Fluid overload control (unbalance infusion requirements/pt weight) 2) Cytokine Clearance (CPB associated SIRS , post op

2. RRT in pediatricHeartSurgery : Specificindications • 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

4. RRT in pediatricHeartSurgery : Specificmodalities • CPB with UF • CPB with CRRT • CRRT during ECMO • “Traditional” CRRT

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

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

7. Conventional Ultrafiltration • Afteraorticdeclamp • Duringrewarming • UF in parallelwith CPB • Inletafter the oxygenator • Ultrafilteredbloodreturnsintovenousreservoire • Advantages: • Itdoesnotdelaysurgicaltimes • Itremoves UF duringhighestmediator production phase • Disadvantages: • Itmightquicklyemptyreservoire volume From Chang AC, Hanley FL, Wernovsky G, Wessel DL. Pediatric Cardiac Intensive Care ed W&W 1998

8. Modified Ultrafiltration • Advantages: • Significantlyhigherefficiency • Disadvantages: • Cumbersome procedure • Patientcooling • Hemodynamicinstability From Chang AC, Hanley FL, Wernovsky G, Wessel DL. Pediatric Cardiac Intensive Care ed W&W 1998

9. POTENTIAL ROLE OF ULTRAFILTRATION IN POST CPB CAPILLARY LEAK SYNDROME • Inflammationmediatorsremoval - C3a, C5a, IL-6a, IL-8a, TNF, MDF, ET-1 • Total body water reduction • Tissue edema decrease • Hematocritincrease • Coagulationfactorsconcentration • Decreasedneedofhemoderivates

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

11. HIGH-VOLUME, ZERO BALANCED ULTRAFILTRATION (Z-BUF) • Twentychildrenundergoingcardiacsurgeryassignedto Z-BUF or a controlgroup. • C3a, IL-1, IL-6, IL-8, IL-10, TNF, myeloperoxidase, and leukocytecountweremeasuredbefore (T1) and after (T2) hemofiltration and 24 h later (T3). • Isovolumetric UFduringrewarmingwith high UF volumes and equivalentamountofreinfusionsolution (average 4.972 ml/m2) • MUF after CPB weaning in bothgroups in ordertoremoveexcessfluids Journois et al, Anesthesiology: Volume 85(5) November 1996 pp 965-976

12. MEMBRANES (NOT UF) CLEAR MEDIATORS in CHILDREN UNDERGOING CVVH • Decreaseof body temperature at T2 and T3 • Decreaseofneutrophilscount • Decreaseofinotropicsupport • Decreaseofblood loss at T2 and T3 • DecreaseofpostoperativeΔAaO2 (320 vs. 551 mmHg) • Positive correlationbetweenΔAaO2 and UF/TBV ratio. • Decreaseoftimetoextubation (10.8 vs. 28.2 h) Journois et al, Anesthesiology: Volume 85(5) November 1996 pp 965-976

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. 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 Roscitano et al, Asian Cardiovasc Thorac Ann 2009

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 controlgroup 5.8 ± 0.94 h, P < 0.001 ICU STAY: CVVH group 29.5 ± 6.7 vs. controlgroup 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. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation Neonates Children 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 Urine output creatinine Ricci Z, unpublished, 2010

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

25. NGAL Ricci Z, unpublished, 2010

26. CASE REPORT 1

29. CVVH + Berlin Heart: 1) Cardiac index2) REDVI 3 2,7 2,4 2,1 1,8 1,5 450 400 350 300 250

30. CASE REPORT 1 Body water distribution BW TBW ECW ICW 100 80 60 40 20 0 1° D 2° D 3° D 4° D 5° D

32. CASE REPORT 2 • Patient on ECMO fordilativecardiomyopathy, 35 kg • Anuric • Fenoldopam 0,4 mcg/Kg/min, no diuretics, no vasopressors • Ischemic/thromboemboliceventto right inferiorlimb (previousfemoralarterycannulation): Right inferiorlimbcompartmentsyndrome (no surgery). Serummyoglobin > 50000 ng/ml • CVVHDF 50 ml/kg/h • After 3 ECMO days, Htx. • Needfor CVVHDF for 22 POD days • ICU discharge on POD 25 withnormalrenalfunction Ricci et al, Blood Purif 2010

33. CASE REPORT 2 • Needfor up to 12 grams/dayofivphosphatereplacement • NeedforKClcorrection in the replacement/dialysatebags • (about 500 mEq/day) • Vancomycinecontinuousinfusion (7 days) increasedfrom 50 mg/kg/dieto 100 mg/kg/die on serumlevels • Immunosuppressionwithivcontinuouscyclosporineincreasedfrom 100 to 150 mg/die on serumlevels Ricci et al, Blood Purif 2010

34. Patient n. Age Weight Preoperative diagnosis Presence of ECMO (yes/no) 1 4 days 3.5 HLHS Y 2 2 years 9 Dilated miocardiopathy N 3 35 days 4 AoCo+SubAoSt Y 4 45 days 4.2 TGA with coronary restenosis Y 5 28 days 3.8 PA with IS N 6 25 days 3.1 TGA Y 7 5 days 2.8 HLHS Y 8 10 days 3.5 HLHS Y 9 1 year 6 Dilated miocardiopathy Y 10 2 months 5.2 CAVC N Allthatglittersisnotgold

35. BNP

37. BNP

38. CONCLUSIONS AKI in pediatriccardiacsurgeryisfrequent. UF during CPB isbeneficial. Applicationof CRRT toextracorporealcirculatorydevicesispossible. High expertise, safemachines and trained staff ismandatory. Dedicatedequipment and prospectivestudies are dramaticallylacking