Thursday, October 01, 1998

Brain Death in an Age of Heroic Medicine

When the technology of heart transplantation and life-support machines overtook the traditionally accepted criterion of death—cessation of heartbeat—an alternative criterion emerged. Irreversible loss of brain function, or “brain death,” for all the debates and recent attacks it has provoked, has worked well as a determinant of death, argues Dr. McKhann.

The advent of heart transplantation some 30 years ago challenged age-old assumptions about death. A patient's heart may have stopped beating (once the universal criterion of death) but, transplanted to another patient, it is expected to restart and persist. No technology, however, can resuscitate, transplant, or restart the dead brain.

As an advisor to the Vatican on the biological and ethical validity of the criterion of brain death, Dr. Guy McKhann argues it has worked well in transplantation and end-of-life decisions. Although the concept of brain death is now being challenged, says Dr. McKhann, it remains biologically sound, clinically useful, and—with some additional analysis—capable of precise definition.  We should stick with it.

Since before Biblical times, the accepted criterion of death has been cessation of cardiorespiratory function. The heart has stopped, breathing has stopped, the person is dead. Every paramedic is trained to determine if the accident or heart-attack victim is breathing and has a pulse. Even in the modern hospital, cessation of cardiorespiratory function is sufficient to pronounce death in 90-95 percent of cases. Only recently has the triumphant advance of medical technology brought our deep-seated assumptions about death into question and given rise to an alterative criterion: the irreversible loss of brain function that we call “brain death.”

The first challenge to the traditional criterion came from life-support machines. With their aid, the heart of a person who has suffered irreversible brain damage may continue to beat—either spontaneously or aided by the machine—for months. By the traditional criterion of cardiorespiratory function, the person is “alive.” But at some point in the course of care we may ask: “Should this person be maintained in this state, not only with no chance to return to a level of functioning life, but with no chance to return to interaction with the external or internal environment?”

The other challenge arising from this century’s medical and technological advances is to determine when a person is a potential donor of vital organs such as the heart, lungs, or liver. It seems obvious that in these circumstances irreversible cessation of heart function cannot be the criterion for death. This same heart is going to be removed and transplanted into a recipient, where it is expected to return to normal functioning—for years, one hopes.

Over the past 30 years, a new criterion—brain death—has come into use. This criterion has worked well in medical practice, and is now widely applied (although with vastly differing interpretations); but it also has spawned a host of medical, legal, ethical, and philosophical debates. Lately, it has come under attack by groups as disparate as the religious right in the United States, the German Green Party, and some physicians and ethicists.

My involvement with the idea of brain death began 30 years ago when, as a neurologist, I was asked to help develop criteria for brain death in connection with the first heart transplants in the United States. I have continued this involvement at the Johns Hopkins Hospital. Most recently, I have been one of a small group of advisors to the Vatican on the biological and ethical validity of using brain death as a criterion for death of a person. This committee consisted of physicians, philosophers, and theologians, some who favored the concept of brain death and others who, on various biological and ethical grounds, did not.

My position is that cessation of brain function, if clearly defined, is an appropriate, defensible criterion of death at our current stage of technology. The alternative criteria being proposed are less coherent, and some raise implications that are troubling indeed.

ENTER THE HEART TRANSPLANT

In 1967, Dr. Christian Barnard of South Africa performed the first heart transplant in a human being. Shortly thereafter, Dr. Norman Shumway of Stanford University, who did much of the animal research that made heart transplants feasible, performed the first human heart transplant in the United States. I was at Stanford and became the neurologist involved in questions raised by transplantation. Our committee, comprising physicians from Stanford, Stanford trustees, and people from the community, including clergy, met repeatedly to discuss the biological, ethical, and legal implications. Concerns that dominated those discussions persist today. 

...death was seen as an irreversible biological process that occurred in all species. But the transplantation of a heart, and subsequent restoration of its function in the recipient, threw these assumptions into doubt. 

