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Use of CRRT in ECMO: Is It
Valuable?
James D. Fortenberry MD, FCCM, FAAP
Associate Professor of Pediatrics
Emory Universit...
2
CRRT and ECMO
 What are potential benefits?
 What is the experience?
 How do you do it?
 What are the risks?
 What ...
3
CRRT on ECMO: Potential
Benefits
Management of fluid balance
Decreasing fluid overload
Removal of inflammatory mediat...
4
Is Fluid Overload Bad?
Remember: fluid is good in
resuscitation!
Early goal directed therapy outcome
benefits
However...
5
Fluid Overload
 Texas Children’s
Hospital
 21 pediatric ARF
patients
 Survival benefit
remains even after
adjusted fo...
6
Fluid Overload
 Children’s Healthcare
of Atlanta at Egleston
 113 pediatric patients
on CVVH
 Multivariate analysis
•...
7
Fluid Overload Decreased in 3
Organ MODS CRRT Survivors
-Foland JA et al. Crit Care Med, 2004
8
Fluid Overload and ECMO:
Neonates
 As weight gain decreases, ECMO flow
decreases  which comes first?
• As weight reduc...
9
Fluid Overload and Outcome
 Seattle Children’s Hospital
 77 pediatric patients
• If pre-CRRT percent fluid overload >1...
10
Fluid Overload/Oliguria is
Common on ECMO
 Children's Healthcare of Atlanta
 30 consecutive neonates meeting ECMO
cri...
11
ECMO and Urine Output
-Roy BJ, Pediatrics 1995
12
Blood
Black BileYellow
Bile
Phlegm
Requisite Bad Humour Slide
13
Good Humours
CRRT/Plasma Exchange
CRRT/Plasma Exchange
Time
Time
SIRS/CARS
SIRS CARS SIRS CARS
Immunohomeostasis
Immunohomeostasis
Pro-...
15
Hemofiltration Cytokine
Clearance
 Children’s Healthcare of Atlanta at Egleston
 6 pediatric patients with culture pr...
16
Absolute cytokine changes in
septic shock/ARF patients
1
10
100
1000
10000
100000
IL-6 IL-10
Pre-
CVVH
End of
CVVH
LogC...
17
CVVH Associated With Decreased
Cytokines in Children with Septic
Shock
Cytokine Levels at the End of CVVH
-100
-80
-60
...
18
Cytokine Results: Sample
CVVH Patient-Nonseptic
Non-septic ARF Patient #3
0
10
20
30
40
50
60
70
80
90
Concentration(pg...
19
Cytokine Results in Sample
CVVH Patient: Septic
Septic ARF Patient #5
0
200
400
600
800
1000
1200
1400
1600
1800
2000Co...
20
ECMO/CVVH Produces
Cytokine Reduction
 In vitro study –
• Increased cytokine levels overall due to ECMO
membrane activ...
21
Skogby M, et al. Scand Cardiovasc J. 2000 Jun;34(3):315-20
IL – 8 Reduction with
CRRT in ECMO
22
Is Avoiding Lasix Overuse
Important?
Potential ototoxicity-particularly in
neonates
Lasix use associated with worsene...
23
Diuretics and Critical Illness
 4 University of California Hospitals
 552 adults
 Use of diuretics increased risk of...
24
CRRT and ECMO
 What are potential benefits?
 What is the experience?
 How do you do it?
 What are the risks?
 What...
25
CRRT on ECMO: Published
Experience with Use
 Michigan
• PICU
• Cardiac surgery
 Vanderbilt
 Atlanta
 Chile
26
CRRT/ECMO Experience:
Michigan
 U of M ECMO Database
 35 neonatal and pediatric patients who
received ECMO + hemofilt...
27
CRRT/ECMO Experience:
Cardiac Surgery
 University of Michigan
 74 post-operative congenital heart disease
patients
• ...
28
CRRT/ECMO Experience:
Cardiac Surgery
 Vanderbilt University
 84 post-operative congenital heart disease
patients
• T...
29
ECMO/CVVH Experience:
Atlanta
 Children’s at Egleston ECMO Database
(11/97-12/05)
 95 neonatal and pediatric patients...
30
Comparison of CVVH/ECMO
vs. ECMO without CVVH
 26/86 peds respiratory failure patients received
CVVH for >24 hours
 C...
31
Fluid Balance With CVVH/ECMO
vs. No CVVH/ECMO
FluidBalance(cc/kg/day)
-50
0
50
100
150 ECMO/non-CVVH
ECMO/CVVH
ECMO/CVV...
32
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Lasix
use
Days to
desired
calories
CVVH/ECMO
ECMO alone
Comparison of CVVH/ECMO
vs. ECM...
