CRRT: Dose & Modality Synthesis 1.-Seminal Study of Ronco on Dose 2.- Large Randomized Studies on Lower Dose CRRT 5.- Modality :CVVH vs CVVHDF Re Acid-Base 3.- Large Randomized Studies on High Dose CRRT (High Volume) Prof P.M. Honoré,MD,PhD Intensivist-Nephrologist Head of Clinics ICU,UZB-VUB University,Bxl, Belgium -Acute Kidney Injury Session Annual Italian ICU Congress-Florence-Nov 2013 6.-Modality: CVVH or CVVHDF Re Small Molecules 4.- Modality ; CVVH vs CVVHDF Re Mortality 7.-Perspectives- Conclusions
Survival (%) 60 50 40 30 20 P < 0,0016 * 10 0 20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr Ultrafiltration rate 2
(Neg)Prospective Randomized Studies with Septic Subpopulations The VA/NIH Study 1124 patients Between 2003 et 2007 + CVVD at 18 ml/kg/h In total = 35 ml/kg/h CVVH at 17 ml/kg/h 561 HIT 563 LIT Mean ICU > 7 Days >7 Days Stay Before Randomisation CVVH at 10 ml/kg/h + CVVD at 10 ml/kg/h In total = 20 ml/kg/h Palevsky P et al. NEJM 2008;359:7-20 Excluding 3216 patients Survival at day 60 46.4 % 48.5 % Sepsis 43.0 % 47.4 % Predilution 100 % 100 % Ronco C,Honore PM. Letter.NEJM 2008;359:1959 1962 Ronco C, Cruz D, Oudemans HM,Honore PM et al.review.crit Care 2008;308:EAP
(Neg)Prospective Randomized Studies with Septic Subpopulations RENAL Trial 1500 patients 35 sites 3 years Randomization Intensive CRRT (post-dilution CVVHDF at 40 ml/kg/hr of effluent) (750 patients) CVVHDF1/1 Conventional CRRT (post-dilution CVVHDF at 25 ml/kg/hr of effluent) (750 patients) CVVHDF1/1 N. Engl. J. Med 2009; 208:359
The RENAL Study Kaplan Meier graph of survival time from randomisation to day 90 Percentage of patients
From the RENAL & VA/NIH Databases CRRT is now widely accepted as the most appropriate therapy for vasopressor-dependent patients who require renal replacement therapy for AKI in the ICU Prowle J, Bellomo R et al Nature Review Nephrology 2010;6:521-529
«Negative» PRTS With Severe Sepsis Without AKI To conclude, in septic patients without AKI, hemofiltration with an ultrafiltration rate of 2 L/hr did not limit organ failure. Payen D et al.crit Care Med 2009;37:803-810
«Negative» PRTS With Septic Shock No AKI P=O.1NS Payen D et al.crit Care Med 2009;37:803-810
Intensive Care Med 2013;39:1535-1546
«IVOIRE study» 200 Patients with Septic Shock and Acute Kidney Injury Randomization within 24 hours of ICU admission (! Early septic shock) Any dose of vasopressors (Noradrenaline) Or > 5µg/kg/m of Dopamine - Oliguria < 0.5 ml/kg/h - creatinine X 2 RIFLE Injury 35 ml/kg/h 70 ml/kg/h Mortality D28 D90 10
High Volume PRT s : The IVOIRE Study Risk Injury GFR Criteria* Increased creatinine x1.5 or GFR decrease > 25% Increased creatinine x2 or GFR decrease > 50% Urine Output Criteria UO <.5ml/kg/h x 6 hr UO <.5ml/kg/h x 12 hr High Sensitivity Failure Increased creatinine x3 or GFR dec >75% or creatinine 4mg/dl (Acute rise of 0.5 mg/dl) UO <.3ml/kg/h x 24 hr or Anuria x 12 hrs High Specificity Loss ESRD Persistent ARF** = complete loss of renal function > 4 weeks End Stage Renal Disease Joannes-Boyau O, Honore PM.et al ICM 2013;39:1545-1546
