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CRRT for Pediatric ARF
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  1. CRRT for Pediatric ARF Stuart L. Goldstein, MD Assistant Professor of Pediatrics Baylor College of Medicine

  2. Ronco et al. Lancet 2000; 351: 26-30

  3. Ronco et al. Lancet 2000; 351: 26-30 • Conclusions: • Minimum UF rates should reach at least 35 ml/kg/hr • (2000/1.73m2/hr when adapted for children) • Survivors in all their groups had lower BUNs than non-survivors prior to commencement of hemofiltration • Begs the question does early CRRT effect outcome?

  4. Pediatric ARF:RRT Modalities • PD most commonly used RRT modality until mid-1990’s • Ease of application • Limited staffing requirements • Unit experience • Cost

  5. Year CRRT PD HD 1995 18 45 38 1999 36 31 33 2003* 53 20 25 Pediatric ARF:RRT Modality Preferences • 92 pediatric centers • Most frequently used (% of centers) modality • *2003 was a projection Warady and Bunchman: Pediatr Nephrol 15:11-13 (2000)

  6. 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

  7. 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!

  8. Renal Replacement Therapy in the PICU:Pediatric Outcome Literature • Few pediatric studies (all single center) use severity of illness measure to evaluate outcomes in pediatric RRT: • 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

  9. Pediatric ARF: Modality and Survival P<0.01 P<0.01 % Survival Bunchman TE et al: Ped Neph 16:1067-1071, 2001

  10. 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

  11. CRRT and Outcome in Children • 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

  12. Percent Fluid Overload Calculation [ ] Fluid In - Fluid Out ICU Admit Weight * 100% % FO at CVVH initiation = Fluid In = Total Input from ICU admit to CRRT initiation Fluid Out = Total Output from ICU admit to CRRT initiation Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12

  13. CRRT and Outcome in Children • 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 107:1309-12

  14. CRRT and Outcome in Children • 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 107:1309-12

  15. CRRT and Outcome in Children • Survival curve demonstrates that nearly 75% of deaths occurred less than 25 days into the ICU course Goldstein SL et al: Pediatrics 2001 107:1309-12

  16. CRRT and Outcome in Children • 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 107:1309-12

  17. CRRT and Outcome in Children Goldstein SL et al: Pediatrics 2001 107:1309-12

  18. Variable Survivors, n Non-survivors, n P value PRISM III at CVVH 14.0 (9.0, 17.0), 42 16.0 (12.0, 20.0), 39 0.02 Hospital days prior to CVVH 3.5 (1.0, 8.5), 42 16.0 (4.0, 23.0), 39 0.001a Days in ICU prior to CVVH 2.0 (1.0, 5.0), 42 3.0 (1.0,6.0), 39 0.34 Fluid overload,% 9.2 (5.1, 16.7), 33 15.5 (8.3, 28.6), 37 0.01a ICU fluid overload,% 6.5 (4.5, 16.0), 26 10.0 (3.6, 14.7), 28 0.57 % vasoactive infusions 88.1, 42 92.3, 39 0.71 Pediatric MODS and CRRT Foland J et al: Journal Society of Critical Care Medicine (in press)

  19. Pediatric MODS and CRRT p Variable Hazard Ratio 95% CI Percent fluid overload 1.5 High ( > 10%) 3.02 - 6.10 0.002 Low (<10%) 1 Dose of replacement fluid High ( > >25.6 ml/kg/h) 1.23 0.63 7- 2.39 0.533 Low (<25.6 ml/kg/h) 1 PRISM - 2 Score High ( > 11) 1.67 0.855 - 3.25 0.133 Low (<11) 1 Number of pressors High 3-5 - 2.03 0.65 8- 6.30 0.658 None 1 Number of pressors Low (1 - 1-2) 2.13 1.05- 4.32 0.036 None 1 Gillespie R et al: ASN 2003 [abstract]

  20. Prospective Pediatric CRRT (ppCRRT ) Registry Registry: Phase 1 Design • Collect prospective data from 10 pediatric centers treating 15 to 20 patients annually (200-300 patients over 4 years) • Each center follows own institutional practice • Patient selection • Initiation and termination • Anti-coagulation protocols • Convection versus diffusion versus hemodiafiltration • Fluid composition • Cytokine clearance study

  21. ppCRRT Experience • First patient enrolled on 1/1/01 • 231 patients entered into database as of 05/31/04 • Currently 12 active participating pediatric centers, 11 have entered at least one patient • Texas Children’s • Boston Children’s • Seattle Children’s • UAB • University of Michigan • Mercy Children’s, KC • Egleston Children’s, Atlanta • All Children’s, St. Petersburg • DC Children’s • Columbus Children’s • Packard Children’s, Palo Alto • DeVos Children’s, Grand Rapids

  22. Patient Demographics • Newborn to 25 years • 59% males • Weights 1.3 – 160kg (mean 33.5 kg) • Mean 6.5 days in ICU prior to CRRT • (range 0 – 135 days, median 2) • Modality • CVVH (33%) • CVVHD (54%) • CVVHDF (13%)

  23. ppCRRT Data: Size Distribution

  24. Indications for CRRT and Survival

  25. ppCRRT MODS Data • BASELINE DEMOGRAPHICS • 231 patients entered (1/1/2001 to 5/31/04) • 169/231 (73%) with MODS (2+ organs involved) • Mean age 8.6 + 6.9 years (2 days to 25.1 years) • Mean weight 33.7 + 25.1 kg (1.9 to 160 kg) • Mean GFR 37.9+ 31.1 at CRRT initiation • Median 3 ICU days prior to CRRT initiation • Range 0 to 103 days • 114/169 (67%) less than 7 days

  26. ppCRRT MODS Data: Survival

  27. ppCRRT MODS Data: Clinical Variables

  28. ppCRRT MODS Data: Other Analyses • %FO associated with outcome when CRRT initiation PRISM 2 controlled in multiple regression analysis • Survival rates similar by CRRT modality • Survival rates similar for patients on: 0-1 (54%), 2 (54%) or 3+ (44%) pressors • Survival rates better for patients with: <20% FO (61%) versus >20% FO (35%) at CRRT initiation (p<0.001)

  29. CRRT for Pediatric ARF: Summary • CRRT is the most popular therapy for critically ill children with ARF • Single center data and multi-center data show that worse fluid overload is associated with worse outcome • Would early initiation of CRRT to prevent worsening fluid overload improve survival? • Prospective randomized controlled trials do not exist (and could be unethical) • Medication adjustment based on volume status?

  30. Acknowledgements: The ppCRRT Group Devos Children’s: Timothy Bunchman, MD Richard Hackbarth, MD Stanford: Annabelle Chua, MD Steven Alexander, MD All Children’s: Francisco Flores, MD Columbus Children’s: John Mahan, MD Texas Childrens: Cheryl Baker, RN Leisha Sanders, RN David Wilson, RN Helen Currier, RN DC Children’s: Kevin McBryde, MD Boston Children’s: Michael Somers, MD Michelle Baum, MD Seattle Children’s: Jordan Symons, MD Nancy Hawkins-McAfee, RN CS Mott Children’s: Patrick Brophy, MD Theresa Mottes, RN UAB: Gloria Morrison, RN Joni Barnett, RN Children’s Mercy: Douglas Blowey, MD Eggleston, Atlanta: James Fortenberry, MD Kristine Rogers, RN

  31. Acknowledgement: ppCRRT Sponsors Gambro Renal Products (Cathy DiMuzio) Dialysis Solutions, Incorporated (Walter O’Rourke) Baxter Healthcare (Joseph Villanova)