1. BRAIN DEATH Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta

2. 2 Background Before the 1960’s, donation after cardiac death (DCD) was the general approach to organ donation 1968, an ad hoc committee at Harvard Medical School proposed a neurologic based death definition, which replaced DCD

3. 3 Background 1980, with modifications, by the President’s Commission for the Study of Ethical Problems in Medicine & Biomedical Research, as a recommendation for state legislature & court The “brain death” standard was also employed in the model legislation known as the Uniform Determination of Death Act, which has been enacted by a large number of jurisdictions & the standard has been endorsed by the influential American Bar Association

4. 4 Background Even though there has been legal acceptance of the concept of brain death, there is a lack of a standardized approach No national brain death law exists State law & statutes may restrict the determination of brain death Reasons for revising guidelines –Allow physicians to pronounce brain death in pediatric patients in a more precise and orderly manner –Appropriate documentation

5. 5 Brain Death An individual who has sustained either –Irreversible cessation of circulatory & respiratory functions –Irreversible cessation of all functions of the entire brain, including the brainstem, is dead

6. 6 The Examination – human brain Cerebrum: memory, consciousness & higher mental function Cerebellum: controls various muscle functions Brain stem consisting of the midbrain, pons & medulla, which extends downwards to become the spinal cord –Controls respiration & various basic reflexes (e.g., swallow & gag)

7. 7 Coma Deep coma –Non responsive to most external stimuli –At most, such patients may have a dysfunctional cerebrum but, by virtue of the brain stem remaining intact, are capable of spontaneous breathing & heartbeat PVS: persistent vegetative state

8. 8 Organ function Heart –Needs O 2 to survive & w/o O 2 will stop beating –Not controlled by the brain but it is autonomous Breathing –Controlled by vagus nerve, located in the brain stem –Main stimulant is increase in CO 2 in the blood »Causes the diaphragm & chest muscles to expand »Spontaneous breathing can not occur after brain stem death With artificial ventilation, the heart may continue to beat for a period of time after brain stem death Time lag between brain death & circulatory death is ~2-10 days

9. 9 Initial requirements Clinical or radiographic evidence of an acute catastrophic cerebral event c/w dx of brain death Exclusion of conditions that confound clinical evidence (i.e. metabolic) Confirmation of absence of drug intoxication or poisoning –Including barbituratds, NMB;s Core body temp > 35 o C

10. 10 Term – 18 yrs of age Determination of brain death by neurologic examination should be performed in the setting of normal age- appropriate physiological parameters –Corrected hypotension, metabolic disturbances, recent administration of neuromuscular blockaded, or any drug intoxication Placement of an arterial line is recommended for close monitoring of BP & PaCO 2

11. 11 Hypothermia & Brain Death An adjunctive therapy for acute brain injury –Reduces cerebral metabolic activity Hypothermia is known to depress cerebral activity –May lead to a false diagnosis of brain death –Adequately re-warm with rec. 12 hrs of normal temperature prior to performing brain death exam A core body temperature of >35 o C should be achieved prior to doing brain death exam –Previous guidelines stated that the patient should not be significantly hypothermic but no definition was provided

12. 12 Drugs Long acting or continuous infusions of sedative agents should be discontinued When available levels should be obtained & documented to be in a low to mid therapeutic range If a neuromuscular blocking agent has been used, confirmation of it’s clearance should be established

13. 13 Observation Period General consensus was the younger the child the longer the waiting period –If ancillary studies supported the diagnosis of brain death, the observation period could be shortened

14. 14 Observation Period 2011 Guidelines –Examinations should be performed by 2 separate attendings –Both apnea tests may be performed by the same physician –Recommends: »37 weeks up to 30 days: 24 hours »>30 days – 18 yrs: 12 hours

15. 15 It is reasonable to defer neurologic examination to determine brain death for >24 hrs if dictated by clinical judgment –After cardiopulmonary arrest –If apnea testing cannot be performed If patient is not stable enough to perform certain parts of the exam, ancillary testing may be used to assist in the diagnosis

