Pediatric Acute Renal Failure: CRRT/Dialysis Outcome Studies Stuart L. Goldstein, MD Assistant Professor of Pediatrics Baylor College of Medicine

Pediatric Acute Renal Failure:CRRT/Dialysis Outcome Studies

Stuart L. Goldstein, MDAssistant 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, 19942. JASN 6:1401-9, 19953. Pediatr Nephrol 7:703-7, 19944. 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

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90

Patients % Pressors % Survival

IHDCRRT

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

Pediatric ARF: IHD and CRRT

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40

60

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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%


Pediatric ARF: Modality and Survival

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IHD PD CRRT

% Survival


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



• 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%


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)


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)



• 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

n

0

5

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15

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25

30

35

40

45

Death Survival

p = 0.03



-5

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Max Pressor GFR Paw Change

SurvivorNon-Survivor


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


N Percent

Diagnosi sCongenital heart dis eas e 14 16.5Metabolic disorder 14 16.5Multiorgan dys function 13 15.3Seps is s yndrome 12 14.1Liver failure 9 10.5Congenital nephrotic s yndrome 7 8.2Malignancy 5 5.9Congenital diaphragmatic hernia 3 3.5Heart failure 2 2.4Other 6 7.1

Table 1. Patient diagnoses at CRRT initiation



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81 5 9 13 17 21 25 29 33 37 41 45 49

Days on C RR T

No

. of P

atie

nts

Survivors

Non-Survivors

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



3824

41

0

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100

All Patients <3kg >3kg

%S

urv

ivo

rsFigure 3. Percent survival


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

Documents

Pediatric Acute Renal Failure: CRRT/Dialysis Outcome Studies Stuart L. Goldstein, MD Assistant Professor of Pediatrics Baylor College of Medicine