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
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...
to the
mid-brain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', "m ...
,
cerebellum and
cerebral hemispheres
The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...
– in a deeply comatose,
ventilator
A ventilator is a piece of medical technology that provides mechanical ventilation by moving breathable air into and out of the lungs, to deliver breaths to a patient who is physically unable to breathe, or breathing insufficiently. Ventilators ...
-dependent patient.
Identification of this state carries a very grave
prognosis for survival; cessation of
heartbeat often occurs within a few days, although it may continue for weeks if intensive support is maintained.
[A Code of Practice for the Diagnosis and Confirmation of Death. Academy of Medical Royal Colleges, London, 2008]
In 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 Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...
,
death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
can be certified on the basis of a formal diagnosis of brainstem death, so long as this is done in accordance with a procedure established in "A Code of Practice for the Diagnosis and Confirmation of Death", published in 2008 by the
Academy of Medical Royal Colleges
The Academy of Medical Royal Colleges (AoMRC) is the coordinating body for the United Kingdom and Ireland's 23 Medical Royal Colleges and Faculties. It ensures that patients are safely and properly cared for by setting standards for the way doc ...
.
The premise of this is that a person is dead when consciousness and the ability to breathe are permanently lost, regardless of continuing life in the body and parts of the brain, and that death of the brainstem alone is sufficient to produce this state.
[Criteria for the diagnosis of brain stem death. J Roy Coll Physns of London 1995;29:381–82]
This concept of brainstem death is also accepted as grounds for pronouncing death for legal purposes in
India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
and
Trinidad & Tobago
Trinidad and Tobago (, ), officially the Republic of Trinidad and Tobago, is the southernmost island country in the Caribbean. Consisting of the main islands Trinidad and Tobago, and numerous much smaller islands, it is situated south of Gr ...
. Elsewhere in the world, the concept upon which the certification of death on neurological grounds is based is that of permanent cessation of all function in all parts of the brain –
whole brain death – with which the British concept should not be confused. The
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
'
President's Council on Bioethics
The President's Council on Bioethics (PCBE) was a group of individuals appointed by United States President George W. Bush to advise his administration on bioethics. Established on November 28, 2001, by Executive Order 13237, the council was dire ...
made it clear, for example, in its White Paper of December 2008, that the British concept and clinical criteria are not considered sufficient for the diagnosis of death in the United States.
[
]
Evolution of diagnostic criteria
The United Kingdom (UK) criteria were first published by the Conference of Medical Royal Colleges (with advice from the Transplant Advisory Panel) in 1976, as prognostic guidelines.
[Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1976;2:1187–88] They were drafted in response to a perceived need for guidance in the management of deeply comatose patients with severe
brain damage who were being kept alive by
mechanical ventilators but showing no signs of recovery. The Conference sought "to establish diagnostic criteria of such rigour that on their fulfilment the mechanical ventilator can be switched off, in the secure knowledge that there is no possible chance of recovery". The published criteria – negative responses to bedside tests of some reflexes with pathways through the brainstem and a specified challenge to the brainstem respiratory centre, with caveats about exclusion of
endocrine influences,
metabolic factors and drug effects – were held to be "sufficient to distinguish between those patients who retain the functional capacity to have a chance of even partial recovery and those where no such possibility exists". Recognition of that state required the withdrawal of further
artificial support so that death is allowed to occur, thus "sparing relatives from the further
emotional trauma of sterile hope".
In 1979, the Conference of Medical Royal Colleges promulgated its conclusion that identification of the state defined by those same criteria – then thought sufficient for a diagnosis of brain death – "means that the patient is dead".
[Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1979;1:332.] Death certification on those criteria has continued in the United Kingdom (where there is no statutory legal definition of death) since that time, particularly 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 transpor ...
purposes, although the conceptual basis for that use has changed.
In 1995, after a review by a Working Group of the
Royal College of Physicians
The Royal College of Physicians (RCP) is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of physicians by examination. Founded by royal charter from King Henry VIII in 1 ...
of
London
London is the capital and List of urban areas in the United Kingdom, largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary dow ...
, the Conference of Medical Royal Colleges
formally adopted the "more correct" term for the syndrome, "brainstem death" – championed by
Pallis in a set of 1982 articles in the ''
British Medical Journal''
[Pallis, C. From Brain Death to Brain Stem Death, BMJ, 285, November 1982] – and advanced a new definition of human death as the basis for equating this syndrome with the death of the person. The suggested new definition of death was the "irreversible loss of the capacity for consciousness, combined with irreversible loss of the capacity to breathe". It was stated that the irreversible cessation of brainstem function will produce this state and "therefore brainstem death is equivalent to the death of the individual".