33
CRRT/ECMO Experience in
Infants: Chile
 6 of 12 infants on ECMO received CRRT
 Observed complication: excessive
ultra...
34
CRRT and ECMO
 What are potential benefits?
 What is the experience?
 How do you do it?
 What are the risks?
 What...
35
CRRT on ECMO: How to
Perform It
 Options:
• Parallel use of stand-alone CRRT devices
(Gambro, Braun)
 Pros
 Cons
• U...
ECMO/CRRT Arrangement: The “Michigan Method”
37
Use of Standard CRRT Devices
for Delivery on ECMO
38
CRRT and ECMO
 What are potential benefits?
 What is the experience?
 How do you do it?
 What are the risks?
 What...
39
CVVH/ECMO: Are There
Risks?
Complexity of machinery
Errors due to replacement fluids
Underestimation of fluid removal
40
Sometimes it gets a little
crowded
41
CRRT Error Rate Increases with
Increasing Flow/Pressure
-Sucosky, Paden et al., JMD, in press 2008
42
Error Rate in CRRT/ECMO
Circuits
 Potential error rate noted in stand-alone CVVH
 Ex vivo ECMO circuit
 Compared mea...
43
Potential Solutions
 Collaboration with
GeorgiaTech
 Paden, Sucosky
 Development of
fluid
management/CRRT
device
 H...
44
What Further Work Needs to
be done?
 Improved control of fluid management
 Randomized trial to compare CVVH/ECMO
to E...
45
Conclusions
 CRRT on ECMO can potentially provide a variety of
benefits
 CRRT can be provided
• without worsening ren...
46
MODS & ≥ 3 Organ Involvement
Effect β SE OR 95% CI p
PRISM III 0.049 0.058 1.10 0.88, 1.39 0.4
% FO 0.058 0.023 1.78 1....
Pro-Inflammatory
Mediators
Anti-Inflammatory
Mediators (Inhibitors)
Pro/Anti-Inflammatory
Mediators
Activation Depression
...
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Use of CRRT in ECMO

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  • P=0.03
  • P=0.02
  • No difference in BP, protein intake, albumin, or diuretics
  • IL-6 12704 to 183
    IL-10 706 to 45
  • Because of such large differences in starting cytokine concentrations, we compared values at the end of CVVH and 24 hours afterwards to baseline (Pre-CVVH) values in both septic and control patients. We found that IL-8,10 concentrations had signficant decreases in septic patients. This same decrease was not seen in the control population.
  • Still see the same overall pattern, the scale is just smaller. Lack a rebound after coming off of CVVH.
  • Point 1 is pre-CVVH, point 5 is discontinuation of CVVH. Generally, you see a decrease overtime with institution of CRRT. Is this because the patient is getting CRRT or just because the patient is getting better? Note what happens in septic patients 24 hours after off CVVH (time point 6). Argues that CVVH is at least having some response in clearing these and not just patient improving. Also note scale – levels at d/c of CVVH in septic patients are more than the highest levels in non-septic patients.
  • Transcript of "Use of CRRT in ECMO"

    1. 1. 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
    2. 2. 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?
    3. 3. 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
    4. 4. 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
    5. 5. 5 Fluid Overload  Texas Children’s Hospital  21 pediatric ARF patients  Survival benefit remains even after adjusted for PRISM scores 0 5 10 15 20 25 30 35 Survivors Non- Survivors Goldstein SL, et al: Pediatrics 107:1309-1312, 2001 PercentFluidOverload *
    6. 6. 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 0 2 4 6 8 10 12 14 16 Survivors Non- Survivors -Foland JA, Fortenberry et al. Crit Care Med, 2004 * PercentFluidOverload
    7. 7. 7 Fluid Overload Decreased in 3 Organ MODS CRRT Survivors -Foland JA et al. Crit Care Med, 2004
    8. 8. 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 111 cc/kg 97 cc/kg 73 cc/kg 30 cc/kg 9.1% 3.8% 2.0% 5.4% 0 20 40 60 80 100 120 25% 50% 75% 100% Duration of ECMO ECMOFlow(cc/kg) 0.0% 1.0% 2.0% 3.0% 4.0% 5.0% 6.0% 7.0% 8.0% 9.0% 10.0% WeightGain(percent)
    9. 9. 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
    10. 10. 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
    11. 11. 11 ECMO and Urine Output -Roy BJ, Pediatrics 1995
    12. 12. 12 Blood Black BileYellow Bile Phlegm Requisite Bad Humour Slide
    13. 13. 13 Good Humours
