1. Renal Replacement Therapy in the CICU Stuart L. Goldstein, MD Professor of Pediatrics University or Cincinnati College of Medicine Director, Center for Acute Care Nephrology Medical Director, Pheresis Service Nephrology and Hypertension The Heart Institute Cincinnati Children’s Hospital Medical Center

2. The Center for Acute Care Nephrology Consultancy: Gambro Renal Products, Baxter Healthcare, Otsuka, La Jolla Pharmaceuticals, Bellco Ownership Interest: Hemametrics Educational/Research Funding: Gambro Renal Products, Baxter Healthcare, NxStage Inc Scientific Advisor/Membership: Baxter-Gambro Renal Products Disclosures: Stuart Goldstein, MD

3. The Center for Acute Care Nephrology No Therapy has Ever Been Shown via a Randomized Trial to Improve Outcomes in Patients with AKI after CPB THANK YOU FOR YOUR ATTENTION AND GOOD NIGHT! QUESTIONS?

4. The Center for Acute Care Nephrology Outline Refocus the timing of intervention Review the available options Future potential options

5. The Center for Acute Care Nephrology Post-operative AKIN III conferred increased risk of systemic ventricular dysfunction by echocardiography at discharge (OR 5.1, 2.1-12.3, p=0.0003)

6. The Center for Acute Care Nephrology Emerging Paradigm Early RecognitionEarly TreatmentEarly Recovery

7. The Center for Acute Care Nephrology What patients are at-high risk for AKI? Infants < 90 days Bypass time > 120 minutes Single ventricle Pre-operative AKI RACHS 5 - 6

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9. What are the Targets of AKI Treatment/Prevention? Refractory electrolyte abnormalities Fluid overload Allow provision of optimal therapies and their associated solute loads/volumes –Nutrition –Blood products –Medications

10. The Center for Acute Care Nephrology Poor Outcome RRT provision Upper quartile of MV time ICU Stay Death within 30 days

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12. What are the Available Options that Have Been Studied? Diuretics Fenoldopam Peritoneal dialysis

13. The Center for Acute Care Nephrology Wait Wait Wait!!!! Why are we talking about dialysis??!! What about Furosemide!??? Vitamin L always works!

14. The Center for Acute Care Nephrology Conservative Management of AKI: Diuretics Increase urine output Improve fluid balance Permit delivery of fluid to patient –Nutrition, other therapies May augment loss of potassium

15. The Center for Acute Care Nephrology Do Diuretics Help in AKI? 8 non-randomized studies 6 randomized studies 2. But no improvement in clinical outcomes 1. Majority of ICU patients get diuretics

16. The Center for Acute Care Nephrology Single center review of peritoneal dialysis provision for infants post- op congenital heart surgery PD catheters placed in 209/882 patients (24%) at discretion of CV surgeon Indications for PD provision included –Anasarca –Oliguria (<2 ml/kg/hour) non-responsive to furosemide –Metabolic abnormalities PD provided as 10 ml/kg dwell, 5 minute fill, 45 minute dwell, 10 minute drain for 24 hours

17. The Center for Acute Care Nephrology 20 patients who received PD reviewed More complex surgeries associated with PD provision

18. The Center for Acute Care Nephrology CCHMC CICU post-CPB fluid management practice changed November 2010 –Era 1: diuretics, PD catheter placed only in diuretic resistant, fluid overloaded patients –Era 2: PD catheter placed in OR at time of CPB in high-risk patients (next slide) 55 Era 2 patients identified in the study period 42 Era 1 patients matched 1:1 for age, surgical procedure, RACHS-1 and ventricular physiology

19. The Center for Acute Care Nephrology PD Initiation Criteria

20. The Center for Acute Care Nephrology Outcome Assessments Percent of patients with negative fluid balance –POD 1, 2 and 3 Time to negative fluid balance –8 hour shifts Time to extubation –8 hours shifts Electrolyte imbalance Cost

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22. Group A = Patients with PDC, Group B = PDC -

23. The Center for Acute Care Nephrology Prevention of Fluid Overload

24. The Center for Acute Care Nephrology Prospective Randomized Study in Progress

25. The Center for Acute Care Nephrology Does RRT delay renal recovery?

26. The Center for Acute Care Nephrology Patients all on PD for oliguria after CPB When CICU team thought patient was clinically ready to stop PD: –Furosemide challenge given at 6 PM –If a response (> 1 ml/kg/hr x 6 hours UOP) Randomized to PD for another 24 hours vs. DC PD at 6 am Endpoints –UOP –Total fluid output –Novel AKI biomarkers

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28. What if PD is not an Option? Hemodialysis or CRRT –Each has advantages & disadvantages –Choice is guided by Patient Characteristics –Disease/Symptoms –Hemodynamic stability Goals of therapy –Fluid removal –Electrolyte correction –Toxin removal Availability, expertise and cost ESRD? Toxin removal? AKI with likely recovery? VS

29. The Center for Acute Care Nephrology Smaller children in ppCRRT have lower survival Askenazi et al. Journal of Pediatrics 2013;162:587-92.

30. The Center for Acute Care Nephrology Fluid overload is bad for those < 10 kg VariableAdjusted ORp-value PRISM II score at CRRT1.1 (1.0 – 1.2)0.02 Fluid Overload Groups < 10 % vs. 10-20 %0.9 (0.17 – 4.67)0.25 20 %4.8 (1.3-17.7)0.01 UOP (ml/kg/hr) @ CRRT start0.72 (0.53-0.97)0.04 *66/84 observations used for analysis (40 death vs 26 Survival). variables used in the model include: PRISM 2 score, mean airway pressure (P aw ) and urine output at CRRT, % fluid overload (categorically divided by 10% intervals), MODS and Inborn error of metabolism. Askenazi et al. Journal of Pediatrics 2013;162:587-92.

31. The Center for Acute Care Nephrology Let’s use a new filter…. HF-20 filter (0.2m 2 surface area) –Optimized tubing diameters for improved hemodynamic properties Currently Available in Europe United States –Pre-clinical FDA approval (Dec 2013) –Study begins in March 2015

32. The Center for Acute Care Nephrology Dedicated rather than adapted machine 3 sets: –27.2, 33.5, 41.5 ml ECV Scale error 1 gram/hour

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34. Lets adapt a machine Aquadex™ – FDA -- 2007 Indication fluid overload not responsive to diuretics 33 cc circuit volume HCT line optional Courtesy of D. Askenazi, MD

35. The Center for Acute Care Nephrology Cooper Endorsed™

36. The Center for Acute Care Nephrology Conclusions Cardiac surgery provides an ideal setting to study AKI Patients at risk for AKI can be easily identified pre- operatively Given the high rate of CS-AKI –Therapeutic intervention should occur at early signs –Perspective should change from treating classic AKI to preventing serious AKI sequelae The future is bright as more neonatal RRT options will be available soon