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Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ donation within your hospital” 1
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Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

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Page 1: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

Diagnosis of Death Masterclass

Alex ManaraDale GardinerPaul Murphy

31 March 2010

“Improving organ donation within your hospital”

1

Page 2: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation2

Page 3: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation3

Diagnosis of Death MasterclassThe six big wins

Page 4: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation4

Diagnosis of Death Masterclass

2. Increased diagnosis of brain stem death

3. Increased donation after cardiac death

Page 5: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

20461928

17161628 1575

14951370 1338

1243 12681161 1165

0

500

1000

1500

2000

2500

2003/04 2004/05 2005/06 2006/07 2007/8 2008/9

BSD possible diagnosis Patient confirmed BSD

Incidence of Brainstem Death on ICU(< 75 years, non-cardiac ICUs)

Page 6: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

20461928

17161628 1575

14951370 1338

1243 12681161 1165

0

500

1000

1500

2000

2500

2003/04 2004/05 2005/06 2006/07 2007/8 2008/9

BSD possible diagnosis Patient confirmed BSD

Incidence of Brainstem Death on ICU(< 75 years, non-cardiac ICUs)

• 350 missed potential donors

• 172 actual donors

• 619 additional transplanted patients

• Extra 2.8 donors pmp

Page 7: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

Diagnosis of Brainstem Death

Reasons for not testing (approx 650 / year)

30.4

28.1

14.6

11

8.4

6.1

0.7

0.7

0 10 20 30 40

cardiovascular instability

unknow n

residual neurological function

family-related

problems w ith testing

contra-indication to donation (including age)

coroner

others

% total

Reasons for not testing (approx 350 / year)

Page 8: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

Diagnosis of Brainstem Death

Difficulties with BSD testing

0

2

4

6

8

10

12

preconditions drugs biochemicaldisturbances

hypothermia apnoea

% t

ota

l re

as

on

s f

or

no

t te

sti

ng

all

ICH

trauma

Page 9: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

• Significant regional variation

– Only 50% of suitable patients given the option of NHBD

• Significant clinical variation

– Diagnosis of death

– warm ischaemic times

– organ retrieval

Is NHBD organ donation maximised in the UK?

9

The Potential Donor Audit has been assessing the potential for NHBD in the UK for the last five years. The map below shows NHB donor numbers by DTC region for 2009.

Page 10: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation10

Aims:

1. Promote national consistency in the use of the criteria used to diagnose death.

2. You to feel confident in the criteria used to diagnose death whilst being alert to potential pitfalls.

3. For you to be aware of potential criticisms by colleagues and the literature and have thought about possible counter arguments.

Page 11: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation

Agenda

1 Introduction 09.30-09.45

2 Diagnosis of Death: A defence of the British criteria 09.45-10.15

3 Quiz: Dead or not dead? 10.15-10.30

Break 10.30-10.40

4 The confirmation of death 10.40-11.15

5 Case study activity 11.15-12.15

6 Questions 12.15-12.25

7 Summary & close 12.25-12.30

11

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A Defence of the British Criteria

Dale Gardiner

12

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Professional Development Programme for Organ Donation13

30 years on…

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Professional Development Programme for Organ Donation

UK criticsDavid EvansDavid HillPhilip Keep

Critics

Rinaldo Bellomo

Margaret Lock

Alan Shewmon

14

Edmund Pellegrino

Peter Singer

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Professional Development Programme for Organ Donation15

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Professional Development Programme for Organ Donation16

Criteria for Human Death

= The irreversible cessation of brain-stem function

=> Irreversible unconsciousness + Irreversible apnoea

=> intra-cranial or extra-cranial cause

DO NOT restore Cerebral Circulation

=> 5 mins absent cerebral circulation

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Professional Development Programme for Organ Donation17

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Professional Development Programme for Organ Donation18

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Professional Development Programme for Organ Donation19

Transplant Technique• Split livers• Marginal Donors

Immunosuppressants• Tacrolimus• Mycophenolate

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Professional Development Programme for Organ Donation20

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Professional Development Programme for Organ Donation21

