Traitement de la défaillance

cardiaque post-op
DIU Réanimation Cardiopathies Congénitales
Novembre 2019
Dr N TAFER
Hôpital cardiologique Haut Lévèque
Unité Réa cardiopathies congénitales
CHU Bordeaux

1
n Savoir le reconnaitre
n Comprendre la cause
n Savoir l’anticiper et le prévenir
n Savoir le gérer
2
q ± 70% des patients de chirurgie cardiaque
pédiatrique sont en défaillance cardiaque ±
aiguë après la CEC (exemple NEM)
q Tt : inotrope et/ou assistance circulatoire ± prolongée

3
n Bordeaux 2009:
¨ 218 patient: 60% LCOS
n 128 ttt inotropes
n 16 FSR

n 16 Assistance

n Littérature: 25% LCOS en chirurgie

cardiaque pédiatrique

4
Classification INTERMACS
1 - Choc cardiogénique critique
INTERagency registry for Mechanically Assisted Circulatory Support
2 - Aggravation malgré Tt
n
n Il existe EUROMACS et PEDIMACS
inotrope
3 - Stable mais inotrope dépendant
4 - Symptômes au repos avec Tt
oral
5 - Intolérance à l’effort
6 - Effort limité
7 - NYHA III
 Eléments diagnostiques LCOS
n Cliniques: oligurie, hypoperfusion périphérique, tachycardie
n Biologiques:
¨ acidose métabolique: Approche de Stewart F meilleure prédictibilité
Durward et AL The strong ion gap predicts mortality in children following
cardiopulmonary bypass surgery.
Pediatr Crit Care Med 2005;6(3):281–5.

¨ lactates élevées: seuil à 6 mmol/l ou ascencion >0.75mmol/l/h

Charpie JR et Al Serial blood lactate measurements predict early outcome after neonatal
repair or palliation for complex congenital heart disease.
J Thorac Cardiovasc Surg 2000;120(1):73–80.
¨ BNP, Troponine. cinétique de la Troponine et du BNP plus élevée que la norme pour la
pathologie concernée

n Svo2 ou Svco2 : Norme variable selon la malformation et sa réparation

n NIRS:

6
n Echographie:
Permet d’apprécier:
¨ la fonction de chaque ventricule
n Diastolique: Profil transmitral,Tei

n Systolique: FR, FE, IMdp/dt, TAPSE

¨ Ces indices n’ont été validé par aucune étude en pédiatrie

¨ La tachycardie constitue la principale limite

¨ La cinétique de ces indices peut être intéressante

¨ La cinétique globale et segmentaire

¨ L’œdème myocardique
¨ Les pressions pulmonaires
¨ La volémie
¨ Les lésions résiduelles

7
n Traquer la lésion résiduelle

15% des ECMO post cardiotomies présentaient des lésions résiduelles

•Obstruction à l’éjection ventriculaire
•Shunt residuel
•Fuite d’une VAV

8
 CIV CIV résiduelle

IAo Patch étanche

Accélération
Sous Ao

9
100% de mortalité chez les enfants mis sous ECMO avec des
lésions résiduelles

10
 Check list des causes à éliminer

n Vérifier l’airway: position sonde, taille

n Vérifier la ventilation: atélectasie, pneumothorax
n Tamponnade
n Crise d’HTAP
n Troubles du rythme
n Lésions résiduelles (CIV résiduelle, gradient sur les voies
d’éjection…), montages vicieux.
n Troubles électrolytes (Hypocalcémie)

11
 LCOS origines
Conditions pre-opératoires
Défaillance connue : coronaire anormale
Anatomique : adaptation progressive à la réparation
(petit VG)
Conditions per-opératoires
Longue durée de clampage aortique
Défaut de protection myocardique
Sevrage trop précoce de la CEC sans phase
d’assistance
Lésions coronariennes, ventriculaires
Réparation incomplète
12
 Physiopathologie LCOS
Incapacité du myocarde à maintenir un
débit cardiaque suffisant pour assurer la
demande en O2 de la circulation régionale.
Sans traitement : activation d’un cercle
vicieux
Morbidité et Décès
Insuffisance cardiaque chronique
Si le bas débit est d’origine ischémique et/
ou stunning et/ou hibernation, réversible
par un traitement adhoc, initié rapidement.13
Stunning
Produit par
l’afflux de radicaux libres pendant la reperfusion
(=> augmentation du Ca intracellulaire)
La perte de la sensibilité au calcium des filaments
contractiles
Survenue : situations dans lesquelles le cœur est
exposé à un épisode ischémique
Angine instable, SCA avec reperfusion précoce,
ischémie à l’effort
Clampage aortique en chirurgie cardiaque et en
transplantation
14
Hibernation

