Chapter 93 Organ donation
Intensivists often have responsibility for the care of organ transplant recipients and have seen the benefits they obtain from transplantation. Clinical results continue to improve, despite increasing recipient case complexity and increasing use of organs from extended-criteria deceased donors, and this success continues to drive demand for transplantation.1 At the same time, deaths from road trauma (once the most common cause of death in deceased-donor organ donation) continue to fall in many countries as a result of both primary prevention and better treatment of traumatic brain injury. Decompressive craniectomy in particular is effective in controlling refractory intracranial hypertension2 (and thereby reducing brain death), although whether outcomes are improved overall await the results of two ongoing clinical trials. Similarly, population-based studies have shown falls in the incidence and mortality of subarachnoid haemorrhage3 and perhaps also intracerebral haemorrhage. Treatments for some other conditions which uncommonly contribute to deceased-donor donation (e.g. hypoxic–ischaemic encephalopathy, meningitis) have also improved.
With the exception of the USA, many countries are now experiencing a fall in brain dead organ donation. Transplant numbers have been maintained, or only modestly increased, by other strategies, including donation after cardiac death (DCD, formerly called non-heart beating donation), live donors (including altruistic donors) and the use of split livers for two recipients. There is considerable pressure on intensivists and others to provide a solution to the ‘organ donor shortage’, but less consideration given to restricting access to waiting lists. Despite widespread condemnation of the practice, desperate recipients from wealthy countries take part in ‘transplant tourism’4,5 in Asia (particularly in China, including organs from executed prisoners), Africa and South America. The internet has facilitated a form of altruistic but directed live donation which also is potentially vulnerable to commercial exploitation (e.g. http://www.matchingdonors.com). Slow progress continues in alternative approaches to end-stage organ failure, including artificial organs, xenotransplantation and the engineering of organs and tissues from stem cells, but none is yet available for routine clinical use.
RESPONSIBILITIES OF THE INTENSIVIST
Most intensivists are supportive of deceased-donor organ donation.6 Those who are not should make arrangements with other intensivist colleagues for the care of potential organ donors and discussions with their families.7 Intensivists’ responsibilities include the care of dying patients and of their families in the intensive care unit – the location of organ donation itself. Intensivists therefore must either define and take responsibility for good practice in organ donation, or accept that these processes will be taken over by others with the objective of ‘transforming the greatest possible number of cadavers into real donors’.8 This personal epiphany9,10 is not yet widely shared in intensive care medicine.
CARE OF THE DYING PATIENT AND THEIR FAMILY
Intensivists are familiar with the care of the dying patient, including the need to avoid suffering and maintain patient dignity. The respect of the intensive care unit (ICU) staff for the humanity of the dying person is expressed in the ‘patient comfort care’ provided by the nursing staff, the continued involvement and attentiveness of the medical staff, and in evident compassion of all staff for the family.11
On behalf of all the treating team, an intensivist should establish rapport during an early meeting (e.g. the morning after admission) with the family of every intensive care patient. This is particularly important for families of patients at high risk of death or disability with whom there will often need to be several ‘bad news’ meetings over several days. Family meetings should be attended by whomsoever the family defines itself to include, by the intensivist, and by a member of the nursing staff supporting the family (preferably the ‘bedside nurse’ looking after the patient). If the family wishes, the meeting might include a chaplain, social worker or cultural health worker. The ‘support’ role should be kept separate from the ‘bearer of bad news’ role. Family meetings should be held in a separate private room large enough to accommodate all the participants, away from the bedside and protected from interruption. With evident compassion11 the intensivist should convey an accurate account of the sequence of events, a realistic prognosis (in as much as this is possible) and the immediate treatment plan. Some families find CT or other visual information helpful. There must be enough time to answer any questions that the family may have. At the end of the meeting the intensivist should ascertain that the family understands what has been said11 and agrees with the immediate plan. Ensuring that all team members give the family congruent messages is an essential part of maintaining the trust of the family in the ICU team. Ideally, one intensivist should speak with the family but where this is impractical it is vital that there be detailed and explicit discussions between one intensivist and another before the next family meeting. A relationship of mutual understanding and trust will enable the ICU team and the family to work together through difficult and painful issues, including withdrawal of intensive therapies,12 death of the patient and consideration of organ donation.
