2. Brain Death Clinical evaluation & Ancillary tests P. Sariaslani
Brain Death Clinical evaluation & Ancillary tests P.Sariaslani. MD Assistant Professor of Neurology Medical College of Kermanshah

3. The state of consciousness (arousal)
The ascending RAS, from the lower border of the pons to the ventromedial thalamus
The cells of origin of this system occupy a paramedian area in the brainstem

4. To cause coma, as defined as a state of unconsciousness in which the eyes are closed and sleep–wake cycles absent
Lesion of the cerebral hemispheres extensive and bilateral
Lesions of the brainstem: above the lower 1/3 of the pons and destroy both sides of the paramedian reticulum

5. Reticular Activating System
Normal Brain Anatomy
Cerebral Cortex
Reticular Activating System
Brain Stem

7. Brain Stem

8. Brain Stem
Midbrain
Cranial Nerve III
pupillary function
eye movement

9. Brain Stem Pons Cranial Nerves IV, V, VI conjugate eye movement
corneal reflex

10. Brain Stem Medulla Cranial Nerves IX, X Pharyngeal (Gag) Reflex
Tracheal (Cough) Reflex
Respiration

11. In most adult series, trauma and subarachnoid hemorrhage are the most common event leading to brain death.
Others include intracerebral hemorrhage, hypoxic ischemic encephalopathy, and ischemic stroke. Any condition causing permanent widespread brain injury can lead to brain death.

12. Causes of Brain Death
Normal
Cerebral Hemorrhage

13. Causes of Brain Death
Cerebral Anoxia
Normal

14. Subarachnoid Hemorrhage
Causes of Brain Death
Subarachnoid Hemorrhage
Normal

15. Causes of Brain Death
Normal
Trauma

16. Causes of Brain Death
Meningitis
Normal

17. Mechanism of Cerebral Death
ICP>MAP is incompatible with life
Increased Intracranial
Pressure

18. Conditions Distinct From Brain Death
Persistent Vegetative State
Locked-in Syndrome
Minimally Responsive State

19. Vegetative state (coma vigil, apallic syndrome)
Patients who survive coma do not remain in this state for > 2–3 weeks, but develop a persistent unresponsive state in which sleep–wake cycles return.
After severe brain injury, the brainstem function returns with sleep–wake cycles, eye opening in response to verbal stimuli, and normal respiratory control.

20. Locked in syndrome
Patient is awake and alert, but unable to move or speak.
Pontine lesions affect lateral eye movement and motor control
Lesions often spare vertical eye movements and blinking.

21. Vegetative
Locked-in

22. Minimally Responsive State
Static Encephalopathy
Diffuse or Multi-Focal Brain Injury
Preserved Brain Stem Function
Variable Interaction with Environmental Stimuli

23. Brain Death Neurological Examination
Clinical Prerequisites:
Known Irreversible Cause
Exclusion of Potentially Reversible Conditions
Drug Intoxication or Poisoning
Electrolyte or Acid-Base Imbalance
Endocrine Disturbances
Core Body temperature > 32° C

25. To ensure that the cessation of brain function is “irreversible,” physicians must:
determine the cause of coma
exclude mimicking medical conditions
- observe the patient for a period of time to exclude the possibility of recovery

26. ●Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death, ie, the cause of brain death should be known.
●Core temperature >36ºC (97ºF). Hypothermia may also confound the diagnostic assessment of brain death and can also delay the increase in PaCO2 necessary to complete the apnea test.
● There is little evidence base for a choice of threshold temperature. Canadian forum recommendations published in 2006 use 34ºC as a standard .
●Normal systolic blood pressure >100 mm Hg. Vasopressors may be required.

27. Brain Death Current Consensus
Absent Cerebral Function
Absent Brainstem Function
Apnea

29. Coma No Response to Noxious Stimuli Nail Bed Pressure Sternal Rub
Supra-Orbital Ridge Pressure

30. Flexion of the upper limb with extension of the lower limb (decorticate response) and extension of the upper and lower limb (decerebrate response) indicate a more severe disturbance and prognosis.

