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Use of CRRT in ECMO: Is It Valuable? James D. Fortenberry MD, FCCM, FAAP Associate Professor of Pediatrics Emory University School of Medicine Director, Critical Care Medicine and Pediatric ECMO/Advanced Technologies Children’s Healthcare of Atlanta at Egleston
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2 CRRT and ECMO What are potential benefits? What is the experience? How do you do it? What are the risks? What more do we need to know?
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3 CRRT on ECMO: Potential Benefits Management of fluid balance Decreasing fluid overload Removal of inflammatory mediators Enhanced nutritional support Control of electrolyte abnormalities Decreased use of furosemide
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4 Is Fluid Overload Bad? Remember: fluid is good in resuscitation! Early goal directed therapy outcome benefits However, multiple studies (adults, pediatric) suggest survival benefit with decreased fluid overload in critical illness
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5 Fluid Overload Texas Children’s Hospital 21 pediatric ARF patients Survival benefit remains even after adjusted for PRISM scores Goldstein SL, et al: Pediatrics 107:1309-1312, 2001 Percent Fluid Overload *
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6 Fluid Overload Children’s Healthcare of Atlanta at Egleston 113 pediatric patients on CVVH Multivariate analysis Percent fluid overload independently associated with survival in ≥ 3 organ MODS -Foland JA, Fortenberry et al. Crit Care Med, 2004 * Percent Fluid Overload
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7 Fluid Overload Decreased in 3 Organ MODS CRRT Survivors -Foland JA et al. Crit Care Med, 2004
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8 Fluid Overload and ECMO: Neonates As weight gain decreases, ECMO flow decreases which comes first? As weight reduces, ECMO flow reduces -Kelley RE, et al. J Pediatr Surg, 1991
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9 Fluid Overload and Outcome Seattle Children’s Hospital 77 pediatric patients If pre-CRRT percent fluid overload >10% 3.02 times greater risk of mortality (95% CI 1.5-6.1, p=0.002) Gillespie RS, et al. Pediatr Nephrol 19:1394-1399, 2004
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10 Fluid Overload/Oliguria is Common on ECMO Children's Healthcare of Atlanta 30 consecutive neonates meeting ECMO criteria – 18 VV ECMO, 12 conventional management Patients who went onto ECMO had: Greater fluid overload Lower UOP Higher BUN Higher creatinine -Roy BJ, Pediatrics 1995
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11 ECMO and Urine Output -Roy BJ, Pediatrics 1995
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12 Blood Black Bile Yellow Bile Phlegm Requisite Bad Humour Slide
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13 Good Humours
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15 Hemofiltration Cytokine Clearance Children’s Healthcare of Atlanta at Egleston 6 pediatric patients with culture proven bacterial septic shock and ARF 2 on ECMO Compared to 3 ARF patients without septic shock 1 on ECMO -Paden M et al., submitted 2008
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16 Absolute cytokine changes in septic shock/ARF patients Log Concentration (pg/ml) p<0.02 * p=0.04 * -Paden et al., submitted 2008
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17 CVVH Associated With Decreased Cytokines in Children with Septic Shock Septic ARF Patients Non-septic ARF Patients * p<0.05 * * -Paden et al., submitted 2008
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18 Cytokine Results: Sample CVVH Patient-Nonseptic Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH24 Hours off CVVH Note Scale
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19 Cytokine Results in Sample CVVH Patient: Septic Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH 24 Hours off CVVH
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20 ECMO/CVVH Produces Cytokine Reduction In vitro study – Increased cytokine levels overall due to ECMO membrane activation Adding a hemofiltration circuit significantly reduced : IL-1beta IL-1ra IL-6 IL-8 -Skogby M, et al. Scand Cardiovasc J. 2000
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21 Skogby M, et al. Scand Cardiovasc J. 2000 Jun;34(3):315-20 IL – 8 Reduction with CRRT in ECMO
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22 Is Avoiding Lasix Overuse Important? Potential ototoxicity-particularly in neonates Lasix use associated with worsened outcomes in adult renal failure
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23 Diuretics and Critical Illness 4 University of California Hospitals 552 adults Use of diuretics increased risk of death or renal non-recovery in adults with ARF Overall 1.77 times greater risk -Mehta RL, et al. JAMA 2002
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24 CRRT and ECMO What are potential benefits? What is the experience? How do you do it? What are the risks? What more do we need to know?
