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Brain death 

Brain death
Chapter:
Brain death
Author(s):

Jeanne Teitelbaum

and Sam Shemie

DOI:
10.1093/med/9780198739555.003.0029
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date: 12 November 2018

Death determined by neurological criteria, or brain death, is better considered as brain arrest, or the final clinical expression of complete and irreversible neurological failure. A review of the history of brain death has been published by Baron et al. (1). Despite widespread national, international, and legal acceptance of the concept of brain death, substantial variation exists in the definition of terms, as well as in the standards for diagnosis and their application (2,3,4,5,6).

In 2002, a survey conducted by Wijdicks (2) explored the international practices for diagnosing brain death and found stunning, often troubling differences. Whilst there is relative consistency in the requirement for examination of brainstem reflexes, there is surprising variation in the performance, methods, and targets of the apnoea test, in the number of physicians required to complete the tests, and in the type and requirement for confirmatory tests. In leading US hospitals, variations have also been found in the prerequisites for the diagnosis of brain death, including acceptable core temperature and the number of required examinations, amongst others (7). Chart audits have also revealed incomplete documentation of the findings during the confirmation of brain death (8). In an attempt to address this considerable practice variation, the United Kingdom, Canada, Australia, and the United States have issued national guidelines and checklists in order to standardize practice (9,10,11,12,13). Yet, despite this, considerable practice variation remains. The current evidence base for the existing guidelines on the determination of death by neurological criteria is inadequate, but clear medical standards, in association with clarification of the required qualifications of physicians making the diagnosis, will improve the quality and rigor of its determination.

In this chapter, we will review the history of death determined by neurological criteria, and the specific criteria and requirements for the diagnosis of brain death, paying special attention to areas of controversy and practice inconsistency.

Terminology

There remains a need to clarify and standardize terminology. Even widely applied terms, such as brain death or the neurological determination of death (NDD), are often used loosely and mean different things to different people.

Brain death

Brain death is ubiquitous in the medical, nursing, and lay literature, and is based on the concept of the complete and irreversible loss of brain function. Brain death is equivalent to the death of the individual, even though the heart may continue to beat and spinal cord function may persist. The Canadian Neurocritical Care guidelines define brain death as ‘the irreversible loss of the capacity for consciousness combined with the irreversible loss of all brainstem functions, including the capacity to breathe’ (10). Whether whole-brain or only brainstem destruction is required is not addressed in this guidance, and both are accepted if they fulfil the clinical criteria of brain death. In the United States, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research defines brain death as ‘irreversible cessation of all functions of the entire brain, including the brainstem’ (14).

Neurological death

Neurological death is a term that is similar to brain death, but is not now commonly used.

Brainstem death

Brainstem death is the irreversible loss of brainstem function through the irremediable damage of all brainstem structures. It is used as the standard for the determination of brain death in some countries, including the United Kingdom.

Neurological determination of death

The NDD is the process and procedure for determining the death of an individual using neurological criteria. NDD is not a new definition of death, but represents a clarification and standardization of the processes for the determination of death based on neurological, or brain-based, criteria.

History of brain death

With the advent of mechanical ventilation and the evolution of resuscitative measures came the ability to artificially maintain patients with severe brain injury long after brain function had ceased. In 1959, Mollaret and Goulon coined the term ‘coma dépassé’, meaning ‘a state beyond coma’, to describe this condition which is characterized by loss of consciousness, brainstem areflexia and the absence of spontaneous respiration, in association with absent encephalographic activity (15). The original intent of this work was to describe the futility of care in such cases. However, the introduction of organ transplantation later led to an inexorable linking of the issues of brain death, organ procurement, and transplantation which has continued to this day.

In 1968, the ad hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death undertook to define irreversible coma and brain death (16). The committee deliberations focused on a whole-brain formulation of brain death which, to this day, serves as the foundation of the concept of brain death in the United States. In 1971, Mohandas and Chou emphasized the importance of the irreversible loss of brainstem function in brain death (17), and this primordial importance of the brainstem subsequently became the focus of a published statement in 1976 by the Conference of Medical Royal Colleges and their Faculties in the United Kingdom (18). Championed by Pallis and Harley, the brainstem formulation of brain death was formally adopted by the United Kingdom (19).

