CONTENTS

• Brain death basics
• Clinical presentation of brain death
  • Clinical context
  • Clinical findings in brain death
  • Spinal reflexes
• Diagnosis of brain death
  • (1) Initial suspicion
  • (2) Evaluate for confounders
    • Excluding drug intoxication
  • (3) Dedicated neurologic examination
  • (4) Apnea test
  • (5) Confirmatory test PRN
• If brain death is confirmed:
  • Immediate next steps
  • Supportive care prior to organ donation
• Notes about relevant ethics
• Podcast
• Questions & discussion
• Pitfalls
• Supplemental media

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brain death basics

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definition of brain death

• Defined as irreversible cessation of all cerebral and brainstem functioning.
• Brain death is legally recognized as equivalent to cardiopulmonary death in the United States.
• Brain death is defined by a strict set of criteria that, once met, confers zero likelihood of awakening from coma.

pathophysiology of brain death

• The final common pathway of brain death is shown below.
• Regardless of the initial injury, eventually brain death occurs via a spiral of progressive intracranial hypertension, tissue damage, and edema.   This is essentially an intracranial compartment syndrome.
• Complete brain death occurs when there is complete circulatory arrest of the brain – no blood is entering the brain.

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clinical context

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Clinical context may either support the possibility of brain death, or it may suggest the possibility of a brain-death mimic.  Be extremely cautious about pursuing a diagnosis of brain death in patients who lack an underlying process that explains why they should be brain dead.

(1) common causes of brain death (if present, these support the diagnosis of brain death)

• Traumatic brain injury.
• Intracranial hemorrhage.
• Anoxic brain injury (usually due to cardiopulmonary arrest).
• Fulminant meningitis or encephalitis.
• Fulminant hepatic failure causing cerebral edema.
• Ischemic stroke with cerebral edema and herniation.

(2) potential mimics of brain death

• Neuromuscular paralysis:
  • Fulminant Guillain-Barre syndrome.*
  • Botulism.*
• Hypothermia.*
• Variety of drug intoxications, for example:
  • Tricyclic antidepressants.*
  • Lidocaine.*
  • Baclofen.*
  • Sedatives, especially barbiturates.*
  • Paralytics.*
  • Anticholinergics.*
  • Bupropion.*
  • Valproic acid.*
• High C-spine injury.
• Locked-in syndrome.
• (* = full recovery is probable)

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clinical findings in brain death

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cardinal findings

• (1) Coma (e.g., no cerebrally-mediated response to pain).
• (2) No cranial nerve function:
  • No pupillary or corneal reflex.
  • No oculocephalic reflex (doll's eyes).
  • No cough reflex (when suctioning endotracheal tube).
• (3) No respiratory drive (patient doesn't over-breathe the ventilator).
  • ⚠️ Note that if the ventilator's set respiratory rate is high enough to cause a respiratory alkalosis, which will normally suppress the patient's own respiratory drive.
  • An informal apnea test may be used to provide more accurate information about whether the patient has an intact respiratory drive.  If safe, decrease the respiratory rate on the ventilator to a very low rate (e.g., 4 breaths/min).  Observe the patient's vital signs, respiratory efforts, and end tidal CO2 for about five minutes.  If the patient makes any respiratory effort, then they have an intact respiratory drive (so brain death is excluded).  Alternatively, if the patient makes no respiratory effort despite a substantially elevated end tidal CO2, this suggests loss of respiratory drive.  A formal apnea test is still required before diagnosing brain death (more on this below 📖).

additional findings: 

• Patient is not chemically paralyzed (e.g., deep tendon reflexes are preserved).
• If EEG is attached, it will be completely suppressed (totally flat EEG).
  • ⚠️ Note, however, that various EEG artefacts can easily confuse this picture.
• Spinal reflexes may be seen – which can be confusing (more on this in the next section).
• Diabetes insipidus is commonly seen, but not always.