Dysfonction liée à une réduction

importante et chronique du débit
coronaire (ALCAPA)
Les cellules myocardiques sont
normales
Après restauration du débit coronaire,
à terme, la fonction peut être normale
(ALCAPA opérée)
Hibernation et stunning peuvent
associés
Ex : ALCAPA post CEC avec protection
myocardique insuffisante 15
 Stratégies thérapeutiques
n Anticiper le LCOS:
¨ Protection myocardique: respect des délais de réinjection….
¨ Ultrafiltration per CEC
¨ Autres stratégies anti-inflammatoires
¨ Phase d’assistance post déclampage
n Traiter le LCOS:
¨ Optimiser la précharge (Kt OG – PVC..)
¨ Support inotrope
¨ Optimiser la post charge:
n VD: NOi, IPDE5
n VG:IPDE3
¨ Traitement des oedemes interstitiels:
n Diuretiques à fortes doses
n Dialyse péritonéale

16
 Stratégies thérapeutiques 2

n Autres
¨ Corticoïdes: bolus 10 à 50 mg/m²/j, si besoins de remplissage
importants à cause des troubles de la microcirculation sur SIRS +++
→Rescue
¨ Création de CIA
¨ Fermeture sternale retardée
¨ Assistance mécanique

En somme:
Optimiser le débit cardiaque et la perfusion tissulaire sans
augmenter la consommation en oxygène du myocarde

17
 Support inotrope
Pas de consensus pour traiter le LCOS
en chirurgie cardiaque et pédiatrique
Peu de publications sur les inotropes
les + utilisés, encore moins en pédiatrie
Rares études avec niveau d’évidence
élevé
Niveau 1 a : au moins 2 études
randomisées avec une faible marge
d’erreur
Catécholamines
IPDE
Levosimendan 18
Mécanismes d’action des inotropes

19
Toller WG. et al. Anesthesiology 2006 n°3
 b1 Ca2+

P
PKA
AC Ca2+
ATP cAMP
PDE III

M
Tn Tn
A
Ca2+
M
A
Ca2+
Réticulum
Sarcoplasmique

ATP
Ca2+
20
 b1 Ca2+
Catécholamines

P
PKA
Ca2+
cAMP
AC
ATP
Inhibiteurs
PDE III
de la
PDE III
Tn

2+
Tn
Tn

Ca
M Tn
Ca2+
M TnTnTn
MA
MMA A
MA
MA
A
A Réticulum
Sarcoplasmique

Ca2+ ATP
21
 Ca2+

P
PKA
AC Ca2+
ATP cAMP
PDE III

Tn

2+
Tn
Tn

Ca
M Tn Levosimendan
M TnTnTn
MA
MM A ATn
Ca2+
MA
MA
MA
A
A Réticulum
Sarcoplasmique

Ca2+ ATP

22
 Dobutamine
Etude 100 pts. Romson JL. Anesthesio 1999
La fréquence augmente de 1,45 bpm par µg/kg/min
Risque de tachycardie + rapide
Le débit cardiaque augmente principalement par
l’augmentation de fréquence
Dobu vs Milrinone (120 pts). Feneck RO.
JCVA 2001
Dobu 10 à 20 µg/kg/min, Milrinone 0,5 µg/kg/min
H1, débit cardiaque : Dobu + 55%, Milrinone + 36%
Fc : Dobu + 35%, Milrinone + 10%
PAM : Dobu + 31%, Milrinone + 7%
Dobu : hypertension et fibrillation atriale

23
Milrinone

24
Association IPDE III + Epinéphrine

Baisse des SVR et RVP avec A, A+E, mais pas avec E

Fraction d’éjection du VD augmente avec A, A+ E,
mais pas avec E
Royster RL, Anesth Analg 1993 25
 Pourquoi le levosimendan ? Recent Patents on Cardiovascular Drug Discovery, 2011, 6, 9-15

Levosimendan: From Basic Science to Clinical Trials

No. 1 10 Recent Patents on Cardiovascular Drug Discovery, 2011, Vol. 6, No. 1
Rognoni et al.

