University of Pittsburgh PCRRT Congress London 2015 CVVHD is Best! Joseph A Carcillo University of Pittsburgh

Questions? Is there an optimal form of RRT in children independent of cause of AKI? Are there studies comparing outcome randomized by RRT modality in children?

Dialysis (diffusive) PD vs. HD vs. CVVHD vs CVVHDF Works with solute clearance across a semi-permeable membrane The greater the gradient the greater the clearance The greater the solution exposure per unit of time the greater the clearance

RRT for AKI: Which Modality is Best? In-hospital mortality No Difference in Adult Survival Rabindranath et al., Cochrane Database of Systematic Reviews (2007)

Dialysis - Diffusion

Ultrafiltration-Convection

Continuous Veno Venous Hemofiltration Applicable to following diseases : Fluid overload Congestive heart failure Acute renal failure Crush syndrome

CVVH-Continuous Veno Venous Hemodialysis Applicable to following diseases : Acute renal failure Lactic acidosis

CVVHDF

ECMO can be used as a stable base filtration therapies in the very small or in the hemodynamically unstable patient

RRT for Pediatric AKI: Which Modality is Best? RRT modality (40% survival with HF, vs. 49% survival with PD, vs. 81% survival with HD; P<0.01 HD vs PD or HF), Years of study: 1992-1998 N=226; P<0.01 (HD vs other) P < 0.01 Bunchman et al., Pediatr Nephrol (2001) 16:1067–1071

Pediatric ARF: Modality and Survival (ns) Ped Neph 16:1067-1071, 2001

Includes Flores Study Friedrich JO, Wald R, Bagshaw SM, Burns KE, Adhikari NK. Hemofiltration compared to hemodialysis for acute kidney injury: systematic review and meta-analysis. Crit Care. 2012 Aug 6;16(4):R146. doi: 10.1186/cc11458

Mortality No Difference Friedrich JO, Wald R, Bagshaw SM, Burns KE, Adhikari NK. Crit Care. Crit Care. ‘Continuous’ Hemofiltration compared to hemodialysis for acute kidney injury: systematic review and meta-analysis. Crit Care. 2012 Aug 6;16(4):R146. doi: 10.1186/cc11458.

Filter life Hemofiltration leads to a shorter filter life Friedrich JO, Wald R, Bagshaw SM, Burns KE, Adhikari NK. Crit Care. ‘Continuous’ Hemofiltration compared to hemodialysis for acute kidney injury: systematic review and meta-analysis. Crit Care. 2012 Aug 6;16(4):R146. doi: 10.1186/cc11458.

Parakininkas, Daiva; Greenbaum, Larry; MD, PhD Comparison of solute clearance in three modes of continuous renal replacement therapy. Parakininkas, Daiva; Greenbaum, Larry; MD, PhD Pediatric Critical Care Medicine. 5(3):269-274, May 2004. DOI: 10.1097/01.PCC.0000123554.12555.20 Figure 1. The configuration of the Prisma continuous renal replacement therapy machine. Different pumps control the rate of dialysate, predilution, and effluent. The sampling port is used to obtain effluent for the clearance calculations described in this study. ©2004The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Published by Lippincott Williams & Wilkins, Inc. 2

Messer, Jennifer; Mulcahy, Brendan; Fissell, William Figure 1. Dialysate-side Ficoll clearance as a function of molecular weight. Y-axis, clearance in ml/min. X-axis, molecular weight. Black lines, 2.0 m2 dialyser; Gray lines, 0.4 m2 dialyser; Solid lines, continuous venovenous hemofiltration (CVVH); Dashed lines, continuous venovenous hemodialysis (CVVHD). Middle-Molecule Clearance in CRRT: In Vitro Convection, Diffusion and Dialyzer Area. Messer, Jennifer; Mulcahy, Brendan; Fissell, William ASAIO Journal. 55(3):224-226, May/June 2009.DOI: 10.1097/MAT.0b013e318194b26c Copyright © 2009 by the American Society for Artificial Internal Organs. Published by Lippincott Williams & Wilkins, Inc. 2

Comparison of solute clearance in three modes of continuous renal replacement therapy. Parakininkas, Daiva; Greenbaum, Larry; MD, PhD Pediatric Critical Care Medicine. 5(3):269-274, May 2004. DOI: 10.1097 / 01.PCC.0000123554.12555.20 Figure 3. Urea clearance data for predilution continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) over changing rates of either replacement fluid or dialysis fluid. Blood flow was kept at 60 mL/min while predilution or dialysate was run at 600 mL/hr (16.7% of blood flow rate), 1200 mL/hr (33% of blood flow rate), or 1800 mL/hr (50% of blood flow rate). CVVHD had a superior clearance at all comparisons, with a 15% greater clearance at 600 mL/hr (p < .001). ©2004The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Published by Lippincott Williams & Wilkins, Inc. 7

Parakininkas, Daiva; Greenbaum, Larry; MD, PhD Figure 4. Creatinine clearance data for predilution continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) over changing rates of either replacement fluid or dialysis fluid. Blood flow was kept at 60 mL/min while predilution or dialysate was run 600 mL/hr (16.7% of blood flow rate), 1200 mL/hr (33% of blood flow rate), or 1800 mL/hr (50% of blood flow rate). The clearance of CVVHD was 15% higher at both 1200 mL/hr and 1800 mL/hr (p < .05). The 10% difference at 600 mL/hr was not statistically significant. Comparison of solute clearance in three modes of continuous renal replacement therapy. Parakininkas, Daiva; Greenbaum, Larry; MD, PhD Pediatric Critical Care Medicine. 5(3):269-274, May 2004. DOI: 10.1097/01.PCC.0000123554.12555.20 ©2004The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Published by Lippincott Williams & Wilkins, Inc. 8

Univariate Odds Ratio (95% confidence interval) Variable1 Univariate Odds Ratio (95% confidence interval) Multivariate Odds Ratio (95% confidence interval) Percentage of fluid overload 1.02 (1.01-1.03)a 1.03 (1.01-1.05)a Oncologic diagnosis 1.61 (0.94-2.76)b 3.16 (1.64-6.07)c Diagnosis of MODS 5.54 (2.69-11.41)d 4.66 (2.04-10.65)d Convective CRRT modality 0.48 (0.30-0.77)a 0.80 (0.41-1.55) PRISM II score at PICU admission 1.04 (1.01-1.06)a 1.02 (0.99-1.05) Inotrope no. 1.50 (1.22-1.85)d 1.26 (0.99-1.60)b Fluid overload × convective CRRT modality NA 0.98 (0.95-0.99)a Includes CVVH + CVVHDF Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM, Flores FX, Benfield M, Askenazi D, Chand D, Fortenberry JD, Mahan JD, McBryde K, Blowey D, Goldstein SL. Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis. 2010 Feb;55(2):316-25. doi: 10.1053/j.ajkd.2009.10.048. Epub 2009 Dec 30.

The nomenclature is fraught with confusion Because even during intermittent hemodialysis, hemofiltration is performed for fluid removal Leading us to the straw man…. Since almost all PICU patients are fluid overloaded or at the least require fluid to be removed because so much intravenous fluid is being given…Of course All patients on CRRT need to have CONVECTIVE therapy for fluid removal The question is whether one should also perform Hemodialysis in what I consider CVVHDF. We do this Because HD gives maximum clearance with maximum filter life, whereas HF gives needed fluid removal My question for Tim is ‘In your present study do you continue hemofiltration for fluid removal when you crossover to the hemodialysis arm?’ Then of course convection is King! But dialysis is his Queen or, as in the case of the UK, convection is Queen and dialysis is her husband!