Brain death and organ donation in ICU · ICU Topics

Cinematic ICU scene of a brain-dead donor on monitoring with apnoea test documentation, a cerebral blood flow study on the screen, hormonal resuscitation (vasopressin, triiodothyronine, insulin) running, an organ donation team coordinating, clinical-blue lighting, medical educational, no faces, no text — FigureThe brain death and the organ donation — the irreversible cessation of the brainstem function, confirmed by the prerequisites, the exclusion of the confounders, and the bedside testing (the pupil, the corneal, the oculovestibular, the gag, the cough, the apnoea). The donor management is the normotension, the normoxia, the normothermia, and the hormonal resuscitation.

Brain death (DBD) vs circulatory death (DCD) donation

Feature	DBD (brain death)	DCD (circulatory death)
Definition	Brain death diagnosed	Death after cardiac arrest (withdrawal of life support)
Patient status	Brain DEAD, heart BEATING	Brain intact or damaged, heart STOPPED
Organ quality	BETTER (organs perfused until retrieval)	Variable (warm ischaemia time after arrest)
Timing of death	Time of brain death declaration	Time of cessation of circulation (2-5 min asystole)
Organs available	All (heart, lungs, liver, kidneys, pancreas, intestines)	Most (heart — controversial; lungs, liver, kidneys, pancreas)
Consent	Family (or patient registration)	Family (or patient registration)
ICU management	Donor optimisation (maintain perfusion until retrieval)	Withdrawal in OR/ICU → observe → death → rapid retrieval
Frequency	~60% of donations	~40% (increasing)

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Brain death diagnosis and donation process in ICU

SUSPECT brain death — patient with catastrophic brain injury (TBI, SAH, anoxia), deeply comatose (GCS 3), no brainstem reflexes, on mechanical ventilation
PRECONDITIONS (must be met before testing): (a) Known cause of irreversible brain damage (CT/MRI evidence). (b) Exclusion of REVERSIBLE causes: hypothermia (core temp >35°C), CNS depressant drugs (check levels — barbiturates, benzodiazepines, opioids), metabolic (severe hyponatraemia, hypoglycaemia, hepatic encephalopathy), neuromuscular blockade (train-of-four). (c) Adequate oxygenation + haemodynamics (PaO2 ≥200 for apnoea test, SBP ≥100)
CLINICAL EXAMINATION (two doctors, independently): (a) COMA (GCS 3 — no response to pain). (b) ABSENT brainstem reflexes: pupil reflex (fixed, dilated — no response to light), corneal reflex (no blink on touch), oculocephalic (doll's eyes — absent), oculovestibular (caloric — ice water in ear, no eye movement), gag/cough reflex (absent on suctioning). (c) APNOEA TEST: disconnect ventilator, oxygen via catheter at 6 L/min, PaCO2 must rise to ≥60 mmHg (or ≥20 above baseline) with NO respiratory effort
DOCUMENT — two examinations, two doctors (per jurisdictional requirements). Time of death = time of second examination (or first — varies by jurisdiction). Record all findings
NOTIFY — organ donation team (IMMEDIATELY after first positive examination — if family supportive or patient registered). Family discussion (trained requestor — separate from end-of-life discussion)
DONOR MANAGEMENT (if donation proceeding): maintain MAP ≥65 (noradrenaline, vasopressin), normothermia (36-37°C), normoglycaemia, electrolytes, lung protective ventilation (if lung donation), hormone resuscitation (vasopressin, T3/T4, insulin — if haemodynamically unstable)
ORGAN RETRIEVAL — surgical retrieval in operating theatre. Coordinate with transplant teams

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Exam practice — SAQs

SAQ — Brainstem death testing prerequisites after subarachnoid haemorrhage

10 minutes · 10 marks

A 54-year-old man is in ICU on day 3 after an aneurysmal subarachnoid haemorrhage. He is intubated and sedated, GCS 3 with fixed dilated pupils and no cough on tracheal suctioning. The consultant plans to perform brainstem death tests this afternoon. Current observations: core temperature 34.2 degrees C; thiopentone infusion 4 mg/kg/h running for the last 48 hours for intracranial pressure control; noradrenaline 0.3 mcg/kg/min with MAP 72 mmHg; chest X-ray shows right lower lobe consolidation.

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SAQ — Donation after circulatory death (DCD) pathway and warm ischaemia time

10 minutes · 10 marks

A 62-year-old man has devastating anoxic brain injury after an out-of-hospital cardiac arrest with a down-time of 35 minutes. After multiple multidisciplinary meetings, the treating team and family have agreed to withdraw life-sustaining therapy on the basis of futility. The family has consented to organ donation. The patient does not fulfil brain death criteria and the agreed pathway is donation after circulatory death (DCD). He is ventilated (FiO2 0.4), on noradrenaline 0.15 mcg/kg/min with MAP 70 mmHg. Creatinine 110 micromol/L; liver function normal.

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Clinical pearls

High-yield brain death/donation points for CICM/FFICM exam

Brain death = LEGAL death. The patient is DEAD (not dying, not brain-injured). In most jurisdictions: irreversible cessation of ALL brain function (whole brain — cerebrum + brainstem). UK: brainstem death (brainstem alone — but in practice equivalent). DOCUMENT precisely — medico-legal implications. Time of death = time of brain death determination (not when heart stops).[1] }
Apnoea test: PaCO2 ≥60 mmHg with NO respiratory effort. Disconnect from ventilator. Give oxygen via catheter at 6 L/min into trachea (prevent hypoxia during test). Allow PaCO2 to rise (passive — ~3-6 mmHg/min). Target: PaCO2 ≥60 mmHg (or ≥20 above baseline). ABG before and after. OBSERVE for respiratory effort (chest/abdominal movement). If ANY effort → NOT brain dead. If NO effort at PaCO2 ≥60 → POSITIVE (brain dead). CAUTION: arrhythmia/hypotension during test (from hypercapnia/acidosis) → may need to stop.[1] }
Exclusion of REVERSIBLE causes — ESSENTIAL before testing. (1) HYPOTHERMIA: core temp must be >35°C (rewarm if hypothermic — hypothermia mimics brain death). (2) DRUGS: check levels — barbiturates (used for ICP management — wait until level <5 mg/L or 5 half-lives), benzodiazepines (flumazenil challenge or wait), opioids (naloxone challenge or wait), neuromuscular blockers (train-of-four — ensure full recovery). (3) METABOLIC: check Na, glucose, ammonia, LFTs — correct severe derangements first.[1] }
Hormonal resuscitation of brain-dead donor — controversial but used. Brain death → hypothalamic-pituitary axis fails → diabetes insipidus (ADH deficiency), hypothyroidism (TSH deficiency), adrenal insufficiency (ACTH deficiency). HORMONE REPLACEMENT: (a) VASOPRESSIN (1-2 U/h or 0.01-0.04 U/min) — for diabetes insipidus + vasoplegia. (b) T3/T4 (triiodothyronine 4 mcg bolus then 3 mcg/h OR levothyroxine 20 mcg IV) — for cardiovascular stability (controversial — some evidence improves haemodynamics, reduces vasopressor need). (c) INSULIN infusion — for hyperglycaemia + inotropic support (high dose — controversial). (d) CORTICOSTEROIDS (methylprednisolone 15 mg/kg) — for adrenal insufficiency + immunosuppression (reduces donor immune reaction).[5] }
Diabetes insipidus is COMMON in brain-dead donors. ADH deficiency → massive urine output (3-20 L/day) → hypovolaemia, hypernatraemia, hyperosmolarity. MANAGEMENT: (1) DESMOPRESSIN (1-2 mcg IV) or vasopressin infusion (for DI). (2) Replace urine output mL-for-mL with D5W (or oral/hypotonic). (3) Monitor: serum Na (target 135-155), osmolality (target 280-310), urine output. (4) If Na >155: hypotonic fluids (D5W, 0.45% saline).[3] }
Donor lung management — lung-protective ventilation. If lungs being considered for transplantation: maintain with LUNG-PROTECTIVE settings (Vt 6-8 mL/kg, PEEP 5-8, plateau <30, FiO2 as low as possible for SpO2 ≥95). AVOID: tidal volume >10 (barotrauma), high FiO2 (>60 for prolonged — oxygen toxicity). Recruitment manoeuvres (before retrieval — to optimise). Pulmonary toilet (suction — clear secretions). TARGET: PaO2/FiO2 >300 for viable lungs.[3] }
DCD (donation after circulatory death) — increasing. PATIENT: devastating brain injury, not brain dead, family has decided to WITHDRAW life-sustaining treatment. PROCESS: (1) Withdrawal in ICU or OR (extubate, stop vasopressors). (2) Observe for cardiac arrest (may take 30 min to 2h — if >2h: DCD not proceeding — return to ICU for palliative). (3) After arrest: wait 2-5 minutes (ensure irreversible — no auto-resuscitation). (4) Declare death (circulatory). (5) Rapid retrieval (cold perfusion — minimize warm ischaemia time). (6) WARM ISCHAEMIA TIME: time from arrest to cold perfusion (target <30 min for liver, <60 min for kidney).[4] }
Family discussion — SEPARATE from end-of-life. (1) FIRST discussion: end-of-life/brain death diagnosis (by treating team — intensivist, neurosurgeon). Explain: what happened, brain death determination, prognosis (dead). Allow: questions, time, grief. (2) SECOND discussion (separate): organ donation (by TRAINED REQUESTOR — donation specialist, not treating doctor). Discuss: donation process, what organs, consent. AVOID: discussing donation at SAME time as death notification (overwhelming — family can't process both). The 'decoupled' approach is BEST.[1] }
Australia/NZ: organ donation register. Patients can REGISTER their wish to donate (Australian Organ Donor Register — AODR). If registered: family is INFORMED (but in practice, family consent still sought and respected — even if registered, family refusal usually overrides). If NOT registered: family decides. FAMILY CONSENT RATE: ~60% (when asked) — higher if patient was registered. IMPORTANT: discuss donation wishes WITH FAMILY before crisis (so they know your wishes).[1] }
Brain death is a CLINICAL diagnosis (not requiring confirmatory tests in most jurisdictions). CLINICAL EXAMINATION (coma + absent brainstem reflexes + apnoea test) is SUFFICIENT for brain death determination in most countries (US, UK, Australia, NZ, most of Europe). CONFIRMATORY TESTS (NOT routinely required): (a) EEG (isoelectric — flat line — no brain activity). (b) Cerebral angiography (no intracranial blood flow). (c) CT angiography (no intracranial perfusion). (d) Nuclear medicine (no uptake). (e) Transcranial Doppler (no flow). When to USE confirmatory tests: (i) Cannot complete clinical exam (e.g., severe facial trauma — can't do corneal/caloric). (ii) Uncertain (complex case — specialist input). (iii) Jurisdictional requirement (some countries require).[2] }
Potential for SPINAL REFLEXES in brain death. BRAIN-DEAD patients may have SPINAL REFLEXES (not brain-mediated — from spinal cord, which is intact). These can be DISTRESSING to witness (family, staff): (a) Lazarus sign (arms rise and cross — dramatic). (b) Reflex withdrawal (limb moves on pain). (c) Respiratory-like movements (chest/abdominal — from spinal roots, NOT brainstem-driven). IMPORTANT: these are SPINAL (not brain) — do NOT indicate brain function. Explain to family: these are reflexes from the spinal cord — the brain is dead. Don't confuse with brain-mediated responses.[1] }
Preservation time for organs. ORGANS can survive for limited time after retrieval: (a) HEART: 4-6 hours (shortest — most urgent). (b) LUNG: 6-8 hours. (c) LIVER: 12-15 hours. (d) KIDNEY: 24-36 hours (can be on pump — up to 48-72h). (e) PANCREAS: 12-24 hours. LOGISTICS: coordinate with transplant centres (may be in different cities/countries). Cold ischaemia time matters (shorter = better function).[3] }
Ethical considerations. (1) CONFLICT OF INTEREST: treating ICU team (focused on patient/family) vs donation team (focused on organ procurement). SOLUTION: separate teams — donation specialist handles donation discussion; ICU team handles clinical care. (2) DCDD TIMING: when to withdraw? (patient/family decision, not for donation). (3) DONOR OPTIMISATION: interventions (vasopressors, fluids, hormones) performed for DONOR BENEFIT (organ quality) — ethical (benefits recipients — patient is already dead — harm only if discomfort — but brain-dead → no suffering). (4) CONSENT: informed, voluntary, family understanding (not coerced).[1] }
1 organ donor can save up to 8 lives. ORGANS from 1 donor: heart (1), lungs (2 — left + right), liver (1 or split into 2), kidneys (2), pancreas (1), intestines (1). TISSUES (from 1 donor): corneas (2), skin, bone, heart valves, tendons — benefit up to 50+ people. SHORTAGE: demand >> supply (waiting lists years). Every donor matters. ICU clinicians: KEY role in identifying and referring potential donors.[1] }

Red flags

Prognosis

Brain death diagnosis and organ donation (ANZICS data)

Brain death determination: clinical exam + apnoea test is STANDARD (no confirmatory test needed in most jurisdictions). Sensitivity ~100%, specificity ~100% (when criteria met correctly). Donor optimisation: vasopressin + T3/T4 + corticosteroids — reduces vasopressor need, improves organ function in some studies (controversial — UNOS trial 2007 showed no mortality benefit for heart transplant recipients from hormone-treated donors). DCD: increasing — now ~40% of donations in Australia/NZ. Outcomes comparable to DBD for kidney, liver, pancreas. Lung: DCD outcomes similar to DBD. Heart: DCD controversial (some centres — emerging, using ex-vivo perfusion). 1 donor: up to 8 organs + 50 tissue grafts. Australia/NZ consent rate: ~60% (family asked). Higher if patient registered (AODR). Waitlist: ~1,400 Australians waiting for transplant (2019). ~50 die waiting each year.