Brain Death

Cushing1st Renal auto-Tx(unsuccessful)

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplantsTransplantsTransplants

Transplants

1902

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

Page 22: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation22

Brain Death

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplantsTransplants

Transplants

1902

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

1st xeno-Tx (unsuccessful)

EEG discovered In electric potential =

Death

Loss cortical potentials seen in ischaemia1st Renal cadaveric Tx

(unsuccessful)1950

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Professional Development Programme for Organ Donation23

Brain Death

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplants

Transplants

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

1950 Cessation of brain blood flow = Death

Cortical circulatory arrest seen in coma patients

1st successful live Renal Tx

1960Death of the nervous system

= Coma dépassé

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Professional Development Programme for Organ Donation24

Brain Death

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplants

Transplants

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

19601st successful

cadaveric Renal Tx

Irreversible cessation of the EEG= Death

Page 25: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation25

Brain Death

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplants

Transplants

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

1967-68

1st successful Heart Tx

Harvard CriteriaBrain Death = DEATH

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Professional Development Programme for Organ Donation26

3rd December 1967

Page 27: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation27

Ad Hoc Committee of the Harvard Medical SchoolJAMA

5th Aug 1968

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Professional Development Programme for Organ Donation28

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Professional Development Programme for Organ Donation29

‘Our Primary purpose is to define irreversible coma as a new criterion for death…

…Obsolete criteria for the definition of death can lead to controversy in obtaining organs for transplantation.’

Page 30: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation30

Brain Death

TransplantsTransplantsTransplants

Transplants

TransplantsTransplantsTransplantsTransplantsTransplants

Transplants

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

Future

1st xeno Tx

1st lab grown organ Tx

Brain Death = DEATH

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Professional Development Programme for Organ Donation31

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Professional Development Programme for Organ Donation32

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Professional Development Programme for Organ Donation33

diagnosis decision

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Brain Stem Death

UK

Whole Brain Death

Rest of the World

Higher Brain DeathPhilosophers

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Professional Development Programme for Organ Donation36

Higher Brain DeathPhilosophers

Peter Singer

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Professional Development Programme for Organ Donation37

Whole Brain Death

Rest of the World

Rinaldo BellomoICM 2004

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Brain Stem Death UK

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Professional Development Programme for Organ Donation39

Whole Brain DeathRest of the World

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Professional Development Programme for Organ Donation40

Whole Brain DeathRest of the World

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Professional Development Programme for Organ Donation41

Whole Brain DeathRest of the World

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Brain Stem Death UK

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Professional Development Programme for Organ Donation43

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Professional Development Programme for Organ Donation44

NEJM 2010

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Professional Development Programme for Organ Donation45

Page 46: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation46

ALIVE DEAD

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Professional Development Programme for Organ Donation47

Brain Stem DeathUK

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Professional Development Programme for Organ Donation48

Brain Stem DeathUK

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Professional Development Programme for Organ Donation49

Brain Stem DeathUK

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Professional Development Programme for Organ Donation51

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Professional Development Programme for Organ Donation52

D. Alan Shewmon, MD

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Professional Development Programme for Organ Donation53

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Professional Development Programme for Organ Donation54

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Professional Development Programme for Organ Donation55

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Professional Development Programme for Organ Donation56

Doctors fight to save brain-dead mom’s foetus...

… for 3½ months

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Whole Brain DeathRest of the World

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Professional Development Programme for Organ Donation59

Brain Stem Death UK

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Professional Development Programme for Organ Donation60

The inferior hypophysial artery is an artery supplying the posterior pituitary gland. It is a branch of the cavernous carotid artery (internal carotid artery) which is extradural at this point.

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Professional Development Programme for Organ Donation62

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Whole Brain DeathRest of the World

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Professional Development Programme for Organ Donation64

Criteria for Human Death

= The irreversible cessation of brain-stem function

=> Irreversible unconsciousness + Irreversible apnoea

Page 65: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation65

Alan Shewmon MD

Page 66: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation66

‘Although we were unable to restore his consciousness or spontaneous breathing, the boy lived several more years.’

