Use of CRRT in ECMO: Is It Valuable

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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
• Childrens Healthcare of Atlanta at Egleston

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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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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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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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Fluid Overload

• Texas Childrens Hospital
• 21 pediatric ARF patients
• Survival benefit remains even after adjusted for
  PRISM scores

Percent Fluid Overload
Goldstein SL, et al Pediatrics 1071309-1312,
2001
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Fluid Overload

• Childrens Healthcare of Atlanta at Egleston
• 113 pediatric patients on CVVH
• Multivariate analysis
• Percent fluid overload independently associated
  with survival in 3 organ MODS

Percent Fluid Overload
-Foland JA, Fortenberry et al. Crit Care Med,
2004
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Fluid Overload Decreased in 3 Organ MODS CRRT
Survivors
-Foland JA et al. Crit Care Med, 2004
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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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Fluid Overload and Outcome

• Seattle Childrens Hospital
• 77 pediatric patients
• If pre-CRRT percent fluid overload gt10
• 3.02 times greater risk of mortality (95 CI
  1.5-6.1, p0.002)

Gillespie RS, et al. Pediatr Nephrol
191394-1399, 2004
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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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ECMO and Urine Output
-Roy BJ, Pediatrics 1995
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Requisite Bad Humour Slide
Blood
Phlegm
Black Bile
Yellow Bile
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Good Humours
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Hemofiltration Cytokine Clearance

• Childrens 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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Absolute cytokine changes in septic shock/ARF
patients


p0.04
plt0.02
Log Concentration (pg/ml)
-Paden et al., submitted 2008
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CVVH Associated With Decreased Cytokines in
Children with Septic Shock
plt0.05


Septic ARF Patients
Non-septic ARF Patients
-Paden et al., submitted 2008
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Cytokine Results Sample CVVH Patient-Nonseptic
Note Scale
24 Hours off CVVH
End of CVVH
12 Hours
24 Hours
Pre-CVVH
48 Hours
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Cytokine Results in Sample CVVH Patient Septic
24 Hours off CVVH
End of CVVH
24 Hours
12 Hours
48 Hours
Pre-CVVH
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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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IL 8 Reduction with CRRT in ECMO
Skogby M, et al. Scand Cardiovasc J. 2000
Jun34(3)315-20
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Is Avoiding Lasix Overuse Important?

• Potential ototoxicity-particularly in neonates
• Lasix use associated with worsened outcomes in
  adult renal failure

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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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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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CRRT on ECMO Published Experience with Use

• Michigan
• PICU
• Cardiac surgery
• Vanderbilt
• Atlanta
• Chile

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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 Wegeners as underlying cause of renal
  failure-subsequently transplanted

-Meyer RJ, et al Pediatr Crit Care Med 2001
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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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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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ECMO/CVVH Experience Atlanta

• Childrens 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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Comparison of CVVH/ECMO vs. ECMO without CVVH

• 26/86 peds respiratory failure patients received
  CVVH for gt24 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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Fluid Balance With CVVH/ECMO vs. No CVVH/ECMO
-Hoover et al., Intensive Care Medicine, in press
2008
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Comparison of CVVH/ECMO vs. ECMO without CVVH



-Hoover et al., Intensive Care Medicine, in press
2008
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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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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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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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Use of Standard CRRT Devices for Delivery on ECMO
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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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CVVH/ECMO Are There Risks?

• Complexity of machinery
• Errors due to replacement fluids
• Underestimation of fluid removal

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Sometimes it gets a little crowded
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CRRT Error Rate Increases with Increasing
Flow/Pressure
-Sucosky, Paden et al., JMD, in press 2008
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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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Potential Solutions

• Collaboration with GeorgiaTech
• Paden, Sucosky
• Development of fluid management/CRRT device
• High accuracy in delivery
• Patent pending

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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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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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Pediatric Patients Receiving CVVHFactors
Associated with Mortality
- Foland, Fortenberry et al., CCM 2004
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