Improving outcomes in AKI and CRRT: Does Quality matter?

1. Improving outcomes in AKI and CRRT: Does Quality matter? Timothy E. Bunchman Professor and Director Pediatric Nephrology & Transplantation Timothy.bunchman@vcuhealth.org pedscrrt@gmail.com www.pcrrt.com

2. Overview • What has occurred to improve the diagnosis and outcome in AKI in children • What has occurred to improve the use of CRRT in children

3. How do you diagnosis AKI? • Severity of illness score? • Biomarkers? • FO? • Uremia?

4. Historically • AKI diagnosis was synominous with the need for renal replacement therapy • Uremia, hyperkalemia, metabolic acidosis • In 2000 ADQI occurred and began to quantitate and measure markers of AKI

5. RIFLE Criteria

6. Modified Pediatric RIFLE Goldstein et al , KI 2007 Now validated in 3 additional Pediatric Studies

7. LIMITATIONS OF AKI CLASSIFICATION CRITERIA pRIFLE AKIN KDIGO • inconsistency in application • urinary output criteria often excluded → loss of additional cases • exclusion of patients with elevated initial SCr • UO and sCr are late markers • Biomarkers…

8. AKI diagnosis: pRIFLE 51%, AKIN 37.3%, KDIGO 40.3%

9. Urine NGAL as an Early AKI Biomarker after Cardiopulmonary Bypass AKI = 50% or greater increase in serum creatinine from baseline Mishra et al, Lancet 2005, 365:1231-1238

10. Dialysis Dose and OutcomeRonco et al. Lancet 2000; 351: 26-30 • Conclusions: • Minimum UF rates should be ~ 35 ml/kg/hr • Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

11. 26.9% of all patients 11.6% of all patients 3.5% of all patients AWARE Investigators– submitted

12. So what! • The diagnosis of AKI and the need for RRT are discreptent • But • If AKI at risk is 25% of all PICU admissions then attention to detail of nephrotoxins and fluid over load are needed to avoid the worsening of AKI

13. SPECIAL FIBERS AND FILTERS HAVE BEEN DESIGNED FOR SPECIAL CONDITIONS AND PATIENTS Minifilters Ronco C, et al Treatment of acute renal failure in newborns by Continuous Arterio-Venous Hemofiltration. Kidney International, 1984

14. 1980s • Following Ronco’s paper little was published except for a descriptive paper by Leone et al describing CAVH in children • Early experience with continuous arteriovenous hemofiltration in critically ill pediatric patients. Crit Care Med. 1986 Dec;14(12):1058-63. • Neonatal work by Zobel • Continuous arteriovenous hemofiltration in premature infants. Crit Care Med. 1989 Jun;17(6):534-6.

15. 1990s • Equipment during this era was “adaptive” • Solutions for convection or diffusion was pharmacy made or lactate based • Latter part of 1990s industry began to market machines that did not take momentum until turn of the decade

16. 1990s • Important work on Access was presented by John Gardner RN describing the MAHURKAR™Catheter that is now marked by Covidien • “how to do it papers” • Continuous arterial-venous diahemofiltration and continuous veno-venous diahemofiltration in infants and children. PediatrNephrol. 1994 Feb;8(1):96-102. • Continuous venovenoushemodiafiltration in infants and children. Am J Kidney Dis. 1995 Jan;25(1):17-21. • Out come paper by Smoyer et al on • Determinants of survival in pediatric continuous hemofiltration. J Am SocNeph 1995 Nov;6(5):1401-9. Comparison paper on CAVH vs CVVH by our group in Am J Kid Dis 1995 • Maxvold and colleagues began comparison of modalities • Management of acute renal failure in the pediatric patient: hemofiltration versus hemodialysis. Am J Kidney Dis. 1997 Nov;30(5 Suppl 4):S84-8.

