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Brain death is the permanent, irreversible, and complete loss of
brain function The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for special senses ...
, which may include cessation of involuntary activity (e.g.,
breathing Breathing (spiration or ventilation) is the rhythmical process of moving air into ( inhalation) and out of ( exhalation) the lungs to facilitate gas exchange with the internal environment, mostly to flush out carbon dioxide and bring in oxy ...
) necessary to sustain life. It differs from
persistent vegetative state A vegetative state (VS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative state, the patie ...
, in which the person is alive and some autonomic functions remain. It is also distinct from
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
s as long as some brain and bodily activity and function remain, and it is also not the same as the condition
locked-in syndrome Locked-in syndrome (LIS), also known as pseudocoma, is a condition in which a patient is aware but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in their body except for vertical eye movements and ...
. A
differential diagnosis In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...
can medically distinguish these differing conditions. Brain death is used as an indicator of legal death in many jurisdictions, but it is defined inconsistently and often confused by the public. Various parts of the brain may keep functioning when others do not anymore, bringing questions about whether they should truly be considered dead. The term "brain death" has been used to refer to various combinations. For example, although one major medical dictionary considers "brain death" to be synonymous with "cerebral death" (death of the
cerebrum The cerebrum (: cerebra), telencephalon or endbrain is the largest part of the brain, containing the cerebral cortex (of the two cerebral hemispheres) as well as several subcortical structures, including the hippocampus, basal ganglia, and olfac ...
), the US National Library of Medicine
Medical Subject Headings Medical Subject Headings (MeSH) is a comprehensive controlled vocabulary for the purpose of indexing Academic journal, journal articles and books in the Life science, life sciences. It serves as a thesaurus of index terms that facilitates searc ...
(MeSH) system defines brain death as including the
brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...
. The distinctions are medically significant because, for example, in someone with a dead cerebrum but a living brainstem, spontaneous breathing may continue unaided, whereas in whole-brain death (which includes
brainstem death Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem – the "stalk" of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres – in a dee ...
), only
life support Life support comprises the treatments and techniques performed in an emergency in order to support life after the failure of one or more vital organs. Healthcare providers and emergency medical technicians are generally certified to perform bas ...
equipment would maintain
ventilation Ventilation may refer to: * Ventilation (physiology), the movement of air between the environment and the lungs via inhalation and exhalation ** Mechanical ventilation, in medicine, using artificial methods to assist breathing *** Respirator, a ma ...
. In certain countries, patients classified as brain-dead may legally have their organs surgically removed for
organ donation Organ donation is the process when a person authorizes an organ (anatomy), organ of their own to be removed and organ transplantation, transplanted to another person, #Legislation and global perspectives, legally, either by consent while the d ...
.


