The Prospective Pediatric CRRT ppCRRT Registry

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The Prospective Pediatric CRRT (ppCRRT) Registry

• Stuart L. Goldstein, MD Principal Investigator
  and Founder

Timothy E Bunchman Helen DeVos Childrens
Hospital Grand Rapids MI USA
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How did the ppCRRT registry come to exist?

• Stu Goldstein MD originated the concept and
  identified a group who work well together to
• Initially look at what is being done as standard
  of practice
• Perform studies on
• New devices
• Drug clearance
• What can be done in the future

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The Founding Five
Bunchman Brophy Goldstein
Symons Somers
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Co-Investigators/Data Coordinators

• Michael Somers
• Michelle Baum
• Cheryl Baker
• Pat Brophy
• Theresa Mottes
• Jordan Symons
• Nancy McAfee
• Tim Bunchman
• Rick Hackbarth
• Dawn Eding
• Mark Benfield
• David Askenazi

• James Fortenberry
• Kristine Rogers
• Renee Robinson
• John Mahan
• Deepa Chand
• Francisco Flores
• Kevin McBryde
• Steven Alexander
• Annabelle Chua
• Douglas Blowey
• Stuart Goldstein

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ppCRRT Sponsors
The ppCRRT Registry receives grant funding from
Gambro Renal Products Dialysis Solutions,
Incorporated Baxter Healthcare B Braun, Inc
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ppCRRT Registry Phase 1 Observational Data

• Assess for potential associations between various
  practices and pediatric patient outcomes in 300
  patients
• Assess for potential associations between varying
  practices and CRRT machine functioning

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ppCRRT Registry Design

• Prospective, observational format
• Informed consent required
• All centers practice according to their local
  protocol with respect to
• initiation and termination criteria
• modality
• prescription
• clearance
• fluids
• anticoagulation

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ppCRRT Data Collected

• Divided into three electronic or paper forms
• Pre-Initiation/Demographic Data
• ICU data
• Filter data
• Each patient has unique identifier to describe
  center site and patient number (e.g., the third
  Texas Childrens patient is 1003)
• Some sites IRBs prevent listing date of birth,
  so investigator calculates age

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Pre-CRRT Registry Data

• Demographics
• primary disease leading to CRRT
• co-morbid illness
• MODS (yes/no)
• gender
• days in PICU prior to CRRT
• ICU admit weight and height/length
• CRRT specifics
• Modality
• CRRT reason(s)
• Treatment or prevention of fluid overload and/or
• Treatment or prevention of electrolyte imbalance
• Access size, configuration and site
• Pediatric Risk of Mortality 2 (PRISM 2) score

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PRISM 2 score

• 14 variables, 5 organ domains
• Cardiovascular (SBP, DBP, pulse)
• Respiratory (Resp rate, pO2, pCO2)
• Neurological (Glasgow Coma score, pupillary
  reaction)
• Hepatic (bilirubin)
• Metabolic (potassium, calcium, total CO2,
  glucose)
• Direct assessment of renal function not included
• Easy to calculate
• Data remains with ppCRRT and not sent elsewhere
  for analysis

Pollack M Crit Care Med. 1988 161110-6
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Pre-CRRT Registry Data CRRT Initiation

• Renal failure indices at CRRT initiation
• GFR (Schwartz)
• Urine output in previous 24 hours
• Percent fluid overload (FO)
• PRISM 2 score
• CVP
• Mean airway pressure
• Number of inotropic agents used
• Diuretics? (yes/no)

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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
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Registry PICU Data

• Cardiopulmonary
• Maximum inotrope doses
• Pressors weaned? (yes/no)
• MAP change
• ICU length of stay

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ppCRRT Registry Circuit Data

• Separate dataset for each circuit
• Machine brand
• Extracorporeal circuit volume
• Priming fluid
• Dialysis or replacement fluid composition
• Anticoagulation
• Citrate
• Heparin rate
• ACT measured per hour
• Mean ACT
• ACT lt 180 seconds

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ppCRRT Registry Circuit Data

• Clearance prescription
• CVVH versus CVVHD versus CVVHDF
• ml/1.73m2/hour
• Nutrition prescription at each circuit initiation
• Kcal/kg/day
• Grams protein/kg/day
• Total fluid intake
• Total fluid output
• Total and net ultrafiltration
• Percent blood volume UFd per hour

