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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1739_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Preface
- •Contents
- •1. Introduction
- •2. God of Transplant Surgery
- •3. History of Transplant
- •4. Organ Transplantation
- •8. Brain Stem Death
- •10. Monitoring of Organ Donor
- •11. Medical Issues and Management
- •12. Complexities of Intensive Care
- •13. Donor Management
- •15. Legal Aspects
- •17. Apnoea Test Protocols
- •19. Preparing an Organ Recipient
- •Bibliography
- •The Author’s Infography
- •Index

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Dr Gopi Ayyaswamy
d. Plasma drug concentration measurements should indicate levels below
the therapeutic range. For example, alcohol levels should be below the
legal limit for driving. The median concentration of thiopentone that
allows for a motor response is 12 mg/L, but individual variation exists,
and some individuals may require levels as low as 4 mg/L to regain a
motor response. Excluding sedative agents as a contributing cause of
coma may require signicant knowledge and experience. In complex
cases, seeking advice from an intensive care medicine specialist who
regularly performs brainstem tests is recommended. Ultimately, the
clinician must rely on their knowledge and judgment to decide whether
to proceed with brainstem testing. If sedation may be contributing to
the absence of brainstem reexes, a diagnosis of brain death cannot be
made based on clinical testing alone. Additional conrmatory tests, such
as cerebral angiography, may be employed (refer to Section D below).
e. Hypothermia as a cause of coma must be ruled out. The core body
temperature should be above 35°C when conducting clinical assessments
of brainstem reexes.
f. Metabolic or endocrine causes that can contribute to coma should be
excluded. Conditions such as hypothyroidism, panhypopituitarism,
adrenal dysfunction, uremia, and hepatic failure can lead to a signicant
decrease in the level of consciousness. Disorders affecting sodium,
phosphate, magnesium, and glucose levels can also affect the response
to brainstem tests. The most common metabolic abnormality observed
in brain-dead patients is hypernatremia, often associated with diabetes
insipidus. The serum sodium level should not be signicantly abnormal,
and a value of 150 mmol/dl is considered the upper acceptable limit for
brainstem tests.
g. Severe hypotension hinders the testing of brainstem reflexes. The
blood pressure should be greater than 90 mmHg systolic (mean arterial
pressure > 60 mmHg) for brainstem tests. Infusion of fluids and
vasoactive drugs may be necessary to maintain blood pressure.
Formal Clinical Testing for Brain stem Reflexes
The formal examination for brain stem reexes can be conducted once the
patient meets the pre-conditions outlined in (a) and (b) above. Additionally,

International Guidelines and Advisory for the Diagnosis of Brain Death
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Dr Gopi Ayyaswamy
the patient must have xed pupils and absent cranial nerve reexes for a
minimum of four hours.
1. No motor response: Adequate stimulation of the trigeminal area and
limbs should be performed to assess for any motor response within
the cranial nerve distribution. It is crucial to test within the cranial
nerve distribution, as the lack of response to a painful stimulus
applied peripherally could be due to a high cervical injury. Trigeminal
stimulation can be achieved by applying pressure on the supraorbital
notch or at the temporo mandibular joint. The reex involves afferent
nerve V and efferent nerve VII.
2. No pupillary response to light. A history of pre-existing abnormalities
of the pupil or previous surgery to the eye (e.g. iridectomy) may
inuence interpretation of this test. Examine each eye with lights in
the room dimmed and use a strong light. The pupils should be more
than 4 mm in diameter. The normal response is brisk constriction of the
pupil. Round, oval or irregularly shaped pupils are compatible with
brain death. In most brain dead patients pupils are in the mid position
(4–6 mm). Reex: Afferent nerve II and efferent nerve III.
3. No corneal reex: Test the corneal reex by touching the cornea with a
wisp of cotton wool. If no response is elicited, a stronger stimulus can
be applied with a sterile throat swab and rm direct pressure. Normal
response includes blinking of both eyelids. The reex involves afferent
nerve V and efferent nerve VII.
4. No oculocephalic reex (Doll’s head eye phenomenon): Caution: This
test should not be performed in patients with an unstable cervical spine
injury. The examiner holds the patient’s eyes open and turns the head
suddenly from the middle position to 90 degrees on both sides. In an
intact reex, the eyes move opposite to the direction of head movement,
appearing to lag behind. If the reex is absent, the eyes move with
the head and do not move within the orbits. If Oculovestibular Reex
(Caloric Testing) can be performed, this test may be omitted.
5. No oculovestibular reflex (caloric testing): Before conducting this
reex test, inspect both ears using an auroscope to ensure the tympanic
membrane is intact and the external auditory canal is clear. If there is a
fractured base of the skull or any obstruction in the external auditory