In 1981, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research reaffirmed the application of a whole-brain definition of brain death in the United States, and addressed the use of ancillary diagnostic testing in the NDD (14). The Commission also made recommendations regarding the length of the observation period required before brain death assessment could be undertaken. Amongst their decisions was the recommendation that patients suffering from hypoxic brain injury should be observed for no less than 24 hours prior to the determination of brain death.

Since the 1980s, multiple guidelines (and revisions) on the diagnosis of brain death have been published in many jurisdictions. A 2002 survey by Wijdicks explored the international practices for diagnosing brain death and found important variations in the performance, methods and targets of apnoea testing, the number of physicians required to make the diagnosis, and the type and requirement for ancillary or confirmatory tests (2).

Concept of the neurological determination of death

Of interest in the international context are the differences between ‘whole brain’- and ‘brainstem’-based definitions of brain death. In most jurisdictions, brain death remains principally a clinical, bedside determination based on the confirmation of the absence of brainstem function. In Canada, neurologically determined death is defined as the irreversible loss of the capacity for consciousness combined with the irreversible loss of all brainstem functions, including the capacity to breathe (11). There is no insistence on whole-brain death and no explicit brainstem death because of the view that brain death is the permanent cessation of brain function as a whole, rather than a destruction of the whole brain. In the United States, the Uniform Determination of Death Act (UDDA) defines brain death as the irreversible cessation of all functions of the entire brain, including the brainstem (13). The important difference between the United States and Canada is that the US definition of brain death requires the death of all areas of the brain, whereas the Canadian definition is a clinical one that can be met either by whole-brain or brainstem death, and which may therefore result as a consequence of intracranial hypertension, primary direct brainstem injury, or both. Unlike in Pallis’s original description, the hypothalamus is not specifically identified as being an integral part of the brainstem in any Canadian guidance. There are currently no satisfactory ancillary tests for the confirmation of death in instances of isolated primary brainstem injury, hence the reliance on a clinical diagnosis.

In the United Kingdom, a brainstem-based definition of brain death is applied, and this approach is supported by the 1976 statement from the Conference of Medical Royal Colleges and their Faculties that permanent functional death in the brainstem constitutes brain death (18). Although irreversible loss of brainstem function is defined as the irremediable damage of all brainstem structures, it is determined in clinical terms with the caveat that reversible causes of brainstem dysfunction have been excluded. The argument is that loss of ascending reticular activating system function will lead to loss of consciousness, and that supplemental testing is therefore not required. As noted earlier, although Pallis included the hypothalamus and interruption of the corticothalamic tract as an extended brainstem in his original diagrams, these areas cannot be tested using the clinical criteria for the determination of brainstem death, and the UK Code of Practice also does not require evidence that the brainstem (medullary) centres controlling heart rate and blood pressure have ceased to function (13). Proponents of the brainstem formulation of brain death have no difficulty with the whole-brain criteria because the clinical determinants are fundamentally similar.

In most countries, the concept of brain death is legally accepted as death, when its determination is made according to accepted medical standards.

Determination of death by neurological criteria

The determination of death by neurological criteria is summarized in Box 29.1, and there are several components that are worthy of specific consideration.

Timing of the initial assessment

There are two key timing issues in the declaration of brain death. One relates to the timing of the first examination relative to the primary injury, and the other to the time interval between examinations if more than one is required.

Pallis and Harley in the United Kingdom defined the time of the first assessment for brain death as the first point at which the pre-conditions for the determination of brain death had been met. These are the presence of unresponsive apnoeic coma, a cause of coma capable of producing brain death, a determination that the neurological damage is irremediable, and the absence of confounding factors (19). Most countries support this approach. The most difficult aspect to determine is the irremediable nature of the event, especially when the damage is hypoxic/ischaemic in nature or due to a severe metabolic condition, such as insulin overdose with extreme and prolonged hypoglycaemia, or severe electrolyte abnormalities. For this reason, many countries’ guidelines recommend a minimum observation period, although with a time frame that varies widely, in addition to the presence of the aforementioned pre-conditions.