(page 195)

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Brain Stem DeathUK

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Professional Development Programme for Organ Donation69

trauma unit PET scan brainno blood flowingUnited Regional

Healthcare System Wichita Falls, Texas

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Professional Development Programme for Organ Donation71

Regions only Level III Trauma Centre

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Professional Development Programme for Organ Donation72

USA Trauma Center Level I - Highest toLevel III - Lowest

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Professional Development Programme for Organ Donation77

Criteria for Human Death

= The irreversible cessation of brain-stem function

=> Irreversible unconsciousness + Irreversible apnoea

=> intra-cranial or extra-cranial cause

DO NOT restore Cerebral Circulation

=> 5 mins absent cerebral circulation

Page 78: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation78

75 seconds, 2 minutes, 5 minutes

2 minutes

5 minutes

Page 79: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation79

Dr Michael DeVitaUniversity of Pittsburgh

Page 80: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation80

3.7 days old donor

Taken to the operating room

Lined and given heparin

Extubated & sedated

Waited 75 seconds of PEA

“Best interests of the recipient”

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Professional Development Programme for Organ Donation81

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Professional Development Programme for Organ Donation82

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Professional Development Programme for Organ Donation83

One Thousand One Hundred and Seven NHBD

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Professional Development Programme for Organ Donation84

ALIVE DEAD

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Professional Development Programme for Organ Donation85

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Professional Development Programme for Organ Donation86

Questions?

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Quiz: Dead or not Dead?

87

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Professional Development Programme for Organ Donation8888

Question 1

1. The patient flexes their arm at the elbow following

imposition of a painful stimulus to the nail bed on that

side?

Dead - May represent a spinal reflex

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Professional Development Programme for Organ Donation8989

Question 2

2. The ventilator registers the patient as making

spontaneous respirations?

Dead - May represent the heart beat creating flow

that is triggering ventilation

Page 90: Professional Development Programme for Organ Donation Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ.

Professional Development Programme for Organ Donation9090

Question 3

3. The patient has a generalised tonic clonic seizure?

NOT brain stem dead – the patient must have intact

neural connections to have a grand mal fit

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Professional Development Programme for Organ Donation9191

Question 4

4. The patient’s pulse increases from 70bpm to 110 bpm

during apnoea testing?

Dead - Hypercarbia (which occurs during apnoea

testing) results in endogenous adrenaline release.

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Professional Development Programme for Organ Donation9292

Question 5

5. There is slow drift of one eye away from the ear in which

cold water is injected?

NOT brain stem dead – any eye movements in

response to caloric testing signifies the presence of

some reflex brain stem arc function.

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Professional Development Programme for Organ Donation9393

Question 6

6. The patient sits up during apnoea testing (Lazarus sign)?

Dead - A spinal reaction to the acidosis which

follows hypercarbia. Very unsettling and disturbing!

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Professional Development Programme for Organ Donation9494

How are you going?

These six questions were asked in the Australian JFICM

exam 2008 and the pass rate was only 65%!

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Professional Development Programme for Organ Donation9595

Question 7

7. During an apnoea test on a mechanical ventilator after

20 seconds the patient starts to breathe and then

continues to breathe at 16 breaths per minute?

Dead – ventilator apnoea ventilation has kicked in.

Are you convinced not to do your apnoea tests still

connected to the ventilator?

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Professional Development Programme for Organ Donation9696

Question 8

8. Supra-orbital painful stimulus leads to movement in one

of the arms?

Not dead – although one primarily looks for

movement in the cranial nerve distribution one must

actively ensure (by repetition) that this was a

coincidental spinal reflex but until proven this may

represent the patient is not brain stem dead.

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Professional Development Programme for Organ Donation9797

Question 9

9. During the second set of brain stem testing the second

clinician finds the ears full of wax and can't visualise the

drum?

Not dead – this finding may invalidate the first

oculovestibular test and thus the patient may not be

dead.

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Professional Development Programme for Organ Donation9898

Question 10

10.Due to left orbital trauma you can't visualise or observe

the left eye?

Dead – may still be dead even if one can’t carry out

the full test. Some of the options we discuss in our

case based discussions after morning tea.

