Neuro-réanimation: coma & conscience neuroreanimation_sante_publique.pdfcoma & conscience Prof...

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Neuro-réanimation: coma & conscience

Prof Steven Laureys Coma Science Group Centre de Recherches du Cyclotron & Service de Neurologie Université de Liège & Centre Hospitalier Universitaire de Liège

2ème Master en sciences de la Santé publique, Finalité spécialisée Soins Intensifs et d’Urgences

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Courte histoire du coma

Anoebis

cœur Maät

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Respirateur artificiel (1952)

The resuscitation greats. Bjørn Ibsen Resuscitation. 2003

Bjørn Ibsen - Copenhagen

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Pope Pius XII (1957) Consciousness | History | Death | Coma | Locked-in | Disorders of Consciousness

•! it remains for the doctor to give a definition of the “moment of death”

•! no obligation to use extraordinary means to prolong life in critically ill patients

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Coma dépassé (1959)

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Première transplantation d’un donneur en mort cérébrale (1963)

Jean Morelle & Guy Alexandre Neurology, 2005;64;1938-1942

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Christiaan Barnard (1967)

Louis Washkansky

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Définition de la mort cérébrale

Comité de Harvard 1968

Wijdicks, NEJM 2001 Bueri et al Mov Disord. 2000, 15:583-6

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys, Owen and Schiff, Lancet Neurology, 2005

Conscience & éveil

NORMAL

EVEI

L

CO

NSC

IEN

CE

DE

L’EN

VIR

ON

NEM

ENT

COMA ANESTHESIE

SOMMEIL

EVEI

L

CO

NSC

IEN

CE

DE

L’EN

VIR

ON

NEM

ENT

ETAT VEGETATIF

EVEI

L

CO

NSC

IEN

CE

DE

L’EN

VIR

ON

NEM

ENT

ETAT DE CONSCIENCE

MINIMAL

EVEI

L

CO

NSC

IEN

CE

DE

L’EN

VIR

ON

NEM

ENT

LOCKED-IN SYNDROME

EVEI

L

CO

NSC

IEN

CE

DE

L’EN

VIR

ON

NEM

ENT

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L’erreur diagnostique

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Peur d’être enterré vivant (1896)

1896, Karnice-Karnicki, chamberlain of the tsar of Russia

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La mort et les medias (1980)

Transplants - Are the donors really dead ?

mort clinique ! mort

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Erreur de diagnostic et mort cérébrale

Depuis les années 50, aucun patient en mort cérébrale n’a récupéré sa conscience (test d’apnée!)

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Locked-in syndrome

Laureys et al., Progress in Brain Research, 2005

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unconsciousness ! “coma”

Monti, Laureys & Owen, British Med J, 2010

1972 1966 1952

2002

1994


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A new name for « vegetative »

Laureys et al, BMC Medicine 2011

“There’s nothing we can do… he’ll always be a vegetable.”


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Eye response

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Motor response

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Brainstem reflexes

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Respiration

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Diagnostic error

n=103 post-comatose patients –! 45 clinical consensus diagnosis ‘vegetative state’ –! 18 signs of awareness (Coma Recovery Scale)

!! 40% potential misdiagnosis

Schnakers et al, BMC Neurology 2009


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Eye tracking : use a mirror!

Vanhaudenhuyse et al J Neurol Neurosurg Psychiatry 2008

n=52


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Functional MRI PET scan High-density EEG Transcranial magnetic stimulation

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Sustained visual fixation is a reflex

Bruno et al, BMC Neurology 2010


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Automated consciousness classifier

Phillips et al, NeuroImage, 2010

“Relevance Vector Machine” on FDG-PET data in DOC


www.comascience.org Owen, Coleman, Boly, Davis, Laureys & Pickard, Science, 2006

Signs of consciousness on fMRI

“He’s not in coma… he’s playing tennis!”


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EEG-based Brain Computer Interfaces

ms -200 50 300 550 800 1050 1300

-5 -10 -15 -20 -25

5 10 15 20 25

Pz (!V)

Count TARGET (own name)

Coma or total locked-in syndrome?

