CRRT for Pediatric ARF

1
CRRT for Pediatric ARF

• Stuart L. Goldstein, MD
• Assistant Professor of Pediatrics
• Baylor College of Medicine

2
Ronco et al. Lancet 2000 351 26-30
3
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?

4
Pediatric ARFRRT Modalities

• PD most commonly used RRT modality until
  mid-1990s
• Ease of application
• Limited staffing requirements
• Unit experience
• Cost

5
Pediatric ARFRRT Modality Preferences

• 92 pediatric centers
• Most frequently used ( of centers)
  modality
• 2003 was a projection

Warady and Bunchman Pediatr Nephrol 1511-13
(2000)
6
Pediatric Acute Renal FailureIdeal 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

7
Pediatric Acute Renal FailureIdeal 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
  co-morbid diseases --- Some information
• Adequate power to detect effect of an
  intervention on or an association of a clinical
  variable with outcome --- Do not exist!

8
Renal Replacement Therapy in the PICUPediatric
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 gt 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 13613-7, 1994 2. JASN
61401-9, 1995 3. Pediatr Nephrol 7703-7,
1994 4. Child Nephrol Urol 1014-7, 1990
9
Pediatric ARF Modality and Survival
Plt0.01
Plt0.01
Survival
Bunchman TE et al Ped Neph 161067-1071, 2001
10
Pediatric ARF Modality and Survival

• Patient survival on pressors (35) lower than
  without pressors (89) (plt0.01)
• Lower survival seen in CRRT than in patients who
  received HD for all disease states

Bunchman TE et al Ped Neph 161067-1071, 2001
11
CRRT and Outcome in Children

• Retrospective review of all patients who received
  CVVH(D) in the Texas Childrens Hospital PICU
  from February 1996 through September 1998 (32
  months)
• Pre-CVVH initiation data
• 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
Jun107(6)1309-12

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Percent Fluid Overload Calculation


Fluid In - Fluid Out ICU Admit Weight
100
FO at CVVH initiation
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
Jun107(6)1309-12
13
CRRT and Outcome in Children

• PRISM scores at PICU admission and CVVH
  initiation calculated by same nurse
• PICU Course Data
• 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 1071309-12
14
CRRT and Outcome in Children

• 22 pt (12 male/10 female) received 23 courses
  (3028 hrs) of CVVH (n10) or CVVHD (n12) 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
  (pNS).
• Conditions leading to CVVH (D)
• Sepsis (11)
• Cardiogenic shock (4)
• Hypovolemic ATN (2)
• End Stage Heart Disease (2)
• Hepatic necrosis, viral pneumonia, bowel
  obstruction and End-Stage Lung Disease (1 each)

Goldstein SL et al Pediatrics 2001 1071309-12
15
CRRT and Outcome in Children

• Survival curve demonstrates that nearly 75 of
  deaths occurred less than 25 days into the ICU
  course

Goldstein SL et al Pediatrics 2001 1071309-12
16
CRRT and Outcome in Children

• Lesser FO at CVVH (D) initiation was associated
  with improved outcome (p0.03)
• Lesser FO at CVVH (D) initiation was also
  associated with improved outcome when sample was
  adjusted for severity of illness (p0.03
  multiple regression analysis)

Goldstein SL et al Pediatrics 2001 1071309-12
17
CRRT and Outcome in Children
Goldstein SL et al Pediatrics 2001 1071309-12
18
Pediatric MODS and CRRT
Foland J et al Journal Society of Critical Care
Medicine (in press)
19
Pediatric MODS and CRRT
p
Variable

Hazard Ratio

95 CI


Percent fluid overload




1.5

High (
gt
10)

3.02

-
6.10

0.002


Low (lt10)

1

Dose of replacement fluid




High (

gt
gt25.6 ml/kg/h)

1.23

0.63
7-
2.39

0.533


Low (lt25.6 ml/kg/h)

1

PRISM
-
2 Score





High (
gt
11)

1.67

0.855
-
3.25

0.133


Low (lt11)

1

Number of pressors





High 3-5
-

2.03

0.65
8-
6.30

0.658


None

1

Number of pressors





Low (1
-
1-2)

2.13

1.05-
4.32

0.036


None

1

Gillespie R et al ASN 2003 abstract

20
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
• 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 Childrens
• Boston Childrens
• Seattle Childrens
• UAB
• University of Michigan
• Mercy Childrens, KC
• Egleston Childrens, Atlanta

• All Childrens, St. Petersburg
• DC Childrens
• Columbus Childrens
• Packard Childrens, Palo Alto
• DeVos Childrens, Grand Rapids

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Patient Demographics

• 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
24
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
27
ppCRRT MODS Data Clinical Variables
28
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 0-1
  (54), 2 (54) or 3 (44) pressors
• Survival rates better for patients with lt20 FO
  (61) versus gt20 FO (35) at CRRT initiation
  (plt0.001)

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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?

30
Acknowledgements The ppCRRT Group
Boston Childrens Michael Somers, MD Michelle
Baum, MD Seattle Childrens Jordan Symons,
MD Nancy Hawkins-McAfee, RN CS Mott
Childrens Patrick Brophy, MD Theresa Mottes,
RN UAB Gloria Morrison, RN Joni Barnett,
RN Childrens Mercy Douglas Blowey,
MD Eggleston, Atlanta James Fortenberry,
MD Kristine Rogers, RN
Devos Childrens Timothy Bunchman, MD Richard
Hackbarth, MD Stanford Annabelle Chua,
MD Steven Alexander, MD All Childrens Francis
co Flores, MD Columbus Childrens John Mahan,
MD Texas Childrens Cheryl Baker, RN Leisha
Sanders, RN David Wilson, RN Helen Currier,
RN DC Childrens Kevin McBryde, MD
31
Acknowledgement ppCRRT Sponsors
Gambro Renal Products (Cathy DiMuzio) Dialysis
Solutions, Incorporated (Walter ORourke) Baxter
Healthcare (Joseph Villanova)