crrt for pediatric arf
DESCRIPTION
CRRT for Pediatric ARF. Stuart L. Goldstein, MD Assistant Professor of Pediatrics Baylor College of Medicine. Ronco et al. Lancet 2000; 351: 26-30. Ronco et al. Lancet 2000; 351: 26-30. Conclusions: Minimum UF rates should reach at least 35 ml/kg/hr - PowerPoint PPT PresentationTRANSCRIPT
Goldstein S: pCRRT 2004 meeting
CRRT for Pediatric ARF
Stuart L. Goldstein, MDAssistant Professor of Pediatrics
Baylor College of Medicine
Goldstein S: pCRRT 2004 meeting
Ronco et al. Lancet 2000; 351: 26-30
1 4 6 U F ra te 20 m l/kg /h rsu rv iva l sig n if ica n tly lo w er
in th is g ro up com pa redto th e o the rs
1 3 9 U F ra te 35 m l/kg /h rp = 0 .00 07
1 4 0 U F ra te 45 m l/kg /h rp = 0 .00 13
4 2 5 pa tien tsE n d p o in t = su rv iva l 1 5 d a ys a fte r D /C H F
Goldstein S: pCRRT 2004 meeting
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?
Goldstein S: pCRRT 2004 meeting
Pediatric ARF:RRT Modalities
• PD most commonly used RRT modality until mid-1990’s– Ease of application– Limited staffing requirements– Unit experience– Cost
Goldstein S: pCRRT 2004 meeting
Pediatric ARF:RRT Modality Preferences
• 92 pediatric centers
• Most frequently used (% of centers) modality
• *2003 was a projection 2520532003*
3331361999
3845181995
HDPDCRRTYear
Warady and Bunchman: Pediatr Nephrol 15:11-13 (2000)
Goldstein S: pCRRT 2004 meeting
Pediatric Acute Renal Failure:Ideal 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
Goldstein S: pCRRT 2004 meeting
Pediatric Acute Renal Failure:Ideal 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!
Goldstein S: pCRRT 2004 meeting
Renal Replacement Therapy in the PICU:Pediatric 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 > 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 13:613-7, 19942. JASN 6:1401-9, 19953. Pediatr Nephrol 7:703-7, 19944. Child Nephrol Urol 10:14-7, 1990
Goldstein S: pCRRT 2004 meeting
Pediatric ARF: Modality and Survival
0
10
20
30
40
50
60
70
80
90
IHD PD CRRT
% Survival
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
P<0.01
P<0.01
Goldstein S: pCRRT 2004 meeting
Pediatric ARF: Modality and Survival
• Patient survival on pressors (35%) lower than without pressors (89%) (p<0.01)
• Lower survival seen in CRRT than in patients who received HD for all disease states
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
Goldstein S: pCRRT 2004 meeting
CRRT and Outcome in Children
• Retrospective review of all patients who received CVVH(D) in the Texas Children’s 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 Jun;107(6):1309-12
Goldstein S: pCRRT 2004 meeting
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
Goldstein S: pCRRT 2004 meeting
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 107:1309-12
Goldstein S: pCRRT 2004 meeting
CRRT and Outcome in Children• 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)
Goldstein SL et al: Pediatrics 2001 107:1309-12
Goldstein S: pCRRT 2004 meeting
CRRT and Outcome in Children
• Survival curve demonstrates that nearly 75% of deaths occurred less than 25 days into the ICU course
Survival Time (days)
Cum
ulat
ive
Pro
port
ion
Sur
vivi
ng
0.4
0.6
0.8
1.0
0 20 40 60 80 100
Goldstein SL et al: Pediatrics 2001 107:1309-12
Goldstein S: pCRRT 2004 meeting
CRRT and Outcome in Children
• 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
n0
5
10
15
20
25
30
35
40
45
Death Survival
p = 0.03
Goldstein SL et al: Pediatrics 2001 107:1309-12
Goldstein S: pCRRT 2004 meeting
CRRT and Outcome in Children
-5
0
5
10
15
20
25
Max Pressor GFR Paw Change
SurvivorNon-Survivor
Goldstein SL et al: Pediatrics 2001 107:1309-12
Goldstein S: pCRRT 2004 meeting
Pediatric MODS and CRRTVariable Survivors, n Non-survivors, n P value
PRISM III at CVVH 14.0 (9.0, 17.0), 42