31. Absence of Brain Stem Reflexes
Pupillary Reflex
Eye Movements
Facial Sensation and Motor Response
Pharyngeal (Gag) Reflex
Tracheal (Cough) Reflex

32. Pupillary Reflex
Pupils dilated with no constriction to bright light

34. Eye Movements
Occulo-Cephalic Response
“Doll’s Eyes Maneuver”

36. Oculo-Vestibular Response “Cold Caloric Testing”

37. Facial Sensation and Motor Response
Corneal Reflex
Jaw Reflex
Grimace to Supraorbital or
Temporo-Mandibular Pressure

42. Confounding Clinical Conditions
Facial Trauma
Pupillary Abnormalities
CNS Sedatives or Neuromuscular Blockers
Hepatic Failure
Pulmonary Disease

43. Observations Compatible with Brain Death
Sweating, Blushing
Deep Tendon Reflexes
Spontaneous Spinal Reflexes- Triple Flexion
Babinski Sign

44. Dramatic spontaneous movements when severe hypoxia is attained upon terminal disconnection from the ventilator for Several minutes:
These include opisthotonos with chest expansion that simulates a breath, elevation of the arms and crossing them in front of the chest or neck
( Lazarus sign ), head-turning, shoulder-shrugging,
and variants of these posturing-like movements.
For this reason the advice that the family not be in attendance immediately after mechanical ventilation has been discontinued.

48. :Confirmatory Testing
- Recommended when the proximate cause of coma is not known or - when confounding clinical conditions limit the clinical examination

52. Confirmatory Testing
Cerebral Angiography
Normal
No Intracranial Flow

55. Electrocerebral Silence
Confirmatory Testing
EEG
Normal
Electrocerebral Silence

57. Confirmatory Testing
MR- Angiography

58. interpreted as consistent with brain death.
Brain death confirmed by small systolic peaks in early systole without diastolic flow, or reverberating flow, indicating very high vascular resistance associated with greatly increased intracranial pressure
Since as many as 10% of patients may not have temporal insonation windows
because of skull thickness, the initial absence of Doppler signals cannot be
interpreted as consistent with brain death.
CT, transcranial Doppler (TCD), and SPECT findings(A) Noncontrast head CT. (B) Multi-depth TCD power-motion mode (upper panel) and single-depth spectral analysis (lower panel) show reverberating flow in the right vertebral artery characterized by brief forward flow in systole (long arrow) followed by abrupt flow reversal in diastole (short arrow). (C) Brain scintigraphy reveals absent intracranial flow.

59. Somatosensory Evoked Potentials
Confirmatory Testing
Somatosensory Evoked Potentials

62. Clinical Questions
Are there patients who fulfill the clinical criteria of brain death who recover brain function?
What is an adequate observation period to ensure that cessation of neurologic function is permanent?
Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death?
What is the comparative safety of techniques for determining apnea?
Are there new ancillary tests that accurately identify patients with brain death?

63. Methods MEDLINE and EMBASE January 1996 to May 2009
A secondary bibliography search of all full-text articles
Relevant, fully published, peer-reviewed articles
Search terms included the MeSH term brain death and the text words brain death, irreversible coma, and apnea test.

64. Literature Review 367 abstracts 38 articles Exclusion criteria:
Articles that studied patients younger than 18 years
Articles that confirmed prior observations
Review articles, bioethical reviews, articles without description of a brain death examination
Articles with questionable practices or describing rarely used ancillary technology

65. AAN Level of Recommendations
A = Established as effective, ineffective or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population.
B = Probably effective, ineffective or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population.
C = Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population.
U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
Note that recommendations can be positive or negative.

66. Analysis of Evidence
Question 1: Are there patients who fulfill the clinical criteria of brain death who recover brain function?

67. Conclusion/Recommendation
In adults, recovery of neurologic function has not been reported after the clinical diagnosis of brain death has been established using the criteria given in the 1995 AAN practice parameter.
Recommendation:
The criteria for the determination of brain death given in the 1995 AAN practice parameter have not been invalidated by published reports of neurological recovery in patients who fulfill these criteria (Level U).

68. Analysis of Evidence
Question 2: What is an adequate observation period to ensure that cessation of neurologic function is permanent?

69. Conclusion/Recommendation
There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly.
Recommendation:
There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly (Level U).

70. Analysis of Evidence
Question 3: Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death?

71. Conclusion/Recommendation
For some patients diagnosed as brain dead, complex, non-brain-mediated spontaneous movements can falsely suggest retained brain function. Additionally, ventilator autocycling may falsely suggest patient-initiated breathing.
Recommendation:
Complex–spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead (Level C).

72. Analysis of Evidence
Question 4: What is the comparative safety of techniques for determining apnea?

73. Conclusion/Recommendation
Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing.  
Recommendation:
There is insufficient evidence to determine the comparative safety of techniques used for apnea testing (Level U).

74. Analysis of Evidence
Question 5: Are there new ancillary tests that accurately identify patients with brain death?

75. Conclusion/Recommendation
Because of a high risk of bias and inadequate statistical precision, there is insufficient evidence to determine if any new ancillary tests accurately identify brain death.
Recommendation:
There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain (Level U).

79. Thanks for your attention!