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Determination of brain death — preconditions in detail

Brain death determination pathway: preconditions checklist, brainstem reflex testing, apnoea test PaCO2 targets, optional ancillary cerebral blood flow study — FigureDetermination pathway — exclude confounders, examine brainstem reflexes, complete the apnoea test to target PaCO2, and use ancillary tests only when the clinical exam cannot be completed.

Preconditions that MUST be met before clinical brain death testing

Domain	Requirement	Threshold / detail
Known cause	Irreversible catastrophic brain injury established	CT/MRI showing catastrophic injury (massive SAH, herniation, diffuse cerebral oedema, anoxic injury). Cause MUST be known — "unexplained coma" is NOT a basis for diagnosing brain death
Core temperature	Normothermia	Core temp ≥36°C (AAN 2010). Hypothermia mimics brain death — rewarm actively (forced warm air, warmed IV fluids, haemofiltration). Below 35°C reflexes are unreliable
Neuromuscular blockade	Fully recovered	Train-of-four ≥4/4 (no fade), OR documented time elapsed ≥ 4 half-lives since last dose. Rocuronium/suxamethonium clearance must be confirmed
CNS depressant drugs	Sub-therapeutic	Check levels: pentobarbital < 5 mg/L; benzodiazepines (flumazenil 0.2 mg challenge if uncertain); opioids (naloxone 0.4 mg challenge). If therapeutic levels likely — wait ≥ 5 half-lives
Severe metabolic/endocrine	Corrected	Na 130-160; glucose 5-15 mmol/L; normal pH/PaCO2; ammonia normal; no severe hepatic/renal encephalopathy
Blood pressure	SBP ≥ 100 mmHg, MAP ≥ 75	Use vasopressors/inotropes to maintain — hypotension abolishes brainstem reflexes. Avoid over-correction (vasopressors may mask mild brain function)
Oxygenation	PaO2 ≥ 200 mmHg	Pre-oxygenase before apnoea test to prevent hypoxia during disconnection
Acid-base	Normal or pre-existing baseline pH	Chronic CO2 retainers — target PaCO2 rise to ≥ 20 mmHg above their (elevated) baseline

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Precondition pitfalls — the diagnosis will be CHALLENGED if any are wrong

Hypothermia after cardiac arrest: must be ≥ 36°C — the most common reason an exam is invalid. Rewarm and re-examine.
Thiopentone/pentobarbital for ICP control: levels can persist for DAYS after cessation. Always send a level — do NOT test until < 5 mg/L.
ECMO patients: PaO2 sampling is unreliable (pre/post oxygenator mixing); venous/arterial PO2 from right radial differs from systemic. Get specialist input.[10] }
Spinal cord injury co-existing (e.g., high cervical trauma) can abolish peripheral reflexes and confound — but brainstem reflexes are still testable.
Paediatric age: preterm and neonatal brains are more resistant — longer observation intervals required (e.g., 2 exams + 24-48 h observation in neonates).

Brainstem reflex examination — component by component

The six cranial nerve brainstem reflexes tested in brain death determination

Reflex	Afferent / efferent nerves	Normal response	Brain-dead (absent)	Notes
Pupillary light	CN II / III (parasympathetic)	Pupils constrict briskly to bright light	Fixed, dilated (4-9 mm); no constriction	Record size; anisocoria acceptable if both unresponsive. Pre-existing iris surgery / atropine can confound
Corneal	CN V / VII (facial)	Blink on corneal touch with cotton wisp	No blink, no globe movement	Touch cornea (not sclera). Avoid trauma — may damage donor corneas for transplantation
Oculocephalic (doll's eyes)	CN III, IV, VI + vestibulospinal	Eyes move OPPOSITE to head turn	Eyes remain fixed mid-position (move WITH head)	CONTRAINDICATED if cervical spine not cleared
Oculovestibular (cold caloric)	CN VIII / III, IV, VI	Slow tonic deviation TOWARDS irrigated ear, then nystagmus away	No eye movement whatsoever	50 mL ice-cold water into each external auditory canal after confirming clear tympanic membrane. Wait 60 s between ears
Gag	CN IX / X	Gag on posterior pharynx stimulation	Absent	Use suction catheter to posterior pharynx
Cough	CN X (vagus)	Cough on tracheal suctioning	Absent	Pass suction catheter to carina and oscillate
Facial grimace (CN V/VII)	CN V / VII	Grimace to deep supraorbital pressure	No facial movement	Tests pontine facial pathways

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Apnoea test — the detailed protocol (PaCO2 must reach ≥ 60 mmHg)

PRE-OXYGENATE — ensure PaO2 ≥ 200 mmHg with FiO2 100% for ≥ 10 min before starting. Prevents hypoxia during disconnection
CONFIRM preconditions — core temp ≥ 36°C, SBP ≥ 100, Na/glucose normal, no residual sedation/NMB. Document on the form
BASELINE ABG — record PaO2, PaCO2, pH. Note the starting PaCO2 (critical for the "rise by ≥ 20" threshold if baseline is elevated)
DISCONNECT from ventilator. Insert an oxygen catheter / T-piece delivering 100% O2 at 6-12 L/min directly into the trachea (apnoeic oxygenation — diffuses across alveoli, prevents desaturation)
OBSERVE — watch chest/abdomen continuously for ANY respiratory effort for 8-15 minutes
IF ANY respiratory effort (chest rise, abdominal contraction, accessory muscle use) → TEST NEGATIVE → patient NOT brain dead. Reconnect immediately. Reconsider diagnosis / seek confirmatory test
IF NO effort — repeat ABG at 8 min. If PaCO2 ≥ 60 mmHg (or ≥ 20 mmHg above baseline) AND pH < 7.30 → TEST POSITIVE (consistent with brain death)
IF haemodynamic instability (severe hypotension, arrhythmia, desaturation) → ABORT the test, reconnect, treat, and re-attempt later (or proceed to confirmatory test). The test must NEVER cause harm to the donor organs
DOCUMENT — exact times, baseline/final ABG values, presence/absence of effort, observer names

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Apnoea test — common errors and red flags

The test is POSITIVE only if PaCO2 ≥ 60 mmHg (or rises ≥ 20 from baseline) with NO respiratory effort — both components required.[7] }
Hypoxia during disconnection is the #1 reason tests are aborted — pre-oxygenate and use a tracheal oxygen catheter, not just room air.
Obese/restrictive patients desaturate faster — may need continuous positive airway pressure via T-piece (CPAP + apnoeic O2).
Severe COPD / chronic CO2 retainer — baseline PaCO2 may already be 60; use the "≥ 20 mmHg rise from baseline" criterion.
** NEVER leave the bedside during the test** — observer must watch for any chest movement continuously; movement can be subtle.
Refractory hypotension during the test → abort and use a confirmatory test instead (e.g., radionuclide perfusion) rather than risk organ damage.

Confirmatory (ancillary) tests

Confirmatory tests for brain death — when clinical exam is incomplete

Test	What it shows	Sensitivity	Specificity	Practical notes
Cerebral angiography (4-vessel)	Gold standard — no intracranial blood flow above the petrous segment	Very high	Very high	Invasive, requires transfer to angiography suite — impractical in unstable donor. External carotid flow preserved
CT angiography (CTA)	No intracranial arterial enhancement (suspended filling of cortical vessels)	~85-95%	~95-100%	Fast, widely available. Protocols vary — "7-vessel" and "venous phase" techniques. False positives in high ICP with delayed circulation
CT perfusion	No cerebral blood flow	Good	Good	Adjunct to CTA; helpful when CTA equivocal
Radionuclide scintigraphy (HMPAO SPECT)	No cerebral / cerebellar / brainstem perfusion / uptake	High	High	Portable gamma camera at bedside. Distinguishes scalp/skull flow (preserved) from cerebral (absent). Useful in ECMO/therapeutic hypothermia
EEG	Isoelectric (electrocerebral silence — flat line ≥ 30 min, ≥ 8 electrodes, ≥ 30 µV/mm sensitivity)	High	Lower (false positives)	Detects CORTICAL activity only — does NOT confirm brainstem death. Deep sedation/hypothermia cause false-positive "flat line". Largely superseded in US/Australia; still used in some jurisdictions
Transcranial Doppler (TCD)	Oscillating / to-and-fro flow OR systolic spikes with no diastolic flow (high-resistance pattern)	~90-99%	~98-100%	Bedside, repeatable, non-invasive. ~10% of patients have no temporal acoustic window. Requires experienced operator

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When to use a confirmatory test (rather than clinical exam alone)

Inability to complete one or more components of the clinical exam — e.g., severe facial/orbital trauma (cannot test corneal/caloric), otic disruption (cannot caloric), unstable cervical spine (cannot oculocephalic)
Chronic severe lung disease making the apnoea test unsafe (rapid desaturation, severe acidosis)
Inability to exclude confounders completely — e.g., prolonged sedative clearance in renal failure, concurrent therapeutic hypothermia protocol
ECMO — apnoea test PaCO2 measurement unreliable; clinical exam possible but confirmatory test advised
Paediatric / neonatal cases — some jurisdictions mandate ancillary testing, especially in neonates
Medico-legal / jurisdictional requirement — several countries (e.g., some European nations, parts of Asia) REQUIRE an ancillary test for legal documentation
Family or staff disagreement — to provide objective corroborative data (though legal determination remains clinical)

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EEG vs cerebral angiography vs TCD — choosing the ancillary test

Feature	EEG	Cerebral angiography	TCD
What it confirms	Cortical electrical activity	Cerebral blood flow (anatomical gold standard)	Cerebral blood flow (physiological)
Detects brainstem death?	NO — cortex only	YES — covers all territories	YES — anterior + posterior circulation
Bedside?	Yes	No (angiography suite)	Yes
Sensitivity to sedation/hypothermia	HIGH — causes false-positive isoelectric trace	None	Minimal
Time	30 min minimum	1-2 h + transfer	15-30 min
Current preference	Falling out of favour	When definitive flow documentation needed	Increasing — repeatable, bedside

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DBD vs DCD pathways in detail

Controlled DCD vs uncontrolled DCD vs DBD

Feature	DBD (brain death)	Controlled DCD (cDCD)	Uncontrolled DCD (uDCD)
Setting	ICU, ventilated patient declared brain dead	Planned withdrawal of life-sustaining therapy (WLST) in ICU/OR	Failed resuscitation in ED/ICU/community (unexpected cardiac arrest)
Pre-mortem planning	None (death by neurologic criteria)	Extensive — family discussion, timing, location, retrieval team on standby	None — sudden death; rapid response protocol (preservation within minutes)
Circulation at organ retrieval	Heart BEATING — perfused organs	Heart STOPPED after planned withdrawal + stand-off	Heart STOPPED after failed CPR
Warm ischaemia time	None	Defined — measured from SBP < 50 to cold perfusion (target < 30 min liver, < 60 min kidney)	Long, uncontrolled — often limits usable organs
Organs typically transplantable	All — heart, lungs, liver, kidneys, pancreas, intestine	Kidneys, liver, lungs, pancreas; HEART now possible with ex-vivo perfusion	Mostly kidneys (most ischaemia-tolerant); rarely liver
Frequency (ANZ)	~ 60% of deceased donors	~ 40% (rising rapidly)	Rare / regional only

