50ème Séminaire Interrégional de Réanimation Médicale Clermont-Ferrand, 7 & 8 Décembre 2006

Prise en charge du syndrome post-arrêt cardiaque

Alain CariouRéanimation Médicale

Cochin - Université Paris 5

« The post-resuscitation disease is a specific pathophysiologic state that should be considered an independent nosological entity » P. Safar & W. Negovski

Post-resuscitation care

ROSC must be the beginning of a complex treatment

Aims of post-resuscitation care are:• To stabilize cardio-respiratory status in order to improve tissue perfusion

(particularly cerebral and splanchnic)

• To find the cause of CA, to treat it and to prevent recurrence

• To manage the post-resuscitation syndrome

Post-resuscitation care should permit: • To reach neurological evaluation in the best conditions

• To improve the prognosis?

Pronostic de l’arrêt cardiaque

350000 morts subites par an

100000 tentatives de RCP

Période pré-hospitalière40000 patients

réanimés…

…et hospitalisés

Mortalité hospitalière:

Choc → décès précoce

Lésions neurologiques

20000 survivants

10000 sans séquelles neuro. majeures

Survival to 1 month in 12 hospitals among patients with a bystander-witnessed cardiac arrest with a cardiac aetiology who were alive on hospital admission after OHCA

Main hypothesis:

« The most plausible explanation for this difference is variability in the level of post-resuscitation treatment provision between hospitals. Since this information was not available, it remains a matter of speculation »

Adjusted OR for 1-month survival2.63 (95% CI 1.77-3.88)

Herlitz et al. Resuscitation 2006

ut

1. Ischemia and reperfusion syndrome2. Inflammatory response3. Myocardial dysfunction4. Adrenal dysfunction5. Coagulopathy

Current Opinion in Crit Care. 2004

Successful CPR After Cardiac Arrest as a "Sepsis-Like" Syndrome

Kinetics of cytokines and sTNFRII levels on admission and over a 7-day period in 61 resuscitated survivors (n=18, open diamonds) and nonsurvivors (n=43, black squares) of OHCA

Adrie et al. Circulation. 2002;106:562

Pene F et al. Intensive Care Med 2005

T0 T60

Pts with relative adrenal insuff.

n=33

Pts without relative adrenal insuff.

n=31

Seru

m c

orti

solc

once

ntr

atio

n (m

cg/d

L)

T0 T60

p=0.001

Non-responders, n=22

Responders, n=16

Log-rank, p=0.02

Post-resuscitation shock related mortalitySerum cortisol concentrations

0 10 20 300

20%

40%

60%

80%

100%

Myocardial Dysfunction After Resuscitation From Cardiac Arrest: An Example of Global Myocardial Stunning

Design: 28 domestic swine studied before and after CA

Pre-arrest

30 min

2 hours

5 hours

48 hours

Myocardialblood flow

Ejection fraction

Base Base5 H 5 H

Kern KB. JACC 1996

17 Excluded

YES n=73Death: 64.2%

NO n=75Death: 58.8%

Early shockRequiring vaspopressive drugs

148 Included

165 patientsadmitted after cardiac arrest

Laurent et al. JACC. 2002;40:2110-6

LA PHASE INITIALE : Une défaillance multi-viscérale sévère

Tenir jusqu ’à…

… une évaluation neurologique fiable

Choc après RCP: Facteurs de risque

Caractéristiques GroupeChocn=73

Groupe contrôle

n=75

P

Durée de la réanimation (mn)

25 [14-39] 15 [7-30] 0.005

Nombre de chocs électriques

3 [1-6] 2 [1-3] 0.005

Bolus total d’adrénaline (mg)

10 [3-16] 2 [0-10] 0.0002

Infarctus en phase aiguë

53.7 % 38.2 % 0.06

Laurent et al. JACC. 2002;40:2110-6

0

20

40

0 20 40 60heures après l'ACR

mmHg

0

2

4

L/min/m²

POD PAPO IC

**** ****

** p< 0.05p< 0.05

**

**** p< 0.01p< 0.01

Laurent et al. JACC. 2002;40:2110-6

0

10

20

30 mmHg

0

5000

10000

ml

Remplissage cumulé POD PAPO0

2,5

5

7,5

10

0 20 h 40 h 60 h

mg/h

40

65

90

115

mmHg

Adrénaline PAM

Delayed vasodilatationrequiring vasopressive drugs

Leak-syndromerequiring large volume expansion

**

**

** p< 0.01

Laurent et al. JACC. 2002;40:2110-6

Prise en charge : Points particuliers

Monitorage précis et completCorrection des troubles métaboliques

DyskaliémiesAcidose métabolique

Adaptation de la ventilation mécaniquePressions bassesNomocapnie

Thérapeutiques d’exceptionCoronarographie ?Hémofiltration ?Assistance circulatoire ?

