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Death and Brainstem Death

Definitions

• Death: Irreversible cessation of circulatory, respiratory and brain function. In South Africa, legally defined as brain death (National Health Act, Ch 8).
• Brainstem Death: Irreversible loss of all brainstem function in a deeply comatose, mechanically ventilated patient, after excluding reversible causes.

Mechanisms of Death

System	Insult	Pathway to Failure
Cardiovascular	Distributive (sepsis, anaphylaxis) Obstructive (tamponade, PTE) Hypovolaemic (haemorrhage) Myopathic/arrhythmic Metabolic (electrolytes, toxins)	↓ SVR, ↓ preload, ↓ contractility, arrhythmia → ↓ CO → shock
Respiratory	Hypoxaemia (Type I) Hypercapnia (Type II) Airway loss	↓ PaO₂, ↑ PaCO₂ → acidosis → respiratory arrest
Neurologic	↑ ICP, stroke, infection, metabolic	CNS depression → loss of drive → seizure or coma → apnea

Brainstem Death: Preconditions

1. Coma: Known irreversible cause; no sedatives, hypothermia, metabolic derangement.
2. Support: Apnoeic; ventilated; normothermic (> 35 °C); SBP ≥ 90 mmHg.
3. Exclusion: CNS depressants, neuromuscular blockers, endocrine/metabolic confounders.

Clinical Brainstem Death Criteria

• Must satisfy preconditions and then demonstrate on two occasions (interval ≥ 6 h; if arrest cause, ≥ 24 h):

Reflex/Test	Brainstem Nuclei	Expected Finding
Pupillary	II → III	No constriction
Corneal	V → VII	No blink
Oculo-cephalic (Doll’s eyes)	VIII → III/IV/VI	Absent movement
Oculo-vestibular (cold calorics)	VIII → III/IV/VI	No eye deviation
Gag & cough	IX → X; brainstem motor	Absent
Facial pain response	V → VII	No grimace
Apnoea test	Respiratory centres (medulla)	No respiratory effort with PaCO₂ > 60 mmHg

• Time of death recorded at completion of first set of tests

Tests to Be Performed

1. Pupillary Reflex
   • Pupils should be fixed although not necessarily dilated
2. Corneal Reflex
   • No response to light touch with cotton wool. Avoid damaging the cornea.
3. Gag Reflex
   • Absent on stimulating the back of the pharynx
4. Cough Reflex
   • No response to suctioning via endotracheal tube.
5. Pain Response in Facial Distribution Absent (Supra-orbital Compression)
   • Supra-orbital compression must not elicit any response in a facial distribution. Spinal and tendon reflexes may be present.
6. Oculo-cephalic Reflex (Doll’s Eye Movement)
   • A negative doll’s eye reflex (eyes remain midline or move in same direction of head movement) indicates severe brainstem dysfunction.
7. Oculo-vestibular Reflex (Cold Caloric Test)
   • There is no eye movement in response to the injection of 50mL of ice-cold water into the external auditory meatus—direct access to the tympanic membrane should be verified using an auroscope. The eyes should be observed for at least 1 minute after each injection.
8. Apnea Test (Done Last)
   • Ventilate the patient fully on 100% oxygen for 10 minutes. Do an arterial blood gas to check the pCO2 is within the normal limit (4.0—5.3 kPa or 35—45 mmHg). Then disconnect the ventilator and place the patient on a T-piece with an O2 flow rate of 15L/min. One of three things may take place:
     1. The patient may show some respiratory effort. The patient is not brain dead, although he may become brain dead at a later time. Replace on the ventilator. Consider for donation after circulatory death if the decision is still to withdraw support and death is expected.
     2. After 10 minutes there may be no signs of spontaneous respiration. A blood gas is done to confirm a raised pCO2 of >6.6 kPa (50 mmHg). In this setting, the patient may be certified brain dead.
     3. The patient may desaturate or become haemodynamically unstable. Reconnect the ventilator but do a blood gas to see if the PCO2 is adequately raised. If it is and there was no spontaneous respiration then the patient may be certified brain dead. If not consider ancillary testing. At the end of the test, it is essential to reconnect the ventilator as breathing or not breathing through an ET tube unsupported by ventilation hastens cardiac arrest.
9. Some transplant centers request an atropine test. This is done by administering 2mg of atropine and noting that the heart rate does not change (< 10 beats / minute). This is not used by the majority of brain death determination guidelines.

