If a patient has:
> Catastrophic brain injury (confirmed with imaging)
> They are not sedated or paralysed
> They are haemodynamically stable
> There is no other reason why they would be unconscious
> They can be clinically assessed
> They are not spontaneously breathing
> They appear to have no cerebral function including no brainstem reflexes
– they may be brain dead.
Certain specific pre-conditions must be met before clinical Neurological Determination of Death (NDD) may occur.
If clinical NDD is not possible but brain death is clinically suspected, this may be confirmed with a DSA, Radionuclide imaging or a CTA.
Permanent loss of brain function should always be determined whenever it has occurred and determination regardless of whether donation is being considered.
The rigour of neurological determination of death provides certainty to the patient’s family that an individual who meets criteria is dead, irrespective of organ donation.
Neurological determination of death can be conducted without undue intrusion or distress for the family and the certainty may assist families in decision-making.
The criteria for neurological determination of death are not altered by the consideration of organ donation. REF
The Clinical Exam
Offer family members the opportunity of being present for the clinical exam
If they attend, explain what is happening
After 4 hours observation while:
> All preconditions are met
> GCS is 3
> Pupils non-reactive to light
> Absent cough/tracheal reflex
> Apparent apnoea on a ventilator
EXCEPT if:
> Acute hypoxic-ischaemic encephalopathy OR
> Hypothermia (<35°C) of duration greater than 6 hours
> Then you must wait for 24 hours or use imaging
> Imaging consistent with brain death
> Normothermia — temp ≥ 35 °C.
> Normotension — SBP ≥ 90 mmHg, MAP ≥ 60 mmHg in adults
> Exclusion of effects of sedative medications taking hepatic and renal function into account
> Absence of severe electrolyte, metabolic or endocrine disturbances:
Glucose 3 -25 mmol/L
Sodium 125 – 160 mmol/L
Phosphate > 0.5 mmol/L
Magnesium > 0.5 mmol/L
Urea <40 mmol/L
No severe endocrine dysfunction (untreated severe hypothyroidism or severe hypoadrenalism)
> Absence of acute liver failure or decompensated chronic liver disease.
> Absence of neuromuscular-blocking drugs
> Ability to adequately examine the brainstem reflexes — it must be possible to examine all brainstem reflexes, with at least one ear and one eye examination.
> In context of SCI it must be possible to assess the motor response in the facial nerve (VII) to painful stimulus in the upper limbs and to assess the motor response in the upper limbs to painful stimulus in the trigeminal (V) sensory region. This will depend on the level of SCI.
> Ability to perform apnoea testing — this may be precluded by severe hypoxic respiratory failure or a high cervical spinal cord injury.
In Australia & NZ:
> Two medical practitioners with specific experience and qualifications (definition varies between states)
> The two clinical examinations are performed separately, so that the doctors and the tests are truly independent (and seen to be so).
> One medical practitioner performs a complete set of tests, including an apnoea test and a blood gas, and reinstitutes mechanical ventilation.
> Then, the other medical practitioner performs a complete set of tests, including an apnoea test and a blood gas, and reinstitutes mechanical ventilation.
> No fixed interval between the two clinical examinations is required, except in neonates
> The examinations may be done consecutively but not simultaneously.
> It is acceptable, but not required, for one of the doctors to be present during the examination by the other doctor, but each doctor must be responsible for performing a complete clinical examination.
Equipment needed:
> Bright light
> Soft cotton wool for corneal reflex test
> Otoscope (to check ear canal patent)
> Tongue depressor (gag reflex)
> Cotton swab (gag reflex)
> 2 x 50 ml ice cold water in syringe
> Blood gas sampling equipment
> Self-inflating bag with a positive end-expiratory pressure (PEEP) valve to prevent atelectasis
Exam performed:
Spinal reflexes can be either spontaneous or elicited by stimulation outside the cranial nerve distribution
They occur in up to 50% of patients with permanent loss of brain function and are the result of a functioning spinal arc with loss of higher centre inhibitory control
Reflex movements generally occur within the first 24 hours of death being determined but can occur hours or days after a period of flaccid paralysis
Spinal reflexes can be quite complex in form and can be confronting when observed by family members and staff. It is essential that these movements are acknowledged and their origin explained
It is recommended that a cerebral blood flow study be performed if there is any doubt about whether movements are spinal in origin.
Examples of spinal reflexes include:
> Extension-pronation movements of the upper limbs or non-specific flexion of the lower limbs
> Undulating toe reflex (plantar flexion of great toe, followed by brief plantar flexion sequentially of second to fifth toes)
> Lazarus sign (bilateral arm flexion, shoulder adduction, hand raising to above the chest, and may include flexion of trunk, hips and knees)
> Deep tendon reflexes
> Plantar responses, either flexor or extensor
> Head turning
Other physiological signs that do not preclude permanent loss of brain function include:
> Sweating, blushing, tachycardia
> Normal blood pressure without the need for pharmacological support
> Absence of diabetes insipidus
> Having intracranial pressure less than mean arterial pressure
> Decerebrate or decorticate posturing
> True extensor or flexor motor responses to painful stimuli
> Seizures
> Limb movement elicited by stimulation of the cranial sensory nerves or facial movement elicited by stimulation of torso/limbs
Cerebral Blood Flow Investigations
If the clinical exam can’t be completely done or leaves doubt, cerebral blood flow investigations may be done.
