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The Prospective Pediatric CRRT (ppCRRT) Registry
Stuart L. Goldstein, MD Principal Investigator and Founder
Timothy E Bunchman Helen DeVos Children’s HospitalGrand Rapids MI USA
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
Bunchman Brophy Goldstein Symons Somers
The Founding Five
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
ppCRRT Sponsors
The ppCRRT Registry receives grant funding from
Gambro Renal Products
Dialysis Solutions, Incorporated
Baxter Healthcare
B Braun, Inc
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
ppCRRT Registry Design
Prospective, observational format Informed consent required All centers practice according to their
local protocol with respect to initiation and termination criteriamodalityprescription
clearance fluids anticoagulation
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 Children’s patient is #1003)
Some sites’ IRB’s prevent listing date of birth, so investigator calculates age
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
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 16:1110-6
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)
Percent Fluid Overload Calculation
% FO at CVVH initiation =[ Fluid In - Fluid OutICU Admit Weight ] * 100%
Fluid In = Total Input from ICU admit to CRRT initiationFluid Out = Total Output from ICU admit to CRRT initiation
Registry PICU Data
CardiopulmonaryMaximum inotrope dosesPressors weaned? (yes/no)MAP change
ICU length of stay
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 < 180 seconds
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 UF’d per hour
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
ppCRRT Registry Circuit Data: Outcome
Filter life-span (hours) Reason for circuit change
clottingaccess malfunctionmachine malfunctionunrelated patient indication (e.g., needs CT
scan)CRRT discontinued
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 >60,000 hours of CRRT
–Texas Children’s–Boston Children’s–Seattle Children’s–UAB–University of Michigan–Mercy Children’s, KC–Egleston Children’s, Atlanta
–All Children’s, Tampa–DC Children’s–Columbus Children’s–Packard Children’s, Palo Alto–DeVos Children’s, Grand Rapids
Fluid Overload and CRRT
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)
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)
Percent Fluid Overload Calculation
% FO at CVVH initiation =[ Fluid In - Fluid OutICU Admit Weight ] * 100%
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Fluid In = Total Input from ICU admit to CRRT initiationFluid Out = Total Output from ICU admit to CRRT initiation
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)
Mean+SEMean-SE
Mean
OUTCOME
%F
O a
t CV
VH
Initi
atio
n
0
5
10
15
20
25
30
35
40
45
Death Survival
p = 0.03
N=113 *p=0.02; **p=0.01
Kaplan-Meier survival estimates, by percentage fluid overload category
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
Anticoagulation and CRRT
Heparin and citrate anticoagulation most commonly used methods
Heparin: bleeding risk Citrate: alkalosis, citrate lock
(Citrate = 1.5 x BFR150 mls/hr)
(Ca = 0.4 x citrate rate60 mls/hr)
Normocarb Dialysate
Normal Saline Replacement Fluid
Calcium can be infused in 3rd lumen of triple lumen access if available.
(BFR = 100 mls/min)
ACD-A/Normocarb Wt range 2.8 kg – 115 kgAverage life of circuit on citrate 72 hrs (range 24-143 hrs)
Pediatr Neph 2002, 17:150-154
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
Access If you don’t 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
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
Figure 1: Catheter Location by Size
0
10
20
30
40
50
60
70
80
90
100
5 French 7 French 8 French 9 French 10 French 11.5 French 12.5 French
Catheter Size
%
Femoral
IJ
Subclavian
Unknown
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
Number of Patients % Survival at 60
hours
Catheter Size*
5 6 0 (p <0.0000)
7 57 43 (p < 0.002) 8 65 55 (NS) 9 35 51 (p < 0.002) 10 46 53 (NS)
11.5 71 57 (NS) 12.5 64 60 (NS)
Insertion Site
Internal Jugular 58 60 (p < 0.05) Subclavian 31 51 (NS)
Femoral 260 52 (NS)
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
Cum ulat ive P roport ion S urviving (K aplan-M eier)
Com plete Cens ored
Fem oral Internal Jugular0 10 20 30 40 50 60 70 80
Circ uit S urvival (hours )
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cum
ulat
ive
Pro
port
ion
Sur
vivi
ng
• p<0.03 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
Cum ulat ive P roport ion S urviving (K aplan-M eier)
Com plete Cens ored
7 F r 8 F r 9 F r 10 F r 11F r 12 F r0 10 20 30 40 50 60 70 80
Circ uit S urvival (hours )
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cum
ulat
ive
Pro
port
ion
Sur
vivi
ng
• p<0.02• All ACG• 8 Fr > 9Fr survival• 9 Fr > 8 Fr femoral
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
Cum ulat ive P roport ion S urviving (K aplan-M eier)
Com plete Cens ored
CV V H(D) CV V H CV V H(DF)0 10 20 30 40 50 60 70 80
Circ uit S urvival (hours )
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cum
ulat
ive
Pro
port
ion
Sur
vivi
ng
• p<0.001• No difference in cath size or ACG used between three modalities• Modality strongest predictor in CoxProportional hazards model
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
At high risk for death with AKI needing CRRT
Fluid overload >12% associated with mortality in BMT patients with AKI
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%), p<0.05
Survival lower in MODS and ventilated patients
Flores FX et al: Pediatric Nephrology 2008, 23: 625-630
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
Variable Survivors Non-survivors p Value
Patient Admit Age (yr) 12.281.44 10.381.31 NS
Patient Admit Weight (kg) 49.826.1 41.935.53 NS
PRISM 2 at PICU admit 10.671.37 14.251.19 0.05
PICU Days to CRRT Initiation 3.451.69 5.561.45 NS
PRISM 2 at CRRT Initiation 12.951.39 16.611.21 0.05
CRRT Initiation GFR (mL/min/1.73) 50.176.55 52.535.94 NS
%FO at CRRT Initiation 10.605.55 13.905.03 NS
No. Inotropes at CRRT Initiation 0.50.23 1.10.19 0.05
CVP at CRRT Initiation 12.52.05 13.891.68 NS
Paw at CRRT Initiation (mmH2O) 15.152.5 17.461.84 NS
Paw at End CRRT (mmH2O) 8.72.94 25.762.03 <0.001
Urine Output (mL/kg/hr) 1.550.3 1.360.23 NS
CRRT Duration (day) 7.562.25 13.282.04 NS
Filtration (mL/min/1.73 m2) 2187.49189.26 2569.28201.76 NS
Flores FX et al: Pediatric Nephrology 2008, 23: 625-630
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 modalityDrug clearance by modality