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