Brain death and the vegetative state
Death can be defined as the irreversible loss of the capacity for consciousness and brain stem function, combined with irreversible loss of the capacity to breathe. The irreversible cessation of brainstem function, whether caused by a primary intracranial catastrophe (e.g. trauma, haemorrhage) or the result of extracranial cranial events (e.g hypoxia), will result in the same clinical state, hence brain stem death is the same as death of the patient.
Brain death and death of the brainstem
The distinction between these is of key importance: (1) ‘brain death’ implies death of the entire nervous system, but focal electrical activity is often discoverable under such circumstances; (2) ‘brainstem death’ is an alternative term, representing irreversible loss of brainstem function. Criteria for these diagnoses have been promulgated and require formal tests (see also Chapter 17.9).
This describes patients who are awake but not aware as a result of loss of cortical function, but with a functioning brain stem. The diagnosis of this condition requires documentation by skilled clinicians carried out over periods of time—care is needed to exclude the minimally conscious state or brainstem injury causing widespread paralysis, but with preserved cortical function. Recovery from the vegetative state is possible, but most patients remain severely disabled and dependent.
Declaration of permanence of the vegetative state may allow withdrawal of artificial nutrition and hydration within a legal framework in many countries; in the United Kingdom, it is a legal requirement to seek approval from a court before taking such action.
Despite advances in prehospital, accident and emergency, and intensive care management of neurological conditions, including cerebral trauma, haemorrhage, hypoxia, and infarction, there remain many who succumb. The mechanism of death from these conditions may be sudden with cardiorespiratory decompensation and arrest, or the heart may continue to beat with respiration maintained by artificial ventilation but in the context of irreversible loss of brain function—the state of ‘brain death’. The loss of brainstem function results in failure of neural transmission caudally to maintain respiration and cranially to maintain activation of the cerebrum by the reticular activating system. It is important to distinguish between the definitions of brain death and brainstem death. The original term ‘brain death’ (US Harvard criteria 1968) implied complete death of the whole nervous system (flat electroencephalogram or EEG) but islands of electrical activity may persist in the cortex and/or spinal reflexes may persist. This state is, however, consistent with irreversibility. In the United Kingdom, therefore, the term ‘brainstem death’ (death following irreversible cessation of brainstem function) is preferred. Of patients who are determined as brainstem dead, approximately half are due to trauma, a third due to spontaneous intracranial haemorrhage, and the remainder due to a number of other causes including hypoxia secondary to cardiac arrest.
Criteria for diagnosis
The current criteria in the United Kingdom for diagnosis have been defined by a working group convened in 1998 by the Royal College of Physicians on behalf of the UK conference of Medical Royal Colleges and their Faculties. The working party included doctors, nurses, lawyers, Community Health Council representatives, a member of the Patients’ Association, and others representing transplant coordinators and carers. The group produced a document A code of practice for the diagnosis of brainstem death (see ‘Further reading’).
Brainstem death testing
Confirmation of brainstem death is made by formal brainstem death testing. This follows strict protocols comprising a number of stages.
◆ There should be no doubt that the patient’s condition is due to irremediable brain damage of known aetiology. This may be obvious with CT confirmation of a severe head injury or spontaneous haemorrhage, but may be much more difficult to establish, e.g. after cardiac arrest with an indefinite period of hypoxia. Continued observation and investigation may be required.
◆ The patient is deeply unconscious. Reversible causes such as depressant drugs (e.g. narcotics, hypnotics, tranquillizers), primary hypothermia, and potentially reversible circulatory, metabolic, and endocrine causes must be excluded.
◆ The patient is maintained on a ventilator because spontaneous respiration has ceased. The effects of neuromuscular blocking drugs and other respiratory depressants must be excluded. Confirmation with a nerve stimulator is advisable.
◆ In the United Kingdom, the diagnosis of brainstem death should be made by at least two medically qualified practitioners who fulfil the following criteria:
• both must have been registered for more than 5 years and be competent in the conduct and interpretation of brainstem testing
• at least one should be a consultant
• neither should be members of the transplant team.
◆ Two sets of tests should always be performed. The tests may be carried out by the two practitioners separately or together. The interval between tests is at the discretion of the clinicians.
◆ In the United Kingdom, radiological or neurophysiological studies do not form part of the criteria unless clinical tests alone cannot be relied on, e.g. multiple facial and orbital fractures.
The following criteria must be satisfied in order to diagnose brainstem death:
◆ The pupils are fixed and do not respond to sharp changes in the intensity of incident light. A strong light, e.g. ophthalmoscope with ambient light dimmed, is recommended.
◆ The corneal absent is absent. This is tested using a wisp of cotton-wool, taking care not to damage the cornea.
◆ The oculovestibular reflexes are absent. After clear visualization of the tympanic membrane with an auroscope, and with the head flexed to 30° provided that no cervical injury is present, at least 50 ml of ice-cold water are injected into each external auditory meatus in turn over the course of 1 min.