21-y old woman basilar artery thrombosis - day 49

Other names PASSIVE

Count TARGET (other name)

Own name PASSIVE


Schnakers et al, Neurology, 2008 Schnakers et al, Neurocase, 2009

www.decoderproject.eu

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vegetative state

ATYPICAL ‘HIGH LEVEL’ CORTICAL ACTIVATION

Di et al, Neurology, 2007

ACTIVATION TO THE OWN NAME

fMRI predictor of outcome? Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion

PUBLISHED DATA (n=48 patients) 6 fMRI (n=17) & 8 PET studies (n=32)

“low level” or absent activation •! low level activation 84% no recovery

•! no cortical activation 100% no recovery

“high level” activation •! 82% recovery (93% specificity 69% sensitivity)

Di et al, Clinical Medicine, 2008

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Traitement "…le cerveau (d’une femme) est un mystère...

est encore plus dans cet état là"

www.comascience.org Schnakers et al, JNNP 2008

Traitement pharmacologique

www.comascience.org Schiff et al., Nature, 2007 Laureys, De Ridder, Schiff et al., European DBS study in EMCS

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Stimuler le cerveau

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PRONOSTIQUE

www.comascience.org Eisenberg NEJM 2001 Laureys et al, Nature Clinical Practice 2008

Outcome after cardiac arrest EMERGENCE

MINIMALLY CONSCIOUS STATE

BRAIN DEATH

functional communication

VEGETATIVE STATE

COMA

brainstem reflexes

voluntary movements or command following

eye opening only reflex movements

CARDIAC ARREST

Hemodynamic stabilisation

20-50% >80%

77-98%

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Clinical outcome markers

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Circumstances surrounding CPR

•! Time between collapse and CPR > 5 min (FPR 20%; 95% CI 14-25)

•! Duration CPR > 20 min (FPR 23%; 95% CI 17-29)

•! Asystole or electro-mechanic dissociation versus ventricular fibrillation or tachycardia

(FPR 27 %; 95% CI 21-33) •! Cause of the cardiac arrest (cardiac vs noncardiac)

Rogove et al Crit Care Med 1995;23:18–25 (N=774; class I study)

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Hyperthermia

•! each °C > 37° (tympanic thermometry < 48h) -> 2 x more likely to die or remain VS after 6m

Zeiner et al Arch Intern Med 2001;161:2007–2012 (class II study)

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Clinical examination

•! at 72 hours: GCS motor score <=2 or absence of pupillary & corneal reflexes (FPR 0%; 95% CI 0 to 3)

•! Myoclonus status epilepticus (repetitive, generalized myoclonus; not single seizures or sporadic focal myoclonus)

(FPR 0%; 95% CI 0 to 8.8)

Wijdicks et al Neurology 2006 (analysis of 3 class I, 2 class II, 5 class III studies)

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Electroencephalography

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Electroencephalography

1929 Hans Berger

50 "V

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Generalized slowing baseline activity

Cerebral blood flow < 25 ml/100g/min

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EEG: burst supression

FPR= 3%, 95% CI: 0.9 à 11

Wijdicks et al 2006 1 class II 4 class III studies

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EEG: isoelectrical

Cerebral blood flow < 15 ml/100g/min

BRAIN DEATH

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Evoked potentials

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Somatosensory evoked potentials

FPR = 0.7%; 95% CI: 0.1 - 3.7

Carter Intensive Care Med, 2005 (25 studies) Zanbergen et al, Lancet 1998

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Visual evoked potentials

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Auditory brainstem evoked potentials

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N 1 0 0 s t d N 1 0 0 d e v

M M N

1 0 0 m s

1 µ V -

+

d e v i a n t n = 1 4 1 s t a n d a r d n = 7 2 6

d i f f = d e v - s t d

Mismatch negativity

Fischer et al, Crit Care Med, 2006 Naccache et al, Clin Neurophysiol 2005

presence of MMN -> outcome better than VS

n=64; 100% specificity

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Biochemical markers

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Biochemical markers

•! NSE : neuron specific enolase < neurons & neuroectodermal cells

>33 "g/l at D 1 to 3 (1 class I 4 class III and 1 class IV studies)

(FPR = 0%; 95% CI: 0 – 3) •! time-consuming >24h •! hemolysis increases values (NSE < platelets) •! cutoff points for a 0 FPR vary from 20 to 65 "g/l •! NSE is lower in induced hypothermia

•! S100 protein : calcium-binding astroglial protein (1 class I 4 class III and 1 class IV studies) values measured <D2 : poor prognostic indicator

•! Creatine kinase brain isoenzyme (CKBB) < neurons & astrocytes (6 class III studies) poor prognostic ability

•! Neurofilament in CSF (1 class IV study) FPR of 10%.