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spinal reflexes

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unusual spinal reflexes are often observed in brain death 

• Brain death leads to the disinhibition of spinal cord reflexes (which are normally suppressed).   This may lead to some strange movements, which are often misinterpreted as intentional.  A list of described spinal reflexes is above.(32761206) 
• To complicate matters, spinal reflexes are often triggered by stimuli (e.g., painful stimuli below the diaphragm may lead to head turning).  This may closely mimic the appearance of someone who is responding to stimuli in a meaningful fashion.
• The most classic spinal reflex is triple flexion, wherein stimulation of the feet causes flexion at the ankles, knees, and hips.  This is often misinterpreted as representing volitional “withdrawal from pain.”

differentiating spinal reflexes from volitional movements

• Features that should never be seen with spinal reflexes:
  • Spinal reflexes should not occur with stimulation of the cranial nerves (e.g., painful stimuli at the supraorbital ridge or temporomandibular joint).(Torbey, 2019)
  • 💡Pay particular attention to facial movement when applying noxious stimuli.  Any grimacing in response to stimulation excludes brain death.  However, some patients may exhibit random twitching of facial muscles (myokimia), which is compatible with brain death if it is occurring spontaneously.(Nelson, 2020)
• Features that are consistent with spinal reflexes:
  • Reflexes are often triggered by stimulation below the foramen magnum.
  • The movement induced by a reflex is often precisely repeatable.
• Sorting out spinal reflexes from intentional responses to stimuli may be very challenging, even for examiners who are experienced with brain death.
  • If all other elements of the examination and neuroimaging are entirely consistent with brain death (e.g., CT scan showing herniation and failure to breathe during apnea test), reflexive-appearing movements are likely spinal reflexes.
  • When in doubt, ancillary testing may be necessary to provide reassurance.

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diagnosis of brain death

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• The following is a general approach to diagnosing brain death.
• If at any point the patient shows evidence of cerebral activity, then brain death is excluded.
  • It's much easier to exclude brain death than to prove it.

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dx step 1 = clinical suspicion

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initial suspicion of brain death involves roughly two components

• (1) Known catastrophic brain injury consistent with brain death.
  • Brain death should primarily be considered within the context of known catastrophic brain injury.
  • For a patient with undifferentiated coma, brain death is a diagnosis of exclusion (e.g., only after alternative and treatable processes have been excluded).
  • Common causes of brain death are listed above. 📖
  • ⚠️ It's generally unwise to pursue the diagnosis of brain death in the absence of a known catastrophic injury compatible with brain death (e.g., if the CT scan doesn't show either herniation or severe cerebral edema).
• (2) Clinical examination consistent with brain death (described above 📖).

is it worthwhile to pursue a formal brain death diagnosis?

• Potential reasons to pursue a formal diagnosis of brain death:
  • Will resolve confusion regarding goals of care and/or issues with surrogate decision-makers.
  • Reassures the family that nothing further can be done.
  • Avoids future criticism regarding premature withdrawal of life-sustaining therapy.
  • Required prior to organ donation.
• Occasionally, it may be reasonable to simply transition to comfort-directed care without formally declaring brain death.  This may be reasonable if:
  • The patient is in multiorgan failure and obviously moribund (without any potential for organ donation).
  • There is no confusion regarding goals of care.
  • Comfort-directed care is clearly appropriate, so brain death declaration wouldn't affect management.

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dx step 2 = exclude confounders

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exclude common confounding factors:  

• Temperature must not be hypothermic (>36C) using esophageal, bladder, or rectal core temperature measurement.(32761206)  
• Blood pressure must be adequate (SBP>100 mm or MAP >60 mm).(32761206)  
• Severe metabolic, acid-base, or endocrine derangements that could affect the neurological examination.(32761206)  Glucose and chemistries must be relatively normal.
• Paralytics must be discontinued (if there is doubt about whether the patient might be paralyzed, paralysis must be excluded using a train-of-four nerve stimulator demonstrating four twitches, or the presence of deep tendon reflexes).
• Residual effect of sedating medications.  Any sedating medications should be stopped and five half-lives should be allowed to pass, prior to brain death evaluation.  For patients who may be undergoing brain death evaluation, it's optimal to avoid any sedating medications that don't wear off rapidly (e.g., with preferential use of propofol and/or dexmedetomidine).  
• Drug intoxication (more on this in the section below).
• Recent cardiac arrest or rewarming from therapeutic hypothermia.  It's generally recommended to observe patients for at least >24 hours after arrest or rewarming, prior to declaring brain death.(32761206)  However, if a radionuclide cerebral flow scan shows no cerebral blood flow, brain death may be declared prior to 24 hours.

