Dr. Mercado of Boston University School of Medicine has no relevant financial relationships to disclose.)
This article includes discussion of brain death, brainstem death, cerebral death, death by brain criteria, and death by neurologic criteria. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
“Brain death” is the common term for the determination of human death by showing the irreversible cessation of all clinical brain functions. It has been accepted as a legal definition of death in the United States, Canada, most European countries, and many Western and non-Western countries. Brain death must be determined by careful neurologic examination showing apnea, cranial nerve areflexia, and unresponsiveness that is irreversible and caused by a structural lesion that accounts for the clinical findings. Tests showing the absence of intracranial blood flow can establish the diagnosis and should be used whenever any doubt arises over the clinical examination or if portions of it cannot be performed safely or adequately. The public, and many medical and nursing personnel, remain confused about the meaning of the term “brain death.” In the update of this article, the author discusses the need for uniformity in brain death determination, the use of ancillary tests in brain death, and several reports on specific topics, including brain death in pregnancy, declaring brain death in the setting of drug intoxication, the legal acceptance of brain death, and portrayals of brain death in the popular media.
• Brain death is human death determined by establishing the irreversible cessation of all clinical and physiologic functions of the brain.
• Brain death is the legal standard for human death throughout the Western world and much of the developing world.
• The essential criteria for brain death are: complete unresponsiveness, brainstem areflexia, apnea, and irreversibility.
• Tests showing the absence of intracranial circulation can confirm brain death in cases in which examiners are inexperienced or the complete examination cannot be performed.
• The brain-dead patient is the ideal multi-organ donor, and families of brain-dead patients should be offered the opportunity for organ donation.
Historical note and terminology
"Brain death" is the commonly accepted name for human death determined by clinical evaluation showing the irreversible cessation of all clinical functions of the entire brain. The concept of brain death originated with observations made by French neurologists in the late 1950s that patients with irreversible structural brain lesions maintained on ventilators showed an unprecedented depth of coma, cranial nerve areflexia, and apnea, a state they termed “coma dépassé,” meaning a “state beyond coma” (Mollaret and Goulon 1959). Their key findings included: deep coma, lack of spontaneous breathing, inability to vary heart rate and blood pressure in response to appropriate stimuli, polyuria, and subsequent cardiac arrest days later. In a landmark paper in 1968, an ad hoc Harvard Medical School committee proposed the first definition of brain death, which required the presence of coma (no response to external stimuli), no spontaneous movements or spontaneous breathing, lack of brainstem reflexes, and an isoelectric EEG (Ad Hoc Committee 1968). Since that time, guidelines for the determination of brain death have been published, and the “Uniform Determination of Death Act” has been adopted by most states in the United States, establishing brain death as a legal definition of death (President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research 1981).
The term “brain death” is misleading because it incorrectly implies that only the brain has died and not the human organism. This term alone may be responsible for much of the confusion about it by the public and by some professionals. Yet because the term “brain death” has been generally accepted, it is likely to remain in common use. A more appropriate term would be “death by neurologic criteria.”
The prevalence of brain death practice is expanding internationally. A 2002 survey of brain death practices worldwide disclosed the accepted practice of brain death determination in 80 countries surveyed. Practice guidelines were available in 70 of these countries; legal standards were in effect in 55 countries. Although there was widespread agreement on the concept of brain death, differences were detected in the clinical practices of determining brain death (Wijdicks 2002; Hornby et al 2006). A detailed survey of international brain death practices in 91 countries showed legal provisions in 70% and found that the presence of institutional brain death protocols correlated highly with the presence of an organized organ transplantation network (Wahlster et al 2015). The World Federation of Neurology Ethics Committee has proposed an attempt to standardize brain death determination throughout the world. A similar international effort sponsored by the Neurocritical Care Society is underway. A comparison of the standards among the UK, Canada, and Australia has been published (Gardiner et al 2012).
