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HEMOFILTRATION à HAUT VOLUMEEspoir et déception
Dr Vincent Bourquin - service de néphrologie - http://nephrohug.com
1.quelques rappels et définitions
2.théories, hypothèses et philosophie
3.revue de quelques études clés
4.CONCLUSION & DISCUSSION
passage de nos données au crible fin
CVVHDFPression
filtrePompe à sang Pression
d’entrée
Seringue anticoagulant
Pompe de réinjection
Détecteur d’air ClampPressionretour
liquide réinjection
Dialysat
Pompedialysat
Sac recueileffluent
Détecteurfuite sang
Pompeeffluent
Pressioneffluent
HVHFHIGH VOLUME HEMOFILTRATION
50-70 ml/kg/h sur 24h«pulse» HVHF
100-120 ml/kg/h pour 4-8h
Source: Proc 2nd Czech Conference on Critical Care Nephrology 2007
Position paper
“HVHF could be used by clinicians in catecholamine
resistant septic shock”
Source: Int J Artif Organs 2005
by ADQI group (Acute Dialysis Quality Initiative)
[Level V evidence and grade E recommendation]
cytokine storm
Immunomodulation par HVHF
Source: Critical Care Nephrology 2nd Edition, chapter 252
LPS+
-
Compensatory anti-inflammatory response syndrome
Systemic inflammatory response syndrome
SIRS CARS
“Peak concentration” hypothesis
“Threshold modulation” hypothesis
“Mediator delivery” hypothesis
Hypothèses
Source: Critical Care Nephrology 2nd Edition, chapter 255
“Peak concentration” hypothesis
Source: Ronco et al. Artif Organs 2003
“Threshold modulation” hypothesis
Source: Honoré et al. Crit Care Med 2004; Int J Artif Organs 2004
“Mediator delivery” hypothesis
Source: Alexander et al. Int J Artif Organs 2005
Eicosanoid derivatives (< 1 kD)
Inflammatory lipids: PAF (< 1 kD)
Kinine cascade (± 1 kD)bradykinine
Endothelin (< 1 kD)
Complement cascade (± 10 kD)
Procalcitonine (13 kD)
IL-8 (8 kD)
MIF (13 kD)
TNF-α (M) (M: 17.5 kD)
INF-γ (25 kD) MDF(30 kD)
IL-18 (18 kD)
IL-18 (18 kD)
IL-1β (17 kD)
IL-6 (26 kD)Factor D (23 kD) CRP (23 kD)
IL-12 (75 kD) Protein C (70 kD)
TNF-α (T) (T: 51 kD)
Endotoxin fragments (± 100 kD)100
60
50
40
30
20
10
5
1
PRO ANTI
TGF-β (25 kD)
s-TNFR-I (30 kD)
s-TNFR-II (33 kD)
IL-10 (40 kD)
Soluble receptors of IL-1 (50 kD)
Soluble receptors of IL-6 (65 kD)
IL-4 (60 kD)
Mol
ecul
ar w
eigh
t (k
D)
Cut-off of classic filtration membranes
Types of mediatorsSource: Critical Care Nephrology 2nd Edition, chapter 255
“homeostasis is not a state of stability per se but the
ability to stay stable while the status is permanently
changing”
Théorie du chaos...
Source: Honoré et al. Blood Purif 2009
Source: Seely et al. Crit Care Med 2000
Complex nonlinear systems
CRRT
“lack of specificity”
“Chacun a raison de son propre point de vue, mais il n’est pas impossible que tout le monde ait tort.”
Gandhi
Quelques études
Regardons de plus près...
Beneficial effect of high-volume hemofiltration (HVHF)
on the hemodynamics of pigs in endotoxic shock.
The ultrafiltrate from endotoxin (LPS)-infused pigs caused a 50% decrease in mean
arterial pressure (MAP)...
