tarek.sharshar@rpc.aphp.fr

TROUBLES DE LA CONSCIENCE

EN REANIMATION

Raymond Poincaré Teaching hospital

AP-HP

University of Versailles

Garches - France

REANIMATION

Conscience

normale

Coma

sommeil

anesthésie

État

végétatif

État de

conscience

minimale

Locked in

syndrome

Conscience

normale

Coma

sommeil

anesthésie

État

végétatif

État de

conscience

minimale

Locked in

syndrome

Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004

Conscience normale

Coma sommeil

anesthésie

État végétatif

État de conscience minimale

Locked in syndrome

DELIRIUM

SEDATION

ENJEUX

1. Coma 1. Cause

2. Traitement

3. Pronostic

2. Delirium 1. Cause

2. Prevention

3. Traitement

3. Sedation 1. Modèle pharmacologique

2. Detection d’une souffrance cérébral sous jacente

3. Facteur de risque de delirium

COMA

• Present in 25-60% of ICU patients

• Leading predictor of – Death

– Length of mechanical ventilation

– LOS

• Coma assessment (GCS) is an integral component in the most widely used intensive care scoring systems – APACHE

– SAPS

– SOFA

Stevens - Crit Care Med - 2006

OR death 95% CI

Age 1.38 1.16-1.65

Shock 3.87 1.96-7.65

Coma 20.22 9.42-54.09

CPR 13.4 5.18-34.63

COMATOSE PATIENT

BRAINSTEM RESPONSES

1. Eyes spontaneous movement

2. Eyes position

3. Oculocephalogyre response

4. Oculovestibular response

5. Pupillar size

6. Pupillar light reflex

7. Corneal reflex

8. Grimace

9. Cough reflex

10. Oculocardiac response

11. Respiratory pattern

FOCAL SIGNS

Comparison between right

and left body

1. Motor responses to order

or painful stimulation

2. Limbs tone

3. Tendon reflexes

4. Plantar reflex

Verbal response Eyes response Motor response

SCALE

MYOCLONUS

1. Limbs

2. Lids

ALGORITHM

Fever

Medical history (Alcohol,

Epilepsia…)

Circonstances (CO…)

Glycemia

Imaging,

± AB ±

CSF

Neck stiffness Focal sign Trauma

Imaging

Seizure

Imaging

± AB ±

CSF

Imaging

± CSF

EEG,

Imaging

± CSF

FOUR COMA SCORE

Wijdicks et al – Ann Neurol - 2005

EYE RESPONSES

MOTOR RESPONSES

FOUR COMA SCORE

Wijdicks et al – Ann Neurol - 2005

RESPIRATION

BRAINSTEM REFLEXES

78 years old woman, with hypertension and diabetes, treated by anticoagulant for an atrial fibrillatrion was referred to our ICU for a coma. Neurological examination showed: Glasgow coma scale at 7, myosi,s generelized hypotonia and a bilateral Babinski sign. Biological screening is normal, but PT of 49%.

BASILAR ARTERY OCCLUSION

Ferbert et al – Stroke - 1990

ELECTROENCEPHALOGRAMME

• Interêt diagnostique

• Intérêt pronostique

• Place du neuromonitoring

• If etiology is known, EEG can often be a reliable predictor

of outcome.

• EEG usually has little specificity with regards to etiology,

but some patterns do favor particular diagnoses:

– triphasic waves (TWs) are frequently seen with hepatic

and renal insufficiency in young adults;

– spindle coma patterns are believed to indicate

dysfunction at the brainstem level.

• EEG is most useful

– in differentiating organic from psychiatric conditions,

– in excluding nonconvulsive status epilepticus (NCSE),

ELECTROENCEPHALOGRAM

Kaplan – J Clin Neurophysiol - 2005

EPIDEMIOLOGY

ENCEPHALOPATHIE SEPTIQUE

1. Excessive theta

2. Predominant delta

3. Triphasic waves

4. Burst suppresssion

Young et al JCN 1992; Straver et al Neurol Res 1998

0

10

20

30

40

50

60

Normal Theta Delta Triphasic Burst

suppression

NORMAL MILD SEVERE

ENCEPHALOPATHIE SEPTIQUE

• Using multivariable analysis, sepsis at admission to the ICU was the only significant predictor of electrographic seizure (ESZs) or periodic epileptiform discharges (PEDs) : OR: 4.6, 95% CI 1.9–12.7, p = 0.002.

