1. David Askenazi MD, MSPH Associate Professor of Pediatrics 2Smaller Circuits for Smaller Patients Improving Renal Support with Aquadex™ Machine

2. Potential conflict of interest Speaker for AKI foundation

3. Small children are dialyzed differently! < 5kg N = 170 > 5kg N = 251 Anticoagulation Protocol <0.001 Citrate76 (45%)155 (62%) Heparin94 (55%)96 (38%) Prime<0.001 Blood164 (96.5%)202 (80%) Saline5 (3%)29 (12%) Albumin1 (0.5%)20 (8%) Blood Flow * (ml/kg/min) 12 (7.9-15.6)6.6 (4.8-8.8)<0.001 Daily Effluent Volume* (ml/hr/1.73m 2 ) 3328 (2325-4745) 2321 (1614- 2895) <0.001 Circuit LIfe 28 (11-67)37 (16-67)0.15 Askenazi et al. Journal of Pediatrics 2013;162:587-92.

4. Neonatal CRRT Circuit Priming Smaller patients require blood priming to prevent hypotension/hemodilution Smaller patients require blood priming to prevent hypotension/hemodilution Circuit volume > 10-15% patient blood volume Circuit volume > 10-15% patient blood volume Example Example 4 kg infant : Blood Volume = 320 cc (80/kg) 4 kg infant : Blood Volume = 320 cc (80/kg) Circuit (extracorporeal volume = 165 ml) Circuit (extracorporeal volume = 165 ml) Therefore ≈ 50% extracorporeal volume Therefore ≈ 50% extracorporeal volume

5. Added Risk for PRBC prime Packed RBCs Packed RBCs HYPOCALCEMIC HYPOCALCEMIC Citrate Citrate HYPERKALEMIC HYPERKALEMIC LYSIS OF CELLS LYSIS OF CELLS ACIDIC ACIDIC There are no Plts in packed pRBC’s There are no Plts in packed pRBC’s Every prime you start CRRT you should expect for your plts count to drop Every prime you start CRRT you should expect for your plts count to drop There are no coagulation factors in pRBC’s There are no coagulation factors in pRBC’s Every prime you start CRRT you should expect for your coagulation factor to drop. Every prime you start CRRT you should expect for your coagulation factor to drop.

6. What if you did that to me? 4 kg70 kg Blood Volume320 ml5000 ml Extracorporeal volume 165 ml (50% of ECV)2.5 L Blood Flow12 ml/kg/min840 ml/min Clearance100 ml /kg/hr7000 ml/hr Filter5 times BSA8.6 m2

7. We must then acknowledge Its amazing we do CRRT in babies…. Even with the best practices….this approach exposes the smallest children to added risk Benefit RISK ≠

8. We must then acknowledge Its amazing we do CRRT in babies…. Even with the best practices….this approach exposes the smallest children to added risk You have reason to be nervous… What about the 1-2 kg baby? Do we just ignore him/her….? If we believe that critically ill patients do better with renal support…we must strive to do better?

9. Lets adapt a machine Aquadex – FDA approved for ultrafiltration in 2007 33 cc circuit volume 4 kg = 10 % ECV In 2012, received a Impact Grant from Children’s of Alabama

10. Lets adapt a machine Rx Blood flow = 40 ml/min Prismasol with additives at 30 ml/kg/hr Heparin anti-coagulation

11. 12 children received CVVH on Aquadex™ 5 in CICU and 7 in NICU 9 for AKI and 3 for severe congenital CKD median age at initiation = 30 days (IQR = 13, 38 days) median weight at initiation was 3.4 kg (IQR = 3.0 – 4.3 kg) The median duration = 14.5 days (IQR = 10, 22.8 days). Access double lumen vascular access (n=9) (4 = 8F; 4 = 7F; 1 = 6F) 2 x single lumen catheters in 3 with congenital heart disease had 2 single lumen catheters. Children’s of Alabama (Dec 2013 – April 2015)

12. Can we use umbilical lines?

13. 101 circuits – 261 days 12 new starts 89 restarts 59 (61%) circuits lasted 72 hours Prime 80% Blood Prime ECV > 10% (<4 kg) pRBC + NaHC03 + CaCl 80% for Saline prime in 20% Cross prime circuit for routine change out 20% Saline Prime Children’s of Alabama (Dec 2013 – April 2015)

14. Clearance

15. 7/12 survived to come off CVVH 6/12 survived to hospital discharge 1 died before hospital discharge for non-renal complications 5 died due to progressive cardiac/pulmonary disease Complications from CVVH 4/101 (4%) initiation associated with need for increased BP support All very mild and transient 3 hypothermia 4 bleeding 1 had a right atrial thrombus Children’s of Alabama (Dec 2013 – April 2015)

16. Summary Aquadex – CRRT experience Nephrologist Like it! Renal Support Goals Achieved Steady reduction in BUN / Cr Excellent control of electrolytes balance. Fluid goals achievable No crashes on initiation! Critical Care Docs Like it! Dialysis Nurses Like it! Bedside Nurses Like it! Babies hardly know they are on it!

17. Limitations Small retrospective case series IV infusion system does not communicate to machine We probably can, but haven’t tried citrate anti-coagulation No counter-current dialysis A circuit <24 ml would mean all saline primes in our case series!

18. Smaller circuits will revolutionize how neonatal ICU care!

19. Acknowledgements Pediatric Nephrologist Colleagues Dan Feig MD Sahar Fathallah MD Monica Cramer MD Frank Tenney MD Critical Care Faculty Dialysis Nurses Lynn Dill RN Daryl Ingram RN Bedside Nurses