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BRAIN DEATH Ali ShahAbbasi , M.D. Board certified in Anesthesiology , Critical Care & Pain Medicine MPH

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The traditional concept of death is that life begins with the first inspiration after birth and death comes with the last expiration, and that cardiac activity ceases within a few minutes of the last expiration. In contrast, the modern concept of brain death adopts the conclusions of modern biologic science (central integrator theory of the brain): that the central nervous system (CNS),including the brainstem, is the control center for the living organism; that cessation of CNS functions represents cessation of the harmony of life; and that without CNS control, the living organism is nothing more than an aggregation of living cells.


DEFINITION The three essential findings in brain death are coma , absence of brain stem reflexes , and apnea . An evaluation for brain death should be considered in patients who have suffered a massive, irreversible brain injury of identifiable cause. the irreversible loss of all function of the brain, including the brain stem.

Etiology of Brain Death:

Etiology of Brain Death Severe head trauma Aneurismal subarachnoid hemorrhage Cerebrovascular injury Hypoxic-ischemic encephalopathy Fulminant hepatic necrosis Prolonged cardiac resuscitation or asphyxia Tumors In most adult series, trauma and subarachnoid hemorrhage are the most common event leading to brain death .

Conditions Distinct From Brain Death:

Conditions Distinct From Brain Death Persistent Vegetative State (VS) Locked-in Syndrome Minimally Conscious State (MCS)

Persistent Vegetative State (Cerebral Death):

Persistent Vegetative State (Cerebral Death) Diffuse Brain Injury with Preservation of Brain Stem Function Normal Sleep-Wake Cycles No Response to Environmental Stimuli

Locked-in Syndrome:

Locked-in Syndrome The locked-in syndrome is a consequence of a focal injury to the base of the pons , usually by embolic occlusion of the basilar artery. Preserved Consciousness Complete Paralysis except that voluntary blinking and vertical eye movements remain intact. Patients with this syndrome have been mistakenly believed to be unconscious .

Locked-in syndrome:

Locked-in syndrome Basilar artery thrombosis Ventral Pontine Infarct

The Minimally Conscious State (MCS) (Static Encephalopathy):

The Minimally Conscious State (MCS) (Static Encephalopathy) Diffuse or Multi-Focal Brain Injury Preserved Brain Stem Function Variable Interaction with Environmental Stimuli and presence of specific behavioral features This condition is often transient but may also exist as a permanent outcome.

Comparison of clinical features ::

Comparison of clinical features :

Determination of Brain Death:

Determination of Brain Death The American Academy of Neurology (AAN) delineated the medical standards for brain death in 1995. This practice parameter was reviewed in 2010.

The steps for determining brain death :

The steps for determining brain death Establish proximate cause and irreversibility of coma and monitor the patient for an appropriate waiting period in order to exclude the possibility of recovery; Conduct and document the clinical assessment of brain stem reflexes; Perform and document the apnea test; Perform ancillary testing, if indicated; Certify brain death.

Step 1: Establish Proximate Cause and Irreversibility of Coma:

Step 1: Establish Proximate Cause and Irreversibility of Coma The evaluation of a potentially irreversible coma should include: Clinical or neuro -imaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis; Exclusion of complicating medical conditions that may confound clinical assessment ( e.g., no severe electrolyte, acid-base, or endocrine disturbance); Exclusion of significant hypothermia or hypotension; Normal core temperature should be: (age ≥ 18 years) > 36°C Normal systolic blood pressure should be: (age ≥ 18 years) ≥ 100 mm Hg (Option: mean arterial pressure ≥ 65 mm Hg) Exclusion of drug intoxication or poisoning and neuromuscular blockade. Patients admitted for the treatment of drug overdose should have confirmatory tests to ensure that drug levels have decreased to clinically insignificant levels. No spontaneous respirations.

Step 2: Clinical Assessment of Brain Stem Reflexes :

Step 2: Clinical Assessment of Brain Stem Reflexes If an appropriate period of time has passed since the onset of the brain insult to exclude the possibility of recovery, one clinical assessment of brain function and an apnea test should be sufficient to pronounce brain death. The following clinical indications verify the occurrence of brain death: Coma Absence of brain stem reflexes


Coma No evidence of responsiveness. Eye opening or eye movement to noxious stimuli is absent. Noxious stimuli should not produce a motor response other than spinally mediated reflexes. Movements originating from the spinal cord or peripheral nerve are common (33 to 75 percent) and may be triggered by tactile stimuli or occur spontaneously. Brain-originating movements include cortically originating complex, purposeful movements, and also decerebrate or decorticate posturing, facial grimacing, and seizures.

