Brain Death

Brain death and circulatory death are both death, and do not differ in type or degree, but in the way they are determined.

Brain Death is the irreversible loss of all functions of the brain, including the brainstem. Brain death is also referred to as neurological death.

This covers epidemiology and determination of brain death in a general Australasian context. Management of the brain dead patient proceeding to organ donation is covered at Brain Death Management.

Some suggested phrases for describing brain death to families are listed under Organ Donation.

Epidemiology and Risk Factors

Brain death:

  • Accounts for 1-2% of all death
    • 5-10% of ICU death
  • Rates decline as treatment of brain injury improves
  • Is poorly understood by both physicians and the general public
    • In a 2015 survey, 57% of physicians did not believe that brain death equates to cardiorespiratory death

Pathophysiology

Brain death occurs when ICP exceeds arterial perfusion pressure and cerebral blood flow ceases. This leads to a relatively predictable pattern of autonomic responses:

  • Autonomic storm
    • Transient ↑ BP with vasoconstriction, tachyarrhythmia
    • Less commonly tachypnoea, seizures, sweating, pupillary dilation
  • Autonomic collapse
    • Loss of reflex brainstem activity
    • Loss of respiratory drive
    • Loss of temperature regulation
    • Loss of vascular tone and HR regulation
    • DI

Determination of Brain Death

The definitions and process discussed here are specific to brain death in the Australian context, which requires whole brain death. Some other jurisdictions accept brain-stem death as sufficient, and vary as to the procedural requirements to determine brain death.

Determination of brain death requires:

  • Meeting preconditions
    • Consistent lesion
    • No reversible cause
    • Possible to diagnose
  • Clinical assessment
    Consisting of both:
    • Observation period
      Sustained period with absence of neurological activity.
    • Clinical testing
      Formal testing by two clinicians.

Time of death is the completion of examination by the second doctor.

Preconditions

For brain stem testing to be appropriate, the following preconditions must be met:

Due to the immaturity of brain-stem reflexes, brain death cannot be determined in preterm neonates, and ↑ caution should be used in neonates and infants.

  • A brain lesion consistent with a diagnosis of brain death
    Neuroimaging consistent with acute brain pathology that could cause brain death. Only in the case of HIE is imaging not required, and the diagnosis may be made on history alone.
  • Absence of physiological and anatomical confounders of assessment:
    • No high cervical spine injury
      Must be able to assess:
      • Upper limb motor response to central stimulus
      • Central response (grimace) to upper limb stimulus
      • Cough reflex
    • Normotensive
      SBP ≥90mmHg or MAP >60mmHg in adults, or age-appropriate perfusion pressure in children.
    • No effect of sedation or analgesia
      The amount of elapsed time required since the last administration varies on the drug, dose, and degree of any renal or hepatic dysfunction.
      • This is fundamentally a question of clinical judgment
      • Thiopentone plasma levels should be <10mg/L
      • Drug antagonists can be used if there is any doubt about persisting drug effect
    • No muscle relaxation
      Confirm with train-of-four.
    • Normothermia
      ≥ 36.5°C. Hypothermia depresses consciousness, and brainstem reflexes may be absent <28°C.
    • Absence of severe metabolic, endocrine, and electrolyte derangements
      • Glucose: <3 or >25mmol/L
      • Sodium: <125 or >160mmol/L
      • Phosphate: <0.5mmol/L
      • Magnesium: <0.5mmol/L
      • Urea: >40mmol/L
      • Severe hypothyroidism
      • Severe hypoadrenalism
    • No acute liver failure or decompensated chronic liver disease
  • Ability to perform clinical testing
    • Ability to assess brain stem reflexes
      At least one functioning eye and ear.
    • Ability to perform apnoea test
      Neuromuscular system capable of independent respiration (e.g. no high cervical spine injury), saturations able to be maintained with supplemental oxygen.

Conditions which may mimic brain death include:

  • Neurological
    • GBS
      • Miller-Fisher
  • Drug and Toxin
    • Baclofen
    • Valproic acid
    • Organophosphate intoxication

Observation Period

Prior to performing clinical testing, a minimum of 4 hours of observation should be performed during which the:

The observation period should be extended to 24 hours in the case of HIE or hypothermia >6 hours.

  • Preconditions are met
  • GCS is 3
  • Non-reactive pupils
    May be mid-sized or dilated.
  • No spontaneous respiratory effort
  • Absent cough reflex

Since all patients undergoing brain death testing will be intubated, GCS 3 is GCS 2T.

Clinical Testing

Each Australian state has slightly different requirements around the qualifications, experience, and relationship to the patient of the clinicians determining brain death.

Equipment required for testing:

  • Pen torch
  • Gauze or cotton wool
  • Otoscope
  • 50mL syringe
    And a cannula, or use a Toomey syringe.
  • Laryngoscope
  • Tongue depressor
  • Cold ice water
  • Kidney dish
    To collect cold ice water.

In order to help the testing process flow smoothly, ↓ the minute ventilation so that the PaCO2 is close to the upper limit of normal and place the patient on 100% oxygen at the start of testing. If the minute ventilation and PaCO2 are stable, the pre-apnoea ABG can also be taken prior to commencing testing.

