Technical Assistance for Alignment in Organ Donation- EuropeAid/131052/D/SER/TR

Key Points in Brain Death Diagnosis

Clinical aspects and ConfirmationFrancesco Procaccio

ISS – CNT - Rome

Neuro Intensive Care Unit

University City Hospital, Verona - Italy

Total Brain Infarct 2

What is Brain Death?

Brain Death is the irreversible loss of capacity for consciousness combined

with the irreversible loss of all brainstem functions including the

capacity to breathe.

The Canadian Neurocritical Care Group, 1999

BD Definition

F Procaccio 2012

Certainty of death: Irreversibility

Karnice-Karnicki, 1896

Brain Death or Brain Dying?

Death is a process

Neurological functions must have ceased

irreversibly

“Irreversible loss of all cerebral functions”

(Brain) Death

Brainstemdeath

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WhyBrain death is the only

death ?

Pathophysiological reasons

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When a person is dead?Definitive, irreversible total damage of the

brainCerebral functions are totally lost

Due to two different mechanisms:

1) Respiratory and circulatory arrest causing secondary irreversible damage of brain (non Heart Beating cadaver)

2) Devastating cerebral lesions which cause total irreversible damage of the brain (Brain Death – Heart Beating cadaver)

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Definition of death (Universal death)

Capron , May 2012 Montreal Forum

Simple uniform reliable concepts & definitions

may increase public confidence and trust

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Heart, Lung, Liver, Kidneys etc.are vital organs

butcan be supported by technology or replaced by transplantation.

except The Brain

Whyonly Brain death is death ?

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Who may become brain dead ?

Only patients with acute cerebral lesion under

mechanical ventilation in ICU

Brain injury – Cerebral Hemorrhage Ischemic Stroke – Brain Tumour Anoxia – Cerebral Infection etc.

Determination of deathby neurological criteria

“All the cerebral functions are irreversibly lost”

Clinical

REFLEXES

EEG

Determination of Death by Neurological criteria

CBF

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Total Brain InfarctAbsence of cerebral blood flow

Death

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Harvard Criteria - 1968

The Neurological Standard

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Wijdicks E. N Engl J Med 2001

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Brain Death Diagnosis Milestones

1. The etiology of the brain lesion is known

2. Exclude all potential confounding factors

3. The neurological examination is complete and all clinical criteria are fulfilled 18

Etiology

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NMR

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Clinical examination

Prerequisites

• Etiology must be known• Imaging of irreversible cerebral

damage• Temp. >32 °C (“Normal” BP – SO2 – Na+)• Exclusion of medical confounding

factors • Exclusion of drug effects on CNS• Exclusion of drug effects on clinical

exam (muscle relaxant agents, atropine etc.)

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The Brainstem

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II

III

V

VI VII

VIII

X

XI

Light response

Corneal

OculocephalicOculovestibular

Brainstem reflexes:pathways

Painful stimuli

Tracheal

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25

Pupillary response to lightMethodology & clinical experience

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APNEA TEST

Absence of respiratory drive 13098

130 78 23

PaCO2 > 60mmHg

100% Oxygen

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Why brain dead patients may move ?

Spinal reflexes in Brain Death

Brain infarct

Spine without superior control

SpinalShock

Spinal function recovery

Hyperexcitability

1

2

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Are there factors that may cause unreliable brain death

diagnosis?

CONFOUNDING FACTORSSevere derangement in temperature,

blood pressure, oxygenation, electrolytes, glusose, cortisol, T4)

Drugs (sedative/anesthetic - barbiturates ! – muscle relaxants )

Facial trauma – Cranial nerves lesions31

Facial Trauma

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If potentially confounding factors

may be present confirmatory tests

must be used

The absence of cerebral perfusion is a simple,

clear, acceptable criteria, easily to be

understood and demonstrated.

Cerebral angiogram. Arch injection

Wijdicks, 200135

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TCD

Brain Deathpatterns

Trans Cranial Doppler

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F Procaccio 2012

Girlanda

R

Angio-CT scan

BD standard – no confounding factors

Persistence of cerebral blood “flow” after brain death

Flowers WM et al. Southern Medical Journal 93:364,2000

• Decompressing fractures• Ventricular shunts• Reperfusion (post-anoxic !)• Decompressive Hemicraniectomy

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F Procaccio 2012

Possible Pitfalls in BD diagnosis

1. the BD declared patient is not Deadzero mistake must be ensured

2. the BD person is not BD declaredsilent BD – Death is not equal - missing PODs

Mimicking Disorders

• Hypothermia• Barbiturates• Acute poisoning• Endocrine crisis

(glucose – cortisol – T4)

