Andrew Durward St Thomas NHS Foundation Trust Orlando 2017 CRRT IN AKI

Why use renal replacement in AKI? AKI In critically ill is common >30% Mortality with AKI increased (40-50%) sepsis Macedo Nephrol Dial Transplant 2010

Untreated AKI – is CCRT harmful 29 vs 43% sepsis Schneider A G et al. Nephrol. Dial. Transplant. 2012;27:947-952

CCRT in AKI – Benefit? Mortality benefit? With or with kidney injury ? Mechanism benefit? Dialysis mode benefit ? GENETICS?

Treatment bundles – Outcomes in Sepsis Over 1 million adult patients (171 ICU’s Australia / NZ) Absolute mortality in severe sepsis 35% to 18% in 2012 (1.3% reduction per year) ARF 55% ARF 35% Giving antibiotics quicker 8% increase death / hour delay CCM 2006;34:1589-1596

Paediatric sepsis 2002 – 2012 (Australia / NZ) 97127 children 2.9% sepsis 2.1% septic shock Mortality severe sepsis unchanged 19% 2002-2007 15% 2008-20012 Lancet Infect Dis 2015;15: 46–54

What are we trying to dialyse ? Fluid overload Electrolyte balance (Na/K/Ca/Phos) 3) Acid base balance 4) Waste products (Urea / Ammonia) 5) Cytokines (sepsis) 6) Mystical blood purification

Why are we using CCRT? Fluid overload Electrolyte balance (Na/K/Ca/Phos) 3) Acid base balance 4) Waste products (Urea / Ammonia) 5) Cytokines (sepsis) 6) Mystical blood purification

Fluid overload and mortality risk N=297 children Multicentre 3% mortality per 1% increase fluid overload Sepsis 25% 37% 40%

Which mode renal replacement in AKI All modes work in AKI Peritoneal Continuous Renal Replacement Intermittent Haemodialysis Patient size Vascular access Expertise and skill Use the mode you have experience with

Wide variation in practice Not evidence based No co-ordinated “plan of attack”

CVVHD vs CVVH CVVHD CVVH predilution Post dilution Dialysate filtrate

Blood flow rate vs solute clearance

Blood flow rate vs solute clearance

Bigger dialysis dose is better?

Mode dialysis in sepsis: CVVH vs CVVHD Acute Kidney Injury (OMAKI) Canadian Trial group CVVH vs CVVHD n=78 adults (80% sepsis) Same dialysis dose of 35ml/kg/hr effluent rate No difference mortality CVVH 12/35 35% CVVHD 10/38 27% Wald et al. Critical Care 2012, 16:R205

Dose dialysis in sepsis: No effect RENAL study (n=1508) NEJM 2009 CVVHDF 25ml/kg vs 40ml/kg/hr No difference mortality Tolwani (n=200) J Am Soc Neph 2008 CVVHDF 20ml/kg vs 35ml/kg/hr No difference mortality NIH ATN (n=1124) NEJM 2008 CVVHDF 35ml/kg vs 20ml/kg/hr

Sieving coefficients

Nitrogen loss N=6 children BFR 4ml/kg/min 11-12% Amino acids lost of dialy intake Maxfold CCM 28(4):1161-5

ECMO in AKI N=154 children CVVH On ECMO (44%) N=43 children ECMO 44% survived 26% Ongoing CCRT 96% recovered renal function at discharge N=43 children ECMO 32% needed dialysis for ARF (double creatinine) Survival only 19% vs 92% if no renal injury Weber Ann Thorac Surg. Nov; 1990 50(5):720–3 Padden Pediatr Crit Care Med. 2011; 12(2): 153–158

CRRT Efficiency - Blood flow rate 400 200 100

Blood flow rate issues in children: Efficacy Blood flow rate dependence: Getting most of filter performance 2mm 4mm

CRRT Efficiency - Recirculation long femoral 25cm Short femoral 15cm Internal Jugular Subclavian

15cm short femoral Internal Jugular, Subclavian, Long femoral 25cm

Could CRRT Be harmful? n=76 adults sepsis CVVH (35ml/kg/hr) vs standard care Worse organ failure scores with CVVH Longer ventilation and inotrope need Worsening SOFA Score Time to death Payen Crit Care Med 2009; 37:803–810

Conclusion CRRT is effective therapy for AKI Use CCRT to achieve target goal Modality less important (CVVH vs CVVHD) Optimal Dose and Timing of CCRT unknown