Medicolegal history

Brain death is a medicolegal death of a person due to the complete and irreversible loss of all brain functions, including the brain stem. The definition of brain death is accepted in numerous regions, it is one of the most complicated topics in medical ethics today. In
operational definition An operational definition specifies concrete, replicable procedures designed to represent a construct. In the words of American psychologist S.S. Stevens (1935), "An operation is the performance which we execute in order to make known a concept." F ...
s of death have obvious medicolegal implications (in
medical jurisprudence Medical jurisprudence or legal medicine is the branch of science and medicine involving the study and application of scientific and medical knowledge to legal problems, such as inquests, and in the field of law. As modern medicine is a legal ...
and
medical law Medical law is the branch of law which concerns the prerogatives and responsibilities of medical professionals and the rights of the patient. It should not be confused with medical jurisprudence, which is a branch of medicine, rather than a br ...
). Traditionally, both the legal and medical communities determined
death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
through the permanent end of certain bodily functions in
clinical death Clinical death is the medical term for cessation of blood circulation and breathing, the two criteria necessary to sustain the lives of human beings and of many other organisms. It occurs when the heart stops beating in a regular rhythm, a condit ...
, especially
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
and heartbeat. With the increasing ability of the medical community to resuscitate people with no respiration, heartbeat, or other external signs of life, the need for another definition of death occurred, raising questions of legal death. This gained greater urgency with the widespread use of
life support Life support comprises the treatments and techniques performed in an emergency in order to support life after the failure of one or more vital organs. Healthcare providers and emergency medical technicians are generally certified to perform bas ...
equipment and the rising capabilities and demand for
organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be trans ...
. Since the 1960s, laws governing the determination of death have been implemented in all countries that have active organ transplantation programs. The first European country to adopt brain death as a legal definition (or indicator) of death was
Finland Finland, officially the Republic of Finland, is a Nordic country in Northern Europe. It borders Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bothnia to the west and the Gulf of Finland to the south, ...
in 1971, while in the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
, the state of
Kansas Kansas ( ) is a landlocked U.S. state, state in the Midwestern United States, Midwestern region of the United States. It borders Nebraska to the north; Missouri to the east; Oklahoma to the south; and Colorado to the west. Kansas is named a ...
had enacted a similar law earlier. An ''
ad hoc ''Ad hoc'' is a List of Latin phrases, Latin phrase meaning literally for this. In English language, English, it typically signifies a solution designed for a specific purpose, problem, or task rather than a Generalization, generalized solution ...
'' committee at
Harvard Medical School Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
published a pivotal 1968 report to define irreversible
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
. The Harvard criteria gradually gained consensus toward what is now known as brain death. In the wake of the 1976
Karen Ann Quinlan case ''In re Quinlan'' (70 N.J. 10, 355 A.2d 647 (NJ 1976)) was a landmark 1975 court case in the United States in which the parents of a woman who was kept alive by artificial means were allowed to order her removal from artificial ventilation. Kar ...
, state legislatures in the United States moved to accept brain death as an acceptable indication of death. In 1981, a presidential commission issued a landmark report entitled ''Defining Death: Medical, Legal, and Ethical Issues in the Determination of Death'', which rejected the "higher-brain" approach to death in favor of a "whole-brain" definition. This report formed the basis for the Uniform Determination of Death Act, since enacted in 39 states. Today, both the legal and medical communities in the US use "brain death" as a legal definition of death, allowing a person to be declared
legally dead ''Legally Dead'' is a 1923 American drama film directed by William Parke and written by Harvey Gates. The film stars Milton Sills, Margaret Campbell, Claire Adams, Eddie Sturgis, Faye O'Neill, and Charles A. Stevenson. The film was released o ...
even if life support equipment maintains the body's metabolic processes. In the UK, the
Royal College of Physicians The Royal College of Physicians of London, commonly referred to simply as the Royal College of Physicians (RCP), is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of ph ...
reported in 1995, abandoning the 1979 claim that the tests published in 1976 sufficed for the diagnosis of brain death, and suggesting a new definition of death based on the irreversible loss of brain-stem function alone. This new definition, the irreversible loss of the capacity for consciousness and for spontaneous breathing, and the essentially unchanged 1976 tests held to establish that state, have been adopted as a basis of death certification for organ transplant purposes in subsequent Codes of Practice. The Australia and New Zealand Intensive Care Society (ANZICS) states that the "determination of brain death requires that there is unresponsive coma, the absence of brain-stem reflexes and the absence of respiratory centre function, in the clinical setting in which these findings are irreversible. In particular, there must be definite clinical or
neuro-imaging Neuroimaging is the use of quantitative (computational) techniques to study the neuroanatomy, structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive ...
evidence of acute brain pathology (e.g. traumatic brain injury, intracranial haemorrhage, hypoxic encephalopathy) consistent with the irreversible loss of neurological function." In Brazil, the Federal Council of Medicine revised its regulations in 2017, including "a requirement for the patient to meet specific physiological prerequisites and for the physician to provide optimized care to the patient before starting the procedures for diagnosing brain death and to perform complementary tests, as well as the need for specific training for physicians who make this diagnosis." In 2020, an international panel of experts, the World Brain Death Project, published a
guideline A guideline is a statement by which to determine a course of action. It aims to streamline particular processes according to a set routine or sound practice. They may be issued by and used by any organization (governmental or private) to make ...
that:
provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria (BD/DNC) in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries. The World Brain Death Project, published in 2020 by Greer et al., provides some of the most comprehensive and globally recognized recommendations for determining brain death. Their *JAMA* The agreement statement offers detailed evidence in protocols for diagnosing brain death in adults and children. It focuses on a standard clinical process, additional testing when necessary, and special considerations in difficult cases. One of the project's main goals is to reduce variability in brain death diagnosis by creating a consistent, internationally framework (Greer et al., 2020).


