Organ and Tissue Transplantation

David Price

• Publisher: Routledge
• Year: 2017
• Print ISBN: 9780754625391
• eBook ISBN: 9781351913454
• Edition: 1
• Topic: Law
• Subtopic: Medical Law
• Index: Law

Organ transplantation has been one of the miracles of modern-day medicine but, in addition to presenting enormous technical and clinical challenges, it throws up major ethical and legal issues principally from the perspective of the donor. Evolving capabilities in the spheres of both organ and tissue transplantation, coupled with rapidly-escalating demand, assert consistent and critical pressure on our ethical and legal principles and frameworks, including the expansion of the potential donor pool beyond the conventional categories of donor. This volume brings together seminal papers analyzing such matters in the context of an ever-increasingly important area of clinical practice.

Part I
Meaning of Death

[1]
Is It Time to Abandon Brain Death?

by Robert D. Truog

Despite its familiarity and widespread acceptance, the concept of "brain death" remains incoherent in theory and confused in practice. Moreover, the only purpose served by the concept is to facilitate the procurement of transplantable organs. By abandoning the concept of brain death and adopting different criteria for organ procurement, we may be able to increase both the supply of transplantable organs and clarity in our understanding of death.

Over the past several decades, the concept of brain death has become well entrenched within the practice of medicine. At a practical level, this concept has been successful in delineating widely accepted ethical and legal boundaries for the procurement of vital organs for transplantation. Despite this success, however, there have been persistent concerns over whether the concept is theoretically coherent and internally consistent.¹ Indeed, some have concluded that the concept is fundamentally flawed, and that it represents only a "superficial and fragile consensus."² In this analysis I will identify the sources of these inconsistencies, and suggest that the best resolution to these issues may be to abandon the concept of brain death altogether.

Definitions, Concepts, and Tests

In its seminal work "Defining Death," the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research articulated a formulation of brain death that has come to be known as the "whole-brain standard."³ In the Uniform Determination of Death Act, the President's Commission specified two criteria for determining death: (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brainstem."

Neurologist James Bernat has been influential in defending and refining this standard. Along with others, he has recognized that analysis of the concept of brain death must begin by differentiating between three distinct levels. At the most general level, the concept must involve a definition. Next, criteria must be specified to determine when the definition has been fulfilled. Finally, tests must be available for evaluating whether the criteria have been satisfied.⁴ As clarified by Bernat and colleagues, therefore, the concept of death under the whole-brain formulation can be outlined as follows:⁵

Definition of Death: The "permanent cessation of functioning of the organism as a whole."

Criterion for Death: The "permanent cessation of functioning of the entire brain."

Tests for death: Two distinct sets of tests are available and acceptable for determining that the criterion is fulfilled:

(1) The cardiorespiratory standard is the traditional approach for determining death and relies upon documenting the prolonged absence of circulation or respiration. These tests fulfill the criterion, according to Bernat, since the prolonged absence of these vital signs is diagnostic for the permanent loss of all brain function.

(2) The neurological standard consists of a battery of tests and procedures, including establishment of an etiology sufficient to account for the loss of all brain functions, diagnosing the presence of coma, documenting apnea and the absence of brainstem reflexes, excluding reversible conditions, and showing the persistence of these findings over a sufficient period of time.⁶

Critique of the Current Formulation of Brain Death

Is this a coherent account of the concept of brain death? To answer this question, one must determine whether each level of analysis is consistent with the others. In other words, individuals who fulfill the tests must also fulfill the criterion, and those who satisfy the criterion must also satisfy the definition.⁷

First, regarding the tests-criterion relationship, there is evidence that many individuals who fulfill all of the tests for brain death do not have the "permanent cessation of functioning of the entire brain." In particular, many of these individuals retain clear evidence of integrated brain function at the level of the brainstem and midbrain, and may have evidence of cortical function.

For example, many patients who fulfill the tests for the diagnosis of brain death continue to exhibit intact neurohumoral function. Between 22 percent and 100 percent of brain-dead patients in different series have been found to retain free-water homeostasis through the neurologically mediated secretion of arginine vasopressin, as evidenced by serum hormonal levels and the absence of diabetes insipidus.⁸ Since the brain is the only source of the regulated secretion of arginine vasopressin, patients without diabetes insipidus do not have the loss of all brain function. Neurologically regulated secretion of other hormones is also quite common.⁹

In addition, the tests for the diagnosis of brain death require the patient not to be hypothermic.¹⁰ This caveat is a particularly confusing Catch 22, since the absence of hypothermia generally indicates the continuation of neurologically mediated temperature homeostasis. The circularity of this reasoning can be clinically problematic, since hypothermic patients cannot be diagnosed as brain-dead but the absence of hypothermia is itself evidence of brain function.