In the United Kingdom, the Academy of Medical Royal Colleges recommends that ‘brain-stem testing should be undertaken only if, after continuing clinical observation and investigation, there is no possibility of a reversible or treatable underlying cause being present’ (13). The 1998 guidelines from the Australian and New Zealand Intensive Care Society (ANZICS) are more specific and recommend that no fewer than 4 hours of documented coma should precede the first examination for brain death; edition 3.2 of the guidance, published in 2013, clarifies that, in cases of acute hypoxic/ischaemic brain injury including cardiac arrest, the clinical testing for brain death should be delayed for 24 hours following the injury or arrest (12). In the United States, the 1995 American Academy of Neurology (AAN) guidelines, and its 2010 update, concludes that there is insufficient evidence to determine a minimally acceptable period of observation to ensure that neurological functions have ceased irreversibly (9). Their recommendation is therefore vague, stating that ‘a certain period of time must have passed’ (usually several hours) between the initial insult and the clinical examination for brain death.

The Canadian forum addresses this issue at length and offers the most clarity. For the timing of the first examination, even though there was no compelling evidence, several practical factors were taken into consideration in developing the recommendations. First, neurological assessment may be unreliable in the acute (up to 24 hours) post-resuscitation phase after cardiorespiratory arrest (20). Indeed, restoration of initially absent pupillary and motor responses has been reported in the first 24 hours after cardiac arrest (21). In addition, there are case reports in which brain death was confirmed 6 hours after a cardiac arrest but with return of some brainstem function by 24 hours; there were however several confounders in these reports (22). Second, after severe metabolic or pure hypoxic injury (e.g. hypoglycaemia, asphyxia, or hypernatraemia), it may be very difficult to determine at what time the neurological status can be deemed irreversible. With these factors in mind, the Canadian recommendations are as follows:

  • In cases of acute hypoxic-ischaemic brain injury, clinical evaluation for the NDD should be delayed for 24 hours after the cardiorespiratory arrest, or an ancillary test performed.

  • In the situation of hypothermia post cardiac arrest there are insufficient data to make a firm recommendation. Twenty-four hours after re-warming to 36°C is insufficient (20), and 72 hours after restoration of normothermia and discontinuation of sedation may be reasonable (21,22,23).

  • In cases of extreme metabolic insult, sufficient time should have passed for the clinician to believe that the insult is permanent, and, in addition, there should be evidence of diffuse cerebral insult on imaging (e.g. magnetic resonance imaging (MRI)). If irreversibility remains an issue, an ancillary test should be performed in addition to the clinical examination.

Number of examinations

Although there is no scientific evidence that a second examination enhances the diagnostic accuracy of brain death, most jurisdictions require a second assessment for the purposes of organ donation. In the United Kingdom, two assessments are always required and two physicians must be present at each assessment (13). If two assessments are required, the recommended time interval between them varies widely. In Canada, the assessments can be performed concurrently except in children under 1 year of age. In the United Kingdom and Australia, they must be performed separately, with a full clinical examination, including the apnoea test, being performed on each occasion, but with no fixed examination interval regardless of the primary cause. In the United Kingdom, the 2008 guidance from the Academy of Medical Royal Colleges states that the interval can be quite short, although always long enough to allow recovery of stable arterial blood gases after the first apnoea test (13). The initial ANZICS guidelines (1998) recommended that the interval between the two assessments should be no less than 2 hours, although the 2010 update requires no fixed interval between assessments except where age-related criteria apply (12). The two independent and complete assessments can be performed consecutively, but not simultaneously, and each by separate physicians.

The legal time of death is marked by the first determination of death in Canada and the United Kingdom, and after the second assessment in the United States and Australia. The timings and findings of the examinations to determine brain death must be clearly documented (Figure 29.1).

Fig. 29.1 Documentation form for adults and children aged 1 year and older (example from the United Kingdom).

Fig. 29.1 Documentation form for adults and children aged 1 year and older (example from the United Kingdom).

