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 . 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 abuse, sought. The presence of HIV infection is an absolute contraindication to organ donation, as is hepatitis B infection (in most countries) and active systemic sepsis, for example major abdominal infection. The presence of malignancy within the past 5 years is also an absolute contraindication to organ donation, with the exceptions of low-grade primary turnouts of the CNS, nonmelanotic turnouts of the skin and carcinoma in situ of the uterine cervix. If there are no general contraindications to organ donation consideration is then given to organ-specific selection criteria.
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.
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 organs to be procured, they are perfused in situ. The heart is perfused with cold cardioplegia solution via a cannula in the ascending aorta, and the lungs are perfused via a cannula in the pulmonary artery. The abdominal organs are perfused with chilled organ preservation solution via an aortic and portal cannula. Blood and perfusate are vented from the left atrial appendage and the inferior vena cava. This produces rapid cooling of the organs, reduces their metabolic activity and preserves their viability. Additional surface cooling of the abdominal organs may be achieved by application of saline ice slush. The heart and lungs are excised followed by the liver and pancreas and then the kidneys, either en bloc or separately. The extent to which the abdominal organs are dissected prior to cold flush depends on the preference of the surgical team. Some surgeons perform minimal dissection prior to cold perfusion and complete the dissection of the abdominal organs in situ or on the back table after the organs have been removed en bloc. During procurement of the liver care is taken to ensure that, if there is an aberrant hepatic artery arising from the superior mesenteric artery, it is included in the aortic patch. Similarly, care is taken to ensure that any polar renal arteries are included on an arterial patch with the renal artery. A length of the donor iliac artery is excised for use in reconstructing the arterial supply of the pancreas.
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.
The use of UW solution (developed by Belzer and colleagues) is particularly effective for liver grafts and, after perfusion with UW, the liver can be stored safely for up to 24 hours. The length of time for which an organ can be stored before transplantation varies depending on the type of organ.After arriving at the recipient transplant centre any necessary bench surgery is undertaken prior to implantation.
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. Live donation should proceed only after the prospective donor has undergone rigorous assessment to ensure that they are suitable. Before the donation it is essential to perform renal imaging (commonly a selective renal angiogram) to delineate the anatomy of the arterial supply to the kidneys. If the left kidney has a single renal artery it is usually chosen for transplantation because it has a longer renal vein which simplifies the transplant operation. Donor nephrectomy is undertaken either through a loin incision and retroperitoneal approach or through a midline abdominal incision and transperitoneal approach. Laparoscopic donor nephrectomy has recently attracted interest but its role in living donation is not established . The mortality rate for live donation is less than 0.05 per cent and the major complication rate is around 5 per cent. In the long term, a slight elevation in proteinurea and a small rise in blood pressure accompany unilateral nephrectomy.
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 living related liver transplants have been performed worldwide, predominantly in countries where cadaveric donation is not practised. The left lateral segment or left lobe from an adult is transplanted into a paediatric recipient. In countries where heart-beating cadaver donation is undertaken, live donor liver transplantation has been superceded by the techniques of liver reduction or liver splitting. The latter approach allows the liver from a cadaver donor to be split in two, so that the right lobe can go to an adult and the left lobe to a paediatric recipient. In North America, living donor combined kidney and segmental pancreas transplantation has been undertaken to treat insulin-dependent diabetics with end-stage renal disease. In occasional patients living donor small bowel transplantation has been performed using a small bowel graft which comprises a length of around 1.5 m of ileum. Finally, a small number of living donor segmental lung transplants has been performed. To provide sufficient pulmonary tissue without compromising the donor it is necessary to use segments from two different donors for each recipient. The ethical issues raised by living donation for extrarenal organs are understandably complex.
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.
No comments yet.