16.0 (12.0, 20.0), 39
0.02
Hospital days prior to CVVH
3.5 (1.0, 8.5), 42 16.0 (4.0, 23.0), 39 0.001a
Days in ICU prior to CVVH
2.0 (1.0, 5.0), 42 3.0 (1.0,6.0), 39 0.34
Fluid overload,% 9.2 (5.1, 16.7), 33
15.5 (8.3, 28.6), 37 0.01a
ICU fluid overload,% 6.5 (4.5, 16.0), 26
10.0 (3.6, 14.7), 28 0.57
% vasoactive infusions 88.1, 42 92.3, 39 0.71
Foland J et al: Journal Society of Critical Care Medicine (in press)
Goldstein S: pCRRT 2004 meeting
Pediatric MODS and CRRTVariable Hazard Ratio 95% CI p
Percent fluid overload
High (> 10%)
Low (<10%)
3.02
1
-6.10
0.002
Dose of replacement fluid
High ( >>25.6 ml/kg/h)
Low (<25.6 ml/kg/h)
1.23
1
0.637-2.39
0.533
PRISM- 2 Score
High (>11)
Low (<11)
1.67
1
0.855- 3.25
0.133
Number of pressors
High 3-5-
None
2.03
1
0.658-6.30
0.658
Number of pressors
Low (1-1-2)
None
2.13
1
1.05-4.32
0.036
Gillespie R et al: ASN 2003 [abstract]
1.5
Goldstein S: pCRRT 2004 meeting
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
Goldstein S: pCRRT 2004 meeting
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 Children’s–Boston Children’s–Seattle Children’s–UAB–University of Michigan–Mercy Children’s, KC–Egleston Children’s, Atlanta
–All Children’s, St. Petersburg–DC Children’s–Columbus Children’s–Packard Children’s, Palo Alto–DeVos Children’s, Grand Rapids
Goldstein S: pCRRT 2004 meeting
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%)
Goldstein S: pCRRT 2004 meeting
ppCRRT Data: Size Distribution
ICU Admit Weight (kg)
Pat
ient
Num
ber
0
10
20
30
40
50
60
70
80
<10 10 to 30 30 to 50 50 to 70 >70
Goldstein S: pCRRT 2004 meeting
Indications for CRRT and Survival
OUTCOME: Death
OUTCOME: Survival
CRRT Reason
Pa
tien
t N
um
be
r
0
4
8
12
16
20
24
28
32
36
40
44
48
Elec ImbFO & Elec Imb
FO OnlyOther
Prevent FO
Goldstein S: pCRRT 2004 meeting
ppCRRT MODS Data
BASELINE DEMOGRAPHICS231 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 initiationMedian 3 ICU days prior to CRRT initiationRange 0 to 103 days114/169 (67%) less than 7 days
Goldstein S: pCRRT 2004 meeting
ppCRRT MODS Data: Survival
OUTCOME
Pat
ient
Num
ber
49.4% 50.6%
0
10
20
30
40
50
60
70
80
90
100
Death Survival
Goldstein S: pCRRT 2004 meeting
ppCRRT MODS Data: Clinical Variables
Variable (values mean +/- SD) Survivors Non-Survivors
p-value (t-test)
Age (years) 9.2 + 6.8 8.0 + 7.3 NS
Weight (kg) 35.9 + 25.9 31.7 + 30.5 NS
PRISM at ICU Admit 13.9 + 8.1 16.3 + 10.1 NS
PRISM at CRRT Initiation 14.7 + 7.6 19.8 + 8.3 <0.001
CVP at CRRT Initiation 16.4 + 6.2 18.4 + 8.3 NS
GFR at CRRT Initiation 37.0 + 31.9 39.2 + 31.7 NS
% FO at CRRT Initiation 14.2 + 15.5 22. + 18.3 <0.005
No. of Pressors 1.4 + 1.0 1.6 + 1.1 NS
Goldstein S: pCRRT 2004 meeting
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: <20% FO (61%) versus >20% FO (35%) at CRRT initiation (p<0.001)
Goldstein S: pCRRT 2004 meeting
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?
Goldstein S: pCRRT 2004 meeting
Acknowledgements: The ppCRRT Group
Boston Children’s: Michael Somers, MDMichelle Baum, MD
Seattle Children’s: Jordan Symons, MDNancy Hawkins-McAfee, RN
CS Mott Children’s: Patrick Brophy, MD Theresa Mottes, RN
UAB: Gloria Morrison, RNJoni Barnett, RN
Children’s Mercy: Douglas Blowey, MD
Eggleston, Atlanta: James Fortenberry, MDKristine Rogers, RN
Devos Children’s: Timothy Bunchman, MDRichard Hackbarth, MD
Stanford: Annabelle Chua, MDSteven Alexander, MD
All Children’s: Francisco Flores, MD
Columbus Children’s: John Mahan, MD
Texas Childrens: Cheryl Baker, RNLeisha Sanders, RNDavid Wilson, RNHelen Currier, RN
DC Children’s: Kevin McBryde, MD
Goldstein S: pCRRT 2004 meeting
Acknowledgement: ppCRRT Sponsors
Gambro Renal Products (Cathy DiMuzio)
Dialysis Solutions, Incorporated (Walter O’Rourke)
Baxter Healthcare (Joseph Villanova)