Qualifications of the physicians performing the assessment

The required qualifications of the physicians performing the clinical assessment of brain death are extremely variable. Canadian practitioners need full and current licensure for independent medical practice in the relevant Canadian jurisdiction, skill and knowledge in the management of patients with severe brain injury and in the NDD, and no association with a proposed transplant recipient that might influence their judgement in the case of potential organ donors (11). In the United States, the required expertise varies by state and sometimes by individual institution. The United Kingdom requires two medical practitioners who have been registered for more than 5 years with a licence to practice, and who are competent in the conduct and interpretation of brainstem testing; at least one of the doctors must be a consultant (13). Those carrying out the tests must have no clinical conflict of interest, and neither doctor should be a member of a transplant team. The ANZICS guidance states that the ‘NDD should be performed by two medical practitioners whose expertise is defined by local legislation’ (12). However, it goes on to say that ‘care of the donor and family must be provided by an intensivist with specific expertise that may be acquired through specialized education, reference documents and ongoing clinical experience’.

Despite some international differences, all would agree that the physician diagnosing brain death should be a licensed experienced practitioner with skill and knowledge in the management of patients with severe brain injury as well as specific expertise in the neurological determination of death.

Clinical evaluation

The requirements for the confirmation of brain death are quite uniform across guidelines and are cautious to exclude any potential diagnostic error or reversible conditions. The prerequisites for the clinical assessment for the NDD usually include normal blood pressure and temperature although exact values are not always stipulated and vary between guidelines (see below).

The minimum clinical criteria for the NDD in adults (Box 29.1) include:

  • An established cause capable of causing neurological death, with definite clinical or neuroimaging evidence of an acute central nervous system (CNS) event that is consistent with the irreversible loss of neurological function, and the absence of reversible conditions capable of mimicking neurological death. Neurological death may occur as a consequence of intracranial hypertension, primary direct brainstem injury (United Kingdom, Canada), or both.

  • The presence of deep unresponsive coma with bilateral absence of motor responses (excluding spinal reflexes), which implies a lack of spontaneous movements, and an absence of movement originating in the CNS, including cranial nerve function, CNS-mediated motor response to pain in any distribution, seizures, and decorticate and decerebrate responses. Spinal reflexes confined to spinal distribution may persist, and have been reported in up to 75% of patients progressing to brain death (22). Several spinal-originating movements have been documented and described in brain-dead patients, and should not confuse the determination of brain death (24).

  • Absence of confounding factor (see below).

  • Brainstem areflexia defined by the absence of:

    • bilateral corneal responses

    • bilateral pupillary responses to light, with pupils at midsize or greater

    • gag reflex

    • cough reflex

    • bilateral vestibulo-ocular responses (Box 29.2).

  • Absent respiratory effort confirmed by the apnoea test (see below).

There are different requirements in neonates and infants as follows:

  • For infants aged 30 days to 1 year (corrected for gestational age) the criteria include the oculocephalic reflex instead of the vestibulo-ocular reflex because of the unique anatomy of the external auditory canal.

  • For neonates from term (36 weeks of gestation) to 30 days, clinical criteria have primacy, as they do in the child and adult. Minimum clinical criteria include the absence of oculocephalic reflex and suck reflex.

Confounding factors

All guidelines place the achievement of normal blood pressure and temperature in the prerequisites for clinical evaluation but the acceptable threshold values differ. The list of possible confounding factors is otherwise identical and shown in Box 29.3.

When assessing for neurological death, examiners are cautioned to review these confounding factors in the context of the cause of the neurological injury and their clinical assessment. If physicians are confounded by any finding or investigation, either absolutely or from their own perspective, they should not proceed with the NDD. Clinical judgement is always the deciding factor.

There are key considerations that must be specifically addressed in the neurological determination of death.

Unresuscitated shock

The AAN guidelines in the United States require a systolic blood pressure above 100 mmHg before brain death assessment, whereas Canadian, UK, and Australian guidelines require systolic pressures greater than 90 mmHg.

