Bill Knight explains the concept of death by neurological criteria and the complexities surrounding organ donation in such situations. Bill discusses the process of dying, the definition of death, how to approach the neurologically dead patient and how to consider organ donation. Death is a complex topic. Due to advancements in medical technology and processes, the definition of death is a challenging one. Bill talks at length about the definition of death by the neurological criteria. Dying is an active process, whereas death is an event. The acceptance of death by the neurological criteria is often challenging as Bill will highlight. Bill talks about the care of the dying or dead patient. There is a point at which care will transition from supporting the patient to supporting the organs. This is still good care. There is an alignment of parallel intentions – first and foremost resuscitation of patients and then failing that, proceeding to considering and actioning organ donation. This is important due to the shortage of viable donor organ worldwide. The donation process itself is complex. Bill provides his thoughts. He insists that an intensivist be involved as this has been shown to increase the number of viable and healthy organs made available. The timing is also important. Available evidence does not support the need for immediate procurement after brain death. Taking time to optimise perfusion and allow recovery and cardiac function is appropriate and should be done. Bill also discusses other treatment options at the time of death such as optimising endocrine function. Finally, Bill will provide some practical considerations when communicating with the dead patient’s family. This involves being clear on your messaging. You are supporting organs, not life. To reinforce this point, Bill suggests not examining or talking to the patient. He also recommends using all of the available hospital support services. Similarly, it is best to not introduce the topic of organ donation to the family yourself as the treating clinician. Utilise the Organ Procurement Organisations (or similar services) and get them involved early to speak with the family. Join Bill Knight in his talk on the North American perspective on Organ Donation, brain death and management of the brain dead donor prior to organ donation. For more like this, head to our podcast page. #CodaPodcast

1. 14 June 2016
WilliamA Knight IV, MD, FACEP, FNCS
University of Cincinnati
Our role in organ donation and death by neurologic criteria
William.Knight@uc.edu
@waknight4

2. whoever saves a life…
it is considered as if he saved an entire world.
-- Mishnah Sanhedrin 4:5
BabylonianTalmud
Tractate Sanhedrin 37a

3.  Where is the soul/life force?
 Heart vs. Brain (vs. Liver)
 Stethoscope improvements
▪ Notion of heart as a fuel pump took some getting used to

4.  The majority of the patients that proceed to
donation are neurologically injured
 We areTERRIBLE at accurate prognosis

6. • Overall 50.8 % survived
• 13.2% had good functional outcome
• Bilaterally reactive pupils and GCS 3 = 75% survival

9.  There are no instances in which physiologically sound
resuscitation of the patient will harm organ donation
 Nor should that matter (in general)
 Alignment of parallel intentions
 Resuscitation of patient
 If that fails  organ viability

11.  Good critical care trumps all else
 Care for them like any other patient
 Do no more, do no less
 Good for the brain is good for the body
 Don’t be confused by rumor and innuendo

13.  Solid organs:
 2 lungs
 Heart
 2 kidneys
 Pancreas
 Liver
 Small bowel
 Tissues:
 Heart valves
 Skin
 Corneas
 Bone
 Inner ear
 Cartilage / tendons

14.  Organ donation is part of the thought process
well before brain death occurs
 Any patient in whom we are considering
limitation of care should be thought of as a
potential donor
 Donor management begins and ends with
autonomy

16. Donation
Brain Death
Donation
(BDD)
Donation after
Circulatory
Death (DCD)

19. • Physician role to predict death within 60 – 90 minutes
• Challenging to do well– family is relying on you

22.  Establish irreversible and proximate cause of coma
 Known neurologic process
▪ Guillain-Barre, brainstem encephalitis
▪ Hepatic failure, uremia, hyperosmolar coma, hypophosphatemia
 No metabolic or electrolyte abnormalities
 Absence of hypotension
▪ pressors
 Core body temperature > 92.5 F (vs 96.5F)
 No central nervous system depressants
▪ Intoxication
▪ Medical therapy
▪ Barbiturates, paralytics, narcotics, benzodiazepines, amitriptyline, toxic alcohols

