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SOE 792: Brainstem Death
Introduction
A 20-year-old boy was admitted to ICU with a traumatic brain injury following a road traffic accident 48 hours ago. His initial GCS at the scene was 5/15. He was intubated and ventilated by a paramedic and transferred to Accident and Emergency. A CT scan shows extensive cerebral contusions, massive haematoma and significant cerebral oedema. He has now developed fixed pupils bilaterally and has stopped triggering the ventilator. Both the neurosurgeons and intensivists have decided to perform brainstem death testing…
Question No. 2
Q: How is brainstem death defined in the UK?
Answer No. 2
- No universally accepted definition of what constitutes death within either medicine or law
- A definition of brainstem death is taken from the unitary state of death as proposed by the Academy of Medical Royal College's (AoMRC) 2008 Report 'Code of Practice for Confirmation of Diagnosis of Death'
‘Irreversible loss of the capacity for consciousness, combined with irreversible loss of the capacity to breathe’
- On this basis, brainstem death is considered to equate with cardiac death of the individual
- Whilst not a legal definition, the courts in England and Wales have adopted the definition proposed by the Academy of Royal Colleges and forms part of case law
Question No. 3
Q: What are the common causes of brainstem death?
Answer No. 3
-
The most frequently seen pathologies associated with brainstem death are:
Direct Insult
- Shearing injury due to trauma or hanging
- Focal ischaemia of vertebral / basilar artery pathology:
- Traumatic vertebral dissection
- Subarachnoid haemorrhage
Indirect Insult
- Focal Pathology:
- Posterior fossa haematoma
- Any global increase in ICP with tonsillar herniation:
- Trauma
- Hypoxia
- Hydrocephalus
- Infection (meningitis)
- Ischaemic or haemorrhagic stroke
- Hepatic encephalopathy
Question No. 4
Q: Who should carry out brain stem death testing and how should this be performed?
Answer No. 4
- Carried out by two medical practitioners holding full GMC registration for more than five years:
- One of whom should be a consultant
- Experienced in interpreting the results
- Independent of the transplant team (represents a conflict of interest)
- The doctors may carry out the tests separately or together, but two sets of tests should always be performed to reduce the risk of observer error
Question No. 5
Q: When should brains stem death testing be performed?
Answer No. 5
- Testing should be performed a minimum of 6 hours after loss of last brain stem function
- Longer period should be given in atypical presentations:
- A minimum of 24 hours should be given if primary aetiology hypoxic brain injury
- Prolonged observation may be required in cases of unclear aetiology
- No statutory interval must elapse between the tests, but this should be sufficient to reassure all those involved
Question No. 6
Q: What is the legal time of death following brainstem death testing?
Answer No. 6
- Legal time of death is retrospectively noted as the time the first set of tests confirms brainstem death, though death is not declared until after the 2nd test
Question No. 7
Q: What are the essential components in assessing death by neurological criteria?
Answer No. 7
The Academy of the Medical Royal Colleges UK (AoMRC) code for the diagnosis of death by neurological criteria outlines three essential components:
1. Evidence of irreversible brain damage of known aetiology
2. Exclusion of reversible causes of coma and apnoea
3. Formal demonstration of coma, apnoea, and the absence of brainstem reflex activity
Question No. 8
Q: What are the essential preconditions for brainstem death testing?
Answer No. 8
- The patient is comatose and mechanically ventilated for apnoea
- There should be no doubt that the patient's condition is due to irreversible brain damage of known aetiology
Question No. 9
Q: Which situations should be ‘red flags’ to diagnosis of irreversible brain damage?
Answer No. 9
- Testing less than 6 hours of the loss of the last brainstem reflex
- Testing less than 24 hours of the loss of the last brainstem reflex, where aetiology primarily anoxic damage
- Patients with any neuromuscular disorders
- Prolonged fentanyl infusions
- Steroids given in space occupying lesions such as abscesses
- Aetiology primarily located to the brainstem or posterior fossa
- Hypothermia - a 24-hour observation period following rewarming to normothermia recommended
- Therapeutic decompressive craniectomy
Question No. 10
Q: What is done where a primary diagnosis for brain damage cannot be reached?
Answer No. 10
- Brainstem testing should not be performed when significant diagnostic uncertainty remains
- Rare occasions occur where the primary diagnosis causing loss of brainstem function cannot be reached despite extensive investigation: (e.g. presumed hypoxic brain injury, cerebral fat embolism or drug overdose):
- Testing should only be performed after an extended period of clinical observation and support
- Required to confirm that an irreversible and untreatable underlying cause is present
Question No. 11
Q: Which conditions may mimic brainstem death?
Answer No. 11
- A number of reversible lesions of the brainstem may closely mimic irreversible brain death:
- Severe Guillain–Barré and Miller–Fisher syndromes
- Bickerstaff's brain stem encephalitis progressive cranial nerve dysfunction associated with ataxia, coma and apnoea
- Ventral pontine infarction associated with the 'locked-in syndrome', involving both corticospinal and corticobulbar tracts leading to tetraplegia
- Brainstem death testing should not be performed if these conditions are suspected
Question No. 12
Q: What are the reversible causes of coma and apneoa that must be excluded in brain death?
