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A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
on graft success. Different treatment protocols have been explored, including
techniques such as ischemic preconditioning, the use of anti-intercellular
adhesion molecule antibody, anti-C5a, selectin inhibitors, n-acetyl cysteine,
mannitol, and corticosteroids. The effectiveness of these approaches may
vary, and ongoing research aims to rene and optimize their use.
During the organ retrieval surgery, donor care presents unique
challenges that go beyond routine anesthesiology practice. The primary
focus shifts from preserving the patient’s well-being to preserving
the organs for transplantation. Multiple surgical teams often work
simultaneously and sequentially during the procedure, and effective
interdisciplinary communication is essential. Anesthesiologists play a
pivotal role in facilitating information sharing and fostering constructive
interaction among the teams involved.
The standard protocol for organ removal follows a specific order,
with the heart and lungs being removed rst, followed by hepatectomy,
pancreatectomy, and bilateral nephrectomies. Throughout the procedure,
maintaining cardiovascular function, adequate oxygenation, acid–base
balance, electrolyte levels, glucose levels, and temperature within the
physiological range is of utmost importance. Ensuring an adequate urine
output exceeding 100 ml/hour is also recommended. The multidisciplinary
team administers heparin, phentolamine (a vasodilator), antibiotics, and
corticosteroids based on consensus guidelines.
To facilitate optimal surgical exposure and prevent patient movement
due to spinal reexes, neuromuscular blocking agents are administered.
Mechanical ventilation is typically not required after the cross clamping
of the aorta, and this milestone is documented accordingly. It is crucial to
note that this point in the procedure is not considered the “time of death.”
The declaration of brain death previously established the time of death.
Advancements in donor care for organ transplantation have shown
promising outcomes in improving organ viability and transplantation
success. The administration of specic medications, the implementation
of cytoprotective therapy, and effective interdisciplinary communication
during the organ retrieval surgery are all vital elements in optimizing
organ preservation and increasing the likelihood of successful
transplantation. Ongoing research and collaborative efforts among
Donor Management
105
Dr Gopi Ayyaswamy
healthcare professionals continue to drive advancements in the eld,
offering hope for patients in need of life-saving organ transplants.
Post-Brain Death Organ Preservation Protocol
• Non-pharmacological support should be continued according to comfort
care orders for post-brain death patients.
• Discontinue all medications, except antibiotics and those necessary for
maintaining hemodynamics, homeostasis, and uid balance.
• If the patient is using cardiac assist devices or cardiac pacemakers, keep
them in place until consent discussion for organ donation.
• Administer intravenous 0.9% saline at a rate of 1 ml/kg/hour to
maintain normal blood volume.
• Utilize intermittent positive pressure ventilation (IPPV) with a tidal
volume of 10 ml/kg, positive end-expiratory pressure (PEEP) of 5 mmHg,
and maintain plateau pressures at –20 mm Hg.
• Perform manual lung hyperination therapy immediately after declaring
death to optimize lung function.
• Administer a 15 mg/kg intravenous bolus of methylprednisolone to
reduce inammation.
• Administer an intravenous bolus of T3 (Triiodothyronine) at 4 µg,
followed by a continuous infusion of 3 µg/hour to support thyroid
function.
• Administer an intravenous bolus of 1 unit of vasopressin, then adjust
the infusion rate between 0.5–2.4 units/hour to maintain an optimal
urine output of 200 ml/hour.
• Administer a slow intravenous bolus of vecuronium at a dosage of
0.5 mg/kg to induce muscle relaxation.
• Maintain a central venous pressure between 6 and 12 mmHg to ensure
proper blood volume.
• Maintain a systolic blood pressure between 90 and 140 mm Hg (or mean
arterial pressure of 60–80 mm Hg) to support adequate perfusion.
• Maintain a heart rate between 60 and 120 beats per minute for optimal
cardiac function.
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A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
• Maintain the core temperature between 34°–37.5°C to prevent
hypothermia or hyperthermia.