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Controlled DCD pathway — step-by-step (the cDCD process after WLST decision)

DECISION to withdraw life-sustaining therapy (WLST) — made independently by treating team + family, on best-interest / futility grounds. Donation is NEVER a reason to withdraw
ASSESS DCD ELIGIBILITY — donor team evaluation: age, comorbidities, organ function, projected warm ischaemia time. Consent for donation obtained (separate from WLST decision)
PRE-MORTEM PLANNING / STAND-BY — coordinate timing between ICU, OR, retrieval surgeons, anaesthetics, transplant teams. Determine location of withdrawal (ICU vs OR — affects warm ischaemia time). Plan cannulation strategy (in-situ cold perfusion via aorta)
PRE-EMPTIVE PREPARATION (after WLST decision, BEFORE withdrawal) — may include: heparin administration (controversial — not universal), arterial/venous lines for rapid cannulation, family time
WITHDRAWAL OF LIFE-SUSTAINING THERAPY — extubation (or terminal wean), cessation of vasopressors/inotropes, comfort measures only. Family may be present
OBSERVATION PERIOD — monitor for circulatory arrest. If asystole / absence of circulation < 60 min from withdrawal → proceed. If > 60-120 min (centre threshold) → DCD abandoned, return to comfort care (organs would sustain excessive warm ischaemia)
DEATH DECLARATION — after confirmation of absent circulation (no pulse, no heart sounds, asystole on monitor) and a mandatory NO-TOUCH / STAND-OFF PERIOD (5 minutes in Australia/UK; 2-5 minutes US — varies by jurisdiction) to rule out autoresuscitation[4] }
RAPID RETRIEVAL + COLD PERFUSION — immediate transfer to OR (if withdrawn in ICU) or in-situ cannulation. Cold preservation solution (UW / HTK) flushed via aorta. Document functional warm ischaemia time (from SBP < 50 to perfusion)
EX-VIVO PERFUSION (modern practice) — DCD hearts/lungs now resuscitated on ex-vivo machine perfusion (Organ Care System / TransMedics) before transplantation — has enabled DCD heart transplantation

Time-of-death determination: DBD vs DCD

Aspect	DBD	DCD
Time of death	Time the second brain death examination confirms death (or first, jurisdiction-dependent)	Time of completion of the no-touch observation period after circulatory arrest
Definition of death applied	Neurologic criteria (irreversible cessation of all brain function)	Circulatory criteria (irreversible cessation of circulation)
Documentation	Two clinician signatures, two examinations, full reflex + apnoea record	Single clinician confirms circulatory arrest; documents no-touch period
Permanence	Established by brain death examination	Established by no-touch period (5 min) + absence of autoresuscitation

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Donor management — physiology of the brain-dead donor

ICU donor optimisation scene after brain death: ventilator support, haemodynamic monitoring, vasopressin and metabolic infusions, organ donation coordination — FigureDonor management — support perfusion and oxygenation after death by neurological criteria: MAP targets, diabetes insipidus control (vasopressin), temperature, electrolytes, and early donation-team coordination.

Physiological derangements following brain death — the catecholamine storm and after

Phase	Time	Pathophysiology	Clinical consequence
Catecholamine storm (autonomic crisis)	0-30 min post herniation	Massive sympathetic outflow → noradrenaline/adrenaline surge; then abrupt vagal (brainstem) shutdown	Severe hypertension, tachyarrhythmias, vasoconstriction → myocardial injury, pulmonary oedema, capillary leak. Then sudden hypotension
Vasoplegic shock	30 min onward	Loss of sympathetic vasomotor tone + myocardial depression	Hypotension, low SVR, high cardiac output (distributive shock). Often requires multiple vasopressors
Endocrine failure	1-2 h onward	Hypothalamic-pituitary axis ceases — ADH, TSH, ACTH deficiency	Diabetes insipidus (hypernatraemia, hypovolaemia), low T3/T4, low cortisol
Coagulopathy	Variable	Release of tissue factor, hypothermia, dilution	DIC-like picture, bleeding at retrieval
Hypothermia	Universal	Hypothalamic thermostat loss — poikilothermia	Core temp drifts to ambient; worsens coagulopathy and arrhythmia
Metabolic	Progressive	Hyperglycaemia (insulin resistance + deficiency), acidosis, hyperkalaemia	Multi-organ cellular dysfunction

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Haemodynamic donor management

Haemodynamic targets in the brain-dead donor (organ-protective)

MAP ≥ 65 mmHg (70 mmHg preferred) — noradrenaline first-line for vasoplegia; vasopressin SPARING (reduces catecholamine dose, treats DI)
SBP ≥ 100 mmHg — avoid hypotension (organ hypoperfusion) AND hypertension (worsens neurogenic pulmonary oedema)
Heart rate 60-120 bpm — bradycardia suggests high vagal tone / AV block; tachycardia worsens myocardial O2 demand. Persistent bradycardia unresponsive to atropine is itself a sign of brainstem death (vagal nuclei destroyed)
Cardiac index ≥ 2.5 L/min/m² — if low, add inotrope (adrenaline, milrinone, dobutamine)
CVP / fluid balance — euvolaemia; titrate to CVP 6-10 mmHg or dynamic indices (PPV, SVV, IVC variability). AVOID fluid overload — damages lungs (degrades PaO2/FiO2) and heart
Echocardiography — baseline LV function; recheck after resuscitation. LV dysfunction may recover with hormone therapy. LVEF < 45% after optimisation → heart often unsuitable for transplantation
Arterial line + central access — continuous BP, frequent sampling. Pulmonary artery catheter / TEE in unstable donors

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Vasopressor selection in the brain-dead donor

Agent	Role	Rationale	Cautions
Noradrenaline	First-line vasopressor	α-agonist restores SVR in vasoplegia	High doses > 0.5 mcg/kg/min may worsen organ microcirculation — review
Vasopressin	SPARING + DI treatment	Low-dose (0.01-0.04 U/min) restores vascular smooth muscle tone, treats ADH deficiency, halves catecholamine requirements	Avoid overshoot hypertension; reduces need for noradrenaline
Adrenaline	Inotrope + vasopressor	If MAP low with bradycardia / myocardial depression	Lactic acidosis at high doses (worsens organ viability); use cautiously
Methylprednisolone	Adjunct (15 mg/kg)	Treats relative adrenal insufficiency; downregulates donor immune activation; thought to improve lung / liver yield	Give early once brain death declared

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Electrolyte, metabolic and temperature management

Electrolyte and metabolic targets in the brain-dead donor

Parameter	Target	Common derangement	Management
Serum Na⁺	135-155 mmol/L	Hypernatraemia (DI — water loss)	D5W / 0.45% saline; desmopressin / vasopressin for DI. AVOID Na > 160 — associated with worse liver graft function
Serum K⁺	3.5-5.5 mmol/L	Hypokalaemia (DI urinary losses, alkalosis) — OR hyperkalaemia (acidosis, cell leak)	Replace carefully; correct acidosis first; avoid over-correction (arrhythmia)
Serum Mg²⁺ / PO₄²⁻	Normal	Hypomagnesaemia / hypophosphataemia common	Replace — prevents arrhythmia, respiratory muscle weakness
Glucose	6-10 mmol/L	Hyperglycaemia (insulin resistance + deficiency)	Insulin infusion titrated; conventional (not tight — risk of hypoglycaemia)
pH	7.35-7.45	Metabolic acidosis (shock, renal failure)	Treat cause; bicarbonate if pH < 7.20 with metabolic acidosis
Hb	≥ 70-80 g/L	Anaemia (haemodilution, bleeding)	Transfuse to maintain O2 delivery; balance with risk of TRALI
Core temp	≥ 36°C	Hypothermia (poikilothermia)	Forced warm air, warmed IV fluids, haemofiltration circuit. Hypothermia worsens coagulopathy + arrhythmia

[1]

Hormone replacement therapy — vasopressin, T3/T4, corticosteroids

Hormone replacement in the brain-dead donor — what, why, dosing, evidence

Hormone	Deficiency it treats	Typical dose	Evidence	When to use
Vasopressin (low-dose)	ADH deficiency (DI) + catecholamine-sparing in vasoplegia	0.01-0.04 U/min (1-2.4 U/h) continuous	Strong — reduces noradrenaline requirement, treats DI, well-tolerated	Standard — almost all haemodynamically unstable donors
Desmopressin (DDAVP)	ADH deficiency (DI) when vasoplegia absent	1-4 mcg IV bolus (every 6-12 h)	Effective for DI alone	When DI present but BP stable (no need for vasopressor effect)
Triiodothyronine (T3) / Levothyroxine (T4)	Low-T3 syndrome; cardiovascular instability	T3: 4 mcg bolus then 3 mcg/h OR 20 mcg bolus then 10 mcg/h × 24 h. T4: 20 mcg bolus then 10 mcg/h	CONTROVERSIAL — meta-analyses conflicting; landmark randomised UNOS study showed NO survival benefit for heart recipients from hormone-treated donors, but haemodynamics often improve	Use selectively — haemodynamically unstable donors requiring escalating vasopressors (especially for heart/liver procurement)
Insulin	Hyperglycaemia + (high-dose) inotropic support	Glucose control: 1-4 U/h titrated. High-dose inotropic: controversial	Standard for glucose control; high-dose protocol unproven	Glucose control routine; high-dose rarely used
Methylprednisolone	Relative adrenal insufficiency + dampen donor immune activation	15 mg/kg IV (1 g typical) every 24 h	Reasonable evidence — reduces inflammatory cytokines, may improve lung / liver yield	Standard once brain death declared, especially for lung procurement

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Hormonal resuscitation protocol (haemodynamically unstable brain-dead donor)

CONFIRM brain death declared and donation proceeding — do NOT initiate hormone protocol on a patient who is not yet legally dead
VASOPRESSIN 0.01-0.04 U/min IV continuous — first-line. Aim for urine output 0.5-3 mL/kg/h (treats DI AND vasoplegia). Titrate to MAP and to Na⁺ normalisation
METHYLPREDNISOLONE 15 mg/kg IV (typically 1 g) — give as a single bolus; repeat q24h. Reduces inflammatory cascade, supports adrenal insufficiency
T3 (liothyronine) 4 mcg IV bolus then 3 mcg/h infusion — IF haemodynamically unstable on escalating catecholamines OR poor LV function on echo. Reassess at 2-4 h
INSULIN infusion titrated to glucose 6-10 mmol/L — hyperglycaemia is universal. Some protocols use high-dose insulin (1 U/kg/h) as inotrope — controversial; not routine
REASSESS haemodynamics every 1-2 h — typically vasopressor requirements FALL after 2-6 h of combined therapy. Recheck echocardiography — LV function may recover sufficiently for heart donation
DOCUMENT — record baseline and serial vasopressor doses, echo findings, hormone doses — required for organ acceptance decisions by transplant teams

[1]

Additional clinical pearls — advanced

Brain death and donation — advanced exam pearls (CICM/FFICM/EDIC)

