horizon scanning hypothermic machine perfusion & normothermic machine perfusion
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Horizon scanningHypothermic Machine Perfusion
&Normothermic Machine Perfusion
Gabriel C. OniscuConsultant Transplant Surgeon
Honorary Clinical Senior LecturerNRS Career Research Fellow
Royal Infirmary of Edinburgh
Organdonation Transplant
SNOD network
CLOD network
50% increase
No significant changes
NORS
Cold static storage
Immunossupression
Surgical techniques
Surveillance
Organretrieval
Organ preservation
Hypothermic perfusion
Normothermic perfusion
Oxygenated perfusion
Pulsatile perfusion
In-situ
Ex-situ
Blood perfusate
Sub-normothermic perfusion
Oxygen carriers
Pre-conditioningReconditioning
The drivers of change
697664
637 634609 611 624 637 652
705
73 87127
159200
288335
373
436
507472 485
599
702
858
961
1062 1046 10551101
0
200
400
600
800
1000
1200
2003-2004 2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013
Year
Num
ber
DBD donorsDCD donorsLiving donors
Number of deceased and living donors in the UK, 1 April 2003 - 31 March 2013
Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant
Donation and transplantation rates of organs from DBD organ donors in the UK, 1 April 2012 – 31 March 2013
1 Hearts – in addition to age criteria, donors who died due to myocardial infarction are excluded
0
10
20
30
40
50
60
70
80
90
100
Organs fromactual DBD
donors
Donor agecriteria met
Consent fororgan donation
Organs offeredfor donation
Organs retrievedfor transplant
Organstransplanted
Per
cent
age
Kidney Liver Pancreas Heart Lungs
% of all organs
% of all organsmeeting age
criteria1
85%83%
28%
22%20%
85%83%
37%
26%25%
1
Transplanted:
Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant
0
10
20
30
40
50
60
70
80
90
100
Organs fromactual DCD
donors
Donor agecriteria met
Consent fororgan donation
Organs offeredfor donation
Organs retrievedfor transplant
Organstransplanted
Per
cent
age
Kidney Liver Pancreas Lungs
Donation and transplantation rates of organs from DCD organ donors in the UK, 1 April 2012 – 31 March 2013
% of all organs
% of all organsmeeting age
criteria
79%
27%
8%6%
79%
27%
14%8%
Transplanted:
Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant
• Increased utilisation of ECD and DCD• Lower organ recovery rate• Higher rate of complications • Poorer long term organ function• Logistic constrains• Cost benefit
Machine perfusionEvaluation criteria
• Better outcome• Prediction of function• Expansion of organ pool• Organ reconditioning• Ease of implementation• Costs
Evolution of the HMP
Evidence for HMP?
• Reduced DGF in MP group (21% vs 27%)• Shorter period of DGF• Lower risk of graft failure• Better one year survival
NO survival benefit in DCD (despite a lower DGF)
MP (n=45) CS (n=45)
DGF 26 (58%) 25 (56%)
eGFR (3 months)(ml/min/1.73m2)
46 48.9
eGFR (12 months)(ml/min/1.73m2)
46.6 46.2
Transplant survival 42 (93.3%) 44 (97.8%)
Patient survival 42 (93.3%) 45 (100%)
Watson et al, AJT 2010
Systematic review
• 5 RCT• One cohort study• One registry study• 4 data review• 844 MP (381 in RCT)• ? Clinical effectiveness
Bond et al, Health Technology Assessment 2009; 13:38
…Depends on which trial data is used
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.
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.
Moers et al. Transplantation 2010;90:966-703.
• MP trial data• 306 donor kidneys• GST, NAG and H-FABP predict DGF
• 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
• 5 DCD livers• Early function comparable with DBD• No biliary complications in the first 6 months
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.
• 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
Normothermic machine perfusion
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?
Reference Potential/Actual donors n)
Transplanted Kidneys (n)
Maastricht category
Sanchez-Fructoso, 2006Madrid, Spain
NR 320 I (85.3%) II (14.7%)Uncontrolled
Valero, 2000Barcelona, Spain
17 8 (47%) 16 IIUncontrolled
Reznik, 2010St Petersburg, Russia
NR 10 20 IIUncontrolled
Magliocca, 2005Michigan, USA
20 15 (75%) 24 IIIControlled
Farney, 2008North Carolina, USA
NR 25 IIIControlled
Lee, 2005Taiwan
16 16 (100%) 31 IIIControlled
Koyama, 2002Tokyo, Japan
23 23 (100%) 46 IVControlled
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
Reference Potential Actual donors
Maastricht category
Fondevila, 2007Barcelona, Spain
40 10 (25%)II
Jimenez-Galanes, 2009Madrid (Octubre), Spain
40 20 (50%) II
Otero, 2003Madrid, (San Carlos) Spain
NR 14 II
Pelletier, 2009Michigan, USA
19 12 (63%) III
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)
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