hout
n Andrea
Vasodilatory Rognoni,
Effects Alessandro
Effets2+ vasodilatateurs: Lupi, Maurizio
Ouverture Lazzero,
calcium
canaux leading Angelomyocardial
K+ to increased S. Bongo and Giorgio
contraction without Rog
Va
cium increasing intracellular cAMP or intracellular calcium
The Ca sensitizing is accompanied by vasodilation; this
dent ¨ Vasodilatation Coronaire
effect is explained by combined effect of levosimendan on concentration. Levosimendan displays calcium - dependent
with eff
dellabinding to theNovara,
N- terminal domain of cardiac troponin C with
+
ower
different Vasodilatation
K channels.
¨ Coronary Care The artères
Unit, opening
Hospitalpulmonaires
of“Maggiore
ATP - sensitive Carità”, Italy, Catheterization Laboratory an
dif
potassium channels has been first identified during voltage a higher affinity at high calcium concentration and a lower
the ¨ Cardiology,
Vasodilatation
and current
Sant’Andrew
clamp recordings systémique Hospital, Vercelli, Italy
in isolated rat arterial myocytes affinity at low calcium concentration. By stabilizing the pot
the and
[15]; it was suggested that levosimendan hyperpolarized the calcium - troponin C complex, levosimendan inhibits the
oss - Effets
narterial surFebruary
Received:
myocytes
la fonction
through3,an 2010; myocardique:
Accepted:
activation ofNovember 22, 2010; Revised:
a glibenclamide - December 1, 2010 [15
ct is troponin I effects and prolongs the actin - myosin cross -
sensitive +
¨ Augmente
K channel and la that
sensibilité
this mechanismdes protéines
may contribute contractiles à larate.troponine: Effet inotrope arte
cen- bridge association This positive inotropic effect is
to the vasodilating Abstract:
action of Levosimendan
levosimendan.isFurthermore, it
one of the documented pharmacological agents usedcalcium
in the management sen
an
ygen ¨ Sans augmenter le flux calcique obtained
intracellulaire: without
Effet increasing intracellular
lusitrope concen-
was, also, shown that levosimendan activates
acute and chronic heart failure; voltage gated
it is a noveltration to
ndan +inodilator
or with agent which enhanced
a significant increase myocardial
in myocardial performance
oxygen with
K+ channels
¨ Pasand large - conductance
d'augmentation de Ca2+ - activated K
consommation d'oxygène wa
dent oxygen consumption. The combination of demand, positive usually
inotropic seenandwith
vasodilator
other effects of
inotropes. levosimendan rela
Levisimendan
uscle
channel in rat and porcine large epicardial
sensitizing and K +
channels
arteries. It seems
+ opening effects.
K+n
nthatCombinaison
the involvement of des these deux
differenteffets:
K channels varies was also shown
Levosimendan to open
has the
been mitochondrial
proposed, in ATP
the - dependent
recent past, to be
ease cha
with the origin of the vascular beds. Energetictoconsiderations
may have some advantages potassiumfurther
standard inotropes; channels in myocites
possible and vascular
indications smooth musclehave bee
for levosimendan
other ¨ onAmélioration du couplage ventriculo-artériel tha
relying pressuresome observational
- volume studies,
relationship such as suggest
analyses cells, which
a perioperative causes
use, vasodilatation;cardiogenic
cardioprotection, these properties
shock,decrease
sepsis and r
wit
increased efficiencydysfunction.
of myocardial The work
ability onofthe application
levosimendan bothto preload
improve and afterload, function
myocardial increase coronary
without and other
substantially incr
The nof Effet
arterial antistunning: organ blood flow
rely
vasodilators; the vasodilators
consumption may appearproperty
paradoxical of but
levo-is possible via [8].
improved efficacy not only with regard to inc the
dose ¨ Evite
simendan la surcharge
is probably involved calcique
in its mitochondriale
favorable energetic de l’ichémie - reperfusion
contractile apparatus of the cardiomyocytes. The The aim of this reviewofis Levosimendan
pharmacokinetics to describe theis pharmacological
linear. The ofch
ndan profile [16].
6 to ¨ Stabiliselevosimendan
le potentielandmembranaire et préserve
its clinical applications. The patent
concentration la review
fonction data des
increased mitochondries
regarding the use
proportionally of Levosimendan
with the dose are
sim
- to CardiacinFunction
thisles
review article. administered; the usual dosage of intravenous levosimendan pro
Effects
¨ onEconomise phosphates de haute énergie et limite l’apoptose
used in clinical trials of patients with heart failure is 6 to
Keywords: positive
Levosimendan’s Calcium-sensitizer, heart is
inotropic effect failure
due &to levosimendan.
the
12 g/kg loading dose over 10 minutes followed by 0.05 - to Eff
 Adamopolous [12] No Yes No rogeneity. Changes in haemodynamic parameters and BNP
Tziakis [41] No Yes No
were pooled using weighted mean differences [30]. All ana-
REVIVE II [42] No International
No Journal ofYes
Cardiology 138 (2010) 281 – 289
Al-Shawaf [32] Yes Yes No lyses were performed using STATA 8.2 (Statcorp, College
www.elsevier.com/locate/ijcard

Insuffisance cardiaque aigue « médicale »

Alvarez [33] No No No Station, Tx). The authors had full access to the data and take
SURVIVE [31] Yes Yes Yes responsibility for its integrity. All authors have read and agree
DeHert [35] Yes Yes No to the manuscript as written.