    14. 14. CRRT/Plasma Exchange CRRT/Plasma Exchange Time Time SIRS/CARS SIRS CARS SIRS CARS Immunohomeostasis Immunohomeostasis Pro-inflammatory Mediators Anti-inflammatory Mediators IL-1 TNF PAF IL-10 Adapted from Ronco et al. Artificial Organs 27(9) 792-801, 2003
    15. 15. 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
    16. 16. 16 Absolute cytokine changes in septic shock/ARF patients 1 10 100 1000 10000 100000 IL-6 IL-10 Pre- CVVH End of CVVH LogConcentration(pg/ml) p<0.02 * p=0.04 * -Paden et al., submitted 2008
    17. 17. 17 CVVH Associated With Decreased Cytokines in Children with Septic Shock Cytokine Levels at the End of CVVH -100 -80 -60 -40 -20 0 20 %DecreaseFromBaseline IL-6 IL-8 IL-10 Septic ARF Patients Non-septic ARF Patients *p<0.05 * * -Paden et al., submitted 2008
    18. 18. 18 Cytokine Results: Sample CVVH Patient-Nonseptic Non-septic ARF Patient #3 0 10 20 30 40 50 60 70 80 90 Concentration(pg/ml) Human IL-10 Human IL-6 Human IL-8 Pre-CVVH 12Hours 24Hours 48Hours EndofCVVH 24Hoursoff CVVH Note Scale
    19. 19. 19 Cytokine Results in Sample CVVH Patient: Septic Septic ARF Patient #5 0 200 400 600 800 1000 1200 1400 1600 1800 2000Concentration(pg/ml) Human IL-10 Human IL-6 Human IL-8 Pre-CVVH 12Hours 24Hours 48Hours EndofCVVH 24Hoursoff CVVH
    20. 20. 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
    21. 21. 21 Skogby M, et al. Scand Cardiovasc J. 2000 Jun;34(3):315-20 IL – 8 Reduction with CRRT in ECMO
    22. 22. 22 Is Avoiding Lasix Overuse Important? Potential ototoxicity-particularly in neonates Lasix use associated with worsened outcomes in adult renal failure
    23. 23. 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
    24. 24. 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?
    25. 25. 25 CRRT on ECMO: Published Experience with Use  Michigan • PICU • Cardiac surgery  Vanderbilt  Atlanta  Chile
    26. 26. 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
    27. 27. 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
    28. 28. 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
    29. 29. 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)
    30. 30. 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
    31. 31. 31 Fluid Balance With CVVH/ECMO vs. No CVVH/ECMO FluidBalance(cc/kg/day) -50 0 50 100 150 ECMO/non-CVVH ECMO/CVVH ECMO/CVVH - CVVH days only All Patients Survivors * ** # -Hoover et al., Intensive Care Medicine, in press 2008
    32. 32. 32 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Lasix use Days to desired calories CVVH/ECMO ECMO alone Comparison of CVVH/ECMO vs. ECMO without CVVH -Hoover et al., Intensive Care Medicine, in press 2008 ** *
    33. 33. 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
    34. 34. 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?
    35. 35. 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
    36. 36. ECMO/CRRT Arrangement: The “Michigan Method”
    37. 37. 37 Use of Standard CRRT Devices for Delivery on ECMO
    38. 38. 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?
    39. 39. 39 CVVH/ECMO: Are There Risks? Complexity of machinery Errors due to replacement fluids Underestimation of fluid removal
    40. 40. 40 Sometimes it gets a little crowded
    41. 41. 41 CRRT Error Rate Increases with Increasing Flow/Pressure -Sucosky, Paden et al., JMD, in press 2008
    42. 42. 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)
    43. 43. 43 Potential Solutions  Collaboration with GeorgiaTech  Paden, Sucosky  Development of fluid management/CRRT device  High accuracy in delivery  Patent pending
    44. 44. 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?
    45. 45. 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
    46. 46. 46 MODS & ≥ 3 Organ Involvement Effect β SE OR 95% CI p PRISM III 0.049 0.058 1.10 0.88, 1.39 0.4 % FO 0.058 0.023 1.78 1.13, 2.82 0.01 Pediatric Patients Receiving CVVH Factors Associated with Mortality - Foland, Fortenberry et al., CCM 2004
    47. 47. Pro-Inflammatory Mediators Anti-Inflammatory Mediators (Inhibitors) Pro/Anti-Inflammatory Mediators Activation Depression Time Time Parallel Serial IL1 TNF PAF IL10 IL6 MediatorLevelsMediatorLevels Adapted from Ronco et al. Artificial Organs 27(9) 792-801, 2003
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