Source: Grootendorst et al. Intensive Care Med 1992, J Crit Care 1993
Etudes chez le cochon
Source: Ronco et al. Lancet 2000
probablement la courbe de Kaplan Meier la plus reprise...
important pour la suite
Source: Ronco et al. Lancet 2000
Study Type n Comparison MortalityMortality end point Comment
RENAL(2009)
Multicenter RCT 1’508
40 ml/kg per h vs 25 ml/l per h post-
dilution CVVHDF
45% vs 45%(P = ns) Day 90 -
ATN(2008)
Multicenter RCT 1’124
35 ml/kg per h vs 20 ml/kg per h pre-
dilution CVVHDF
54% vs 52%(P = ns) Day 60
CRRT/SLEDD vs IHD
Tolwani et al.
(2008)
Single center RCT 200
20 ml/kg per h vs 35 ml/kg per h pre-
dilution CVVHDF
56% vs 49% (P = ns)
ICU discharge or day 30 -
Saudan et al.
(2006)
Single center RCT 204
CVVHF (1-2.5 l/h) vs CVVHDF (1-2.5 l/h HF + 1-1.5 l/h HD)
59% vs 39%(P = 0.0005) Day 28
Addition of HD to HF (as HDF vs HF alone)
Bouman et al.
(2002)
Two-center RCT 106
CVVHF 72-96 l per day early vs 24-36 l per day early vs late
26% vs 31% (P = ns) vs
25% (P = ns)Day 30
Combined trial of dose and timing
Ronco et al.
(2000)
Single center RCT 425
20 ml/kg per h vs 35 ml/kg per h vs 45 ml/kg per h post-dilution CVVHF
41% vs 57% vs 58% (P < 0.02
for 20 vs 35 and 45)
Day 15Unorthodox
mortality outcome
Randomized controlled trials comparing CRRT dose in the ICU
Source: Prowle et al. Nat. Rev. Nephrol 2010
Study Type n Dose(ml/kg/h)
Clinical setting Improved survival
P
Jiang2005
RCT 37 54 SAP, sepsis yes < 0.05
Laurent2005
RCT 61 200 O-H-C-A, MI, SIRS yes 0.018
Oudemans..1999
P, cohort, UNC
306 65 SIRS, shock, AKI benefit of Obs vs Ex Morta
< 0.05
Piccini2006
R, UNC 80 45 septic shock, AKI, ALI Benefit of Obs vs Ex Morta
< 0.05
Bouman2002
Two-center RCT
106 48 SIRS, AKI, MOF no 0.8
Honoré I2000
P, cohort, UNC
20 115 refractory septic shock Benefit of Obs vs Ex Morta
< 0.05
Honoré II2006
P, cohort, UNC
38 100 refractory septic shock Benefit of Obs vs Ex Morta
< 0.05
Cornejo2006
P, cohort, UNC
20 100 refractory septic shock Benefit of Obs vs Ex Morta
0.03
Joannes...2004
P, cohort, UNC
24 60abdominal refractory
septic shockBenefit of Obs vs Ex Morta
< 0.05
Ronco2000
RCT, subgroup
425 45 ICU-AKI yes < 0.05
Most important studies on HVHF in sepsis and SIRS + AKI
Source: Prowle et al. Nat. Rev. Nephrol 2010
70 ml/kg/h vs 35 ml/kg/h
The IVOIRE study
Source: NCT00241229, Honoré et al. Réanimation 2010
[hIgh VOlume in Intensive caRE]
5 ans (oct 2005-oct 2010)
480 patients
139 patients avec mortalité à J28 de 39% et J90 de 52% soit nettement inférieure à la mortalité attendue
avec scores (SOFA, SAPS II, LOD) de 68%
Regardons d’encore plus près...