Many patients who develop apparent loss of brainstem function do so despite continuance of all available surgical and medical therapy. In these circumstances, brain-oriented intensive therapies (including sedatives, opioids, neuromuscular blockers, hypothermia and osmotherapy) should be withheld pending formal assessment of brain death. In order to meet the preconditions for brain death assessment,7 extracranial homeostasis must be maintained, and these conditions also preserve the possibility of organ donation in the future.
Withdrawal of intensive therapies is common practice in Australasian ICUs.12–14 In the setting of severe brain damage this first involves assembling definitive prognostic information. Although neurophysiology and imaging provide important supportive information, a sedative-free clinical assessment of CNS function is an essential aspect of prognostication. During the period of sedative-free CNS assessment, some patients will suffer apparent loss of brainstem function. If brain death does not occur, but devastating brain damage has clearly occurred, those treating the patient (e.g. intensivists, neurosurgeons and others) should achieve a consensus view of prognosis and a recommended treatment plan, which might include withdrawal of intensive treatments (e.g. artificial airway, ventilatory or inotropic support, further neurosurgery). The intensivist should then discuss the prognosis and recommended plan with the family and facilitate a consensus. Withdrawal of treatment may subsequently occur, either because death is seen to be imminent and inevitable or because the likely survival outcome would not be in accord with the patient’s previously expressed wishes or inferred best interests. Such a decision to limit or withdraw treatment is guided by the principles of non-malfeasance and respect for autonomy.15 It is appropriate to withdraw all intensive therapies from such patients, while continuing to provide ‘comfort care’ to the patient and support to the family.15
IDENTIFICATION OF THE POTENTIAL FOR ORGAN DONATION TO OCCUR
Most ICUs admit patients with very severe brain damage whose probability of recovery is low. The rationale for this practice is to identify any (small) subgroup of patients with reversible conditions and provide them with the necessary treatment to facilitate their recovery. There are, however, more extreme situations when the chance of recovery is thought so remote that admission of the patient to ICU would not ordinarily occur. Some intensivists advocate admitting these patients to ICU solely to allow for the future possibility that organ donation may occur, sometimes with accompanying explicit discussion and agreement of the family to such a plan.16 Although it seems likely16 that such an utilitarian approach might increase the number of organs available for transplant, ethical,17 legal18 and clinical17 objections to the practice have all been raised.
Organ donation is possible in most situations where brain death has been confirmed. The absolute general contraindications to organ donation are few and present in a small minority of brain-dead patients. They include situations where there is an unacceptably high risk of transmission of malignancy or infection to the recipient, or where the function of the possible donor organs is likely to be unacceptably poor. Most extracerebral malignancies and certain infections (e.g. HIV) are likely to remain absolute contraindications but other donor factors (e.g. advanced age, recent bacterial sepsis,19 treated HSV encephalitis, positive HCV20 or HBV20 serology, some ‘apparently cured’ malignancies) are no longer absolute contraindications. Intensivists should discuss the specific issue with the appropriate agency (donor coordinator or organ procurement organisation) rather than decide that organ donation is contraindicated on medical grounds. Similarly, the organ-specific contraindications to organ donation have reduced in recent years as the outcomes of recipients transplanted with donor organs formerly rejected have been found to be acceptable.21 Finally, all contraindications vary somewhat between transplant centres and continue to change in a more permissive direction. Intensivists should discuss these organ-specific issues with the donor coordinator or appropriate agency before deciding that any particular organ is unsuitable for possible donation and subsequent transplantation. In most jurisdictions an appropriate authority (e.g. a coroner or medical examiner) may legally interdict organ donation under certain circumstances (e.g. homicide) and this issue must also be clarified with the donor coordinator. The donor coordinator will clarify with the transplant teams whether any organ donation is possible and whether particular organs may not be suitable, and the intensivist should ensure that the information (Table 93.1) necessary for these decisions is provided.