consider less common confounders:  

• Any pathology (acute or chronic) that interferes with the ability to perform an adequate neurological exam, for example:
  • Severe neuromuscular disorder (especially:  fulminant Guillain-Barre syndrome).
  • High C-spine injury.
  • Fracture of the skull base or petrous temporal bone (may damage cranial nerves).(32761206)  
  • Chronic eye pathology (e.g., surgical pupils).
  • Orbital edema that interferes with eye evaluation/movement.
  • (Note: the absence of four limbs does not necessarily prevent performing an adequate examination.)(32761206)  
• Isolated brainstem lesion or posterior circulation stroke (may cause Locked-in syndrome, which mimics brain death).(32761206)  

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excluding drug intoxication

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Excluding drug overdose can be tricky (since patients may take varying doses of a wide range of substances).  Unfortunately, much of the available literature and guidelines on this are substantially flawed.  

🛑 urine toxicology panels should not be used

• The World Brain Death project recommended using urine toxicology panels to evaluate for brain death.  This is a profoundly flawed approach that is causing confusion and harm.
• There are numerous reasons that urine toxicology panels are inappropriate for this use:
  • (1) Urine toxicology panels are plagued by wholly false-positive results, due to cross-reaction with a variety of other medications and substances (more on this here: 📖).
  • (2) Even if the urine toxicology is a true-positive, toxicology panels may remain positive for days following exposure.  For example, a toxicology panel positive for cocaine could reflect exposure some days previously.  This often has nothing to do with the patient's acute illness.
  • (3) Urine toxicology panels will fail to detect many of the substances that mimic brain death (e.g., fentanyl, carfentanil, baclofen).  Thus, a negative toxicology screen could mislead clinicians into believing that an intoxicated patient was actually brain dead.  This would be an enormous and unacceptable mistake.
• ⚠️ There is no room for uncertainty in the diagnosis of brain death.  Urine toxicology screens are inadequately sensitive and inadequately specific to have any role here.
• Further discussion of the role of urine toxicology in brain death here: 🌊

🛑 waiting five half-lives should not be used as an approach to drug overdose

• Traditionally, many guidelines have recommended that for a patient with an overdose it may be permissible to declare brain death after waiting >5 half-lives to allow medication metabolism.
• There are several reasons that waiting five half-lives is impractical and dangerous:
  • (1) Waiting five half-lives requires confident knowledge of the intoxicating substance.  In clinical practice, intoxication histories are usually flawed and unreliable.
  • (2) Large ingestions often saturate drug metabolism, extending the drug's half-life.  Thus, the half-life in the context of intoxication may be unpredictably long.  This could cause 5 half-lives to be inadequate to allow for drug clearance.
  • (3) Patients may have altered drug half-life due to renal impairment, hepatic impairment, older age, or multiorgan failure.  Half-life data quoted in pharmacopoeias are generalizations that don't apply perfectly to every individual patient.
  • (4) Waiting for five half-lives may impose a very long duration of waiting.  This may lead to delays in the declaration of brain death in patients who are quite surely brain dead (imposing agonizing waiting for families and high medical costs).  In contrast, the use of ancillary testing may allow for immediate and definitive diagnosis of brain death.
• (Note that waiting five half-lives is acceptable if the patient has been exposed to therapeutic, known doses of a short-acting agent like propofol.)

quantitative measurement of drug levels may be used in very, very rare situations

• Quantitative measurement of drug levels may be helpful in very rare situations, where there is a unique concern regarding a single substance.  For example, imagine that a patient is treated with pentobarbital for elevated intracranial pressure and later transitions to brain death.  A quantitative pentobarbital level might help clarify whether pentobarbital was affecting the clinical examination.  (However, pentobarbital is a send-out laboratory test in most hospitals, so it might be more expeditious to simply use an ancillary test to confirm brain death.)
• A serum ethanol level might be useful in situations where there is a specific concern regarding alcohol intake.  To allow for brain death testing, the alcohol level should be <80 mg/dL (below the legal limit to allow driving).(34618768)
• In actual clinical practice, quantitative measurement of drug levels has little role in the evaluation of brain death.

