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 deeply comatose, ventilator-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.[1]

In the United Kingdom, the formal diagnosis of brainstem death by the procedure laid down in the official Code of Practice[1] permits the diagnosis and certification of death on the premise 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.[2]

This concept of brainstem death is also accepted as grounds for pronouncing death for legal purposes in India[3] and Trinidad & Tobago.[4] 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' President's Council on Bioethics 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 of America.[5]

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.[6] 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 fruitless further artificial support so that death might be allowed to occur, thus "sparing relatives from the further emotional trauma of sterile hope".[6]

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".[7] 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 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 of London, the Conference of Medical Royal Colleges[2] 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[8]—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".[2]

Diagnosis

In the UK, the formal rules for the diagnosis of brainstem death have undergone only minor modifications since they were first published[6] 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[1] reaffirms the preconditions for its consideration. These are:

  1. 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.
  2. There should be no evidence that this state is due to depressant drugs.
  3. Primary hypothermia as the cause of unconsciousness must have been excluded, and
  4. Potentially reversible circulatory, metabolic and endocrine disturbances likewise.
  5. Potentially reversible causes of apnoea (dependence on the ventilator), such as muscle relaxants and cervical cord injury, must be excluded.

With these pre-conditions satisfied, the definitive criteria are:

  1. Fixed pupils which do not respond to sharp changes in the intensity of incident light.
  2. No corneal reflex.
  3. 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).
  4. No response to supraorbital pressure.
  5. No cough reflex to bronchial stimulation or gagging response to pharyngeal stimulation.
  6. 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 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.[9][10][11][12]

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 gases 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 is inadequate to support synaptic function although there is still sufficient blood flow to keep brain cells alive[9] 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 abnormalities commonly seen in this early stage.[13]

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.[14] However, there have been some very long-term survivals[15] 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.[16]

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 from the first.[17][18] 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.[19] In 1995, that claim was abandoned[7] 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, viz. 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).[19] Knowledge of this arousal system is based upon the findings from animal experiments[20][21][22] as illuminated by pathological studies in humans.[23] The current neurological consensus is that the arousal of consciousness depends upon reticular components which reside in the midbrain, diencephalon and pons.[24][25] 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 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.[20] 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.[26]

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 raising thoughts about the "plasticity" of the nervous system.[23] Other theories of consciousness place more stress on the thalamocortical system.[27] 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 – 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[28][29][30] strongly suggestive of the persistence of brainstem blood pressure control in organ donors.

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[1] and that in terms of its ability to diagnose de facto brainstem death it falls far short.

References

  1. ^ a b c d A Code of Practice for the Diagnosis and Confirmation of Death. Academy of Medical Royal Colleges, 70 Wimpole Street, London, 2008
  2. ^ a b c Criteria for the diagnosis of brain stem death. J Roy Coll Physns of London 1995;29:381–2
  3. ^ The Transplantation of Human Organs Act, 1994. Act No.42 of 1994. s. 2
  4. ^ Human Tissue Transplant Act 2000. s. 19(1)
  5. ^ Controversies in the determination of death. A White Paper by the President's Council on Bioethics, Washington, DC. p 66
  6. ^ a b c Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1976;2:1187–8
  7. ^ a b Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1979;1:332.
  8. ^ Pallis, C. From Brain Death to Brain Stem Death, BMJ, 285, November 1982
  9. ^ a b Coimbra CG. Implications of ischemic penumbra for the diagnosis of brain death. Brazilian Journal of Medical and Biological Research 1999;32:1479–87
  10. ^ Coimbra CG. The apnea test – a bedside lethal 'disaster' to avoid a legal 'disaster' in the operating room. In Finis Vitae – is brain death still life? pp.113–45
  11. ^ Saposnik G et al. Problems associated with the apnea test in the diagnosis of brain death. Neurology India 2004;52:342–45
  12. ^ Yingying S et al. Diagnosis of brain death : confirmatory tests after clinical test. Chin Med J 2014;127:1272–77
  13. ^ Coimbra CG. Are 'brain dead' (or 'brain stem dead') patients neurologically recoverable? In Finis Vitae—'brain death' is not true death. Eds. De Mattei R, Byrne PA. Life Guardian Foundation, Oregon, Ohio, 2009, pp. 313–378
  14. ^ Pallis C, Harley DH. ABC of brain stem death. BMJ Publishing Group, 1996, p.30
  15. ^ Shewmon DA. 'Brain body' disconnection : implications for the theoretical basis of 'brain death'. In Finis Vitae – is brain death still life? Ed. De Mattei R. Consiglio Nazionale delle Richerche. Rubbettino, 2006, pp. 211–250
  16. ^ Powner DJ, Bernstein IM. Extended somatic support for pregnant women after brain death. Crit Care Med 2003;31:1241–49
  17. ^ Evans DW, Lum LC. Cardiac transplantation. Lancet 1980;1:933–4
  18. ^ Evans DW, Lum LC. Brain death. Lancet 1980;2:1022
  19. ^ a b 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. 139–158
  20. ^ a b G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalog Clin neurophysiol 1949;1:455–73
  21. ^ Ward AA. The relationship between the bulbar-reticular suppressor region and the EEG. Clin Neurophysiol 1949;1:120
  22. ^ Lindsley DB et al. Effect upon the EEG of acute injury to the brain stem activating system. EEG Clin Neurophysiol 1949;1:475–8627
  23. ^ a b Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem coma. Brain 2003;126:1524–36
  24. ^ Textbook of clinical neurology, 2nd Edn. Ed. Goetz CG. Elsevier Science, 2003
  25. ^ Bleck TP. In Textbook of clinical neurology, 3rd Edn. Ed. Goetz CG. Elsevier Science, 2007
  26. ^ Zwarts MJ, Kornips FHM. Clinical brainstem death with preserved electroencephalographic activity and visual evoked response. Arch Neurol 2001;58:1010
  27. ^ Tononi G. An information integration theory of consciousness. BMC Neuroscience 2004;5:42
  28. ^ Hall GM et al. Hypothalamic-pituitary function in the 'brain dead' patient. Lancet 1980;2:1259
  29. ^ Wetzel RC et al. Hemodynamic responses in brain dead organ donor patients. Anesthesia and Analgesia 1985;64:125–8
  30. ^ Pennefather SH, Dark JH, Bullock RE. Haemodynamic responses to surgery in brain-dead organ donors. Anaesthesia 1993;48:1034–38

External links

Algor mortis

Algor mortis (Latin: algor—coldness; mortis—of death), the second stage of death, is the change in body temperature post mortem, until the ambient temperature is matched. This is generally a steady decline, although if the ambient temperature is above the body temperature (such as in a hot desert), the change in temperature will be positive, as the (relatively) cooler body acclimates to the warmer environment. External factors can have a significant influence.

The term was first used by Dowler in 1849. The first published measurements of the intervals of temperature after death were done by Dr John Davey in 1839.

Brain death

Brain death is the complete loss of brain function (including involuntary activity necessary to sustain life). It differs from persistent vegetative state, in which the person is alive and some autonomic functions remain. It is also distinct from an ordinary coma, whether induced medically or caused by injury and/or illness, even if it is very deep, as long as some brain and bodily activity and function remains; and it is also not the same as the condition known as locked-in syndrome. A differential diagnosis 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 lay public. Various parts of the brain may keep functioning when others do not anymore, and 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 US National Library of Medicine Medical Subject Headings (MeSH) system defines brain death as including the brainstem. The distinctions are medically significant because, for example, in someone with a dead cerebrum but a living brainstem, the heartbeat and ventilation can continue unaided, whereas in whole-brain death (which includes brainstem death), only life support equipment would keep those functions going. Patients classified as brain-dead can have their organs surgically removed for organ donation.

Chris Pallis

Christopher Agamemnon Pallis (2 December 1923, Bombay – 10 March 2005, London) was an Anglo-Greek neurologist and libertarian socialist intellectual. Under the pen-names Martin Grainger and Maurice Brinton, he wrote and translated for the British group Solidarity from 1960 until the early 1980s. As a neurologist, he produced the accepted criteria for brainstem death, and wrote the entry on death for Encyclopædia Britannica.

Dead on arrival

Dead on arrival (DOA), also dead in the field and brought in dead (BID), indicates that a patient was found to be already clinically dead upon the arrival of professional medical assistance, often in the form of first responders such as emergency medical technicians, paramedics, or police.

