Transcript CRRT for Pediatric ARF - Pediatric Continuous Renal

CRRT for Pediatric ARF
Stuart L. Goldstein, MD
Assistant Professor of Pediatrics
Baylor College of Medicine
Goldstein S: pCRRT 2004 meeting
Ronco et al. Lancet 2000; 351: 26-30
425 patients
Endpoint = survival 15 days after D/C HF
146 UF rate 20ml/kg/hr
survival significantly lower
in this group compared
to the others
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139 UF rate 35ml/kg/hr
p=0.0007
140 UF rate 45ml/kg/hr
p=0.0013
Ronco et al. Lancet 2000; 351: 26-30
• Conclusions:
– Minimum UF rates should reach at least 35
ml/kg/hr
• (2000/1.73m2/hr when adapted for children)
– Survivors in all their groups had lower BUNs
than non-survivors prior to commencement of
hemofiltration
• Begs the question does early CRRT effect outcome?
Goldstein S: pCRRT 2004 meeting
Pediatric ARF:
RRT Modalities
• PD most commonly used RRT modality
until mid-1990’s
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Ease of application
Limited staffing requirements
Unit experience
Cost
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Pediatric ARF:
RRT Modality Preferences
• 92 pediatric centers
• Most frequently used
(% of centers) modality
• *2003 was a projection
Year
CRRT
PD
HD
1995
18
45
38
1999
36
31
33
2003*
53
20
25
Warady and Bunchman: Pediatr Nephrol 15:11-13 (2000)
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Pediatric Acute Renal Failure:
Ideal Study Design
• Prospective protocol driven entry criteria to
ensure that patients and their respective
disease receive similar treatment
• Control for severity of illness, primary and
co-morbid diseases
• Adequate power to detect effect of an
intervention on or an association of a clinical
variable with outcome
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Pediatric Acute Renal Failure:
Ideal Study Design
• Prospective protocol driven entry criteria to ensure
that patients and their respective disease receive
similar treatment --- Do not exist!
• Control for severity of illness, primary and comorbid diseases --- Some information
• Adequate power to detect effect of an intervention
on or an association of a clinical variable with
outcome --- Do not exist!
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Renal Replacement Therapy in the PICU:
Pediatric Outcome Literature
• Few pediatric studies (all single center) use
severity of illness measure to evaluate outcomes in
pediatric RRT:
– Lane noted that mortality was greater after bone marrow transplant
who had > 10% fluid overload at the time of HD initiation
– Smoyer2 found higher mortality in patients on pressors
– Faragson3 found PRISM to be a poor outcome predictor in patients
treated with HD
– Zobel4 demonstrated that children who received CRRT with worse
illness severity by PRISM score had increased mortality
• Did not stratify by modality
1. Bone Marrow Transplant 13:613-7, 1994
2. JASN 6:1401-9, 1995
3. Pediatr Nephrol 7:703-7, 1994
4. Child Nephrol Urol 10:14-7, 1990
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Pediatric ARF: Modality and Survival
P<0.01
90
80
P<0.01
70
60
% Survival
50
40
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10
0
IHD
PD
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
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CRRT
Pediatric ARF: Modality and Survival
• Patient survival on pressors (35%) lower than
without pressors (89%) (p<0.01)
• Lower survival seen in CRRT than in patients who
received HD for all disease states
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
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CRRT and Outcome in Children
• Retrospective review of all patients who received
CVVH(D) in the Texas Children’s Hospital PICU from
February 1996 through September 1998 (32 months)
• Pre-CVVH initiation data:
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Age
Primary disease leading to need for CVVH
Co-morbid diseases
Reason for CVVH
Fluid intake (Fluid In) from PICU admission to CVVH initiation
Fluid output (Fluid Out) from PICU admission to CVVH initiation
GFR (Schwartz formula) at CVVH initiation
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
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Percent Fluid Overload Calculation
[
% FO at CVVH initiation =
Fluid In - Fluid Out
ICU Admit Weight
]
* 100%
Fluid In = Total Input from ICU admit to CRRT initiation
Fluid Out = Total Output from ICU admit to CRRT initiation
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
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CRRT and Outcome in Children
• PRISM scores at PICU admission and CVVH initiation
calculated by same nurse
• PICU Course Data:
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Maximum number of pressors used
Pressors completely weaned (y/n)
Mean Airway Pressure (Paw) at CVVH initiation and termination
ICU length of stay (days)
CVVH complications
Outcome (death or survival)
Goldstein SL et al: Pediatrics 2001 107:1309-12
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CRRT and Outcome in Children
• 22 pt (12 male/10 female) received 23 courses (3028 hrs) of
CVVH (n=10) or CVVHD (n=12) over study period.
