Renal replacement therapy in Pediatric Acute Kidney Injury ASCIM 2014 Dr Adrian Plunkett Consultant Paediatric Intensivist Birmingham Children s Hospital, UK
Aims of the presentation Important topic: AKI is common in PICU and associated with poor clinical outcomes 1. AKI in PICU: definitions. 2. Indications and types of RRT in AKI in PICU. 3. Controversies and issues in CRRT in PICU.
Acute Kidney Injury definition Many definitions (>30) of AKI exist in the literature Hallmarks of AKI definitions: Rise in plasma creatinine from baseline Fall in (e)gfr Fall in urine output (not essential) Standardised definitions needed: prifle standardised definition proposed in 2007 Other standardised definitions: AKIN
Acute Kidney Injury definition
Acute Kidney Injury - definition 150 admissions to PICU 82% AKI by prifle definitions prifle max: 48.8% = R 26% = I 25.2% = F AKI defined by prifle associated with longer LOS (PICU and hospital) prifle max commonly reached early in admission Alkan-Arikan et al Kid Int 2007
Acute Kidney Injury - aetiology Pre-renal: volume depletion / redistribution of circulation / decreased CO Renal: ATN / ischaemia / toxins / nephritis / glomerulonephritis / vascular /congenital Post-renal: obstructive uropathy Aetiology varies according to context Commonest cause of pre-renal AKI worldwide = dehydration from gastroenteritis Commonest cause of renal AKI worldwide = HUS But most AKI now seen in PICU is secondary to other primary or systemic disease e.g. Post cardiac surgery / ATN / sepsis / nephrotoxic medication Co-morbidities in AKI therefore common
Acute Kidney Injury - trends The epidemiology of AKI is changing over time: Pediatric AKI patients are showing rise in: Comorbidities Severity of illness Fluid overload Therefore, indications and type of RRT are also changing: Commonest form of RRT in pediatric AKI in PICU is now continuous RRT (CRRT): Changing patient cohort Improved technology better stability and control of RRT
Acute Kidney Injury indication for RRT Indications similar to adults, with some unique features in children e.g. Inborn errors of metabolism Renal Oliguria / anuria Acidosis Hyperkalaemia Indications for RRT Non-renal Fluid-overload Inborn errors of metabolism Sepsis From ppcrrt registry: Indications for CRRT 90% related to AKI 29% FO 13% eletrolyte abnormalities 46% both FO and electrolyte abn 3% to eliminate fluid restriction Azotemia / uraemia symptoms Hyperphosphataemia Drug overdose / toxins
Acute Kidney Injury indication for RRT Diagnosis associated with AKI from ppcrrt registry Sutherland and Alexander Pediatr Nephrol 2012 27
Acute Kidney Injury type of RRT 3 main types of RRT: PD HD CRRT Choice depends on clinical characteristics PD HD CRRT Vascular access No Yes Yes Complexity Low High Moderate Systemic anticoagulation No Frequent Frequent Toxin removal Moderate High High Fluid removal Moderate Moderate High Use in haemodynamic instability? Use in abdominal surgery? Yes No Yes +/- Yes Yes Adapted from Roger s Pediatric Intensive Care Table 37.2
Acute Kidney Injury PD PD is the oldest form of RRT Commonest form of RRT in children, but decreasing in PICU Common choice in small children Low cost, simple technology Usually tenckhoff catheter Bidirectional exchange of fluid and solutes across the peritoneal membrane Clearance depends on: Volume of PD fluid (usually 10-20ml/kg) Dwell time (usually 20-40 mins) Osmolality of PD fluid (varied dextrose concentration (1.5% / 2.3% / 4.25%) Complications relatively rare: Infection Drainage / filling problems Fluid imbalance
Acute Kidney Injury PD BCH PD prescription Includes cross-flow PD In BCH, mostly used in post-cardiac surgery AKI in infants.
