Horizon scanning Hypothermic Machine Perfusion & Normothermic Machine Perfusion

1. Horizon scanningHypothermic Machine Perfusion&Normothermic Machine Perfusion Gabriel C. Oniscu Consultant Transplant Surgeon Honorary Clinical Senior Lecturer NRS Career Research Fellow Royal Infirmary of Edinburgh

2. Surgical techniques Surveillance Immunossupression No significant changes NORS • Organ preservation • Transplant 50% increase CLOD network SNOD network Cold static storage • Organ • donation • Organ • retrieval

4. Oxygen carriers Hypothermic perfusion Blood perfusate Normothermic perfusion Pulsatile perfusion Oxygenated perfusion In-situ Ex-situ Sub-normothermic perfusion Pre-conditioning Reconditioning

6. The drivers of change

9. Increased utilisation of ECD and DCD • Lower organ recovery rate • Higher rate of complications • Poorer long term organ function • Logistic constrains • Cost benefit

10. Machine perfusionEvaluation criteria • Better outcome • Prediction of function • Expansion of organ pool • Organ reconditioning • Ease of implementation • Costs

11. Evolution of the HMP

12. Evidence for HMP?

13. Reduced DGF in MP group (21% vs 27%) • Shorter period of DGF • Lower risk of graft failure • Better one year survival

14. NO survival benefit in DCD (despite a lower DGF)

15. Watson et al, AJT 2010

16. Systematic review • 5 RCT • One cohort study • One registry study • 4 data review • 844 MP (381 in RCT) • ? Clinical effectiveness …Depends on which trial data is used Bond et al, Health Technology Assessment 2009; 13:38

17. Cost effectiveness? • SCS is cheaper • DGF related dialysis costs: 7,581$ vs 4,390 • MP is better in the long run (survival) Groen et al. Am J Transplant 2012;12:1624-1630 • USRDS and Medicare • MP associated with $2130 lower hospital costs and lower DGF • No difference in long term Medicare costs • ? MP utilisation or population differences Buchanan et al. Am J Transplant 2008;8:2391-401.

18. Graft assessment? • MP trial data • 111 Older donor kidneys (>55) • Lipid peroxidation markers predict DGF Nagelschmidt et al. J Surg Res 2013;180:337-42. • MP trial data • 306 donor kidneys • GST, NAG and H-FABP predict DGF Moers et al. Transplantation 2010;90:966-703.

19. PNF: no difference • PS/ GS: no difference • Lower early dysfunction rates (5% vs 25%) • Biliary complications 10% vs 20% • Shorter hospital stay Guarrera et al. Am J Transplant 2010

20. First Results on End-Ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) of Human Liver Grafts Donated after Cardiac Arrest. Philipp Dutkowski, Andrea A. Schlegel, Michelle DeOliveira, Olivier DeRougemont, Fabienne Neff, Pierre-Alain Clavien. Department of Surgery& Transplantation, University Hospital Zurich, Zurich, Switzerland. • 5 DCD livers • Early function comparable with DBD • No biliary complications in the first 6 months

21. 90 min CA and HMP vs CS • Hepatocellular injury and function improved with HMP • Significant endothelial cell and Kupfer cell injury • Progressive lesions 24-48h post-reperfusion leading to graft failure

22. Normothermic machine perfusion

23. Normothermic perfusion • Bridge between asystole and organ transplantation • In the donor • Ex situ • Rehabilitation at a cellular level (replenish mitochondrial stores of ATP) • Dynamic organ assessment • Organ modulation?

24. NRP and kidney Tx • Function comparable with living donors and DBD kidneys • Lower rate of DGF • Increases organ pool (DCD II) • Expansion of acceptance criteria

25. NRP and liver Tx • IC rates: 5-10% • 80% graft survival • PNF rates 1/10 and 2/20 • Liver recovery rate 25-50% (DCD II)