• Aim for a urine output between 0.5 and 1.0 ml/kg/hour, not exceeding
200 ml/hour to ensure proper renal function.
• Maintain oxygen saturation at 92% or above to support adequate tissue
oxygenation.
• Ensure normocarbia, (is a state of normal arterial carbon dioxide
pressure) with a partial pressure of carbon dioxide (pCO
2
) around
40 mmHg for proper acid–base balance.
• Maintain arterial pH within the range of 7.35–7.45 for optimal
physiological function.
• Target a hematocrit level of 30% to maintain adequate oxygen-carrying
capacity.
• Maintain a platelet count above 50,000 per cubic millimeter to support
proper coagulation function.
• Control glycemic levels between 80 and 200 mg/dl, utilizing an
intravenous insulin protocol as needed to prevent hyperglycemia or
hypoglycemia.
• Maintain sodium levels between 130 and 150 mEq/L for proper
electrolyte balance.
• Keep potassium levels within the range of 3.5–5.0 mEq/L to support
normal cellular function.
• Ensure magnesium levels between 1.8 and 2.5 mEq/L for optimal
neuromuscular function.
• Maintain phosphorus levels between 2.0 and 4.5 mEq/L for proper bone
health and energy metabolism.
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.
Maintaining Homeostasis for Organ Preservation
To ensure optimal organ viability, it is crucial to maintain the physiological
state of the organs as close to normal as possible. This involves employing
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Dr Gopi Ayyaswamy
quick and uniform cooling techniques to minimize warm ischemic damage.
Although cooling alone does not completely halt metabolic processes
within cells, the utilization of an appropriate washout technique and
preservation solution becomes vital for preserving organ viability.
Complete removal of all blood cells from the vascular space through
thorough washout ensures uniform distribution of the preservation
solution throughout the microvessels. This helps decrease immune
reactions and the formation of oxygen-free radicals upon reperfusion. The
preservation solution plays a critical role in establishing colloid-oncotic,
osmotic, and electrolyte balances across cellular membranes within the
preserved organ. These balances are essential for maintaining constant
cellular volume, membrane integrity, physiological pH, and nutrient
supply. By maintaining the Na
+
and K
+
gradients across the membrane,
ATP-ase activity is preserved, ensuring sufcient energy for cellular
functions.
The preservation solution also includes components that act as precursors
to rapidly restore ATP concentration upon reperfusion, scavengers that
neutralize free radicals, and antibiotics to control bacterial growth. Organ
preservation serves as the supply line for organ transplantation. Currently,
the University of Wisconsin (UW) organ preservation solution is utilized
for successful preservation of the liver, pancreas, and kidney for up to two
days. This preservation solution employs cell impermeant agents such as
lactobionic acid, rafnose, and hydroxyethyl starch to prevent cell swelling
during cold ischemic storage. Additionally, the UW solution contains
glutathione and adenosine, which can enhance antioxidant capacity and
stimulate high-energy phosphate generation upon reperfusion, respectively,
thereby promoting recovery of normal metabolism.
The implementation of the aforementioned techniques has signicantly
extended the functional viability of procured organs and has reduced
time constraints throughout the entire transplant process, including
transportation, preparation, and surgery.
Organ Retrieval and Optimization
There is a growing understanding of the importance of allowing sufcient
time in the intensive care unit (ICU) to optimize organ function, leading to
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A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
improved outcomes in transplantation. During this period, therapy can be
administered to address reversible organ dysfunction, such as myocardial
dysfunction, impaired gas exchange in the lungs, bacterial infections,
and acute impairment in renal or hepatic function. This treatment period
typically lasts between 12 and 24 hours and should involve frequent
reassessment to monitor improvements in organ function towards
predened targets. Ultimately, the nal decision regarding transplant
suitability rests with the transplant teams responsible.