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canal, the test should not be performed. The patient’s head is elevated
30° from the supine position, ensuring the lateral semicircular canal is
vertical to maximize the response. A soft catheter is introduced into the
external auditory canal for gentle and slow irrigation with at least 50 ml
of iced water, while an assistant holds the eyes open. The eyes should
be observed for a minute after irrigation, and there should be a 5-minute
interval before repeating the test on the opposite side. In an unconscious
patient with an intact oculovestibular reex, the eyes exhibit tonic (slow)
deviation towards the irrigated ear. During testing to conrm brain death,
any eye movement, whether conjugate or not, excludes a diagnosis of
brain death. When the reex is absent, the eyes remain xed. The reex
involves afferent nerve VIII and efferent nerves III and VI.
6. No pharyngeal (Gag) reex: Use a tongue depressor to stimulate each
side of the oropharynx and observe for any pharyngeal or palatal
movement. The reex involves afferent nerve IX and efferent nerve X.
7. No laryngeal (cough) reflex: Introduce a suction catheter into the
endotracheal or tracheostomy tube to deliberately stimulate the carina.
Observe the patient for any cough response or movement of the chest or
diaphragm. The reex involves afferent nerve IX and efferent nerve X.
8. Apnoea test: The apnoea test is a crucial component of conrming brain
death and should be performed when all other brainstem reexes are
absent. However, it may not be feasible to conduct this test in patients
with a high cervical cord injury that has resulted in the loss of phrenic
nerve function. In such cases, clinical determination of brain death
becomes challenging, and additional tests, such as demonstrating the
absence of intracranial blood ow, may be necessary for conrmation
(refer to item (D) below).
Three Key Elements of Apnoea Test
1. Disconnection from mechanical ventilation: The patient is disconnected
from the mechanical ventilator for a sufcient period to allow the arterial
CO
2
tension (PaCO
2
) to reach a critical point, leading to acidaemia. Before
the test, the patient should be pre-oxygenated with 100% oxygen. Arterial
blood gases should be checked, and if the PaCO
2
is not within the normal
range, adjustments should be made to the ventilator settings until a PaCO
2
between 36 and 44 mmHg (4.8–5.8 kPa) is achieved.

International Guidelines and Advisory for the Diagnosis of Brain Death
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Dr Gopi Ayyaswamy
2. Prevention of hypoxaemia: It is crucial to maintain adequate oxygenation
during the test to prevent hypoxaemia. Oxygen should be delivered to
the patient either through a C-circuit with the valve fully open or via a
narrow suction catheter inserted into the endotracheal tube. Monitoring
of respiration can be done by inspecting the reservoir bag and visually
examining for any chest and abdominal movement. Typically, minimal
movement synchronous with the heartbeat is observed. Oxygen
saturation levels should be maintained within the normal range, and
precautions should be taken to avoid a Valsalva effect or barotrauma.
In case of hypotension, adjustments to vasopressor medications may be
required.
3. Absence of spontaneous respiratory efforts: During the test, the patient
should exhibit no spontaneous respiratory efforts despite the presence
of hypercarbia (elevated PaCO
2
) and acidaemia. The arterial blood gases
should be checked at ve-minute intervals until the PaCO
2
rises above
8.0 kPa (60 mmHg) or higher and acidaemia develops. In some cases,
the test may take longer than 10 minutes to achieve the required changes
in PaCO
2
. It is important to note that the apnoea test can potentially
cause instability in the patient’s condition, and there have been reported
deaths during this procedure. Therefore, close monitoring of vital signs
is essential throughout the test.
If no attempt at spontaneous respiration occurs despite the presence
of hypercarbia and acidaemia, the test is considered positive, indicating
brain death. However, it is crucial to consider the patient’s history of
chronic respiratory disease, as decreased sensitivity to high PaCO
2
levels
may affect the interpretation of the test. Achieving the desired level of
acidaemia should be ensured for accurate results.
Additional Information on Spinal Reflexes
Following the occurrence of death, various body movements arising from
spinal cord reexes have been observed. These movements can persist even
after the cessation of all circulation. However, it is of utmost importance to
emphasize that these postmortem movements solely arise from spinal cord
activity and should not be misconstrued as indicators of brain function.
In cases where brain death is clinically documented, conrmation can be
achieved through specic tests such as an isoelectric electroencephalogram
or the absence of intracranial blood ow.