Ancillary Tests (When Clinical Tests Impossible)

Modality	Principle
Cerebral angiography	Absent intracranial circulation (gold standard)
Radionuclide scan	No cerebral uptake of lipophilic tracer
Transcranial Doppler	Diastolic reversal or absent flow
EEG	Isoelectric trace (caveats: artefact, seizures)

Ancillary Testing Explained

1. Cerebral Angiography is the gold standard of ancillary testing.
   • A 4-vessel angiogram will demonstrate a complete lack of brain perfusion from both the anterior and posterior cerebral circulation.
   • Radionuclide imaging techniques with a lipid-soluble radio-isotope which easily crosses the blood-brain barrier (such as technetium-99) will demonstrate a complete lack of uptake by the brain. Such studies are the preferred ancillary test at Red Cross Children’s Hospital.
2. Transcranial Doppler Ultrasonography
   • Can demonstrate cerebral circulatory arrest.
   • Requires clinical expertise and is not always technically possible.
3. Electroencephalography
   • Most commonly used supplementary test for brain death.
   • (NB. Status epilepticus precludes the diagnosis of brain death.)
   • There are technical guidelines relating to its use in determining brain death; however, it cannot be used as an isolated test (unlike a cerebral angiogram) due to its limitations from electric interference.
   • Some authors argue that an isoelectric EEG does not preclude deep thalamic function.

Pathophysiology of Brainstem Death

• Catecholamine surge → transient hypertension, tachycardia, myocardial injury
• Autonomic collapse → hypotension, bradycardia resistant to atropine
• Neurogenic pulmonary oedema → acute lung injury
• Endocrine: ↓ T3/T4, insulin; ↑ reverse T3, hyperglycaemia, diabetes insipidus
• Coagulopathy: Release of tissue plasminogen activators→ fibrinolysis
• Thermoregulation loss → hypothermia

Confounders & Special Considerations

Situation	Consideration
Sedatives/toxins	Wait ≥ 5 half-lives or antagonise; confirm absence
Metabolic/endocrine derangements	Correct gradually; delay testing if unstable
Paediatric (< 2 months)	Require ancillary tests; retest after 24 h
Spinal reflexes	Common (e.g. Lazarus sign); not exclusionary
Persistent vegetative state	Preserved brainstem functions; distinguish from brain death

Confounding Situations When Declaring a Patient Brain Dead

1. Potentially Reversible Circulatory, Metabolic and Endocrine Disturbances
   • Major disturbances can accompany brain death. These may be the effect of brain death rather than the cause of the coma and it is therefore important to know the proximate cause. It may be detrimental to correct such abnormalities too rapidly and targeting absolute electrolyte concentrations can delay brainstem testing unnecessarily.
     • Electrolyte disturbances Na/K/Mg
       • Raised Na can accompany brain death.
     • Hyper/hypoglycaemia
     • Endocrine: A thyroid storm, myxoedematous state, or an Addisonian crisis may cause coma.
2. Sedatives
   • An accurate drug history is essential and any possibility of intoxication contributing to the patient’s clinical condition precludes the diagnosis of brain death.
   • The length of time between the last dose and brain death testing is dependent on several factors including the total dose, duration of treatment, underlying renal and hepatic function, and the availability of drug level testing.
   • Drug antagonists such as naloxone and flumazenil can be used if suspected.
   • In the setting of preserved renal and hepatic function, a waiting period of more than 5 drug half-lives is accepted.
3. Paediatrics
   • Guidelines vary internationally about the assessment of brain death in children. Some countries advocate retesting after a period of 24 hours following the initial testing and specify that tests must be carried out by two consultants.
   • It is important that testing be approached in an unhurried manner and it may be prudent to measure drug levels given the altered pharmacokinetics in children.
   • Adult criteria for brain death are valid in children older than 2 months. Under this age, the clinical validity of brainstem testing is not clear and ancillary testing is recommended.
4. Spinal Reflexes
   • Can be preserved in brain-dead patients.
   • Important to be clear about this with the family as their presence can be misleading.
   • The most dramatic presentation of a reflex arc through the spinal cord is the Lazarus reflex where the arms seem to rise-up and fall back across the body.
   • Ancillary testing (or repeated brainstem testing) may be warranted to reconfirm the diagnosis of brain death in such a situation.
5. Persistent Vegetative State
   • Brain death must not be confused with persistent vegetative state: loss of brainstem function is not complete and although the reticular system is affected such that there is complete loss of consciousness some autonomic functions remain, namely breathing, a stable circulation, and a simulated sleep and waking cycle.

