1. Renal Replacement Therapy in Hyperammonaemia Andrew Durward London, UK

2. Practical approach

3. Thrane Nature 2013:19:1572 Astrocytes shrinkage (not swelling) with high ammonia Impaired buffering of K+: Gabba transmission altered Neural dysfunction Neurotoxicity Ammonia (astrocyte role) Ammonia aqueous (NH3) 1-2% of plasma ammonia this form at physiologic pH: readily permeates membranes into brain 25% blood derived ammonia converted to glutamine in cytosol astrocyte

4. pH dependent Blood-brain transport Alkalosis increases ammonia transport Into brain Acidosis is protective Hypoxia worsens ammonia toxicity

5. 1.Time critical (get patient to your PICU)  Time to make diagnosis  Time to transfer to PICU  Time to start medical detox 1.Secure IV access for dialysis  Largest vascath possible  Best site (least recirculation)  Peritoneal dialysis may by time 1.Time of effective dialysis  Mode dialysis you are familiar with  Minimise circuit downtime Time critical condition 2.5 kg 8Fr Vascath (RIJ) 100ml/min BFR 60 ml/kg/hr UFR 4HRS

6. Choose mode dialysis (CVVH/CVVHD/HD)

7. BFR dependence: Maximise filter performance Maximise filter peerformance

8. Use large vascath Site where flow best (RIJ) HIGH FLOWS = RECIRCULATION VASCATH 8Fr (2.6mm) 10Fr (3.3) 11Fr (3.6mm) 12Fr (4mm) Adequate Vascath to maximise flow

9. Manipulating vascath tip for bets flow

10. Vascath tip position

11. Le blanc Am Jour of Kid Dis 31, 1998: pp 87-92 Recirculation higher with greater BFR Probably at least 10% in neonates Can be as high as 50% DONT SWAP LUMENS OF VASCATH AROUND Beware recirculation

12. Paediatric haemofilters: BFR vs UFR

13. Summary Time critical Choose dialysis mode you know Large vascath with good flows Watch for recirculation Close monitoring Attention to acid / base Metabolic support / detoxification