17. 1990s • Evaluation of PICU needs and RRT beyond AKI began • Parekh RS et al • Dialysis support in the pediatric intensive care unit. Adv Renal Replac Therapy 1996 Oct;3(4):326-36. • Quigley and associates on use of HD and hemofiltration in TLS • Hyperphosphatemia in tumor lysis syndrome: the role of hemodialysis and continuous veno-venous hemofiltration. PedsNephrol 1994, 8: 351-3

18. 2000s • This era exploded with advancements in • Equipment • FDA approval of bicarbonate based Solutions • Nutrition in AKI/CRRT • Avoidance of complications • Anticoagulation protocols

19. 2000s • Gambro and B Braun (and soon to follow Baxter) came out with machines with commonality of warmer, accurate fluid control as well as blood flow and solutions controllers

20. 2000s • FDA approval of bicarbonate based Solutions by Dialysis Solution Inc and Walter O’Rourke • Pediatric hemofiltration: Normocarb dialysate solution with citrate anticoagulation. PediatrNephrol 2002 17:150-4 • Maxvold et al described Nutrition needs and losses in AKI/CRRT • Amino acid loss and nitrogen balance in critically ill children with acute renal failure: a prospective comparison between classic hemofiltration and hemofiltration with dialysis. Crit Care Med 2000 28:1161-5

21. 2000s • Anticoagulation Protocols • Pediatric acute renal failure: outcome by modality and disease. PediatrNephrol 2001, 16:1067-71 • Pediatric convective hemofiltration: Normocarb replacement fluid and citrate anticoagulation. Am J Kid Dis 2003 42: 1248-52 • Brophy et al • Multi-centreevaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). NDT 2005 20:1416-21

22. Seven ppCRRT centers • 138 patients/442 circuits • 3 centers: hepACG only • 2 centers: citACG only • 2 centers: switched from hepACG to citACG • HepACG = 230 circuits • CitACG= 158 circuits • NoACG = 54 circuits • Circuit survival censored for • Scheduled change • Unrelated patient issue • Death/witdrawal of support • Regain renal function/switch to intermittent HD

24. Heparin vs citrate prospective studyZaoral et al, Pediatric Critical Care Medicine. 17(9):e399–e405, SEP 2016 • “ We showed in our study that citrate provided significantly longer circuit lifetimes than heparin for continuous venovenous hemodialysis in children. Citrate was superior to heparin for the transfusion requirements. Citrate was feasible and safe in children and infants”.

25. Convective Clearance • CVVH • Convective clearance • Replacement Solutions • Physiologic sterile solution that is either infused pre filter (NA) or post filter (outside of NA) that infused at a set rate (Qr)

26. Diffusive Clearance • CVVHD/HD/PD • Diffusive clearance • Dialysate • Physiologic sterile solution that is infused countercurrent to the blood flow rate (Qd)

27. Convective and Diffusive Clearance (? Confusion) • CVVHDF/CAVHDF • Convective clearance • Replacement Solutions • Diffusive clearance • Dialysis solution

28. Stem Cell Transplant: ppCRRT • 51 patients in ppCRRT with SCT • Mean %FO = 12.41 + 3.7%. • 45% survival • Convection: 17/29 survived (59%) • Diffusion: 6/22 (27%), p<0.05 • Survival lower in MODS and ventilated patients Flores FX et al: Pediatr Nephrol. 2008 Apr;23(4):625-30

29. Prospective Pediatric Study • 40 patients with Sepsis/ARF at 4 ppCRRT centers • Randomized crossover design • 24 hours of CVVH or CVVHD, then crossover • 2500 ml/hr/1.73m2 clearance • Dialysis/Replacement fluid with [HC03]=35mmol/l • Citrate ACG • Serum collection at 0,1, 24, 25 and 48 hours • TNF-alpha • IL-1 beta • IL-6, IL- 8, IL-10, IL-18 • Six hours of effluent for CK’s for clearance estimation

30. ppCRRT Sepsis Study • 10 patients enrolled to date • 6 male, 4 female • Mean age 12 + 4.8 years • Mean weight 44 + 21 kg • PELOD • Mean = 27 + 10 • Median = 22 (range 11-42)

31. ppCRRT [Cytokine] % Change: Convection vs. Diffusion

32. Leaders in the Field • Stu Goldstein began the ppCRRT and now the ppAKI study groups that have balanced research, QI with advancements

33. Has RRT improved out come? • All modalities of RRT have changed from adaptive to newer products for children of all ages • In the 90’s reports of 45 % survival rates have been replaced by current 65% survival rates in sepsis AKI

34. Has RRT improved out come? • In the 90’s reports of 17 % survival rates have been replaced by current 53% survival rates in liver AKI as reported by Deep and Colleagues

35. Conclusion • QI and Research have improved the diagnosis of AKI and the use of RRT • Since the beginning of this time, patients have more co-morbidities and are more complicated

36. Future • Areas primed for prospective and future research/QI include • Optimal med dosing • Optimal nutrition delivery • Non dialytic options of treatment of AKI • Science around starting and stopping RRT