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Several examples of these movements generated by the spinal cord
include abduction or adduction of the arms, leg movements, head rotation
(attributed to cervical muscle activity), and, quite remarkably, brief
attempts by the body to sit up to an angle of 40–60 degrees, often referred
to as the Lazarus sign. Notably, a recent prospective study involving
38 brain-dead patients, predominantly comprising young adults, reported
a 39% occurrence rate of such spinal reex movements.
As we advance our understanding of neurological phenomena and
the intricacies of brain function, these observations of post-mortem
spinal reexes contribute valuable insights to the medical community.
However, it is crucial to interpret such movements in the appropriate
context, ensuring the accurate diagnosis of brain death and avoiding
any misinterpretation that could have signicant implications, especially
in cases involving organ donation and transplantation decisions. The
integration of advanced diagnostic techniques and a comprehensive
approach to brain death determination further enhances our ability to
discern genuine signs of brain function from spinal reex activity after
death.
Note: Please consider these as guidelines only. It is advisable to refer to more current and advanced
medical literature for the most up-to-date information.
Challenging Scenarios
Diagnosing brain death represents a critical juncture in medical practice,
with profound implications for patient care and ethical considerations.
This process marks the point at which ventilator support is withdrawn,
ultimately leading to cardiac death. To ensure a reliable diagnosis,
several prerequisites for testing must be met, and a series of clinical
examinations, including the crucial apnoea testing, are imperative to
validate the absence of brainstem function. However, the diagnostic path
is not always straightforward, and challenging scenarios can emerge,
particularly when dealing with patients who have suffered severe head
and facial injuries. These traumatic injuries can create substantial obstacles
in assessing all brainstem reexes. For instance, evaluating pupillary and
corneal reexes can be impeded due to pronounced facial or periorbital
swelling or direct eye injury. Furthermore, head and facial injuries may
also disrupt the oculovestibular reflex, especially in cases involving

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Dr Gopi Ayyaswamy
complications like cerebrospinal uid leakage or blockage of the external
auditory canal. Despite these challenges, there is no universally agreed-
upon consensus regarding the minimum number of brain stem reexes that
must be assessed. Nevertheless, apnoea testing is universally considered
indispensable. International guidelines offer a practical approach by
highlighting the need to have the capability to test “one eye and at least
one ear” when clinical limitations exist.
It is paramount to acknowledge that the diagnosis of brainstem death
primarily hinges on the clinical judgment of healthcare professionals
who must draw upon their expertise and adhere to formal guidelines.
The weight of this diagnosis necessitates that clinicians not only meet
the prerequisites but also be prepared to provide robust justications if
questioned later. In situations where limitations or contraindications exist
for conducting clinical tests, conrming brain death remains a possibility
through the utilization of conrmatory tests. These additional tests serve
as invaluable tools in verifying brain death, even in cases where patients
do not fully meet the prerequisites, such as individuals who have received
high doses of sedative agents.
When the prerequisites for clinical determination of brain death
cannot be met or when conducting sufficient clinical tests becomes
unfeasible, it is essential to recognize that a diagnosis of brain death
cannot solely rely on clinical examination. In such circumstances, it
becomes appropriate to supplement the clinical signs indicating brain
death with conrmatory tests. The “gold-standard” conrmatory test
for brain death is four-vessel cerebral angiography, which visually
demonstrates the absence of blood ow within the intracranial region.
However, it is worth noting that this test can only be performed in
specialized centers equipped with the necessary cerebral angiography
facilities. More comprehensive descriptions and guidelines regarding the
application of this conrmatory test can be found in international medical
guidelines.
The accurate diagnosis of brain death is a multifaceted and highly
consequential process that requires careful consideration of prerequisites,
clinical judgment, and, when necessary, the use of conrmatory tests to
ensure patient safety and ethical standards are upheld.