Clinical testing is performed separately by two suitably trained and experienced clinicians (at least one a specialist), and requires:

  • Coma
    GCS 3, confirmed by absence of motor response following painful stimulus applied centrally (bilaterally) and to all four limbs.

Family should be offered the opportunity to observe clinical testing, after appropriate explanation (particularly about spinal reflexes) and support. Consider using the second set of testing, as the family can be warned about any spinal reflexes that may occur.

  • Absence of brainstem reflexes
    Should be tested sequentially and bilaterally.
    • Pupils
      Absence of light response. Pupils should be at least mid-diameter.
    • Corneal reflex
      Use of cotton wool or gauze are appropriate stimuli. Touch the cornea until visible deformation of the gauze is seen, and use a fresh corner for the opposite side.
    • Oculo-vestibular reflexes
      • Firstly, inspect both ear canals to confirm absence of canal occlusion
        A damaged eardrum does not preclude testing.
      • Secondly, hold eyelids open
      • Thirdly, inject cold ice water into each EAM via a small catheter:
        • 50mL should be infused
        • The eyes should be observed for 60 seconds after instillation
        • A normal reflex is either:
          • Nystagmus
            Slow-phase towards irrigated ear in intact brainstem.
          • Ocular deviation
    • Gag
      • Expose the chest to evaluate for respiratory effort
      • Use a tongue depressor or cotton swab to stimulate the posterior pharynx on each side
        A laryngoscope is usually required to adequately visualise the pharynx.
    • Cough
      • Expose the chest to evaluate for respiratory effort
      • Pass a a tracheal suction catheter to evaluate for cough

Expose the abdomen prior to testing cough, gag, and apnoea.

  • Apnoea
    Conducted last so that an ↑ PaCO2 does not confound neurological assessment. Apnoea testing assesses ventilatory drive, and is performed by:
    • Preoxygenation with 100% O2
    • Expose the chest to evaluate for respiratory effort
    • Ventilator disconnection
      Hypoxia (SpO2 <88%) should be avoided; attach a self-inflating bag with a PEEP valve to prevent atelectasis and provide some passive entrainment.
    • No respiratory effort when:
      • PaCO2 is ≥60mmHg, OR
        Expect PaCO2 to ↑ by ~3mmHg/min as a guide for when to perform the ABG.
      • PaCO2 has risen 20mmHg above baseline
        Expect ~3mmHg of rise per minute, so leave 7-10 minutes until testing.

Use of suction catheter or t-piece to provide passive oxygenation during apnoea testing is not recommended.

For patients on ECMO during apnoea testing:

  • Preoxygenate via the lung and circuit
  • ↑ PaCO2 to >45mmHg on the circuit
  • Attach a CPAP circuit as describe above
  • ↓ Sweep to 0.5-1L/min

The time of death is the time of the second set of testing. This should be discussed with family in advance as:

  • Certain times may be important for the family
  • The patient will look the same after they have died as they did before
    Still warm, “breathing” on the ventilator.

Spinal Reflexes

Spinal reflexes are movements due to loss of higher centre inhibition of a reflex arc, are compatible with brain death and:

  • Occur:
    • In up to 50% of patients
    • Usually within 24 hours of death, though can stretch to days
    • Consistently
      May be highly variable between patients, but usually repeatable within a given patient.
  • Include:
    • Upper limb extension-pronation
    • Lower limb flexion
    • Deep tendon reflexes
    • Lazarus sign
      Bilateral arm flexion, shoulder adduction, hand raising above chest.
    • Plantar response

Investigations

If there is any doubt as to whether there is a confounding effect of sedation, then radiological testing should be performed.

Cerebral perfusion imaging is used when brain death cannot be determined because the preconditions are not met.

Obviously, if the preconditions are met then clinical testing should be performed, and that will determine whether or not brain death has occurred. Some institutions may routinely perform radiological investigations in addition to clinical assessment, but this is not required to establish a diagnosis of brain death.

Key investigations:

  • 4-vessel angiogram
    Demonstrating absence of flow above the carotid siphon in the anterior circulation and foramen magnum in the posterior circulation. Reliable, easy to interpret, but limited access.
  • Tc-99 HMPAO Spect
    Nuclear medicine study that determines lack of perfusion in the brain parenchyma.
  • CT Angiography
    Acceptable when formal angiography or radionuclide imaging is not available.

Other investigations:

  • MRI
    Should not be used to determine brain death.
  • Transcranial doppler
    Should not be used to determine brain death, although may be helpful to time formal imaging if brain death is expected as presence of MCA flow indicates radiographic evidence of brain death will not be present.
  • EEG
    No benefit. Absence of cortical activity does not confirm brainstem death and electrical activity in some cortical cells does not indicate brain functioning.

References

  1. ANZICS. Brain Death Determination. 2018.
  2. ANZICS. The Statement on Death and Organ Donation. Edition 4.1. 2021.
  3. Wijdicks EF. The bare essentials: coma. Pract Neurol. 2010 Feb;10(1):51-60.
  4. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  5. Dünser MW, Dankl D, Petros S, Mer M. Clinical Examination Skills in the Adult Critically Ill Patient. Springer International Publishing; 2018.