The terminology in this area is confusing. The old terms "cerebral death" and "neocortical death" should be abandoned because they imply incorrectly that the destruction of the cerebrum or neocortex alone is sufficient for death. The term "brainstem death" has been used in the United Kingdom to acknowledge that most of the bedside tests demonstrating the absence of clinical brain functions examine brainstem functions specifically (Pallis and Harley 2009). However, the term "brainstem death" adds confusion to an already confused terminology (Molinari 1982; Youngner et al 1989) and should not be used in place of "brain death." Public surveys show persistent confusion of the meaning of the term brain death and its distinction from the persistent vegetative state (Siminoff et al 2004; Long et al 2008). Similarly, surveys of American neurologists disclosed an inadequate understanding of brain death (Joffe et al 2012).
The concept of "whole brain death" embodies the most useful and widely accepted criterion of death (Bernat 1998; Bernat 2005; Bernat 2009). Except for the United Kingdom, all brain death clinical and ancillary tests in current use are based on the “whole brain” criterion of death, which requires that the clinical functions of all portions of the brain, including the brainstem, must have ceased irreversibly. Even the UK brainstem death concept was based on the brainstem consequences of a supratentorial catastrophe caused by transtentorial herniation (Wijdicks 2012).
Brain death has been the subject of several comprehensive reviews (Wijdicks 1995; Wijdicks 2001; Wijdicks 2011; Bernat 2005; Bernat 2008b; 2013; Hwang et al 2013; Wijdicks 2013; Wijdicks 2015). The American Academy of Neurology updated their evidence-based practice parameter for determining brain death in adults, which represents the contemporary standard for determining brain death in the United States (Wijdicks et al 2010). In 2011 and 2012, a multisociety committee published the current standards for brain death determination in infants and children (Nakagawa et al 2011; Nakagawa et al 2012). The American Academy of Neurology is currently exploring the possibility of a merged guideline that would apply to both adults and children.
There remains variability in how physicians determine brain death. A study of the brain death determination policies of the top 50 neurology departments in the United States revealed a disturbing pattern of non-uniformity (Greer et al 2008). The authors found significant variations from accepted guidelines or from each other in many areas: who can perform the testing; whether more than one examination is required and the duration of the interval between examinations; the preconditions for testing (eg, establishing an underlying cause and requiring the exclusion of reversible metabolic or toxic factors, hypothermia, and shock); the techniques for testing brainstem function; whether and how to perform apnea testing; and whether and which ancillary electrophysiologic or neuroimaging tests are used. Similar results of practice variability were found in a more recent survey of 68 hospitals in the United States (Shappell et al 2013). A more recent survey of 508 brain death hospital policies in the United States showed significant noncompliance with the American Academy of Neurology standards, particularly by not excluding hypotension and hypothermia, and in the details of apnea testing and ancillary tests (Greer et al 2016). The most recent such survey showed progress in increasing the uniformity of brain death determination guidelines among the leading United States medical centers in compliance with the American Academy of Neurology s 2010 standards (Wang et al 2017).
The existing guidelines should be updated, and a process should be implemented to assure uniformity of testing and physician adherence (Bernat 2008a; Shappell et al 2013). After finding similar results in a survey of pediatric brain death determinations, Mathur and colleagues suggested that physicians determining brain death use a checklist, such as those that have been shown to reduce errors in other medical settings (Mathur et al 2008).
Not all scholars accept the conceptual validity of brain death. A few physicians, philosophers, and theologians continue to hold that patients clinically determined to be brain-dead are not truly dead (Shewmon 1998; Shewmon 2001; Shewmon 2004). Some of these opponents to brain death have argued persuasively that brain death is not an entirely coherent concept, but these arguments have not persuaded medical or public policy bodies to stop recognizing brain death as human death. Brain death continues to be an accepted legal standard of death throughout the majority of the Western and undeveloped world, and its practice is increasing in prevalence. In its analysis, the United States President s Council on Bioethics acknowledged certain conceptual shortcomings in the concept of brain death but recommended that brain death continue to serve as a legal definition of death for the United States (President s Council on Bioethics 2008).
The highly publicized brain death cases in the United States of Jahi McMath and Marlise Muñoz sparked controversy, with much public and scholarly commentary concerning whether they were truly dead and what the law stipulated (Burkle et al 2014; Bernat 2014; Lewis et al 2017b). These discussions culminated in the identification of areas of uncertainty and the further work needed on brain death (Bernat and Larriviere 2014).
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