In some jurisdictions, first responders must consult verbally with a physician before officially pronouncing a patient deceased, but once cardiopulmonary resuscitation is initiated, it must be continued until a physician can pronounce the patient dead.

Death messenger

Death messengers, in former times, were those who were dispatched to spread the news that an inhabitant of their city or village had died. They were to wear unadorned black and go door to door with the message, "You are asked to attend the funeral of the departed __________ at (time, date, and place)." This was all they were allowed to say, and were to move on to the next house immediately after uttering the announcement. This tradition persisted in some areas to as late as the mid-19th century.

Death rattle

Terminal respiratory secretions (or simply terminal secretions), known colloquially as a death rattle, are sounds often produced by someone who is near death as a result of fluids such as saliva and bronchial secretions accumulating in the throat and upper chest. Those who are dying may lose their ability to swallow and may have increased production of bronchial secretions, resulting in such an accumulation. Usually, two or three days earlier, the symptoms of approaching death can be observed as saliva accumulates in the throat, making it very difficult to take even a spoonful of water. Related symptoms can include shortness of breath and rapid chest movement. While death rattle is a strong indication that someone is near death, it can also be produced by other problems that cause interference with the swallowing reflex, such as brain injuries.It is sometimes misinterpreted as the sound of the person choking to death, or alternatively, that they are gargling.

Dignified death

Dignified death is a somewhat elusive concept often related to suicide. One factor that has been cited as a core component of dignified death is maintaining a sense of control. Another view is that a truly dignified death is an extension of a dignified life. There is some concern that assisted suicide does not guarantee a dignified death, since some patients may experience complications such as nausea and vomiting. There is some concern that age discrimination denies the elderly a dignified death.

Fan death

Fan death is a well-known superstition in Korean culture, where it is thought that running an electric fan in a closed room with unopened or no windows will prove fatal. Despite no concrete evidence to support the concept, belief in fan death persists to this day in Korea, and also to a lesser extent in Japan.

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 phenomenon is named after the Biblical figure Lazarus of Bethany, whom Jesus Christ raised from the dead in the Gospel of John.

Legal death

Legal death is the recognition under the law of a particular jurisdiction that a person is no longer alive. In most cases, a doctor's declaration of death (variously called) or the identification of a corpse is a legal requirement for such recognition. A person who has been missing for a sufficiently long period of time (typically at least several years) may be presumed or declared legally dead, usually by a court. When a death has been registered in a civil registry, a death certificate may be issued. Such death certificate may be required in a number of legal situations, such as applying for probate, claiming some benefits or making an insurance claim, etc.

Megadeath

Megadeath (or megacorpse) is one million human deaths, usually caused by a nuclear explosion. The term was used by scientists and thinkers who strategized likely outcomes of all-out nuclear warfare.

Necronym

A necronym (from the Greek words νεκρός, nekros, "dead" and ὄνομα ónoma, "name") is a reference to, or name of, a person who has died. Many cultures have taboos and traditions associated with referring to such a person. These vary from the extreme of never again speaking the person's real name, often using some circumlocution instead, to the opposite extreme of commemorating it incessantly by naming other things or people after the deceased.

For instance, in some cultures it is common for a newborn child to receive the name (a necronym) of a relative who has recently died, while in others to reuse such a name would be considered extremely inappropriate or even forbidden. While this varies from culture to culture, the use of necronyms is quite common.

Necrophobia

Necrophobia is a specific phobia which is the irrational fear of dead things (e.g., corpses) as well as things associated with death (e.g., coffins, tombstones, funerals, cemeteries). With all types of emotions, obsession with death becomes evident in both fascination and objectification. In a cultural sense, necrophobia may also be used to mean a fear of the dead by a cultural group, e.g., a belief that the spirits of the dead will return to haunt the living.Symptoms include: shortness of breath, rapid breathing, irregular heartbeat, sweating, dry mouth and shaking, feeling sick and uneasy, psychological instability, and an altogether feeling of dread and trepidation. The sufferer may feel this phobia all the time. The sufferer may also experience this sensation when something triggers the fear, like a close encounter with a dead animal or the funeral of a loved one or friend. The fear may have developed when a person witnessed a death, or was forced to attend a funeral as a child. Some people experience this after viewing frightening media.The fear can manifest itself as a serious condition. Treatment options include medication and therapy.The word necrophobia is derived from the Greek nekros (νεκρός) for "corpse" and the Greek phobos (φόβος) for "fear".

