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Prise en charge de l'IRA au cours du sepsis " Quelle place pour l’hémofiltration continue ? " Bertrand Souweine Clermont-Ferrand Acute renal failure in ICU Uchino S, JAMA 05 oliguria <200 ml/12 h or BUN=30 or need for RRT; 1738 / 29269 (5.7%) patients ICU mortality = 52% hospital mortality = 60% Acute renal failure in ICU Uchino S, JAMA 05 ICU mortality = 52% hospital mortality = 60% oliguria <200 ml/12 h or BUN=30 or need for RRT; 1738 / 29269 (5.7%) patients CVVH CVVHD 53% 34% Uchino BEST Study ICM 07 to waste Blood In (from patient) QUF = CH O x PTM x S replacement Solution 2 Blood Out (to patient) LOW PRESS HIGH PRESS (Convection) Christaki, Cur Opin Crit Care 08 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 20-35 ml/kg/h (> 100) • Requires replacement solution to drive convection • No dialysate CVVHF as renal support in septic acute renal failure Arm Global survival Sepsis group survival 20 ml/kg/h 41% 25% 35 ml/kg/h 57% 18% 45 ml/kg/h 58% 47% Ronco C, Lancet 00 48 patients 270 filters Median filter life = 15.0 h (8.9-26.1) Median down time = 3.0 h (1.0-8.3) per day in patients with septic acute renal failre 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 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 Mi M=DxC Blood In (from patient) MUF Repl. Solution Mads Blood Out (to patient) MO CLHF = S x Quf TdM = Mi-MO Membrane permeability (cut-off…) Molecular weight of the substance Free substance or protein bound Hemofiltration and immunomodulation Honore PM, CCI 03 C3a IL-6 IL-10 C5a IL-8 TNF 4/12 DC dans chaque bras CVVHF for sepsis support renal dose is no sufficient to improve survival Cole L, CCM 02 cytokine TNF IL-1 IL-6 IL-10 TNF CS <0.2 0.07-0.40 0.1-0.8 0 <0.01 < 20% < 25% < 25% 0 < 20% clairance extra-corporelle CLHF = S x Quf De Vriese AS, JASN 1999 10 patients with CVVH cross over study QB = 100 ml/min, UF rate = 25.4 +/- 0.7 ml/min followed by QB = 200 ml/min, UF rate = 44.3 +/- 1.5 ml/min change of filter change of filter 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 delay time (hrs) non survivors survivors 20 patients with refractory septic shock 4-hr HVHF followed by standard CVVH HVHF, QB=450 ml/mn + 35-L UF volume CVVH, UF volume = 24-L/day Honore PM, CCM 00 Pulse HVVHF and vasopressor requirements 15 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% Ratanarat R, Crit Care 03 Pulse HVVHF QUF=100 ml/kg/h in 20 patients with septic shock 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 Piccini, ICM 06 HVHF decreases vasopressor requirements in septic shock Short lived physiological effect 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) Cole L, ICM 01 Early HVHF in ARF with shock 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 Bouman CSC, CCM 02 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. PA < -150 mmHg QUF = CH O x PTM x S 2 QUF : PTM QB : 250 ml/mn abord vx, volémie… Ratio UF/[QB x (1-hte)] pré / post / mixte PUF < -150 mmHg P R I S M A P R I S M A P R I S M A Pharmacokinetic data of AB for 70 kg patient receiving CVVHF 35 ml/kg/h clinically significant if >0.25 Bouman LOADING DOSE IS UNAFFECTED BY CVVHF 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 MAINTENANCE DOSE FrCVVHF >0.25 requires dosage increase in comparison with renal failure concentration dependent ABs : shorten dosing interval maintained fixed dosage) IntervalCVVHF = Tanuric x (1 - FrCVVHF) time-dependent Abs Doseanuric dose CVVHF = 1-FrCVVHF 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 amino acid losses approximatively 10-15 g /day approximatively 3 g /day Amino acid losses during CRRT • depend upon the rate of ultrafiltration and free serum amino acid levels • losses approximatively 10-15 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 - 11.6% for tyrosine during CVVH [2]. - glutamine accounted for 33% of AA loss [3]. 1-Bellomo R. Am J Kidney Dis 1993 2-Davies SP et al. Crit Care Med 1991 3-Novák I et al. Artif Organs 1997 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