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Verification of Death
In order to ensure accuracy, it is common practice to repeat the
aforementioned tests in order to confirm the absence of brainstem
reexes. This step holds particular importance, especially in cases where
organ donation is being considered. It is advised to allow a reasonable
time interval between the two sets of tests, although there is no specic
minimum duration recommended. The apnoea test serves as the nal
examination in this process. If the test results are positive for the second
time, the patient is ofcially declared deceased, and the precise time
and date of death are duly recorded. Many critical care units adhere to
a comprehensive checklist that is completed by the responsible medical
professionals. An exemplication of such a checklist may be provided.
Performing the Tests
The tests for determining brain death should be carried out by two distinct
doctors. One of the doctors should be a consultant, possessing specialized
expertise in the relevant field. The second doctor should be a fully
registered medical professional who has been actively engaged in acute
patient care within the hospital for a minimum of ve years. It is crucial
to ensure that the doctors certifying brain death are not involved in any
potential transplant procedures if organ donation is being considered. This
separation of responsibilities aims to maintain the integrity and objectivity
of the diagnostic process.
Communication, Organ Donation, and other Considerations
In the event that the initial set of formal tests reveals no signs of brainstem
activity, it is of utmost importance to communicate the ndings to the
patient’s family in a compassionate and sensitive manner. It is crucial to
explain that conrmation of these ndings during the anticipated second
testing will lead to a diagnosis of brain death. Recognizing that brain death
provides an opportunity for organ donation and considering the urgent
needs of patients on transplant waiting lists, it becomes the responsibility
of the clinicians, typically the intensive care team, to sensitively discuss
with the family the likelihood of this option arising. The family may be
asked to reect on the patient’s potential wishes regarding organ donation
once brain death is conrmed.

International Guidelines and Advisory for the Diagnosis of Brain Death
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Dr Gopi Ayyaswamy
In situations where organ donation is being considered, it is advisable
to reach out to the transplant coordinator to assess the patient’s suitability
as a potential organ donor. If a diagnosis of brain death is conrmed and
the circumstances surrounding the brain injury require reporting to the
appropriate State Transplant Authority, in accordance with the guidelines
set forth by the National Organ & Tissue Transplant Organisation (NOTTO)
and the Transplant Authority Government of Tamil Nadu (TRANSTAN),
it becomes necessary to inform the Transplant Authority and seek their
permission for organ retrieval intended for transplantation purposes.
Typically, the Transplant Authority grants permission for organ donation;
however, they may require a post-mortem examination and impose certain
limitations on the transplant procedures.
In cases where organ donation is not planned, it becomes important
to establish a specific time for the withdrawal of ventilation. It is
commonly observed that most families prefer to be present during the
subsequent cessation of circulation, which typically occurs over a period
of 10–20 minutes. During this signicant time, every effort should be made
to respect the family’s privacy and accommodate any religious or other
ceremonial practices as much as possible.
Points to Consider
The availability of donor organs remains limited, and the success of
transplantation is heavily reliant on the appropriate management of organ
donors. Therefore, it is of utmost importance that, following the diagnosis
of brain death and consent for organ donation, organs are maintained at
their optimal level of function, and organ procurement procedures are
promptly carried out.
It is essential to note that the guidelines provided in this context are
specically applicable after the diagnosis of brain death in patients who
have the potential to become organ donors. Prior to the diagnosis of
brain death, patients should receive appropriate medical management
based on their underlying medical conditions. However, once brain
death is conrmed, the focus of treatment shifts from protecting the
brain to maximizing the viability and functionality of organs that can be
successfully transplanted.