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Professional Development Programme for Organ Donation9999

Question 11

10.After a complete set of brain stem tests, confirming

clinical brain stem death, your colleague organises a CT

angiogram which reveals persisting intracerebral blood

flow?

Dead – Brain Stem Death is the UK Criteria

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The Confirmation of Death

Alex ManaraICU Frenchay Hospital

100

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Professional Development Programme for Organ Donation101101

Confirmation vs. Certification

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Professional Development Programme for Organ Donation102102

600,000 UK deaths per annum

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Professional Development Programme for Organ Donation103103

Confirming Death

• Cessation of heart beat

• Cessation of breathing

• Unresponsiveness

• Relatively easy to make

• Reproducible

• Recognizable

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Professional Development Programme for Organ Donation104104

Confirming Death

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Professional Development Programme for Organ Donation105105

Confirming Death: Most doctors.

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Professional Development Programme for Organ Donation106106

Confirming Death: Neurosurgeons...

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Professional Development Programme for Organ Donation107107

Confirming Death: Orthopods...

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Professional Development Programme for Organ Donation108108

Confirming Death: What the public think...

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Professional Development Programme for Organ Donation109109

The Law

• There is no statutory definition of death in the United Kingdom

(Unlike USA)

• The determination of death using neurological criteria has been

accepted by the courts of England and Wales.

• Otherwise you’re dead when a doctor says so = accepted medical

practice

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Variation in Practice

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Professional Development Programme for Organ Donation111111

What is accepted medical practice?

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Definition of death

“The irreversible loss of those essential characteristics which are necessary to the existence of a living human person”

=

“The irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe”

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Professional Development Programme for Organ Donation113113

All Death is Brain Death

1. Cardio-respiratory determination of death

2. Neurological determination of death

3. Somatic determination of death

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Cardio-respiratory criteria

“The heart and lung are not important as basic prerequisites to continue

life but rather because the irreversible cessation of their functions shows

that the brain has ceased functioning”

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Cardio-respiratory criteria

• Need to be applicable to primary care / out of hospital setting

• Simultaneous and irreversible onset of apnoea, and

unconsciousness in the absence of a circulation.

• Irreversible cessation of brain stem function rapidly follows

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Preconditions for cardiac criteria

• Decision made to abandon CPR

• The individual meets the criteria for not attempting CPR (ROLE)

• Active treatment is being withdrawn as declared not in the patient’s

best interests

• Patient has an advance directive refusing CPR

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At “asystole”

• Person confirming death present and continuously observes apnoea,

asystole and unresponsiveness for a minimum of 5 minutes

• Absent circulation confirmed clinically or with monitors

• Return of circulation or respiration prompts start of a further 5

minutes from point of next cardio-respiratory arrest

• Confirm absent pupillary and corneal reflexes and no central

response to pain

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At “asystole”

• Person confirming death present and continuously observes apnoea,

asystole and unresponsiveness for a minimum of 5 minutes

• Absent circulation confirmed clinically or with monitors

• Return of circulation or respiration prompts start of a further 5

minutes from point of next cardio-respiratory arrest

• Confirm absent pupillary and corneal reflexes and no central

response to pain

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Irreversibility

• Heart will not be restarted because patient not for CPR

• Cardiac activity will not resume spontaneously

• Cannot be restarted even with CPR

No post-mortem procedures that have the potential to restore cerebral perfusion

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Post mortem Interventions

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108827.pdf

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Post Mortem Interventions

Anything that places the person at risk of serious harm or distress is

unlikely ever to be in the person’s best interests. (CPR, femoral

cannulation, heparinisation)

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International Differences

• 2 minutes

Pittsburgh protocol 1993

ANZICS

• Minimum of 2 minutes, no more than 5 minutes recommended

Society of Critical Care Medicine, USA

• Minimum of 5 minutes:

Academy of Medical Royal Colleges UK

Intensive Care Society, UK

Institute of Medicine, USA

Canadian Council for Donation and Transplantation

• Minimum of 10 minutes

Maastricht Conference, Holland

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80 year old male with pancreatitis, cerebral infarction and MRSA sepsisCPR abandoned - Doctor went to showerIPPV continuedROSC noted on return at 5 minutesPatient died 2 days later

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UK Deceased Organ Donors

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Organ Donation USA

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Lazarus?