Diagnosis
In the UK, the formal rules for the diagnosis of brainstem death have undergone only minor modifications since they were first published
in 1976. The most recent revision of the UK's Department of Health Code of Practice governing use of that procedure for the diagnosis of death
reaffirms the preconditions for its consideration. These are:
# There should be no doubt that the patient's condition – deeply comatose, unresponsive and requiring
artificial ventilation – is due to irreversible brain damage of known cause.
# There should be no evidence that this state is due to
depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
drugs.
# Primary
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 ...
as the cause of unconsciousness must have been excluded, and
# Potentially reversible circulatory, metabolic and endocrine disturbances likewise.
# Potentially reversible causes of
apnoea
Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there may ...
(dependence on the ventilator), such as
muscle relaxant
A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therap ...
s and cervical cord injury, must be excluded.
With these pre-conditions satisfied, the definitive criteria are:
# Fixed pupils which do not respond to sharp changes in the intensity of
incident light
In optics a ray is an idealized geometrical model of light, obtained by choosing a curve that is perpendicular to the ''wavefronts'' of the actual light, and that points in the direction of energy flow. Rays are used to model the propagation o ...
.
# No
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. S ...
.
# Absent
oculovestibular reflexes – no eye movements following the slow injection of at least 50ml of ice-cold water into each ear in turn (the
caloric reflex test
In medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of ...
).
# No response to supraorbital pressure.
# No
cough reflex The cough reflex occurs when stimulation of cough receptors in the respiratory tract by dust or other foreign particles produces a cough, which causes rapidly moving air which usually remove the foreign material before it reaches the lungs. This typ ...
to bronchial stimulation or gagging response to pharyngeal stimulation.
# No observed respiratory effort in response to disconnection of the ventilator for long enough (typically 5 minutes) to ensure elevation of the arterial partial pressure of
carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
to at least 6.0 kPa (6.5 kPa in patients with chronic carbon dioxide retention). Adequate
oxygenation is ensured by pre-oxygenation and diffusion oxygenation during the disconnection (so the brainstem respiratory centre is not challenged by the ultimate, anoxic, drive stimulus). This test – the
apnoea test – is dangerous, and may prove lethal.
Two doctors, of specified status and experience, are required to act together to diagnose death on these criteria and the tests must be repeated after "a short period of time ... to allow return of the patient's
arterial blood gas
An arterial blood gas (ABG) test, or arterial blood gas analysis (ABGA) measures the amounts of arterial gases, such as oxygen and carbon dioxide. An ABG test requires that a small volume of blood be drawn from the radial artery with a syringe an ...
es and baseline parameters to the pre-test state". These criteria for the diagnosis of death are not applicable to infants below the age of two months.
Prognosis and management
With due regard for the cause of the coma, and the rapidity of its onset, testing for the purpose of diagnosing death on brainstem death grounds may be delayed beyond the stage where brainstem reflexes may be absent only temporarily – because the
cerebral blood flow
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Art ...
is inadequate to support synaptic function, although there is still sufficient blood flow to keep
brain cell
Brain cells make up the functional tissue of the brain. The rest of the brain tissue is structural or connective called the stroma which includes blood vessels. The two main types of cells in the brain are neurons, also known as nerve cells, an ...
s alive
[Coimbra CG. Implications of ischemic penumbra for the diagnosis of brain death. Brazilian Journal of Medical and Biological Research 1999;32:1479–87] and capable of recovery. There has recently been renewed interest in the possibility of neuronal protection during this phase by use of moderate hypothermia and by correction of the
neuroendocrine
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
abnormalities commonly seen in this early stage.
Published studies of patients meeting the criteria for brainstem death or whole brain death – the American standard which includes brainstem death diagnosed by similar means – record that even if ventilation is continued after diagnosis, the heart stops beating within only a few hours or days. However, there have been some very long-term survivals and it is noteworthy that expert management can maintain the bodily functions of
pregnant brain dead women for long enough to bring them to term.
Criticism
The diagnostic criteria were originally published for the purpose of identifying a clinical state associated with a fatal prognosis (see above). The change of use, in the UK, to criteria for the diagnosis of death itself was protested immediately.
[Evans DW, Lum LC. Cardiac transplantation. Lancet 1980;1:933–34] The initial basis for the change of use was the claim that satisfaction of the criteria sufficed for the diagnosis of the death of the brain as a whole, despite the persistence of demonstrable activity in parts of the brain.