Furthermore, studies have shown that many patients (20 percent in one series) who fulfill the tests for brain death continue to show electrical activity on their electroencephalograms.¹¹ While there is no way to determine how often this electrical activity represents true "function" (which would be incompatible with the criterion for brain death), in at least some cases the activity observed seems fully compatible with function.¹²

Finally, clinicians have observed that patients who fulfill the tests for brain death frequently respond to surgical incision at the time of organ procurement with a significant rise in both heart rate and blood pressure. This suggests that integrated neurological function at a supraspinal level may be present in at least some patients diagnosed as brain-dead.¹³ This evidence points to the conclusion that there is a significant disparity between the standard tests used to make the diagnosis of brain death and the criterion these tests are purported to fulfill. Faced with these facts, even supporters of the current statutes acknowledge that the criterion of "whole-brain" death is only an "approximation."¹⁴

If the tests for determining brain death are incompatible with the current criterion, then one way of solving the problem would be to require tests that always correlate with the "permanent cessation of functioning of the entire brain." Two options have been considered in this regard. The first would require tests that correlate with the actual destruction of the brain, since complete destruction would, of course, be incompatible with any degree of brain function. Only by satisfying these tests, some have argued, could we be assured that all functions of the entire brain have totally and permanently ceased.¹⁵ But is there a constellation of clinical and laboratory tests that correlate with this degree of destruction? Unfortunately, a study of over 500 patients with both coma and apnea (including 146 autopsies for neuropathologic correlation) showed that "it was not possible to verify that a diagnosis made prior to cardiac arrest by any set or subset of criteria would invariably correlate with a diffusely destroyed brain."¹⁶ On the basis of these data, a definition that required total brain destruction could only be confirmed at autopsy. Clearly, a condition that could only be determined after death could never be a requirement for declaring death.

Another way of modifying the tests to conform with the criterion would be to rely solely upon the cardiorespiratory standard for determining death. This standard would certainly identify the permanent cessation of all brain function (thereby fulfilling the criterion), since it is well established by common knowledge that prolonged absence of circulation and respiration results in the death of the entire brain (and every other organ). In addition, fulfillment of these tests would also convincingly demonstrate the cessation of function of the organism as a whole (thereby fulfilling the definition). Unfortunately, this approach for resolving the problem would also make it virtually impossible to obtain vital organs in a viable condition for transplantation, since under current laws it is generally necessary for these organs to be removed from a heart-beating donor.

These inconsistencies between the tests and the criterion are therefore not easily resolvable. In addition to these problems, there are also inconsistencies between the criterion and the definition. As outlined above, the whole-brain concept assumes that the "permanent cessation of functioning of the entire brain" (the criterion) necessarily implies the "permanent cessation of functioning of the organism as a whole" (the definition). Conceptually, this relationship assumes the principle that the brain is responsible for maintaining the body's homeostasis, and that without brain function the organism rapidly disintegrates. In the past, this relationship was demonstrated by showing that individuals who fulfilled the tests for the diagnosis of brain death inevitably had a cardiac arrest within a short period of time, even if they were provided with mechanical ventilation and intensive care.¹⁷ Indeed, this assumption had been considered one of the linchpins in the ethical justification for the concept of brain death.¹⁸ For example, in the largest empirical study of brain death ever performed, a collaborative group working under the auspices of the National Institutes of Health sought to specify the necessary tests for diagnosing brain death by attempting to identify a constellation of neurological findings that would inevitably predict the development of a cardiac arrest within three months, regardless of the level or intensity of support provided.¹⁹

This approach to defining brain death in terms of neurological findings that predict the development of cardiac arrest is plagued by both logical and scientific problems, however. First, it confuses a prognosis with a diagnosis. Demonstrating that a certain class of patients will suffer a cardiac arrest within a defined period of time certainly proves that they are dying, but it says nothing about whether they are dead.²⁰ This conceptual mistake can be clearly appreciated if one considers individuals who are dying of conditions not associated with severe neurological impairment. If a constellation of tests could identify a subgroup of patients with metastatic cancer who invariably suffered a cardiac arrest within a short period of time, for example, we would certainly be comfortable in concluding that they were dying, but we clearly could not claim that they were already dead.

Second, this view relies upon the intuitive notion that the brain is the principal organ of the body, the "integrating" organ whose functions cannot be replaced by any other organ or by artificial means. Up through the early 1980s, this view was supported by numerous studies showing that almost all patients who fulfilled the usual battery of tests for brain death suffered a cardiac arrest ...

Table of contents

• Cover
• Half Title
• Title
• Copyright
• Contents
• Acknowledgements
• Series Preface
• Introduction
• PART I THE MEANING OF DEATH
• PART II THE BODY AS PROPERTY
• PART III COMMERCE IN ORGAN PROCUREMENT
• PART IV CADAVERIC ORGAN AND TISSUE DONATION
• PART V LIVING DONOR TRANSPLANTATION
• PART VI SPECIFIC CLASSES OF DONORS
• PART VII ORGAN ALLOCATION
• PART VIII XENOTRANSPLANTATION
• Name Index