be similar to the euthyroid sick
syndrome commonly observed in the non–brain injured patient
with multisystem organ failure
43. – Hyperglycemia is commonly encountered in brain-dead donors
because of decreased insulin concentrations and increased insulin
resistance
– Hypothalamic function and control of body temperature are lost
• Initially hyperpyrexia occurs, followed by hypothermia
(↓metabolic rate and muscle activity, peripheral vasodilation)
– DIC is present in up to 1/3rd of isolated patients with head injuries and
is believed to be caused by the release of tissue thromboplastin from
brain tissue
44. ANAESTHETIC CONSIDERATIONS
• The critical care literature supports the normalization of donor physiology
to maximize the long-term viability of organs for donation
• This strategy should continue from the ICU into the operating room during
donation surgery
45. • Cardiovascular system
– Restore intravascular volume, replacing evaporative and DI urinary
losses
– Use vasopressors as necessary to maintain adequate organ perfusion
– Myocardial damage caused by catecholamine storm may be prevented
or attenuated by controlling cardiovascular responses, which may
increase the number of heart transplants
– large doses of norepinephrine are associated with increased cardiac
graft dysfunction and increased recipient mortality
• Myocardial injury
• Loss of vascular tone
• Hemodynamic instability
• Hypovolemia
46.
47. • Pulmonary management
– ‘‘Lung-protective’’ ventilatory strategy: TV 6-8 ml/kg, PEEP 8-10 cm
H2O, low FiO2
– The focus of pulmonary management is to recruit and retain lung units
while limiting tidal volume and inspiratory pressure
– Judicious intravenous fluid; CVP 4-8 (<10) mmHg
• Increased pulmonary capillary
permeability
• Pulmonary edema
48. • Temperature management
– Current practice should include active warming to maintain
temperature >35 C before and during the retrieval operation
– Cold preservation is integral to organ storage, however, and it has
been hypothesized that active rapid cooling of organs before
circulatory arrest might improve organ viability
49. • Hormones, steroids, and electrolytes
– Hormonal deficiency is common in brain-dead donors and hormonal
replacement is beneficial
– Exogenous replacement of antidiuretic hormone in brain-dead donors
improves graft function in kidney, liver, and cardiac recipients
– Consider hormone replacement—thyroxine or T3 infusion,
corticosteroids
– The systemic inflammatory response associated with brain death leads
to pulmonary infiltration of neutrophils and the elevation of
interleukins
• Pituitary infarction may lead to diabetes
insipidus and obliteration of thyroid axis
• Hyperglycemia
• Hypernatremia
50. – The systemic inflammatory response of the donor is associated with
graft failure and recipient mortality
– Methylprednisolone administration can moderate the inflammatory
response and may improve oxygenation, reduce lung water, and
increase lung yield
– Methylprednisolone administration can also decrease inflammation in
the liver, heart, and kidney.
51. – Intravascular volume replacement is essential in the management of
diabetes insipidus
• After administering initial fluid to correct hypovolemia,
hypernatremia should be treated by giving a hypotonic solution
• Vasopressin to support hemodynamics and control polyuria
– Hyperglycemia in the donor is common and exacerbated by steroid
therapy
• Poor glucose control adversely affects donor renal function
• Insulin management should target a glucose level between 120
and 180 mg/dL
52. • Coagulation
– Transfuse for hemoglobin <7 or 8 g/dl for optimal oxygen delivery to
organs
– Correct coagulopathy with clotting factors or platelets if evidence of
ongoing bleeding
Coagulopathy, which may progress to
disseminated intravascular coagulation
53. • Musculoskeletal system
– Skeletal muscle paralysis using muscle relaxants
Reflex somatic movements mediated
by spinal reflexes
54. • Other considerations
– Prior to the start of organ donation surgery, intravenous catheters
adequate for rapid large-volume intravascular fluid replacement
should be in place
– In addition, the presence of a central venous catheter is
recommended prior to the start of surgery
– An arterial catheter should be placed so that blood pressure can be
continuously followed and managed intraoperatively
55. – It is important to communicate with the surgical team and know which
organs will be procured for transplant as this can effect anaesthetic
management
– Prior to heparinization, the cardiac team may ask for removal of
indwelling central lines or pulmonary artery catheters that traverse
the superior vena cava, as they will subsequently clamp these vessels
prior to removal of the heart
– After the Anaesthesiologist administers heparin, the surgical teams
cannulate the major arterial blood vessels; the cardiac team utilizes
the ascending aorta, and the abdominal team utilizes the infrarenal
abdominal aorta
56. – Following cannulation and when all teams are in readiness, aortic
cross-clamps are placed (one in the chest and one in the abdomen)
and then intravascular flushing of cold solution is begun as well as
topical cooling of the organs
– For the heart, cold cardioplegia is utilized and it is often Celsior
solution and the abdominal team often uses University of Wisconsin
(UW) solution
57. – For lung procurement, the Anaesthesiologist will likely be asked to
administer positive pressure breaths to inflate the lungs prior to
removal and subsequent packaging for transport
– At this point, the ventilator and monitors are turned off, and there is
no longer a need for further anaesthesia care while the organs are
removed in the following order: heart, lung, liver, pancreas, kidneys.