90 days survival 100 S U R V I V A L 75 50 Log-rank p = 0.94 Standard Volume High Volume 25 0 20 40 60 80 100 Days
Hemodiafe study ATN study Renal study IVOIRE 66 /Mortality 73 % 60 % 52 % 49 %
250 Patients with severe Sepsis and AKI Randomization 50 ml/kg/h 85 ml/kg/h Mortality D28 14
DoReMi Retrospective Study (N=865) 60 50 Median delivered = 27 ml/kg/h Vesconi S et al.crit Care 2009;13: R 57 Median prescribed = 34 ml/kg/h Patients (%) 40 30 20 10 0 <5 5-10 10-15 15-20 20-25 25-30 30-35 35-40 40-45 45-50 50-55 55-60 60-65 65-70 70-75 >=75 Dose Dose of of CRRT CRRT (ml/kg/hr) (ml/kg/h) Delivered dose Prescribed dose
Studies Regarding CVVHDF vs CVVH The Geneva Study 206 patients Between 2000 et 2003 CVVH at 25 ml/kg/h CVVH at 25 ml/kg/h 102 CVVH 104 CVVHDF Survival at day 28 34 % 59 % Excluding 26 moribound patients Survival at day 28 44 % 64 % Sepsis 56 % 64 % Predilution 100 % 100 % + CVVD at 18 ml/kg/h In total = 42 ml/kg/h Saudan P et al. Kidney Int 2006;70:1312-1317
Studies Comparing CVVHDF & CVVH The Melbourne I Study 100 patients Between 2000 et 2002 CVVH at 25 ml/kg/h CVVHDF at 25 ml/kg/h 50 CVVH 50 CVVHDF + CVVD at 12.5 ml/kg/h In total = 25 ml/kg/h Diff in HCO3-- Morimatsu H, Uchino S, Bellomo R et al Int J artif Organs 2003 ;26:289-296.
Studies Comparing CVVHDF & CVVH:HCO3-- Morimatsu H, Uchino S, Bellomo R et al Int J artif Organs 2003 ;26:289-296.
Studies CVVHDF & CVVH :HCO3-- However, CVVH was associated with a lower incidence of metabolic acidosis (13.8% for CVVH vs. 34.5% for CVVHDF; p<0.0001) And so CVVH was a better Tool to correct Metabolic Acidosis Morimatsu H, Uchino S, Bellomo R et al Int J artif Organs 2003 ;26:289-296.
Studies Comparing CVVHDF & CVVH The Melbourne II Study 100 patients Between 2000 et 2002 CVVH at 25 ml/kg/h CVVHDF at 25 ml/kg/h 50 CVVH 50 CVVHDF + CVVD at 12.5 ml/kg/h Total = 25 ml/kg/h Diff in K +, Urea, Creat Morimatsu H, Uchino S, et al Int J Artif Organs 2003 ;26:289-296 Saif I et al. J Pak Med Assoc 2008;58:41-43
Studies CVVDHF Comparing CVVH & CVVHDF: Potassium Morimatsu H, Uchino S, Bellomo R et al, Int J artif Organs 2003 ;26:289-296 Saif I et al. J Pak Med Assoc 2008;58:41-43
Studies Regarding CVVHDF & CVVH :Urea Morimatsu H, Uchino S, Bellomo R et al Renal Fail 2002 ;24:289-296
Studies Regarding CVVHDF & CVVH: Creatinine Morimatsu H, Uchino S, Bellomo R et al Renal Fail 2002 ;24:289-296
We have now 5 PRT s Negative on dosing Two Large Randomized Trials are Negative for High Volume Delivered Dose should be 25 ml (so 30-35 prescribed )(KDIGO) Conclusions & Perspectives High Volume is No Longer Recommended in Septic AKI Do Not Start CRRT in Sepsis Without AKI Starting at Rifle Injury in Septic AKI could be Better but Needs to be Confirmed or Not in An Other Large Randomized Trial CVVH seems to be the best modality regarding small molecule removal because competition between diffusion & convection.. In Hemodynamical Unstable AKI Patients, CRRT should be the First Choice Therapy