The 'catecholamine storm' is a real phenomenon — and it injures organs. The 15-30 min after herniation sees massive sympathetic surge (hypertension up to 300 mmHg, tachyarrhythmias, intense vasoconstriction) followed by abrupt brainstem shutdown and vasoplegia. The surge causes myocardial injury (subendocardial necrosis), neurogenic pulmonary oedema, and capillary leak. Donor hearts from donors with a stormy course have worse outcomes — early recognition and aggressive donor resuscitation mitigate this.[5] }
The AAN 2010 guideline formalised 3 prerequisites, 4 examination domains, 1 apnoea test. Memorise the structure: PREREQUISITES (cause known; no confounders) → establish coma (GCS 3, no cerebral motor response to pain) → brainstem AREflexia (pupils, corneal, oculocephalic, oculovestibular, gag, cough) → APNOEA test (PaCO2 ≥ 60 mmHg or ≥ 20 mmHg rise from baseline). All components must be documented for every examination.[1] }
UK uses 'brainstem death' (Code of Practice 2008, updated); US / Australia / NZ use 'whole brain death' — but the CLINICAL examination is identical. The conceptual difference (brainstem alone vs whole brain) is philosophical; in practice the bedside tests are the same. The World Brain Death Project 2020 consensus (JAMA) sought to harmonise terminology — uses 'death by neurologic criteria (DNC)'.[6] }
Persistent bradycardia unresponsive to atropine is BRAINSTEM death (Cushing's reflex variant). The vagal nuclei (nucleus ambiguus) are destroyed. Normal hearts with intact vagal input accelerate with atropine; brain-dead donors do not. This is occasionally used as an adjunctive sign but is NOT part of the formal protocol.
Diabetes insipidus — the SINGLE most common endocrine complication (>80% of donors). ADH deficiency → polyuria (3-20 L/day), hypernatraemia, hyperosmolarity, hypovolaemia. Untreated → rapid cardiovascular collapse. FIRST-LINE: vasopressin infusion (treats DI AND vasoplegia). DESMOPRESSIN if BP stable. Replace urine output mL-for-mL with D5W. Target Na 135-155 — sustained Na > 160 worsens liver graft function.[3] }
Hypernatraemia at retrieval is associated with worse liver graft outcomes. Multiple studies show Na > 155-160 mmol/L in the donor linked to early graft dysfunction and primary non-function. Aggressive Na control (D5W, desmopressin) is a KEY modifiable donor management target, especially for liver donors.
Donor lung optimisation is the single most impactful intervention — lungs are the organ most often lost. Only ~ 15-25% of multi-organ donors yield transplantable lungs (vs > 80% for kidneys). LUNG-PROTECTIVE ventilation (Vt 6-8 mL/kg PBW, PEEP 5-8, plateau < 30, FiO2 minimised), alveolar recruitment manoeuvres before retrieval, pulmonary toilet, AVOID fluid overload (target neutral-to-negative fluid balance — every 1 L positive reduces PaO2/FiO2 and lung usability).[3] }
The no-touch / stand-off period in DCD: 5 minutes (Australia, UK, Canada); 2-5 minutes (US states vary). This is the time after cessation of circulation during which NO intervention occurs, to ensure PERMANENT (not just absent) circulation — i.e., autoresuscitation will not occur. The 2023 systematic review (Manara et al) found zero cases of autoresuscitation beyond 4 min 20 s in over 600 cases — supporting 5 min as safe and conservative.[4] }
'Functional' warm ischaemia time in DCD is measured from SBP < 50 mmHg (or SpO2 < 70%), NOT from asystole. This is a high-yield exam point. The organs become ischaemic from the moment perfusion pressure is inadequate — well before the heart stops. Liver: target ≤ 30 min; kidney: ≤ 60 min; lung: more tolerant (up to 60-90 min) as it is oxygenated passively.
ECMO brain death determination requires special protocol — apnoea test is unreliable. On VA-ECMO, blood gas from the right radial artery reflects native cardiac output (mixed poorly); PaO2/PaCO2 do not correlate with systemic values. The clinical brainstem exam is still valid (pupils, corneal, caloric, gag) IF the patient is not on extracorporeal sedation. Most centres add a confirmatory test (radionuclide or TCD) on ECMO.[10] }
Spinal reflexes and the 'Lazarus sign' occur in ~ 40-50% of brain-dead patients and do NOT indicate brain function. Saposnik's systematic review documented over 150 reports — finger jerks, toe responses, facial myokymia, head turning, and the dramatic Lazarus sign (arms flex, rise, cross midline — sometimes for several seconds, occasionally triggered by hypoxia during apnoea test). Pathophysiology: spinal cord ischaemia-reperfusion + loss of supraspinal inhibition. WARN families and staff before testing so they are not distressed.[8] }
The WHO-ICAO / Madrid Resolution (2011) and Istanbul Declaration (2008) underpin ethical donation practice. They establish: donation must be voluntary and uncoerced; transparency in priority; prohibition of organ trafficking and transplant tourism; separation of treating team and donation team; declaration of conflicts. Examiners may ask about the ethical framework — 'dead donor rule' (no donation until death declared; no causing death to retrieve organs).
Pre-mortem interventions in DCD (heparin, femoral cannulae) are ethically contested — jurisdiction-specific. Australian practice: NO pre-mortem heparin (risk of hastening death in non-brain-dead patient); rapid post-mortem cannulation + in-situ cold perfusion instead. UK / some US centres: pre-mortem heparin with explicit consent. The principle: any intervention before death must not cause harm to the dying patient (so large heparin doses that could cause bleeding / hasten death are NOT given in Australia).
Pulmonary artery catheter / TEE guided fluid management improves organ yield. Goal-directed therapy (PPV, SVV, IVC collapse, SVR, cardiac index) — same principles as any shocked patient. The donor is in distributive shock; the goal is euvolaemia + adequate perfusion WITHOUT pulmonary oedema. Echo at baseline AND after resuscitation — LV recovery may make a 'marginal' heart transplantable.
Ex-vivo machine perfusion has transformed DCD transplantation. Organ Care System (OCS Heart, OCS Lung — TransMedics) and ex-vivo liver / kidney perfusion allow assessment, resuscitation, and transport of DCD organs that would previously have been discarded. DCD HEART transplantation — once considered impossible — is now performed routinely in specialist centres (UK, Australia, US, Spain) with 1-year graft survival comparable to DBD hearts. This is an exam-worthy recent advance.
Two doctors, two examinations — the interval and seniority vary. Australia / NZ (ANZICS): two medical practitioners, each registered ≥ 5 years, neither part of the transplant team; tests conducted independently, ideally with a short interval (no mandated minimum). US: two physicians, exams often separated by an observation period (varies by state / hospital policy — historically 6-24 h in adults, longer in children). UK: two doctors, two sets of tests, interval historically specified. KNOW YOUR LOCAL POLICY.[2] }
Variability of brain death policies between institutions and countries is itself a high-yield topic. Greer's 2016 JAMA Neurol study showed significant inter-hospital variability in observation intervals, number of examiners, apnoea test PaCO2 thresholds (some ≥ 60, some ≥ 55), use of confirmatory tests, and required qualifications. The 2020 World Brain Death Project consensus (JAMA) was created to address this. Examiners may ask: 'Why does practice vary?' — answer: legal/cultural variability, lack of universal protocol, but the SCIENCE is consistent.[2][6] }
The corneal reflex must be tested gently — the donor's corneas may be used for transplantation. Repeated/aggressive corneal stimulation can scar the cornea and make it unsuitable for transplantation. Use a cotton wisp / saline drop, not a swab. This is a frequently missed clinical courtesy that protects tissue viability.

More red flags

Brain death determination — clinical red flags and pitfalls

Core temperature < 36°C → exam INVALID. Rewarm and re-test. Hypothermia is the most common confounder.[1] }
Pentobarbital level not checked → exam INVALID. Send a level if thiopentone/pentobarbital was used for ICP control; wait until < 5 mg/L.[1] }
Apnoea test aborted for hypotension/desaturation → use a confirmatory test, not a 'best guess'.[7] }
Persistent bradycardia during apnoea test is EXPECTED (loss of brainstem vagal tone) — not a reason to abort. Hypotension IS a reason to abort.
Diabetes insipidus with Na > 160 mmol/L → may render liver non-transplantable. Aggressive Na control with D5W + desmopressin/vasopressin.
Positive fluid balance > 3 L → lungs often unusable. Aim for neutral-to-negative balance if lung donation considered.
DCD: functional warm ischaemia from SBP < 50, NOT asystole. Liver ceiling ≤ 30 min.[4] }
No-touch / stand-off period must be OBSERVED, not shortened. 5 minutes minimum (ANZ/UK). Zero cases of autoresuscitation beyond ~ 4-5 min in systematic review.[4] }
Do NOT discuss organ donation at the same time as breaking news of death. Decouple the conversations; trained requestor for donation discussion.[1] }
Family override of registered consent — most Australian ICUs still respect family wishes even if the patient was registered on AODR. Document the conversation.

Donor management red flags — actions that lose organs

Sustained hypotension (MAP < 60) → organ injury. Aggressive resuscitation within minutes of brain death declaration.
Hypothermia < 35°C → coagulopathy + arrhythmia + worsened organ viability. Active rewarming mandatory.
Sustained hypernatraemia > 160 mmol/L → liver graft dysfunction. Treat with D5W + desmopressin.
Untreated diabetes insipidus → hypovolaemic collapse within hours. Recognise early (urine output > 4 mL/kg/h, dilute urine, rising Na).
Over-transfusion / fluid overload → lungs unusable. Use dynamic fluid responsiveness, not fixed boluses.
High-dose noradrenaline alone (no vasopressin) → unnecessary catecholamine load. Add low-dose vasopressin early — it SPARES catecholamines and treats DI.
Failure to escalate to hormone therapy in refractory shock → lost heart/liver. Add T3 + methylprednisolone in unstable donors.

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Key trials and consensus documents

Wijdicks EFM et al, 2010 — AAN Evidence-Based Guideline Update: Determining Brain Death in Adults (Neurology)

Design: Systematic evidence review forming the basis of the American Academy of Neurology guideline update. Findings: No published evidence of neurologic recovery in patients who fulfil AAN brain death criteria. Confirmed the sufficiency of the clinical examination (prerequisites + brainstem areflexia + apnoea test). No evidence that confirmatory tests are routinely needed. Significance: Established the modern standard for adult brain death determination in the US and beyond; basis for most hospital protocols. [1] }

Greer DM et al, 2020 — World Brain Death Project Consensus (JAMA)

Design: International multidisciplinary consensus (AAN, AAP, CNS, SCCM, ESICM, WFSICCM, WFN, ANZICS) — the most comprehensive attempt to harmonise brain death determination globally. Recommendations: Uniform minimum clinical criteria (prerequisites, examination, apnoea test); when ancillary testing is required; special populations (ECMO, paediatric, therapeutic hypothermia). Significance: The 2020 reference document for international practice — cited in most updated hospital policies; promotes standardisation across jurisdictions. [6] }

McKeown DW et al, 2012 — Management of the Heart-Beating Brain-Dead Organ Donor: a Systematic Review and Meta-Analysis (BJA)

Design: Systematic review of donor management interventions. Findings: Hormonal resuscitation (vasopressin + T3/T4 + corticosteroid) — evidence suggests haemodynamic improvement and reduced vasopressor need; outcome benefit for recipients remains controversial. Specific donor-management targets (MAP, Na, fluid balance, lung-protective ventilation) shown to influence organ yield. Significance: Established the evidence base for the structured donor-care bundle used by organ procurement organisations worldwide. [3] }

Manara AR et al, 2023 — Autoresuscitation After Circulatory Arrest: an Updated Systematic Review (CJA)

Design: Updated systematic review examining cases of autoresuscitation (spontaneous return of circulation after cessation of CPR) — directly relevant to the DCD no-touch period. Findings: Across > 600 reported cases, no autoresuscitation occurred beyond ~ 4 min 20 s after cessation of circulation. Supports the 5-minute no-touch period used in DCD as safe. Significance: Provides the empirical basis for the irreversibility criterion in DCD death determination. [4] }

Greer DM et al, 2016 — Variability of Brain Death Policies in the United States (JAMA Neurology)

Design: Survey of brain death determination policies across US hospitals. Findings: Substantial variability in prerequisite thresholds (e.g., apnoea test PaCO2 ≥ 55 vs ≥ 60), number of required examinations, observation intervals, qualifications of examiners, and use of ancillary testing — despite uniform underlying criteria. Significance: Documented the practice variability that motivated the 2020 World Brain Death Project consensus; raised concerns about consistency and medicolegal defensibility. [2] }

Saposnik G et al, 2009 — Spontaneous and Reflex Movements in Brain Death: a Systematic Review (Neurology)

Design: Systematic review of reported motor movements in clinically brain-dead patients. Findings: Movements (finger jerks, toe responses, the Lazarus sign, respiratory-like movements) reported in a substantial minority of brain-dead patients — all attributable to spinal cord reflexes, not brain-mediated activity. Significance: Reassures clinicians and families that spinal reflexes do NOT invalidate a brain death determination; pre-emptive explanation prevents distress. [8] }

Donor management quick-reference bundle

The brain-dead donor care bundle (memorise for exams)

Domain	Target	Intervention
MAP	≥ 65-70 mmHg	Noradrenaline + low-dose vasopressin ± inotrope
Heart rate	60-120 bpm	Treat bradycardia (not atropine-responsive — accept); treat tachyarrhythmia
Core temp	≥ 36°C	Active warming (forced air, warmed fluids)
Serum Na	135-155 mmol/L	D5W + desmopressin / vasopressin for DI
Glucose	6-10 mmol/L	Insulin infusion
CVP / volume	Euvolaemia; neutral balance (negative if lung donor)	Goal-directed fluids; avoid overload
Ventilation	Vt 6-8 mL/kg, PEEP 5-8, plateau < 30, FiO2 minimised	Lung-protective ventilation (especially if lungs donated)
Hormones	Per protocol	Vasopressin 0.01-0.04 U/min + methylprednisolone 15 mg/kg + T3 if unstable
Hb	≥ 70-80 g/L	Transfusion if below
Urine output	0.5-3 mL/kg/h	Treat DI to bring high output down

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The first 60 minutes after brain death declaration — donor resuscitation sequence

CONFIRM brain death legally declared and documented; family informed; donation team notified
SECURE invasive monitoring — arterial line, central line (if not present); ensure reliable access
HAEMODYNAMICS — establish MAP ≥ 65; start noradrenaline; add vasopressin 0.01-0.04 U/min; escalate to adrenaline/inotrope if low cardiac output
FLUID / VOLUME — assess fluid responsiveness; titrate to euvolaemia (avoid overload, especially for lung donors)
ELECTROLYTES — check Na, K, Mg, PO4, glucose every 1-2 h; treat DI (desmopressin if BP stable, vasopressin if not); insulin for glucose
TEMPERATURE — measure core temp; active warming to ≥ 36°C
VENTILATION — switch to lung-protective settings (Vt 6-8 mL/kg, PEEP 5-8); minimise FiO2; consider recruitment
HORMONE PANEL — start methylprednisolone 15 mg/kg; add T3 if haemodynamically unstable
INVESTIGATIONS — baseline echo; CXR; cross-match; serology; cultures; ABG
DOCUMENT — serial haemodynamics, vasopressor doses, echo findings, electrolytes, hormones — communicated to retrieval team

[1]

References

[1]Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology, 2010.PMID 20530327
[2]Greer DM, Wang HH, Lewis AJ, et al. Variability of Brain Death Policies in the United States JAMA Neurol, 2016.PMID 26719912
[3]McKeown DW, Bonser RS, Kellum JA Management of the brain-dead organ donor: a systematic review and meta-analysis Transplantation, 2013.PMID 23545508
[4]Manara AR, Thomas I, Harding R Autoresuscitation after circulatory arrest: an updated systematic review Can J Anaesth, 2023.PMID 37131027
[5]Rostron A, Farmery AD, Laing HE, et al. Pharmacological normalization of circulation after acute brain death Acta Anaesthesiol Scand, 2012.PMID 22651688
[6]Greer DM, Shemie SD, Lewis A, et al. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project JAMA, 2020.PMID 32761206
[7]Russell JA, Epstein LG, Greer DM Apnea testing during brain death assessment: a review of clinical practice and published literature Respir Care, 2013.PMID 22709413
[8]Saposnik G, Bueri JA, Mauriño J, et al. Movements in brain death: a systematic review Can J Neurol Sci, 2009.PMID 19378707
[9]Russell JA, Aleccia E Brain Death/Death by Neurologic Criteria Determination Continuum (Minneap Minn), 2021.PMID 34618768
[10]Nair S, Lingappa L, Rajshekhar V The challenges with brain death determination in adult patients on extracorporeal membrane oxygenation Neurocrit Care, 2011.PMID 21327575

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Brain death (DBD) vs circulatory death (DCD) donation

Feature	DBD (brain death)	DCD (circulatory death)
Definition	Brain death diagnosed	Death after cardiac arrest (withdrawal of life support)
Patient status	Brain DEAD, heart BEATING	Brain intact or damaged, heart STOPPED
Organ quality	BETTER (organs perfused until retrieval)	Variable (warm ischaemia time after arrest)
Timing of death	Time of brain death declaration	Time of cessation of circulation (2-5 min asystole)
Organs available	All (heart, lungs, liver, kidneys, pancreas, intestines)	Most (heart — controversial; lungs, liver, kidneys, pancreas)
Consent	Family (or patient registration)	Family (or patient registration)
ICU management	Donor optimisation (maintain perfusion until retrieval)	Withdrawal in OR/ICU → observe → death → rapid retrieval
Frequency	~60% of donations	~40% (increasing)

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Brain death diagnosis and donation process in ICU

SUSPECT brain death — patient with catastrophic brain injury (TBI, SAH, anoxia), deeply comatose (GCS 3), no brainstem reflexes, on mechanical ventilation
PRECONDITIONS (must be met before testing): (a) Known cause of irreversible brain damage (CT/MRI evidence). (b) Exclusion of REVERSIBLE causes: hypothermia (core temp >35°C), CNS depressant drugs (check levels — barbiturates, benzodiazepines, opioids), metabolic (severe hyponatraemia, hypoglycaemia, hepatic encephalopathy), neuromuscular blockade (train-of-four). (c) Adequate oxygenation + haemodynamics (PaO2 ≥200 for apnoea test, SBP ≥100)
CLINICAL EXAMINATION (two doctors, independently): (a) COMA (GCS 3 — no response to pain). (b) ABSENT brainstem reflexes: pupil reflex (fixed, dilated — no response to light), corneal reflex (no blink on touch), oculocephalic (doll's eyes — absent), oculovestibular (caloric — ice water in ear, no eye movement), gag/cough reflex (absent on suctioning). (c) APNOEA TEST: disconnect ventilator, oxygen via catheter at 6 L/min, PaCO2 must rise to ≥60 mmHg (or ≥20 above baseline) with NO respiratory effort
DOCUMENT — two examinations, two doctors (per jurisdictional requirements). Time of death = time of second examination (or first — varies by jurisdiction). Record all findings
NOTIFY — organ donation team (IMMEDIATELY after first positive examination — if family supportive or patient registered). Family discussion (trained requestor — separate from end-of-life discussion)
DONOR MANAGEMENT (if donation proceeding): maintain MAP ≥65 (noradrenaline, vasopressin), normothermia (36-37°C), normoglycaemia, electrolytes, lung protective ventilation (if lung donation), hormone resuscitation (vasopressin, T3/T4, insulin — if haemodynamically unstable)
ORGAN RETRIEVAL — surgical retrieval in operating theatre. Coordinate with transplant teams

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Exam practice — SAQs

SAQ — Brainstem death testing prerequisites after subarachnoid haemorrhage

10 minutes · 10 marks

[1]

SAQ — Donation after circulatory death (DCD) pathway and warm ischaemia time

10 minutes · 10 marks

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Clinical pearls

High-yield brain death/donation points for CICM/FFICM exam

Brain death = LEGAL death. The patient is DEAD (not dying, not brain-injured). In most jurisdictions: irreversible cessation of ALL brain function (whole brain — cerebrum + brainstem). UK: brainstem death (brainstem alone — but in practice equivalent). DOCUMENT precisely — medico-legal implications. Time of death = time of brain death determination (not when heart stops).[1] }
Apnoea test: PaCO2 ≥60 mmHg with NO respiratory effort. Disconnect from ventilator. Give oxygen via catheter at 6 L/min into trachea (prevent hypoxia during test). Allow PaCO2 to rise (passive — ~3-6 mmHg/min). Target: PaCO2 ≥60 mmHg (or ≥20 above baseline). ABG before and after. OBSERVE for respiratory effort (chest/abdominal movement). If ANY effort → NOT brain dead. If NO effort at PaCO2 ≥60 → POSITIVE (brain dead). CAUTION: arrhythmia/hypotension during test (from hypercapnia/acidosis) → may need to stop.[1] }
Exclusion of REVERSIBLE causes — ESSENTIAL before testing. (1) HYPOTHERMIA: core temp must be >35°C (rewarm if hypothermic — hypothermia mimics brain death). (2) DRUGS: check levels — barbiturates (used for ICP management — wait until level <5 mg/L or 5 half-lives), benzodiazepines (flumazenil challenge or wait), opioids (naloxone challenge or wait), neuromuscular blockers (train-of-four — ensure full recovery). (3) METABOLIC: check Na, glucose, ammonia, LFTs — correct severe derangements first.[1] }
Hormonal resuscitation of brain-dead donor — controversial but used. Brain death → hypothalamic-pituitary axis fails → diabetes insipidus (ADH deficiency), hypothyroidism (TSH deficiency), adrenal insufficiency (ACTH deficiency). HORMONE REPLACEMENT: (a) VASOPRESSIN (1-2 U/h or 0.01-0.04 U/min) — for diabetes insipidus + vasoplegia. (b) T3/T4 (triiodothyronine 4 mcg bolus then 3 mcg/h OR levothyroxine 20 mcg IV) — for cardiovascular stability (controversial — some evidence improves haemodynamics, reduces vasopressor need). (c) INSULIN infusion — for hyperglycaemia + inotropic support (high dose — controversial). (d) CORTICOSTEROIDS (methylprednisolone 15 mg/kg) — for adrenal insufficiency + immunosuppression (reduces donor immune reaction).[5] }
Diabetes insipidus is COMMON in brain-dead donors. ADH deficiency → massive urine output (3-20 L/day) → hypovolaemia, hypernatraemia, hyperosmolarity. MANAGEMENT: (1) DESMOPRESSIN (1-2 mcg IV) or vasopressin infusion (for DI). (2) Replace urine output mL-for-mL with D5W (or oral/hypotonic). (3) Monitor: serum Na (target 135-155), osmolality (target 280-310), urine output. (4) If Na >155: hypotonic fluids (D5W, 0.45% saline).[3] }
Donor lung management — lung-protective ventilation. If lungs being considered for transplantation: maintain with LUNG-PROTECTIVE settings (Vt 6-8 mL/kg, PEEP 5-8, plateau <30, FiO2 as low as possible for SpO2 ≥95). AVOID: tidal volume >10 (barotrauma), high FiO2 (>60 for prolonged — oxygen toxicity). Recruitment manoeuvres (before retrieval — to optimise). Pulmonary toilet (suction — clear secretions). TARGET: PaO2/FiO2 >300 for viable lungs.[3] }
DCD (donation after circulatory death) — increasing. PATIENT: devastating brain injury, not brain dead, family has decided to WITHDRAW life-sustaining treatment. PROCESS: (1) Withdrawal in ICU or OR (extubate, stop vasopressors). (2) Observe for cardiac arrest (may take 30 min to 2h — if >2h: DCD not proceeding — return to ICU for palliative). (3) After arrest: wait 2-5 minutes (ensure irreversible — no auto-resuscitation). (4) Declare death (circulatory). (5) Rapid retrieval (cold perfusion — minimize warm ischaemia time). (6) WARM ISCHAEMIA TIME: time from arrest to cold perfusion (target <30 min for liver, <60 min for kidney).[4] }
Family discussion — SEPARATE from end-of-life. (1) FIRST discussion: end-of-life/brain death diagnosis (by treating team — intensivist, neurosurgeon). Explain: what happened, brain death determination, prognosis (dead). Allow: questions, time, grief. (2) SECOND discussion (separate): organ donation (by TRAINED REQUESTOR — donation specialist, not treating doctor). Discuss: donation process, what organs, consent. AVOID: discussing donation at SAME time as death notification (overwhelming — family can't process both). The 'decoupled' approach is BEST.[1] }
Australia/NZ: organ donation register. Patients can REGISTER their wish to donate (Australian Organ Donor Register — AODR). If registered: family is INFORMED (but in practice, family consent still sought and respected — even if registered, family refusal usually overrides). If NOT registered: family decides. FAMILY CONSENT RATE: ~60% (when asked) — higher if patient was registered. IMPORTANT: discuss donation wishes WITH FAMILY before crisis (so they know your wishes).[1] }
Brain death is a CLINICAL diagnosis (not requiring confirmatory tests in most jurisdictions). CLINICAL EXAMINATION (coma + absent brainstem reflexes + apnoea test) is SUFFICIENT for brain death determination in most countries (US, UK, Australia, NZ, most of Europe). CONFIRMATORY TESTS (NOT routinely required): (a) EEG (isoelectric — flat line — no brain activity). (b) Cerebral angiography (no intracranial blood flow). (c) CT angiography (no intracranial perfusion). (d) Nuclear medicine (no uptake). (e) Transcranial Doppler (no flow). When to USE confirmatory tests: (i) Cannot complete clinical exam (e.g., severe facial trauma — can't do corneal/caloric). (ii) Uncertain (complex case — specialist input). (iii) Jurisdictional requirement (some countries require).[2] }
Potential for SPINAL REFLEXES in brain death. BRAIN-DEAD patients may have SPINAL REFLEXES (not brain-mediated — from spinal cord, which is intact). These can be DISTRESSING to witness (family, staff): (a) Lazarus sign (arms rise and cross — dramatic). (b) Reflex withdrawal (limb moves on pain). (c) Respiratory-like movements (chest/abdominal — from spinal roots, NOT brainstem-driven). IMPORTANT: these are SPINAL (not brain) — do NOT indicate brain function. Explain to family: these are reflexes from the spinal cord — the brain is dead. Don't confuse with brain-mediated responses.[1] }
Preservation time for organs. ORGANS can survive for limited time after retrieval: (a) HEART: 4-6 hours (shortest — most urgent). (b) LUNG: 6-8 hours. (c) LIVER: 12-15 hours. (d) KIDNEY: 24-36 hours (can be on pump — up to 48-72h). (e) PANCREAS: 12-24 hours. LOGISTICS: coordinate with transplant centres (may be in different cities/countries). Cold ischaemia time matters (shorter = better function).[3] }
Ethical considerations. (1) CONFLICT OF INTEREST: treating ICU team (focused on patient/family) vs donation team (focused on organ procurement). SOLUTION: separate teams — donation specialist handles donation discussion; ICU team handles clinical care. (2) DCDD TIMING: when to withdraw? (patient/family decision, not for donation). (3) DONOR OPTIMISATION: interventions (vasopressors, fluids, hormones) performed for DONOR BENEFIT (organ quality) — ethical (benefits recipients — patient is already dead — harm only if discomfort — but brain-dead → no suffering). (4) CONSENT: informed, voluntary, family understanding (not coerced).[1] }
1 organ donor can save up to 8 lives. ORGANS from 1 donor: heart (1), lungs (2 — left + right), liver (1 or split into 2), kidneys (2), pancreas (1), intestines (1). TISSUES (from 1 donor): corneas (2), skin, bone, heart valves, tendons — benefit up to 50+ people. SHORTAGE: demand >> supply (waiting lists years). Every donor matters. ICU clinicians: KEY role in identifying and referring potential donors.[1] }