Immediate coronary angiography in survivors of out-of-hospital cardiac arrest

Variables

ST-segment elevation and chest painPresent

Absent

ST-segment elevation or chest painPresent

Absent

No of patients

15

69

49

35

No with recentcoronary-arteryocclusion (%)

13 (87)

27 (39)

31 (63)

9 (26)

Etude prospective, non randomisée84 ACR d’origine cardiaque - Survie hospitalière: 38%48% des patients avaient une occlusion coronaire récenteL’ATL réussie est un facteur indépendant de survie (OR:5.2, p=0.04)

Spaulding et al. N Engl J Med. 1997; 336:1629-33

Hémofiltration (convection)Mode prédilutionnel

Ultrafiltrat

Liquide de réinjection

TNF-α

IL-6

C3a, C5a

Six-month survival: Controls 21%HF alone 42%HF + HT 32%

p=0.28

Death by intractable shock (IS): Controls 42%HF alone 10%HF + HT 14%

p=0.009

Laurent I et al. JACC 2005

p=0.026

p=0.018

Controls n=19HF alone n=20HF + HT n=22

Multivariate analysis: HF and six-month death: OR 0.21 (95% CI 0.5-0.85)HF and death by IS: OR 0.29 (95% CI 0.09-0.91)

Relative risk of death by IS: HF alone 0.21 (95% CI 0.5-0.85)HF + HT 0.29 (95% CI 0.09-0.91)

Support circulatoirepartiel

Support circulatoiretotal

Choc cardiogénique Arrêt cardiaque Support de procédures

ECLS : Evolution des indications

Massetti M et al. AnnThorac Surg 2005

En salle de KT, on ne fait pas que des coros….

LA PHASE TARDIVEL’évaluation du pronostic neurologique

Savoir jeter l’éponge…

Zandbergren EGJ et al. Intensive Care Med 2003

01020304050607080

MOF Causeneuro

Choc

FV/TV PEA/asyst

The Most Important Changes in the International ECC and CPR Guidelines 2005

Prognostication

Relying on the neurologic exam during cardiac arrest to predictoutcome is not recommended and should not be used.No laboratory analyses (NSE, S-100b, base deficit, glucose, or soluble P-selectin) provide reliable prediction of the outcomeafter cardiac arrest.Median nerve somatosensory-evoked potentials measured 72 hours after cardiac arrest can be used to predict a fatal outcomein patients with hypoxic-anoxic coma.The use of the EEG performed a minimum of 24 to 48 hours after a cardiac arrest can help define the prognosis in patients with grade I, IV, and V EEGs.

Circulation 2005; Vol 112, Supplement IIIResuscitation 2005; Vol 67, Supplement I

I must say … Brain ismy second favouriteorgan…

Causes(embolie, thrombose, ischémie, hypoxie,

choc direct, décélération,hémorragie intratissulaire, effet de

masse)

Dommages primaires(excito-toxicité, radicaux libres,

inflammation, nécrose, apoptose)

Tt de la cause si "fenêtre temporelle"

Maturation de la lésion tissulaire- au niveau "physiologique"- au niveau cellulaire(œdème, HTIC, engagement, perte de la vasoréactivité, vasospasme, lésions de reperfusion, radicaux libres, inflammation, excito-toxicité)

Désordres systémiques "ACSOS"hypoxie, hypercapnie, acidosehypo/hypertensionhyperthermie

Dommages secondaires(nécrose, apoptose)

Lésion cérébrale "aiguë" définitive

Tentatives de neuroprotection et ACR ….

• ThiopentalBrain Resuscitation Clinical Trial I Study Group. Randomised clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med 1986 ; 314 : 397-403

• CorticoïdesJastremski M, Sutton-Tyrrell K, Vaagenes P. Glucocorticoid treatment does not improveneurological recovery following cardiac arrest. Brain Resuscitation Clinical Trial I study Group. JAMA 1989 ; 262 : 3427-30

• NimodipineRoine RO. Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled double-blinnd randomised trial. J Am Med Assoc 1990 ; 264 : 3171-7

• LidoflazineBrain Resuscitation Clinical Trial II Study Group. A randomized study of calcium entry blocker(lidoflazine) administration in the treatment of comatose survivors of cardiac arrest. N Engl J Med1991 ; 324 : 1225-31

Resuscitation from accidental hypothermia of 13.7°C with circulatory arrest Gilbert et al. Lancet 2000; 355: 375-6