Answer No. 12
Coma
Specific criteria are laid out in guidance from the AOMRC
- Metabolic or endocrine disturbance
- Circulatory disturbance
- Sedative/depressant drugs
- Hypothermia
Apnoea
Rare but should be actively sought if the history or clinical examination suggests their presence
- Severe neuromuscular weakness of any cause
- Spinal cord injury following trauma – should be excluded through x-ray, CT or MRI imaging
- Residual neuromuscular blockade - it is sensible to routinely use a nerve stimulator to confirm the absence of drug-related block
Question No. 13
Q: Which physiological criteria would exclude a patient from brainstem death testing?
Answer No. 13
Factor
Lower Limit
Upper Limits
Comments
Temperature Disturbance
34°c
-
Impaired consciousness can occur below 34°c
Biochemistry Disturbance
-
-
Derangements clearly the result of brainstem death (e.g. hyponatraemia of DI) may not require correction prior to testing
Sodium
115 mmol/l
160 mmol/l
-
Potassium
2 mmol/l
-
-
Magnesium
0.5 mmol/l
3.0 mmol/l
-
Phosphate
0.5 mmol/l
3.0 mmol/l
-
Glucose
3 mmol/l
20 mmol/l
-
Endocrine Disturbance
-
-
If there is any clinical reason to expect endocrine disturbances, hormonal assays should be undertaken.
Respiratory and Haemodynamic Disturbance
-
-
Requirement for cardiorespiratory stability is an important new prerequisite
pH
7.35
7.45
-
pCO2
-
6.0 kPa
-
pO2
10 kPa
-
-
MAP
60 mmHg
-
Question No. 14
Q: How can sedative or depressant drug intoxication be excluded as a cause of coma in brainstem death?
Answer No. 14
- May complicate assessment on occasions where:
- Patient has received infusions of sedative drugs as part of their critical care treatment
- Brain injury as a result of drug-induced self-harm - especially problematic when substance unknown
- Possible approaches include:
- A period of observation:
- Should approximate four times the elimination half-life of the agent involved to allow effective drug elimination
- Best suited to circumstances where short-acting agents such as propofol and alfentanil have been given to patients with normal hepatic and renal function
- Administration of specific antagonists:
- Flumazenil or naloxone may be used
- Plasma analysis:
- Can confirm that a suspected sedative is either not detected or at a subtherapeutic level
- Particularly suited for agents with long or unpredictable half-lives such as thiopental or phenobarbital.
- A confirmatory test to demonstrate the absence of cerebral blood flow/perfusion
- For example, cerebral angiography
- A period of observation:
Question No. 15
Q: How are tests for brainstem reflex activity performed and what does each test check ?
Answer No. 15
Test
Procedure
Confirmatory Response in Brainstem Death
Pupillary Reflex
A bright light is shone into each eye in turn. Direct and consensual reflexes should be sought
Pupils are fixed and do not respond or constrict to light
Corneal Reflex
Cornea is brushed lightly with a swab with care taken to avoid damage to the cornea.
No blinking elicited by stimulation
Caloric (Oculo-vestibular) Reflex
At least 50ml of ice cold water is instilled into the external auditory meatus over one minute. Head should be at 30 degrees to the horizontal plane. Clear access to the tympanic membrane must be confirmed by direct visualisation with and otoscope before testing
No eye movement during or following injection
Painful Stimulation
Painful stimulus is applied to the supra-orbital ridge (pons), and also to the limbs and trunk
No motor response in cranial nerve distribution elicited by stimulation
Gag Reflex
Posterior pharynx is stimulated with a spatula
No gag elicited by stimulation
Cough Reflex
Bronchial stimulation is performed by passing a suction catheter down the trachea to the carina
No cough elicited by stimulation
Question No. 16
Q: How is the apnoea test performed?
Answer No. 16
Preparation
- Only be performed once the absence of brainstem reflex activity has been confirmed
- Ensure cardiovascular stability maintained
- Ensure utilization of end tidal carbon dioxide (EtCO2) monitoring, pulse oximetry, blood pressure monitoring and blood gas analysis:
- Prevents the development of significant hypoxia
- Prevents the development of excessive hypercarbia
- Minimizes the development of hypotension which could risk further injury to potentially recoverable brain tissue
- Preoxygenate with an FiO2 1.0.