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ppCRRT Registry Patient Data Outcome

• Survival versus death (discharge from PICU)
• Attainment of target dry weight
• Reason to discontinue CRRT
• Death
• Regained renal function
• Underlying illness resolved
• Tolerates intermittent hemodialysis

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ppCRRT Registry Circuit Data Outcome

• Filter life-span (hours)
• Reason for circuit change
• clotting
• access malfunction
• machine malfunction
• unrelated patient indication (e.g., needs CT
  scan)
• CRRT discontinued

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ppCRRT Experience

• First patient enrolled on 1/1/01
• 376 patients entered into database as of 07/31/05
  (study end)
• 342 with complete data
• gt60,000 hours of CRRT

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

• All Childrens, Tampa
• DC Childrens
• Columbus Childrens
• Packard Childrens, Palo Alto
• DeVos Childrens, Grand Rapids

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Fluid Overload and CRRT
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• 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)

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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
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• 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)

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N113
p0.02 p0.01
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Kaplan-Meier survival estimates, by percentage
fluid overload category
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• Seven center study from the ppCRRT Registry
• 116 patients with MODS
• PRISM 2 score used to assess patient severity of
  illness
• Survival defined at PICU discharge

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Anticoagulation and CRRT

• Heparin and citrate anticoagulation most commonly
  used methods
• Heparin bleeding risk
• Citrate alkalosis, citrate lock

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(Ca 0.4 x citrate rate 60 mls/hr)
(Citrate 1.5 x BFR 150 mls/hr)
Pediatr Neph 2002, 17150-154
(BFR 100 mls/min)
Normal Saline Replacement Fluid
Calcium can be infused in 3rd lumen of triple
lumen access if available.
Normocarb Dialysate

• ACD-A/Normocarb Wt range 2.8 kg 115 kg
• Average life of circuit on citrate 72 hrs (range
  24-143 hrs)

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• Seven ppCRRT centers
• 138 patients/442 circuits
• 3 centers hepACG only
• 2 centers citACG only
• 2 centers switched from hepACG to citACG
• HepACG 230 circuits
• CitACG 158 circuits
• NoACG 54 circuits
• Circuit survival censored for
• Scheduled change
• Unrelated patient issue
• Death/witdrawal of support
• Regain renal function/switch to intermittent HD

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Access

• If you dont have a functional access, you may as
  well go home
• Small studies show
• Short femoral catheters have greater
  recirculation
• Femoral catheters have shorter functional survival

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ppCRRT Access

• Data from entire ppCRRT
• Assessed for association between functional
  survival and
• Catheter size
• Catheter site
• Modality (convection vs. diffusion)
• Femoral (69)
• IJ (16)
• SCV (8)
• Not specified (7)

Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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• plt0.03 in favor of IJ
• 5 Fr removed from analysis
• All ACG
• No difference in citACG

Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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• plt0.02
• All ACG
• 8 Fr gt 9Fr survival
• 9 Fr gt 8 Fr femoral

Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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• plt0.001
• No difference in cath size or ACG
• used between three modalities
• Modality strongest predictor in Cox
• Proportional hazards model

Hackbarth R et al IJAIO Dec 2007, 30 1116-1121
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• At high risk for death with AKI needing CRRT
• Fluid overload gt12 associated with mortality in
  BMT patients with AKI

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Stem Cell Transplant ppCRRT

• 51 patients in ppCRRT with SCT
• Mean FO 12.41 3.7.
• 45 survival
• Convection 17/29 survived (59)
• Diffusion 6/22 (27), plt0.05
• Survival lower in MODS and ventilated patients

Flores FX et al Pediatric Nephrology 2008, 23
625-630
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ppCRRT SCT

• Patients kept dry prior to CRRT initiation
• No difference in any parameter at CRRT initiation
• Paw worse for non-survivors at CRRT end

Flores FX et al Pediatric Nephrology 2008, 23
625-630
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ppCRRT

• Under the guidance of Stu this group has been
  very productive producing to data 11 papers in
  CRRT
• Under the guidance of Stu we are now looking
  prospectively
• Impact of cytokine clearance by modality
• Drug clearance by modality