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Recognizing the signicance of adhering to these guidelines, it is crucial
to acknowledge that their implementation can significantly improve
the outcomes for up to seven transplant recipients. It is important to
emphasize that these guidelines are primarily designed for adult organ
donors, and modifications should be made when applying them to
pediatric organ donors. These guidelines have been formulated based
on recommendations derived from various reputable sources, including
guidelines from Canada, the United States, the United Kingdom, and the
Australian and New Zealand Intensive Care Societies.
In the management of organ transplant programs, continuous monitoring
and laboratory investigations play a vital role. It is crucial to monitor various
parameters such as uid intake/output, pulse oximetry, ECG, temperature,
arterial blood pressure, and central venous pressure to ensure stability
and support for the patient. Regular laboratory investigations, including
blood count, electrolytes, liver enzymes, glucose, arterial blood gas, and
cultures, should be conducted every 12 hours. Targets for heart rate, blood
pressure, mean arterial pressure, cardiac output, urine output, and central
venous oxygen saturation should be maintained within appropriate ranges.
Fluid administration should focus on maintaining organ perfusion without
causing overload, aiming for a central venous pressure of 6–10 mmHg.
These measures are essential in optimizing the management of multi-organ
donors and ensuring successful transplantation outcomes.
Hypotension after brain death can result from various causes: Absolute
hypovolemia, effective hypovolemia (neurogenic shock), and myocardial
dysfunction. Hypertension may also occur in response to stimuli, requiring
treatment with short-acting agents like nitroglycerin, nitroprusside,
esmolol, or labetalol. Optimal management of hypertension and uid
balance is crucial in supporting the multi-organ donor.
Fluid balance is crucial in managing multi-organ donors. Adequate
volume loading with the right combination of crystalloids and colloids
is vital. Dynamic indicators are preferred over static measurements for
uid requirements. Maintaining low-normal ranges for CVP and PAOP
while ensuring organ perfusion has shown improved recipient outcomes.
Echocardiography can guide uid therapy and assess heart suitability
for transplantation. Balancing uid administration and restriction can

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Dr Gopi Ayyaswamy
be challenging, but experienced clinicians can manage it effectively.
Vasopressors like vasopressin and phenylephrine are commonly used,
while inotropes may be guided by central venous oxygen saturation. These
guidelines aim to optimize hypertension and uid management in organ
donors for successful transplantation.
Respiratory management is critical in the care of organ donors due
to the common occurrence of pulmonary dysfunction. Factors such as
pneumonia, aspiration, edema, trauma, and lung injury contribute to this
dysfunction. Optimizing respiratory function is essential to increase the
availability of viable lungs for transplantation. Monitoring oxygenation,
ventilation, and chest X-rays is vital. Endotracheal tube suctioning and
physiotherapy should be performed with strict asepsis. Recommendations
include maintaining positive end-expiratory pressure (PEEP) at 5 cm H
2
O,
using recruitment maneuvers, managing uid balance, positioning the
patient, and maintaining targeted blood gas parameters. Lung-protective
strategies and appropriate tidal volume are crucial. Active measures are
being explored to improve lung function and expand the pool of available
lungs for transplantation.
Diabetes insipidus and hypernatremia are important considerations
in the management of organ donors. Diabetes insipidus causes excessive
urine output and increasing serum sodium levels. Managing uid decits
and ongoing uid losses is essential, typically using hyponatremic uids.
Vasopressin infusion or desmopressin administration may be necessary
to control diuresis. Glycemic control is crucial to prevent hyperglycemia-
related complications, and maintaining a target blood glucose level of
5–8 mmol/L through insulin infusion is recommended. Adequate nutrition
through enteral feeding is important, while total parenteral nutrition
(TPN) should be continued if already initiated. Effective management of
diabetes insipidus, hypernatremia, and glycemic control promotes optimal
outcomes for organ donors.
Maintaining normothermia is crucial in the management of organ
donors. Hypothermia, commonly observed in donors, can lead to various
complications. The primary goal is to keep the core temperature above
36°C. Active measures such as warming blankets, uid warmers, and
heated humidiers are utilized to raise body temperature. By preventing
and counteracting hypothermia, healthcare professionals can minimize
adverse effects and optimize the donor’s condition.
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