Brain death definition

  • brain death (BD) is defined as the irreversible loss of all brain functions (including the brainstem), regardless of the continued function of the cardiovascular system and other organs


  • traumatic brain injury (TBI)
  • stroke
  • global cerebral hypoxia/anoxia (post-CPR conditions)
  • brain tumors
  • inflammatory diseases (vasculitis, encephalitis, etc.)
  • intoxication (methanol, opioids, carbon monoxide, etc.)
  • metabolic causes (hypoglycemia, Reye’s syndrome, etc.)
These conditions lead to intracranial hypertension (with brain herniation) and a decrease and subsequent disappearance of cerebral perfusion. This results in necrosis of brain cells and loss of function.

Diagnostic evaluation

Legal aspects of brain death diagnosis and organ donation vary in different countries (personnel specialization requirements, permitted confirmatory methods, etc.). The protocol approved by the local authorities must be followed.

  • the diagnosis of brain death is generally based on the following:

Clinical signs of brain death

Deep non-reactive coma (GCS 3)
Absent cortical functions
  • absence of spontaneous movements
  • loss of motor and vocal responses to visual, auditory, and pain stimuli in the area innervated by the trigeminal nerve
Absent brainstem functions
  • cessation of brainstem reflexes 
  • respiratory arrest → positive apnea test
  • absence of abnormal postural responses such as decorticate Decorticate posture or decerebrate Decerebrate posture  posturing or their combinations evoked by pain stimuli
  • absence of spontaneous eye movements or abnormal eye position (usually only slightly divergent eyeballs can be seen)
  • non-reactive moderately dilated or mydriatic pupils (may remain miotic 1-2 mm in patients with myasthenia and glaucoma)
  • proprioceptive reflexes or pyramidal extensor responses (of spinal origin) may remain intact

Following items are usually part of the clinical brain death protocol and should ALL be negative:

  • brainstem reflexes
  • motoric response to pain stimuli in the area innervated by the trigeminal nerve
  • cough reflex (provoked by deep tracheobronchial suction)
  • caloric vestibulo-ocular reflex
  • oculocardiac reflex (OCR – trigeminovagal reflex)- tests the integrity of the caudal brainstem – the eyeball is compressed for 10-20 sec; the test is positive if pulse drops by more than 20% (8-10)
    • most commonly, the reflex induces bradycardia, though it may cause arrhythmias and, in extreme cases, cardiac arrest
  • atropine test
    • administration of atropine 1mg IV does not cause tachycardia in brain death
    • atropine test is not a standard part of the protocol for diagnosing brain death 
  • the patient must not be pharmacologically depressed and relaxed to a degree that inhibits brainstem reflexes
  • these activities may be preserved:
    • vasomotor activity maintaining blood pressure without vasopressor support (cervical sympathetic activity is probably sufficient to maintain it temporarily)
    • osmoregulation (e.g., diabetes insipidus is not a prerequisite for brain death; it is absent in up to 20% of cases)
  • repeated tests show the irreversibility of the clinical condition (interval > 4 hours)

Known cause of brain damage

  • there must be no doubt about the cause of brain death and the irreversibility of brain damage
    • it may not be an etiological diagnosis (e.g., in the case of extensive intracranial hemorrhage, the exact etiology may not be known)
    • death may be caused by a primary structural brain lesion or a secondary metabolic or hypoxic lesion
  • exclude all potentially reversible causes:
    • the effects of drugs altering the central nervous system function (sedatives, hypnotics, and opioids)
    • the effects of myorelaxants or other agents that alter effective ventilation
      • the metabolism of sedatives and myorelaxants may be significantly altered in critically ill patients, and their effects may persist for many hours after the last administration
    • intoxication (a combination of alcohol and organic brain lesions is common)
    • mydriatic agents may cause non-reactive mydriasis
    • hypothermia
      • may reduce the metabolic demands of brain cells and lead to a clinical image of “brain death”
      • body temperature above 32°C is required to establish brain death
    • severe metabolic disorder

Proof of irreversibility

  • confirmation of the permanent cerebral circulatory arrest
    • DSA
    • TCD/TCCD
    • CTA
    • perfusion scintigraphy
  • functional testing (proof of absence of brain activity)
    • evoked potentials (BAEP, SSEP)
    • EEG
Digital subtraction angiography (DSA)
  • perform angiography with MAP > 60 mmHg
  • technical aspects of DSA
    • injection of contrast agent from the aortic arc – 0.5 mL/kg (minimum of 30 mg) at a rate of 15-25 mL/s
    • selective angiogram of carotid arteries and one vertebral artery (CCA 5-8 mL at 4-8 mL/s, VA 3-6 ml at 4-6 mL/s)
    • imaging should take ≥ 15 s after contrast administration
    • both extra and intracranial circulation should be evaluated
  • the circulatory arrest is confirmed when intracranial vessels are visualized only to the A1 and M1 segments and the proximal basilar artery (without filling of PICA and AICA)
    • conventional angiographic evidence of cerebral circulatory arrest is of value only in the presence of simultaneous clinical evidence of oblongata involvement
    • in proven cerebral circulatory arrest,  the oblongata survival with persistent reflexes (gag or oculocardiac reflexes) can be explained by collaterals from the spinal arteries
  • in patients with a traumatic defect of calva or after craniectomy, some blood flow through the brain may be preserved. Intracranial penetration of contrast agent does not exclude brain death. In these patients, however,  brain death cannot be confirmed by angiography (⇒ perform BAEP)
Cerebral circulatory arrest on DSA
Cerebral circulatory arrest on DSA
Brain death on DSA

Brain death on DSA

CT angiography
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Normal CTA (0 points on 4-ponints scale)
Brain death patient with cerebral circulatory arrest on CTA (4 points)
Brain dead patient with a cerebral circulatory arrest on CTA

Transcranial Doppler sonography (TCD, TCCD)
  • many countries acknowledge TCD/TCCD as the official method for confirming cerebral circulatory arrest
  • non-invasive, with good availability and the possibility of monitoring/serial examinations
  • vessels to be examined: ICA, MCA, PCA, ACA, VA, BA (access via foramen magnum, temporal window, or orbit)
Evoked potentials (EP)

SSEP (SomatoSensory Evoked Potentials)

  • potentials evoked by bilateral median nerve stimulation show responses only from Erb’s point and the spinal component (N13)
  • cortical and subcortical responses are absent

BAEP (Brainstem Auditory Evoked Potential)

  • quick and easy to perform + BAEP can be used for monitoring
  • min. 100 dB, max. frequency 10Hz and at least 2000 stimuli
  • BAEP directly tests the function of the receptor, vestibulocochlear nerve, inferior pons, mesencephalon, and diencephalon; it does not test the medulla oblongata
    • the examination requires intact receptor structures (exclude bilateral fractures of the temporal bone and trauma to the auditory system!)
    • BAEP is virtually unaffected by pharmacotherapy incl., medically induced coma
  • findings associated with brain death:
    • bilateral disappearance of waves II-V while wave I is preserved  (this excludes peripheral lesions)
    • the disappearance of all components
SSEP in brain death showing no cortical or subcortical response
BAEP in brain death - absent waves II-V
Brain perfusion scintigraphy
  • the principle of the method IV bolus of radioactive technetium (99mTc-HMPAO) followed by several minutes of brain perfusion imaging
  • MAP > 80 mmHg is required during the scan
  • dynamic and static scintigraphy + SPECT imaging are performed
  • brain death is indicated by a complete absence of brain perfusion
Decreased perfusion on static scintigraphy and SPECT
Brain death - static scintigraphy and SPECT
Electroencephalography (EEG)
  • isoelectric line
  • EEG should be recorded for 60 minutes, and activity must not exceed 2-3 μV (system noise level)
Flat EEG in brain death
Cerebral perfusion pressure (CPP) monitoring
  •  CPP represents the difference between mean arterial pressure (MAP) and intracranial pressure (ICP), measured in mmHg
    • continuous invasive ICP monitoring is required
  • cerebral perfusion arrest occurs when ICP ≥ MAP

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Brain death diagnosis