Transcript The Prospective Pediatric CRRT (ppCRRT) Registry

The Prospective Pediatric CRRT
(ppCRRT) Registry
Stuart L. Goldstein, MD Principal Investigator and Founder
Timothy E Bunchman
Helen DeVos Children’s Hospital
Grand 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
The Founding Five
Bunchman
Brophy
Goldstein
Symons
Somers
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 criteria
 modality
 prescription
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 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
Registry PICU Data

Cardiopulmonary
 Maximum
inotrope doses
 Pressors 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

 clotting
 access
malfunction
 machine malfunction
 unrelated 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 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

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)
4
5
4
0
3
5
3
0
p=
0
.0
3
2
5
%FOatCVVHInitiation

2
0
1
5
1
0
5
0
M
e
a
n
+
S
E
M
e
a
n
-S
E
D
e
a
th
O
U
T
C
O
M
E
S
u
rv
iv
a
l
M
e
a
n
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

(Ca = 0.4 x citrate rate
60 mls/hr)
(Citrate = 1.5 x BFR
150 mls/hr)
Pediatr Neph 2002,
17:150-154
(BFR = 100 mls/min)
Normocarb
Dialysate
Normal
Saline
Replaceme
nt Fluid
Calcium can be infused in 3rd
lumen of triple lumen access if
available.
ACD-A/Normocarb Wt range 2.8 kg – 115 kg
Average life of circuit on citrate 72 hrs (range 24-143 hrs)

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
 Catheter
size
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
100
90
80
70
60
Femoral
%
IJ
50
Subc lavian
U nknown
40
30
20
10
0
5 F renc h
7 F renc h
8 F renc h
9 F renc h
1 0 F renc h
Cathet er Size
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
1 1 .5 Frenc h 1 2 .5 Frenc h
Number of Patients
% Survival at 60
hours 
Catheter Size*
5
7
8
9
10
11.5
12.5
6
57
65
35
46
71
64
0 (p <0.0000)
43 (p < 0.002)
55 (NS)
51 (p < 0.002)
53 (NS)
57 (NS)
60 (NS)
Insertion Site
Internal Jugular
Subclavian
Femoral
58
31
260
60 (p < 0.05)
51 (NS)
52 (NS)
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
Cumulative Proportion Surviving (Kaplan-Meier)
Complete
Censored
Cumulative Proportion Surviving
1.0
0.9
0.8
•
•
•
•
0.7
0.6
p<0.03 in favor of IJ
5 Fr removed from analysis
All ACG
No difference in citACG
0.5
0.4
0
10
20
30
40
50
60
70
80
Femoral
Internal Jugular
Circuit Survival (hours)
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
Cumulative Proportion Surviving (Kaplan-Meier)
Complete
Censored
1.0
Cumulative Proportion Surviving
0.9
• p<0.02
• All ACG
• 8 Fr > 9Fr survival
• 9 Fr > 8 Fr femoral
0.8
0.7
0.6
0.5
0.4
0.3
0
10
20
30
40
50
60
70
Circuit Survival (hours)
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
80
7 Fr
8 Fr
9 Fr
10 Fr
11Fr
12 Fr
Cumulative Proportion Surviving (Kaplan-Meier)
Complete
Censored
1.0
Cumulative Proportion Surviving
0.9
0.8
•
p<0.001
•
No difference in cath size or ACG
used between three modalities
•
Modality strongest predictor in C
Proportional hazards model
0.7
0.6
0.5
0.4
0.3
0
10
20
30
40
50
60
70
80
Circuit Survival (hours)
Hackbarth R et al: IJAIO Dec 2007, 30: 1116-1121
CVVH(D)
CVVH
CVVH(DF)


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 nonsurvivors at CRRT end
Variable
Survivors
Non-survivors
p Value
Patient Admit Age (yr)
12.281.44
10.381.31
NS
Patient Admit Weight (kg)
49.826.1
41.935.53
NS
PRISM 2 at PICU admit
10.671.37
14.251.19
0.05
PICU Days to CRRT Initiation
3.451.69
5.561.45
NS
PRISM 2 at CRRT Initiation
12.951.39
16.611.21
0.05
CRRT Initiation GFR (mL/min/1.73)
50.176.55
52.535.94
NS
%FO at CRRT Initiation
10.605.55
13.905.03
NS
No. Inotropes at CRRT Initiation
0.50.23
1.10.19
0.05
CVP at CRRT Initiation
12.52.05
13.891.68
NS
Paw at CRRT Initiation (mmH2O)
15.152.5
17.461.84
NS
Paw at End CRRT (mmH2O)
8.72.94
25.762.03
<0.001
Urine Output (mL/kg/hr)
1.550.3
1.360.23
NS
CRRT Duration (day)
7.562.25
13.282.04
NS
2
Filtration (mL/min/1.73 m )
Flores FX et al: Pediatric Nephrology 2008, 23: 625-630
2187.49189.26 2569.28201.76
NS
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