Use of CRRT in ECMO: Is It Valuable? by wZ9puf

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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
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

       Texas Children’s                                 35
        Hospital
                                                         30
       21 pediatric ARF




                                Percent Fluid Overload
        patients                                         25
       Survival benefit                                 20
        remains even after                                        *
        adjusted for PRISM                               15
        scores
                                                         10

                                                         5

                                                         0
                                                              Survivors     Non-
                                                                          Survivors
  5
                      Goldstein SL, et al: Pediatrics 107:1309-1312, 2001
Fluid Overload

       Children’s Healthcare                                  16
        of Atlanta at Egleston
                                                               14
       113 pediatric patients




                                      Percent Fluid Overload
        on CVVH                                                12

       Multivariate analysis                                  10
         • Percent fluid overload                              8
                                                                        *
           independently
           associated with survival                            6
           in ≥ 3 organ MODS                                   4

                                                               2

                                                               0
                                                                    Survivors     Non-
                                                                                Survivors
  6               -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
                                                                                                     9.0%
                                   9.1%
                             100




                                                                                                             Weight Gain (percent)
                                                             97 cc/kg                                8.0%
         ECMO Flow (cc/kg)




         • As weight reduces, ECMO flow reduces
            80
                                                                                                     7.0%

                                                                               73 cc/kg              6.0%

                             60                       5.4%                                           5.0%

                                                                                                     4.0%
                             40                                                           30 cc/kg
                                                                        3.8%                         3.0%

                                                                                                     2.0%
                             20
                                                                                          2.0%
                                                                                                     1.0%

                              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                     Phlegm




     Yellow                   Black Bile
      Bile

12
Good Humours




 13
Pro-inflammatory    Anti-inflammatory
 Mediators          Mediators


                     IL-10                                            Immunohomeostasis

                          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


                                  100000

                                   10000                                            Pre-
      Log Concentration (pg/ml)




                                                                                    CVVH
                                    1000                                   p=0.04
                                                  *   p<0.02
                                                                       *            End of
                                                                                    CVVH
                                     100

                                      10

                                       1
                                           IL-6                IL-10

 16
                                                       -Paden et al., submitted 2008
CVVH Associated With Decreased
Cytokines in Children with Septic
Shock


                                                   Cytokine Levels at the End of CVVH

                                     20
         % Decrease From Baseline




                                      0                                                        IL-6
                                     -20                                                       IL-8
                                     -40
                                                                                               IL-10
                                     -60
                                                                                            *p<0.05
                                     -80

                                    -100
                                                   *     *
                                           Septic ARF Patients    Non-septic ARF Patients



  17
                                                                 -Paden et al., submitted 2008
Cytokine Results: Sample
CVVH Patient-Nonseptic


                                                       Non-septic ARF Patient #3
                                  90
                                  80
          Concentration (pg/ml)




                                  70
                                  60
                                                                                                                Human IL-10
                                  50
                                                                                                                Human IL-6
                                  40
                                  30
                                                                                                                Human IL-8
                                  20
                                  10
                                   0



                                                                                   End of CVVH

                                                                                                 24 Hours off
           Note
                                       Pre-CVVH

                                                  12 Hours


                                                             24 Hours


                                                                        48 Hours


           Scale

                                                                                                 CVVH
 18
Cytokine Results in Sample
CVVH Patient: Septic

                                                               Septic ARF Patient #5
                                  2000
                                  1800
          Concentration (pg/ml)


                                  1600
                                  1400
                                                                                                                      Human IL-10
                                  1200
                                                                                                                      Human IL-6
                                  1000
                                                                                                                      Human IL-8
                                   800
                                   600
                                   400
                                   200
                                     0


                                                                                         End of CVVH


                                                                                                       24 Hours off
                                         Pre-CVVH




                                                                   24 Hours
                                                    12 Hours




                                                                              48 Hours




                                                                                                       CVVH
 19
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




                                  150                                                ECMO/non-CVVH
                                                                                     ECMO/CVVH
                                                                                     ECMO/CVVH -
                                                                                     CVVH days only
                                                       *                **
      Fluid Balance (cc/kg/day)




                                  100


                                                                                 #
                                  50




                                   0




                                  -50


                                        All Patients                 Survivors
 31
                                             -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   Days to
              use    desired
                                -Hoover et al., Intensive Care
 32                  calories
                                  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




                     -Paden et al., ppCRRT Conference 2008 (abstr)
 42
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
                                Pro-Inflammatory         Anti-Inflammatory
                                 Mediators               Mediators (Inhibitors)
           Mediator Levels                   IL10
                             TNF
                             IL1                   PAF                           IL6
Serial



                                             Time
                                     Pro/Anti-Inflammatory
                                      Mediators
           Mediator Levels




                             Activation                    Depression
Parallel



                                              Time
                                                    Adapted from Ronco et al. Artificial Organs 27(9) 792-801, 2003

								
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