Brain Death

OVERVIEW

• Brain death is the irreversible loss of all functions of the brain, including the brainstem
• The three essential findings in brain death are coma (unresponsiveness), absence of brainstem reflexes, and apnoea

Important considerations in the determination and management of brain death are:

• Preconditions for diagnosis of brain death
• Examination
• Investigations
• Pathophysiology
• Management and organ donation process

PRECONDITIONS

• cause for coma consistent with brain death
• at least 4 hours of observation during which preconditions must be met (GCS 3, pupil non-reactive, no cough, apnoea)
• neuro-imaging consistent with acute brain pathology that could cause brain death
• normothermia (T>35C)
• normotension (SBP>90 or MAP>60mmHg in an adult)
• no sedation or analgesia (dependent on types of drugs used, renal and hepatic function; use antagonists if concerned)
• absence of severe electrolyte, metabolic and endocrine disturbances (glucose, Na+, PO43-, Mg2+, renal and hepatic function)
• no paralysis (use NMJ monitor or electromyography if concerned)
• ability to assess brain stem reflexes (at least one eye and ear)
• ability to perform apnoea test (doesn’t have severe hypoxic respiratory failure or have a high cervical spine injury)

EXAMINATION

Summary
1. absence of responsiveness
2. absence of brainstem reflexes
3. apnoea

Procedure

• ‘Train of Four’ nerve stimulation test (40 mV) to rule out neuromuscular blockade
• GCS 3 – no response in CN distribution (supraorbital compression) and deep nail bed pain in all four limbs
• pupils fixed, no reaction to light (CN II, III)
• no corneal reflex (CN V, VII)
• no oculo-vestibular reflexes (CN III, IV, VI, VIII)
• no gag (CN IX, X)
• no cough (CN X)
• positive apnoea test (after preoxygenation, and pH 7.3, no breath taken after disconnection from ventilator with a PaCO2 > 60mmHg; or increase in PCO2 by 20 mmHg if COPD/ CO2 retainer)

• independent examination by 2 suitably trained and experienced doctors
• can be sequential (don’t have to wait 2 hours between testing)
• time of death is the time of completion of the second examination

Note that the legal requirements differ in the UK, however the physical examination elements of brain death testing are similar.

INVESTIGATIONS

• the indication for cerebral perfusion imaging is when clinical brain death can not be determined (any of the preconditions can not be met)
• an investigation showing absent cerebral parenchymal blood flow is required:

(1) 4 vessel angiogram (no flow above the carotid siphon in anterior circulation and foramen magnum in posterior circulation)

(2) Tc-99 HMPAO SPECT radionuclide imaging (lack of perfusion across the BBB to be retained by the brain parenchyma)

(3) CT angiography (less experience with this technique, absent enhancement at 60 seconds in different cerebral arterial distributions, presence of contrast in external carotid artery must occur to establish a technically adequate study)

• transcranial doppler (TCD) may be used as a screening test optimise the timing of the contrast study (TCD can rule out brain death, but cannot confirm it)

PATHOPHYSIOLOGY

• brain death is generally preceded by increasing intracranial pressure
• following brain death a predictable pattern of multi-organ failure ensues

Cardiorespiratory

• Initial Cushing’s response usually occurs (bradycardia, hypertension)
• Dysrhythmias (‘catecholamine storm’; myocardial damage; reduced coronary blood flow)
• Hypotension (vasoplegia; hypovolaemia; reduced coronary blood flow; myocardial dysfunction; DI)
• Pulmonary edema (acute blood volume diversion; capillary damage)

Other

• Hypothermia (hypothalamic damage; reduced metabolic rate; vasodilation and heat loss)
• Diabetes insipidus (posterior pituitary damage)
• Endocrine dysfunction (hyperglycemia, sick euthyroid state, anterior pituitatry function usually maintained)
• DIC (tissue factor release; coagulopathy)
• SIRS

MANAGEMENT OF ORGAN DONATION PATIENT

• See Management of the organ donation patient

References and Links

• CCC — Brain death hot case
• CCC — Changes in Brain Death Consensus Statement (2010)
• CCC — Observations Compatible and Incompatible with Brain Death
• CCC — Management of the organ donation patient
• ANZICS Statement on Death and Organ Donation – 3.1 (2010)