Levosimendan for the treatment 3.of acute severe heart failure: A

Results

2.4. Datameta-analysis
synthesis of randomised controlled trials
3.1. Study characteristics

Agreement on RCT inclusion was assessed using the There were 393 reports identified by the search, 41 full
a,b,⁎ a,b a
kappaAnthony Delaney
statistic. Heterogeneity was assessed using , Celia
the chi- Bradford , John
text articles were retrieved for inMcCaffrey
depth review. In total,, 19
square statistic and quantified using the I2 statistic, with an c,d a,b fulfilled all eligibility
studies enrolling 3650 participants
2 Sean M. Bagshaw
I of N50% taken as representing at least moderate hetero-
, Richard Lee
criteria. Fig. 1 shows the flow of studies and the reasons for
geneity [26]. The Intensive Care Unit, Royal North Shore Hospital,Of
a potential for bias was assessed by the exclusion. St.the trials included,
Leonards, NSW,16Australia
[12–14,17,18,31–41]
International Journal of Cardiology 138 (2010) 281 – 289
b A. Delaney et al. / International Journal of Cardiology 138 (2010) 281–289 285
Northern Clinical School, University of Sydney, St. Leonards, NSW, Australia
c
Division of Critical Care Medicine, University of Alberta Hospital, Edmonton, AB, Canada
d
Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

Levosimendan for the treatment of acute severe

Received 30 October 2007; received in revised form 27 June 2008; accepted 10 August 2008
Available online 24 September 2008
meta-analysis of randomised controlled
Abstract Anthony Delaney a,b,⁎, Celia Bradford a,b , John McC
Sean M. Bagshaw c,d , Richard Lee a,b
Background: The objective of this study was to critically review the literature to evaluate whetheralevosimendan compared to standard therapy,
Intensive Care Unit, Royal North Shore Hospital, St. Leonards, NSW, Au
in patients with acute severe heart failure, is associated with improved clinical outcomes. b
Northern Clinical School, University of Sydney, St. Leonards, NSW, Aus
Methods: Medline, EMBASE, and the Cochrane central register of clinical trials were searched. c
Division We alsoCare
of Critical searched clinicaloftrials
Medicine, University Alberta registries,
Hospital, Edmonton,
d
bibliographies of included studies and review articles and contacted the manufacturers of levosimendan Faculty of Medicine
to identify and Dentistry, University
unpublished studies.ofRandomised
Alberta, Edmonton, AB,
clinical trials comparing levosimendan to standard therapy or placebo, in adult patients with acuteReceived severe30heartOctoberfailure, reporting
2007; received at least
in revised form 27oneJuneoutcome
2008; accepted 10
of interest were included. Data were extracted regarding the characteristics, methodological quality and clinical outcomes, Available online
and24combined
September 2008 using a
fixed-effect meta-analysis.
Results: We identified 19 RCTs enrolling 3650 patients, only two studies fulfilled all of the validity criteria. There was a non-significant reduction in
Abstract
mortality with levosimendan compared with placebo (OR 0.83, 95%CI, 0.62–1.10, p = 0.20). Levosimendan was associated with reduced mortality
compared to dobutamine (OR 0.75, 95%CI, 0.61–0.92, p = 0.005). Levosimendan was associated
Background: The objective of this study waswith improvements
to critically in haemodynamic
review the literature to evaluate whether levos
parameters when compared to either placebo or dobutamine. in patients with acute severe heart failure, is associated with improved clinical outcomes.
Conclusions: Levosimendan improved haemodynamic parameters when compared
Methods: with placebo,
Medline, EMBASE, withoutcentral
and the Cochrane showing
register evidence of were
of clinical trials survival
searched. W
Fig. 3. The effect of levosimendan compared to dobutamine
bibliographies of on mortality.
included studies and review articles and contacted the manufacturers of levosimendan to i
benefit. Levosimendan improved both haemodynamics and survival when compared with dobutamine.
clinical trials comparing levosimendan to standard therapy or placebo, in adult patients with acute severe he
Crown Copyright ©were 2008 Published
available by Elsevier
as full reports and 3 Fig. Ireland
[42–44]
2. Thein Ltd.
abstract
effect All rights
form
of levosimendan reserved.
to placebo
compared and on
to placebo reported
mortality.mortality. There was no evidence of
of interest were included. Data were extracted regarding the characteristics, methodological quality and
2 2
only. Agreement on study inclusion was reached in 39 of 41 significant
fixed-effect heterogeneity
meta-analysis. (χ p = 0.24, I = 25.7%). Neither
cases
Keywords: Heart failure; (kappaMeta-analysis;
Drugs; = 0.90). The trialLevosimendan;
characteristics areInotropic
shown in agents
inspection
Results: Weofidentified
the funnel plot enrolling
19 RCTs (Appendix)
3650nor Egger's
patients, onlybias
two studies fulfilled all of the validity criteria
Table 1. The validity assessments are shown in Table 2. Only statistic (bias = −0.41, p = 0.07) revealed evidence of bias.
mortality with levosimendan compared with placebo (OR 0.83, The95%CI, 0.62–1.10, p = 0.20). Levosimend
Pharmacocinétique
100.0 Levosimendan
OR-1896
OR-1855
Concentration (ng/ml)