◆ No motor response within the cranial nerve distribution can be elicited by adequate stimulation of any somatic area. In practice, there is no limb response to supraorbital pressure.
◆ There is no gag reflex to stimulation of the posterior pharynx with a spatula or cough reflex response to bronchial stimulation elicited by placing a suction catheter down the trachea.
◆ Apnoea test: no respiratory responses occur when the patient is disconnected from the ventilator. This is the last test to be performed if all the preceding tests confirm the absence of brainstem reflexes. The patient should be preoxygenated with 100% oxygen for 10 min. The patient should then be disconnected from the ventilator and observed for respiratory effort for 10 min. Oxygenation is continued by administering oxygen at a rate of 6 l/min via a fine-bore catheter down the endotracheal tube. A blood gas must be taken to ensure that the arterial pressure of carbon dioxide has reached 6.65 kPa. The patient is reconnected to the ventilator. A more detailed protocol will be included in the Code of Practice of the Diagnosis and Confirmation of Death that is under revision by the Royal Colleges and Department of Health Working Party.
Brainstem death testing in children has been the subject of a report of a working party of the British Paediatric Association in 1991 (see ‘Further reading’). In children over the age of 2 months, the brainstem death criteria should be the same as those for adults. Between 37 weeks of gestation and 2 months of age, it is rarely possible confidently to diagnose brainstem death and below 37 weeks of gestation the criteria for brainstem death cannot be applied.
Action following brainstem death testing
The legal time of death is the time of completion of the first set of tests. Following conformation of brainstem death, mechanical ventilation and life support should be withdrawn. Before this it is essential to explain to relatives that brainstem death is an irretrievable state—when the brain is dead the person is dead, even though the heart may still be beating. Where appropriate, transplantation should be considered: the opportunity is offered for the relatives to discuss this with the transplant coordinator. Transplantation should be considered when there are no systemic contraindications, e.g. malignancy, and when the organs are still functioning despite the patient’s final illness.
It is important that after completion of the second set of tests either the patient is taken for organ transplantation as soon as is practically possible or the patient is disconnected from the ventilator to allow a dignified death. Expeditious retrieval of organs maintains their function, so it is important, when it is a recognized that a patient is a potential organ donor, that the transplant coordinator is contacted as soon as possible and the stage that proceedings have reached is made clear. Personal experience has shown that the transplant coordinator can provide strong and essential support to the relatives, irrespective of the decision of whether or not to donate.
The vegetative state and the minimally conscious state
The term ‘vegetative state’ was introduced in 1972 by Jennett and Plum to describe the clinical condition resulting from loss of function in the cerebral cortex with a functioning brainstem (patients who are awake but not aware). Vegetative patients breathe spontaneously and are not ventilator dependent; another difference from brain death is that they can survive for many years if adequately fed and nursed. The most common cause of vegetative survival after acute brain damage is severe head injury, the mechanism being severe diffuse axonal injury severing the subcortical connections over a wide area. Secondary hypoxic brain damage is a contributing factor in some traumatic cases. Most nontraumatic cases result from severe hypoxia–ischaemia of the brain after a cardiac arrest, near drowning, or strangulation, while a few result from severe hypoglycaemia in people with diabetes. Other causes are acute intracranial haemorrhage or infection. In adults the vegetative state can evolve gradually during the late stages of chronic dementing conditions, and in children can result from severe congenital malformations of the brain or from progressive metabolic or chromosomal diseases affecting the brain.
At postmortem examination after acute hypoxic insults, there is commonly a widespread loss of cortical neurons. After acute traumatic and nontraumatic damage leading to vegetative survival, there is almost always severe bilateral thalamic damage, although the cortex may be relatively spared. There is also progressive degeneration over many months of neurons, nerve fibres, and their myelin sheaths remote from the site of initial damage, which is reflected during life in progressive enlargement of the ventricles as visualized by CT or MRI. Findings on the EEG are variable, but there is often loss of evoked cortical responses to somatic stimuli. Positron emission tomography in hypoxic cases shows severe depression of glucose metabolism in cortical grey matter, to levels found only in experimental deep barbiturate narcosis.