Table 93.1 Information likely to be required by transplant teams
DETERMINATION OF BRAIN DEATH
This is a clinical responsibility of the intensivist and must be carried out according to appropriate codes of practice or clinical guidelines (see Chapter 46). The determination of brain death7,22,23 involves several stages:
The examination and determination of brain death is facilitated by a proforma and should be documented in the medical record. When clinical examination is confounded (e.g. by barbiturate coma), then absent cerebral blood flow must instead be demonstrated by reliable imaging.7
The intensivist should convey the fact of brain death and its medical and legal implications to the family. It can be difficult to accept brain death as death, given the life-like appearance of the skin, the rise and fall of the chest and the warmth of the hands that are preserved by ventilatory and circulatory support.24 Some family members appreciate an offer to view the (second) clinical examination for brain death (taking care to explain beforehand the possibility of spinal reflexes), or the cerebral blood flow study when clinical examination is confounded. This may help them to understand and accept the final awful implication of this diagnosis. Intensivists should be open to offering these options.
DONATION AFTER CARDIAC DEATH
In all but Category III the situation is ‘uncontrolled’.25
DCD practice varies considerably worldwide. Category II donors are most common in the Dutch experience but donation does occur from all categories. Almost all DCD donors in the UK, USA, Canada and Australasia are Category III (and a very few are Category IV). By contrast, in Spain, although withdrawal of treatment in ICU is far less common than in Holland or the UK,26,27 and Category III donors are rare, immediate postmortem organ preservation measures (including cardiopulmonary bypass) can be implemented with prior consent and most DCD donors are Category I and II.28 Recent advocates for DCD commonly assert that ‘all organ donation occurred this way’ before brain death was accepted as legal death. Although organs were removed after circulatory arrest, there are differences which are not discussed and which negate the assertion that the processes are identical. Although brain death was not accepted as legal death, the syndrome had been recognised many years earlier (e.g. absent cerebral blood flow29 was reported in 1956 and the clinical syndrome30 in 1959). The final awful meaning of the brain death syndrome (‘apnoea, fixed dilated pupils, polyuria, hyperglycaemia and spontaneous hypothermia’31) was understood by intensivists and nephrologists and conveyed to families at that time, prior to a discussion of organ donation (PB Doak, RV Trubuhovich, personal communications). Organ donation was not discussed with the family if some brainstem function (usually only a tracheal reflex) was known to be present. Apnoea at hypercarbia was not specifically tested for but the shared expectation of the family and the treating team was that the patient would not breathe after withdrawal of ventilatory support (although a few did, for a short time and inadequately). Cardiac arrest usually occurred in 15–20 minutes, at which point death was declared and the kidneys were removed.
Delayed graft function is more common (∼40% vs. ∼20%) in recipients of DCD kidney grafts,32 but long-term recipient outcomes are equivalent to those who receive a graft from a brain-dead donor.33 Both graft and patient survival after DCD liver grafts are lower than after grafts from brain-dead donors (e.g. 5-year graft survival 52% vs. 66%, 5-year patient survival 65% vs. 72%),34,35 probably reflecting both intolerance of the liver to more than 15 minutes of warm ischaemia and impaired small vessel washout of the biliary system. Less viscous preservation solutions may ameliorate this latter problem. Patient survival is less impacted than graft survival but at the expense of an increased frequency of retransplantation. Recipient and graft outcomes after pancreas transplantation with grafts from DCD donors are similar to those from brain-dead donors.36 Although successful lung and even heart transplantation from DCD donors is being reported, experience so far is insufficient to characterise the long-term recipient outcomes.