Hypothermia

Canadian guidelines require that core temperature is measured through central blood, rectal, or oesophageal-gastric routes, whereas methods of temperature measurement are not specified by the AAN. The accepted temperature for performing the clinical examination of brain death varies in different guidelines between 34°C and 36°C. There is no evidence to favour a particular temperature within this range, but 34°C is the minimum at which the tests are accepted as valid; there are no reports of hypothermia-related loss of brainstem reflexes above 34°C. Further, increasing hypothermic patients’ temperature to 34°C does not pose significant risk to the patient or difficulty for the treating physician. Canadian and UK guidelines require the core temperature to be 34°C or higher, the ANZICS guidance states 35°C or higher, and the AAN guidelines stipulate a minimum temperature of 36°C. Ideally temperature should be as close to normal as possible prior to performing the assessment for brain death, although this is not always achievable.

Drug intoxication

Although clinically significant drug intoxications (e.g. alcohol, barbiturates, sedatives, or hypnotics) are confounders that must be addressed before clinical assessment for brain death, therapeutic levels, or therapeutic dosing of anticonvulsants, sedatives, and analgesics do not preclude the diagnosis of brain death. The administration of paralytic or anaesthetic medication is a major confounder and these agents must be discontinued and eliminated from the system prior to any clinical assessment of brain death.

The approach to the presence of medications (e.g. sedation, analgesia, or barbiturates) that may depress CNS function varies throughout the world. Issues to consider when assessing the potential to confound the clinical evaluation of brain death include drug type, dose, duration of administration, and hepatorenal function. If uncertainty exists, drugs should be discontinued and adequate time allowed for elimination, drug levels should be monitored, specific antagonists administered, the absence of neuromuscular blockade be confirmed, or an ancillary test performed.

Severe metabolic disturbance

Severe metabolic disorders capable of causing a potentially reversible coma should be excluded. If the primary cause does not fully explain the clinical picture, and/or if the treating physician’s judgement is that a metabolic abnormality may play a role in the coma, it should be corrected or an ancillary test performed.

Apnoea testing

Demonstration of the failure to breathe must be assessed in a reliable and consistent manner, and is an integral part of the assessment for brain death. This is achieved by confirming the absence of a breathing drive in response to an increase in PaCO2 to higher than normal levels, with clear documentation of the test. Apnoea testing requires the presence of normotension, normothermia, euvolaemia, adequate oxygenation, and eucapnia (PaCO2 4.67–6 kPa (35–45 mmHg)) at the start of the test, and the absence of prior CO2 retention (i.e. chronic obstructive pulmonary disease or severe obesity). Canadian guidelines recommend that the thresholds at the completion of the apnoea test be a PaCO2 of 8 kPa (60 mmHg) or higher, and 2.67 kPa (20 mmHg) higher than the pre-apnoea test level, with a pH of 7.28 or lower (11). The United States also requires a CO2 rise of at least 2.67 kPa (20 mmHg) but has no threshold for the pH (9), whereas ANZICS requires a pH threshold of 7.3 (12). The UK code requires that the PaCO2 should be 6.0 kPa (45 mmHg) or higher at the start of the apnoea test and that it should rise by at least 0.5 kPa (3.75 mmHg) to above 6.5 kPa (48.8 mmHg) at the conclusion of the test (13). In cases of chronic carbon dioxide retention, the PaCO2 should be adjusted to ensure that the pH is lower than 7.4 at the completion of the test. All guidelines agree that these thresholds must be documented by arterial blood gas measurement at the start and end of the apnoea test.

To interpret an apnoea test correctly, the certifying physician must continuously observe the patient for respiratory effort, and ensure that adequate oxygenation and blood pressure is maintained, throughout the test. For patients with severe lung disease, caution must be exercised in considering the validity of the apnoea test. If there is a history of chronic respiratory insufficiency and responsiveness to only supranormal levels of carbon dioxide, or if the patient depends on a hypoxic drive, the validity of the apnoea test might be in doubt. In such circumstances an ancillary test should be administered. The conduct of the apnoea test is described in detail in Box 29.4.

In potential organ donors, the application of continuous airway pressure between 8 and 10 cmH2O during the apnoea test is associated with an increase in the number of eligible and retrieved lungs suitable for transplantation (25).