10.0

1.0

0.1

0 2 4 6 8 10 12 14

Time (days)

Figure 5. Mean plasma concentration-time curves of levosimendan, OR-1855

and OR-1896 after 24-hour infusion of 0.2 µg/kg/min in patients with NYHA
III-IV heart failure.8

The mean elimination half-life values for the levosimendan metabolite

OR-1896 is approximately 80 hours and its plasma protein binding is
137, 138
 separately using ANOVA contrasts for same model.
3 0.819 Markers for myocardial injury and natriuretic peptides
0.08 0.838
Insuffisance cardiaque aigue « chirurgicale »
violatedCARDIOTHORACIC
the normality assumption
thethenonparametric
To take
ANESTHESIOLOGY:

CME activity relatedFriedman

for the ANOVA test.
The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org.
Therefore, test
to this article, youwas
mustapplied.
have either an STS member or an
Time to start of rescue medication, and other time-to-
individual non-member subscription to the journal.
0.407
event type of end points were analyzed using Cox pro-
ADULT CARDIAC

Levosimendan
portional hazards model Facilitates
with effects forWeaning treatment. Cu-From
mulative doses of selected medications were compared
0.4 0.555 Cardiopulmonary Bypass in Patients Undergoing
between treatment groups using the Mann-Whitney test
46 0.466 Coronary
(M-W). Artery Bypass Grafting With Impaired
22 0.457
Left Ventricular Function
Results
Heidi I. Eriksson, MD, PhD, Jouko R. Jalonen, MD, PhD, Leo O. Heikkinen, MD, PhD,
Baseline
Matti Kivikko,dataMD, andPhD,demographics
Mika Laine, are
MD,presented ERIKSSON
PhD, Kari in
A. TableET AL
Leino, MD,Ann 449
PhD,Thorac Surg
• Chirurgie coronarienne FEVG altérée
PROPHYLACTIC LEVOSIMENDAN IN CPB WEANING 2009;87:448 –54
1. Altogether,
Anne H. Kuitunen, 30 MD,
patients
PhD, received levosimendan
Kari T. Kuttila, MD, PhD,(21 Tarjain K. Peräkylä, MD, PhD,
• Levosimendan
r continuous and Toni Sarapohja,
center 1, and en9MS,pré conditionnement
Raili
in center T.2)Suojaranta-Ylinen,
and 30 received placebo MD, PhD, (21 Mika
in Valtonen, MD, PhD,
• Diminution andcenter des
Markku1, andéchecs
T. Salmenperä, de sevrage
9 in center 2).MD,
ThePhD de CEC
groups were comparable
coronary artery Departments of Anesthesiology and Intensive Care, Cardiothoracic Surgery, and Cardiology, Helsinki University Central Hospital,
• Evite
opean System les assistances
for Helsinki, post op rinone). However, contractilit
hese agents is in- levosimendan
Departments solution,
of Anesthesiology and
and Cardiovascular was
Surgery,
ntricular ejection Cardiology Unit, Clinical Research and Development, Espoo, Finland
diluted
Turku and
University infused
Hospital, Turku, and Orion Pharma,
creased at the expense of inc
myocardial
New York Heart energy according to an identical schedule to levosimendan. consumption, risk of ischemia
ercutaneous coro-
rhythmias [5]. A CPB circuit with a membrane oxygenator (Dideco Levosimendan does not inc
Background. Levosimendan is a compound with vaso- 1.8 (0.3) L/min/m2 in the levosimendan group and 1.9 (0.4)
e concentrationdilatory of andAvant, Mirandola,
inotropic properties. Italy, data
Experimental or Affinity,
sug- Medtronic,
L/min/m 2 Brooklyn
in the placebo intracellular
group. The mean calcium.
duration of Instea
duces a calcium- Park,
gest effective MN)
reversal was primed
of stunning with 1500CPB
and cardioprotective to to
2000
primarymLweaning
of Ringer’s
dependent
attempt conformational
was 104 (25) minutes in ch

