Organ
donation
Most of the organs used for transplantation are obtained from
brainstem-dead, heart-beating cadaveric donors and in the majority of cases
multiple organs are procured. However, the number of organs required to satisfy
the needs of transplantation far exceeds the number of cadaveric organs
available. This has prompted a relaxation in the organ-specific donor selection
criteria and the use of organs from so-called ‘marginal donors’. In the case
of kidney transplantation there is a trend towards increased living donor
transplantation and the use of kidneys from nonheart-beating cadaver donors.
Determination
of brainstem death
Brain death occurs when severe brain injury causes irreversible loss
of the capacity for consciousness combined with the irreversible loss of the
capacity for breathing. In most countries, it is accepted that the condition of
brain death equates in medical, legal and religious terms with death of the
patient. The concept of brain death arose through necessity in the management
of patients with irreversible brain damage on life support where there was no
prospect for recovery. It was not in the interest of such patients, their
relatives or the hospital in which they were being treated to delay their
inevitable demise by continuing with futile life support. Acceptance of the
concept of brain-death had major implications for organ transplantation as it
allowed the possibility for removal of viable organs from brain-dead patients
before their circulation failed.
In
the UK, and many other countries, brain death is defined in terms of permanent
functional death of the brain-stem as neither consciousness nor spontaneous
respiration is possible in the absence of a functional brainstem. A diagnosis of
brainstem death should only be considered when certain preconditions have been
met. The patient must have suffered major brain damage of known aetiology, be
deeply unconscious and require artificial ventilation. Traumatic head injury and
sudden intracranial haemorrhage are the most common causes of brainstem death.
Particular care must be taken to ensure that muscle-relaxant agents and drugs
with known CNS-depressant effects are not contributing to the clinical picture.
Hypothermia, profound hypotension and metabolic or hormonal conditions that may
contribute to CNS depression and confound the diagnosis of brainstem death must
also be excluded. When the necessary preconditions have been satisfied formal
clinical assessment of the brainstem reflexes can be undertaken (Table
11.3).
The UK guidelines state that the tests should be performed on two separate
occasions by two clinicians experienced in this area. At least one of the two
clinicians should be a consultant and neither should be connected with the
transplant team. The time that must elapse between the two sets of brainstem
tests is not specified in the guidelines and is determined on the basis of
clinical judgement. In the UK there is no requirement to perform
electrophysiological or brain perfusion studies to aid the diagnosis of
brainstem death. Particular care is required in the diagnosis of brainstem death
in neonates and infants.
Evaluation
of the cadaveric donor
After a brainstem-dead donor has been referred to the transplant team
with a view to organ donation the general suitability of the potential organ
donor must be carefully assessed. Particular care must be taken to assess the
donor from the point of view of transmissible infectious agents and malignancy.
The medical history should be carefully scrutinized and evidence of risk
factors for human immunodeficiency virus (HIV), such as intravenous drug
The
demand for cadaveric organs for transplantation far exceeds the supply and,
consequently, there has been a progressive relaxation in the organ-specific
selection criteria. The chronological age of the donor is less important than
the physiological function of the organs under consideration for
transplantation. As a rough guide acceptable donor age ranges for each of the
commonly transplanted organs are as follows:
• kidney — 2—74 years;
• liver — 0—75 years;
• heart — 0—65 years;
• lung — 0—60 years;
• pancreas — 10—50 years.
The organs to be donated should generally be free from primary disease.
Kidney donors should not have evidence of primary renal disease. They should
have a reasonable urine output and normal serum urea and creatinine, although
acute terminal elevations are acceptable. Liver donors should not have hepatic
disease, although impaired liver function tests are common in cadaver donors and
do not necessarily preclude donation. Heart donors should not have a history
of pre-existing heart disease. They should have a normal electrocardiogram (ECG);
in doubtful cases an echocardiogram may also be necessary. Lung donors should
have no history of primary lung disease. The chest X-ray and gas exchange should
be satisfactory, and bronchial aspirates should be free from fungal and
bacterial infection. Pancreas donors should not have a history of diabetes
mellitus, but elevations of blood glucose and serum amylase are not uncommon in
cadaveric donors and do not preclude transplantation.
Organ
procurement
When brainstem death has been confirmed, management of the donor is
aimed at preserving the functional integrity of the organs to be procured.
Brainstem death produces profound metabolic and neuroendocrine disturbances
leading to cardiovascular instability. Careful monitoring and management of
fluid balance is essential. Inotropic support is given and there may be a role
for the use of tri-iodothyronine (13) and argipressin.
Procurement
of multiple organs from a cadaveric donor requires co-operation between the
thoracic and abdominal surgical teams. A midline abdominal incision and median
sternotomy are used to obtain access. After dissection of the
After
removal from the donor the organs may undergo a further flush with chilled
preservation solution and are then each placed in two sterile plastic bags and
stored at 0—40C by immersion in ice while they are transported to
the recipient centre to await implantation. After the donor organs have been
excised, samples of donor spleen and mesenteric lymph nodes are obtained for
determination of tissue type and for the cross-match test.
Various
organ-preservation solutions are available for flushing organs before simple
cold storage. They all contain impermeants to limit cell swelling, buffers to
counter acidosis and electrolytes, the composition of which reflects that of
intracellular rather than extracellular fluid. Commonly used preservation
solutions include University of Wisconsin (UW) solution and Eurocollins
solution, but there are many others.
Nonheart-beating
(asystolic) donors
There is renewed interest in the use of kidneys from nonheart-beating or
asystolic donors in an attempt to address the shortage of organs for
transplantation. Kidneys may be procured from patients who are dead on arrival
at the hospital or who have died in hospital after withdrawal of support or
following unsuccessful resuscitation. In order to minimise the warm ischaemic
time, a double-balloon catheter is introduced into the aorta via a femoral
cutdown and used to cool the kidneys in situ by chilled perfusate,
preferably within 30 minutes of circulatory arrest. Kidneys obtained from
nonheart-beating donors invariably suffer from delayed function and this
approach is not suitable for organs other than the kidney.
Living
kidney donors
Currently, living donor renal transplants account for around 20 per cent
of the total renal transplant activity. The justification for living donor
renal transplantation is based on the shortage of cadaveric transplants and the
superior results obtained. Most living donor transplants are between genetically
related individuals. However, living donor kidney transplants performed
between genetically unrelated individuals also fare better than even
well-matched cadaveric grafts, and this observation has given rise to an
increase in living unrelated kidney transplantation activity, usually between
spouses or partners. It is essential to ensure in all cases of living donation
that the prospective donor is fully informed and is free from coercion to donate
and that the risk to the donor is small.
Living
donors: extrarenal organs
Living donors have occasionally been used to provide segments of
liver, pancreas, small bowel and lung for transplantation but this is more
controversial. Several hundred
Resumption
of function following organ transplantation
It is crucial that following heart, lung or liver transplantation, the
transplanted organ resumes satisfactory function immediately. If primary
nonfunction occurs the only option is rapid re-transplantation. After kidney,
pancreas or small bowel transplantation immediate graft function is desirable
but not vital. The factors that influence the functional integrity of a
transplanted organ are shown in Table 11.6.