While there are clear benets to delaying organ retrieval in order to
improve the condition of the organs, it is important to balance this with
the potential distress it may cause to the patient’s family. The actual
retrieval of donated organs in the operating theater can take approximately
2 to 4 hours to complete. To ensure cardiovascular stability and create
optimal operating conditions (although general anesthesia to prevent
awareness is not required in brain-dead patients), a volatile agent (with
or without an opiate) and a muscle relaxant are typically administered.
Measures to optimize the condition of the organs should be continued until
the organs are removed. At the conclusion of the procedure, the ventilator
is switched off, and the endotracheal tube is removed.
Psychological Considerations for Staff and Relatives
Medical and nursing staff involved in caring for patients who are legally
deceased need to have a comprehensive understanding of the moral,
ethical, legal, and clinical principles guiding their care. It is crucial
to provide education and training to these healthcare professionals.
Managing such cases can be psychologically demanding, both in terms of
clinical management of the patient and in interactions with their relatives.
Junior medical and nursing staff, in particular, require education and
support to appropriately manage the patient and effectively communicate
with the relatives.
Legal Framework for Organ Donation in India
The legal framework pertaining to organ donation in India is clearly
outlined in the Transplantation of Human Organs Act (THOA) guidelines
of 1994, which are regularly updated with amendments. This Act provides
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Dr Gopi Ayyaswamy
guidelines for regulating the removal, storage, and transplantation of
human organs for therapeutic purposes, as well as preventing commercial
dealings in human organs. Specic guidelines for organ donation in the
armed forces in India are based on similar regulations established by the
Armed Forces Organ Retrieval & Transplantation Authority (AORTA).
Establishment and Functions of AORTA
The Director General of Armed Forces Medical Services approved the
establishment of the Armed Forces Organ Retrieval & Transplantation
Authority (AORTA) at Army Hospital (Research & Referral), New Delhi
on 11 April 2007. AORTA has various functions, including operating a
24-hour referral service for organ donation, maintaining a donor registry,
providing family counseling and support, and coordinating organ retrieval
and transplantation activities between different service hospitals and civil
organizations.
Addressing the Organ Shortage
Increasing organ donation is a crucial and commendable objective. There is
a signicant gap between the number of patients awaiting transplantation
and the availability of organs. Although resolving this disparity may seem
practically impossible at present, it is essential to make every effort to
identify potential donors, obtain consent, and convert potential donors
into actual organ donors. It is necessary to continually expand the pool of
live donors and explore new techniques for procuring viable organs from
deceased donors. This includes the growing consideration of donation
after cardiac death in some centers. However, in many parts of the world,
the majority of organs retrieved come from conventional donation after
brain death, highlighting the importance of providing optimal care to these
donors before and after the diagnosis of brain 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.
Dr Gopi Ayyaswamy
International Guidelines and
Advisory for the Diagnosis of
Brain Death
14
The concept of brain death is widely recognized and accepted in the
medical community, as well as in nursing and general literature. It
acknowledges that patients who have suffered severe brain injuries and are
being articially ventilated can experience a complete and irreversible loss
of brain stem function. Brain death is considered to be equivalent to cardiac
death, which is the legal denition of death in many jurisdictions. Despite
ongoing mechanical ventilation and supportive therapy, cardiac asystole,
the cessation of cardiac activity, typically occurs within a few days or
weeks after brain death. Certifying death in cases of irreversible brainstem
function loss allows intensive care specialists and healthcare professionals
to discontinue futile treatments, such as mechanical ventilation, based on
considerations of compassion, ethics, and practicality.
In the Republic of Ireland, there is currently no specic statutory
law that governs brain death. However, the proposed Human Tissue
Bill (2009) includes a clear denition of brain death as “the irreversible
cessation of all functions of the entire brain, including the brain stem.”
The draft Bill also emphasizes the importance of making a determination
of death in accordance with accepted medical standards. While awaiting
the passage of this Bill into law, healthcare professionals in the Republic
of Ireland are advised to follow the recommendations outlined in the
Irish Memorandum on Brain Death, which aligns with the approach
described in this document. Adhering to these recommendations carries
the legal status of “custom and practice” in the Republic of Ireland,
providing guidance for healthcare professionals in the absence of specic
legislation.
