CRRT for Pediatric ARF

Goldstein S: pCRRT 2004 meeting

CRRT for Pediatric ARF

Stuart L. Goldstein, MDAssistant Professor of Pediatrics

Baylor College of Medicine


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


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?


Pediatric ARF:RRT Modalities

• PD most commonly used RRT modality until mid-1990’s– Ease of application– Limited staffing requirements– Unit experience– Cost


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)


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


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!


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


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


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


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


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



• 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


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)




• 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




• 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




-5

0

5

10

15

20

25

Max Pressor GFR Paw Change

SurvivorNon-Survivor



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)


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


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


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


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%)


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


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


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


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


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


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)


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?


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


Acknowledgement: ppCRRT Sponsors

Gambro Renal Products (Cathy DiMuzio)

Dialysis Solutions, Incorporated (Walter O’Rourke)

Baxter Healthcare (Joseph Villanova)

Documents

CRRT for Pediatric ARF