Pediatric Acute Renal Failure:

CRRT/Dialysis Outcome Studies

Stuart L. Goldstein, MD
Assistant Professor of Pediatrics
Baylor College of Medicine

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 a severity of
illness measure to evaluate outcomes in pCRRT:
Lane

noted that mortality was greater after bone marrow transplant
who had > 10% fluid overload at the time of HD initiation
Smoyer
2
found higher mortality in patients on pressors.
Faragson
3
found PRISM to be a poor outcome predictor in patients
treated with HD
Zobel
4
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, 1994
2. JASN 6:1401-9, 1995
3. Pediatr Nephrol 7:703-7, 1994
4. Child Nephrol Urol 10:14-7, 1990
Renal Replacement Therapy in the PICU Pediatric
Outcome Literature
122 children studied
No PRISM scores
Most common diagnosis
IHD: primary renal failure
CRRT: sepsis
31% survival
Conclusion: patients who
receive CRRT are more ill
0
10
20
30
40
50
60
70
80
90
Patients % Pressors % Survival
IHD
CRRT
Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8


Pediatric ARF: IHD and CRRT
0
20
40
60
80
100
120
CRRT IHD PD
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
Pediatric ARF: Disease and Survival
Diagnosis N Survival Diagnosis N %Survival
BMT 26 42% HUS 16 94%
TLS/Malig 17 58% ATN 46 67%
CHD 47 39% Liver Tx 22 17%
Heart Tx 13 67% Sepsis 39 33%
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
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
Renal Replacement Therapy in the PICU Pediatric
Outcome Literature
Retrospective review of all patients who received CVVH(D) in the
Texas Childrens 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 Out
ICU Admit Weight
]
* 100%
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Renal Replacement Therapy in the PICU Pediatric
Literature
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 Jun;107(6):1309-12
Pediatric RISk of Mortality (PRISM) Score
PRISM evaluates severity of illness by examining 14 clinical variables
in 5 organ systems.
PRISM does not directly evaluate renal function--only BUN and
potassium levels.
Higher PRISM scores (>10) on admission to the PICU have been
associated with poorer prognosis.
The mean PRISM score at admission to the Texas Childrens Hospital
PICU is 14.
RESULTS
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 Jun;107(6):1309-12
Renal Replacement Therapy in the PICU Pediatric
Literature
Survival curve
demonstrates that nearly
75% of deaths occurred
less than 25 days into the
ICU course
Survival Time(days)
C
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P
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S
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g
0.4
0.6
0.8
1.0
0 20 40 60 80 100
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Renal Replacement Therapy in the PICU Pediatric
Literature
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+SE
Mean-SE
Mean
OUTCOME
%
F
O

a
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C
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I
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i
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0
5
10
15
20
25
30
35
40
45
Death Survival
p=0.03
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Renal Replacement Therapy in the PICU Pediatric
Outcome Literature







-5
0
5
10
15
20
25
Max Pressor GFR Paw Change
Survivor
Non-Survivor
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Neonatal CRRT
36 critically ill neonates
mean age 9.8 + 1.5 days
mean weight 3.0 + 0.1 kg
CAVH (17)
CVVH (15)
SCUF/ECMO (4)
Therapeutic Intervention Scoring System (TISS)
Acute Physiologic Scoring System for Children
(APSC)
Zobel G et al: Kid Int 53:S169-S173, 1998
Neonatal CRRT
Mean CRRT duration of 97 + 20 hours
Mean filter life-span 40.7 + 6.1 hours
Overall survival of 66%
No difference between survivors and non-survivors with
respect to
number of failed organs
TISS points
Significant difference between S and NS with respect to
MAP (49.2 mmHg versus 38.3 mmHg)
APSC 24 hours after starting CRRT


Zobel G et al: Kid Int 53:S169-S173, 1998
Neonatal/Infant CRRT Outcome
Multicenter retrospective review of CRRT in
neonates/infants (n=85) less than 10kg
655 patient-days (7.6+8.6 days/pt)
Mean weight 5.3 + 2.8kg (16 pt < 3 kg)
Mean Qb of 9.5 + 4.2ml/min/kg

Symons JM et al: CRRT meeting 2002
Neonatal/Infant CRRT Outcome
N Percent
Diagnosis
Congenital heart disease 14 16.5
Metabolic disorder 14 16.5
Multiorgan dysfunction 13 15.3
Sepsis syndrome 12 14.1
Liver failure 9 10.5
Congenital nephrotic syndrome 7 8.2
Malignancy 5 5.9
Congenital diaphragmatic hernia 3 3.5
Heart failure 2 2.4
Other 6 7.1
Table 1. Patient diagnoses at CRRT initiation
Symons JM et al: CRRT meeting 2002
Neonatal/Infant CRRT Outcome
0
1
2
3
4
5
6
7
8
159
1
3
1
7
2
1
2
5
2
9
3
3
3
7
4
1
4
5
4
9
Days on CRRT
N
o
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o
f

P
a
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n
t
s
Survivors
Non-Survivors
Figure 2. Days on CRRT, survivors and non-survivors
Symons JM et al: CRRT meeting 2002
Neonatal/Infant CRRT Outcome
38
24
41
0
20
40
60
80
100
All Patients <3kg >3kg
%
S
u
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v
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v
o
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s
Figure 3. Percent survival
Symons JM et al: CRRT meeting 2002
Pediatric CRRT Outcome Literature:
Summary
Children with ARF requiring CRRT exhibit 40-50%
survival
PRISM score not predictive
Infants >3kg have similar survival rates as older
children
Most mortality occurs within 3 weeks of ICU admission
Children with increased degrees of fluid overload at CRRT
initiation may have increased mortality

Pediatric CRRT Outcome Literature:
Conclusions
Earlier might be better
Early mortality
Prevent fluid overload
Allow nutrition, blood product administration
Single center data are limited
No differences with respect to
initiation protocols
anticoagulation
machines
nutrition
data assessed