Following the Institute of Medicine report37 in 1997 there has been an explosion of publications on the legal, ethical and medical issues raised by DCD25,38,39 and more recently several national guidelines or recommendations have been produced which address these issues.35,40,41 Recommendations for Australasia have been developed by the Australian and New Zealand Intensive Care Society.7
OFFERING THE OPPORTUNITY FOR ORGAN DONATION TO THE FAMILY
Organ donation (from deceased donors) is an activity that takes place at the end of life, usually involving an intensive care unit. It is separate from transplantation which is concerned with the care of patients with end-stage organ failure who may receive donated organs. Appreciating this distinction is fundamental to an understanding of important issues that are often ignored or dismissed in transplant-oriented publications. Organ donation fundamentally modifies human rituals at the time of death, even of death in the ICU. Organ retrieval is an invasive procedure carried out in the operating room. Although it is done respectfully and with identical surgical processes to those used on living people, it is nevertheless viewed by some42 as ‘mutilating’. Discussion of organ donation is an emotionally intense activity involving a newly bereaved family and a health professional, and requires very clear and sensitive communication. This discussion takes place when family members are experiencing the death of their family member. They must consider the issue amidst their intense grief – there is no other time. Knowledge of transplantation varies widely in the community and there is even less knowledge of organ donation processes. Some families may not previously have known that organ donation and transplantation occur! Similarly, discussion of organ donation and willingness to be part of it vary widely in the community. There is greater support of ‘organ donation in principle’ than either individual willingness to donate or willingness to agree to donation on behalf of a family member. Discussion of organ donation among families is promoted as a way of increasing organ donation rates and it may do so. However, some family members hold strong views against organ donation based on spiritual, religious or cultural beliefs.42
There are several utilitarian attitudes about organ donation including the notion that organ donation is the only possible positive outcome that can occur in the setting of brain death,43 that it is appropriate to refer to dead or dying persons in a utilitarian way as sources of organs for transplant,44 that for many families organ donation can assist with easing the pain of loss, and that fulfilling the previously expressed wishes of the donor should be the primary or indeed the only45 consideration. In some jurisdictions these wishes have indeed been defined to be legally sufficient for organs to be retrieved, and are often assumed to be a means of increasing the organ donation rate46 by excluding the family from the opportunity to prohibit organ donation and ‘returning control to the individual’. This assumption may well be erroneous.47,48 Although many countries (including Australia) have defined the status of an individual’s wishes about organ donation after their death to constitute legally sufficient ‘consent’, it is contentious whether the word itself is appropriate in this context10 as the person is dead at the time that the issue becomes ‘live’ and further, it is unlikely that any current ‘register-based’ record of such wishes would meet standards for informed consent49 in a personal health care context.50
Implicit in a ‘transplant-oriented’ moral economy51 is the judgement that for a family to agree to organ donation is both desirable and of greater moral value (‘the right thing to do’) than the contrary decision, particularly if organ donation was the previously expressed wish of the dead person. This judgement implicitly denies the legitimacy of the close human relationship between the family and the deceased to determine what should happen to their loved one after death,52 but is now explicitly acknowledged, practised and advocated by many USA organ procurement organisations (S Gunderson, personal communication). Even in countries that legally allow the previously expressed wishes of the deceased to determine whether organ donation may take place, usual practice continues to both involve the family and not to proceed against family objection – accepting that the impact on the deceased’s family is the most important factor determining consent practice.53 However, in many countries this has resulted in the evolution, exposition and advocacy of strategies ‘to overcome family objections’. The likely injurious effect of such ‘strategies’ on family bereavement54 is not considered or reported by those who advocate for it, and whose sole measure of ‘quality’ or ‘success’ in organ donation practice is the proportion of situations in which donation occurs.
Intensivists should be aware of their own views on these matters, and indeed the views of others that might discuss organ donation with family members. Whilst intensivists most often initiate discussion of organ donation with families in Australasia, this is increasingly unusual elsewhere. Whoever undertakes this discussion should be skilled in communication with grieving people. In Australasian clinical practice, the intensivist has already established a relationship with the family, involving mutual trust and respect, in prior family meetings during the patient’s final illness. This relationship naturally allows the intensivist to initiate and facilitate discussion of organ donation. Defining the discussion as ‘offering the option of organ donation’ rather than ‘obtaining consent’ (or even ‘persuasion’55) is not coercive in language and enables the intensivist to provide complete and unbiased information, support the family in their decision-making and thank them for their consideration, whatever the decision about organ donation might be.