Legal & Procedural Requirements (SA)

• Two doctors, ≥ 5 years’ experience; one consultant; neither on transplant team.
• Timing: ≥ 6 h post-apnoeic coma or ≥ 24 h post-resuscitation from arrest; ≥ 24 h after normothermia if hypothermia used.
• Documentation: Complete first and second tests; time of death = first test complete.

Types of Death: Natural Vs Unnatural

Natural Death

Deaths Due to Natural Causes

• Natural causes include deaths resulting from diseases such as ischemic heart disease, cancer, stroke, complications of diabetes, etc.

Unnatural Death

Deaths Due to Unnatural Causes

1. Deaths Due to the Application of Violence and the Complications Thereof
   • Physical, Chemical, and Thermal Violence
   • Injury Caused by Nature
     • Examples: Dog bite, bee sting anaphylaxis.
   • Complications Following Trauma
     • Examples: Gas gangrene/necrotising fasciitis after gunshot wound, stab wound, pneumonia/pulmonary embolism after traumatic injury.
2. Anaesthetic-Associated Deaths
   • Description: Deaths occurring while the patient is under the influence of a local, general, or regional/spinal anaesthesia.
   • Criteria: Includes death at any stage following the anaesthetic procedure where any aspect of the procedure has been a contributory cause. Note that there is no time limit of 24 hours stipulated by law.
3. Sudden, Unexpected Deaths
   • Description: Deaths that are sudden, unexpected, or unexplained, or where the cause of death is not apparent.
4. Deaths Suspected to Be Due to an Act of Omission or Commission
   • Description: Any death, including those that would otherwise be classified as “natural,” where it is suspected that the death was due to an act of omission or commission by any person or medical staff.

Links

• Death on table
• Transplants and organ donation

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References:

1. Neyrinck, A., Raemdonck, D. V., & Monbaliu, D. (2013). Donation after circulatory death. Current Opinion in Anaesthesiology, 26(3), 382-390. https://doi.org/10.1097/aco.0b013e328360dc87
2. Stevens RD et al. A framework for diagnosing and classifying ICU-acquired weakness. Crit Care Med. 2009;37(10 Suppl):S299–S308.
3. Wijdicks EFM et al. Evidence‐based guideline update: Determining brain death in adults. Neurology. 2010;74(23):1911–1918
4. Greer DM et al. Guidelines for the determination of brain death in adults (AAN). Neurology. 2013;80(9): 784–778.
5. South African National Health Act, Chapter 8, Regulations for organ transplantation.
6. The Calgary Guide to Understanding Disease. (2024). Retrieved June 5, 2024, from https://calgaryguide.ucalgary.ca/
7. FRCA Mind Maps. (2024). Retrieved June 5, 2024, from https://www.frcamindmaps.org/
8. Anesthesia Considerations. (2024). Retrieved June 5, 2024, from https://www.anesthesiaconsiderations.com/
9. ICU One Pager. (2024). Retrieved June 5, 2024, from https://onepagericu.com/

Summaries:
Brainstem death
DCD

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© 2025 Francois Uys. All Rights Reserved.

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