ADULT CARDIAC
properties. the levosimendan and 109 (22) minutes in the placebo
hrine infusion,C and
f troponin Methods. solution andrandomized,
This prospective, 100 mL placebo-con-
of 15% mannitol. group. Primary A nonpulsatileenhances
weaning was successfulthe
in 22rate and exten
patients
ne.
traction of cardiac flow of 2.4
trolled, double-blind studyL/min/m
included 602 patients with
or more, Pao(73%) exceeding 30 kPa,
in the levosimendan myofilaments
andand in 10 (33%)
group during systole [6
in the
3-vessel coronary disease and left ventricular ejection 2
placebo group (p " 0.002).cardiac
The odds output
ratio for failure in
ive care unit
imendan increases hematocrit of 22 or higher were provided to maintain without incre
fraction (LVEF) of less than 0.50. Levosimendan admin- primary weaning was 0.182 (95% confidence interval,
al guidelines. consumption in patients ear
myocardial oxygen
istration (12mixed
!g/kg bolus, followedoxygen
venous by an infusion of 0.2
saturation 0.060
(SVO to 0.552).
2 ) Four
of patients
70%. in the placebo group
Perfu- failed
at thefordiscre- !g/kg/min) was started immediately after induction an- artery bypass
the second weaning and underwent grafting
IABP compared with (CABG
CPB coronary sion pressure
esthesia. Predefined was kept
strict hemodynamic between
criteria were 60 in
none tothe80levosimendan
mm Hg.dilatory Me-(p "and
group 0.112).
possible antiisch
t also exerts vaso- used to assess the success of weaning. If weaning was not
chanical ventilation of the lungs Conclusions. Levosimendan significantly enhanced
was stopped during
effects bywithopening
successful, CPB was reinstituted and an epinephrine infu- primary weaning from CPB compared placebo inof the
d cardioprotective Fig 1. Weaning
CPB,If and
sion was started. from cardiopulmonary
Pacoweaning
the second wasattempt bypass
kept failed, (CPB). First
at 5 to patients weaning
6 kPaundergoing
by adjusting3-vessel the
dependent potassium
on-pump coronary artery (K )-
 Leppikangas 2011 Unclear Yes Yes Unclear Yes Yes Low 40% was chosen as
Lomivorotov 2011 Unclear Yes Unclear Unclear
published in 2012,
Yes
by including
Yes
a recently published clinical
Moderate surgery patients to d
12
Momeni 2011 Yes Yes Yes Unclear trial and, more Yesimportantly, Yes
by stratifying
Low studies according
Levin
Insuffisance cardiaque aigue post
2012 Unclear Unclear

(Fig 4). Subgroup analysis showed that this benefit was

Unclear Unclear to the left ventricular
Yes function of enrolledModerate
Yes patients. The primary
hypothesis was that the beneficial effects of levosimendan are
greatest in patients with reduced EF.
relied on the detection of either persistent ST-segment changes
From the *Duke
Durham, NC and †V

chirurgie cardiaque
confined to the low-EF studies in which the RD was –14.9%
(95% CI −21.3%, −8.4%, p < 0.001). No benefit was observed
in the preserved-EF studies (RD +3.3%; 95% CI −5.2%, 11.9%;
or new Q waves on postoperative ECG. Three studies

cardiac biomarkers.
Search Overall,
METHODS
employed a combination of ECG changes and elevations in
Strategythere was a significant reduction
Nashville,
Address
TN.
reprint re
Research Institute,
robert.w.harrison@d
p ¼ 0.45). The difference in effect between these subgroups in the risk of myocardial injury with levosimendan (RD
Effect of Levosimendan on Survival and Adverse Events After Cardiac Surgery:
was statistically significant (p < 0.001). "5.0% (95%
PubMed, Embase, and the Cochrane database of clinical trials were
CI −8.3%,
searched −1.7%;
for randomized p ¼trials
clinical 0.003) (Fig 5).theThe
investigating perioperative use
© 2013 Elsevier I
1053-0770/2601-0
CI −10.0%,
A Meta-analysis
Nine studies reported rates of myocardial injury, 5 low-EF
studies and 4 preserved-EF studies. Three studies defined
reduction inofmyocardial
levosimendaninjury was "6.6%
in patients (95% cardiac
undergoing
−3.3%; p < 0.001) in the low-EF subgroup. No significant
surgery. The term, http://dx.doi.org/1

