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)