Advantages and disadvantages of CRRT in ARF patients. Norbert Lameire Renal Division University Hospital Ghent, Belgium

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1 Advantages and disadvantages of CRRT in ARF patients Norbert Lameire Renal Division University Hospital Ghent, Belgium Alexandria, 17/2/2005

2 Indications for RRT in critically ill ARF patients Renal Replacement Life-threatening indications Hyperkalemia Acidemia Pulmonary edema Uremic complications Solute control Fluid removal Regulation of acid-base and electrolyte status Nutrition Renal Support Fluid removal in congestive heart failure Cytokine manipulation id sepsis Cancer chemotherapy Treatment of respiratory acidosis of ARDS Fluid management in multiorgan failure

3 Advantages and disadvantages of intermittent vs.crrt Lameire et al, The Lancet 2005,365:

4 Comparison of hemodynamic tolerance between CAVH and HD mm Hg or percent CAVH 742,1996. IHD mean MAPmmHg maxi fall MAPmmHg %MAP drops>10mmhg Misset et al Int Care Med 22:742, 1996

5 Use of adrenergic drugs in CAVH and IHD Dobutamine µg kg.min Dopamine µg kg.min Epinephrine mg.h 5 0 CAVH IHD Misset et al. Int Care Med 22:742,1996.

6 Intermittent hemodialysis guidelines in critically ill patients Recommendations for systematic use Use only modified cellulosic membranes Connect simultaneously both lines of the circuit filled with 0.9% saline to the catheter Set dialysate sodium concentration > 145 mmol/l Set dialysate temperature < 37 Advice for the most hemodynamically unstable patients Start session by dialysis and continue with ultrafiltration (UF) alone Cool dialysate at 35 C Additional recomendations Stop vasodilator therapy Start session without UF, then adapt UF/h rate according to hemodynamic response Strictly adapt UF order to patient s volemia and weight loss requirement Schortgen et al Am J Resp Crit Care Med 162, ,2000

7 Schorttgen et al Am. J. Respir. Crit. Care Med. 2000, 162, Hemodynamic Tolerance of Intermittent Hemodialysis in Critically Ill Patients Usefulness of Practice Guidelines

8 How much ultrafiltration needed in Nutrition 30 kcal/kg/day (75 kg = 2250 kcal acute renal failure? Dialysis mode Continuous ( CVVH, CVVHD) UF-rate needed in case of anuria 2400 ml/day = 100 ml/h 1000 ml AA 10 % 750 ml Glucose 40 % 350 ml Lipids 20 % + i. v. medication Intermittent 3 x 4 h per week 5 x 4 h per week 5600 ml / HD = 1400 ml /h 3360 ml / HD = 840 ml / h about 3000 ml / day 7 x 4 h per week 2400 ml/hd

9 Dose of CRRT and outcome Ronco et al Lancet 2000 % survival * * * Vicenza Heidelberg 425 ARF pts CVVH lactate * p < 0.05 no sepsis sepsis UF ml/kg/h daily UF vol l

10 Patient survival in early high volume, early low volume, and late low volume hemofiltration EHV:72-96L/24hr LLV:24-36L/24hr ELV: 24-36L/24hr Bouman et al Crit Care Med 2002, 30:

11 Treatment Dose for ARF on the ICU retrospective analysis of of dosing patterns of of continuous renal replacement therapy (CRRT) in in critically ill ill patient treated in in a large tertiary care care hospital in in the the U.S. U.S. average treatment time: ± hours per per day day average treatment dose: ± liter liter per per hour mean delivered dose: 68% 68% of of prescribed dose Venkataraman R et al. J Crit Care 2002; 17: 246

12 Cytokine removal: clinical studies removal rate, % of inlet rate TNFα IL-1β IL-6 0 t=1 t=6 t=12 t=13 t=18 t=24 Time (hours) De Vriese & Lameire, J Am Soc Nephrol 1999

13 Cytokine removal: clinical studies plasma concentration, % of t= * TNFα IL-1b IL-6 * * p< Time (hours) De Vriese & Lameire, J Am Soc Nephrol 1999

14 Cytokine removal: pro/anti-inflammatory balance Ratio anti/proinflammatory cytokines stnfr-i/tnf α stnfr-ii/tnf α IL1ra/IL Time (hours) De Vriese & Lameire, J Am Soc Nephrol 1999