• neurological diseases41

“Neurological” conditions that may be confused with Brain

Death• Locked-in syndrome• Guillain-Barré syndrome• Demyelinating conditions • Post-anoxic coma• Brainstem encephalitis• “Medulla man”

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The Medulla Man

Wijdicks E. J Neurol Neurosurg Psych 200143

F Procaccio 2012

Post-anoxic BD

Neuro ICU, Verona - 2005

swelling “flow”6 hours

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F Procaccio 2012

Possible Pitfalls in BD diagnosis

1. the BD declared patient is not Deadzero mistake must be ensured

2. the BD person is not BD declared

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Brain Death Declaration

Certain diagnosis

plus

Legal procedures

Clinical Diagnosis simple and reliable

Must be complete

methodicalrigorous

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Deceased Organ Donation Dead Donor Rule

Death determination (diagnosis)

• Threshold of irreversibility• Clinical standard• Confirmatory tests

Dying process

(legal) Death declaration• Adherence to guidelines• Legal procedures • The moment of Death

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Brain death diagnosis (clinical criteria)

etiology

ComaBrainstemreflexes

+apnea

MandatoryEEG

MandatoryCBF

CBFIn

DefinedConditions children

All pts or only potential donors?

other

x x x no x x all >24hrs anoxic

BD declaration (legal procedures)

Observationperiod

N° MD

Repeated clincial tests

RepeatedEEG

Repeated CBF Children

All ptsOr only

Potential Donors?

6 hrs 3 2 2 no x all Italy

Law –Decree ? !x!National Guidelines ? !x! Country: Italy

Death determination by neurological criteria

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ICU Admission Vegetative

Storm(coning)

Brain DeathDeclaration

1 2 3 4

Patient treatment

Timing in Death declaration

BDcriteria observation

Death53

Common Principles for present/future ?

Citizens equal in death: Death declaration independent from organ donation

Clear, simple and acceptable definitions, criteria and procedures in death diagnosis

A «Universal death» independent from clinical and (new) technical aspects

Clear legal procedures for death declaration

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1. Treating physicians (Intensivists!) should be more involved in BD diagnosis and potential donor identification.

2. BD Pathophysiology based guidelines should guide BD diagnosis and donor treatment.

3. Law and decrees should have (few) technical details aimed to BD (legal) declaration

Suggestions

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1. Specific education and common language are needed.

2. Quality of critical care may facilitate BD diagnosis.

3. The probability of success in organ donation reflects the capacity of declaring brain death in all the patients fulfilling BD criteria.

Key factors

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Case study

Reversible Brain Death

A 55-yr-old man presented with cardiac arrest preceded by respiratory arrest.

Cardiopulmonary resuscitation was performed, spontaneous perfusion restored, and therapeutic hypothermia was attempted for neural protection.

After rewarming to 36.5°C, neurologic examination showed no eye opening or response to pain, spontaneous myoclonic movements, sluggishly reactive pupils, absent corneal reflexes, and intact gag and spontaneous respirations.

Day 1Facial Myoclonus

Over 24 hours, remaining cranial nerve function was lost.

The neurologic examination was consistent with brain death.

Apnea test and repeat clinical examination after a duration of 6 hrs confirmed brain death.

Death was pronounced and the family consented to organ donation.

Are there factors that may cause unreliable brain death

diagnosis?

Twenty-four hrs after brain death pronouncement, on arrival to the operating room for organ procurement, the patient was found to have regained corneal reflexes, cough reflex, and spontaneous respirations.

The care team faced the challenge of offering an adequate explanation to the patient's family and other healthcare professionals involved.

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Would you consider propofol/fentanyl a potential confounding factor at hour 80 ?

1) Yes2) No3) maybe

The ideal practice is to use confirmatory tests

only if necessary to confirm the clinical examination.

Physicians should not go far as to place blind faith in machinery and

the clinical diagnosis remains a sacrosant principle.

EFM Wijdicks, 2001

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Is an ancillary test

1) Useful

2) Mandatory

3) Unreliable

F Procaccio 2012

SEPs NMR CBF CCA

170

195 200 202

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latio

nw

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awal

Ope

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1°- 2

° clin

ical

exa

m +

apn

ea te

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HypothermiaSedation

Although the reversal was transient and did not impact the patient's prognosis, it impacted his eligibility for organ donation and cast doubt about the ability to determine irreversibility of brain death findings in patients treated with hypothermia after cardiac arrest.

CONCLUSIONS:

We strongly recommend caution in the determination of brain death after cardiac arrest when induced hypothermia is used. Confirmatory testing should be considered and a minimum observation period after rewarming before brain death testing ensues should be established.