myocardial injury as an increase in cardiac biomarkers HARRISONreduction was found in the preserved-EF subgroup (RD
ET AL Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2013: pp ]]]–]]]
(creatine kinase MB fraction and troponin I or T). Two studies "2.1%; 95% CI −8.9%, +4.8%; p ¼ 0.55). The difference
Robert W. Harrison, MD,* Vic Hasselblad, PhD,* Rajendra H. Mehta, MD, MS,* Ricardo Levin, MD,†
Robert
baseline A.
EF Harrington,
with preoperative MD,* and JohnoneH. Alexander, MD, MHS*
21,25,29
traction and Study Characteristics ventriculogram,
17
owing study characteristics were recorded: Last name of the utilized intraoperative TEE, three utilized preoperative trans-
year of publication, design details, number of participants, thoracic echocardiography,18 and two utilized either preoper-
95% CI −7.2%, −1.1%; p ¼ 0.008). Subgroup
12,24
rvention, timing of Objective: Left ventricular
levosimendan administration, dosing of systolic
ative dysfunction
ventriculogram is associ- Eight[RD]–4.2%;
or echocardiography. studies
an, and duration of follow-up. Baseline population charac- were categorized as low-EF. Four of these studies exclusively
atedsurgery,
uding type of cardiac withage,increased morbidity
and left ventricular EF and mortality in patients analysis showed that this benefit was confined to the low-
enrolled patients with a preoperative EF <35%. An additional 4
undergoing cardiac surgery. The
ecorded. The primary outcome of interest was the study studiesauthors performed
utilized inclusion a meta-
criteria such that the mean EF EFforstudies
the (RD −7.0%; 95% CI −11.0%, −3.1%; p < 0.001).
rtality out to postoperative day 30. In cases in which both
analysis investigating the o40%.
for effects of levosimendan in cardiac No benefit was observed in the preserved-EF subgroup (RD
population was One study (Lahtinen 2011) did not
and 30-day outcomes were reported, the latter was used report a mean or median ejection fraction, but did report that
surgery patients withhemo- and 73% of patients in the placebo arm and 77% of patients in the 95% CI −3.8%, +5.9%; p ¼ 0.66). Significant reduc-
without preoperative systolic +1.1%;
condary outcomes included renal failure requiring
ostoperative atrial fibrillation, and myocardial injury as
dysfunction.
by cardiac biomarkers and/or electrocardiographic changes.
levosimendan arm had an EF 450%.26 Therefore, this tions
study also were seen in the need for dialysis (RD "4.9%;
idity and risk of Design: was included
Meta-analysis of randomized controlled trials.
bias were assessed according to the in the preserved-EF subgroup. The study
95%byCI −8.2%, −1.6%; p ¼ 0.003), myocardial injury (RD
ollection methods.15 Momeni et al did not report a mean or median ejection fraction
Setting: Hospital. and was included in the preserved-EF subgroup.28 "5.0%; Table 2 95% CI −8.3%, −1.7%; p ¼ 0.003), and postoperative
thesis and Analysis Participants: The 1,155 patients provides anwho participated
assessment of the quality and for eachfibrillation (RD "8.1%; 95% CI −13.3%, −3.0%; p ¼ 0.002).
14 of bias atrial
in risk
of the included studies.
al heterogeneityrandomized
was measured usingcontrolled
the Cochran’s Q trials
test of perioperative levosimendan Conclusions: Levosimendan was associated with reduced
d as I2. Several of
were included.
the included studies had zero outcomes in mortality and other adverse outcomes in patients under-
arm. Studies that had no deaths in either arm suggested that Mortality
Interventions: None.
o difference in the mortality rates, and yet a meta-analysis going cardiac surgery, and these benefits were greatest in
In-hospital mortality was reported for 7 studies, and the
Measurements and Main Results: PubMed, EMBASE, the
sk ratios would discard these studies. Instead, the authors patients with reduced EF. These data support the need for
work with the risk differences (RD). This method was remaining 7 reported 30-day mortality. A total of 30 deaths
y Hasselblad etCochrane
al and has thedatabase
16
advantage of usingof clinical
all trials,
occurred amongand conference
578 patients allocated topro-
levosimendan adequately
(5.2%) powered randomized clinical trials to confirm the
ceedings were searched for clinical trials of perioperative
convention, a negative RD connotes a smaller risk of events compared with 54 deaths among 577 patients allocated benefits of levosimendan in patients with reduced EF under-
to control
mendan compared with control. Data were analyzed by (9.4%). Pooled results demonstrated a significant reduction in the
levosimendan in
2 patients
e Mantel-Haenszel fixed-effects method as I was <25% for undergoing cardiac surgery
risk of death with levosimendan (RD −4.2%; 95% CI −7.2%,
going cardiac surgery.
me and subgroup. through May 1, 2012. Studies −1.1%; were
p ¼ 0.008) grouped by mean
(Fig 2). Subgroup analysis showed& 2013
that this Elsevier Inc. All rights reserved.
f subgroup differences was performed between the low-EF
ejection
ed-EF studies. For the primaryfraction (EF).mortal-
endpoint of 30-day Those with a mean EF <40% were
benefit was confined to the low-EF studies in which the RD was
–7.0% (95% CI −11.0%, −3.1%; p < 0.001). No benefit was
designated as low-EF. Pooled
al subgroup analyses were performed based on the timing
observedresults demonstrated
in the preserved-EF studies (RD +1.1%; a 95% CIKEY −3.8%, WORDS: cardiopulmonary bypass, intensive care, heart
ndan administration and the type of control intervention.
reduction in mortality
sion was performed to determine the influence of the mean with levosimendan
5.9%; p ¼ 0.66). The (risk
difference difference
in effect between EF failure,
subgroups statistics, meta-analysis
tion of each study, as a continuous variable, on the effect of was statistically significant (p ¼ 0.01). Neither the timing of
an on mortality. Sensitivity analysis was performed by levosimendan administration (preoperative or intraoperative v
ach study, one at a time, and repeating the meta-analysis for