16. 16 Ancillary Studies Four vessel cerebral angiography is the gold standard for determining the absence of CBF EEG & radionuclide CBF are the most widely used methods Radionuclide CBF can be used in patients with high dose barbiturate therapy

17. 17 Ancillary Studies Ancillary studies are not required and should not be used as a substitute to the clinical exam They must be used when –Components of the exam or apnea test cannot be completed safely –Uncertainty about the results –Medication effect may be present –Reduce the inter-examination observation period

18. 18 Basic exam 1 - Pain Cerebral motor response to pain –Supra-orbital ridge, the nail beds, trapezius –Motor responses may occur spontaneously during apnea testing (spinal reflexes) –Spinal reflex responses occur more often in young –If patient had NMB, then confirm clearance with train-of-four Spinal arcs are intact!

19. 19 Basic exam 2 - Pupils Round, oval or irregularly shaped Midsize 94-6 mm0, but may be totally dilated Absent pupillary light reflex –Although drugs can influence pupillary size, the light reflex remains intact only in the absence of brain death –IV atropine does not markedly affect response –Paralytics do not affect pupillary size –Topical administration of drugs and eye trauma may influence pupillary size and reactivity –Pre-existing ocular anatomic abnormalities may also confound pupillary assessment in brain death

20. 20 Basic exam 3 – Eye movement Oculocephalic reflex = doll’s eyes Vestibulo-ocular = cold caloric test

21. 21 Doll’s eyes Oculocephalic reflex –Rapidly turn the head 90° on both sides –Normal response = deviation of the eyes to the opposite side of head turning –Brain death = oculocephalic reflexes are absent (no Doll’s eyes) = no eye movement in response to head movement Not Barbie, but old fashioned type dolls –Painted vs. wooden eyes in porcelain heads

22. 22 Doll’s eyes

23. 23 Cold calorics Elevate the HOB 30° Irrigate both tympanic membranes with iced water –Observed pt for 1 min after each ear irrigation, with a 5 min wait between testing of the other ear –Facial trauma involving the auditory canal & petrous bone can also inhibit these reflexes

24. 24 Cold calorics Nystagmus both eyes slow toward cold, fast to midline –Not comatose Both eyes tonically deviate toward cold water –Coma with intact brainstem Movement only of eye on side of stimulus –Internuclear ophthalmoplegia –Suggests brainstem structural lesion No eye movement –Brainstem injury/death

25. 25 Basic exam 4 – Facial sensory & motor responses Corneal reflexes are absent in brain death –Corneal reflexes – tested by using a cotton-tipped swab –Grimacing in response to pain can be tested by applying deep pressure to the nail beds, supra-orbital ridge, TMJ, or swab in nose –Severe facial trauma can inhibit interpretation of facial brain stem reflexes

26. 26 Basic exam 5 – Pharyngeal & tracheal responses Both gag & cough reflexes are absent in pts w/brain death –Gag reflex can be evaluated by stimulating the posterior pharynx w/a tongue blade, but the results can be difficult to evaluate in orally intubated patients –Cough reflex can be tested by using ETT suctioning, past end of ETT

27. 27 Apnea Testing Should be performed with each test unless there is a clinical contraindication –If cannot be performed an ancillary test should be performed to assist PaCO 2 >60 mmHg has been used as the threshold to stimulate ventilatory efforts

28. 28 Apnea Testing Technique: –Normalization of pH & PaCO 2 –Maintenance of core temperature > 35 o C degrees –Normalization of BP – age appropriate –Pre-oxygenation for 5-10 min with 100% oxygen via connectin to t- piece or self-inflating bag –Apneic oxygenation for ~6 min PaCO 2 should rise >20 mmHg above baseline & >60 mmHg

29. 29 Ancillary Studies Four vessel cerebral angiography is the gold standard for determining the absence of CBF EEG & radionuclide CBF are the most widely used methods –Cerebral blood flow = perfusion scan

