réanimation du sepsisréanimation du sepsis traitements symptomatique et adjuvants didier payen,...
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Réanimation du Sepsis Traitements symptomatique et adjuvants
Didier Payen, MD, Ph D Département d’Anesthésie-Réanimation-SMUR Hôpital Lariboisière AP-HParis Université Paris 7 Denis Diderot; INSERM 1160
Stratégie gobale • Traitement curatif
– AB « the faster the better »; contrôle de la source
• Traitement symptomatique – Volume; presseurs; ± I+;
– Assistance respiratoire si besoin
– Assistance rénale si besoin
– Coagulation si besoin…
• Traitement adjuvent: – Anti- / pro- / temps dépendant?
– RCT négatifs… revoir les concepts
Mr B., 55 ans
• Histoire de la maladie:
– Le 24/12/06, Orthopnée + toux, pas de fièvre ni expectoration
– Le 26/12/06, CS aux urgences devant majoration de la dyspnée
– Aux urgences, PA=90/60, FC=108/min, T°=36°1, SpO2=82%AA, FR=30/min
• Radio: images alvéolo-interstitielles bilatérales
Mr B., 55 ans
• Biologie:
• pH=7,39, PaCO2=21,PaO2=44, HCO3=12, BE=-9
SaO2=79%
• Na=128( Nau 30),K=3,2;Cl=98; protides=108; AG 18
• urée=13mmol/l;créatininémie=130 µmol/L
• GB=16000;Hb=13;PQ=196000, CRP=222
• ASAT/ALAT=58/37;PAL/gGT=43/75;BILI T/C =21/10
• TP=43%,TCA=1,52, fV=59%,fII=75%
• BNP=493 (nl = 500)
Au total: 1. Hypoxie, hypocapnie 2. Acidose metab a TA normal elevé Minérale car
• Prot elevé; et Cl- elevé (Na 128) 3. Insuffisance rénale… 4. Fonction hepatoque OK 5. Coag anormale: FII 75 pas antithrombique
• Fv 49% 6. Synd inflamm: CRP, GB, Tachyc, hypoTA
4 OF mais cause n’est pas claire!!
Mr B., 55 ans • Attitude initiale? Sur quel critères guidés vous votre
réanimation? • Remplissage vasculaire (comment)? Hydratation? Dépletion? 750
cc Salé rapide teste le système CV
• Bilan étiologique: – infectieux;
– Echo2D (VCI 27; VD dilate)
• Antibiothérapie par AB Large spectre (SAU)
• Solumedrol 120 mg ? (SAU)
• Ventilation: – PaO2 44; PaCO2 28; pH 7.36; BE – 8; Bicar 15
– VNI a FiO2 100% ?
• Quel est votre monitorage? • KTA/KTC cave inf (?)/ DC; VES? mais en VS…
Mr B., 55 ans (H43 hrs)
en réanimation :
• Évolution non favorable sous VNI : hypoxie malgré VNI (spO2=80%),
• collapsus non amélioré par le remplissage
• Intubation: dip/fent/celo Hypotension
– Échographie cardiaque
– Pose KT Sganz? jug Dte cote? macrocirculation
– StO2 microcirculation, ?
Mr B., 55 ans
ETT:
–VG de taille normale ; hyperkinétique, FEVG >65%
– OG et OD non dilatées, VD dilaté, Fct normale (!),
pas de foramen ovale perméable; VCI 27 !!!
DC non fait!!!
Rivers 2001, Gattinoni 1995, and Hayes 1994 (NEJM)
EGDT (Rivers) Gattinoni Hayes
Setting ED ICU ICU
Time (hrs) <1 Up to 72hrs 24hrs
Lactate (mM/L)
6.9 - 7.7 -- 2.2 – 3.5
SvO2 (%) 48.6 - 49.2 67.3 - 69.7 --
CVP (mmHg) 5.3 - 6.1 10.6 Optimized
C I (l/min/m2) 1.7 – 1.9 3.7 – 3.8 3.2 – 3.4
SVRI 1181 – 1192 708 - 735 --
Mr B., 55 ans
PA syst/dias 96/50/65
PAPs/PAPd 61/29 mmHg
POD 6 mmHg
PAPo 7 mmHg
DC 9 l/min
SvO2 82 %
Après remplissage faible. HypoTA majorée par AG NE
Crit Care Med 2006
Patients with global tissue hypoxia at early stage of disease
Nobel Prize 2011 in Medicine to innate immunity!!!
R Steinman B Beutler J Hoffmann
Nobel Price 2011
da
Impact of sepsis on innate and adaptive immune cells
pathogène Molécules du non soi
Pathogen Associated Molecular Patterns
PAMPs
Molécules du soi libérées
lors d’une destruction cellulaire
Damage Associated Molecular Patterns
DAMPs
RECEPTEURS COMMUNS Pathogen
Recognition Receptors
PRRs
• Toll-like receptors (TLRs)
• NOD-like receptors (NLRs)
• RIG-1 like receptors (RLRs)
• DNA sensors
1994 Matzinger: Danger model Réponse à la mort cellulaire non physiologique
Tolérance # Autoimmunité
0 5 10 15 20 25 30
0.0
0
.1
0.2
0
.3
0.4
0
.5
0.6
Low IL10/Low comorbidities
High IL10/Low comorbidities
Low IL10/High comorbidities
High IL10/High comorbidities
Days
Surv
ival
rat
e
221 severe sepsis: 87% septic shock
Impact of systemic inflammatory response and co-morbidity on mortality
IL-10 IL-6
Traitement adjuvent
hydrocortisone
“Tight control of Glycemia”
LA PROTEINE C ACTIVEE
PROWESS-SHOCK
Percent in study hospital @ 28d: DrotAA 305 (49%) Placebo 279 (43%)
Ranieri et al NEJM 2012
Removal of mediatorsCVVH
Payen et al, Crit Care Med 2009 Vol. 37, No. 3
Comparison: conventional therapy vs conventional therapy + CVVH (25ml/kg/h)
Inclusion within 24 hours after meeting the inclusion criteria • Conventional treatment: treatment decided by the physician in charge
• HF treatment: CVVH started within 24 hrs for at least 96 hrs
Primary end point: reduction of number and duration of sepsis-induced organ failure at day 14
Secondary end point:
mortality at day 14;
withdrawal of catecholamines infusion and
length of mechanical ventilation
Primary end point
Evolution of SOFA score in the 2 groups:
SOFA was compared to Day 0. A positive value indicates a maintenance
or a deterioration
Log Rank test: Chi2 : 8.73; p<0.003 HF group
CT group
Time,days
HF group CT group
Log Rank test: Chi2 :p=0.104 p<0.04
Time,days
CVVH was associated to longer need for cathecolamines and trend toward higher mortality
Payen et al, Crit Care Med 2009 Vol. 37, No. 3
Clinical evidence of immunodepression
25 000
19 000
13 000
7 000
19-6 21-6 23-6 25-6 27-6 29-6 1-7 3-7 5-7 7-7
Mr Al… Immuno-inflammatory monitoring for innate and adaptative
immunity L
y c
ou
nt (1
Un
it = 1
00
0 /m
l H
LA
-DR
ex
pre
ss
ion
on
CD
16
+ m
on
o Ly A Count
mHLA-DR expr
27-29 June
solumedrol
20 June
solumedrol
21 June
solumedrol
1
2
interferon g
0
5000
10000
15000
20000
25000
30000
35000
Day3 Day6 Day7
Day9 Day11
Day12 Day13
Day15 Day17
discharge
BAL pseudomonas aeru 109 +++ +++ + 0 0
2603 570
mH
LA-D
R (A
B/C
)
Days after ICU admission (post cardiac arrest)
Lukaszewicz et al.Crit Care Med 2009; 37: 2746–2752
Nl
Patients with a slope of log(mHLA-DR) <0.06 (poor recovery of HLA-DR expression) had a
higher risk of secondary infection than the group with slope >0.06.
Cumulative incidences of secondary infections after 7 days:
Crit Care Med 2009; 37: 2746–2752
(Crit Care Med 2009; 37: 2746–2752)
The Lymphopenia of sepsis (apoptosis and
extravascular distribution)
Monneret et al. Mol Med 2008;14(1-2):64
Sepsis - induced effector cell apoptosis in spleen tissue
Boomer, J. S. et al. JAMA 2011;306:2594-2605
It concerns both innate and adaptive immunity
- Innate: PMNs, Mono-Macro; B Ly; (APC)
- Adaptive: all subsets of Ly pop, except Treg CD25 Foxp3
It concerns both blood and tissue cells
Biomarker guided therapy
To conclude
• Protocolized treatment for acute care positive for outcome avoiding mistakes
• Supportive therapy guidelines are reasonable
– Customized treatment based on comorbidity
• Adjunct therapies: almost all disappeared!!!
• Work on and add some BM for inflammation status
• Immunodepression seems to be a solid concept to be taken potential treatment
Pour conclure:
• Harmoniser les pratiques OUI
• Homogénéiser les prises en charges OUI
• Edicter des Règles plus que des stratégies NON
• Confisquer la connaissance entre quelques mains NON
• Les risques:
– bloquer tout innovation; NON
– bloquer toute publication dans laquelle on ne dira pas avoir suivi la SSC!!! NON