• Overall survival was 41% (9/22).
• Survival in septic patients was 45% (5/11).
• PRISM scores at ICU admission and CVVH initiation
were 13.5 +/- 5.7 and 15.7 +/- 9.0, respectively (p=NS).
• Conditions leading to CVVH (D)
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Sepsis (11)
Cardiogenic shock (4)
Hypovolemic ATN (2)
End Stage Heart Disease (2)
Hepatic necrosis, viral pneumonia, bowel obstruction and EndStage Lung Disease (1 each)
Goldstein SL et al: Pediatrics 2001 107:1309-12
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CRRT and Outcome in Children
0
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CumulativeProportionSurviving
• Survival curve
demonstrates that
nearly 75% of deaths
occurred less than 25
days into the ICU
course
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Goldstein SL et al: Pediatrics 2001 107:1309-12
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CRRT and Outcome in Children
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Goldstein SL et al: Pediatrics 2001 107:1309-12
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p=
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%FOatCVVHInitiation
• Lesser % FO at CVVH (D)
initiation was associated
with improved outcome
(p=0.03)
• Lesser % FO at CVVH (D)
initiation was also
associated with improved
outcome when sample was
adjusted for severity of
illness (p=0.03; multiple
regression analysis)
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CRRT and Outcome in Children
25
20
15
Survivor
Non-Survivor
10
5
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Max Pressor
GFR
Paw Change
Goldstein SL et al: Pediatrics 2001 107:1309-12
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Pediatric MODS and CRRT
Variable
Survivors, n
Non-survivors, n
P value
14.0 (9.0, 17.0),
42
16.0 (12.0, 20.0),
39
0.02
3.5 (1.0, 8.5), 42
16.0 (4.0, 23.0), 39
2.0 (1.0, 5.0), 42
3.0 (1.0,6.0), 39
0.34
Fluid overload,%
9.2 (5.1, 16.7),
33
15.5 (8.3, 28.6), 37
0.01a
ICU fluid overload,%
6.5 (4.5, 16.0),
26
10.0 (3.6, 14.7), 28
0.57
% vasoactive infusions
88.1, 42
92.3, 39
0.71
PRISM III at CVVH
Hospital days prior to
CVVH
Days in ICU prior to
CVVH
Foland J et al: Journal Society of Critical Care Medicine (in press)
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0.001a
Pediatric MODS and CRRT
Variable
Hazard Ratio
95% CI
p
Percent fluid overload
High >( 10%)
3.02
Low (<10%)
1
Dose of replacement fluid
High ( >>25.6 ml/kg/h) 1.23
Low (<25.6 ml/kg/h)
1.5 -6.10
0.002
0.637-2.39
0.533
0.855
- 3.25
0.133
0.658-6.30
0.658
1.05- 4.32
0.036
1
PRISM
- 2 Score
High >11)
(
1.67
Low (<11)
1
Number of pressors
High 3-5
None
2.03
1
Number of pressors
Low (1
-1-2)
None
Gillespie R et al: ASN 2003 [abstract]
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2.13
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Prospective Pediatric CRRT (ppCRRT )
Registry Registry: Phase 1 Design
• Collect prospective data from 10 pediatric centers
treating 15 to 20 patients annually (200-300
patients over 4 years)
• Each center follows own institutional practice
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Patient selection
Initiation and termination
Anti-coagulation protocols
Convection versus diffusion versus hemodiafiltration
Fluid composition
• Cytokine clearance study
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ppCRRT Experience
• First patient enrolled on 1/1/01
• 231 patients entered into database as of 05/31/04
• Currently 12 active participating pediatric centers,
11 have entered at least one patient
–Texas Children’s
–Boston Children’s
–Seattle Children’s
–UAB