Ancillary tests

Sometimes clinical criteria for the determination of brain death cannot be applied reliably. This includes situations where the cranial nerves cannot be adequately examined, when neuromuscular paralysis or drug intoxication is present, in patients in whom the apnoea test is precluded (e.g. respiratory instability or high cervical spine injury) or invalid (high CO2 retainers), and when confounding factors remain unresolved. In these situations, ancillary tests, sometimes called supplementary or confirmatory tests, may be helpful.

Different guidelines specify when ancillary testing should be performed, and the requirements that must still be met prior to testing. Unresuscitated shock and hypothermia must be corrected as a minimum before ancillary tests are performed, and, as with the clinical determination of brain death, specific clinical criteria must be met. An established cause of neurological injury capable of causing neurological death must be present, the patient must be in a deep unresponsive coma, and reversible conditions capable of mimicking neurological death must be excluded.

In 2006, Young and colleagues published a critical review of the various ancillary tests that are used to support the NDD (26). Tests of brain perfusion are the only tests to satisfy standard criteria for suitability, with electrophysiological and other tests considered inadequate. The demonstration of the global absence of intracranial blood flow using established imaging modalities is presently considered the standard for the NDD by ancillary testing. Although many guidelines still require an electroencephalogram (EEG) as part of the NDD (2,3), it is no longer recommended by others because of its substantial limitations. The AAN guideline update lists four acceptable tests, including EEG, but requires only one for validation (9). The UK guidance highlights the pros and cons of various ancillary tests, but does not stipulate the use of any (13).

Recommended ancillary tests

Four-vessel cerebral angiography (12) and radionuclide tests of brain blood flow/perfusion (20) are accepted as valid confirmatory tests of brain death.

Cerebral angiography

A selective radiocontrast four-vessel angiogram visualizing both the anterior and posterior cerebral circulation should be obtained. Cerebral-circulatory arrest is confirmed when intracerebral pressure exceeds arterial inflow pressure. Provided the patient has an adequate blood pressure, absence of blood flow above the level of the carotid siphon in the anterior circulation and above the foramen magnum in the posterior circulation is considered diagnostic of brain death (27). External carotid circulation should be evident and filling of the superior sinus may be present. Angiography requires technical expertise and is performed in the radiology department, necessitating transport of potentially unstable patients. Arterial puncture and catheter-related complications are described and radiocontrast can produce idiosyncratic reactions and end-organ damage, such as renal dysfunction, which can be an issue in potential organ donors.

Radionuclide imaging techniques

Radionuclide angiography (perfusion scintigraphy) has been widely accepted for the confirmation of brain death for several years. In the last decade, radiopharmaceuticals, especially Tc99m hexamethylpropylene-amine oxime (Tc99m HMPAO), have been studied extensively and provide enhanced detection of intracerebral, posterior fossa, and brainstem blood flow (21,23). Tc99m HMPAO is lipid soluble, crossing the blood–brain barrier, and provides information on cerebral blood flow and uptake of tracer within perfused brain tissue. The traditional gamma cameras used in this technique are immobile, necessitating patient transfer for the study, but newer technologies are portable allowing studies to be performed at the bedside.

Newer imaging modalities

Computed tomography (CT) angiography holds future promise because it is a non-invasive, easily accessible, operator-independent, and inexpensive way to measure cerebral perfusion (28). However, it remains insufficiently validated for the confirmation of brain death at this time. MRI-based angiography and imaging also hold future promise but are not easily available and have likewise been insufficiently validated at this time.

Transcranial Doppler ultrasonography

Using a pulse Doppler instrument, the intracerebral arteries, including the vertebral or basilar arteries, are insonated bilaterally. Brain-dead patients display either absent or reversed diastolic flow or small systolic spikes. The non-invasiveness and portability of this technique are advantageous but it requires substantial clinical expertise for proper application and interpretation, and is not widely available. The absence of acoustic windows makes it inapplicable in certain patients, and its interpretation is operator dependent (29). TCD has not been sufficiently validated for the confirmation of brain death at this time and should only be used as a bedside screening tool prior to a definitive investigation of CBF (12).