Testing for responsiveness, examinable brainstem reflexes and breathing effort should be attempted and be consistent with brain death prior to resorting to these tests.
Before testing blood pressure must be adequate SBP > 90 mmHg, MAP > 60 mmHg.
Although the absence of brain perfusion is determined by a radiologist or nuclear physician, it is the responsibility of two medical practitioners who have clinically examined the patient to determine that the patient has died.
> Intra-arterial catheter angiography is regarded as the gold standard test for absence of perfusion
> Intra-arterial contrast must be absent above the level of the carotid siphon in the anterior circulation and above the foramen magnum in the posterior circulation REF
> Four-vessel angiography is direct injection of contrast medium into both carotid arteries and both vertebral arteries
> Three-vessel angiography refers to the injection of contrast medium into both carotid arteries and the basilar artery
> Tc-99m HMPAO (technetium 99m radiolabelled hexamethyl propylene amine oxime) is a radionuclide that demonstrates perfusion and crosses the blood–brain barrier to then be retained by brain parenchyma (by conversion from a lipophilic to a hydrophilic form).
> The absence of radionuclide intracranially is compared to the presence of radionuclide extra cranially.
> Blood pool or blood-flow agents, such as Tc-99m pertechnetate, Tc-99 DTPA (diethylene-triamine-penta-acetate) or Tc-99m glucoheptonate, are not acceptable radionuclides to demonstrate absence of perfusion, because they do not cross the blood–brain barrier and do not remain within the intracranial cavity long enough for static gamma camera imaging, leading to false positive and negative results.
> Although two-planar imaging is still used, single photon emission computerised tomography (SPECT) provides superior imaging
Computed tomography angiography (CTA) to demonstrate absent brain perfusion is acceptable only when DSA or radionuclide imaging is not available
> It is described as 100% specific but only 68-86% sensitive, so it will sometimes say there is perfusion when there isn’t and the patient is brain dead
> This is because more proximal intracranial arteries may show contrast enhancement when there is permanent loss of brain function. This enhancement is a reflection of the high sensitivity of CTA to small amounts of contrast that may admix within the Circle of Willis in the absence of brain perfusion.
> If CTA is performed, ANZICS recommends the use of the “four-point scale” technique which is validated for this context and standardises the test
Use the approved form for your hospital
This is the example documentation form provided by ANZICS:
Explain the results to the family
The test (either clinical exam or blood flow study) may be repeated as a patient may progress to brain death
If the family still want to proceed with organ donation, that can be via the Determination of Circulatory Death pathway
Care of the Brain Dead Patient
As patients progress to brain death the following is common:
> Crescendo sympathetic autonomic response (Autonomic storm):
Hypertension
Tachyarrhythmia
Tachypnoea
Diaphoresis
Seizures
Pupillary dilatation
> Followed by autonomic collapse and loss of all brainstem reflexes:
Hypotension
Loss of temperature regulation
Diabetes insipidus
> Not all these phenomena happen with all patients.
For more detailed explanation and management, see the ANZICS statement
The essentials of management are given below:
> Instrumentation: endotracheal tube, nasogastric tube, urinary catheter, multi-lumen central line, arterial line, large peripheral intravenous line
> Monitoring: ECG, pulse oximetry, intra-arterial pressure, core temperature, urine output (hourly)
> Routine investigations: CXR, ECG, blood group, coag
> Regular blood testing: FBC, ABG, U&Es, LFTs q6h and as necessary
> Review all medications; cease unnecessary orders
> Maintain core temperature 36–38°C
> Eye care, mouth care and all other nursing cares
> Aim for SpO₂ 92–97% by FiO₂ and PEEP adjustment (minimum PEEP 5 cm H₂O)
> Aim for PaCO₂ 35–45 mmHg by ventilator adjustment (TV 6–8 mL/kg ideal body weight, plateau pressure < 30 mmHg)
> Regular turns from side to side; elevate head of bed
> Regular tracheal suctioning, chest physio and
> Lung recruitment after suctioning
> Bronchoscopy as required
Ensure patient is neither hypovolemic nor fluid overloaded
Aim for MAP 70–100 mmHg, good peripheral perfusion
Aim for urine output ~1 mL/kg/hr (range 0.5–3 mL/kg/hr)
Commence noradrenaline or vasopressin infusion (2.4U/h) for hypotension
If inotropic support, such as dobutamine, adrenalin or milrinone, is contemplated, consider further cardiac assessment or output monitoring
If haemodynamically unstable, consider methylprednisolone (15 mg/kg) and T3 (tri-iodothyronine 4 cmg bolus, then 3 mcg/h) – discuss first with organ donation specialist
> Give maintenance fluid as free water e.g. glucose 5% at 1mL/kg/hr
> Continue NG feeding or TPN
> Insulin infusion to keep blood glucose <15 mmol/L
> Maintain urine output between 0.5 and 3 mL/kg/hr
> If polyuric > 300 mL/hr assume diabetes insipidus and immediately give desmopressin (0.5 mcg) and/or commence vasopressin infusion (2.4 U/h)
> If Na+ > 150 mmol/L give additional free water
> Transfuse for Hb > 70 g/L