Transcript Slide 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
CRRT and ECMO
 What are potential benefits?
 What is the experience?
 How do you do it?
 What are there risks?
 What more do we need to know?
2
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
3
Is Fluid Overload Bad?
 Fluid is good in resuscitation!
 However, multiple studies (adults,
pediatric) suggest survival benefit with
decreased fluid overload in critical
illness
4
Fluid Overload
35
Percent Fluid Overload
 Texas Children’s
Hospital
 21 pediatric ARF
patients
 Survival benefit
remains even after
adjusted for PRISM
scores
30
25
20
*
15
10
5
0
Survivors
5
NonSurvivors
Goldstein SL, et al: Pediatrics 107:1309-1312, 2001
Fluid Overload
• Percent fluid overload
independently
associated with survival
in ≥ 3 organ MODS
16
Percent Fluid Overload
 Children’s Healthcare
of Atlanta at Egleston
 Retrospective review
 113 Pediatric patients
on CVVH
 Multivariate analysis
14
12
10
8
*
6
4
2
0
Survivors
6
NonSurvivors
-Foland JA, Fortenberry et al. Crit Care Med, 2004
Fluid Overload Decreased in 3
Organ MODS CRRT Survivors
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-Foland JA, Fortenberry et al. Crit Care Med, 2004
Pediatric Patients Receiving
CVVH
Factors Associated with Mortality
MODS &  3 Organ Involvement
Effect

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
- Foland, Fortenberry et al., CCM 2004
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Fluid Overload and ECMO:
Neonates
 As weight gain decreases, ECMO flow
decreases  which comes first?
120
10.0%
111 cc/kg
97 cc/kg
• As
weight reduces, ECMO flow reduces
80
73 cc/kg
60
8.0%
7.0%
6.0%
5.0%
5.4%
4.0%
40
3.8%
30 cc/kg
3.0%
2.0%
20
2.0%
0
Weight Gain (percent)
ECMO Flow (cc/kg)
100
9.0%
9.1%
1.0%
0.0%
25%
50%
75%
100%
Duration of ECMO
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-Kelley RE, et al. J Pediatr Surg, 1991
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)
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Gillespie RS, et al. Pediatr Nephrol 19:1394-1399, 2004
We Know UOP Decreases 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
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-Roy BJ, Cornish JD, Clark RH. Pediatrics 1995
ECMO and Urine Output
12
- Ref
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
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Requisite Bad Humour Slide
Blood
Yellow
Bile
14
Phlegm
Black Bile
Serial
Mediator Levels
Pro-Inflammatory
Mediators
Anti-Inflammatory
Mediators (Inhibitors)
IL10
TNF
IL1
IL6
PAF
Time
Parallel
Mediator Levels
Pro/Anti-Inflammatory
Mediators
Activation
Depression
Time
Adapted from Ronco et al. Artificial Organs 27(9) 792-801, 2003
Pro-inflammatory
Mediators
Anti-inflammatory
Mediators
Immunohomeostasis
IL-10
CRRT/Plasma Exchange
TNF
PAF
IL-1
SIRS
CARS
SIRS
CARS
Time
Immunohomeostasis
CRRT/Plasma Exchange
SIRS/CARS
Time
Adapted from Ronco et al. Artificial Organs 27(9) 792-801, 2003
Absolute cytokine changes in
septic shock/ARF patients
Log Concentration (pg/ml)
100000
17
10000
1000
*
*
p<0.02
100
p=0.04
PreCVVH
End of
CVVH
10
1
IL-6
IL-10
-Paden M et al., submitted 2008
CVVH Associated With Decreased
Cytokines in Children with Septic
Shock
% Decrease From Baseline
Cytokine Levels at the End of CVVH
20
0
IL-6
-20
IL-8
-40
IL-10
-60
*p<0.05
-80
-100
*
*
Septic ARF Patients
18
Non-septic ARF Patients
-Paden M et al., submitted 2008
Cytokine Results: Sample
CVVH Patient-Nonseptic
Non-septic ARF Patient #3
90
Concentration (pg/ml)
80
70
60
Human IL-10
50
Human IL-6
40
Human IL-8
30
20
10
19
24 Hours off
CVVH
End of CVVH
48 Hours
24 Hours
12 Hours
Note
Scale
Pre-CVVH
0
Cytokine Results in Sample
CVVH Patient: Septic
Septic ARF Patient #5
Human IL-10
Human IL-6
Human IL-8
24 Hours off
CVVH
End of CVVH
48 Hours
24 Hours
600
400
200
0
12 Hours
20
1600
1400
1200
1000
800
Pre-CVVH
Concentration (pg/ml)
2000
1800
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
21
-Skogby M, et al. Scand Cardiovasc J. 2000
IL – 8 Reduction with
CRRT in ECMO
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Skogby M, et al. Scand Cardiovasc J. 2000 Jun;34(3):315-20
Is Avoiding Lasix Overuse
Important?
 Potential ototoxicity-particularly in
neonates
 Lasix use associated with worsened
outcomes in adult renal failure
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
• Some subgroups had as much as 3.12 times
increased risk.
24
-Mehta RL, et al. JAMA 2002
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 Wegener’s as underlying cause of
renal failure-subsequently transplanted
26
-Meyer RJ, et al Pediatr Crit Care Med 2001
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
27
-Kolovos et al. Ann Thorac Surg 2003
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
28
-Shah SA et al. ASAIO J 2005
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
29
-Paden et al., CCM 2007 (abstr)
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
30
Fluid Balance With CVVH/ECMO
vs. No CVVH/ECMO
ECMO/non-CVVH
ECMO/CVVH
ECMO/CVVH CVVH days only
Fluid Balance (cc/kg/day)
150
*
100
**
#
50
0
-50
All Patients
31
Survivors
-Hoover et al., Intensive Care Medicine, in press 2008
Comparison of CVVH/ECMO
vs. ECMO without CVVH
5
4.5
4
3.5
3
2.5
CVVH/ECMO
2
ECMO alone
1.5
*1 *
*
0.5
0
Lasix
use
32
Days to
desired
calories
-Hoover et al., Intensive Care
Medicine, in press 2008
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 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
34
ECMO/CRRT Arrangement: The “Michigan Method”
Use of CRRT Devices for
Delivery on ECMO
36
CVVH/ECMO: Are There
Risks?
 Complexity of machinery
 Errors due to replacement fluids
 Underestimation of fluid removal
37
Sometimes it gets a little
crowded
38
CRRT Error Rate Increases with
Increasing Flow/Pressure
39
-Sucosky, Paden et al., JMD, in press 2008
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
40
-Paden et al., ppCRRT Conference 2008 (abstr)
What Further Work Needs to
be done?
 Improved control of fluid management
 Randomized trial to compare CVVH/ECMO
41
Conclusions
 CRRT on ECMO can potentially provide a variety of
benefits
 Experience suggests CRRT can be provided
without worsening renal insufficiency and with
improved fluid balance, 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
42