Is auto-resuscitation a result of not having a standardised way of

confirming death and also defining what can and cannot happen after

death?

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Neurological Determination of Death in UK

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History

• Improved ICU care of comatose

patients

• Coma depassé described in

Paris in 1959

• Deep irreversible coma

• Nearly always followed by

cardiac arrest

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Cardiac Prognosis After NDD

Pallis 1987:

1300 patients all developed cardiorespiratory arrest even with full

support

Hung et al 1995:

•73 adults and children

• Full and continued CVS support

• All became asystolic; within 10 days

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Rationale for New Guidelines

• Variable practice when

guidelines not specific

• Guidelines not always followed

even when specific

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New Guidelines

• Published 2008

• Attempts further standardisation

• Primarily a clinical diagnosis

• Clinical judgement still required

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Neurological Determination of Death in UK

1. Patient in deep apnoeic coma

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Neurological Determination of Death in UK

2. Known cause capable of causing ND

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Neurological Determination of Death in UK

• Primary hypothermia

• Metabolic disturbances

• Alcohol

• Depressant drugs

• Muscle relaxants

3. No reversible causes / confounding factors

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Neurological Determination of Death in UK

• Temperature > 34o C

• Na+ < 160 mmol/L

• K+ > 2 mmol/L

• Glucose > 3 mmol/L < 20mmol/L

• Phosphate > 0.5 mmol/L < 3 mmol/L

• Magnesium

3. No reversible causes / confounding factors - Metabolic

Serum Na+ > 115mmol/L?

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Neurological Determination of Death in UK

• Clinical judgement essential

• Impossible to create rules covering every situation

• Difficulties mainly with thiopentone and midazolam

• Plasma concentrations not good predictors of effect

• Use of antagonists may help

• Ideally use non cumulative drugs – propofol, remifentanil

3. No reversible causes / confounding factors - Sedatives

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Neurological Determination of Death in UK

4. Absent brainstem reflexes

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Neurological Determination of Death in UK

• Must be done last after other reflexes absent

• Undertaken no more than twice

• Achieve CVS stability at PaCO2 > 6kPa before disconnection

• Disconnect for 5 minutes

• Return PaCO2 to normal on reconnection

Apnoea Test

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Neurological Determination of Death in UK

• 4 vessel cerebral angiography

• CT angiography

• MRI angiography

• EEG

• TCD

• SPECT

• Brain stem evoked potentials

• Response to 2mg atropine

• ICP > MAP

5. Ancillary Tests

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Whole Brain Death ?

http://video.bloodservices.ca/Streaming/nddvideo/

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Reducing Variability in Practice

• Guidelines – Helpful but limited value

• CLODs – Professional Development Programme

• Development of international approach to confirmation

• Prospective observational studies on onset of asystole

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Case Study Activity

143

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Case Study Exercise

• We have 2 case studies which we would like you to discuss and

respond to in your table groups

• You each have a handout of the 2 case studies which provide a case

context and a series of questions

• We will spend 30 mins total on each case study, 15mins to discuss &

answer questions and15 mins to feedback as a wider group

• This part of the session will take an hour to complete and will be

followed by a more general Q&A

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Case Study 1

A middle-aged woman presents to your Emergency Department at 1600

after collapsing at home. She has fixed pupils and is intubated without

drugs. CT head reveals catastrophic subarachnoid haemorrhage.

Neurosurgical opinion is that this is an unsurvivable situation and

withdrawal of life sustaining treatment is advised. The family approach

the ED staff suggesting their relative would wish to be an organ donor.

Brain death is suspected.

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Case Study 2

A young man is admitted to your neuro-critical care unit with severe

traumatic brain injury. Despite aggressive treatment his pupils fix after

four days and irreversible cessation of brain stem function (brain stem

death) is suspected.

 

He has received substantial doses of sedatives (midazolam, alfentanil

and propofol).

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Questions???

147