Red flags

Prognosis

Brain death diagnosis and organ donation (ANZICS data)

[1]

Determination of brain death — preconditions in detail

Preconditions that MUST be met before clinical brain death testing

Domain	Requirement	Threshold / detail
Known cause	Irreversible catastrophic brain injury established	CT/MRI showing catastrophic injury (massive SAH, herniation, diffuse cerebral oedema, anoxic injury). Cause MUST be known — "unexplained coma" is NOT a basis for diagnosing brain death
Core temperature	Normothermia	Core temp ≥36°C (AAN 2010). Hypothermia mimics brain death — rewarm actively (forced warm air, warmed IV fluids, haemofiltration). Below 35°C reflexes are unreliable
Neuromuscular blockade	Fully recovered	Train-of-four ≥4/4 (no fade), OR documented time elapsed ≥ 4 half-lives since last dose. Rocuronium/suxamethonium clearance must be confirmed
CNS depressant drugs	Sub-therapeutic	Check levels: pentobarbital < 5 mg/L; benzodiazepines (flumazenil 0.2 mg challenge if uncertain); opioids (naloxone 0.4 mg challenge). If therapeutic levels likely — wait ≥ 5 half-lives
Severe metabolic/endocrine	Corrected	Na 130-160; glucose 5-15 mmol/L; normal pH/PaCO2; ammonia normal; no severe hepatic/renal encephalopathy
Blood pressure	SBP ≥ 100 mmHg, MAP ≥ 75	Use vasopressors/inotropes to maintain — hypotension abolishes brainstem reflexes. Avoid over-correction (vasopressors may mask mild brain function)
Oxygenation	PaO2 ≥ 200 mmHg	Pre-oxygenase before apnoea test to prevent hypoxia during disconnection
Acid-base	Normal or pre-existing baseline pH	Chronic CO2 retainers — target PaCO2 rise to ≥ 20 mmHg above their (elevated) baseline

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Precondition pitfalls — the diagnosis will be CHALLENGED if any are wrong

Hypothermia after cardiac arrest: must be ≥ 36°C — the most common reason an exam is invalid. Rewarm and re-examine.
Thiopentone/pentobarbital for ICP control: levels can persist for DAYS after cessation. Always send a level — do NOT test until < 5 mg/L.
ECMO patients: PaO2 sampling is unreliable (pre/post oxygenator mixing); venous/arterial PO2 from right radial differs from systemic. Get specialist input.[10] }
Spinal cord injury co-existing (e.g., high cervical trauma) can abolish peripheral reflexes and confound — but brainstem reflexes are still testable.
Paediatric age: preterm and neonatal brains are more resistant — longer observation intervals required (e.g., 2 exams + 24-48 h observation in neonates).

Brainstem reflex examination — component by component

The six cranial nerve brainstem reflexes tested in brain death determination

Reflex	Afferent / efferent nerves	Normal response	Brain-dead (absent)	Notes
Pupillary light	CN II / III (parasympathetic)	Pupils constrict briskly to bright light	Fixed, dilated (4-9 mm); no constriction	Record size; anisocoria acceptable if both unresponsive. Pre-existing iris surgery / atropine can confound
Corneal	CN V / VII (facial)	Blink on corneal touch with cotton wisp	No blink, no globe movement	Touch cornea (not sclera). Avoid trauma — may damage donor corneas for transplantation
Oculocephalic (doll's eyes)	CN III, IV, VI + vestibulospinal	Eyes move OPPOSITE to head turn	Eyes remain fixed mid-position (move WITH head)	CONTRAINDICATED if cervical spine not cleared
Oculovestibular (cold caloric)	CN VIII / III, IV, VI	Slow tonic deviation TOWARDS irrigated ear, then nystagmus away	No eye movement whatsoever	50 mL ice-cold water into each external auditory canal after confirming clear tympanic membrane. Wait 60 s between ears
Gag	CN IX / X	Gag on posterior pharynx stimulation	Absent	Use suction catheter to posterior pharynx
Cough	CN X (vagus)	Cough on tracheal suctioning	Absent	Pass suction catheter to carina and oscillate
Facial grimace (CN V/VII)	CN V / VII	Grimace to deep supraorbital pressure	No facial movement	Tests pontine facial pathways

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Apnoea test — the detailed protocol (PaCO2 must reach ≥ 60 mmHg)

PRE-OXYGENATE — ensure PaO2 ≥ 200 mmHg with FiO2 100% for ≥ 10 min before starting. Prevents hypoxia during disconnection
CONFIRM preconditions — core temp ≥ 36°C, SBP ≥ 100, Na/glucose normal, no residual sedation/NMB. Document on the form
BASELINE ABG — record PaO2, PaCO2, pH. Note the starting PaCO2 (critical for the "rise by ≥ 20" threshold if baseline is elevated)
DISCONNECT from ventilator. Insert an oxygen catheter / T-piece delivering 100% O2 at 6-12 L/min directly into the trachea (apnoeic oxygenation — diffuses across alveoli, prevents desaturation)
OBSERVE — watch chest/abdomen continuously for ANY respiratory effort for 8-15 minutes
IF ANY respiratory effort (chest rise, abdominal contraction, accessory muscle use) → TEST NEGATIVE → patient NOT brain dead. Reconnect immediately. Reconsider diagnosis / seek confirmatory test
IF NO effort — repeat ABG at 8 min. If PaCO2 ≥ 60 mmHg (or ≥ 20 mmHg above baseline) AND pH < 7.30 → TEST POSITIVE (consistent with brain death)
IF haemodynamic instability (severe hypotension, arrhythmia, desaturation) → ABORT the test, reconnect, treat, and re-attempt later (or proceed to confirmatory test). The test must NEVER cause harm to the donor organs
DOCUMENT — exact times, baseline/final ABG values, presence/absence of effort, observer names

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Apnoea test — common errors and red flags

The test is POSITIVE only if PaCO2 ≥ 60 mmHg (or rises ≥ 20 from baseline) with NO respiratory effort — both components required.[7] }
Hypoxia during disconnection is the #1 reason tests are aborted — pre-oxygenate and use a tracheal oxygen catheter, not just room air.
Obese/restrictive patients desaturate faster — may need continuous positive airway pressure via T-piece (CPAP + apnoeic O2).
Severe COPD / chronic CO2 retainer — baseline PaCO2 may already be 60; use the "≥ 20 mmHg rise from baseline" criterion.
** NEVER leave the bedside during the test** — observer must watch for any chest movement continuously; movement can be subtle.
Refractory hypotension during the test → abort and use a confirmatory test instead (e.g., radionuclide perfusion) rather than risk organ damage.

Confirmatory (ancillary) tests

Confirmatory tests for brain death — when clinical exam is incomplete

Test	What it shows	Sensitivity	Specificity	Practical notes
Cerebral angiography (4-vessel)	Gold standard — no intracranial blood flow above the petrous segment	Very high	Very high	Invasive, requires transfer to angiography suite — impractical in unstable donor. External carotid flow preserved
CT angiography (CTA)	No intracranial arterial enhancement (suspended filling of cortical vessels)	~85-95%	~95-100%	Fast, widely available. Protocols vary — "7-vessel" and "venous phase" techniques. False positives in high ICP with delayed circulation
CT perfusion	No cerebral blood flow	Good	Good	Adjunct to CTA; helpful when CTA equivocal
Radionuclide scintigraphy (HMPAO SPECT)	No cerebral / cerebellar / brainstem perfusion / uptake	High	High	Portable gamma camera at bedside. Distinguishes scalp/skull flow (preserved) from cerebral (absent). Useful in ECMO/therapeutic hypothermia
EEG	Isoelectric (electrocerebral silence — flat line ≥ 30 min, ≥ 8 electrodes, ≥ 30 µV/mm sensitivity)	High	Lower (false positives)	Detects CORTICAL activity only — does NOT confirm brainstem death. Deep sedation/hypothermia cause false-positive "flat line". Largely superseded in US/Australia; still used in some jurisdictions
Transcranial Doppler (TCD)	Oscillating / to-and-fro flow OR systolic spikes with no diastolic flow (high-resistance pattern)	~90-99%	~98-100%	Bedside, repeatable, non-invasive. ~10% of patients have no temporal acoustic window. Requires experienced operator

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When to use a confirmatory test (rather than clinical exam alone)

Inability to complete one or more components of the clinical exam — e.g., severe facial/orbital trauma (cannot test corneal/caloric), otic disruption (cannot caloric), unstable cervical spine (cannot oculocephalic)
Chronic severe lung disease making the apnoea test unsafe (rapid desaturation, severe acidosis)
Inability to exclude confounders completely — e.g., prolonged sedative clearance in renal failure, concurrent therapeutic hypothermia protocol
ECMO — apnoea test PaCO2 measurement unreliable; clinical exam possible but confirmatory test advised
Paediatric / neonatal cases — some jurisdictions mandate ancillary testing, especially in neonates
Medico-legal / jurisdictional requirement — several countries (e.g., some European nations, parts of Asia) REQUIRE an ancillary test for legal documentation
Family or staff disagreement — to provide objective corroborative data (though legal determination remains clinical)

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EEG vs cerebral angiography vs TCD — choosing the ancillary test

Feature	EEG	Cerebral angiography	TCD
What it confirms	Cortical electrical activity	Cerebral blood flow (anatomical gold standard)	Cerebral blood flow (physiological)
Detects brainstem death?	NO — cortex only	YES — covers all territories	YES — anterior + posterior circulation
Bedside?	Yes	No (angiography suite)	Yes
Sensitivity to sedation/hypothermia	HIGH — causes false-positive isoelectric trace	None	Minimal
Time	30 min minimum	1-2 h + transfer	15-30 min
Current preference	Falling out of favour	When definitive flow documentation needed	Increasing — repeatable, bedside

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DBD vs DCD pathways in detail

Controlled DCD vs uncontrolled DCD vs DBD

Feature	DBD (brain death)	Controlled DCD (cDCD)	Uncontrolled DCD (uDCD)
Setting	ICU, ventilated patient declared brain dead	Planned withdrawal of life-sustaining therapy (WLST) in ICU/OR	Failed resuscitation in ED/ICU/community (unexpected cardiac arrest)
Pre-mortem planning	None (death by neurologic criteria)	Extensive — family discussion, timing, location, retrieval team on standby	None — sudden death; rapid response protocol (preservation within minutes)
Circulation at organ retrieval	Heart BEATING — perfused organs	Heart STOPPED after planned withdrawal + stand-off	Heart STOPPED after failed CPR
Warm ischaemia time	None	Defined — measured from SBP < 50 to cold perfusion (target < 30 min liver, < 60 min kidney)	Long, uncontrolled — often limits usable organs
Organs typically transplantable	All — heart, lungs, liver, kidneys, pancreas, intestine	Kidneys, liver, lungs, pancreas; HEART now possible with ex-vivo perfusion	Mostly kidneys (most ischaemia-tolerant); rarely liver
Frequency (ANZ)	~ 60% of deceased donors	~ 40% (rising rapidly)	Rare / regional only