Narvik, Norway - May 20, 1999

18:20 19:00 19:39 21:10 21:50 22:00 22:15 5th month

Iced waterimmersion

Removal andCPR

Full CP bypass

ROSC Full recovery

Stop moving OR admission VF MOF

25°c14.4°c 13.7°c

CPR CPB ECMO

9 hours 5 days

Lésion

cérébrale

Radicaux

libres

Apoptose

Pression

intra-cranienne

Cascade

inflammatoire

Excito-

toxicitéDemande

métabolique

Hypothermie

Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest

0

2

4

6

8

10

12

14

16

18

CGOS 1-2 CGOS 3 CGOS 4 DCD

Hypothermie Normothermie

* p<0.05

*

*

InterventionHypothermie modérée 33°cDurée 12 heuresRéchauffement 6 heures

Inclusion 44 patients22 pts groupe contrôle historique22 ACR comateux

Pas d’effet indésirable rapportéBénéfice significatif

Pronostic neurologique Mortalité

Bernard et al. Ann Emerg Med 1997; 30:146-153

P. Safar & PM Kochanek.

Hypothermia after cardiac arrest: a treatment thatworks

Etude européenne Etude australienne• ACR extra-hospitalier• Rythme initial = FV• Coma CGS < 7• Origine cardiaque probable

• ACR extra-hospitalier• Rythme initial = FV• Coma• Origine cardiaque probable

• Température : 32-34°C • Durée 24 h• Curarisation

•Température : 33°C • 12 h, dès le pré-hospitalier• Curarisation

0

20

40

60

%

Etude européenne Etude australienne

RR= 1.44 IC95 [ 1.08-1.81]

p= 0.009

RR= 5.25 IC95 [ 1.47-18.76]

p= 0.011

CPC 1 ou 2 à 6 mois

Hypothermie Normothermie

Hypothermia after cardiac arrest: a treatment that works

0

20

40

60

80

%

Etude européenne Etude australienneHypothermie Normothermie

p= 0.145

Mortalité à 6 mois

RR= 0.74 IC95 [ 0.58-0.95] p= 0.02

Hypothermia after cardiac arrest: a treatment that works

Therapeutic Hypothermia After Cardiac ArrestAn Advisory Statement by the Advanced Life Support Task Force of the

International Liaison Committee on ResuscitationWriting Group

J.P. Nolan, FRCA; P.T. Morley, MD; T.L. Vanden Hoek, MD; R.W. Hickey, MDMembers of the Advanced Life Support Task Force

W.G.J. Kloeck, MBBCh, DipPEC(SA), Chair; J. Billi, MD; B.W. Böttiger, MD; P.T. Morley, MD;J.P. Nolan, FRCA; K. Okada, MD; C. Reyes, MD; M. Shuster, MD, FRCPC; P.A. Steen, MD;

M.H. Weil, MD, PhD; V. Wenzel, MDMember of the Pediatric Life Support Task Force

R.W. Hickey, MDAdditional Contributors

P. Carli, MD; T.L. Vanden Hoek, MD; D. Atkins, MD

« On the basis of the published evidence to date, the Advanced Life Support (ALS) Task Force of the

International Liaison Committee on Resuscitation (ILCOR) made the following recommendations in October

2002 :

• Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrestshould be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was ventricularfibrillation (VF)• Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest »

Circulation. 2003;108:118-121

Hypothermia after cardiac arrest: a treatment that

works

Sterz: Curr Opin Crit Care, Volume 9(3).June 2003.205-210

?

The Hypothermia after Cardiac Arrest Study Group, N Engl J Med 2002;346:549-556

Bladder Temperature in the Normothermia and Hypothermia Groups

?

Refroidissement externe

TheraKool™

www.thermal-eng.co.uk/medical2.htm

Refroidissement externe

Internal Cooling : Heat Exchanging Catheters

www.alsius.com

A prospective, multicenter pilot study to evaluate the feasibility andsafety of using the CoolGardTM System and IcyTM catheter followingcardiac arrest

Al-Senani: Resuscitation 62 (2004) 143–150

Intérêt clinique du refroidissement par cathétérisme endovasculaire à la phase précoce de l’arrêt cardiaque : impact

sur la mortalité et impact médico-économique

Investigateur Coordonnateur: Pr F. BaudInvestigateurs associés : Dr N. Deye & A. CariouMéthodologie et Statistique & Monitoring : Pr E. VicautEconomiste : Pr R. LaunoisPromoteur : AP-HP

PHRC 2005

Objectif principal : Amélioration du pronostic à l’aide du refroidissement endovasculaire comparativement à la technique conventionnelle externe de refroidissement

Neuroprotection post-arrêt cardiaque

Dessin : Étude prospective multicentrique randomisée

Calendrier : Début des inclusions 2ème semestre 2006

Kim et al. Circulation 2005

Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey

Abella et al. Resuscitation 2005

Langhelle et al. Resuscitation 2005