ancillary testing based on blood flow is the best approach to patients with potential intoxication

• If there is a concern regarding intoxication, the best approach is generally an ancillary test based on blood flow (e.g., cerebral flow scan 📖).
  • ⚠️ Note that ancillary tests based on brain electrical activity such as EEG may be confounded by intoxication.
• Advantages of a blood flow-based ancillary test are numerous:
  • (1) Flow-based ancillary testing is accurate, regardless of any intoxication.  Thus, this approach is universally effective for any intoxicant (e.g., for a patient who presents with possible intoxication of unknown nature).
  • (2) Ancillary testing can be done promptly (avoiding long, awkward delays while awaiting drug metabolism).

which patient need ancillary testing to exclude drug intoxication?

• Most patients don't require evaluation for drug intoxication.  If the clinical history, examination, and neuroimaging raise no concerns regarding drug intoxication then further evaluation isn't needed.  For example, a patient with a witnessed cardiac arrest while playing sports wouldn't require investigation for drug intoxication.
• If elements of the history and evaluation raise a concern for intoxication, then ancillary testing may be warranted (e.g., coma is disproportionately severe compared to neuroimaging, history of prior substance use).
• Ultimately, the decision regarding whether ancillary testing is needed to exclude intoxication is a clinical judgement based on review of all available data.

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dx step 3 = dedicated neuro exam

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coma

• There should be no evidence of arousal or awareness to maximal external stimulation, including:
  • Noxious visual stimuli (may be assessed while examining pupils).
  • Pain in any extremity.
  • Pain at the supraorbital notch and at the temporomandibular joints (bilaterally).
  • Deep sternal rub.
  • ⚠️ There should be no vertical eye movements to stimulation or command (as could occur due to locked-in syndrome).
• Spinal reflexes may occur (more on this above 📖).

pupillary reflexes

• There should be an absence of any ipsilateral or contralateral pupillary response.
• In brain death, pupils are generally fixed/midposition or fixed/dilated.
• ⚠️ Very small pupils (<2 mm) are usually not seen in brain death.  Instead, these may suggest the possibility of drug intoxication or locked-in syndrome (“pontine pupils”).(35292111)

corneal reflexes

• Touch the lateral aspect of the cornea of both eyes with a cotton swab.  Enough pressure should be used to slightly depress the eye.(35292111)
• Common mistakes:
  • Testing the corneal reflex by dropping saline onto the eye (this is inadequate to establish brain death, since it doesn't provide the strongest stimulation of this reflex).
  • Applying stimulation to the sclera (rather than the cornea).

oculocephalic and oculovestibular reflexes

• Any extraocular movement is incompatible with brain death.
• Oculocephalic reflexes may be skipped if the patient has an unstable C-spine.(34618768)  
• Oculovestibular reflexes:  Irrigate with at least 30 ml of ice cold water for at least 60 seconds.  Allow five minutes in between testing different sides.

cough and gag reflexes

• No gag reflex (ideally tested by suctioning the back of the throat with a Yankauer catheter, including stimulation of both sides of the posterior pharynx).(32761206)
• No cough reflex (tested by in-line suctioning of an endotracheal tube).

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dx step 4 = apnea test

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prerequisites

• Patient must be deemed stable enough to tolerate apnea (e.g., not severely hypoxemic or acidotic).
• PaCO2 is normal or at the patient's known baseline (in cases of COPD or obesity hypoventilation syndrome).  If the patient has evidence of chronic CO2 retention without a known baseline CO2, the apnea test can't be done.
• Absence of other confounding factors. 📖
• Core temperature should be >36C.
• SBP >100 mm or MAP >60 mm.

prior to the test

• Patient is pre-oxygenated with 100% FiO2 for ~10 minutes.
• Obtain a baseline ABG and ensure that the PaCO2 is normal (35-45 mm, 4.7-6.0 kPa) or at the patient's known baseline.  If necessary, adjust the ventilator and repeat an ABG to document an appropriate baseline PaCO2.
• Guidelines suggest that a functioning arterial line be used to provide continuous blood pressure monitoring and quickly draw blood gasses during the apnea test.(32761206)  
• Consider vasopressor initiation if the blood pressure is borderline.  One of the most commonly encountered complications of apnea is hypotension.  Pre-emptive vasopressor initiation to establish a margin of blood pressure stability (e.g., MAP > 75 mm) may avoid having to abort and repeat the apnea test.