Acute Kidney Injury CRRT Gentler form of fluid / solute removal (cf haemodialysis) Suitable for haemodynamic instability Initially CAVH (1950s) Now pump-driven CVVH Provides solute clearance by diffusion and / or convection CVVH: exclusively convection clearance CVVHD: mostly diffusion clearance CVVHD: both mechanisms
Acute Kidney Injury CRRT From ppcrrt registry: CVVH: 21% CVVHD: 48% CVVHDF: 30% Edwards life sciences Symons et al 2007 Santiago et al ICM 2010
Acute Kidney Injury CRRT Issues / controversies with CRRT: 1. Access 2. Modality 3. Dose 4. Timing 5. Anticoagulation 6. Use of CRRT in small children
Acute Kidney Injury CRRT: access Longer circuit survival associated with larger bore catheters and internal jugular site From: Hackbarth et al. a report from the PPCRRT registry. Int J Artif Organs 30:1116 1121
Acute Kidney Injury CRRT: modality Choice of modality: ppcrrt registry: 344 children on CRRT in US: CVVHD: 48% CVVHDF: 30% CVVHF: 21% Symons et al Clin J Am Soc Nephrol 2:732-8 Choice tends to be centredependent Theoretical improved clearance of: -small solutes with diffusion -middle-sized solutes with convection Does it make a difference to outcome? No strong evidence to favour one modality Observational (ppcrrt registry) evidence of improved survival when using convective methods (vs. CVVHD) in cohort of stem-cell transplant patients 59% vs. 27% p<0.05 Flores et al Ped Neph 2008 Filer life preserved in CVVHD cf. CVVHF
Acute Kidney Injury CRRT: dose High dose vs. lower dose of ultrafiltrate 35ml/kg/hr vs. 20ml/kg/hr RENAL study 1508 adults AKI. Just CVVHDF No survival benefit at 90 days Historical evidence from adult studies for better outcome with higher dose (Single-centre - Ronco et al, Lancet 2000) Large multi-centre trials show no survival benefit for higher dose: Acute Renal Failure Network study 1124 adults with AKI 60 Palevsky day et survival NEJM 2008 equivalent in high dose and low dose Bellomo et al NEJM 2009
Acute Kidney Injury CRRT: timing Determining optimal timing of initiation of CRRT in ICU is a high priority research goal Strong evidence that fluid overload in ICU is associated with worse outcomes Modem et al, CCM 2014 Single-centre, observational study 190 PICU pts on CRRT (AKI / FO) Overall mortality 47% Survivors commenced CRRT earlier in admission compared with nonsurvivors 2d vs 3.4d (p=0.001)
Acute Kidney Injury CRRT: timing Effect of degree of fluid overload at time of initiation of CRRT Cohort of PICU pts on CRRT, ppcrrt registry 153 pts 3% increase in mortality for 1% increase in FO Sutherland et al Am J Kidney Disease 2010
Acute Kidney Injury CRRT: anticoagulation CRRT in children: elevated risk of clotting cf. adults: Lower blood flows Smaller catheters Commonest options: Heparin or Citrate Multi-centre evaluation of anticoagulation Heparin vs citrate ppcrrt registry: 138 patients Brophy et al. Nephrol Dial Transplant 2005 No diff in circuit life Higher risk of bleeding in heparin group
Acute Kidney Injury CRRT: small children CRRT uniquely difficult in small children Vascular access may be limited 5Fr catheters associated with poor filter lifespan Relatively high blood flow relative to blood volume Higher circuit volume relative to blood volume Risk of hypothermia ppcrrt registry: 84 children < 10kg Higher mortality (67%) vs >10kg (36%) But technology and expertise improving
Acute Kidney Injury CRRT: small children Ronco Lancet 2014 CarpeDiem Miniaturised CRRT 2.9kg MODS / FO 5cm, 22g catheter >400hrs CRRT
Acute Kidney Injury CRRT: complications Complications of CRRT in PICU Prospective, observational study Single-centre in Spain 174 PICU patients on CRRT (43% <1 yr of age) High complication rate. Main complications: Catheterisation-related: 13 pts (7.4%) hematoma, bleeding, venous congestion Hypotension: 53 pts (30.4%) Haemorrhage: 18 pts (10.3%) Electrolyte disturbance common Santiago et al, Critical Care 2009
Acute Kidney Injury RRT summary AKI in PICU is common, and associated with worse clinical outcomes Standardised definitions of AKI are available Epidemiology of AKI is changing Modality and indications for RRT is changing CRRT commonest form of RRT in PICU Large catheter in IJV improves circuit life No trial evidence for modality or dose of CRRT in PICU Observational evidence to support early initiation of CRRT
Acute Kidney Injury in PICU the future Need RCTs currently lacking in this area in pediatrics cf adults pprrt registry is a good start More collaborative data and research needed AKI biomarker-based decision algorithms may help detect and predict need for RRT Emerging technology and expertise (e.g. Carpediem)