2. 1)Fluid overload control (unbalance infusion requirements/pt weight) 2) Cytokine Clearance (CPB associated SIRS, post op sepsis) 3) Capillary leak syndrome (extracorporeal surface contact, RAAS/BNP disequilibrium, hypothermia, cyanosis) 4) Cardiorenal-renocardiac syndromes RRT in pediatric Heart Surgery : Specific indications

4. RRT in pediatric Heart Surgery : Specific modalities CPB with UF CPB with CRRT CRRT during ECMO “Traditional” CRRT

5. POTENTIAL ROLE OF ULTRAFILTRATION IN POST CPB CAPILLARY LEAK SYNDROME UF/HF

6. ULTRAFILTRATION During CPB Conventional Ultrafiltration Modified Ultrafiltration High Volume Zero Balanced UF NOMENCLATURE

7. Conventional Ultrafiltration After aortic declamp During rewarming UF in parallel with CPB Inlet after the oxygenator Ultrafiltered blood returns into venous reservoire Advantages:  It does not delay surgical times  It removes UF during highest mediator production phase Disadvantages:  It might quickly empty reservoire volume From Chang AC, Hanley FL, Wernovsky G, Wessel DL. Pediatric Cardiac Intensive Care ed W&W 1998

8. Modified Ultrafiltration From Chang AC, Hanley FL, Wernovsky G, Wessel DL. Pediatric Cardiac Intensive Care ed W&W 1998 Advantages:  Significantly higher efficiency Disadvantages:  Cumbersome procedure  Patient cooling  Hemodynamic instability

9. Inflammation mediators removalInflammation mediators removal - C3a, C5a, IL-6a, IL-8a, TNF, MDF, ET-1 Total body water reductionTotal body water reduction –Tissue edema decrease –Hematocrit increase –Coagulation factors concentration –Decreased need of hemoderivates POTENTIAL ROLE OF ULTRAFILTRATION IN POST CPB CAPILLARY LEAK SYNDROME

10. UF ON LEFT VENTRICULAR FUNCTION 1.Myocardial edema decrease 2.DO2 increase 3.Left ventricular compliance increase 4.Systolic and diastolic function improvement Davies MJ. J Thorac Cardiovasc Surg 1998

11. HIGH-VOLUME, ZERO BALANCED ULTRAFILTRATION (Z-BUF) Twenty children undergoing cardiac surgery assigned to Z-BUF or a control group. C3a, IL-1, IL-6, IL-8, IL-10, TNF, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). Isovolumetric UF during rewarming with high UF volumes and equivalent amount of reinfusion solution (average 4.972 ml/m2) MUF after CPB weaning in both groups in order to remove excess fluids Journois et al, Anesthesiology: Volume 85(5) November 1996 pp 965-976

12. MEMBRANES (NOT UF) CLEAR MEDIATORS in CHILDREN UNDERGOING CVVH Journois et al, Anesthesiology: Volume 85(5) November 1996 pp 965-976 –Decrease of body temperature at T2 and T3 –Decrease of neutrophils count –Decrease of inotropic support –Decrease of blood loss at T2 and T3 –Decrease of postoperative ΔAaO2 (320 vs. 551 mmHg) –Positive correlation between ΔAaO2 and UF/TBV ratio. –Decrease of time to extubation (10.8 vs. 28.2 h)

13. Removal of prostaglandin E2 and increased intraoperative blood pressure during modified ultrafiltration in pediatric cardiac surgery Kazuto Yokoyama et al JTCVS 2009

14. Removal of prostaglandin E2 and increased intraoperative blood pressure during modified ultrafiltration in pediatric cardiac surgery Kazuto Yokoyama et al JTCVS 2009

15. Roscitano et al, Asian Cardiovasc Thorac Ann 2009 Intraoperative Continuous Venovenous Hemofiltration during Coronary Surgery CVVH post 35 mL/kg/h Qb 150 ml/min No heparin. Bicarbonate buffer Net UF rate 500–1000 mL/h

16. Intraoperative Continuous Venovenous Hemofiltration during Coronary Surgery Antonino Roscitano, MD, Umberto Benedetto, MD, Massimo Goracci, Fabio Capuano, MD, Remo Lucani, MD1, Riccardo Sinatra, MD Roscitano et al, Asian Cardiovasc Thorac Ann 2009