• In 120 septic patients, poor outcome : 90% versus 55% in patients with vs without ESZs or PEDs.

• This association remained significant after controlling for age, coma, shock, acute renal failure, and acute hepatic failure : adjusted OR 10.4, 95% CI 3.0–50.7, p < 0.001.

Oddo et al Crit Care Med 2008

PROGNOSIS

Hoesch et al – Crit Care Med - 2011

Risk factors for Acute Lung injury in comatose patients

OUTCOME

Greer et al – Crit Care Med - 2012

Dead

PRONOSTIC

Greer et al – Crit Care Med - 2012

PRONOSTIC

Greer et al – Crit Care Med - 2012

PRONOSTIC

Greer et al – Crit Care Med - 2012

IMPORTANCE DE L’ETIOLOGIE

Wijdicks et al - Neurology 2006

PREDICTION-ANOXIA Etudes: 1966-2006

Mauvais pronostic: à 1 mois, décès ou troubles de la conscience ou à 6 mois, troubles

de la conscience ou séquelles sévères (soins infirmiers continus)

A

B

B

B

Am

eric

an

A

cadem

y of

Neu

rolg

y

DELIRIUM & AGITATION

tarek.sharshar@rpc.aphp.fr

Delirium / Confusion DSM IV : Diagnostic Statistical Manual (of American Psychiatric Association)

A. Consciousness alterations: reduce reactivity to environment, difficulty to

keep attention and concentrate

B. Alteration of one or more cognitive functions:

– Speech

– Memory

– Temporo-spatiale orientation

– Judgement and thinking

C. Acute or rapidly progressive (mn, heures ou jours), fluctuating symptoms

D. Due to one or more the following cause:

– Medical disease

– Drugs / intoxication

– Withdrawal

DELIRIUM

Author, year Population ICU, n Criteriae (scale) Freq.

Dubois, ICM 2001 Med-chir, n=216 Delirium (ICDSC) 19%

Ely, CCM 2001 Med, n=48 Delirium (CAM) 60%

Ely, Crit care 2003 Med non ventil, n=261 Delirium (CAM) 48%

Woods, ICM 2004 Med, n=143 Agitation (MAAS) 16%

Ely, JAMA 2004 Med et USIC, n=224 Delirium (CAM) 82%

Jaber, Chest 2005 Med-chir, n=211 Agitation (Ramsay) 52%

Ely, ICM 2007 Chir-Trauma, n=100 Delirium (CAM) 70%

Ely, JAMA 2007 Med-chir, n=106 Delirium (CAM) 80%

Ouimet, ICM 2007 Med-chir, n=820 Delirium (ICDSC) 32%

DISTRIBUTION

Ely et al – JAMA - 2004

Hypoactive and mixed delirium predominate in older and younger ICU patients: percentage of ICU patients with delirium by motoric subtypes (hyperactive, hypoactive, and mixed) stratified

by age

Pun B. T., Ely E. W. Chest 2007;132:624-636

©2007 by American College of Chest Physicians

MORTALITY

Ely et al – JAMA - 2004

OUTCOME

SCALES

- Sedation/Agitation :

- RAMSAY

- Richmond Agitation Sedation Scale (RASS)

- Adaptation to the Intensive Care Unit Environment (ATICE)

-.....

- Delirium :

- Confusion Assessment Method for the ICU (CAM-ICU)

- Intensive Care Delirium Screening Check-list (ICDSC)

-.....