24. Are there patients who fulfill the clinical criteria of brain death who recover
brain function?
 No
What is an adequate observation period to ensure that cessation of
neurologic function is permanent?
 Insufficient evidence to determine
Are complex motor movements that falsely suggest retained brain function
sometimes observed in brain death?
 Yes
Wijdicks, Evidence-based guideline update. Neurology 2010

25. What is the comparative safety of techniques for determining apnea?
 Apnea testing is safe but insufficient data to compare different techniques
Are there new ancillary tests that accurately identify patients
with brain death?
 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.
Wijdicks, Evidence-based guideline update. Neurology 2010

29.  Consequence of raised ICP + herniation
 Brainstem ischemia, rostral to caudal
 MIDBRAIN
▪ Apnea
▪ Bradycardia
▪ Hypotension
▪ Drop in cardiac output (vagal mediation from midbrain ischemia)

30.  PONS:
 Sympathetic stimulation superimposed on vagal
▪ Leads to bradycardia with hypertension
▪ Cushing’s reflex
 MEDULLA:
 Vagal cardiomotor nucleus becomes ischemic
▪ Prevents tonic vagal stimulus
 Unopposed sympathetic stimulation

31.  Rise of epinephrine ~ the rate of rise of the ICP
 Post storm  hypotensive phase secondary to
reduced sympathetic flow
 Diminished end organ blood flow
 Further exacerbates prior ischemia if present
 Much effort targeted at re-establishing normal CO/CI

32.  Cardiovascular response
 Autonomic storm
 Washout instability
 Neuroendocrine Response
 Autonomic storm
 Posterior pituitary – vasopressin
 Anterior pituitary – glycemic control and adrenal function
▪ Usually preserved
 Temporal considerations
 Deregulation will often resolve spontaneously

33.  “Autonomic storm” of brain death
 Pulmonary edema
 End-organ ischemia
 Profound vasoconstriction
▪ End organ ischemia despite hypertension
 Considerable myocardial ischemia
▪ Leads to stunned myocardium
 This is not unfamiliar physiology:
 SAH
 Severe sepsis (EGDT trial, 2001)
Neurogenic pulmonary edema

34. PATIENT A
 Has severe sepsis
 Lactate 6.2 mM
 MAP 59 mmHg
PATIENT B
 Has severe sepsis
 Lactate 6.2 mM
 MAP 105 mmHg
Mortality: 42% Mortality: 61%

40.  Available evidence does not support the need
for immediate procurement after brain death
 Taking time to optimize perfusion and allow
recovery of cardiac function is appropriate

41.  78% of brain dead donors will develop diabetes insipidus
 Vasopressin
▪ V1 – vascular smooth muscle  mediates tone
▪ V2 – renal collecting duct  antidiuretic
▪ V3 – anterior pituitary  mediates ACTH release
 DDAVP is selectiveV2 with no pressor activity
▪ Desmopressin
▪ No effect on graft function or survival

42.  Large debate
 Literature is conflicting
 UNOS data supports it
 Data adjustment lacking in trial analysis

43. Systematic Review and Meta-Analysis of 3 primary donor questions:
• Desmopressin
• T3
• Ischemic Preconditioning

47.  Don’t send mixed messages after brain death
 We are supporting organs, not life
 Do not examine or talk to the patient after declaration
 It is acceptable to be sad
 “Grief teaches the steadiest minds to waver”
 Use all hospital supportive resources
 Chaplains / priests, ODA, Social work, OPO
 Set time limits for continued organ support

48.  Never introduce the topic
 Organ Procurement Organization (OPO) should be involved
early and available to speak with the family once declared
 If family brings up topic
 Support they good intentions and let them know the people
that can help with that decision are available
 Remember an open casket is possible after donation & autopsy