30. 30 Cerebral perfusion scan

31. 31 Common misconceptions Since there is a heartbeat, he is alive –Brain dead pts have permanently lost the capacity to think, be aware of self or surroundings, experience, or communicate w/others He’s in a coma –Reinforce that they are dead With rehab/time he’ll get better –Irreversible, dead brain cells do not regrow

32. 32 How to make it clear Say “dead”, not “brain dead” Say “artificial or mechanical ventilation”, not “life support” Time of death = neurologic determination –NOT when ventilator removed –NOT when heart beat ceases Do not say “kept alive” for organ donation Do not talk to the pt as if he’s still alive

33. 33 Ancillary Studies If EEG shows electrical activity or CBF study shows evidence of flow, patient cannot be pronounced dead Patient should be medically treated until brain death can be established solely on clinical examination & apnea testing If repeat ancillary testing is performed, a waiting period fo 24 hours should be observed

34. 34 Ancillary Studies If an ancillary study, in conjunction with the first neurologic examination, supports the diagnosis of brain death, the inter-examination observation period can be shortened The second test can be performed at any time thereafter for children of all ages

35. 35 2011 Strong Evidence High – further research is very unlikely to change our confidence in the estimate of effect When an ancillary study is used because there are inherent examination limitations, then components of the examination done initially should be completed & documented

36. 36 2011 Strong Evidence High – further research is very unlikely to change our confidence in the estimate of effect When an ancillary study is used because there are inherent examination limitations, then components of the examination done initially should be completed & documented Determination of brain death in neonates, infants & children relies on a clinical diagnosis that is based on the absence of neurologic function with a known irreversible cause of coma. Coma & apnea must coexist to diagnose brain death.

37. 37 2011 Strong Evidence Prerequisites for initiating a brain death evaluation: –Hypotension, hypothermia, & metabolic disturbances that could affect the neurologic examination must be corrected before the examination for brain death

38. 38 2011 Strong Evidence Declaration of death: –Death is declared after confirmation & completion of the second clinical examination & apnea test –When ancillary studies are used, documentation of components from the second clinical examination that can be completed must remain consistent with brain death. All aspects of the clinical examination including the apnea test, or ancillary studies must be appropriately documented

39. 39 2011 Strong Evidence The clinical examination should be carried out by experienced clinicians who are familiar with infants & children & have specific training in neuro-critical care The examination should be performed by different attending physicians involved in the care of the child The apnea test may be performed by the same physician, preferably the attending physician who is managing ventilator care of the child – low evidence but strong recommendation

40. 40 2011 Moderate Evidence Prerequisites for initiating a brain death examination –Sedatives, analgesics, NMB & anti-convulsant agents should be discontinued for a reasonable time period based on elimination half- life of the pharmacologic agent to ensure they do not affect the neurologic examination »Knowledge of the total amount of each agent (mg/kg) administered since hospital admission may provide useful information concerning the risk of continued medication effects

41. 41 2011 Moderate Evidence Prerequisites for initiating a brain death examination –Sedatives, analgesics, NMB & anti-convulsant agents should be discontinued for a reasonable time period based on elimination half- life of the pharmacologic agent to ensure they do not affect the neurologic examination »Knowledge of the total amount of each agent (mg/kg) administered since hospital admission may provide useful information concerning the risk of continued medication effects –Blood or plasma levels to confirm high or supra-therapeutic levels of anti-convulsant with sedative effects should be obtained (if available) & repeated as needed or until the levels are in the low to mid-therapeutic range

42. 42 2011 Moderate Evidence The diagnosis of brain death based on neurologic exam alone should not be made if supra-therapeutic or high therapeutic levels of sedative agents are present –When levels are in the low or in the min-therapeutic range, medication effects sufficient to affect the result of the neurologic exam are unlikely –If uncertainty remains, an ancillary study should be performed

43. 43 2011 Moderate Evidence Assessment of neurologic function may be unreliable immediately after cardiopulmonary resuscitation or other severe acute brain injuries & evaluation for brain death should be deferred for 24-48 hrs if there are concerns or inconsistencies in the exam Number of exams, examiners & observation periods –2 exams including apnea testing with each exam separated by an observation period are required