ALL SCALES HAVE LIMITS- USE ONE

PATHOPHYSIOLOGY

RISK FACTORS

HOST FACTORS FACTORS OF CRITICAL ILLNESS IATROGENIC FACTORS

Age (older) Acidosis Immobilization

Alcoholism Anemia Medications (opioids, bzd)

APOE4 Fever/infection/sepsis Sleep disturbances

Cognitive

impairment Hypotension Dehydration, dyspnea

Depression Metabolic disturbances (for example,

sodium, calcium, BUN, bilirubin)

Hypertension Withdrawal syndrome

Smoking Respiratory disease/ congestive heart

failure

Vision/hearing

impairment High severity of illness

CASE REPORT

• Mq X…, âgée de 53 ans, traited with CS and I- for a LED, was hospitalised acute renal failure related to thrombotic microangiopathy treated with PE that were complicated by a hematoma of the thigh.

• She developed hyperactive delirium Survenue d’un état d’agitation et délirant: « on me vole mon enfant, les

médecins me vole mon enfant… »

ANXIETY AND FEAR

SEPSIS

1. Sepsis is an independant risk factors for agitation

(Jaber et al – ICM - 2003)

2. Sepsis is a major cause of delirium (Ely et al –

JAMA - 2004) ~ 50%

3. Encephalopathy is occuring in 32 to 60% of septic

patients (Eidelman et al -JAMA -1996)

Iwashyna et at – JAMA - 2010

MORTALITY

GLASGOW COMA SCALE n APACHE II MORTALITY

15 19 17.2 (6.3) 16%

13-14 15 20.1 (5.4) 20%

9-12 8 23.1 (5.7) 50%

3-8 8 34.4 (7.0) 63%

Eidelman et al - JAMA - 1996

Delirium has a worst outcome when associated with sepsis

NE

NV

(Brainstem

NE

BHV

(Amygadal DELIRIUM

COMA

IMMUNE

SYSTEM

Psychological

disorders

Cognitive

disorders

PATHOPHYSIOLOGY

Neuroinflammatory process (Delirium => neurodegenerative)

Ischemic process

(Delirium/focal => vascular demantia)

(Sharshar 2007, Polito 2011)

(Sharshar 2007, Sharshar 2004)

Cytokines

NO

40% mortality

60% mortality

SEDATION

(C’est la confusion!)

DELIRIUM

BZD

(Dose/durée)

DXM Interruption

quotidienne

0

- +

Physiothérapie

-

Absence

sédation

+

Confort/amnésie ?

Faux souvenirs

UN CAS DE CONSCIENCE

A 52 years old and alcoholic man was hospitalised in ICU for an hypoxemic community-acquired pneumonia with blood cultures positive to S. pneumoniae.

At admission: conscious and not confused, neurological examination normal and no neck stiffness.

One day later: mechanical ventilation + agitation treated with Haloperidol.

Two days later: heavy sedation for severe agitation ascribed to alcohol withdrawal.

A week later: still sedated, bilateral larged fixed pupils.

CT scan : diffuse brain oedema Lumbar puncture: meningitis.

AGITATION IN A SEPTIC AND ALCOHOLIC PATIENT IMPORTANCE OF SEDATIVES DISCONTINUATION

NEUROLOGICAL COMPLICATIONS

ISCHEMIA

LEUCOENCEPHALOPATHY

HEMORRHAGE

Sharshar et al – Brain Pathology 2004; ICM-2007

WHICH TOOLS IN SEDATED

PATIENTS?

(in non-neurosurgical patients)

CLINICAL EXAMINATION

NEUROPHYSIOLOGY

BIOMARKERS

NEURORADIOLOGY

Interpretation?

Availability/Interpretation?

Controversial?

Not appropriate for monitoring?

DESIGN

[12-24h] Every day Discontinuation

of sedation

1st N.E N.E Coma/Delirium

Within 3 days

Reproducibility of neurological examination was satisfactory

FLOW CHART

Elaboration group

– N=72

– From 2004 to 2007

– Unicentre

– Confusion/Agitation (ATICE)

Validation group – N=72

– From 2008 to 2009

– Multicentre

– Delirium (CAM-ICU)

– Daily interruption

Fitting set

n = 72

Validation set

n = 72

Women (%) 24 (33) 28 (39)

Age (years) 58 (46 to 74) 69 (51 to 80)

Surgical admission (%) 16 (22) 22 (31)