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25 CRRT on ECMO: Published Experience with Use Michigan PICU Cardiac surgery Vanderbilt Atlanta Chile
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26 CRRT/ECMO Experience: Michigan U of M ECMO Database 35 neonatal and pediatric patients who received ECMO + hemofiltration 15 Survivors Renal recovery in 14 of 15 (93%) survivors One had Wegener’s as underlying cause of renal failure-subsequently transplanted -Meyer RJ, et al Pediatr Crit Care Med 2001
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27 CRRT/ECMO Experience: Cardiac Surgery University of Michigan 74 post-operative congenital heart disease patients Use of hemofiltration in 35% 5.01 times increased risk of death Use of hemofiltration indicative of longer ECMO support time worse outcome was from duration, not hemofiltration -Kolovos et al. Ann Thorac Surg 2003
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28 CRRT/ECMO Experience: Cardiac Surgery Vanderbilt University 84 post-operative congenital heart disease patients Temporary renal insufficiency in 41 patients (48.9%) CVVH NOT associated with : Ability to wean off ECMO Survival to discharge -Shah SA et al. ASAIO J 2005
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29 ECMO/CVVH Experience: Atlanta Children’s at Egleston ECMO Database (11/97-12/05) 95 neonatal and pediatric patients who received ECMO + CVVH 55 survivors 14 came off ECMO on RRT (1 on prior to ECMO) 1 needed RRT chronically 1 with CRF but does not need RRT Renal recovery in 53/55 (96%) survivors Both CRF patients had primary vasculitis -Paden et al., CCM 2007 (abstr)
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30 Comparison of CVVH/ECMO vs. ECMO without CVVH 26/86 peds respiratory failure patients received CVVH for >24 hours Case control comparison: 26 CVVH/ECMO pts. and 26 pts. receiving ECMO without CVVH No difference in survival or vent days during or after ECMO Significant differences in fluid balance Significant treatment differences -Hoover et al., Intensive Care Medicine, in press 2008
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31 Fluid Balance With CVVH/ECMO vs. No CVVH/ECMO -Hoover et al., Intensive Care Medicine, in press 2008
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32 Comparison of CVVH/ECMO vs. ECMO without CVVH -Hoover et al., Intensive Care Medicine, in press 2008 * * *
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33 CRRT/ECMO Experience in Infants: Chile 6 of 12 infants on ECMO received CRRT Observed complication: excessive ultrafiltration Survival to discharge in 5 of 6 (83%) All with normal renal function at discharge -Cavagnaro et al., Int J Artif Organs 2007
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34 CRRT and ECMO What are potential benefits? What is the experience? How do you do it? What are the risks? What more do we need to know?
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35 CRRT on ECMO: How to Perform It Options: Parallel use of stand-alone CRRT devices (Gambro, Braun) Pros Cons Use of inline hemofilter with syringe pumps Pros Cons
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ECMO/CRRT Arrangement: The “Michigan Method”
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37 Use of Standard CRRT Devices for Delivery on ECMO
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38 CRRT and ECMO What are potential benefits? What is the experience? How do you do it? What are the risks? What more do we need to know?
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39 CVVH/ECMO: Are There Risks? Complexity of machinery Errors due to replacement fluids Underestimation of fluid removal
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40 Sometimes it gets a little crowded
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41 CRRT Error Rate Increases with Increasing Flow/Pressure -Sucosky, Paden et al., JMD, in press 2008
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42 Error Rate in CRRT/ECMO Circuits Potential error rate noted in stand-alone CVVH Ex vivo ECMO circuit Compared measured versus actual fluid removal rates with inline hemofilter arrangement and with Braun Diapact for CVVH Significant excess fluid removal over “expected” both for inline device and commercial device -Paden et al., ppCRRT Conference 2008 (abstr)
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43 Potential Solutions Collaboration with GeorgiaTech Paden, Sucosky Development of fluid management/CRRT device High accuracy in delivery Patent pending
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44 What Further Work Needs to be done? Improved control of fluid management Randomized trial to compare CVVH/ECMO to ECMO without routine CVVH Potential use of biomarkers for initiation?
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45 Conclusions CRRT on ECMO can potentially provide a variety of benefits CRRT can be provided without worsening renal insufficiency with improved fluid balance with decreased furosemide exposure Potential risks of excessive fluid removal Further work to improve accuracy of fluid balance and to determine if use translates into outcome benefit
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46 Pediatric Patients Receiving CVVH Factors Associated with Mortality - Foland, Fortenberry et al., CCM 2004
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