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, JASN 6:1401-9, Pediatr Nephrol 7:703-7, 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 Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8

Pediatric ARF: IHD and CRRT Bunchman TE et al: Ped Neph 16: , 2001

Pediatric ARF: Disease and Survival Bunchman TE et al: Ped Neph 16: , 2001

Pediatric ARF: Modality and Survival % Survival Bunchman TE et al: Ped Neph 16: , 2001 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: , 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):

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):

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):

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 /- 5.7 and /- 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):

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

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

Renal Replacement Therapy in the PICU Pediatric Outcome Literature Goldstein SL et al: Pediatrics 2001 Jun;107(6):

Neonatal CRRT 36 critically ill neonates –mean age days –mean weight 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 hours Mean filter life-span 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 ( days/pt) Mean weight kg (16 pt < 3 kg) Mean Qb of ml/min/kg Symons JM et al: CRRT meeting 2002

Neonatal/Infant CRRT Outcome Symons JM et al: CRRT meeting 2002

Neonatal/Infant CRRT Outcome Symons JM et al: CRRT meeting 2002

Neonatal/Infant CRRT Outcome 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