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 the 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?
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
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
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
7
-Foland JA et al. Crit Care Med, 2004
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
8
-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)
9
Gillespie RS, et al. Pediatr Nephrol 19:1394-1399, 2004
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
10
-Roy BJ, Pediatrics 1995
ECMO and Urine Output
11
-Roy BJ, Pediatrics 1995
Requisite Bad Humour Slide
Blood
Yellow
Bile
12
Phlegm
Black Bile
Good Humours
13
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
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
15
-Paden M et al., submitted 2008
Absolute cytokine changes in
septic shock/ARF patients
Log Concentration (pg/ml)
100000
16
10000
1000
*
*
p<0.02
100
p=0.04
PreCVVH
End of
CVVH
10
1
IL-6
IL-10
-Paden 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
17
Non-septic ARF Patients
-Paden 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
18
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
19
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
20
-Skogby M, et al. Scand Cardiovasc J. 2000
IL – 8 Reduction with
CRRT in ECMO
21
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
22
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
23
-Mehta RL, et al. JAMA 2002
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?
24
CRRT on ECMO: Published
Experience with Use
Michigan
• PICU
• Cardiac surgery
Vanderbilt
Atlanta
Chile
25
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
33
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?
34
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
35
ECMO/CRRT Arrangement: The “Michigan Method”
Use of Standard CRRT Devices
for Delivery on ECMO
37
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?
38
CVVH/ECMO: Are There
Risks?
Complexity of machinery
Errors due to replacement fluids
Underestimation of fluid removal
39
Sometimes it gets a little
crowded
40
CRRT Error Rate Increases with
Increasing Flow/Pressure
41
-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
42
-Paden et al., ppCRRT Conference 2008 (abstr)
Potential Solutions
Collaboration with
GeorgiaTech
Paden, Sucosky
Development of
fluid
management/CRRT
device
High accuracy in
delivery
Patent pending
43
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?
44
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
45
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
46
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