- Ensure mild hypercarbia (PaCO2 >6.0 kPa) and acidosis (pH <7.4) prior to testing:
- Reduce the minute ventilation to allow PaCO2 to rise
- A PaCO2 >6.5 kPa should be targeted in:
- Patients with chronic CO2 retention
- Patients receiving intravenous bicarbonate
Performance
- Remove patient from ventilator - cardiac pulsation may be sufficient to trigger supportive breaths
- Ensure oxygenation - options include:
- Connect the patient to CPAP circuit (e.g. Mapleson C)
- Administer oxygen via a catheter in the trachea at a rate of >6L/minute
- Perform a pre-test arterial blood gas to confirm PaCO2 is at least 6.0 kPa and pH <7.4
- Observe for respiratory activity for 5 min, confirming the start time
- Perform a confirmatory blood test to ensure an increase in PaCO2 of more than 0.5 kPa
- After completion of the apnoea, test reconnect the ventilator
Question No. 17
Q: Can a patient make movements and still meet criteria for brain death?
Answer No. 17
- Reflex movements of the limbs and torso may still occur in brainstem death:
- Spinally mediated reflexes and automatisms can be retained even after confirmation of death
- Often misinterpreted by laypersons as signs of purposeful brain function
- Careful neurologic examination can differentiate between reflexive movements and purposeful motor movements
Question No. 18
Q: What are the common spinally generated movements?
Answer No. 18
- Non-purposeful movements occur due to lack of descending inhibition of primitive spinal motor reflex pathways:
What are the common spinally generated movements?
Question No. 19
Q: Which situations may ancillary testing be required for diagnosis of brainstem death?
Answer No. 19
- Ancillary tests are not routinely required for diagnosis of brainstem death
- There are several circumstances where brain death cannot be confirmed according to clinical testing alone:
- Inability to exclude the influence of residual sedative drugs
- High cervical cord injury
- Severe maxillofacial injury limiting brainstem death testing
Question No. 20
Q: Which ancillary tests are available for diagnosis of brainstem death?
Answer No. 20
Measures of brain Electrical Activity
Measures of brain Electrical Activity
EEG
- Most popular and validated test worldwide, though there has been a recent move away
- Isoelectric EEG may be mimicked by conditions such as hypothermia, barbiturates, or other central nervous system (CNS) depressants - hence it is of little value when these are suspected
Somatosensory or Auditory Evoked Potential (SSEP)
- A peripheral stimulus given (i.e. median nerve} and a response is measured at the contralateral primary sensory cortex
- Absence of transmission measured 20 ms (N20 response) after stimulation suggests brainstem dysfunction
- May be useful where coma of toxic aetiology is suspected - short-latency responses that are absent in brain death but preserved in toxic and metabolic disorders
Measures of Blood Flow
Measures of Blood Flow
Cerebral Angiography
(4 vessel)
(4 vessel)
- Contrast medium is injected in the aortic arch under high pressure to reach both anterior and posterior circulations
- Confirmatory testing demonstrates absence of intracerebral filling beyond the carotid or vertebral arteries' entry to the skull
Transcranial Doppler
- Useful only if a reliable waveform is found
- Complete absence of flow may not be reliable if inadequate windows exist
- Confirmatory testing should demonstrate either reverberating flow or small systolic peaks in early systole
Cerebral Scintigraphy
- Non-invasive and safe measure of cerebral blood flow
- No patient transport required if a portable gamma camera is available
- Technetium 99 m is given by intravenous bolus with images obtained by a gamma camera every 3 seconds for a total of 60 seconds
- External carotid flow is either digitally subtracted or excluded by forehead tourniquet
- Confirmatory testing demonstrates no radionuclide localization in the middle cerebral artery, anterior cerebral artery, or basilar artery territories of the cerebral hemispheres
Spiral CT or MRI angiography
- Increasingly available and investigated as ancillary tests
- Confirmatory testing demonstrates absence of intracerebral filling beyond the carotid or vertebral arteries' entry to the skull
Question No. 21
Q: Can brainstem testing be performed in children?
Answer No. 21
- Theoretically, criteria should be the same, but significant concerns exist about the applicability, making this a very difficult area:
- The central nervous and respiratory systems are immature in neonates and young infants, leading to concerns about the applicability of brainstem reflex testing
- Anecdotal evidence exists of children who have recovered substantial neurological function despite severe insult and prolonged coma
- Guidance from the Royal Society of Paediatrics & Child Health suggests:
Children aged >2 months
Criteria used to establish death should be the same as those in adults
Children aged between 37 weeks of gestation and 2 months of age
Criteria used to establish death can be confidently used, but modifications must be applied
Children aged <37 weeks of gestation
Criteria used to establish death cannot be used, and testing should not be performed
Question No. 22
Q: Who should perform brainstem death testing in children?
Answer No. 22
- The same recommendations exist as for those performing testing in adults
- In addition:
- One doctor should be a paediatrician or should have experience with children
- One doctor should not be primarily involved in the child's care
Question No. 23
Q: What modifications should be made to brainstem death testing in children aged between 37 weeks of gestation and 2 months of age?
Answer No. 23
- The following precautionary measure should be considered regarding the apnoea test:
- A stronger hypercarbic stimulus is used to establish respiratory unresponsiveness
- There should be a clear rise in the arterial blood PaCO2 of >2.7 kPa above a baseline of at least 5.3 kPa (40 mm Hg) to >8.0 kPa with no respiratory response