induction of apnea

• The goal is to stop ventilating the patient, but to provide apneic oxygenation and some continuous positive pressure to prevent de-recruitment.
• There are various ways of accomplishing this:
  • (a) Simply keep the patient on the ventilator on a CPAP mode with no backup rate.  Unfortunately, many ventilators won't allow the patient to be apneic without kicking into a backup ventilation mode.(27742325)
  • (b) A nice way to achieve this might be to use a flow-inflating bag to provide oxygen and CPAP.🎥
  • (c) Another strategy is the use of a T-piece with CPAP to provide some PEEP and apneic oxygenation.
  • (Traditionally, the apnea test was accomplished by inserting a cannula to deliver oxygen into the endotracheal tube.  This strategy has a risk of causing pneumothorax, so it's not optimal.)(27460062)

apnea

• If there is any respiratory effort then the patient isn't brain dead – reconnect to the ventilator immediately and resume supportive care.  Consider repeating an apnea test after 24 hours, if the clinical examination remains consistent with brain death.(32761206)  
• Abort the apnea test prematurely if the patient becomes unstable, for example:
  • Hypotension refractory to vasopressor titration (e.g., SBP <100 mm or MAP <60 mm).
  • Sustained desaturation <85% for >30 seconds.
  • Unstable arrhythmia.
  • (An ABG should still be obtained at the time of apnea termination; if the PaCO2 is high enough then the test may still be adequate to establish lack of respiratory drive.)
• Continue apnea for 10 minutes if the patient can tolerate this, then check an arterial blood gas.
  • If point-of-care testing is available and the patient is stable, then apnea may be continued while awaiting the blood gas (for a few minutes).  If the ABG doesn't show sufficient hypercapnia, the ABG may be repeated frequently with ongoing apnea.
  • If point-of-care testing isn't available, then draw an ABG after 10 minutes and reconnect the patient to the ventilator.

targets for apnea test

• In order to conclude that the patient has no respiratory drive, the following targets are required:(32761206)
  • (1) pH <7.30.
  • (2) PaCO2 >60 mm (>8.0 kPa).  For patients with preexisting hypercapnia, the PaCO2 should be at least >20 mm (>2.7 kPa) above the patient's baseline PaCO2.
• 10 minutes of apnea should be sufficient to meet these targets.  If PaCO2 doesn't increase sufficiently, the entire test may be repeated following pre-oxygenation and a repeat baseline PaCO2 and extended for 15 minutes of apnea.

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dx step 5 = confirmatory test PRN

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situations where a confirmatory test is needed:  

1. There is no clear cause of catastrophic brain injury that would explain brain death.
2. The presence of any confounding factor(s), as listed above. 📖
3. Inability to perform an apnea test (e.g., the patient is too hypoxemic to tolerate apnea).
4. Uncertainty regarding whether movements are spinally mediated reflexes (discussed further above 📖).
5. Some countries require confirmatory testing by law (not the United States).

the most useful confirmatory test is cerebral scintigraphy:

• Radiolabeled dye is injected into a peripheral vein.  If there is perfusion to the brain, the dye will be taken up in brain tissue.
• In brain death, lack of brain perfusion causes an “empty skull sign” (image above).
• A cerebral scintigraphy which shows lack of blood flow to the brain (based on an official interpretation by an attending radiologist) is extremely solid evidence of brain death.
• Early in the process of brain death, there may be a small amount of perfusion remaining.  In this case, a repeat test in 6-12 hours may show lack of flow. 🌊
• If blood flow is fully preserved, this suggests the possibility of a brain death mimic (e.g., intoxication or locked-in syndrome).  The underlying diagnosis should be reconsidered.

transcranial doppler ultrasonography

• Transcranial doppler (TCD) can be used as a confirmatory test, as discussed further here: 📖
• A single transcranial doppler showing absent flow isn't reliable, as this may be caused by poor bone windows.  Alternatively, a sequence of transcranial doppler results showing progressive reduction in blood flow may be strongly supportive of brain death.
• If available, cerebral scintigraphy is preferred over transcranial doppler ultrasonography.  Cerebral scintigraphy is less operator-dependent, allowing a high-quality cerebral scintigraphy study that is interpreted by a radiologist to be nearly irrefutable evidence of brain death.

flatline EEG supports a diagnosis of brain death

• EEG isn't generally ordered or recommended as a confirmatory test.(32761206)   However, some patients may already be attached to video EEG monitoring (e.g., after anoxic brain injury).
  • If the EEG is used as an ancillary test, specific filters and settings are required (e.g., increased sensitivity to detect low-voltage activity, collection of 30 minutes of interpretable data, testing for reactivity to stimulation, and performance at least eight hours after any cardiac arrest).(27482789) 
• In the presence of brain death, the EEG should be completely suppressed (totally flat).  Any cerebral activity indicates that the patient isn't brain dead (e.g., even highly malignant EEG patterns such as burst suppression).
• Cautions:
  • ⚠️ A flatline EEG is often seen in the absence of brain death (e.g., due to drug intoxication).
  • ⚠️ Muscular artifacts may cause the EEG to appear active, when there is in fact no brain activity.  (Paralysis can remove these artefacts, but administering a long-acting paralytic will greatly complicate the declaration of brain death – so this should generally be avoided.  If brief paralysis is desired to remove EEG artifact, succinylcholine could be a reasonable option.)

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immediate steps if brain death is confirmed

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• The family should be informed that the patient has died (with appropriate explanation of brain death).
• 🛑 Do not discuss organ donation with the family; this should be done by a separate organ procurement team.

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management of the brain dead patient with potential for organ donation

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Ongoing high-quality supportive care is required to maximize organ function.  Optimal management of the donor may increase the likelihood of successful allograft function and favorable long-term outcomes for organ recipients. 

general resuscitative principles

• Overall, the general principles of management of the donor are similar as for any patient receiving high-quality supportive care.
• Resuscitation may be tailored slightly to favor preserving function of the organs for donation.
• Long-term consequences of interventions don't exist (e.g. C. difficile infection due to broad-spectrum antibiotics, myopathy due to high-dose steroid).

corticosteroid

• Reasons to give steroid:
  • (a) Brain death can cause pituitary deficiency, promoting hemodynamic instability.
  • (b) Steroid may reduce inflammation, thereby improving graft organ functionality.
• Large doses are commonly used (e.g. 1,000 mg IV methylprednisolone daily).

management of diabetes insipidus

• Diabetes insipidus commonly occurs, but not always (it is possible to be brain dead and still have a functioning hypothalamus).  If it occurs, it should be treated with a goal of bringing the sodium back to a fairly normal value (hypernatremia may impair liver function).
• Diagnosis:
  • In the context of brain death, diabetes insipidus may be strongly suspected on the basis of copious dilute urine production.
  • The differential diagnosis may include polyuria due to hyperglycemia, hypothermia, or medications.
  • If doubt exists, the diagnosis of diabetes insipidus may be established by labs showing hypernatremia and ongoing production of hypotonic urine (urine osmolarity < 200 mOsm/L or urine specific gravity <1.005).  However, treatment shouldn't be delayed while waiting for these studies to return.
• Treatment option #1 = desmopressin.
  • IV desmopressin 2-4 micrograms q6hr-q8hr.
  • Advantage = easy to do, doesn't tie up an intravenous line.
  • Disadvantage = if hyponatremia occurs, DDAVP will take hours to wear off.
• Treatment option #2 = vasopressin infusion.
  • Very low doses of vasopressin are sufficient to reverse diabetes insipidus (e.g. 0.01 units/minute or lower).  These doses won't necessarily have much effect on hemodynamics.
  • Useful for patients who are hypotensive (in which cases higher doses are generally given, e.g. ~0.04 units/minute).
  • Advantage = titratable (so it can be turned off if hyponatremia or low urine output occurs), may help support blood pressure in hypotension.
  • Disadvantage = slightly more work than DDAVP (ongoing IV infusion).