[Evans DW. The demise of 'brain death' in Britain. In Beyond brain death – the case against brain based criteria for human death. Eds. Potts M, Byrne PA, Nilges RG. Kluwer Academic Publishers, 2006, pp. 139–58
] In 1995, that claim was abandoned
[ and the diagnosis of death (acceptable for legal purposes in the UK in the context of organ procurement for transplantation) by the specified testing of brainstem functions was based on a new definition of death – the permanent loss of the capacity for consciousness and spontaneous breathing. There are doubts that this concept is generally understood and accepted and that the specified testing is stringent enough to determine that state. It is, however, associated with substantial risk of exacerbating the brain damage and even causing the death of the apparently dying patient so tested (see "the apnoea test" above). This raises ethical problems which seem not to have been addressed.
It has been argued that sound scientific support is lacking for the claim that the specified purely bedside tests have the power to diagnose true and total death of the brainstem, the necessary condition for the assumption of permanent loss of the intrinsically untestable consciousness-arousal function of those elements of the reticular formation which lie within the brainstem (there are elements also within the higher brain).] Knowledge of this arousal system is based upon the findings from animal experiments as illuminated by pathological studies in humans.[Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem coma. Brain 2003;126:1524–36] The current neurological consensus is that the arousal of consciousness depends upon reticular components which reside in the midbrain, diencephalon and pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Va ...
. It is said that the midbrain reticular formation may be viewed as a driving centre for the higher structures, loss of which produces a state in which the cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
appears, on the basis of electroencephalographic (EEG) studies, to be awaiting the command or ability to function. The role of diencephalic (higher brain) involvement is stated to be uncertain and we are reminded that the arousal system is best regarded as a physiological rather than a precise anatomical entity. There should, perhaps, also be a caveat about possible arousal mechanisms involving the first and second cranial nerves (serving sight and smell) which are not tested when diagnosing brainstem death but which were described in cats in 1935 and 1938.[G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalog Clin neurophysiol 1949;1:455–73] In humans, light flashes have been observed to disturb the sleep-like EEG activity persisting after the loss of all brainstem reflexes and of spontaneous respiration.
There is also concern about the permanence of consciousness loss, based on studies in cats, dogs and monkeys which recovered consciousness days or weeks after being rendered comatose by brainstem ablation and on human studies of brainstem stroke syndrome
A brainstem stroke syndrome falls under the broader category of stroke syndromes, or specific symptoms caused by vascular injury to an area of brain (for example, the lacunar syndromes). As the brainstem contains numerous cranial nuclei and white ...
raising thoughts about the "plasticity" of the nervous system. Other theories of consciousness place more stress on the thalamocortical system. Perhaps the most objective statement to be made is that consciousness is not currently understood. That being so, proper caution must be exercised in accepting a diagnosis of its permanent loss before all cerebral blood flow has permanently ceased.
The ability to breathe spontaneously depends upon functioning elements in the medulla
Medulla or Medullary may refer to:
Science
* Medulla oblongata, a part of the brain stem
* Renal medulla, a part of the kidney
* Adrenal medulla, a part of the adrenal gland
* Medulla of ovary, a stroma in the center of the ovary
* Medulla of t ...
– the 'respiratory centre'. In the UK, establishing a neurological diagnosis of death involves challenging this centre with the strong stimulus offered by an unusually high concentration of carbon dioxide in the arterial blood, but it is not challenged by the more powerful drive stimulus provided by anoxia – although the effect of that ultimate stimulus is sometimes seen after final disconnection of the ventilator in the form of agonal gasps.
No testing of testable brain stem functions such as oesophageal and cardiovascular regulation is specified in the UK Code of Practice for the diagnosis of death on neurological grounds. There is published evidence[Pennefather SH, Dark JH, Bullock RE. Haemodynamic responses to surgery in brain-dead organ donors. ''Anaesthesia'' 1993;48:1034–38] strongly suggestive of the persistence of brainstem blood pressure control in organ donors
Organ donation is the process when a person allows an organ of their own to be removed and transplanted to another person, legally, either by consent while the donor is alive or dead with the assent of the next of kin.
Donation may be for re ...
.
A small minority of medical practitioners working in the UK have argued that neither requirement of the UK Health Department's Code of Practice basis for the equation of brainstem death with death is satisfied by its current diagnostic protocol and that in terms of its ability to diagnose de facto brainstem death it falls far short.
Most of these criticisms overlook the fact that in practice brainstem death testing would not be conducted in isolation. In most cases this is only performed after running a series of CT and MRI scans to look at brain and brainstem health.
References
External links
Great Ormond Street Hospital for Children
{{DEFAULTSORT:Brain Stem Death
Medical aspects of death
Anatomical pathology
Health law in the United Kingdom