Prise en charge de l'IRA au cours du sepsis " Quelle place pour l’hémofiltration continue ? " Bertrand Souweine Clermont-Ferrand

Uchino S, JAMA 05 Acute renal failure in ICU oliguria <200 ml/12 h or BUN=30 or need for RRT; 1738 / (5.7%) patients ICU mortality = 52% hospital mortality = 60%

Uchino S, JAMA 05 Acute renal failure in ICU oliguria <200 ml/12 h or BUN=30 or need for RRT; 1738 / (5.7%) patients ICU mortality = 52% hospital mortality = 60%

Uchino BEST Study ICM 07 CVVH 53% CVVHD34%

Christaki, Cur Opin Crit Care 08 Blood In Blood Out to waste (from patient) to patient) ( to patient) HIGH PRESS LOW PRESS replacementSolution (Convection) Q UF = C H 2 O x PTM x S

CVVHF Primary therapeutic goal: –Convective removal of water and electrolytes –Management of intravascular volume –higher clearance of middle and large molecular weight solutes Blood Flow rate = 150 ml/min (10 – 180) UF rate ranges ml/kg/h (> 100) Requires replacement solution to drive convection No dialysate

CVVHF as renal support in septic acute renal failure

Ronco C, Lancet 00 Arm 20 ml/kg/h35 ml/kg/h 45 ml/kg/h Global survival41%57% 58% Sepsis group survival25%18% 47%

48 patients 270 filters Median filter life = 15.0 h ( ) Median down time = 3.0 h ( ) per day

CVVHF is probably not less effective than IHD as renal support a-35 ml/kg/h of UF rate is required think of down time and perhaps prescribe a higher CVVHF doses (45 ml/kg/h) to deliver at less 35 ml/kg/h in patients with septic acute renal failre Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

CVVHF from renal support to sepsis support

Annane D, Lancet 05

Blood In Blood Out (from patient) to patient) ( to patient) Repl.Solution TdM = M i -M O M = D x CMiMi MOMO M ads M UF CL HF = S x Quf

Membrane permeability (cut-off…) Molecular weight of the substance Free substance or protein bound

Honore PM, CCI 03 Hemofiltration and immunomodulation

Cole L, CCM 02 CVVHF for sepsis support renal dose is no sufficient to improve survival 4/12 DC dans chaque bras

TNF <0.2 < 20% cytokine CS clairance extra-corporelle IL < 25% IL < 25% IL-10 0 TNF <0.01 < 20%

CL HF = S x Quf

De Vriese AS, JASN patients with CVVH cross over study Q B = 100 ml/min, UF rate = /- 0.7 ml/min followed by Q B = 200 ml/min, UF rate = /- 1.5 ml/min cytokine removal was highest 1 hour after the start of CVHHF and after the change the effect increases when increasing in UF rate the inhibitors were remove at the same extend as the inflammatory cytokines no clinical impact De Vriese AS, JASN 1999

Pulse high volume hemofiltration Honore PM, CCM patients with refractory septic shock 4-hr HVHF followed by standard CVVH HVHF, Q B =450 ml/mn + 35-L UF volume CVVH, UF volume = 24-L/day delay time (hrs)

Ratanarat R, Crit Care patients with severe sepsis/septic shock 8-hrs HVHF (85 ml/kg) followed by 16-hrs LVHF (35 ml/kg) observed 28-days mortality of 47% vs Predicted of 68% Pulse HVVHF and vasopressor requirements

mortality (SMR) = 0.6; 2/11 in responders vs 6/9 in non responders response to HVHF was the only predictor of survival Cornejo, ICM 06 Pulse HVVHF QUF=100 ml/kg/h in 20 patients with septic shock

Piccini, ICM 06

Cole L, ICM 01 Short lived physiological effect HVHF decreases vasopressor requirements in septic shock randomized cross over study, 11 patients with septic shock and MOF either 8 h of CVVH (2l/h) or 8 h of HVHF (6l/h)

Bouman CSC, CCM 02 RCT in 106 cardiac surgery patients with MV + shock + ARF causes of death : cardiac failure = 55.6% septic shock = 6.7% low mortality rate delay time between admission and HF in early groups >1.5 days no sufficient statistical power to demonstrate equivalence Early HVHF in ARF with shock

N. Renal Replacement Grade B There is no current evidence to support the use of continuous venovenous hemofiltration for the treatment of sepsis independent of renal replacement needs.

Q UF = C H 2 O x PTM x S  Q UF :  PTM Q B : 250 ml/mn abord vx, volémie… Ratio UF/[QB x (1-hte)] pré / post / mixte P A < -150 mmHg P UF < -150 mmHg

Pharmacokinetic data of AB for 70 kg patient receiving CVVHF 35 ml/kg/h clinically significant if >0.25 Bouman

since loading dose mainly depends on the VD and not on the elimination VD affected by TBW, Protein binding, tissue perfusion, lipid solubility, pH gradient, active transport LOADING DOSE IS UNAFFECTED BY CVVHF

Fr CVVHF >0.25 requires dosage increase in comparison with renal failure concentration dependent ABs : shorten dosing interval maintained fixed dosage) Interval CVVHF = T anuric x (1 - Fr CVVHF ) time-dependent Abs MAINTENANCE DOSE dose CVVHF = Dose anuric 1-Fr CVVHF

amino acid losses approximatively g /day Conventional CVVH is associated with a broad spectrum of metabolic side effects, including: the loss of amino acids such as glutamine, water-soluble vitamin, minerals, and antioxidants approximatively 3 g /day

depend upon the rate of ultrafiltration and free serum amino acid levels losses approximatively g per day 10% to 13% loss of the total amount infused [1] AA losses largely vary from one AA to another : - 1.5% of AA supply for glutamate % for tyrosine during CVVH [2]. - glutamine accounted for 33% of AA loss [3]. 1-Bellomo R. Am J Kidney Dis Davies SP et al. Crit Care Med Novák I et al. Artif Organs 1997 Amino acid losses during CRRT

Seabra AJKD 08

CVVHF during sepsis is only indicated for renal support must be started without delay requires an UF rate of 45 ml/kg/hr physician must take into account the down time to prescribe the CVHHF dose