Medical criteria

Natural movements also known as the
Lazarus sign The Lazarus sign or Lazarus reflex is a reflex movement in brain-dead or brainstem failure patients, which causes them to briefly raise their arms and drop them crossed on their chests (in a position similar to some Egyptian mummies). The phe ...
or Lazarus reflex can occur on a brain-dead person whose organs have been kept functioning by life support. The living cells that can cause these movements are not living cells from the brain or brain stem; these cells come from the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
. Sometimes these body movements can cause false hope for family members. A brain-dead individual has no clinical evidence of brain function upon
physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...
. This includes no response to
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and no
cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...
reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...
es. Reflexes include
pupillary response Pupillary response is a physiological response that varies the size of the pupil between 1.5 mm and 8 mm, via the optic and oculomotor cranial nerve. A constriction response (miosis), is the narrowing of the pupil, which may be caused by scler ...
(fixed pupils), oculocephalic reflex,
corneal reflex The corneal reflex, also known as the blink reflex or eyelid reflex, is an involuntary blinking of the eyelids elicited by stimulation of the cornea (such as by touching or by a foreign body), though it could result from any peripheral stimulus ...
, no response to the caloric reflex test, and no spontaneous
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
s. Brain death can sometimes be difficult to differentiate from other medical states such as
barbiturate overdose Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). Complic ...
, acute
alcohol poisoning Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of alcohol. The technical term ''intoxication ...
,
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
overdose,
hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...
,
hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...
,
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
, and chronic vegetative states. Some comatose patients can recover to pre-coma or near pre-coma level of functioning, and some patients with severe irreversible neurological dysfunction will nonetheless retain some lower brain functions, such as spontaneous respiration, despite the losses of both cortex and brain stem functionality. Such is the case with
anencephaly Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube ...
. Brain electrical activity can stop completely, or drop to such a low level as to be undetectable with most equipment. An
EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...
will therefore be flat, though this is sometimes also observed during deep
anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...
or
cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...
. Although in the United States a flat EEG test is not required to certify death, it is considered to have confirmatory value. In the UK it is not considered to be of value because any continuing activity it might reveal in parts of the brain above the brain stem is held to be irrelevant to the diagnosis of death on the Code of Practice criteria. The diagnosis of brain death is often required to be highly rigorous, in order to be certain that the condition is irreversible. Legal criteria vary, but in general require neurological examinations by two independent physicians. The exams must show complete and irreversible absence of brain function (brain stem function in UK), and may include two isoelectric (flat-line) EEGs 24 hours apart (less in other countries where it is accepted that if the cause of the dysfunction is a clear physical trauma there is no need to wait that long to establish irreversibility). The patient should have a normal temperature and be free of drugs that can suppress brain activity if the diagnosis is to be made on EEG criteria. Also, a
radionuclide A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ...
cerebral blood flow scan that shows complete absence of intracranial blood flow must be considered with other exams – temporary swelling of the brain, particularly within the first 72 hours, can lead to a false positive test on a patient that may recover with more time.
CT angiography Computed tomography angiography (also called CT angiography or CTA) is a computed tomography technique used for angiography—the visualization of arteries and veins—throughout the human body. Using contrast injected into the blood vessels, im ...
is neither required nor sufficient test to make the diagnosis. Confirmatory testing is only needed under the age of 1. For children and adults, testing is optional. Other situations possibly requiring confirmatory testing include severe facial trauma where determination of brainstem reflexes will be difficult, pre-existing pupillary abnormalities, and patients with severe sleep apnea and/or pulmonary disease. Confirmatory tests include: cerebral angiography, electroencephalography, transcranial Doppler ultrasonography, and cerebral scintigraphy (technetium Tc 99m exametazime). Cerebral angiography is considered the most sensitive confirmatory test in the determination of brain death.