Wijdicks et al Neurology 2006

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Pronostic coma anoxique Kirsch et al, Revue Médicale de Liège 63 (2008) 263-268

DON D’ORGANES

DON D’ORGANES CŒUR NON-BATTANTS

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Epidemiology Consecutive admissions CHU ICU (26 beds) over 5 y : n=5908

631 disorder of consciousness on admission (11%)

! 356 vegetative state (56%) 227 non-traumatic (64%) 129 traumatic (36%)

" 101 died

" 200 emerged from VS 118 obeyed command & oriented (59%) 68 disoriented or inappropriate words (34%) 14 only localised pain (7%)

" 55 remained VS at discharge

Ledoux, Piret, Damas, Moonen & Laureys, in preparation

VS

28%

56% 16%

died

trauma

non- trauma

emerged

# 36% recover # 70% recover

Consciousness | History | Death | Coma | Locked-in | Disorders of Consciousness

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Chronic disorders of consciousness

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Outcome

Ledoux et al, Belgian federal project on VS

! "! #! $! %! &! '! (! )! *!

"!!

" $ ' "#

Minimally conscious state (n=84)

n=35

%

! "! #! $! %! &! '! (! )! *!

"!!

" $ ' "# n=49

%

! "! #! $! %! &! '! (! )! *!

"!!

" $ ' "# +,+-.+/0+1 ,02 3456 72

Vegetative state (n=116)

Trau

mat

ic

n=52

%

! "! #! $! %! &! '! (! )! *!

"!!

" $ ' "#

Non

-tra

umat

ic

n=64

%

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Ethical & social challenges


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Cognition & quality of life Cognitive and behavioral changes in 20-50%

long-term memory, executive function impairment, focal cognitive deficits •! O’Reilly et al Resuscitation 2003;58:73—9 •! Nunes et al Resuscitation 2003 57:287—97. •! Drysdale et al Resuscitation 2000 47:27—32 •! Grubb et al Stroke 2000;31:1509—14 •! Grubb et al BMJ 1996 313:143—6 •! Roine et al J Am Med Assoc 1993 269:237—42

Posttraumatic stress disorder in 20-25% (more in younger patients) •! Griffiths et al Yearbook of IC & EM 2008: 891-905 •! Gamper et al Crit Care Med 2004 32:378—83 •! O’Reilly et al Br J Clin Psychol 2004 43:83—95 •! Ladwig et al Am J Psychiatry 1999 156:912—9

Preserved health related quality of life •! Horsted et al Resuscitation. 2007 72:214-8 •! Bunch et al Crit Care Med. 2004 32:963-7 •! van Alem et al Am J Cardiol. 2004 93:131-5 •! Granja et al Resuscitation. 2002 55:37-44 •! Nichol et al Acad Emerg Med 1999 6:95—102

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Ethical issues

Demertzi et al, J Neurology 2011

2,475 medical professionals


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Quality of life

Bruno et al, BMJ Open, 2011


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Ethics

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Ethical conclusions

•!What is meaningful outcome? •!What is acceptable probability?

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EVALUER LA DOULEUR

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Pain without words ?

Pain is a subjective first-person experience which has to be communicated to be accurately assessed

Only motor response considered indicative of conscious perception is localization to noxious stimulation

Laureys & Boly What is it like to be vegetative or minimally conscious?

Curr Opin Neurol 20 (2007) 609-13

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No brain, no pain

Laureys, 2005

NORMAL BRAIN DEATH COMA VEGETATIVE STATE

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Motor response without pain

Bueri et al Mov Disord. 2000, 15:583-6

Spinal reflexes 75%

extension-pronation plantar responses muscle stretch reflexes abdominal reflexes undulating toe flexion sign “Lazarus’ sign

BRAIN DEATH

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No cortex, no pain

Consciousness in congenitally decorticate children: developmental vegetative state as self-fulfilling prophecy

Shewmon et al Dev Med Child Neurol. 1999

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Some cortex, some pain?

Laureys, 2005

NORMAL BRAIN DEATH COMA VEGETATIVE STATE

www.comascience.org Laureys et al., Current Opinion in Neurology, 2005


Pain after coma?

COGNITIVE CAPACITY

MO

TO

R R

ES

PO

NS

IVEN

ES

S

coma

VEGETATIVE/UNRESPONSIVE

MINIMALLY CONSCIOUS

severe disability

arousal = eye opening

Communication ?

moderate disability

good recovery

live independently

professional reinsertion

Awareness ? = response to command or non-reflex movements


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Laureys et al, Neuroimage, 2002

Laureys, Nature Reviews Neuroscience, 2005

Brain activation to pain

Low level disconnected cortical activation

Noxious electrical stimulation

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Assessing pain

Kappesser and Williams, Pain 2010

overestimation

agreement

underestimation

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Standardized assessment

Schnakers et al, Pain 2010

Standardized stimulation

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Pain in infants & demented

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Nociception coma scale

Checklist of Non-verbal Pain Indicators

NO

CIC

EPTI

ON

CO

MA S

CALE


<4

4-7

>7

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Nociception coma scale

UNCONSCIOUS VEGETATIVE

MINIMALLY CONSCIOUS

NO

CIC

EPTI

ON

CO

MA S

CALE


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Nociception Coma Scale

•! New “pain scale” for disorders of consciousness after coma

•! Assesses motor, verbal (vocal), visual (ocular), and facial responses on scales from 0 (no response) to 3 (total scores 0 – 12) to a quantified standard stimulus

•! Brief time required (1–5 min) to conduct and rate the examination

•! More sensitive compared with 4 other “pain” scales

•! Permits detect, communicate & follow non-communicative patient’s behaviors and their management

•! Allows monitoring treatment avoiding sedative effects & under-uses of analgesics

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EXPERIENCES PROCHE DE LA MORT

www.comascience.org 86

NDE (1975)

Van Lommel 2001 WCEI scale 41 (12%) Parnia 2001 Greyson scale 4 (6%) Schwaninger 2002 Greyson scale 7 (13%) Greyson 2003 Greyson scale 27 (2%) Charland 2011 Greyson scale 17 (10%)

Sensations, illusions, hallucinations, emotional or mystical feelings classically following life-threatening situations:

Cardiac arrest, perioperative or post-partum complications, septic or anaphylactic shock, electrocution, coma TBI, CVA, hypoglycaemia

? -> Neural correlate of NDE


Clinical death ! death

« …defined clinical death (independent of neuro- logical data) as a period of unconsciousness caused by insufficient blood supply to the brain because of inadequate blood circulation, breathing, or both. »


Brain death = death

Transplants - Are the donors really dead ?

Clinically dead ! dead !


Misdiagnosis of death ?

Since the 50s, no single patient showing the clinical signs of brain death ever recovered consciousness (apnea test !)

Laureys, Nature Reviews Neuroscience, 2005

1896, Karnice-Karnicki, chamberlain of the tsar of Russia


NDE dimensions

NDE >7 Greyson Scale Greyson, B. (1985). A typology of near-death experiences. Am J Psychiatry

(n=17 ; 10% of cardiac arrest)

Out of Body Experience (Paranormal) 15 Well-Being (Affective) 13 Light (Affective) 9 Sense of a presence (Transcendental) 6 Life Review (Cognitive) 2

Charland et al, unpublished


NDE = false memories ? Memory Characteristics Questionnaire (Johnson, M.K., et al., J Exp Psychol Gen, 1988)

Thonnard et al, submitted


NDE characteristics ! dreams


Memory Characteristics Questionnaire Johnson, M.K., et al., J Exp Psychol Gen, 1988 qualitatively different

from dreams or drug-induced hallucinations

‘For many years, it was the most real thing that ever happened to me. Yes, far more real and vivid than any real-life incident. It was so real, detailed and so vivid and consistent ...; in fact, so totally un-dream- like!’


NDE characteristics ! dreams


Memory Characteristics Questionnaire Johnson, M.K., et al., J Exp Psychol Gen, 1988


Demertzi et al, Ann N Y Acad Sci. 2009 (fig 3)

NDE = proof of the soul ?... 1858 participants attending scientific meetings on consciousness


… no evidence for that hypothesis

2009 Yearbook - Towards a neuro-scientific explanation of Near-Death Experiences?


Light optic radiation

Ammermann et al. 2007 Els et al. 2004

DWI ADC T2

T1

Hieronymus Bosch 1500s


Flashback mesiotemporal

Britton and Bootzin 2004


Presence left temporoparietal

Arzy, S., et al. (2006) Nature 443:287 Induction of an illusory shadow person.


OBE right temporoparietal

Blanke et al Stimulating illusory own-body perceptions. Nature, 2002 (6904)269-70 De Ridder et al Visualizing out-of-body experience in the brain. N Engl J Med, 2007 (357) 1829-1833


NDE = happening in the brain

NDE dimension Neural substrate OBE Right temporoparietal junction

Tunnel & light occipital & optic radiation (tunnel vision & foveal light)

Life review, memory flashback, enhanced emotions

Hippocampus/amygdala

Meeting of spirits Left temporoparietal junction

Painlessness, wellbeing Anterior cingulate cortex Time distortion Cortico-striatal Mystical & transcendental – oneness, cosmic unity

Biparietal

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