preservation of lung function

• Expert management probably has the greatest impact on lung procurement, compared to other organs.
• Avoid subclavian central line (pneumothorax won't have time to heal, potentially making it more problematic).
• Bronchoscopy is required to evaluate candidacy for lung donation.  Avoid performing bronchoalveolar lavage if possible (or, if mandatory, use the lowest volume of saline possible).
• Use of airway pressure release ventilation (APRV) has been shown to improve candidacy for lung donation. (21422364)
• Avoid volume overload.

improvement in cardiac function

• Myocardial stunning and systolic heart failure are common following brain death.  With supportive care, these often improve over time.
• Supportive care principles are similar to other patients with cardiogenic shock.
• Thyroid hormone supplementation may assist in cardiac recovery.
  • Following brain death, a sick-euthyroid state frequently occurs (with elevated levels of inactive reverse-T3, low levels of active T3, and normal levels of T4).  Exogenous thyroid hormone has commonly been used in efforts to improve cardiac function and candidacy for heart donation.  No high-level evidence supports this practice, which remains controversial.  Consensus guidelines recommend consideration of thyroid hormone supplementation in patients with hemodynamic instability.(25978154)
  • If thyroid hormone is given, either thyroxine (T4) or triiodothyronine (T3) may be used.  Triiodothyronine (T3) may be a bit more effective, but it is less widely available in IV form.  Commonly used doses are:
    • Thyroxine (T4):  20 ug IV bolus followed by 10 ug/hour IV maintenance infusion.
    • Triiodothyronine (T3):  4 ug IV bolus followed by 3 ug/hr IV maintenance infusion (if unavailable, liothyronine has excellent oral bioavailability)

temperature management

• Brain death may lead to spontaneous development of hypothermia.
• Temperature should be monitored.  External warming may be necessary to avoid hypothermia.

empiric antibiotics

• Broad-spectrum antibiotics are often administered (e.g., piperacillin-tazobactam).

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notes about relevant ethics

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evaluation of possible brain death

• Brain death evaluation is a standard component of medical care.
• Consent is not required for evaluation of brain death (including apnea testing) in the United States.(35526888)  Of course, apnea testing should never be performed if the patient isn't sufficiently stable to undergo this evaluation.

removal of medical support after diagnosis of brain death

• If organ donation is not possible, medical support should be discontinued.  Practices surrounding this will vary between different locations.  When in doubt, local ethics committees should be engaged.  The following discussion applies within the United States.
• Once the patient has been declared brain dead they are deceased (“brain dead is dead”).  Families/surrogates do not need to consent to removal of ventilatory support.  Nonetheless, it is customary to allow a short period of time for families to grieve, prior to removal of support.(Nelson, 2019) 

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• In a severely neurologically injured patient, avoid any long-acting sedative (ideally, only propofol or dexmedetomidine would be used).  This facilitates an unclouded neurologic examination.
• Failure to consider a diagnosis of brain death.   For example, if a patient is brain dead following anoxic brain injury, there is no role for therapeutic hypothermia or neuroprognostication:  the patient is dead.
• Brain dead patients may produce a variety of spinal reflexes (e.g. triple flexion).  These shouldn't be mistaken as indicating that the patient is alive.
• Be extremely cautious about declaring brain death in patients with poisoning or brain dysfunction of unclear etiology (otherwise this may happen).
• EEG can be flatline due to medication effects, so be careful about using EEG as a confirmatory test.

Guide to emoji hyperlinks 

•  = Link to online calculator.
•  = Link to Medscape monograph about a drug.
•  = Link to IBCC section about a drug.
•  = Link to IBCC section covering that topic.
•  = Link to FOAMed site with related information.
• 📄 = Link to open-access journal article.
•  = Link to supplemental media.

Going further:

• Organ donation in the Emergency Department (Scott Weingart, EMCrit RACC)
• Brain death, mimics, and flow scans (PulmCrit)
• Brain death & Management of the organ donation patient (Chris Nickson, LITFL)
• Brain death (WikEM)
• Brain death imaging (Radeopaedia)

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supplemental media

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☝️ Isaac Tawil, MD Demonstrating Brain Death Exam from Scott from EMCrit on Vimeo.