At that earlier time, the accepted (indeed only) criterion for death was cessation of the beating heart, leading to absence of circulation and thus lack of perfusion of all organs. The traditional criterion implied another essential principle: irreversibility. The assumption was not only that the heart had ceased beating but also that it could not be resuscitated—or it would have been. In this context, death was seen as an irreversible biological process that occurred in all species. But the transplantation of a heart, and subsequent restoration of its function in the recipient, threw these assumptions into doubt.

If irreversible loss of heart function no longer determined death, could failure of another organ determine it? The brain was the obvious candidate. Without brain function, vital functions of respiration and maintenance of blood pressure could not be sustained, and higher functions, such as communication, attention to the environment, and awareness of surroundings, would not exist. Loss of brain function could be irreversible, and it was (and still is) irreplaceable by any machine.

Our committee repeatedly discussed the distinction between two situations: the first is the person who has had severe brain damage resulting in a non-communicative, non-responsive state; the second is the person who meets the criteria for brain death. In the first situation, the medical and ethical issue is whether or not to stop life-supportive measures where the outcome is hopeless. Many of the legal cases about cessation of supportive measures involve persons in this state. In brain death, the whole brain function (as discussed below) has ceased. This is an important distinction, because withdrawal of life support in a hopelessly brain damaged person will result in brain death, but that person is not “brain dead” while still being supported by machines.

WHO IS A DONOR?

Another focus of our discussion was the patient who might be an organ donor. From the start, it was clear there would be more potential recipients than donors. Demand for donors would be high. There would be pressure to enlarge the donor pool, particularly because, in the 1960s and early 1970s, when little was known about tissue immunology, many patients rapidly rejected the transplanted heart and required another one immediately. Under these circumstances, pressures to “bend the rules” and accept as a donor a patient who had irreversible brain damage but was not brain dead would be enormous. Perhaps the public sensed this, because people were concerned that they might be seen as potential donors, not patients. Our position was clear: The primary responsibility of the potential donor’s physician was proper care of that patient (and the patient’s family). Until the patient was declared “brain dead,” absolutely no measures that differed from the normal standard of care should be introduced to preserve organs that potentially could be donated.

For the patient and family, it was important that the criteria for brain death be precisely definable. When a patient was declared brain dead, the family could be informed, and a decision about transplantation then made. Only after the family had agreed to transplantation would decisions about medical procedures relative to donation be integrated into the physician’s planning. Without clear criteria for brain death, the basis for deciding to stop supportive measures could be vague, variable, and subjective.

The Stanford committee saw the need for a patient (donor) advocate. Thus three people reviewed each possible donor: a neurologist chosen from a pool and often not associated with Stanford, a non-medical person (usually a clergyman chosen by the patient’s family), and me. This group, independently and together, repeatedly reviewed the patient’s examinations and other data before deciding about brain death.

We also considered the rights of the recipient, a person alive but with a heart progressively failing. Considering transplantation implies a medical judgment that this patient’s heart will stop despite all medical measures. If he is to receive a heart, he is taken to the operating room and his own beating heart stopped and removed. For a time, therefore, this person is without heart function, and may be without spontaneous circulation or respiration. It is significant that this person is not considered dead or to have been killed. There are two reasons:

  1. The recipient’s body, including his brain, is protected by machines that maintain blood pressure and oxygen supply. Note that in all cardiac surgery where the heart is stopped and its actions replaced by a machine, the assumption is that supportive procedures will keep the body components not only alive but capable of returning to integrated function after the period of no spontaneous circulation or respiration.
  2. The recipient will receive a replacement heart that will return to normal functioning. 

COMPETING CRITERIA FOR DEATH

Resistance to the concept of brain death arises from several sources. First, there are far fewer organ donors than potential recipients because relatively few patients declared brain dead actually become donors. An increasing number of potential recipients are dying before transplants are available. From the point of view of transplantation needs, then, the criterion of brain death begins to be seen as the limiting factor.

