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 comorbid 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 comorbid 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
– 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, 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
90
80
70
60
50
IHD
CRRT
40
30
20
10
0
Patients
% Pressors
Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8
% Survival
Pediatric ARF: IHD and CRRT
120
100
80
60
40
20
0
CRRT
IHD
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
PD
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
P<0.01
90
80
P<0.01
70
60
% Survival
50
40
30
20
10
0
IHD
PD
Bunchman TE et al: Ped Neph 16:1067-1071, 2001
CRRT
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 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 Out
ICU Admit Weight
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
]
* 100%
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 Children’s 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 EndStage Lung Disease (1 each)
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
Renal Replacement Therapy in the PICU Pediatric
Literature
0
.8
CumulativeProportionSurviving
• Survival curve
demonstrates that nearly
75% of deaths occurred
less than 25 days into the
ICU course
1
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0
.6
0
.4
0
2
0
4
0
6
0
S
u
rv
iv
a
lT
im
e(d
a
y
s
)
Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
8
0
1
0
0
Renal Replacement Therapy in the PICU Pediatric
Literature
4
5
4
0
3
5
3
0
p=0
.0
3
2
5
%FOatCVVHInitiation
• 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)
2
0
1
5
1
0
5
0
M
e
a
n
+
S
E
M
e
a
n
-S
E
D
e
a
th
S
u
rv
iv
a
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O
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Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12
M
e
a
n
Renal Replacement Therapy in the PICU Pediatric
Outcome Literature
25
20
15
Survivor
Non-Survivor
10
5
0
-5
Max Pressor
GFR
Paw Change
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
Table 1. Patient diagnoses at CRRT initiation
Diagnosis
Congenital heart disease
Metabolic disorder
Multiorgan dysfunction
Sepsis syndrome
Liver failure
Congenital nephrotic syndrome
Malignancy
Congenital diaphragmatic hernia
Heart failure
Other
Symons JM et al: CRRT meeting 2002
N
Percent
14
14
13
12
9
7
5
3
2
6
16.5
16.5
15.3
14.1
10.5
8.2
5.9
3.5
2.4
7.1
Neonatal/Infant CRRT Outcome
8
7
6
5
4
3
2
1
0
Survivors
Days on CRRT
Symons JM et al: CRRT meeting 2002
49
45
41
37
33
29
25
21
17
13
9
5
Non-Survivors
1
No. of Patients
Figure 2. Days on CRRT, survivors and non-survivors
Neonatal/Infant CRRT Outcome
Figure 3. Percent survival
%Survivors
100
80
60
41
38
40
24
20
0
All Patients
Symons JM et al: CRRT meeting 2002
<3kg
>3kg
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