Spinally mediated reflexes::

Spinally mediated reflexes: Subtle, semi-rhythmic movements of facial muscles can arise from the denervated facial nerve. Finger flexor movements. Tonic neck reflexes — Passive neck displacements, especially flexion, may be accompanied by complex truncal and extremity movements, including adduction at the shoulders, flexion at the elbows, supination or pronation at the wrists, flexion of the trunk ("sitting up" type movements), and neck-abdominal muscle contraction or head turning to one side. These might be quite dramatic, often called a "Lazarus sign.“ Triple flexion response with flexion at the hip, knee, and ankle with foot stimulation, eg , testing for a Babinski sign. Other truncal movements including asymmetrical opisthotonic posturing of the trunk and preservation of superficial and deep abdominal reflexes. Alternating flexion-extension of the toes with passive displacement of the foot (undulating toe sign), or flexion of the toes after foot percussion, or a Babinski sign. Widespread fasciculations of trunk and extremities.

Absence of brain stem reflexes (all must be checked):

Absence of brain stem reflexes (all must be checked) Absent pupillary light reflex pupils are midposition or dilated (4 to 9 mm)

Absence of brain stem reflexes… (all must be checked):

Oculocephalic reflex testing Absence of brain stem reflexes… (all must be checked)

Absence of brain stem reflexes… (all must be checked):

Oculovestibular reflex testing Absence of brain stem reflexes… (all must be checked)

Absence of brain stem reflexes… (all must be checked):

Absent corneal reflexes There is no blink response to direct corneal stimulation. Absence of brain stem reflexes… (all must be checked)

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Absent gag reflex There is no gag or cough reflex. Absence of brain stem reflexes… (all must be checked)

Absence of brain stem reflexes… (all must be checked):

Absence of brain stem reflexes… (all must be checked) No facial movement to noxious stimuli at supraorbital nerve, temporomandibular joint. Cough reflex absent to tracheal suctioning. Absence of motor response to noxious stimuli in all four limbs (spinally mediated reflexes are permissible).

Step 3: Apnea Test :

Step 3: Apnea Test Generally, the apnea test is the final step in the determination of brain death, and is performed after establishing the irreversibility and unresponsiveness of coma, and the absence of brainstem reflexes.

Step 3: Apnea Test :

Step 3: Apnea Test Before performing the apnea test, the physician must determine that the patient meets the following conditions: Core temperature > 36°C. PaCO2 35-45 mm Hg. Normal PaO2. Option: pre-oxygenation for at least 10 minutes with 100% oxygen to PaO2 > 200 mm Hg. Normotension . Adjust fluids and (if necessary) vasopressors to a systolic blood pressure ≥ 100 mm Hg

Step 3: Apnea Test :

Step 3: Apnea Test After determining that the patient meets the prerequisites above, the physician should conduct the apnea test as follows: Connect a pulse oximeter . Disconnect the ventilator. Apnea can be assessed reliably only by disconnecting the ventilator, as the ventilator can sense small changes in tubing pressure and provide a breath that could suggest breathing effort by the patient where none exists. Deliver 100% O2, 6 L/min by placing a catheter through the endotracheal tube and close to the level of the carina. Option: use a T-piece with 10 cm H20 CPAP and deliver 100% O2, 12 L/min. Draw a baseline arterial blood gas.

Step 3: Apnea Test… :

Step 3: Apnea Test… Look closely for respiratory movements (abdominal or chest excursions that produce adequate tidal volumes) for 8-10 minutes. Measure PaO2, PaCO2, and pH after approximately 8-10 minutes and reconnect the ventilator. If respiratory movements are absent and PaCO2 is ≥ 60 mm Hg ( option: 20 mm Hg increase in PaCO2 over a baseline normal PaCO2), the apnea test supports the diagnosis of brain death. If respiratory movements are observed, the apnea test result is negative ( i.e., does not support the diagnosis of brain death). Connect the ventilator if, during testing, the systolic blood pressure becomes < 90 mm Hg (or below age-appropriate thresholds in children less than 18 years of age) or the pulse oximeter indicates significant oxygen desaturation (< 85% for > 30 seconds), or cardiac arrhythmias develop; immediately draw an arterial blood sample and analyze arterial blood gas.