In practice the diagnosis depends on characteristic clinical features recorded by skilled observers over a period of time. The patient has long periods of spontaneous eye opening (hence the inappropriateness of calling this condition irreversible or prolonged coma). The eyes or head does not track a moving object. There may be a startle reaction to a sudden noise. All four limbs are paralysed and usually spastic, with only reflex posturing and withdrawal from a painful stimulus, and often there is a grasp reflex. The face may grimace and groans may be heard but never words. There is no psychologically meaningful response to external stimuli or any learned behaviour—no evidence of a working mind. There may be emotional behaviours such as smiling, crying, or laughing but these are not related to appropriate external stimuli. It is concluded that, although awake, these patients are not aware and do not have any distress or pain. Misdiagnosis by non-experts is common, and care is needed to exclude the minimally conscious state in which there are very limited responses to indicate some return of cognitive activity. It must also be ascertained that the patient does not have the locked-in syndrome, caused by brainstem damage which results in full awareness but widespread paralysis, leaving the patient able to communicate only by a yes/no code using the sole remaining motor power—blinking the eyelids or moving the eyes. Prolonged observation in a specialized unit is required to make a secure diagnosis of the vegetative state. Recent functional brain imaging studies have revealed that a very few vegetative state patients can hear and understand before responses suggestive of minimally conscious state appear clinically.
Patients in a vegetative state for some time can still make some recovery. Of patients in the vegetative state 1 month after an acute insult, about half of head-injured individuals will regain some consciousness, but only a few of the nontraumatic cases do. Most who recover consciousness remain very severely disabled and dependent, particularly if they have been vegetative for several months. After head injury permanence cannot be declared until 12 months, but after nontraumatic insults it can after 6 months according to United Kingdom criteria and after 3 months in the United States of America. There is a high mortality in the first year after becoming vegetative but, once this period has been survived, patients can live for many years, if tube feeding and good nursing care are maintained and infective complications actively treated.
Action after permanence declared
There is now a consensus in many countries that survival for years in a permanent vegetative state is of no benefit to the patient, and that it is therefore appropriate to withdraw life-sustaining treatment once permanence is declared. Many courts in the United States of America and the United Kingdom have agreed that artificial nutrition and hydration is medical treatment that can be withdrawn if judged to be no longer of benefit to the patient. Once this is done a peaceful death occurs in 8 to 12 days, and the cause of death is regarded as the original brain damage. In the United Kingdom it is a legal requirement to seek court approval before withdrawing such treatment.
Academy of medical royal colleges. A code of practice for the diagnosis and confirmation of death. October 2008. [Most recent United Kingdom update.]Find this resource:
British Paediatric Association (1991). Diagnosis of brain stem death in infants and children. British Paediatric Association, London. [Paediatric perspective of brainstem death.]Find this resource:
Health Departments of Great Britain and Northern Ireland (1998). A code of practice for the diagnosis of brain stem death. Department of Health, London. Available at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4 009 696.
Medical Royal Colleges and their Faculties in the United Kingdom (1976). Diagnosis of brain death. Conference. BMJ, ii, 1187–8.Find this resource:
Medical Royal Colleges and their Faculties in the United Kingdom (1979). Diagnosis of death. Conference. BMJ, i, 322. [Original descriptions of United Kingdom criteria for brainstem death.]Find this resource:
NHS Direct Brain Death. Available at: http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=60. [Lay description.]
Quality Standards Sub-committee of the American Academy of Neurology (1995). Practice parameters for determining brain death in adults. Neurology 45, 1012–14. [Widely accepted United States criteria; available at: http://www.aan.com/professionals/practice/pdfs/pdf_1995_thru_1998/1995.45.1012.pdf.]
Youngner SJ, Arnold RM, Shapiro R (eds) (1999). The definition of death. Johns Hopkins University Press, Baltimore, MA. [Review of controversies, clinical, ethical, legal, and social—primarily from an American viewpoint.]Find this resource:
Adams JH, Graham DI, Jennett B (2000). The neuropathology of the vegetative state after an acute brain insult. Brain, 123, 1327–38. [Detailed pathology of 35 traumatic and 14 nontraumatic cases.]Find this resource:
Jennett B (2002). The vegetative state: medical facts, ethical and legal dilemmas. Cambridge University Press, Cambridge. [Review of medical facts, ethical issues and details of legal cases in several countries.]Find this resource:
Laureys S, Owen AM, Schiff ND (2004). Brain function in coma, vegetative state, and related disorders. Lancet Neurol, 3, 537–46. [Recent United Kingdom review.]Find this resource:
Monti MM, et al. (2010). Willful modulation of brain activity in disorders of unconsciousness, N Eng J Med. [E pub ahead of print ] [Original paper showing that 5154 patients in a vegetative or minimally conscious state have brain activation reflecting some brain activation reflecting some awareness and cognition.]Find this resource:
Multi-Society Task Force on PVS (1994). Medical aspects of the persistent vegetative state. N Engl J Med, 330, 1499–507, 1572–9. [Review of world literature and prognostic data from an American perspective.]Find this resource:
Quality Standard Sub-Committee of the American Academy of Neurology (1995). Practice parameters: assessment and management of patients in PVS. Neurology, 45, 1015–18. [Most recent American criteria.]Find this resource:
Wade DT, Johnston C (1999). The permanent vegetative state: practical guidance on diagnosis and management. BMJ, 319, 841–4 (see also Editorial by B Jennett on pp. 796–7). [Recent United Kingdom review.]Find this resource: