Brain Death: The Neurologists Perspective

1
Brain Death The Neurologists Perspective

• Stephen T. Mernoff, MD
• Clinical Assistant Professor of Neurology, Brown
  Medical School
• Medical Director, Neurorehabilitation Program,
  Rehabilitation Hospital of Rhode Island
• Staff Neurologist, Roger Williams Medical Center

2
Law Order
3
I thought this would be easy

• i.e. a 15 minute discussion outlining the
  standard, uniformly accepted and applied criteria
  for brain death and the method for its
  determination

4
But

• Not uniformly defined between institutions
• Not one universally accepted standard
• Not one universally and consistently applied
  algorithm for determination
• If one subject in health law and bioethics can
  be said to be at once well settled and
  persistently unresolved, it is how to determine
  that death has occurred. Rosenbaum, S. Ethical
  conflicts. Anesthesiology 1999913-4

5
Versalius

• Madrid, 1564
• Anatomist
• At autopsy thorax opened?heart beating!
• Forced to leave Spain
• This event and others ? need for formal
  pronouncement of death

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Death traditional cardiopulmonary definition

• Asystole
• AND
• Apnea

7
Mollaret P and Goulon M. Le coma dépassé a
state beyond coma. Rev Neurol 19591013-15

• Concept of Brain Death introduced authors
  believed there was a definable condition from
  which recovery was impossible
• Criteria suggested
• Not recognized widely

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• Driving forces advances in care
• mechanical ventilation and ICUs
• Organ transplantation cadaver (non-heart-beating)
  donors but some surgeons harvesting from
  patients with neurologic catastrophes patients
  died after transplantation
• Many surgeons uncomfortable with this but live
  donors improved transplant outcomes
• When has irreversible loss of full brain function
  occurred?
• --premise not idea that brain, therefore
  person, is dead
• rather coma irreversible and care futile

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• Purpose to define irreversible coma as a new
  criterion for death.
• There are two reasons why there is need for a
  definition
• 1) improvements in resuscitative and supportive
  measuressometimesonly partial successresult is
  an individual whose heart continues to beat but
  whose brain is irreversibly damaged. The burdern
  is great on patients who suffer permanent loss of
  intellect, on their families, on the hositals,
  and those in need of hospital beds already
  occupied by those comatose patients.

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• Note presented in narrative rather than
  algorithmic form stricter than ever before, but
  not strict enough (e.g. EEG duration criteria)
• Purpose to define irreversible coma as a new
  criterion for death.
• There are two reasons why there is need for a
  definition
• 2) Obsolete criteria for the definition of death
  can lead to controversy in obtaining organs for
  transplantation.

11
Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• An organ, brain or other, that no longer
  functions and has no possibility of functioning
  again is for all practical purposes dead.
• A. determine presence of a permanently
  nonfunctioning brain.
• 1. Unreceptivity and Unresponsitivity total
  unawareness to externally applied stimulieven
  the most intensely painful stimuli evoke no vocal
  or other response, not even a groan, withdrawal
  of a limb, or quickening of respiration.
• 2. No Movements or Breathing no spontaneous
  movements or spontaneous respiration (turn off
  respirator for 3 minutes prior to trial
  breathing room air for 10 minutes and pCO2
  normal) or response to pain, touch, sound or
  light for an hour.

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• A. determine presence of a permanently
  nonfunctioning brain.
• 3. No reflexes pupils fixed, dilated and absence
  of
• Pupillary response to bright light
• ocular movement to head turning and ice water
  irrigation of ears
• blinking
• postural activity (decerebrate or other)
• Swallowing, yawning, vocalization
• Corneal reflexes
• Pharyngeal reflexes
• Deep tendon reflexes
• Respnse to plantar or noxious stimuli

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• B. confirmatory data
• 4. isoelectric EEG (specifies technique have EKG
  and noncephalic leads to r/o confounders At
  least 10 full minutes of recording are desirable,
  but twice that would be better. !)
• EEG when available it should be utilized
• If EEG unavailable, the absence of cerebral
  function has to be determined by purely clinical
  signsor by absence of circulation as judged by
  standstill of blood in the retinal vessels, or by
  absence of cardiac activity.
• A and B all need to be repeated 24 hours later
  with no ? AND in the absence of hypothermia
  (lt90F 32.2C) or CNS depressants, such as
  barbiturates, and determined only by a physician

14
Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• If criteria are met, Death is to be declared and
  then the respirator turned off. The decision to
  do this and the responsibility for it are to be
  taked by the physician-in-charge, in consultation
  with one or more physicians who have been
  directly involved in the case. It is unsound and
  undesirable to force the family to make the
  decision.

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Harvard CriteriaReport of the Ad Hoc Committee
of the Harvard Medical School to Examine the
Definition of Brain Death. A definition of
irreversible coma. JAMA 1968205337-340

• Controversy
• Physicians concerned desire to remove burden of
  decision off the transplant surgeon
• Public concern press concerned that Brigham
  doctors were playing god by removing organs.
  Murray JE. Surgery of the soul reflectins on a
  curious career. Canton, MA Science History
  Publications, 2001.
• Subsequent literature concerned that criteria
  biased by participation of transplant surgeons on
  the committee whose programs could advance with
  brain death defined
• Wijdicks NEUROLOGY 200361970-976 finds little
  basis for this in his review of the committees
  documents

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186

• Report of the Medical Consultants on the
  Diagnosis of Death to the Presidents Commission
  for the Study of Ethical Problems in Medicine and
  Biomedical and Behavioral Research
• Developed as an aid to implementation of the
  proposed Uniform Determination of Death Act
  (endorsed by ABA, AMA, Natl Confernece of
  Commissioners on Uniform State Laws, Presidents
  Commission for the Study of Ethical Problems in
  Medicine and Biomedical and Behavioral Research,
  AAN, AES

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186

• Uniform Determination of Death Act
• An individual who has sustained either (1)
  irreversible cessation of circulatory and
  respiratory functions, or (2) irreversible
  cessation of all functions of the entire brain,
  including the brain stem, is dead. A
  determination of death must be made in accordance
  with accepted medical standards.

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• Note presented in somewhat narrative and
  somewhat algorithmic form improvement from
  Harvard criteria but still room for
  interpretation of what to do and when.
• An individual presenting the findings in either
  section A (Cardiopulmonary) or section B
  (neurological) is dead.a diagnosis of death
  requires that both cessation of functions and
  irreversibilitybe demonstrated.

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• A. An individual with irreversible cessation of
  circulatory and respiratory functions is dead.
• 1. Cessation is recognized by an appropriate
  clinical examination.at least absence of
  responsiveness, heartbeat, and respiratory
  effort.may require the use ofECG.
• 2. Irreversibility is recognized by persistent
  cessation of functions during an appropriate
  period of observation and/or trial of therapy.
  duration of observation period dependent on
  whether is expected vs. unexpected, whether
  resuscitation attempted, or moment of possible
  death is witnessed or not

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• B. An individual with irreversible cessation of
  all functions of the entire brain, including the
  brain stem, is dead.
• 1. Cessation is recognized when evaluation
  discloses findings of a and b
• a. Cerebral functions are absent, and
• Deep coma (unreceptivity and unresponsivity)
• Medical circumstances may require the use of
  confirmatory studies such as an EEG or blood-flow
  study. ??Those circumstances not specified!
• b. Brainstem functions are absent determined by
  testing pupillary light, corneal, oculocephalic,
  oculovestibular, oropharyngeal, and respiratory
  (apnea) reflexes

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• B. An individual with irreversible cessation of
  all functions of the entire brain, including the
  brain stem, is dead.
• 1. Cessation is recognized when evaluation
  discloses findings of a and b
• b. Brainstem functions are absent determined by
  testing pupillary light, corneal, oculocephalic,
  oculovestibular, oropharyngeal, and respiratory
  (apnea) reflexes When these reflexes cannot be
  adequately assessed, confirmatory tests are
  recommended.
• Apnea testing specified O2 ventilation x 10
  minutes then w/d ventilator with passive flow of
  O2,, confirm pCO260 by ABG spontaneous
  breathing efforts indicate that part of the brain
  stem is functioning.

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• B. An individual with irreversible cessation of
  all functions of the entire brain, including the
  brain stem, is dead.
• 1. Cessation is recognized when evaluation
  discloses findings of a and b
• Peripheral nervous system activity and spinal
  cord reflexes may persist after death. True
  decerebrate or decorticate posturing or seizures
  are inconsistent with the diagnosis of death.

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Guidelines for the Determination of Death JAMA
11/13/1981246(19),2184-2186 Criteria

• B. An individual with irreversible cessation of
  all functions of the entire brain, including the
  brain stem, is dead.
• 2. Irreversibility is recognized when evaluation
  discloses findings of a and b and c or by
  absence of blood flow to the brain 10 minutes,
  shown by angiography
• a. The cause of coma is established and is
  sufficient to account for the loss of brain
  functions, and
• b. the possibility of recovery of any brain
  functions is excluded, and (i.e. rule out
  sedation, hypothermia lt32.2C core temp,
  neuromuscular blockade, and shock)
• c. the cessation of all brain functions persists
  for an appropriate period of observation and/or
  trial or therapy (6 hours 12 hours if no
  confirmatory tests 24 hours if anoxic injury)

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014

• Report of the Quality Standards Subcommittee of
  the American Academy of Neurology
• Brain Death Definition the irreversible loss of
  functin of the brain, including the brainstem.
• Justification need for standardization of the
  neurologic examination criteria for the diagnosis
  of brain death.
• Process based on review of literature 1976-1994
  are GUIDELINES (class II evidence or strong
  consensus of class III evidence)
• Format algorithm with precise definitions and
  precisely specified exam methods

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 I. Diagnostic Criteria

• A. Prerequisites
• 1.Clinical or neuroimaging evidence of an acute
  CNS catastrophe that is compatible with the
  clinical diagnosis of brain death
• 2. Exclusion of complicating medical conditions
  (electrolyte, acid-base, endocrine)
• 3.No drug intoxication or poisoning
• 4. Core temperature 32C(90F)

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 I. Diagnostic Criteria

• B. Coma, lack of brainstem reflexes, and apnea
• 1.Coma or unresponsiveness (defined
  specifically)
• 2. Absence of brainstem reflexes (defined
  specifically)
• Pupils
• Ocular movement
• Facial sensation and facial motor response
• Pharyngeal and tracheal reflexes

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 I. Diagnostic Criteria

• B. Coma, lack of brainstem reflexes, and apnea
• 3. Apnea very specific description of apnea
  testing protocol e.g. core temp 36.5C BP,
  volume, baseline PO2 and PCO2

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 II. Pitfalls in the diagnosis
of brain death

• A. Severe facial trauma
• B. Preexisting pupillary abonormalities
• C. Toxic levels of any sedatives,
  aminoglycosides, TCAs, anticholinergics, AEDs,
  chemotherapeutic agents, or NM blocking agents
• D. Chronic CO2 retention

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 III. Clinical observations
compatible with the diagnosis of brain death

• A. Spontaneous movements
• B. Respiratory-like movements
• C. Sweating, blushing, tachycardia
• D. Normal BP without pressors
• E. Absence of diabetes insipidus
• F. DTRs, superficial abdominal reflexes, triple
  flexion response
• G. Babinski reflex

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 IV. Confirmatory laboratory
tests (Options)

• Brain death is a clinical diagnosis. A repeat
  clinical evaluation 6 hours later is recommended,
  but this interval is arbitrary. A confirmatory
  test is not mandatory but is desirable in
  patients in whom specific components of clinical
  testing cannot be reliably performed or
  evaluated.most sensitive test is listed first

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 IV. Confirmatory laboratory
tests (Options)(specific criteria described for
all)

• A. Conventional Angiography
• B. EEG no electrical activity over 30
• C. Transcranial Doppler U/S
• D. Technetium-99m HMPA brain scan
• E. Somatosensory evoked potentials

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Practice parameters for determining brain death
in adults (summary statement) NEUROLOGY
1995451012-1014 V. Medical record
documentation (Standard)

• A. Etiology and irreversibility of condition
• B. Absence of brainstem reflexes
• C. Absence of motor response to pain
• D. Absence of respiration with PCO260 mm Hg
• E. Justification for confimatory test and result
  of confirmatory test
• F. Repeat neurologic examination Option the
  interval is arbitrary, but a 6-hour period is
  reasonable

33
Canadian criteria Guidelines for the diagnosis of
brain death. Canadian Neurocritical Care Group.
Can J Neurol Sci 19992664-6

• I havent obtained this reference yet but
  secondary report
• Doesnt require testing of oculocephalic reflex
• Permits core temperature as low as 32.2C during
  the apnea test
• Interval between exams as short as 2 hours as
  long as 24 hours for anoxic-ischemic insult

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State Law

• Practice parameters for determining brain death
  in adults (summary statement) NEUROLOGY
  1995451012-1014
• Regardless of the conclusions of this statement
  , the Quality Standards Subcommittee of the AAN
  recognizes the need to comply with state law.
• Does RI have an applicable statute?
• RIDOH has no specific policy or guidelines for
  Brain Death determination leaves it to
  institutions to develop their own
• ?should Ethics Network look into standardization
  across the state?

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Brain Death Protocols in some RI hospitals

• Hospital 1 no protocol
• Hospital 2 based on Presidents Commission but
  criteria somewhat vague and only semi-algorithmic
• Hospital 3 based on 1995 Practice Parameters
  precise criteria and precise algorithm provided
• Other hospitals around the state?

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Brain Death around the worldWijdicks EFM. Brain
death worldwide Accepted fact but no global
consensus in diagnostic criteria NEUROLOGY
20025820-25

• Guidelines of 80 countries reviewed
• Legal standards on organ transplantation present
  in 69 (55 of 80 countries)
• Practice guidelines for brain death for adults in
  88
• 50 guidelines require gt1 physician to declare
• All guidelines specified exclusion of
  confounders, presence of irreversible coma,
  absent motor response, and absent brainstem
  reflexes
• Apnea testing required in 59
• differences in time of observation and required
  expertise of examining physicians
• Confirmatory laboratory testing mandatory in 28
  of 70 (40) guidelines

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Brain Death around the worldWijdicks EFM. Brain
death worldwide Accepted fact but no global
consensus in diagnostic criteria NEUROLOGY
20025820-25

• Conclusion uniform agreement on the neurologic
  exam with exception of the apnea test but other
  major differences found in the procedures for
  diagnosing brain death in adults, and
  standardization should be considered.

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Misconceptions

• 1. There is one nationally or internationally
  accepted standard for determination of brain
  death. In fact there is variability and
  inconsistency over time and at single points in
  time including the present
• between published guidelines (differences between
  1968 Harvard criteria, 1981 Presidents
  Commission, 1995 Practice Parameters 1999
  Canadian criteria)
• between jurisdictions (especially
  internationally)
• among patient populations
• in the use of confirmatory tests

39
Misconceptions Brain Death ?sufficient for
withdrawal of mechanical ventilation

• Case ICU patient multi-organ failure, comatose
  since cardiopulmonary arrest. Caregivers feel
  ongoing tx futile but family wants to continue.
  Neurology consult requested to determine if
  Brain Death applies to ?convince family to
  change to CMO. Implication also that if Brain
  Death determined, ICU could d/c vent even if
  family disagreed. No potential for organ
  donation.
• Hospital didnt have Brain Death Protocol
• ?state law doesnt define brain death (???)
• Consultant dont need brain death for this
  need good communication with family so they
  understand fully the prognosis and valid option
  to withdraw interventions (even ventilation)

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?Misconceptions Brain Death ?necessary for
withdrawal of mechanical ventilation

• brain death originally motivated by potential
  for organ transplantation but concept often being
  invoked for decision-making even when there is no
  potential for organ donation

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misconceptions

• All medical personnel, especially ICU staffs,
  have consistent and accurate understandings of
  brain death criteria
• 64 physicians and 28 of non-physician staff
  correctly identified clinical criteria for brain
  death and/or correctly identified patients as
  dead vs. alive in case scenarios
• Brain death loss of cortical function
• i.e. need loss of brainstem function as well

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Pitfalls

• Incorrect application of accepted criteria Van
  Norman GA, A matter of life and death.
  Anesthesiology 199991275-87
• e.g. 2 patients with devastating brain injuries
  certified as brain dead and referred for organ
  donation despite the presence of spontaneous
  respirations and in one of them movement during
  organ retrieval leading to use of muscle
  relaxants and general anesthesia
• e.g. brain death determined after patient
  received IV muscle relaxants and Mg low
  (eventually patient discharged home alert and
  oriented)

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Controversies

• Philosophically, why need loss of brainstem
  function as well? i.e. Harvard criteria based on
  irreversibility of coma and futility of care, not
  death of the person.

44
Going forward

• Are current Brain Death criteria satisfactory?
  Some are calling for additional study to see if
  they are as reliable as conventional wisdom
  suggests and many believe.
• Dead, or Dead Enough? Current algorithms use
  certain measures but those just measure brain
  activity above a certain threshold along a
  continuum. Maybe some cells still functioning?
  How to determine that threshold?

45
Going Forward Doig CJ and Burgess E, Brain Death
resolving inconsistencies in the ethical
declaration of death. Can J Anesth
200350(7)725-31

• Are current Brain Death criteria satisfactory?
  Some are calling for additional study to see if
  they are as reliable as conventional wisdom
  suggests and many believe.
• Tests of cortical and subcortical brain function
  lack specificity
• Inconsistency of clinical criteria

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Going forward

• A need for more uniform criteria note difficulty
  I had in obtaining front-line (i.e. hospital)
  level information and variability between
  hospitals within the state!
• Within the state
• nationally
• ?internationally
• Ethics network look into this, determine what the
  various hospitals have and dont have,
  andadvocate for more uniform criteria within
  Rhode Island?

47
Rosenbaum, S. Ethical conflicts. Anesthesiology
1999913-4

• If one subject in health law and bioethics can
  be said to be at once well settled and
  persistently unresolved, it is how to determine
  that death has occurred.

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