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Controlled DCD pathway — step-by-step (the cDCD process after WLST decision)

DECISION to withdraw life-sustaining therapy (WLST) — made independently by treating team + family, on best-interest / futility grounds. Donation is NEVER a reason to withdraw
ASSESS DCD ELIGIBILITY — donor team evaluation: age, comorbidities, organ function, projected warm ischaemia time. Consent for donation obtained (separate from WLST decision)
PRE-MORTEM PLANNING / STAND-BY — coordinate timing between ICU, OR, retrieval surgeons, anaesthetics, transplant teams. Determine location of withdrawal (ICU vs OR — affects warm ischaemia time). Plan cannulation strategy (in-situ cold perfusion via aorta)
PRE-EMPTIVE PREPARATION (after WLST decision, BEFORE withdrawal) — may include: heparin administration (controversial — not universal), arterial/venous lines for rapid cannulation, family time
WITHDRAWAL OF LIFE-SUSTAINING THERAPY — extubation (or terminal wean), cessation of vasopressors/inotropes, comfort measures only. Family may be present
OBSERVATION PERIOD — monitor for circulatory arrest. If asystole / absence of circulation < 60 min from withdrawal → proceed. If > 60-120 min (centre threshold) → DCD abandoned, return to comfort care (organs would sustain excessive warm ischaemia)
DEATH DECLARATION — after confirmation of absent circulation (no pulse, no heart sounds, asystole on monitor) and a mandatory NO-TOUCH / STAND-OFF PERIOD (5 minutes in Australia/UK; 2-5 minutes US — varies by jurisdiction) to rule out autoresuscitation[4] }
RAPID RETRIEVAL + COLD PERFUSION — immediate transfer to OR (if withdrawn in ICU) or in-situ cannulation. Cold preservation solution (UW / HTK) flushed via aorta. Document functional warm ischaemia time (from SBP < 50 to perfusion)
EX-VIVO PERFUSION (modern practice) — DCD hearts/lungs now resuscitated on ex-vivo machine perfusion (Organ Care System / TransMedics) before transplantation — has enabled DCD heart transplantation

Time-of-death determination: DBD vs DCD

Aspect	DBD	DCD
Time of death	Time the second brain death examination confirms death (or first, jurisdiction-dependent)	Time of completion of the no-touch observation period after circulatory arrest
Definition of death applied	Neurologic criteria (irreversible cessation of all brain function)	Circulatory criteria (irreversible cessation of circulation)
Documentation	Two clinician signatures, two examinations, full reflex + apnoea record	Single clinician confirms circulatory arrest; documents no-touch period
Permanence	Established by brain death examination	Established by no-touch period (5 min) + absence of autoresuscitation

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Donor management — physiology of the brain-dead donor

Physiological derangements following brain death — the catecholamine storm and after

Phase	Time	Pathophysiology	Clinical consequence
Catecholamine storm (autonomic crisis)	0-30 min post herniation	Massive sympathetic outflow → noradrenaline/adrenaline surge; then abrupt vagal (brainstem) shutdown	Severe hypertension, tachyarrhythmias, vasoconstriction → myocardial injury, pulmonary oedema, capillary leak. Then sudden hypotension
Vasoplegic shock	30 min onward	Loss of sympathetic vasomotor tone + myocardial depression	Hypotension, low SVR, high cardiac output (distributive shock). Often requires multiple vasopressors
Endocrine failure	1-2 h onward	Hypothalamic-pituitary axis ceases — ADH, TSH, ACTH deficiency	Diabetes insipidus (hypernatraemia, hypovolaemia), low T3/T4, low cortisol
Coagulopathy	Variable	Release of tissue factor, hypothermia, dilution	DIC-like picture, bleeding at retrieval
Hypothermia	Universal	Hypothalamic thermostat loss — poikilothermia	Core temp drifts to ambient; worsens coagulopathy and arrhythmia
Metabolic	Progressive	Hyperglycaemia (insulin resistance + deficiency), acidosis, hyperkalaemia	Multi-organ cellular dysfunction

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Haemodynamic donor management

Haemodynamic targets in the brain-dead donor (organ-protective)

MAP ≥ 65 mmHg (70 mmHg preferred) — noradrenaline first-line for vasoplegia; vasopressin SPARING (reduces catecholamine dose, treats DI)
SBP ≥ 100 mmHg — avoid hypotension (organ hypoperfusion) AND hypertension (worsens neurogenic pulmonary oedema)
Heart rate 60-120 bpm — bradycardia suggests high vagal tone / AV block; tachycardia worsens myocardial O2 demand. Persistent bradycardia unresponsive to atropine is itself a sign of brainstem death (vagal nuclei destroyed)
Cardiac index ≥ 2.5 L/min/m² — if low, add inotrope (adrenaline, milrinone, dobutamine)
CVP / fluid balance — euvolaemia; titrate to CVP 6-10 mmHg or dynamic indices (PPV, SVV, IVC variability). AVOID fluid overload — damages lungs (degrades PaO2/FiO2) and heart
Echocardiography — baseline LV function; recheck after resuscitation. LV dysfunction may recover with hormone therapy. LVEF < 45% after optimisation → heart often unsuitable for transplantation
Arterial line + central access — continuous BP, frequent sampling. Pulmonary artery catheter / TEE in unstable donors

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Vasopressor selection in the brain-dead donor

Agent	Role	Rationale	Cautions
Noradrenaline	First-line vasopressor	α-agonist restores SVR in vasoplegia	High doses > 0.5 mcg/kg/min may worsen organ microcirculation — review
Vasopressin	SPARING + DI treatment	Low-dose (0.01-0.04 U/min) restores vascular smooth muscle tone, treats ADH deficiency, halves catecholamine requirements	Avoid overshoot hypertension; reduces need for noradrenaline
Adrenaline	Inotrope + vasopressor	If MAP low with bradycardia / myocardial depression	Lactic acidosis at high doses (worsens organ viability); use cautiously
Methylprednisolone	Adjunct (15 mg/kg)	Treats relative adrenal insufficiency; downregulates donor immune activation; thought to improve lung / liver yield	Give early once brain death declared

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Electrolyte, metabolic and temperature management

Electrolyte and metabolic targets in the brain-dead donor

Parameter	Target	Common derangement	Management
Serum Na⁺	135-155 mmol/L	Hypernatraemia (DI — water loss)	D5W / 0.45% saline; desmopressin / vasopressin for DI. AVOID Na > 160 — associated with worse liver graft function
Serum K⁺	3.5-5.5 mmol/L	Hypokalaemia (DI urinary losses, alkalosis) — OR hyperkalaemia (acidosis, cell leak)	Replace carefully; correct acidosis first; avoid over-correction (arrhythmia)
Serum Mg²⁺ / PO₄²⁻	Normal	Hypomagnesaemia / hypophosphataemia common	Replace — prevents arrhythmia, respiratory muscle weakness
Glucose	6-10 mmol/L	Hyperglycaemia (insulin resistance + deficiency)	Insulin infusion titrated; conventional (not tight — risk of hypoglycaemia)
pH	7.35-7.45	Metabolic acidosis (shock, renal failure)	Treat cause; bicarbonate if pH < 7.20 with metabolic acidosis
Hb	≥ 70-80 g/L	Anaemia (haemodilution, bleeding)	Transfuse to maintain O2 delivery; balance with risk of TRALI
Core temp	≥ 36°C	Hypothermia (poikilothermia)	Forced warm air, warmed IV fluids, haemofiltration circuit. Hypothermia worsens coagulopathy + arrhythmia

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Hormone replacement therapy — vasopressin, T3/T4, corticosteroids

Hormone replacement in the brain-dead donor — what, why, dosing, evidence

Hormone	Deficiency it treats	Typical dose	Evidence	When to use
Vasopressin (low-dose)	ADH deficiency (DI) + catecholamine-sparing in vasoplegia	0.01-0.04 U/min (1-2.4 U/h) continuous	Strong — reduces noradrenaline requirement, treats DI, well-tolerated	Standard — almost all haemodynamically unstable donors
Desmopressin (DDAVP)	ADH deficiency (DI) when vasoplegia absent	1-4 mcg IV bolus (every 6-12 h)	Effective for DI alone	When DI present but BP stable (no need for vasopressor effect)
Triiodothyronine (T3) / Levothyroxine (T4)	Low-T3 syndrome; cardiovascular instability	T3: 4 mcg bolus then 3 mcg/h OR 20 mcg bolus then 10 mcg/h × 24 h. T4: 20 mcg bolus then 10 mcg/h	CONTROVERSIAL — meta-analyses conflicting; landmark randomised UNOS study showed NO survival benefit for heart recipients from hormone-treated donors, but haemodynamics often improve	Use selectively — haemodynamically unstable donors requiring escalating vasopressors (especially for heart/liver procurement)
Insulin	Hyperglycaemia + (high-dose) inotropic support	Glucose control: 1-4 U/h titrated. High-dose inotropic: controversial	Standard for glucose control; high-dose protocol unproven	Glucose control routine; high-dose rarely used
Methylprednisolone	Relative adrenal insufficiency + dampen donor immune activation	15 mg/kg IV (1 g typical) every 24 h	Reasonable evidence — reduces inflammatory cytokines, may improve lung / liver yield	Standard once brain death declared, especially for lung procurement

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Hormonal resuscitation protocol (haemodynamically unstable brain-dead donor)

CONFIRM brain death declared and donation proceeding — do NOT initiate hormone protocol on a patient who is not yet legally dead
VASOPRESSIN 0.01-0.04 U/min IV continuous — first-line. Aim for urine output 0.5-3 mL/kg/h (treats DI AND vasoplegia). Titrate to MAP and to Na⁺ normalisation
METHYLPREDNISOLONE 15 mg/kg IV (typically 1 g) — give as a single bolus; repeat q24h. Reduces inflammatory cascade, supports adrenal insufficiency
T3 (liothyronine) 4 mcg IV bolus then 3 mcg/h infusion — IF haemodynamically unstable on escalating catecholamines OR poor LV function on echo. Reassess at 2-4 h
INSULIN infusion titrated to glucose 6-10 mmol/L — hyperglycaemia is universal. Some protocols use high-dose insulin (1 U/kg/h) as inotrope — controversial; not routine
REASSESS haemodynamics every 1-2 h — typically vasopressor requirements FALL after 2-6 h of combined therapy. Recheck echocardiography — LV function may recover sufficiently for heart donation
DOCUMENT — record baseline and serial vasopressor doses, echo findings, hormone doses — required for organ acceptance decisions by transplant teams

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Additional clinical pearls — advanced

Brain death and donation — advanced exam pearls (CICM/FFICM/EDIC)