–University of Michigan
–Mercy Children’s, KC
–Egleston Children’s, Atlanta
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–All Children’s, St. Petersburg
–DC Children’s
–Columbus Children’s
–Packard Children’s, Palo Alto
–DeVos Children’s, Grand Rapids
Patient Demographics
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•
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Newborn to 25 years
59% males
Weights 1.3 – 160kg (mean 33.5 kg)
Mean 6.5 days in ICU prior to CRRT
– (range 0 – 135 days, median 2)
• Modality
– CVVH (33%)
– CVVHD (54%)
– CVVHDF (13%)
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ppCRRT Data: Size Distribution
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Indications for CRRT and Survival
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ppCRRT MODS Data
BASELINE DEMOGRAPHICS
231 patients entered (1/1/2001 to 5/31/04)
169/231 (73%) with MODS (2+ organs involved)
Mean age 8.6 + 6.9 years (2 days to 25.1 years)
Mean weight 33.7 + 25.1 kg (1.9 to 160 kg)
Mean GFR 37.9+ 31.1 at CRRT initiation
Median 3 ICU days prior to CRRT initiation
Range 0 to 103 days
114/169 (67%) less than 7 days
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ppCRRT MODS Data: Survival
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ppCRRT MODS Data: Clinical Variables
Variable (values mean +/- SD)
Survivors
NonSurvivors
Age (years)
9.2 + 6.8
8.0 + 7.3
p-value
(t-test)
NS
Weight (kg)
35.9 + 25.9 31.7 + 30.5
NS
PRISM at ICU Admit
13.9 + 8.1
16.3 + 10.1
NS
PRISM at CRRT Initiation
14.7 + 7.6
19.8 + 8.3
<0.001
CVP at CRRT Initiation
16.4 + 6.2
18.4 + 8.3
NS
GFR at CRRT Initiation
37.0 + 31.9 39.2 + 31.7
NS
% FO at CRRT Initiation
14.2 + 15.5
22. + 18.3
<0.005
1.4 + 1.0
1.6 + 1.1
NS
No. of Pressors
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ppCRRT MODS Data: Other Analyses
 %FO associated with outcome when
CRRT initiation PRISM 2 controlled in
multiple regression analysis
 Survival rates similar by CRRT modality
 Survival rates similar for patients on: 01 (54%), 2 (54%) or 3+ (44%) pressors
 Survival rates better for patients with:
<20% FO (61%) versus >20% FO (35%) at
CRRT initiation (p<0.001)
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CRRT for Pediatric ARF: Summary
• CRRT is the most popular therapy for critically ill
children with ARF
• Single center data and multi-center data show that
worse fluid overload is associated with worse
outcome
– Would early initiation of CRRT to prevent worsening
fluid overload improve survival?
• Prospective randomized controlled trials do not
exist (and could be unethical)
– Medication adjustment based on volume status?
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Acknowledgements: The ppCRRT Group
Boston Children’s: Michael Somers, MD
Michelle Baum, MD
Devos Children’s: Timothy Bunchman, MD
Richard Hackbarth, MD
Stanford:
Seattle Children’s: Jordan Symons, MD
Nancy Hawkins-McAfee, RN
CS Mott Children’s: Patrick Brophy, MD
Theresa Mottes, RN
All Children’s:
Annabelle Chua, MD
Steven Alexander, MD
Francisco Flores, MD
Columbus Children’s: John Mahan, MD
UAB:
Gloria Morrison, RN
Joni Barnett, RN
Texas Childrens:
Cheryl Baker, RN
Leisha Sanders, RN
David Wilson, RN
Helen Currier, RN
DC Children’s:
Kevin McBryde, MD
Children’s Mercy: Douglas Blowey, MD
Eggleston, Atlanta: James Fortenberry, MD
Kristine Rogers, RN
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Acknowledgement: ppCRRT Sponsors
Gambro Renal Products (Cathy DiMuzio)
Dialysis Solutions, Incorporated (Walter O’Rourke)
Baxter Healthcare (Joseph Villanova)
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