50.  UCMC, UC Health Policy # II-312, Determination of Death; 2009
 American Academy of Neurology, Quality Standards Subcommittee. Practice Parameters: Determining
Brain Death inAdults. Neurology 45:1012-1014; 1995.
 Wijdicks, EF. The Diagnosis of Brain Death. NEJM 344(16):1215-1221; 2001.
 Goudreau JL,Wijdicks EF, Eelco FM, Emery S. Complications during apnea testing in the determination
of brain death; Predisposing factors. Neurology 55(7): 1045-1048; 2000.
 Busl KM andGreer DM. Pitfalls in the Diagnosis of Brain Death. Neurocrit Care 11(2):276-287; 2009.
 Saposnik, Basile,Young. Movements in Brain Death: A systemic review. Can J Neurol Sci 36:154-160;
2009.
 Ducrocq, X et al. Consensus opinion on diagnosis of cerebral circulatory arrest using doppler-
sonography. J of Neuro Sci 159:145-150; 1998.
 Munari et al. Confirmatory tests in the diagnosis of brain death: comparison between SPECT and CTA.
Crit Care Med 33(9):2068-2073; 2005.
 Excudero et al. Diagnosing brain death by CT perfusion and multisliceCTA. Neurocrit Care 11:261-271;
2009.
 Wijdicks, EF. Evidence-based guideline update: Determining brain death in adults: Report of the
Quality Standards Subcommittee of theAmerican Academy of Neurology. Neurology 74: 1911-1918;
2010.

52.  Triple flexion
 Babinski sign
 Preserved DTRs
 Abdominal and cremasteric
reflexes
 Sweating
 Blushing
 Respiratory-like movements
without significantTV
 Shoulder elevation and
adduction
 Back arching
 Intercostal expansion
 Head turning
 Spontaneous movements or
with painful stimuli (if no full
decerebrate or decorticate
response considered to be at
spinal level):
 Brief slow movements of upper
limbs
 More complex movements
(Lazarus signs) come from
spinal cord
 Stretching of the arms,
followed by crossing or
touching of the arms on the
chest, and finally falling of the
arms alongside the torso.

53. Report of the Quality Standards Subcommittee of the American
Wijdicks, NEJM 2001

54. ApneaTest
 Vitals: Core temperature > 36.5º C or 97º F
 SBP > 90mm Hg
▪ Can use pressors
 Draw a baseline ABG, PCO2 must be ~ 40
▪ COPD
 Pre-oxygenate with 100% FiO2
 Disconnect ventilator, give O2 at 8-12 lpm by tracheal cannula
 Observe for any respiratory movements
AAN Practice Parameter 1994

55.  ApneaTest
 Duration varies
 Usually 5-10 minutes
▪ General rule:
▪ after 2 minutes off ventilator PCO2 will
increase by 5, then for every additional
minute the PCO2 will increase by 2.
 Draw post-test ABG and reconnect the
ventilator.
 The patient has no CNS
respiratory drive if PCO2 >
60mm Hg.
▪ Adjust criteria for known CO2
retention
▪ 20mm Hg above baseline
 During test if patient
becomes hemodynamically
unstable, stop testing, draw
ABG and reconnect the
ventilator.
▪ Test is indeterminate if PCO2 <
60mm Hg.
▪ Consider confirmatory studies.
AAN Practice Parameter 2010

56.  Complications of apnea testing
 Hypotension
 Hypoxia
 Cardiac arrhythmias
 Death…
 Factors associated with complications
 pH < 7.3 or > 7.5
 Plasma Na <120 or >170
 Serum potassium <3.0 or >6.0
 Calcium <8.0 or >10.5
 Pretest hypotension or administration of vasopressors
 High oxygen requirements
 If apnea test is aborted and pCO2 is not ≥60mmHg 
an ancillary test must be performed
Goudreau et al, Neurology 2000

57.  Brain death criteria are met if there is no response to any component of the
examination.
 Confirmatory tests are NOT necessary.
 Recommended if unable to assess all cranial nerves.
 Options include:
▪ Digital subtraction angiography
▪ EEG
▪ Transcranial Dopplers
▪ Nuclear medicine – brain scintigraphy
 Barbiturate levels are required in setting of barbiturate coma
▪ ½ life = 15-50 hours

58. Systole – brief forward flow
Diastole – abrupt flow reversal

60.  Artifact
 Drug effects
 Sedation
 Hypothermia
 Toxic
 Metabolic