15 Systemic hemodynamics during CRRT in septic shock patients De Vriese et al J Am Soc Nephrol 10: 1999

16 Daily hemodialysis and the outcome of ARF patients Alternate day Hemodialysis (N=80) Daily hemodialysis (N=80) P value Mortality no (%) 37 (46) 22 (28) 0.01 Resolution of ARF - days 16 ± 6 9 ± Schiffl et al N Engl J Med 346: ,2002

17 Daily hemodialysis and the outcome of ARF patients Variable Odds Ratio for Death (95% CI) P value Alternate-day hemodialysis (vs daily hemodialysis) 3.92 ( ) APACHE III score 1.06 ( ) 0.02 Oliguria (vs normal diuresis) 3.02 ( ) Sepsis (vs no sepsis) 3.27 ( ) Schiffl et al NEngl JMed 346: , 2002

18 Treatment Modalities for ARF on the ICU Urea clearance [ml/min] time [h] CRRT SLED IHD

19 Extended Daily Dialysis: what? Offering the choice between the advantages of a IHDF-monitor (high efficiency, low cost, high precision of UF control) in combination with the advantages of CRRT (extended treatment, smooth metabolic control) in a modular fashion, using one single type of dialysis machine Dialysis monitor with: Water treatment module Reverse osmosis unit Hemofiltration capacity Dialysate flow adjustment

20 Comparison of MAP during EDD vs. CVVH CVVH EDD P=NS P=NS P=NS premap midmap endmap Kumar et al, AJKD, 36, , 2000

21 Percentage of treatment days requiring inotropic support. % of treatment days CVVH EDD 1 Inotrope 2 Inotropes 3+ Inotropes Kumar et al, AJKD, 36, , 2000

22 Comparison of hemodynamic tolerance between SLEDD and CVVH in the ICU Mean arterial BP Heart rate Cardiac output Systemic vascular resistance Kielstein et al, Am J Kidney Dis 2004, 43:

23 Tonelli et al, AJKD, 40, , 2002 Simpson Survival IHD vs CRRT Kierdorf Sandy Johns Mehta Uehlinger Total Relative risk (IHD)

24 Comparison CVVHD vs.ihd Augustine,Paganini et al,am J Kidney Dis 44, , 2004 Diuresis Fluid balance N:40 N:40 Hospital mortality CVVHD: 67.5%; IHD: 70%

25 Meta-analysis of randomised, controlled studies comparing IHD vs CVVH in critically ill ARF patients Tonelli et al Am J Kidney Dis 2002, 40: Relative risk of non recovery of renal function

26 Treatment Costs for ARF on the ICU retrospective analysis of of immediate treatment costs in in critically ill ill patient treated either with with intermittent hemodialysis (IHD) or or continuous renal replacement therapy (CRRT) in in two two tertiary care care hospitals in in Canada costs of of IHD: IHD: 1,342 Canadian $ per per week costs of of CRRT: 3,486 to to 5,117 Canadian $ per per week Manns B et al. Crit Care Med 2003; 31: 449

27 Conclusions on dialytic management of ARF Meta-analysis has not shown a significant difference in outcome between CRRT and intermittent forms of RRT in ARF patients With appropriate methodology and experience IHD can also be used in hemodynamically unstable patients There is probably a dialysis dose effect on outcome There is no indication that the type of dialysis membrane plays a direct role in the outcome of the patient There is no definite beneficial effect of removal of cytokines on patient outcome Slow daily extended but intermittent dialysis is probably the RRT therapy of choice in ARF patients since it combines the advantages of a slow and hemodynamically better tolerable dialysis while allowing more time for diagnostic and therapeutic interventions and at a lower cost

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29 Survival IHD vs CRRT A meta analysis based on literature search: 2028 studies on outcome CRRT vs IHD only 116 acceptable quality only 6 randomized controlled trials only 2 reported as full paper 4,5, 3 as abstract 1)Simpson et al, )Kierdorf et al, )Sandy et al, )John et al, )Mehta et al, )Uehlinger et al, 2001

30 Ultrafiltration (L) Cumulative ultrafiltration volume and mean arterial pressure during 18h of extended high-flux HD using the Genius System UF volume MAP 0 Start 2h 4h 6h 8h 10h 12h 14h 16h 18h time of Genius high-flux hemodialysis MAP (mm Hg) Lonnemann et al, NDT, 15, , 2000