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
– 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

90
• 122 children studied 80
• No PRISM scores 70
• Most common diagnosis 60
– IHD: primary renal failure
50 IHD
– CRRT: sepsis
40 CRRT
• 31% survival
30
• Conclusion: patients who
20
receive CRRT are more ill
10
0 Patients % Pressors % Survival

Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8

 Pediatric ARF: IHD and CRRT

120

100

80

60

40

20

0
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

90 P<0.01
80
70 P<0.01
60
50
% Survival
40
30
20
10
0
IHD PD CRRT

Bunchman TE et al: Ped Neph 16:1067-1071, 2001

 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 ] * 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 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 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

Cumulative Proportion Surviving

1.0
• Survival curve
demonstrates that nearly 0.8
75% of deaths occurred
less than 25 days into the
0.6
ICU course
0.4

0 20 40 60 80 100

Survival Time (days)

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 45
improved outcome (p=0.03) 40

%FO at CVVH Initiation

35
• Lesser % FO at CVVH (D) 30
initiation was also associated 25 p = 0.03

with improved outcome when 20

15
sample was adjusted for severity
10
of illness (p=0.03; multiple 5 Mean+SE

regression analysis) 0
Death Survival
Mean-SE
Mean

OUTCOME

Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12

 Renal Replacement Therapy in the PICU Pediatric
Outcome Literature

25

20

15

10 Survivor
Non-Survivor
5

-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
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

Symons JM et al: CRRT meeting 2002

 Neonatal/Infant CRRT Outcome

Figure 2. Days on CRRT, survivors and non-survivors

8
7
6 Survivors
No. of Patients

5
Non-Survivors
4
3
2
1
0
1
5
9
13

25

41

49
17
21

29
33
37

45
Days on CRRT

Symons JM et al: CRRT meeting 2002

 Neonatal/Infant CRRT Outcome

Figure 3. Percent survival

100
80
%Survivors

60
38 41
40 24
20
0
All Patients <3kg >3kg

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