17. Reduction of Early Postoperative Morbidity in Cardiac Surgery Patients Treated With Continuous Veno–Venous Hemofiltration During Cardiopulmonary Bypass VAM in thetreatedgroup: CVVH group 3.55 ± 0.85 h vs control group 5.8 ± 0.94 h, P < 0.001 ICU STAY: CVVH group 29.5 ± 6.7 vs. control group 40.5 ± 6.67 h, P < 0.001. Luciani et al Artif Organs 2009

18. Anti-inflammatory modalities: Their current use in pediatric cardiac surgery in the United Kingdom and Ireland Allen et PCCM 2009 “…there are still widespread variations in practice. Rather than reflecting poor clinical practice, we believe this reflects a lack of good evidence supporting clinical benefit”

19. NeonatesChildren Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation Askenazi et al PCCM 2010

20. PCRRT and ECMO Especially in the smaller children and infants solute clearance on ECMO is greater then standard PCRRT due to the relatively high blood flow rates Ultrafiltration error may not be easily recognized due to the maintenance of hemodynamic stability that ECMO gives Excessive ultrafiltration  due to ultrafiltration controller error  ECMO-CVVH machines “interaction“ Courtesy of Norma J Maxvold (modified)

22. N = 4 pts with AKI (2 neonates +2 children) 1 neonate and 1 child required pCRRT+ECMO 1 neonate a 1 child required pCRRT alone

23. ECMO and NGAL Bambino Gesù experience creatinine Urine output Ricci Z, unpublished, 2010

24. Fluid balance ECMO and NGAL Bambino Gesù experience NGAL ** Ricci Z, unpublished, 2010

25. NGAL Ricci Z, unpublished, 2010

26. CASE REPORT 1

29. 1,5 1,8 2,1 2,4 2,7 3 250 300 350 400 450 CVVH + Berlin Heart: 1) Cardiac index 2) REDVI

30. Body water distribution 0 20 40 60 80 100 1° D2° D3° D4° D5° D BWTBWECWICW CASE REPORT 1

32. CASE REPORT 2 Patient on ECMO for dilative cardiomyopathy, 35 kg AnuricAnuric Fenoldopam 0,4 mcg/Kg/min, no diuretics, no vasopressorsFenoldopam 0,4 mcg/Kg/min, no diuretics, no vasopressors Ischemic/thromboembolic event to right inferior limb (previous femoral artery cannulation): Right inferior limb compartment syndrome (no surgery). Serum myoglobin > 50000 ng/mlIschemic/thromboembolic event to right inferior limb (previous femoral artery cannulation): Right inferior limb compartment syndrome (no surgery). Serum myoglobin > 50000 ng/ml CVVHDF 50 ml/kg/hCVVHDF 50 ml/kg/h After 3 ECMO days, Htx. Need for CVVHDF for 22 POD days ICU discharge on POD 25 with normal renal function Ricci et al, Blood Purif 2010

33. Need for up to 12 grams/day of iv phosphate replacementNeed for up to 12 grams/day of iv phosphate replacement Need for KCl correction in the replacement/dialysate bagsNeed for KCl correction in the replacement/dialysate bags (about 500 mEq/day) Vancomycine continuous infusion (7 days) increased from 50 mg/kg/die to 100 mg/kg/die on serum levelsVancomycine continuous infusion (7 days) increased from 50 mg/kg/die to 100 mg/kg/die on serum levels Immunosuppression with iv continuous cyclosporine increased from 100 to 150 mg/die on serum levelsImmunosuppression with iv continuous cyclosporine increased from 100 to 150 mg/die on serum levels Ricci et al, Blood Purif 2010 CASE REPORT 2

34. Patient n.AgeWeightPreoperative diagnosisPresence of ECMO (yes/no) 14 days3.5HLHSY 22 years9Dilated miocardiopathyN 335 days4AoCo+SubAoStY 445 days4.2TGA with coronary restenosisY 528 days3.8PA with ISN 625 days3.1TGAY 75 days2.8HLHSY 810 days3.5HLHSY 91 year6Dilated miocardiopathyY 102 months5.2CAVCN All that glitters is not gold

35. BNP

37. BNP

38. CONCLUSIONS 1.AKI in pediatric cardiac surgery is frequent. 2.UF during CPB is beneficial. 3.Application of CRRT to extracorporeal circulatory devices is possible. 4.High expertise, safe machines and trained staff is mandatory. 5.Dedicated equipment and prospective studies are dramatically lacking