M
postoperative; p ¼ 0.58) nor the type of control (p ¼ 0.70)
ORE THAN 280,000
y endpoint. A p value of 0.05 was used to designate CORONARY artery
influenced the association bypass
between was combined with the Cochrane highly sensitive
graft and mortality.
levosimendan “levosimendan,”
Fig 2. Forest plot of the effect of levosimendan on postoperative mortality.
gnificance. The risk of publication bias was assessed by
(CABG) procedures, and 40,000 combined CABG/valve
ction of funnel plots. Meta-analysis and subgroup compar-
search strategy for identifying randomized trials in MEDLINE.13 Embase
procedures are performed annually in the United States. Over
performed with Review Manager (RevMan) software was queried using the term “levosimendan” combined with a previously
1. Copenhagen: The Nordic Cochrane Centre, The Cochrane 14
Débit coronaire et levosimendan

Etude expérimentale :
1H post bolus de Lévosimendan
Augmentation significative du débit coronaire droit

31
 Levosimendan et défaillance du
VD
n 40 patients en décompensation cardiaque
n Inclusion : LVEF < 35% RVFAC ≤ 24% TAPSE < 15 mm
n Dobutamine (13) vs levosimendan (27) pendant 24h

32
 Levosimendan et
préconditionement

33
Chirurgie cardiaque pédiatrique
Levosimendan for low cardiac output: a pediatric experience. Egan JR et
al. J Intensive Care Med. 2006 May-Juin
rétrospectif : 19 enfants en défaillance cardiaque
amélioration nette par Levosimendan : lactates, PAM, echo
bonne tolérance - pas d’effets secondaires
Early experience with Levosimendan in children with ventricular
dysfunction. Namachivayam P et al. Pediatr Crit Care Med. 2006 Sep
14 enfants (7 j à 18 ans) : insuffisance cardiaque aigue inotrope dépendante.
Levosimendan (B et/ou 24 h).
Arrêt des inotropes (10 pts), diminution (4 pts). FE augmente de 29 à 40,5%
Use of levosimendan, a new inodilator, for postoperative myocardial
stunning in a premature neonate. Lechner E et al. Pediatr Crit Care Med.
2007 Jan
TGV, 32 S, 1525 g, Switch, bas débit post CEC,
lactates 14.8, SvO2 56%, POG 24, Fr 10%
coronaires ok, adrénaline, milrinone, dobutamine = pas d’amélioration
Levosimendan 0,1 mcg/kg/min (24h)
34
lactates 1.7, SvO2 81%, POG 7, Fr 25%… trop fort !!
corticoïdes

35
 corticoïdes

Savoir y penser en rescue:

SIRS majeur
besoins de remplissage très importants
Hémisuccinate d’Hydrocortisone (divers poso, 50 mg/m2/j
en 4 prises, 5-10 jours)
36
Evaluation et sevrage des inotropes
Amélioration de l’oxygénation (PaO2, SaO2, SvO2,
rSO2)
Reprise du débit urinaire
Amélioration échographique et hémodynamique
Baisse des marqueurs cardiaques : Troponine et
BNP
Sevrage « step by step »
Eviter le sevrage de la VA et des inotropes en même
temps
De préférence sevrage de la VA, puis inotropes

37