nos données
Use of High Volume Hemofiltration in patients with refractory septic shock and acute kidney injury
Choc septique réfractaire: critères Bone, dose de noradrénaline > 0.2 µg/kg/minInsuffisance rénale aiguë: selon classification RIFLECRRT: CVVHDF habituelDose: 70 ml/kg/hAccès: cathéter 13 FSolution remplacement: Hémosol®Timing: dans les 24h du choc septique réfractaire et jusqu’à 96h ou résolution du choc
3 ans (juillet 2007-juillet 2010)
55 patients
297 patients dialysés aux soins intensifs durant cette
période dont 19 % avec choc septique réfractaire
Use of High Volume Hemofiltration in patients with refractory septic shock and acute kidney injury
Mortalité 63%APACHE II 60.5%
SAPS II 66%
pas de différence entre mortalité observée et mortalité attendue par
ces 2 scores
Patient demographics
Les données détaillées ont été retirées car celle-ci sont en attente d’être publiées (!)
Si cela ne donne rien, alors je les mettrai sur ce blog...
Je connais bien le rédacteur en chef (!)
Study Type n Dose(ml/kg/h)
Clinical setting Improved survival
P
Bourquin2011
R, cohort,UNC
55 70 refractory septic shock Benefit of Obs vs Ex Morta
0.5
Jiang2005
RCT 37 54 SAP, sepsis yes < 0.05
Laurent2005
RCT 61 200 O-H-C-A, MI, SIRS yes 0.018
Oudemans..1999
P, cohort, UNC
306 65 SIRS, shock, AKI benefit of Obs vs Ex Morta
< 0.05
Piccini2006
R, UNC 80 45 septic shock, AKI, ALI Benefit of Obs vs Ex Morta
< 0.05
Bouman2002
Two-center RCT
106 48 SIRS, AKI, MOF no 0.8
Honoré I2000
P, cohort, UNC
20 115 refractory septic shock Benefit of Obs vs Ex Morta
< 0.05
Honoré II2006
P, cohort, UNC
38 100 refractory septic shock Benefit of Obs vs Ex Morta
< 0.05
Cornejo2006
P, cohort, UNC
20 100 refractory septic shock Benefit of Obs vs Ex Morta
0.03
Joannes...2004
P, cohort, UNC
24 60 abdominal refractory septic shock
Benefit of Obs vs Ex Morta
< 0.05
Ronco2000
RCT, subgroup
425 45 ICU-AKI yes < 0.05
Most important studies on HVHF in sepsis and SIRS + AKI
Source: my dreams
Possible de le faire (“safe”)
Effet de la température (?)
Effet spectaculaire (!)
Discussion
Elimination médicaments (?)
Meilleure prise en charge du choc septique réfractaire (?)
Trop tard (?)
Discussion
CRRT dose
A resolve issue in favor of conventional dosing (target effluent flow rate 20-25 ml/kg per h)
CRRT versus IHD
Consensus in favor of CRRT in hemodynamically unstable critically ill patients, but without formal evidence
Timing of CRRT
Unresolved issue that requires further research
CRRT outcomes
Unresolved issue; studies to date may have been tooo focused on mortality over renal recovery and other patient-centred outcomes
CRRT modality
Unresolved issue - CRRT modalities might be equivalent
Source: Prowle et al. Nat. Rev. Nephrol 2010
Conclusion
CRRT dose
A resolve issue in favor of conventional dosing (target effluent flow rate 20-25 ml/kg per h)
CRRT versus IHD
Consensus in favor of CRRT in hemodynamically unstable critically ill patients, but without formal evidence
Timing of CRRT
Unresolved issue that requires further research
CRRT outcomes
Unresolved issue; studies to date may have been tooo focused on mortality over renal recovery and other patient-centred outcomes
CRRT modality
Unresolved issue - CRRT modalities might be equivalent
Source: Prowle et al. Nat. Rev. Nephrol 2010
Conclusion
30 ml/kg/hpour tout le monde
DISCUSSION OUVERTEmerci de votre attention
Dr Vincent Bourquin - service de néphrologie - http://nephrohug.com