Second, resistance comes from physicians, ethicists, and others who challenge the validity of brain death as a criterion. They argue that from a biological point of view brain death is imprecise. After all, when life-support machines are stopped, people do not always immediately die. Ethicists and theologians also object that the death of the brain is not the same as the death of the person. They add, for good measure, that the issue of defining death is too important to leave to physicians. Third, groups fundamentally anti-science and antitechnology resist a definition of death inherently based on science and technology.

These dissatisfactions with the concept of brain death have led to proposals for alternative criteria for defining the end of life. Let me comment briefly on their implications.

The spontaneous, irreversible cessation of respiration and circulation is the traditional criterion for death in all parts of the world. Some organs, such as skin, corneas, and perhaps kidneys can be transplanted from a person who, by this criterion, has died (in other words, transplanted from a cadaver without a beating heart). Vital organs like the heart and the lungs, however, cannot be transplanted unless specific preservative measures are instituted before or immediately after death of the donor. Thus, a return to use of this criterion would result in a major decrease in availability of these vital organs for transplantation.

To me, this proposal is a dodge, a way to make transplantation possible without having to consider death by some other criterion than cessation of the heart. The essential issue is still that any heart that will function in a recipient very likely could have been resuscitated in the donor, if the medical team had chosen to do so.

Physicians and ethicists who reject the criterion of absence of brain function have suggested that death be defined as some time point after support systems are discontinued, and the heart stops. Recognizing that a return to the criterion of cessation of heart function would eliminate or greatly reduce certain organ transplantations, they propose that when life-support systems are discontinued and the heart stops, the person be declared dead after an arbitrary interval without heartbeat, (suggestions range from 2 to 30 minutes). They assume that this arbitrary elapse of time is the maximum interval during which the heart could be removed, resuscitated, and transplanted. They also suggest that the heart and lungs might be protected during this period by being perfused with protective solutions.1 To me, this proposal is a dodge, a way to make transplantation possible without having to consider death by some other criterion than cessation of the heart. The essential issue is still that any heart that will function in a recipient very likely could have been resuscitated in the donor, if the medical team had chosen to do so.

Of particular concern to me are the criteria for withdrawing life support from these patients in the first place. Alan Shewmon suggests that any patient who is ventilator-dependent (whether brain dead or not) and for whom the ventilator is about to be legitimately discontinued as an extraordinary or disproportionate means, and who wants to donate his or her organs, is a potential candidate.2 Such a patient would be taken to the operating room with the transplant teams ready, perhaps even with catheters placed for perfusing the organs with cooling solutions prior to death. The problem is that this proposal implies no real criteria for discontinuing life support. Conceivably, a person with a normally functioning brain, such as a person with a high cervical cord transection or a ventilator-dependent person with a medical disease such as Guillain-Barre syndrome, in which full recovery may occur, would be a candidate!

Others, such as Professor Robert Truog of the Boston Children’s Hospital, at least recognize the paradox of this approach and indicate that the process of organ procurement would require substantial changes in the law. The process of organ procurement would have to be legitimated as a form of justified killing, rather than the dissection of a corpse.3

Another proposed criterion for death is the failure of function of other organs. For example, death could be based on failure of the liver or kidneys. In both instances, death will occur if failure of these organs is not reversed. True, but both the liver and kidneys can be replaced by transplantation—and kidney failure can be overcome by dialysis.

CLARIFYING THE BRAIN DEATH CRITERION

We are forced back, it seems to me, to the brain—the organ that cannot be replaced. What is needed is a clarification of the brain death criterion. This requires understanding three concepts related to brain function:

  • higher brain functions, which confer our properties of humanness such as communication and awareness of our environment and response to it;
  • brain stem functions, which support vital processes of breathing, circulatory homeostasis, and maintenance of awareness and attention by activation of the cerebral cortex;
  • whole brain functions, which require both higher brain functions and brainstem functions, as well as ability to integrate sensory, motor, and homeostatic mechanisms to maintain blood pressure, temperature, and similar functions.