Organ donation

While the diagnosis of brain death has become accepted as a basis for the certification of death for legal purposes, it is a very different state from biological death – the state universally recognized and understood as death. The continuing function of vital organs in the bodies of those diagnosed brain-dead, if mechanical ventilation and other life-support measures are continued, provides optimal opportunities for their transplantation. When mechanical ventilation is used to support the body of a brain-dead organ donor pending a transplant into an organ recipient, the donor's date of death is listed as the date that brain death was diagnosed. In some countries (for instance,
Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...
,
Finland Finland, officially the Republic of Finland, is a Nordic country in Northern Europe. It borders Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bothnia to the west and the Gulf of Finland to the south, ...
, the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...
,
Portugal Portugal, officially the Portuguese Republic, is a country on the Iberian Peninsula in Southwestern Europe. Featuring Cabo da Roca, the westernmost point in continental Europe, Portugal borders Spain to its north and east, with which it share ...
,
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
, and by 2026
Switzerland Switzerland, officially the Swiss Confederation, is a landlocked country located in west-central Europe. It is bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. Switzerland ...
), everyone is automatically an organ donor after diagnosis of death on legally accepted criteria, although some jurisdictions (such as
Singapore Singapore, officially the Republic of Singapore, is an island country and city-state in Southeast Asia. The country's territory comprises one main island, 63 satellite islands and islets, and one outlying islet. It is about one degree ...
, Spain, the United Kingdom, France,
Czech Republic The Czech Republic, also known as Czechia, and historically known as Bohemia, is a landlocked country in Central Europe. The country is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the south ...
,
Poland Poland, officially the Republic of Poland, is a country in Central Europe. It extends from the Baltic Sea in the north to the Sudetes and Carpathian Mountains in the south, bordered by Lithuania and Russia to the northeast, Belarus and Ukrai ...
and Portugal) allow opting out of the system. Elsewhere, consent from family members or next-of-kin may be required for organ donation. In
New Zealand New Zealand () is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and List of islands of New Zealand, over 600 smaller islands. It is the List of isla ...
,
Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...
and most states in the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
, drivers are asked upon application if they wish to be registered as an organ donor. In the United States, if the patient is at or near death, the hospital must notify a designated Organ Procurement Organization (OPO) of the details, and maintain the patient while the patient is being evaluated for suitability as a donor. The OPO searches to see if the deceased is registered as a donor, which serves as legal consent; if the deceased has not registered or otherwise noted consent (e.g., on a driver's license), the OPO will ask the next of kin for authorization. The patient is kept on ventilator support until the organs have been surgically removed. If the patient has indicated in an advance health care directive that they do not wish to receive
mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...
or has specified a do-not-resuscitate (DNR) order and the patient has also indicated that they wish to donate their organs, some vital organs such as the heart and lungs may not be able to be recovered.


Demographics


United States

Brain death is responsible for 2% of all adult and 5% of pediatric in-hospital deaths in the United States. In a nationwide survey of pediatric intensive care units (PICU) in the United States in 2019; there were more than 3,000 pediatric brain deaths out of a total of more than 15,344 children who died in PICUs. According to a national study, "brain death evaluations are performed infrequently, even in large PICUs."


See also

*
Brainstem death Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem – the "stalk" of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres – in a dee ...
*
Clinical death Clinical death is the medical term for cessation of blood circulation and breathing, the two criteria necessary to sustain the lives of human beings and of many other organisms. It occurs when the heart stops beating in a regular rhythm, a condit ...
* Consciousness after death *
Death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
*
Persistent vegetative state A vegetative state (VS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative state, the patie ...
* Information-theoretic death * Klaus Schäfer


References


External links

{{DEFAULTSORT:Brain Death Medical aspects of death Anatomical pathology Brain