The Determination of Brain Death James Zisfein, M.D. Chief, Division of Neurology Lincoln Hospital, Bronx, NY

Brain death: the early years 1950's: ACLS and ventilators saved lives1950's: ACLS and ventilators saved lives  But there were also unanticipated outcomes Physicians saw things they never saw beforePhysicians saw things they never saw before  Clinicians saw patients in a state "beyond coma"  EEGers saw electrocerebral silence  Pathologists saw the "respirator brain" 1960's: term "brain death" comes into use1960's: term "brain death" comes into use 1968: Harvard Criteria for brain death1968: Harvard Criteria for brain death  Loss of animation, brainstem reflexes, and respiration  Electrocerebral silence  Persistence of the condition for 24 hours

Published guidelines Harvard Criteria (1968)Harvard Criteria (1968) President's Commission Criteria (1981)President's Commission Criteria (1981) American Academy of Pediatrics (1987)American Academy of Pediatrics (1987) American Academy of Neurology (1995, 2010)American Academy of Neurology (1995, 2010)  This presentation is based on the AAN 2010 guideline New York State Department of Health (2005)New York State Department of Health (2005)  NYSDOH is aware of the AAN 2010 update and is revising its guideline to conform with AAN All of these guidelines are 100% specificAll of these guidelines are 100% specific  Despite aggressive treatment, a patient who is found to be brain dead never regains any brain functions

Definition of brain death Brain death is the irreversible loss of all brain functionsBrain death is the irreversible loss of all brain functions "Functions" are clinically ascertainable"Functions" are clinically ascertainable  Animation and respiration are brain functions  Generation of electrical activity, cerebral blood circulation, and metabolism are not brain functions A person who is brain dead is dead according to standards of medical practice and the law in all US jurisdictionsA person who is brain dead is dead according to standards of medical practice and the law in all US jurisdictions  This is not optional  However, reasonable accommodations can be made to support the family in case of religious or moral objections The time of death is the time that this determination is made (usually at the conclusion of an apnea test)The time of death is the time that this determination is made (usually at the conclusion of an apnea test)  It is not sometime later when the heart stops

The diagnosis of brain death in 5 easy steps 1.The cause of brain failure is irreversible. 2.The patient is unresponsive. 3.Brainstem reflexes are absent. 4.An apnea test shows no breathing. 5.Laboratory tests are not required unless the clinical diagnosis is uncertain. Note: the guidelines are different for diagnosis of brain death in infants under 1 year of age. Note: the guidelines are different for diagnosis of brain death in infants under 1 year of age.

1. The cause of brain failure is irreversible Most brain deaths occur fromMost brain deaths occur from  Severe brain trauma  Massive stroke (usually hemorrhage)  Prolonged cardiac arrest Sufficient time has elapsed to insure irreversibilitySufficient time has elapsed to insure irreversibility  Post-cardiac arrest, 6 hours is a reasonable interval Absence of cerebral blood flow (on a CBF test) also documents an irreversible process.Absence of cerebral blood flow (on a CBF test) also documents an irreversible process.

2. The patient is unresponsive We're talking here about cerebral unresponsiveness.We're talking here about cerebral unresponsiveness.  Grimacing and other cranial-nerve responses are absent (except for CN XI).  Grimacing and other cranial-nerve responses are absent (except for CN XI).  Spinal reflexes, e.g. “spinal withdrawal”, can be present. Less common spinal movements include:Less common spinal movements include:  Fragments of decerebrate posturing (including neck extension)  The undulating toe sign  Lazarus sign

3. Brainstem reflexes are absent Pupillary light reflexPupillary light reflex  Pupils should be mid-position or large Vestibulo-ocular reflex (eye movements)Vestibulo-ocular reflex (eye movements)  Doll's eyes and ice-water calorics Corneal reflexCorneal reflex Gag and cough reflexGag and cough reflex  Response to suctioning

4. An apnea test shows no breathing Prerequisites: absence of respiratory depressants (CNS or peripheral), hypotension (SBP<100), or hypothermia (<36ºC).Prerequisites: absence of respiratory depressants (CNS or peripheral), hypotension (SBP<100), or hypothermia (<36ºC). If ODN or family has not yet been notified, please do so now!If ODN or family has not yet been notified, please do so now! Remove ventilator for at least 10 minutes while giving O 2 by tracheal cannula. Observe closely for breathing. Monitor BP and O 2 saturation continuously.Remove ventilator for at least 10 minutes while giving O 2 by tracheal cannula. Observe closely for breathing. Monitor BP and O 2 saturation continuously. The apnea test confirms brain death if the end-of-test PaCO 2 is ≥60 mmHg (or, ≥20 mmHg above pre-test PaCO 2 ).The apnea test confirms brain death if the end-of-test PaCO 2 is ≥60 mmHg (or, ≥20 mmHg above pre-test PaCO 2 ). If the apnea test cannot be completed, repeat it with better patient preparation, or do a cerebral blood flow test.If the apnea test cannot be completed, repeat it with better patient preparation, or do a cerebral blood flow test.

5. Laboratory tests Are not required unless the clinical diagnosis of brain death is uncertain.Are not required unless the clinical diagnosis of brain death is uncertain. The most commonly performed tests are serum chemistry and toxicology and CT scan of the brain.The most commonly performed tests are serum chemistry and toxicology and CT scan of the brain. Please put laboratory findings in clinical context!Please put laboratory findings in clinical context!  Abnormal chemistry or toxicology does not invalidate a diagnosis of brain death unless the clinical diagnosis is uncertain.  Presence of an intoxicant is relevant only if the quantity present would cause intoxication EEG is of very limited value for diagnosis of brain death, however it is mentioned in some pediatric brain death protocols.EEG is of very limited value for diagnosis of brain death, however it is mentioned in some pediatric brain death protocols.

5. Laboratory tests (continued) Perform a cerebral blood flow study (catheter angiogram, CTA, MRA, radionuclide study, transcranial doppler) when  cranial nerve examination is inhibited by peripheral lesions  the apnea test is invalidated by central or peripheral respiratory depressant drugs (you still do the apnea test)  the apnea test cannot be completed due to hypotension or hypoxia (do as much of the apnea test as can be done safely)  the brain failure is not clearly due to an irreversible process  in infants under the age of 1 year >95% of brain death evaluations do not require a CBF study

One exam or two? Prior to 2010, brain death guidelines specified that the brain death exam had to be performed twicePrior to 2010, brain death guidelines specified that the brain death exam had to be performed twice  AAN (1995): suggested 6 hour interval between exams There was never any evidence supporting this!There was never any evidence supporting this!  There are no reports of recovery after a properly performed brain death exam shows no brain functions  Lustbader et al. (2011): 2nd exam unnecessary on 1300 brain death evaluations, also 24-hour delay in diagnosis AAN 2010: single exam is sufficient if performed by qualified examiner "several hours" after incident eventAAN 2010: single exam is sufficient if performed by qualified examiner "several hours" after incident event  NYSDOH: does not disagree and will be updating state guidelines

Guidelines for infants <1 year of age Below age 1 year, the observation period should be 24 hours, and a confirmatory test should be performed.Below age 1 year, the observation period should be 24 hours, and a confirmatory test should be performed. Below age 2 months, the observation period should be 48 hours.Below age 2 months, the observation period should be 48 hours. Below age 1 week (and in premature infants), the diagnosis of brain death may be unreliable.Below age 1 week (and in premature infants), the diagnosis of brain death may be unreliable. Everyone agrees these guidelines for infants are excessively conservative.Everyone agrees these guidelines for infants are excessively conservative.

"Clinical triggers" for brain death Suspect brain death when a patient with severe brain injury (e.g., from trauma, stroke, or anoxia)Suspect brain death when a patient with severe brain injury (e.g., from trauma, stroke, or anoxia)  Is unresponsive  Has pupils that do not react to light  Requires a ventilator for breathing Do not assume that "triggered" breaths are initiated by patient respiratory activity Do not assume that "triggered" breaths are initiated by patient respiratory activity

When you suspect brain death 1. Document your findings.  You don't have to be a brain death expert to document that the pupils and corneals are nonreactive, the eyes don't move, there is no response to suctioning, and there are no spontaneous breaths. 2. Obtain consultation from a designated brain death expert.  Requirements for privileging vary by institution. Experts do not necessarily have to be neurologists or neurosurgeons. 3. Contact the patient's family or significant other (if known).  Or, contact hospital administration to help find the patient's family.  Or, contact hospital administration to help find the patient's family. 4. Contact the NY Organ Donor Network: GIFT-4-NY  You must do this even if the patient will not be an organ donor.

References  Wijdicks E.F.M, et al. Evidence-based guideline update: Determining brain death in adults: Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2010; 74:  Lustbader D, et al. Second brain death examination may negatively affect organ donation. Neurology 2011; 76:1-6.  New York State Department of Health: Guidelines for determining brain death, December n_death/docs/determination_of_brain_death.pdf