The 'catecholamine storm' is a real phenomenon — and it injures organs. The 15-30 min after herniation sees massive sympathetic surge (hypertension up to 300 mmHg, tachyarrhythmias, intense vasoconstriction) followed by abrupt brainstem shutdown and vasoplegia. The surge causes myocardial injury (subendocardial necrosis), neurogenic pulmonary oedema, and capillary leak. Donor hearts from donors with a stormy course have worse outcomes — early recognition and aggressive donor resuscitation mitigate this.[5] }
The AAN 2010 guideline formalised 3 prerequisites, 4 examination domains, 1 apnoea test. Memorise the structure: PREREQUISITES (cause known; no confounders) → establish coma (GCS 3, no cerebral motor response to pain) → brainstem AREflexia (pupils, corneal, oculocephalic, oculovestibular, gag, cough) → APNOEA test (PaCO2 ≥ 60 mmHg or ≥ 20 mmHg rise from baseline). All components must be documented for every examination.[1] }
UK uses 'brainstem death' (Code of Practice 2008, updated); US / Australia / NZ use 'whole brain death' — but the CLINICAL examination is identical. The conceptual difference (brainstem alone vs whole brain) is philosophical; in practice the bedside tests are the same. The World Brain Death Project 2020 consensus (JAMA) sought to harmonise terminology — uses 'death by neurologic criteria (DNC)'.[6] }
Persistent bradycardia unresponsive to atropine is BRAINSTEM death (Cushing's reflex variant). The vagal nuclei (nucleus ambiguus) are destroyed. Normal hearts with intact vagal input accelerate with atropine; brain-dead donors do not. This is occasionally used as an adjunctive sign but is NOT part of the formal protocol.
Diabetes insipidus — the SINGLE most common endocrine complication (>80% of donors). ADH deficiency → polyuria (3-20 L/day), hypernatraemia, hyperosmolarity, hypovolaemia. Untreated → rapid cardiovascular collapse. FIRST-LINE: vasopressin infusion (treats DI AND vasoplegia). DESMOPRESSIN if BP stable. Replace urine output mL-for-mL with D5W. Target Na 135-155 — sustained Na > 160 worsens liver graft function.[3] }
Hypernatraemia at retrieval is associated with worse liver graft outcomes. Multiple studies show Na > 155-160 mmol/L in the donor linked to early graft dysfunction and primary non-function. Aggressive Na control (D5W, desmopressin) is a KEY modifiable donor management target, especially for liver donors.
Donor lung optimisation is the single most impactful intervention — lungs are the organ most often lost. Only ~ 15-25% of multi-organ donors yield transplantable lungs (vs > 80% for kidneys). LUNG-PROTECTIVE ventilation (Vt 6-8 mL/kg PBW, PEEP 5-8, plateau < 30, FiO2 minimised), alveolar recruitment manoeuvres before retrieval, pulmonary toilet, AVOID fluid overload (target neutral-to-negative fluid balance — every 1 L positive reduces PaO2/FiO2 and lung usability).[3] }
The no-touch / stand-off period in DCD: 5 minutes (Australia, UK, Canada); 2-5 minutes (US states vary). This is the time after cessation of circulation during which NO intervention occurs, to ensure PERMANENT (not just absent) circulation — i.e., autoresuscitation will not occur. The 2023 systematic review (Manara et al) found zero cases of autoresuscitation beyond 4 min 20 s in over 600 cases — supporting 5 min as safe and conservative.[4] }
'Functional' warm ischaemia time in DCD is measured from SBP < 50 mmHg (or SpO2 < 70%), NOT from asystole. This is a high-yield exam point. The organs become ischaemic from the moment perfusion pressure is inadequate — well before the heart stops. Liver: target ≤ 30 min; kidney: ≤ 60 min; lung: more tolerant (up to 60-90 min) as it is oxygenated passively.
ECMO brain death determination requires special protocol — apnoea test is unreliable. On VA-ECMO, blood gas from the right radial artery reflects native cardiac output (mixed poorly); PaO2/PaCO2 do not correlate with systemic values. The clinical brainstem exam is still valid (pupils, corneal, caloric, gag) IF the patient is not on extracorporeal sedation. Most centres add a confirmatory test (radionuclide or TCD) on ECMO.[10] }
Spinal reflexes and the 'Lazarus sign' occur in ~ 40-50% of brain-dead patients and do NOT indicate brain function. Saposnik's systematic review documented over 150 reports — finger jerks, toe responses, facial myokymia, head turning, and the dramatic Lazarus sign (arms flex, rise, cross midline — sometimes for several seconds, occasionally triggered by hypoxia during apnoea test). Pathophysiology: spinal cord ischaemia-reperfusion + loss of supraspinal inhibition. WARN families and staff before testing so they are not distressed.[8] }
The WHO-ICAO / Madrid Resolution (2011) and Istanbul Declaration (2008) underpin ethical donation practice. They establish: donation must be voluntary and uncoerced; transparency in priority; prohibition of organ trafficking and transplant tourism; separation of treating team and donation team; declaration of conflicts. Examiners may ask about the ethical framework — 'dead donor rule' (no donation until death declared; no causing death to retrieve organs).
Pre-mortem interventions in DCD (heparin, femoral cannulae) are ethically contested — jurisdiction-specific. Australian practice: NO pre-mortem heparin (risk of hastening death in non-brain-dead patient); rapid post-mortem cannulation + in-situ cold perfusion instead. UK / some US centres: pre-mortem heparin with explicit consent. The principle: any intervention before death must not cause harm to the dying patient (so large heparin doses that could cause bleeding / hasten death are NOT given in Australia).
Pulmonary artery catheter / TEE guided fluid management improves organ yield. Goal-directed therapy (PPV, SVV, IVC collapse, SVR, cardiac index) — same principles as any shocked patient. The donor is in distributive shock; the goal is euvolaemia + adequate perfusion WITHOUT pulmonary oedema. Echo at baseline AND after resuscitation — LV recovery may make a 'marginal' heart transplantable.
Ex-vivo machine perfusion has transformed DCD transplantation. Organ Care System (OCS Heart, OCS Lung — TransMedics) and ex-vivo liver / kidney perfusion allow assessment, resuscitation, and transport of DCD organs that would previously have been discarded. DCD HEART transplantation — once considered impossible — is now performed routinely in specialist centres (UK, Australia, US, Spain) with 1-year graft survival comparable to DBD hearts. This is an exam-worthy recent advance.
Two doctors, two examinations — the interval and seniority vary. Australia / NZ (ANZICS): two medical practitioners, each registered ≥ 5 years, neither part of the transplant team; tests conducted independently, ideally with a short interval (no mandated minimum). US: two physicians, exams often separated by an observation period (varies by state / hospital policy — historically 6-24 h in adults, longer in children). UK: two doctors, two sets of tests, interval historically specified. KNOW YOUR LOCAL POLICY.[2] }
Variability of brain death policies between institutions and countries is itself a high-yield topic. Greer's 2016 JAMA Neurol study showed significant inter-hospital variability in observation intervals, number of examiners, apnoea test PaCO2 thresholds (some ≥ 60, some ≥ 55), use of confirmatory tests, and required qualifications. The 2020 World Brain Death Project consensus (JAMA) was created to address this. Examiners may ask: 'Why does practice vary?' — answer: legal/cultural variability, lack of universal protocol, but the SCIENCE is consistent.[2][6] }
The corneal reflex must be tested gently — the donor's corneas may be used for transplantation. Repeated/aggressive corneal stimulation can scar the cornea and make it unsuitable for transplantation. Use a cotton wisp / saline drop, not a swab. This is a frequently missed clinical courtesy that protects tissue viability.

More red flags

Brain death determination — clinical red flags and pitfalls

Core temperature < 36°C → exam INVALID. Rewarm and re-test. Hypothermia is the most common confounder.[1] }
Pentobarbital level not checked → exam INVALID. Send a level if thiopentone/pentobarbital was used for ICP control; wait until < 5 mg/L.[1] }
Apnoea test aborted for hypotension/desaturation → use a confirmatory test, not a 'best guess'.[7] }
Persistent bradycardia during apnoea test is EXPECTED (loss of brainstem vagal tone) — not a reason to abort. Hypotension IS a reason to abort.
Diabetes insipidus with Na > 160 mmol/L → may render liver non-transplantable. Aggressive Na control with D5W + desmopressin/vasopressin.
Positive fluid balance > 3 L → lungs often unusable. Aim for neutral-to-negative balance if lung donation considered.
DCD: functional warm ischaemia from SBP < 50, NOT asystole. Liver ceiling ≤ 30 min.[4] }
No-touch / stand-off period must be OBSERVED, not shortened. 5 minutes minimum (ANZ/UK). Zero cases of autoresuscitation beyond ~ 4-5 min in systematic review.[4] }
Do NOT discuss organ donation at the same time as breaking news of death. Decouple the conversations; trained requestor for donation discussion.[1] }
Family override of registered consent — most Australian ICUs still respect family wishes even if the patient was registered on AODR. Document the conversation.

Donor management red flags — actions that lose organs

Sustained hypotension (MAP < 60) → organ injury. Aggressive resuscitation within minutes of brain death declaration.
Hypothermia < 35°C → coagulopathy + arrhythmia + worsened organ viability. Active rewarming mandatory.
Sustained hypernatraemia > 160 mmol/L → liver graft dysfunction. Treat with D5W + desmopressin.
Untreated diabetes insipidus → hypovolaemic collapse within hours. Recognise early (urine output > 4 mL/kg/h, dilute urine, rising Na).
Over-transfusion / fluid overload → lungs unusable. Use dynamic fluid responsiveness, not fixed boluses.
High-dose noradrenaline alone (no vasopressin) → unnecessary catecholamine load. Add low-dose vasopressin early — it SPARES catecholamines and treats DI.
Failure to escalate to hormone therapy in refractory shock → lost heart/liver. Add T3 + methylprednisolone in unstable donors.

[1]

Key trials and consensus documents

Wijdicks EFM et al, 2010 — AAN Evidence-Based Guideline Update: Determining Brain Death in Adults (Neurology)

Greer DM et al, 2020 — World Brain Death Project Consensus (JAMA)

McKeown DW et al, 2012 — Management of the Heart-Beating Brain-Dead Organ Donor: a Systematic Review and Meta-Analysis (BJA)

Manara AR et al, 2023 — Autoresuscitation After Circulatory Arrest: an Updated Systematic Review (CJA)

Greer DM et al, 2016 — Variability of Brain Death Policies in the United States (JAMA Neurology)

Saposnik G et al, 2009 — Spontaneous and Reflex Movements in Brain Death: a Systematic Review (Neurology)

Donor management quick-reference bundle

The brain-dead donor care bundle (memorise for exams)

Domain	Target	Intervention
MAP	≥ 65-70 mmHg	Noradrenaline + low-dose vasopressin ± inotrope
Heart rate	60-120 bpm	Treat bradycardia (not atropine-responsive — accept); treat tachyarrhythmia
Core temp	≥ 36°C	Active warming (forced air, warmed fluids)
Serum Na	135-155 mmol/L	D5W + desmopressin / vasopressin for DI
Glucose	6-10 mmol/L	Insulin infusion
CVP / volume	Euvolaemia; neutral balance (negative if lung donor)	Goal-directed fluids; avoid overload
Ventilation	Vt 6-8 mL/kg, PEEP 5-8, plateau < 30, FiO2 minimised	Lung-protective ventilation (especially if lungs donated)
Hormones	Per protocol	Vasopressin 0.01-0.04 U/min + methylprednisolone 15 mg/kg + T3 if unstable
Hb	≥ 70-80 g/L	Transfusion if below
Urine output	0.5-3 mL/kg/h	Treat DI to bring high output down

[1]

The first 60 minutes after brain death declaration — donor resuscitation sequence

CONFIRM brain death legally declared and documented; family informed; donation team notified
SECURE invasive monitoring — arterial line, central line (if not present); ensure reliable access
HAEMODYNAMICS — establish MAP ≥ 65; start noradrenaline; add vasopressin 0.01-0.04 U/min; escalate to adrenaline/inotrope if low cardiac output
FLUID / VOLUME — assess fluid responsiveness; titrate to euvolaemia (avoid overload, especially for lung donors)
ELECTROLYTES — check Na, K, Mg, PO4, glucose every 1-2 h; treat DI (desmopressin if BP stable, vasopressin if not); insulin for glucose
TEMPERATURE — measure core temp; active warming to ≥ 36°C
VENTILATION — switch to lung-protective settings (Vt 6-8 mL/kg, PEEP 5-8); minimise FiO2; consider recruitment
HORMONE PANEL — start methylprednisolone 15 mg/kg; add T3 if haemodynamically unstable
INVESTIGATIONS — baseline echo; CXR; cross-match; serology; cultures; ABG
DOCUMENT — serial haemodynamics, vasopressor doses, echo findings, electrolytes, hormones — communicated to retrieval team

[1]

References

[1]Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology, 2010.PMID 20530327
[2]Greer DM, Wang HH, Lewis AJ, et al. Variability of Brain Death Policies in the United States JAMA Neurol, 2016.PMID 26719912
[3]McKeown DW, Bonser RS, Kellum JA Management of the brain-dead organ donor: a systematic review and meta-analysis Transplantation, 2013.PMID 23545508
[4]Manara AR, Thomas I, Harding R Autoresuscitation after circulatory arrest: an updated systematic review Can J Anaesth, 2023.PMID 37131027
[5]Rostron A, Farmery AD, Laing HE, et al. Pharmacological normalization of circulation after acute brain death Acta Anaesthesiol Scand, 2012.PMID 22651688
[6]Greer DM, Shemie SD, Lewis A, et al. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project JAMA, 2020.PMID 32761206
[7]Russell JA, Epstein LG, Greer DM Apnea testing during brain death assessment: a review of clinical practice and published literature Respir Care, 2013.PMID 22709413
[8]Saposnik G, Bueri JA, Mauriño J, et al. Movements in brain death: a systematic review Can J Neurol Sci, 2009.PMID 19378707
[9]Russell JA, Aleccia E Brain Death/Death by Neurologic Criteria Determination Continuum (Minneap Minn), 2021.PMID 34618768
[10]Nair S, Lingappa L, Rajshekhar V The challenges with brain death determination in adult patients on extracorporeal membrane oxygenation Neurocrit Care, 2011.PMID 21327575