Each of these concepts has given rise to proposals for different criteria for brain death, particularly in situations involving a potential organ donor.

1. The first proposed criterion is “the irreversible loss of higher brain functions.” This definition would apply to persons who still have intact brain-stem functions (that is, their breathing and cardiac functions are being maintained), but have irreversibly lost higher brain functions.

We see in such patients that death may not be a spontaneous event; it may require that life-sustaining measures be actively discontinued. Using this definition, for death to occur and organs to become available for transplantation, it would be necessary for life-sustaining measures to be discontinued.

To me, however, equating death with the loss of higher brain functions is flawed. First, these patients have lost only one of the groups of functions of the brain. Their brain-based supportive functions may be intact; in some instances, breathing and cardiac function may continue for long periods of time, even without external support.

...I consider that loss of higher brain function cannot be the biological basis for declaring a person dead. It may at some point be the basis for discontinuing treatments and so result in death, but it is not the criterion of death.

In this group of people, the distinction between withdrawal of life support and brain death becomes important. This is not the place to discuss the medical, ethical, and legal issues involved in withdrawing life support, but I will note that there is general (although not universal) acceptance that, when continuing support is futile, this support can be withdrawn. Pope John Paul II states that “euthanasia must be distinguished from the decision to forgo so-called ‘aggressive medical treatment,’ in other words, medical procedures which no longer correspond to the real situation of the patient, either because they are by now disproportionate to any expected results or because they prove an excessive burden on the patient and his family.”4 Under these circumstances, shutting off support machines causes the death of the person, as defined by the brain being irreversibly damaged or the heart stopping.

Therefore loss of higher brain function cannot be the biological basis for declaring a person dead. It may at some point be the basis for discontinuing treatments and so result in death, but it is not the criterion of death.

2. Others, chiefly physicians in the United Kingdom, propose “the irreversible loss of brain-stem functions” as the definition of brain death. As described above, the brain stem has multiple vital functions, primarily support of respiration and circulation. Even if brain-stem functions are lost, however, the integrated activities of the cerebral hemispheres may be intact, and remain functional. Since brain-stem functions could be replaced or bypassed by machines, and the person maintained on life-support systems might retain those very higher brain functions that others promote as the basis of our humanness, I see no biological basis for this criterion of death.

3. In the United States, “brain death” is synonymous with “the irreversible loss of whole brain functions.” This implies that functions essential for the integrated existence of the person are interrupted at all levels of the nervous system: the brain stem, (for support of breathing and the control of circulation), the brain stem and midbrain (for integrating sensory, motor, and regulatory mechanisms), and the cerebral hemispheres and cerebral cortex (for the performance of higher brain functions such as communication and interaction with the environment). Interaction among these levels of brain activity is also interrupted.

In some formulations of this criterion, the words used are “the irreversible cessation of all clinical functions of the entire brain.” Inclusion of the word “entire” has caused confusion, however, because in this context it has no anatomical basis unless it refers to cessation of every function of every neuron, including those of the spinal cord. Opponents of the concept of brain death rightly point out that not all nerve cells may be dead. Neurons stop functioning at different rates after injuries. Isolated functions may persist. For brain death, what is significant is that the integrated activities of neuronal populations supporting the vital functions of the brain be irreversibly lost. I propose, therefore, that the term “brain death” be defined more explicitly as:

“the irreversible cessation of functions of the brain involved with the integrated actions required for support of breathing, circulation, and higher brain functions such as alertness, attention, verbal and non-verbal communication, awareness of one’s environment, and response to the environment.”

In addition, I would emphasize that brain death is irreversible; that the mechanism of the acute global destruction of the brain must be known; and that the integrated functions of the brain cannot be replaced by any machine or organ transplantation.

HOW IS THE CRITERION OF BRAIN DEATH USED?