Step 4: Ancillary Testing as Indicated :

Step 4: Ancillary Testing as Indicated In some patients, however, Confounding Factors may make it impossible to complete parts of the assessment safely. In such circumstances, an ancillary test verifying brain death is necessary. Severe facial or cervical spine trauma, or facial deformity confounding cranial nerve assessment. Incomplete apnea testing. (Severe chronic pulmonary disease or severe obesity resulting in chronic retention of CO2….) Toxic levels of CNS-depressant drugs or neuromuscular blocking agents. Severe electrolyte, acid-base, or endocrine disturbance (defined by severe acidosis or laboratory values markedly deviated from the norm). Children younger than 1 year old. Required by institutional policy. (In some protocols, ancillary tests are used to shorten the duration of the observation period)

Step 4: Ancillary Testing…:

Step 4: Ancillary Testing… The choice of an ancillary test is dictated in large part by practical considerations, i.e., availability , advantages , and disadvantages . Only 1 needs to be performed.

Step 4: Ancillary testing…:

Step 4: Ancillary testing… Cerebral angiography (conventional, computerized tomographic , and magnetic resonance) Cerebral Scintigraphy (Nuclear Brain scanning) EEG TCD

Cerebral angiography:

Cerebral angiography The contrast medium should be injected in the aortic arch under high pressure and reach both anterior and posterior circulations. No intracerebral filling should be detected at the level of entry of the carotid or vertebral artery to the skull. The external carotid circulation should be patent. The filling of the superior longitudinal sinus may be delayed.

Cerebral Angiography:

Cerebral Angiography Normal Blood Flow No Blood Flow

Step 4: Ancillary testing…:

Step 4: Ancillary testing… Cerebral angiography Cerebral Scintigraphy (Nuclear Brain scanning) EEG TCD

Cerebral scintigraphy:

Cerebral scintigraphy The isotope should be injected within 30 minutes after its Reconstitution. Anterior and both lateral planar image counts of the head should be obtained at several time points: immediately, between 30 and 60 minutes later, and at 2 hours. A correct IV injection may be confirmed with additional images of the liver demonstrating uptake (optional). No radionuclide localization in the middle cerebral artery, anterior cerebral artery, or basilar artery territories of the cerebral hemispheres (hollow skull phenomenon). No tracer in superior sagittal sinus (minimal tracer can come from the scalp).

HMPAO-Tc99m imaging:

HMPAO-Tc99m imaging The top figures show anterior posterior and lateral views of a normal scan with uptake in the brain. The bottom figures (same sequence) show lack of brain perfusion and the "empty light bulb" and "hot nose" signs.

Step 4: Ancillary testing…:

Step 4: Ancillary testing… Cerebral angiography Cerebral Scintigraphy (Nuclear Brain scanning) EEG TCD


EEG Normal


Electroencephalography A minimum of 8 scalp electrodes should be used. Interelectrode impedance should be between 100 and 10,000. The integrity of the entire recording system should be tested. The distance between electrodes should be at least 10 cm. The sensitivity should be increased to at least 2 V for 30 minutes with inclusion of appropriate calibrations. The high-frequency filter setting should not be set below 30 Hz, and the low-frequency setting should not be above 1 Hz. Electroencephalography should demonstrate a lack of reactivity to intense somatosensory or audiovisual stimuli.

Step 4: Ancillary testing…:

Step 4: Ancillary testing… Cerebral angiography Cerebral Scintigraphy (Nuclear Brain scanning) EEG TCD

Transcranial Doppler Sonography (TCD) :

Transcranial Doppler S onography (TCD)

Transcranial Doppler ultrasonography:

Transcranial Doppler ultrasonography TCD is useful only if a reliable signal is found. The abnormalities should include either reverberating flow or small systolic peaks in early systole. A finding of a complete absence of flow may not be reliable owing to inadequate transtemporal windows for insonation . There should be bilateral insonation and anterior and posterior insonation . The probe should be placed at the temporal bone, above the zygomatic arch and the vertebrobasilar arteries, through the suboccipital transcranial window. Insonation through the orbital window can be considered to obtain a reliable signal. TCD may be less reliable in patients with a prior craniotomy.

Step 5:Documentation:

Step 5:Documentation The time of brain death is documented in the medical records. Time of death is the time the arterial PCO2 reached the target value. In patients with an aborted apnea test, the time of death is when the ancillary test has been officially interpreted. A checklist is filled out, signed, and dated.

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