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

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• 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

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• 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