MAINTENANCE OF EXTRACEREBRAL PHYSIOLOGICAL STABILITY IN BRAIN DEATH
Immediately prior to brain death there is usually a period of hypertension, tachycardia and occasionally dysrhythmia, mediated by both autonomic activity and catecholamine secretion. Pulmonary oedema, biventricular dysfunction and myocardial injury may develop but there is debate about the implications of these for subsequent cardiac graft function.56 If treatment of this adrenergic phenomenon is thought essential, then a short-acting β-blocker (e.g. esmolol) or only ‘moderating’ doses of a conventional β-blocker should be used. Cardiac arrest can rarely occur during this phase, usually due to tachydysrhythmia, but is often reversible. Hypertension is soon followed by hypotension, associated with marked reduction in sympathetic activity and catecholamine secretion. Hypotension may be profound in the presence of simultaneous hypovolaemia or cardiac dysfunction and can lead to cardiac arrest or loss of donor organ viability, and should be promptly treated by volume expansion and inotropic support.
Diabetes insipidus due to loss of ADH production soon follows in most but not all brain-dead persons and is manifest by brisk hypo-osmolar polyuria, which untreated will quickly lead to hyperosmolality and later to hypovolaemia. Other hormone abnormalities occur but do not have serious implications in the short term. Associated with the loss of cerebral blood flow there is loss of cerebral metabolism and a fall of around 25% in oxygen consumption and carbon dioxide production.57 This leads to a fall in the necessary ventilatory minute volume necessary for normocarbia. The fall in resting energy expenditure (heat production) together with loss of vasomotor tone and the possibility of shivering-induced thermogenesis exacerbate the risk of hypothermia developing.
Spontaneous movements and spinal motor reflexes commonly persist in brain death.58 These rarely include bizarre movements22,59 which are often reproducible. Family members may be offered the opportunity to view the (perhaps second) clinical examination for brain death and should be warned about the possibility of these responses (which may not have occurred at the first examination) and given a prior explanation of them. These movements and sympathetic circulatory responses can also occur during organ retrieval in the operating room. The use of use of neuromuscular blockade and opioids is recommended in the operating room60 although catecholamine responses are not suppressed by opioids in this situation.61
SUGGESTED STRATEGIES FOR MAINTAINING PHYSIOLOGICAL STABILITY
VENTILATORY MANAGEMENT
The aims of ventilatory management are to maintain good oxygenation and normocarbia, minimise circulatory depression and maintain, if possible, sufficiently good lung function to allow for future lung donation to occur. The use of moderate tidal volumes (10–12 ml/kg) and addition of a low level of positive end-expiratory pressure (PEEP) (5 cmH2O) may prevent atelectasis. Originally a PaO2 of more than 350 mmHg on 100% oxygen and 5 cmH2O PEEP was thought a necessary criterion for lung donation but PaO2/FiO2 ratios of 300 or 250 have been found to be acceptable.62 Peak airway pressures above 30 cmH2O should be avoided if possible. Usual pulmonary care including changes of position and sterile endotracheal suctioning must continue. When pulmonary dysfunction is severe, higher levels of PEEP may be required to prevent airway frothing or provide adequate oxygenation. The determination of apnoea during brain-death testing in such patients may require a period of mechanical hypoventilation prior to apnoea and continuation of continuous positive airway pressure (CPAP) during apnoea in such patients if serious hypoxaemia and circulatory depression are to be avoided.
CIRCULATORY MANAGEMENT
The aims of circulatory management are to maintain adequate organ perfusion and arterial pressure without producing fluid overload or excessive vasoconstriction, and without prejudicing future cardiac donation. Reasonable initial haemodynamic goals include normotension (a mean arterial pressure over 70 mmHg), heart rate of 100 beats per minute or less, and central venous pressure of 8 mmHg. Some inotropic support is almost always given (e.g. 92% of the 227 donors in 2006 in Australia and New Zealand63). Having established normotension with an inotrope infusion, the haemodynamic response to a controlled volume challenge should be assessed.