SAPS-II at admission 50 (37 to 61) 57 (45 to 67)

Sepsis 50 (69) 45 (63)

Duration of sedation (days) 5 (2 to 8) 3 (2 to 6)

Confusion/delirium at awakening (%) 26 (43) 26 (53)

Coma (%) 11 (18) 14 (23)

Altered mental status (%) 34 (57)* 34 (55)**

Mortality rate at day 28 (%) 22 (31) 21 (29)

CHARACTERISTICS AND OUTCOME

* 60 and ** 62 patients

NEUROLOGICAL EXAMINATION

12-24H OF SEDATION Fitting set Validation set

Number of patients 72 72

Midazolam (mg/kg) 0.9 (0.6 to 1.8) 1.3 (0.8 to 2.0)

Subfentanyl (µg/kg) 2.0. (0.8 to 4.0) 2.0 (0.7 to 4.6)

sedation to inclusion (hours) 12 (12-24) 12 (12-24)

ATICE (from 0 to 20) 9 (9 to 10) 9 (9 to 10)

RASS Not tested -4 (-4 to -2)

Blinking to strong light (%) 31 (43) 28 (39)

Absent eye movement (%) 66 (93) 67 (93)

Myosis (%) 45 (63) 38 (54)

Pupillary light response (%) 51 (71) 58 (82)

Corneal reflex (%) 65 (90) 66 (92)

Oculocephalic response (%) 32 (47) 33 (46)

Cough response (%) 36 (51) 60 (83)

Grimacing (%) 41 (57) 48 (69)

Gm

g

Cg

h

Ocr B

lk

Myo

Eyp

Crn Lid

Lig

ht

56

78

91

0

Cluster Dendrogram

agnes (*, "ward")

t(x)

He

igh

t

Crn: corneal reflex

Blk: blinking

Gmg: grimace

Cgh: cough

Light: pupillar reflex

Moi: miosis

EyP: eye position

Ocr: oculocephalogyre

NEUROLOGICAL EXAMINATION

Septic shock with ARDS and

severe liver and renal failure

in a aplasic 82 years old man.

1. Coma plus abolition of all

brainstem reflexes

2. After discontinutaion of

sedation, recovery of

cough and oculocephalic

repsonses but not of

corneal reflex and

grimace.

DISCREPANCY

Multiple logistic model

28-DAYS MORTALITY

Sharshar et al - Submitted

Fitting set Validation set

OR (95%CI) P OR (95%CI) P

SAPS-II at inclusion 1.06 (1.02 to 1.09) 0.003 1.03 (1.00 to 1.07) 0.051

Absent cough response 7.80 (2.00 to 30.4) 0.003 5.44 (1.35 to 22.0) 0.017

C-index (SE) 0.836 (0.055) 0.743 (0.067)

RESPONSES ASSESSED BETWEEN THE 12Th AND 24th H OF SEDATION

ALTERED MENTAL STATUS

(after discontinuation of sedation)

Fitting set Validation set

Criteria Confusion or coma Delirium or coma

OR (95%CI) P OR (95%CI) P

SAPS-II at inclusion 1.04 (1.00 to 1.07) 0.058 1.03 (0.99 to 1.08) 0.10

Absent oculocephalic response 4.49 (1.34 to 15.1) 0.015 5.64 (1.63 to 19.5) 0.006

Sharshar et al - Submitted

RESPONSES ASSESSED BETWEEN THE 12Th AND 24th H OF SEDATION

Multiple logistic model

COUGH AND GAG REFLEXES

Hoesch et al – CCM - 2011

192 Neuro-ICU patients

CONCEPT OF BRAINSTEM DYSFUNCTION

CRITICAL

ILLNESS

Oculocephalic response

Apoptosis LC

Effect of DEX

DEATH Autonomic dysfunction

Cough reflex

HR/BP variability

Immune control

RAAS dysfunction DELIRIUM

IMMUNO

DEPRESSION

ProReTro

MERCI!

Iwashyna et at – JAMA - 2010

DISORDERS OF CONSCIOUSNESS

Stevens et al – Crit Care Med - 2006