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A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
History of the Establishment of the Criteria for Brain Death
1959: Moularet P, Goudon M. Coma depasse et necrosis nerveuses centrales
massives. Revue Neurologique 101:116–139. This was the reference
publication proposing a name (Coma depasse) for the ‘death of the nervous
system’, the clinical, electrophysiologic and angiographic features of which
had been described in the French and Scandanavian literature between
1956–1959.
1968: The concept of brain death as death was proposed by an Ad Hoc
Committee of Harvard Medical School.
1976: UK Royal Medical Colleges defined brain death as complete
irreversible loss of brain stem function and specied clinical criteria to
certify brain death.
1981: USA Presidents Commission published Guidelines. Recommended
conrmatory tests to reduce the required period of observation. Recommended
a period of 24 hours observation for patients with anoxic brain damage.
1988: Irish Medical Journal published a Memorandum on Brain Death
from an ad-hoc Irish Working Party essentially constituting guidelines for
Ireland on the clinical criteria for diagnosis of brain death.
1995: Australian publication of Guidelines on clinical conrmation of
brain death.
2006: Canadian Council for Donation and Transplantation published
national guidelines for determination of brain death.
Approach to the Clinical Diagnosis of Brain Death
When evaluating a comatose patient for brain death, it is essential to follow
specic principles and criteria. This includes identifying the cause of the
coma, conrming its irreversibility, ruling out confounding factors, and
conducting comprehensive testing of all possible brainstem reexes. The
clinical diagnosis of brainstem death should only be made if the following
conditions in A and B are met.
Establishing Proof of Irreversible Structural Brain Damage
It is crucial to accurately diagnose a condition that can lead to brain death.
Loss of brainstem reexes can be caused by conditions other than brain stem
International Guidelines and Advisory for the Diagnosis of Brain Death
113
Dr Gopi Ayyaswamy
death, such as brain stem encephalitis, which may have the potential for
recovery with appropriate treatment. If there is any uncertainty regarding
the primary diagnosis, a clinical diagnosis of brain death should not be made.
In each patient, there should be clear evidence and well-documented
documentation of the underlying neurological diagnosis that resulted
in severe neurological injury and loss of brainstem reexes. Additional
evidence of signicant brain pathology, such as abnormalities observed
on CT scan, angiography, or MRI scan, is typically obtained. However,
the presence of abnormalities on a CT scan consistent with brain death
does not eliminate the need to rule out confounding factors. Conversely, a
normal CT scan can be observed shortly after a cardiac or respiratory arrest.
In cases of acute hypoxic-ischemic brain injury, the clinical evaluation
for brain death should be delayed for at least 24 hours after the cardio-
respiratory arrest.
Exclusion of Reversible Causes of Coma
a. Coma can be caused by toxins, poisons, sedative drugs, and other
substances when patients are exposed to high quantities. It is important
to review the patient’s medication history and, if necessary, conduct a
toxicology screen.
b. Adequate time must be allowed for the effects of sedative drugs to
dissipate. In cases where sedatives have been used for a prolonged
period or in high doses, determining whether they still contribute to the
depth of coma can be challenging. This is particularly true for highly
lipid-soluble drugs like thiopentone. Recent recommendations suggest
waiting for a duration equal to four times the elimination half-life of
the sedatives used. However, this approach does not account for factors
such as the duration of infusion (context-sensitive half-life), altered
pharmacokinetics with high doses, or the presence of active metabolites.
c. The use of antagonist agents may be benecial. If muscle relaxants
have been administered, conrming intact neuromuscular conduction
using a peripheral nerve stimulator is important. Administering the
antidotes naloxone and umazenil can be helpful when opioids or
benzodiazepines have been used, and any changes in brainstem reexes
should be observed.