The choice of inotrope is the subject of more controversy than evidence. Dobutamine is not recommended. Noradrenaline (norepinephrine), usually less than 500 μg/hour, is preferred in Australasia (85% of 208 donors in 2006 who received inotrope infusions63) without apparent harm to organ function in recipients. Dopamine may exacerbate tubular polyuria and is not commonly used in Australasia (8% of 208 donors in 2006 who received inotrope). Adrenaline (epinephrine) may have specific benefit on renal blood flow in brain death64 but may also increase glycaemia and thereby osmotic diuresis. Catecholamine infusion may reduce the upregulation of organ immunogenicity that occurs in brain death and lower the incidence of acute rejection in subsequent recipients of kidney grafts.65 Although levels of thyroid hormones fall after brain death, this is probably the ‘sick euthyroid syndrome’ and replacement of thyroid hormone does not improve the circulation after brain death.66–68
Corticosteroids are often given just prior to organ removal from brain-dead donors and commonly recommended (on the basis of retrospective analyses) to increase the number of organs, particularly thoracic organs69 that are retrieved and transplanted. Although steroids improve haemodynamics in an experimental model,70 an early randomised human study71 did not show any benefit in kidney graft outcomes. There are no other trials of steroids alone in human brain death and a single small trial of the combination of steroid and tri-iodothyronine (T3) similarly did not show beneficial circulatory effects.72
Vasopressin infusion, at least in low doses, reduces the amount of catecholamine required to support arterial pressure73 without apparent detriment to subsequently transplanted organs. Whether this translates into improved outcome is uncertain. Following reports using retrospective analysis with multiple logistic regression,74,75 many authors now advocate the use of so-called ‘hormonal resuscitation’ (combined use of T3, steroid and vasopressin), although these authors of papers themselves cautioned that their results ‘are based on a retrospective analysis and the finding should be confirmed in future prospective randomised clinical studies’.75
Control of excessive polyuria will minimise the risks of developing hyperosmolality,76 hypovolaemia or hyperglycaemia secondary to infusion of large amounts of dextrose-containing fluids. Synthetic desmopressin (1-D amino-8 D arginine vasopressin) is commonly given to control diabetes insipidus and appears safe and effective.62,77
Control of diabetes insipidus is an essential aspect of rational fluid therapy, and hypovolaemia should be corrected with resuscitation fluids. Haemoconcentration occurs early after experimental brain death. Crystalloid infusion has been reported to worsen pulmonary function in brain death and somewhat larger volumes will be required than if colloid is used.78 At least moderate anaemia is well tolerated in brain death but red cells may be given if needed to maintain packed cell volume around 0.25 pending organ retrieval. Free water should be given as necessary (1–2 ml/kg per hour as 5% dextrose) to maintain serum osmolality in the range of 280–310 mosm/kg, corresponding to serum sodium below 155 mmol/l. Severe hyperosmolality (probably a marker of inadequate donor care) is associated with poor graft function in subsequent liver recipients.76 Failure to control diabetes insipidus will lead to increased requirements of free water to control serum osmolality. If 5% dextrose is used for this then hyperglycaemia and osmotic diuresis may result.
Metabolic management
Oxygen consumption, carbon dioxide production, heat production and glucose oxidation all fall in brain death due to the loss of cerebral metabolic activity.57 Hypothermia may easily develop in association with vasoparesis, loss of shivering, exposure to room temperature, warm polyuria and infusion of room temperature intravenous fluids. Core temperature should be kept above the 35°C required to confirm brain death.7,22 Keeping the ambient temperature high (24°C) and using infusion fluid warmers, heated humidifiers and external warming systems may be required. Low-dose insulin infusion is occasionally required to prevent hyperglycaemia. Serum potassium should be kept above 3.5 mmol/l but potassium replacement should be given with caution as hyperkalaemia is not uncommon after brain death. Correction of hypophosphataemia does not improve haemodynamics in brain death.79
AFTERCARE OF THE DONOR FAMILY
Routine aftercare is increasingly recommended80 for all families of patients who die in ICUs. Aftercare programs are well received11 and have the potential to improve the care of subsequent families by revealing areas of inadequate or inappropriate communication.
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