Electroencephalography

EEG is readily available in most tertiary medical centres worldwide. It has long been used as a supplementary test for brain death, and can be performed at the bedside. However, it has significant limitations (3,26). The EEG detects only cortical electrical activity and is unable to detect deep cerebral or brainstem function. The high sensitivity requirement for EEG recording may result in the detection of electric interference from many of the devices that are commonplace in the intensive care unit. EEG is also significantly affected by hypothermia, drug administration, and metabolic disturbances, diminishing its clinical utility in the circumstances when ancillary tests are most often required. It is therefore no longer recommended as an ancillary test to confirm brain death.

Children

Regardless of age, clinical examination remains paramount in the determination of neurological death. However, the clinical determination of brain death in children, specifically in the young infant, is more problematic than in adults because of the difficulties in performing the examination, the presence of open cranial sutures and fontanelles, and the relative immaturity of some brainstem reflexes. In most guidelines, the recommendations established for adults are applicable to children older than 1 year, although in the United Kingdom adult guidelines apply to children older than 2 months. The uncertainty surrounding the determination of brain death in those under 36 weeks of gestation is such that no international guidelines currently address this problem.

Canadian forum recommendations

In infants aged less than 1 year, and term newborns (36 weeks of gestation), a full clinical examination, including apnoea test, must be performed by two physicians at two different times; the absence of the suck reflex is added to the brainstem examination in this age group (11). For infants there is no fixed interval between examinations, whereas in newborns the first examination should be delayed until 48 hours after birth, and the interval between examinations should be a minimum of 24 hours.

The ANZICS guidelines for diagnosis of brain death in children have been modelled on the recommendations of the Canadian Forum, and are therefore very similar.

UK guidelines

A 1991 working party of the British Paediatric Association (BPA) produced guidelines for the diagnosis of brain death in infants and children and this is used as the basis for the paediatric section of the Academy of Medical Royal Colleges 2008 guidance on the diagnosis of death (13). This notes that it is rarely possible to diagnose brainstem death confidently in term newborns (from 37 weeks of gestation) to 2 months of age, and that the concept of brainstem death is inappropriate for infants below 37 weeks of gestation. In this age group, decisions on whether or not to continue intensive care should be based on an assessment of the likely outcome of the underlying condition, after close discussion with the family.

US guidelines

The American Academy of Pediatrics has published guidance on the determination of brain death in children (30). In term newborns (37 weeks of gestation) to 30 days of age, two examinations including an apnoea test with each examination, separated by an observation period of 24 hours, are required. In children aged from 30 days to 18 years, two examinations, also including an apnoea test with each examination, separated by an observation period of 12 hours are required. Assessment of neurological function following cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for 24 hours or longer if there are concerns or inconsistencies in the examination.

Conclusion

The accurate and reliable determination of brain death currently has variability in many of its elements, with significant international variation (1,2,3,5). The one constant is the absolute certainty that must attend the diagnosis of brain death. Meticulous attention to detail and strict adherence to local protocols are the essential elements of every diagnosis of brain death. In this way the infallible nature of the confirmation of death by neurological criteria can be assured.

References

1. Baron L, Shemie SD, Teitelbaum J, Doig CJ. Brief review: history, concepts and controversies in the neurological determination of death. Can J Anesth. 2006;53:602–8.Find this resource:

2. Wijdicks EF. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology. 2002;58:20–5.Find this resource:

3. Shemie SD. Variability of brain death practices. Crit Care Med. 2004;32:2564–5.Find this resource:

4. Powner DJ, Hernandez M, Rives TE. Variability among hospital policies for determining brain death in adults. Crit Care Med. 2004;32:1284–8.Find this resource:

5. Mejia RE, Pollack MM. Variability in brain death determination practices in children. JAMA. 1995;274:550–3.Find this resource:

6. Hornby K, Shemie SD, Teitelbaum J, Doig C. Variability in hospital-based brain death guidelines in Canada. Can J Anaesth. 2006;53:613–19.Find this resource:

7. Greer DM, Varelas PN, Haque S, Wijdicks EF. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008;70:284–9.Find this resource:

8. Wang M, Wallace P, Gruen JP. Brain death documentation: analysis and issues. Neurosurgery. 2002;51:731–6.Find this resource:

9. Wijdicks EF, Varelas PN, Gronseth GS, Greer DM, American Academy of Neurology. American Academy of Neurology evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–18.Find this resource:

10. Canadian Neurocritical Care Group. Guidelines for the diagnosis of brain death. Can J Neurol Sci. 1999;26:64–6.Find this resource:

11. Shemie SD, Doig C, Dickens B,Byrne P, Wheelock B, Rocker G, et al. Severe brain injury to neurologic determination of death: Canadian forum recommendations. CMAJ. 2006;174:S1–13.Find this resource:

12. Australian and New Zealand intensive Care Society (ANZICS). The ANZICS Statement on Death and Organ Donation (Edition 3.2). Melbourne: ANZICS, 2013.Find this resource:

13. Academy of the Medical Royal Colleges. A Code of Practice for the Diagnosis and Confirmation of Death. London: Academy of the Medical Royal Colleges; 2008. http://www.aomrc.org.uk/reports-guidance.htmlFind this resource:

14. Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. JAMA. 1981;246:2184–6.Find this resource:

15. Mollaret P, Goulon M. The depassed coma (preliminary memoir). Rev Neurol (Paris). 1959;101:3–15Find this resource:

16. A definition of irreversible coma. Report of the Ad Hoc committee of the Harvard medical school to examine the definition of brain death. JAMA. 1968;205:337–40.Find this resource:

17. Mohandas A, Chou SN. Brain death. A clinical and pathological study. J Neurosurg. 1971;35:211–18.Find this resource:

18. Diagnosis of brain death. Statement issued by the honorary secretary of the conference of Medical Royal Colleges and their Faculties in the United Kingdom on 11 October 1976. Br Med J. 1976;2:1187–8.Find this resource:

19. Pallis C, Harley DH. ABC of Brainstem Death (2nd edn). London: BMJ Publishing Group; 1996.Find this resource:

20. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870–9.Find this resource:

21. Zanbergen EG, DeHaan RI, Stoutenbeck CP, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischemic coma. Lancet. 1998:352:1808–12.Find this resource:

22. Shemie SD, Langevin S, Farrell C. Therapeutic hypothermia after cardiac arrest, another confounding factor in brain-death testing. Pediatr Neurol. 2010;42:304.Find this resource:

23. Webb AC, Samuels OB. Reversible brain death after cardiopulmonary arrest and induced hypothermia. Crit Care Med. 2011;39:1538–42.Find this resource:

24. Saposnick G, Basile VS, Young GB. Movements in brain death: a systematic review. Can J Neurol Sci. 2009;26:154–60.Find this resource:

25. Mascia L, Pasero D, Slutsky A, Arguis MJ, Berardino M, Grasso S, et al. Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial. JAMA. 2010;304:2620–7.Find this resource:

26. Young GB, Shemie SD, Doig CG, Teitelbaum J. Brief review: the role of ancillary tests in the neurological determination of death. Can J Anaesth. 2006;53:620–7.Find this resource:

27. Rosenklint A, Jorgensen PB. Evaluation of angiographic methods in the diagnosis of brain death. Correlation with local and systemic arterial pressure and intracranial pressure. Neuroradiology. 1974;7:215–19.Find this resource:

28. Quesnel C, Fulgencio J-P, Adrie C, Marro B, Payen L, Lembert N, et al. Limitations of computed tomographic angiography in the diagnosis of brain death. Intensive Care Med. 2007;33:2129–35.Find this resource:

29. Kalanuria A, Nyquist PA, Armonda RA, Razumovsky A. Use of transcranial Doppler (TCD) ultrasound in the neurocritical care unit. Neurosurg Clin N Am. 2013;24:441–56.Find this resource:

30. Nakagawa TA, Ashwal S, Mathur M, Mysore M, Society of Critical Care Medicine, Section on Critical Care and Section on Neurology of American Academy of Pediatrics, et al. Clinical report—Guidelines for the determination of brain death in infants and children: an update of the 1987 task force recommendations. Pediatrics. 2011;128:e720–40.Find this resource: