Non-Heart-Beating Organ Transplantation: Medical and Ethical Issues in Procurement (1997)

The IOM principal investigator, a group of senior special experts, who are not directly involved in transplantation or procurement, and IOM staff met on July 30, 1997, to hear presentations from invited professionals representing medical and surgical transplantation, organ procurement, the bioethics of transplantation, donors, recipients, and the federal government as described in Appendix B. On July 31, an open meeting was held during which the principal investigator and senior special experts discussed issues that they identified as important based on the information provided the previous day, their own experience and expertise, and literature and data made available by the IOM. The analysis, findings, and recommendations reported here were informed, directed, and supported by this discussion. Subsequent reviews and critiques were carried out by the senior special experts and others, including those intimately familiar with all aspects of transplantation as well as donors and recipients.

The project on Non-Heart-Beating Organ Transplantation: Medical and Ethical Issues in Procurement accepted two basic premises at the outset. First, organ transplantation should, as a matter of national policy, be considered a medically necessary part of care for patients with organ failures. It is assumed that the American people will continue to devote resources to this expensive and complex, but life-saving, technology, and it is understood that costs might rise significantly if organ procurement rose to meet demand. The scope of this report does not include a debate on the relative cost-effectiveness of high-technology care. Second, the recovery of organs from NHBDs should be considered a reasonable source of organs whose potential deserves a serious exploration. It was further noted that it would be well to address both controlled and uncontrolled NHBDs. Regardless of current preferences, both of these sources are used today

and may be important in the future if supply is to grow. In spite of their cited problems, results of procurement and transplantation of organs from NHBDs apparently can be competitive with those of more ideal donors. It can be concluded, therefore, that the recovery of organs from NHBDs is an important, medically effective and ethically acceptable approach to closing the gap that exists now and will exist in the future between the demand for and the available supply of organs for transplantation.

There is an important message that emerges, in addition, from an extended consideration of the premises, information, and conclusions presented in this report. Organ donation provides an opportunity to restore vital organ function and reduce morbidity and mortality which is of significant societal value. The public, professionals, hospitals, third-party payers, and government should all further the effort to improve levels of organ donation, including more widespread use of donor cards, a greater investment in support of donation, exploration and implementation of more effective procurement methods, enhanced public awareness, and other steps. This effort to provide this value is the context within which policies and procedures of the national transplantation effort are considered, and it is this value, along with the discouraging prospects for major and sufficient increases in donor supply from living and heart-beating donors, that encourages efforts to realize new kinds of donors such as NHBDs.

There are concepts or principles that should be included in the general context. For purposes of the survey described in this report, the IOM, as is common in survey reports, observed individual OPO confidentiality. Nevertheless, the principle should be that OPO policies and protocols are publicly available. Donor families stress that openness and the involvement and approval of interested members of the public are important in protocol development, in OPO governance and transplant program operation, in donor recruitment, and in other public education efforts. Such efforts, carried out through informational material, public advisory groups and boards, and educational campaigns can enhance public trust and support of organ donation and transplantation (Coolican, 1997). Furthermore, because organ donation and transplantation are so closely and intimately related to matters of life and death, meticulous attention should be paid to ethical considerations. Explicit assurance of this attention and a solid ethical foundation for whatever is done in donation and transplantation are the other important elements in public trust and support. This report has identified informed consent, not killing in retrieving organs, respect for donor and family wishes, and prohibition of active euthanasia as among the principles that are important to this ethical foundation. There may also be times when more conservative approaches than those which some might find ethically permissible should be taken in deference to the current state of public perspective and opinion.

Based on discussion among the principal investigator and senior special experts at, and subsequent to the July 31 meeting, it was concluded that five headings encompassed the problems and issues that might fruitfully be investigated and, insofar as possible, resolved. These are: (1) policies and oversight, (2) medical interventions and ethics, (3) conflicts of interest, (4) determination of death, and (5) families. Because the request for this study explicitly required a focus on donors, organ procurement and retrieval, they did not include any recipient issues.

Specific and important pressures are brought to bear during procurement and preparation for transplantation of organs from NHBDs, both controlled and uncontrolled, that exceed those on other types of donors. These pressures generate greater risks of premature cessation of treatment or nonbeneficial or lifeshortening interventions in a living patient, conflicts of interest between care and donation and premature declaration of death, among others. Therefore, policies for all categories of NHBDs must be different from policies for brain-dead (heart-beating) and living donors, although as Robertson (1993) has pointed out, it is not clear that the ethics differ materially among them.

A survey of the NHBD policies and protocols of all active OPOs has been described in detail in chapter 5. This survey revealed importantly that 34 of 63 OPOs had NHBD protocols approved (25) or in differing stages of development (9). As a reflection perhaps of the historical level of local autonomy of OPOs, and perhaps not surprisingly, there was substantial variation among protocols in principles cited and scope and detail of coverage. There were important and sometimes contradictory differences in ethically problematic provisions such as those regarding the timing and kinds of organ-conserving interventions and the standards for determining death. Five OPOs had protocols covering uncontrolled as well as controlled NHBDs, and some OPOs were recovering organs from one or the other kind of NHBD without protocols. The protocols were uniform in separating discussions and decisions on withdrawal of life support from those on donation and in requiring the independence of those responsible for declaration of death from those involved in procurement.

The fact that OPO NHBD protocols differ is not by itself necessarily a problem. Accepted geographic variation in medical practice, local custom, differences in demographic and social characteristics, and the need to accommodate the circumstances of OPOs that cover greatly varying population sizes and numbers of hospitals or transplant centers should be taken into account in protocol content. Protocols also should be able to respond to changes in practice, advances in technology, evolving public views in matters such as withdrawal of life support, or new laws at various jurisdictional levels such as those presuming

consent for, or otherwise authorizing cannulation and cooling. The myriad individual circumstances of patients and the differences in hospitals' and programs' geography, size, capacity, numbers, and types of personnel, as well as their experience and expertise, argue for flexibility in protocols and a commitment to live up to the spirit of a sound, ethical policy rather than an attempt to predict every possible contingency.

On the other hand, protocols should not be inconsistent among OPOs and hospitals in ways that raise questions about the motives and priorities of transplant programs or the scientific and ethical standards of care for donor patients. Fundamental scientific and ethical principles do not vary from region to region. Some of the current anomalies could be damaging to public confidence and in this way destructive to the crucial, life-saving organ donation effort. Organ transplantation is a nationwide effort, and there should be some coherence and uniformity across the country. Among the national initiatives are programs for data collection, organ allocation, OPO certification and oversight from the Health Care Financing Administration (HCFA), oversight from the Health Resources and Services Administration (HRSA), and significant federal funding. Smaller local efforts may benefit from access to the ethical or other expertise available on a national basis. New entrants to transplantation and procurement may find reassurance if there are some national guidelines. A sense that an agreed on, consistent community standard is being met may help these programs to design and be comfortable with their own protocols and policies. A local program that creates adverse public reaction may come to national notice and prejudice the entire national effort.

The European transplant community's 12 Maastricht Statements and Recommendations require (No. 5) that "no NHBD program should be started without a written protocol approved by the local medical ethical committee" (Kootstra, 1995). The Maastricht Statements and Recommendations also list performance and procedural requirements that transplant programs should observe. In a similar fashion, the key principles and provisions in this report can justifiably form a consistent part of NHBD transplantation in all regions of the United States with room left to accommodate other content that provides the necessary flexibility noted above. Such principles and provisions should be nationally required; this could involve consultation, review, and acceptance from those involved in transplantation, which includes donors, recipients, and the public.

Procurement of organs from any kind of NHBD takes hospitals and procurement organizations into difficult ethical and medical territory, exposing them to risks of error or controversial practices and resulting public disapproval. The policies and procedures to be followed should be thought through in advance and codified in a written protocol. Ways should be found to bring health care, ethics, and public representation, particularly organ donors, donor families,

and transplant patients, into the process of developing and approving such a protocol. All protocols should define and describe the kinds and characteristics of donors from whom organs will be procured under the protocol. Because the deadly and growing gap between donor supply and demand will not be closed without new sources of organs, procurement organizations should consider covering all categories of uncontrolled as well as controlled NHBDs under their protocols. They also should decide whether or not to cover conscious donors who can give consent as well as unconscious donors whose families or surrogates consent. The risks and procedures will differ significantly among the various categories of donors. For example, conscious donors who can give consent present particular problems in weaning from life-sustaining treatment, almost always artificial ventilation, without inappropriate hastening of death by pain control and sedation, even though there is essentially 100% confidence that death is inevitable shortly in such patients, and all ethical and family considerations are already satisfactorily in place. Uncontrolled NHBDs such as those in categories I or II, who could not be resuscitated after a heart attack, present the danger that prematurely abandoning resuscitation to turn to organ donation may forfeit the life of a patient who is otherwise a salvageable, competent person. The issues of timing and determination of death do not arise in category IV uncontrolled NHBDs because the patient has already been determined (brain) dead.

Under the headings that follow the IOM recommends certain principles and provisions that should be included in all protocols. This report does not cover all desirable content. The IOM focused on issues that were relevant to the charge of the sponsors of this project, that appeared to need attention at present, and that could be addressed with the time and resources available. Appropriate, additional provisions have been included in many protocols that reflect local considerations. These include ruling in or out various classes of patients by diagnosis, physical or mental condition, or other factors, specific responsibilities of various personnel, and other particular safeguards with respect to conflicts of interest between donor patient care and donation, including ethical consultation and the role of ethics committees, special arbiters, timing of various steps, and the like.

Certain context and principles for protocols have already been noted, such as the social value of donation, disclosure and openness, and the emphasis on a solid ethical basis for protocol provisions. The principles that donation not cause the death of donors and that there be no interventions that might constitute active euthanasia must be inviolate. These principles, respect for donor and family wishes, the primacy of consent based on disclosure and a commitment to informing, and allowing consent to be withdrawn at any time up to the beginning of organ removal are also an important context within which protocols should be developed.

This report concludes under this first heading that a written protocol that is completely open and available to the public should be a requirement for the procurement

and transplantation of organs from NHBDs. Protocols should have some minimal content and uniformity of coverage, content, principles, and definitions as part of a nationwide NHBD effort and as indicated in this report. As the medical, procedural, and ethical concerns about NHBDs are addressed in this report and elsewhere and to the extent that they are resolved, little is gained if the progress made is not reflected in policy and behavior when and where NHBD transplantation is taking place. The issues identified in this report and, in fact, the important progress already made in identifying problems and best practice and in addressing central medical and ethical questions are important elements for a high standard of care in transplantation and for generating both public confidence in the process of donation and public willingness to volunteer. Little purpose is served if these elements exist in a vacuum.

A number of important concerns have been identified under the second heading, medical interventions and ethics. First, this report concludes that it is essential to acknowledge that there must and should be interventions undertaken in the management of a patient for whom consent to become an organ donor has been given, including heart-beating or non-heart-beating, that would not be undertaken in a nondonor patient with similar medical condition. These interventions are taken in furtherance of a donation process that is effective and that safeguards the patient. Some are more common in heart-beating donors (Scheinkestel et al., 1995). Others might be accepted treatment of non-donor patients. This includes those that resuscitate or sustain life and maintain organ function, but under the circumstances of an actual donor patient, perhaps because of the severity of the damage due to injury or disease or because of a prior decision to forgo further treatment, their administration or the timing of their administration raises questions of whose welfare is being served. Still other interventions include organ conservation measures by specific preservation and treatment technologies or by monitoring, which can also ensure that life has ended and organ removal is not premature.

These matters can be described in more detail as those that critically involve (1) timing of interventions; (2) characterization of interventions—those that are provided to conserve organs to be donated also positively affect donor patient medical status, and may or may not prolong dying in the process; those that conserve organs to be donated and do no harm to the donor patient; those that conserve organs and are potentially harmful to the donor patient, and those that are invasive and/or definitely harmful; and (3) family and surrogate informed consent.

Interventions can also be examined as to whether they involve (1) resuscitation, performed primarily for the purpose of enabling a patient to become a donor; (2) monitoring, such as arterial and urethral catheters, to support and inform donation care rather than patient care; (3) insertion and use of perfusion cannulas for organ preservation and, potentially, for organ viability screening; (4) patient stabilization measures, especially in severely brain-damaged patients, such as heating or cooling blankets for temperature control, transfusions and other IV fluids, antibiotics, and hormones or other pharmaceuticals for control of vital functions when aggressive means would ordinarily be forgone; and (5) organ-protecting agents such as anticoagulants, vasodilators, diuretics (osmotic), steroids, and other more experimental agents to inhibit the formation of or to scavenge free radicals (allopurinol, superoxide dismutase), control prostaglandin activity, and the like (D'Alessandro et al., 1995b; Hoshino et al., 1988). Many of the latter agents will likely be limited to postmortem organ perfusion.

As noted, some of these interventions might be accepted treatment of severely ill patients, but they are used here in the context of the NHBD in the sense that they must either by their nature be directed primarily or exclusively at the organs to be transplanted or in the circumstances of a severely ill patient be of questionable use or timing when the usual course might be to avoid aggressive treatment and to let the patient die. Although it referred to potential heart-beating, rather than non-heart-beating donors, a recent financial review (Grossman et al., 1996) provided a quantitative example of the extent to which designation as a donor generates a change in care that can then no longer be assigned to the welfare of the patient but is directed toward organ procurement. Of the average $33,997 hospital stay cost, $17,385 was considered "futile" for the patient, but probably "necessary for improved organ procurement rates." With the understanding that designation as a donor undoubtedly changes, in a similar way, what happens to a NHBD patient, the overarching questions here include the following: is this change and are these interventions ethically acceptable; is the timing of these interventions ethically problematic; for which interventions is informed consent a requirement; and are there modifying conditions to the use of these interventions that might be necessary or helpful?

Within the context of the social value of enhancing donation and the other principles and provisions previously noted, this report concludes that these interventions can be appropriate, although only two are discussed in detail. They should be thought through in advance and be part of the approved protocol. There may be need for some flexibility since not every possible circumstance can be predicted, but provision should be made to err in the direction of disclosure, informing, and obtaining consent. Whatever the level of detail, donor families should, at a minimum, understand that to ensure the best results, some actions will be taken that are specific to the donation process and not of benefit to donor patient care. However, informed consent by itself does not allow or excuse interventions that are injurious or actively life-shortening.

The IOM focused on two interventions, administration of anticoagulants and vasodilators (e.g., heparin and phentolamine) and arterial cannulation for cooling, that are particularly relevant to the reasons for this report. Some have asked whether the principle of double effect might not be germane to the issues involved in interventions such as the administration of heparin and phentolamine. That is, the intentional achievement of a good effect, procurement of a lifesaving organ from a donor, permits the risk and possible occurrence of an unintended bad effect, hastening the death of the donor. Experts have argued that this principle may be applicable in some donor or transplantation situations (Childress, 1993). It is very unlikely that heparin and phentolamine would be part of nondonor patient care in medical circumstances similar to those of NHBDs. In certain patients under certain circumstances, these drugs may actively hasten death although no specific instance of this in any donor has been reported. While withdrawal of life support obviously, and ethically, hastens death in NHBDs, it is not an active lethal intervention taken to benefit mostly unknown and unrelated other individuals. This is a heavy potential burden for the principle of double effect, and there is no consensus about whether the principle can bear it.

In the occasional NHBD with ongoing intracranial bleeding or deficiencies in blood volume, the administration of anticoagulants or vasodilators such as heparin or phentolamine is not indicated because it could actively cause death. On the other hand, the administration of these drugs through circulation by chest compression or in a flush solution after death does not harm the donor and is justifiable as routine. Heparin and phentolamine, however, are recommended frequently during the donation process, based on clinical experience and scientific evidence that they enhance donor organ quality and graft results and usually can be safely used (D'Alessandro, 1997; Miller et al., 1974). Although prescription of these drugs during organ procurement is deemed useful and is undoubtedly safe in the majority of instances (Gould et al., 1980), a blanket policy cannot be recommended because of possible untoward effects in some donor patients.

Physicians responsible for the care of individual donors should be able to make a clinical judgment on the advisability of using either heparin or phentolamine or both without hastening donor death. This report recommends that individual clinical judgments be made and also that consideration be given to involving the donor's attending physician as either the responsible prescriber or a required consultant or co-decision maker with the procurement or transplant team to improve patient protection, lessen conflicts of interest, and strengthen public confidence. Protocols should note that donor families should be specifically informed on these matters, or more generally advised and given an opportunity to question further, that certain interventions (and the determination of death) may involve their own attending physicians on a case-by-case basis to

safeguard patient interests. Provisions for informed consent for heparin and requiring that the order for heparin originate with the attending physician are found in existing NHBD protocols, albeit very rarely.

Review of cases by a relevant committee of the involved facility is a final safeguard which may be desirable. Actions such as whether the attending physician or his designee signed or cosigned an order for an intervention (e.g., phentolamine) or whether chart notes indicate compliance with standards and procedures (e.g., those used in the determination of death) are susceptible to review and control at a subsequent time. Ethics committees would be appropriate for this, although a recent report sheds some doubt on their readiness for this task (Spielman and Verhulst, 1997).

Cannulas can be inserted through leg arteries and veins into major abdominal arteries and veins to allow postmortem organ cooling and preservation by perfusion through the blood vessels of internal donor organs with special cold solutions. Many programs believe that rapid organ flushing and cooling, also associated with general cooling through infusion of cold solutions into the abdominal cavity, are important in recovering viable organs from NHBDs, organs that have not suffered the accelerated deterioration that accompanies loss of circulation in an uncooled body. In controlled NHBDs, decisions to withdrawal life-sustaining measures are followed by decisions to donate. Thereafter, decisions can be made to cannulate before the withdrawl of life support, with the intent to perfuse as soon as cardiopulmonary death has been pronounced. Cannulation can also be performed later in the course of events, including immediately after death. Perfusion, since it usually involves solutions that will stop heart action immediately, must always await the declaration of death. Cannulation does not hasten death, and it is important in preparing for rapid initiation of organ preservation and enhancing the chances of obtaining quality donor organs and the best graft results for recipients. Cannulation is invasive, and, in a conscious person, painful. The report finds that cannulation is acceptable in controlled NHBDs after a decision to donate is made and beginning just before withdrawal of life support or at any time thereafter, but it recommends that consent always be explicitly required and that local anesthesia be used if needed. The issue of cannulation can be resolved at the time consent for organ donation is discussed.

With the possible exception of category IV uncontrolled NHBDs, where donation (and even cannulation) may have been discussed, the great majority of uncontrolled NHBDs suffer cardiopulmonary death unexpectedly and most often without family decisionmakers immediately at hand to give consent for measures such as cannulation and cooling. At the same time, the pressure for cooling is greatest in these donors because they are likely to have the longest intervals of organs unrecovered in the body at normal body temperature. These organs suffer the greatest deterioration, have the most frequent delayed function, and offer lower chances of long-term graft survival. As noted earlier, a delay of

30 or 45 minutes, which many European programs accept, may result in as high as 100% delayed kidney function and has so far ruled out transplantation of other organs (D'Alessandro et al., 1995b; Kootstra and Daemen, 1995). This has led to laws that allow cooling without consent in other countries and in three jurisdictions in the United States and to the practice of nonconsensual cooling, without statutory authority, in Illinois (UNOS, 1992), which was subsequently abandoned. The importance of cooling and preservation to the viability and function of NHBD organs, especially in uncontrolled NHBD cases; the likelihood that actual mechanical perfusion and cooling are superior to cooling alone (Southard and Belzer, 1995; Light et al., 1994); and the possibility that perfusion characteristics may allow useful screening for organ viability (Daemen et al., 1997) make the questions of timing, disclosure, and consent involving insertion of cannulas and initiation of cooling particularly prominent.

After a determination that further resuscitation efforts are futile and a declaration of cardiopulmonary death, the insertion of cannulas and the initiation of cooling pending location of family decision makers and receipt of consent for donation are problematic but can be considered. Patients with valid organ donor cards or other advance directives that grant permission are patients with legal consent, and this report concludes that in such instances, cannulation, cooling, and organ retrieval should proceed consistent with the donor patient's clear wishes. Individual procurement organizations or programs generally discontinue organ preservation and recovery if families are located and object, given the possibility of adverse public reaction. Ignoring the expressed wishes of the true donor in such a way is considered pragmatic local policy, but it is not a legal necessity, and it is hard to imagine how nonadherence to legal advance directives could be justified as a national policy statement.

In cases without donor cards or family consent, procurement organizations and transplant programs face decisions involving ethical concerns that are not definitely resolved. On the one hand, there is a prevailing sense that the public is likely to disapprove of nonconsensual cannulation and cooling. Specific, strong opposition was expressed in surveys in three cities (Arnold, 1997), and public concerns, noted earlier from other surveys, about inadequate treatment efforts on behalf of donors or premature initiation of donation may reflect similar sentiments. It is noteworthy that in Florida a law that presumes consent for cooling goes unimplemented by transplant programs unwilling to test public opinion. Serious damage to donation efforts could be done if unauthorized cannulation generated significant public discontent. Finally, modifiers such as ''minimally" do not change the fact that cannulation and cooling constitute an invasive procedure that may be very objectionable or if enough people find this offensive (and the numbers are not known), it might come to be considered definitely unethical without consent. It might also provoke feelings strong enough to generate a search for legal remedies for mutilation of the corpse, among others.

On the other hand, many people approve. As noted, there are laws in three major U.S. jurisdictions and a number of developed Western democracies that allow cannulation without consent. Many strongly believe in the social value of strengthening organ donation. More and better organs through better and earlier preservation are among the ways to realize that value. Organs that are in good condition may spare recipients the increased likelihood of the pain, morbidity, depression, and death associated with marginal grafts that have higher failure rates. It is argued, and evidence and testimonials have been presented (Coolican, 1997—see Appendix B; Douglass and Daly, 1995), that families take comfort and meaning from the knowledge that their loved one's organs live on and sustain life in other human beings. Organ donation can snatch a small victory from the pain of unexpected death. On a practical level, nonconsensual cannulation has been carried out a number of times and continues to be practiced, it is said, from time to time in the United States without generating any major controversy. This does not seem a strong argument in its favor, however.

Perhaps further study and discussion should be pursued. A consensus on the ethics might be reached, and public opinion may evolve or be favorably influenced through continued education and information. Time may, therefore, provide an answer. Local procurement organizations and programs are certainly free to practice nonconsensual cooling in jurisdictions with statutory authority or to consider it in other parts of the country. Nevertheless, there are risks to proceeding without consent, and offended families are unlikely to be pacified by any of the justifications listed in this report. Cannulation and cooling without consent may be a situation in which a decision based on deference to what the public is prepared to accept may be the wisest policy at the moment.

The third heading, conflicts of interest, has generated the most consistent approaches in protocols reviewed by the IOM. All procurement organizations and transplant programs appear to understand the need for strong safeguards to ensure that conflicts of interest do not lead to violations of prevailing medical and ethical standards of care for patients who may become or already are designated donors. These safeguards require separating major decisions and discussions in patient care (withdrawal of life support, discontinuing CPR, and declaration of death) from major decisions and discussions in organ donation and transplantation (obtaining consent for donation and other transplant-related procedures and involvement in the actual process of organ retrieval). Such safeguards include scrupulous separation of patient care personnel from procurement and transplant personnel. In some cases, such as determination of death, this separation is pursuant to law (Martin, 1970). They include spacing in time, as distinct events, discussions concerning withdrawal of support and discussions about consent to donation. They also include assigning responsibility for the

declaration of death and important aspects of medical management during the dying and donation process, such as weaning from life support, resuscitation decisions, and perhaps in some ways decisions on organ-conserving interventions that may be harmful in certain patients under certain conditions, to attending physicians who are responsible for patient care and not to the physicians who are responsible for organ procurement and transplantation. The decisions made and the care delivered at the time of withdrawal of life-sustaining treatment in the case of controlled NHBDs or at the time of CPR in uncontrolled NHBDs pose particularly challenging conflicts of interest. In the former instance, interventions intended to ensure comfort and pain relief may also be those that can hasten death. In the latter instance, the proper time to discontinue CPR may be subjective and dependent on an assessment of the circumstances of the individual case. Given the importance of the timing of events to organ viability, the types and timing of interventions or decisions on CPR may be perceived to have been influenced by the demands of transplantation. The pressures for a prompt and predictable declaration of death and the complete dependence of patients at these critical times require particular attention to conflict of interest issues and safeguards. As a practical matter, resident physicians may well be those closest to patients and families and therefore most suited to assume some roles in donor care and transplantation. Provision for their involvement under supervision may be desirable.

By agreement with hospitals or under state law OPOs are becoming involved through routine referral and mandatory notification about dying patients. As a result, they are being introduced, and the subject of donation is being introduced from time to time at earlier stages in the course of care of terminal patients when separation of life support withdrawal decisions from the possibility of donation is important. This report is not recommending specific new safeguards to handle the conflicts of interest between withdrawal and donation. Nevertheless, the changes in procedure that follow more aggressive and successful procurement increase the potential for these conflicts. Early interventions are reviewed in chapter 5 of this report and suggest that further thought on the implications of earlier and more pervasive approaches may be needed.

Finally, some NHBD patients may receive care at nontransplant facilities, after which their organs are sent to transplant centers. There are many more hospitals that provide donors (1,300) than there are transplant centers (275). Nevertheless, many NHBD patients are managed at transplant centers. Here, personnel, even if not part of the transplant program, are likely to be at least aware of the possible benefits in prestige, research support, patient care reimbursement, and staff recruitment that may accompany a successful, growing transplant program. Such an "institutional bias" toward improving the supply of donor organs may be difficult to completely resolve by any conflict of interest safeguards (Frader, 1993). Disclosure to donor families that in such facilities

procurement efforts may be more intense and the needs of a transplant program will be in the staff's minds seems a reasonable measure for recognizing and managing this possible bias.

A prevailing attitude in favor of searching out and procuring donors may encourage extra steps to support and maintain patients whose condition suggests that they could go on to become possible donors if life can be sustained. This kind of admixture of patient care and donation objectives provides sustaining care interventions for patients, meets obligations to enhance organ donation, and is reasonable as long as patient and family needs are met within a policy of openness. It is difficult or impossible even to isolate the donation effort in such instances. More overt and less directly patient-supportive steps are not acceptable before donation has been discussed with families and consent given. This report finds that conflict of interest safeguards are among the most important aspects of protocols. Many conflicts of interest provisions were identified in chapter 5, and the particular provision discussed in this chapter should be part of NHBD protocols. Requiring non-heart-beating donation to be initiated always by the family and never at the suggestion of patient care or procurement staff, as provided in one existing protocol, is a level of strictness that this report finds is a local option, not a necessity. Complete elimination of conflicts and separation of withdrawal and donation are probably impossible. Removing hospital or procurement staff from the request process does not ensure completely disinterested family decision making, or preclude the improper influence of institutional or other considerations on the acceptance of donation by professional staff. Therefore it is not recommended.

This report has addressed two important concerns under the fourth heading, determination of death. The definition of cardiopulmonary death as "irreversible cessation of circulatory and respiratory functions" is short and simple. The current variability and, arguably, confusion in practices for the determination of donor death as reflected in existing protocols for controlled NHBDs arise from the controversy over what constitutes "irreversible" and because great precision in the moment of death is rarely crucial in general practice, from the custom of using simple and imprecise standards and technologies to determine death. A little more time can make the diagnosis obvious but, in donors, may result in organs of poor or unusable quality. Timing of death is crucial in NHBD organ procurement, however. Because the incentives are toward the earliest possible determination, NHBD policies that do not have a clear definition with a credible mechanism and standards leave procurement organizations and transplant programs open to charges of inadequate safeguards and practices for preventing premature determination of death and removal of organs.

Some protocols offer very little detail regarding the determination of death. Some controlled NHBD policies specify cessation of circulatory function measured in the usual way but supported by absence of electrocardiographic evidence of heartbeat (no meaningful electrical activity, ventricular fibrillation, or electromechanical dissociation) for 2 minutes. Other programs, particularly in Europe and particularly for uncontrolled NHBDs, specify 10 minutes of cessation measured in various ways. Still another option provides more local discretion: "Irreversibility of cardiopulmonary function is recognized by persistent cessation during an appropriate period of observation and/or trial of therapy. In clinical situations where death is expected, where the cause has been gradual and where irregular, agonal respirations, or cardiac activity finally ceases, the period of observation following the cessation of cardiopulmonary function may need to be only a few minutes in order to establish death. When a possible death is unobserved, unexpected, or sudden, the examination may need to be more detailed or extend over a longer period while appropriate resuscitative efforts are maintained as a test for cardiovascular responsiveness" (U.S. organ procurement and transplant program NHBD policy).

There is an important need for clear definition, method, and standards for determination of death. This involves questions of which and how many physicians should be involved, tests used, the timing, and the consideration given to individual circumstances or kinds of patients that might modify the approach. The key concern is not whether circulation and respiration have ceased, but whether they have irreversibly done so.

Attempts to clarify the meaning of irreversible have revolved around a number of questions. Withdrawal of life support undoubtedly leads to cessation of circulatory function that, even if the possibility of spontaneous return of effective heartbeat is left aside, might sometimes be reversed if life support were restored or other resuscitative measures were initiated. In the situation of the controlled NHBD, however, a valid refusal of further treatment is in hand, and a decision has been made to withdraw life support with an understanding of the consequences. At some interval after the last heartbeat because in this instance medical intervention is not to be attempted, the heart will not have the capacity to autoresuscitate and circulatory failure will be irreversible. Unfortunately, no scientific studies allow a definite conclusion on how long this interval might be. Protocols and practices in the United States and other countries vary significantly in defining this interval, which reflects the lack of scientific certainty. As noted in chapter 5, some controlled NHBD protocols take into account the manner of death, allowing a shorter interval after a longer agonal period. Some do not require any elapsed time, and some leave the definition to the attending physician's discretion. Others prescribe intervals of 1, 2, or 5 minutes or yet other timing. Much longer time periods are accepted in uncontrolled NHBDs, up to 1 hour, with consequences that have been described in other chapters of this

report. The shorter intervals between cessation of circulation and determination of death are problematic as to the assurance of irreversibility. Intervals such as 2 minutes are not supported by any experimental data on the probability of autore-suscitation and are too short to support a determination of brain death due to circulatory arrest (Lynn, 1993). On the other hand, recent enactment by the Swiss National Academy of Medical Sciences of official guidelines on cardiac death, with respect to potential organ donation for uncontrolled NHBDs, that specify 30 minutes of unsuccessful cardiopulmonary resuscitation under hospital conditions has raised a number of issues. Among these is the advisability of a definition of death that is defined specifically in terms of organ donation and that has caused the availability of NHBDs to decrease by 50% (Schlumpf et al., 1997).

Clarification of the meaning of irreversibility and of the determination of death must rest on expert medical opinion. The fact that the controlled NHBD is a severely ill or injured patient, with impaired physiology and near death, informs this opinion. This is the context in which the value of enhancing donation and procuring organs in a timely way is weighed against the ability of organs to tolerate short periods of circulatory failure and the requirement that the public be given credible and meaningful assurance that donor care has not been compromised, and that donors have died and organs are not prematurely being removed. In the final analysis, however, the opinion must and indeed does rest on expert judgment that the interval is long enough to ensure that the probability of return of circulatory function is vanishingly small. In addition, although this is not relevant to a determination of death, the interval of absent circulation recommended here will, in a donor with normal body temperature, produce irreversible brain damage.^* In patients with depressed body temperatures, death is more difficult to determine; time and resource constraints did not allow a thorough exploration of this challenging situation in this report, however. Based on expert information and advice from its senior special experts, this report recommends that in controlled NHBDs, an interval of at least 5 minutes elapse after complete cessation of circulatory function, as measured by standards described later in this chapter, before death is pronounced and organ perfusion or removal begins. It should be noted that the insertion of cannulas, if they are not already in place, can be carried out during the 5-minute wait after the heart stops. Uniform adoption of this recommendation which is on the conservative end of the current range, could ensure that death has occurred, diminish the appearance of haste and reassure the public, and eliminate the uncomfortable situation whereby a donor could be defined as dead in one OPO region and still, however briefly, be defined as alive in another. Since, in the final analysis, this recommendation is only an expert judgment, data should be collected to validate an interval. Clearly, if a 5-minute interval is widely used, within a short time a large number of observations on reversibility during a less than 5-minute interval could be

collected. These observations might be helpful in confirming a 5-minute interval or providing evidence to change from 5 minutes to a shorter interval based on actual clinical data.

Uncontrolled NHBDs present a different set of concerns. Category IV uncontrolled donors are already dead by neurologic criteria. Although they have suffered unexpected cardiac arrest, they are like heart-beating donors who do not pose questions of definition or determination of cardiopulmonary death because death has already been pronounced. CPR and other life support are relevant to organ preservation in these donors, not to a determination of death, and no interval of arrest is at issue. CPR is involved in other uncontrolled NHBDs who suffer unexpected cardiopulmonary arrest yet may have considerable potential for a return to normal life. In these donors there are major concerns regarding the vigor and duration of attempts to restore circulation, the standards for determining death, and the timing of organ removal.

Uncontrolled NHBDs are a trivial percentage of donors currently, but in theory they could comprise the largest group. Less than 10% of OPOs have protocols covering uncontrolled NHBDs, and few express an interest in expanding efforts in this direction. Nevertheless, the potential of this group, the rather ad hoc current approach, and the procurement of some of these donors scattered among OPOs, often without protocols, suggest that relevant issues should be explored and resolved to the extent possible. The interests of the uncontrolled donor patient in a lengthy and intense effort to restore circulation and the interests of the patients who await organ procurement and transplantation in a brief effort and a short interval of arrest that leaves donor organs in the best condition are in powerful potential conflict. Most CPR is not successful, but long-term return of cardiopulmonary function and return to normal life after several hours of CPR are not unheard of. The circumstantial events and medical status of those who suffer unexpected cardiopulmonary arrest are enormously varied. It is difficult, therefore, to design a uniform approach to the determination of death in uncontrolled NHBDs. The approach of the Swiss Academy of Medical Sciences requiring 30 minutes minimum duration of hospital CPR has been mentioned earlier, and major European programs have recommended a general rule of 10 minutes of absent heartbeat after termination of resuscitative efforts before perfusion or organ retrieval (Kootstra and Daemen, 1995).

Continued evaluation and discussion of the determination of death in uncontrolled NHBDs are recommended. In the meantime, given the great individuality of these donors' circumstances, the individual physicians responsible for caring for them should make decisions on duration of CPR and the interval of absent function necessary to determine death based on their best medical judgment under the particular conditions of each situation. Care of these patients must be completely independent of any consideration of organ donation. The societal value of enhancing organ donation should encourage requests to families of potential uncontrolled NHBDs. The necessity for separation of care from

organ procurement and the tight time limits required by medical events, however, may make successful donation difficult unless there is a donor card or until some resolution of the issues discussed earlier with respect to cannulation and cooling allows early cooling and more time to properly carry out the steps necessary for arranging donation. Continued discussion, research, and experience, along with local decision making, could in the interim indicate directions for the future.

A review of current NHBD protocols does not provide a sense that there is a prevailing understanding of the "accepted medical standards" mentioned in law by which cardiopulmonary death is to be determined. As described earlier, protocols vary from no specifics on determination, to the use of palpation and auscultation, to electronic monitoring, to specific descriptions of electrocardiographic results and other confirmatory tests. For the definition of death recommended in this report for controlled NHBDs—or any definition that includes a specific time interval of absent heart function—to be meaningful, an unambiguous time of cessation of function and monitoring to detect any return of function is required. This report recommends, in adhering to the controlled NHBD definition of at least 5 minutes of absent heart function, that accepted medical detection standards include electrocardiographic changes consistent with absent heart function by electronic monitoring and zero pulse pressure as determined by monitoring through an arterial catheter. These standards would require proper placement of electrocardiographic leads and monitoring of cardiac electric activity and the placement of an arterial line (cooling cannulas or a monitoring catheter, which would often be in place anyway) and monitoring of blood pressure. Other findings clearly will also be present, such as absence of breathing and unresponsiveness to stimuli, and notation of these in protocols at local option could be useful.

This report has explored a number of organizational, procedural, and medical issues important to the national transplantation effort. A nontechnical fifth heading—families—is included to reflect the primacy of the principle of respect for donor and donor family wishes and to provide a reminder and some recommendations regarding the essential role of families. Living donors and those heart-beating and non-heart-beating donors who have executed a valid donor card or other advance directive are, as individual members of the public, essential to transplantation. The support of donor families is just as essential. Without them the national effort would amount to a fraction of its present size and hope for future increases in supply would be dim indeed. Procurement organizations and transplant programs undoubtedly recognize that attention to and involvement of families is compassionate, quality medical practice and, in a practical

sense, crucial to maintenance and improvement of a national donor effort. By no means do all protocols reflect this, however, although what donor families want and deserve is clear (National Kidney Foundation, 1994).

The focus here is on a number of issues that could be included in protocols. Protocols require that discussions of donor care, withdrawal of treatment, and determination of death be separated from discussion of donation for reasons of conflict of interest. Also, requests for consent are more likely to be successful if these discussions are decoupled, as noted earlier. This separation is important to donor families, and procedures should be designed to properly accommodate this reason as much as the others. Families need time to understand the medical situation and come to terms with their personal tragedy. They also appreciate and benefit from privacy during these times. The circumstances and the separation of discussions should respond to this need.

Results of several surveys included in this report indicate that families often do not understand the meaning of brain death and feel that they needed, but did not receive, more information and explanation of this and other matters related to the care and potential of the patient for donation. The Bill of Rights for Donor Families emphasizes the needs for information, explanation, and the opportunity to understand, with a properly prepared and trained person, the details of a prospective donor's situation and the implications for the family. The value of follow-up is an issue related to this. Many donor families want information on what organs were removed, how they were used, and the results in transplant recipients. This report takes no position on interactions between donor families and recipients and their families. Many families would also appreciate some follow-up support of the kind mentioned in the Bill of Rights for Donor Families. It is to be hoped that attending physicians and responsible resident physicians would continue to have an interest in donor families and be willing to discuss and explain matters to them, to visit on occasion, and to be willing to help with follow-up questions.

Families are customarily afforded considerable latitude to be with patients who are not donors while they are critically ill and dying. The fact of donation should limit as little as possible, preferably not at all, the opportunities for families to attend patients in the same way they would if organ donation was not contemplated. It is recommended that hospitals arrange for some non-OR site where families can be with patients until death, if this is their wish. If this is not their wish the advantages of an OR site may dictate that setting for withdrawal. Individual facilities have different physical layouts and differing potential for accommodating families, so individual solutions will vary. Procurement organizations and transplant programs should review their protocols and procedures to consider whether there has been adequate consideration of donor family needs to attend patients. Families who will be in attendance (indeed all families) should also be fully informed of the possibilities that death may not occur soon

enough to permit donation and that, in dying, an occasional respiratory effort or electrical response on cardiogram does not represent return of function.

Finally, procurement organizations, transplant facilities, and government and other payers should review experience and payment rules to determine if donor families are at risk for any expenses that are part of the donation process or that because they are not part of routine patient care, are incurred in anticipation of, and are the responsibility of, the donor process whether it occurs or not. Donor families should not be penalized for altruistically contributing to the social good by enhancing organ procurement and for consenting to make a contribution to the national transplantation program. Several NHBD protocols reviewed in this report already provide that no costs after consent for donation will be borne by donor families whether or not donation is successfully accomplished.

This report has reviewed the history of solid organ transplantation and the current balance between supply and demand. Pursuant to an investigation of the current usage and results of organ recovery from NHBDs, it is concluded that controlled and uncontrolled NHBDs are important potential contributors to an improvement in the severe and growing organ shortage. A number of current and potential problems and concerns could limit fully developing the NHBD resource. The public also perceives similar issues and potential for problems in the NHBD donation process, as indicated by public surveys in Tallahassee, Detroit, and Philadelphia that report a lesser willingness to donate as a controlled NHBD of 22%, or as an uncontrolled NHBD of 29.2%, among those recording a willingness to donate as a heart-beating (brain-dead) donor (R.M. Arnold, personal communication, July 30, 1997). By and large, the data show that the organ procurement organizations surveyed by the IOM are doing a dedicated and increasingly successful job, along with transplant centers, in working to improve donor procurement and the state of transplantation. Nevertheless, there are some inconsistencies in the implementation of procurement programs across the nation, and improvements should be made. Given the contributions of the End Stage Renal Disease Program and other sources of federal support, the national data and organ allocation systems, the oversight and OPO standard setting of the Department of Health and Human Services, and most particularly the requirements of the U.S. Organ Procurement and Transplantation Network for national as well as local public appreciation and support of transplantation and donation, it is clear that transplantation is in many ways a nationwide effort. Recommendations to promote a more consistent and publicly explainable approach are likely, if they are appropriate and are thoughtfully implemented, to contribute to a more effective effort. This report understands the need for improvement and some national uniformity with the desirability of local initiative and responsiveness to local practice and conditions. Not all the issues that could have been explored have been addressed. Many have been left for, and deserve, future discussion. A process for involvement of the national transplant community, donor

families, recipients, and the public to continue to develop policy may be desirable. In any case, given the current state of affairs and the strong desirability of, at a minimum, a coherent and defensible national approach, steps should be taken to provide some uniform national policies and improved consistency. This report provides information, analysis, conclusions, and recommendations to the sponsor, the Department of Health and Human Services, regarding the issues that the department raised as particular concerns and regarding additional issues that were identified as currently salient.