Perhaps because cardiac transplantation focused attention on the need to change the criterion of death, it is commonly assumed that the concept of brain death is used only in connection with transplantation of vital organs. This is not the case at my hospital, however, or at several other institutions that I have surveyed. I have reviewed data and procedures in the Neurology-Neurosurgery Intensive Care Unit of Johns Hopkins Hospital, the Maryland Shock Trauma Unit (a state facility for accident victims and others acutely injured), and the University of Washington. Of 703 persons who died at Johns Hopkins between January and August 1997, the outcome of brain death was determined in only 26 patients (3.7% of the deaths). Of these 26 patients, only six became organ donors. Data from the Maryland Shock-Trauma unit are very similar. Of 748 deaths, 67 patients were identified as having brain death. Of these, only 19 became organ donors. In all three institutions, the practice is to make a determination of brain death before there is any discussion of organ donation with the families involved (unless the family spontaneously brings up the issue). These statistics show that many patients defined as brain dead do not become organ donors.

Let me repeat that discussions of brain death per se are substantially different from discussions of irreversible loss of higher brain function. The basic differences are the preciseness of the definition of brain death, the irreversibility of brain death, and that when support measures are discontinued in brain death, the vital functions of breathing and circulation will cease immediately .

End-of-life issues have always been with us. They are particularly poignant now with respect to termination of life support in the irreversibly brain-damaged patient. The concept and precise definition of brain death are important in discussions with families about the futility of continuing therapy. When a patient has had irreversible injury to the brain, and the medical staff has determined that brain death has occurred, continued treatment and support are futile. In talking with family members, some of whom may need reassurance that “everything possible is being done,” the ability to state that the patient meets the clinical criteria for brain death is comforting.

LOOKING AHEAD

The concept of brain death is biologically sound. Brain death can be defined, is irreversible, and represents the cessation of higher brain functions and vital integrating functions that cannot be replaced.

If, in response to current pressures and attacks, the concept of brain death were abandoned, the consequences for patients needing transplants and families making heart-wrenching decisions about ending life support would be tragic. The specific definition of brain death I have proposed, if more widely understood and put into practice, could help to reduce pressures that threaten its acceptance.

The concept of brain death has been used for 30 years, during which there have been remarkable advances in both mechanical and biological replacement of organs, organ systems, cells, and now even cellular components, by transplantation. The global functioning of the brain, however, has so far resisted being replaced by these advances. If, at some time, the brain can be replaced, as the heart is now routinely replaced, then the concept of brain death will have to be reconsidered, much as we are now reconsidering the traditional concept of cessation of cardiorespiratory function.

Almost certainly, there will be further attempts to develop mechanical hearts, or genetically engineer organs from other species to be immunologically compatible with humans and transplanted into them. Donation of organs by one human to another might be eliminated. Despite these advances, we will need not only to accept and use a consistent definition of death but to continually examine this definition to see how it might need to evolve.

Author’s Acknowledgement5

I wish to thank Dr. James Bernat, Professor of Neurology at Dartmouth, for his helpful input. His thoughtful discussion of many of the issues discussed in this paper are in reference 5.

 

References

  1. Younger, S.J. and Arnold R.M.; Ethical, Psychosocial and Public Health Policy Implications of Procuring Organs from Non-Beating Heart Donors. JAMA 269 (1993), 2769-74.
  2. Shewmon A; Recovery from “Brain Death”: A Neurologist’s Apologia. Linacre Quarterly 64 (1997), 30-96
  3. Truog R.D.; Is it Time to Abandon Brain Death? Hastings Center Report 27 (1997) 29-37.
  4. Pope John Paul 11; The Encyclical Letter on Abortion, Euthanasia, and the Death Penalty in Today’s World. The Gospel of Life (Evangelicum Vitae). Random House 1995.
  5. Bernat J.L.; A Defense of the Whole Brain Concept of Death. Hastings Center Report. 28 (1998), 14-23.



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Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
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Donald Price, M.D., The Johns Hopkins University School of Medicine

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