Obituary

An obituary (obit for short) is a news article that reports the recent death of a person, typically along with an account of the person's life and information about the upcoming funeral. In large cities and larger newspapers, obituaries are written only for people considered significant. In local newspapers, an obituary may be published for any local resident upon death. A necrology is a register or list of records of the deaths of people related to a particular organization, group or field, which may only contain the sparsest details, or small obituaries. Historical necrologies can be important sources of information.

Two types of paid advertisements are related to obituaries. One, known as a death notice, omits most biographical details and may be a legally required public notice under some circumstances. The other type, a paid memorial advertisement, is usually written by family members or friends, perhaps with assistance from a funeral home. Both types of paid advertisements are usually run as classified advertisements.

Ocular tremor

Ocular microtremor (OMT) is a constant, physiological, high frequency (peak 80Hz), low amplitude (estimated circa 150-2500nm (1)) eye tremor.

It occurs in all normal people even when the eye is apparently still and is due to the constant activity of brainstem oculomotor units. In coma there is a loss of high frequency components of tremor and the extent of this reduction is related to the patient's prognosis (2). Ocular microtremor can potentially help in the difficult diagnosis of brainstem death, as well as monitoring patients while under anaesthesia (3). Abnormal OMT records are seen in neurological conditions such as Parkinson's disease and multiple sclerosis. The frequency spectrum also changes with age.The first description of what is now known as ocular microtremor was made in 1934 (4). More recent studies are less common for ocular microtremor than for other fixational eye movements. Some have suggested that the reason ocular microtremor studies are more rare may be because of the difficulty inherent in measuring microtremor. It is contentious whether ocular microtremor assists vision. Visual processes deteriorate rapidly in the absence of retinal image motion, with Stabilized Images.Some have suggested that tremor may not be a distinct eye movement at all.

Pallor mortis

Pallor mortis (Latin: pallor "paleness", mortis "of death"), the first stage of death, is an after-death paleness that occurs in those with light/white skin.

Post-mortem interval

Post-mortem interval (PMI) is the time that has elapsed since a person has died. If the time in question is not known, a number of medical/scientific techniques are used to determine it. This also can refer to the stage of decomposition of the body.

Rigor mortis

Rigor mortis (Latin: rigor "stiffness", mortis "of death"), or postmortem rigidity, is the third stage of death. It is one of the recognizable signs of death, characterized by stiffening of the limbs of the corpse caused by chemical changes in the muscles postmortem. In humans, rigor mortis can occur as soon as four hours after death.

Vestibulo–ocular reflex

The vestibulo-ocular reflex (VOR) is a reflex, where activation of the vestibular system of the inner ear causes eye movement. This reflex functions to stabilize images on the retinas (when gaze is held steady on a location) during head movement by producing eye movements in the direction opposite to head movement, thus preserving the image on the center of the visual field(s). For example, when the head moves to the right, the eyes move to the left, and vice versa. Since slight head movement is present all the time, VOR is necessary for stabilizing vision: patients whose VOR is impaired find it difficult to read using print, because they cannot stabilize the eyes during small head tremors, and also because damage to the VOR can cause vestibular nystagmus.The VOR does not depend on visual input. It can be elicited by caloric (hot or cold) stimulation of the inner ear, and works even in total darkness or when the eyes are closed. However, in the presence of light, the fixation reflex is also added to the movement.In other animals, the organs that coordinate balance and motor coordination do not operate independently from the organs that control the eyes. A fish, for instance, moves its eyes by reflex when its tail is moved. Humans have semicircular canals, neck muscle "stretch" receptors, and the utricle (gravity organ). Though the semicircular canals cause most of the reflexes which are responsive to acceleration, the maintaining of balance is mediated by the stretch of neck muscles and the pull of gravity on the utricle (otolith organ) of the inner ear.The VOR has both rotational and translational aspects. When the head rotates about any axis (horizontal, vertical, or torsional) distant visual images are stabilized by rotating the eyes about the same axis, but in the opposite direction. When the head translates, for example during walking, the visual fixation point is maintained by rotating gaze direction in the opposite direction, by an amount that depends on distance.

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