Reconditioning Donor Lungs for Transplantation Andrew Fisher Professor of Respiratory Transplant...
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Transcript of Reconditioning Donor Lungs for Transplantation Andrew Fisher Professor of Respiratory Transplant...
Reconditioning Donor Lungs for Transplantation
Andrew FisherProfessor of Respiratory Transplant Medicine
Academic Director Institute of Transplantation
Freeman Hospital, Newcastle Upon Tyne
Worldwide Adult Lung Transplants
J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
Lung Transplant ActivityFreeman Hospital 1985-2013
32
46
61 63
5534
11 6
14
7 9
12 1621 22
0
10
20
30
40
50
60
70
80
90
100
6 months 1 year 2 years 3 years
Time since listing
Pe
rce
nta
ge Died
Removed
Still waiting
Transplanted
Post-registration outcome for 258 new lung only registrations made in the UK, 1 April 2009 - 31 March 2010
Figure 4
Outcome of 258 UK patients listed for lung transplantation 2009-2010
31%
NHS Blood and Transplant
Waiting Time to Lung Transplantby ABO blood group
NHS Blood and Transplant Activity Report 2011-2012
Data from NHS Blood and Transplant 2012
UK Donor Utilisation for Lung Transplantation 2001-2012
Extended Criteria Donor Lungs
20 – 45 65
>350 >300Donor
OptimisationPulm. Vein
Gas200
NeverCumulative Current
Clear Donor Optimisation Persistent CollapseDense Consolidation
Pan resistant OrganismMycobaterial Disease
Antibiotics HIV+Culture Negative
NeurogenicPulm Edema
<55 60
? Upperlimit
ClearPurulent Inflammation Aspiration Visualised
Tumour
Bronchoscopy
appearance
Microbiology
Chest x-ray
Smoking
History
PO2/FiO2
Age
(years)
Indicator “Ideal”Donor
“Standard”Criteria
Marginal DonorProgression
“Unusable”Donor
Non-Purulent
Gram-stain Negative
Clear
<20 p.y.
Botha, Fisher et al, Transplantation 2006
Donor Lung Assessment• Visual• Radiological• Functional
– oxygenation
• Physiological– haemodynamics
– ventilation
– metabolic
• Microbiological• Biological
Objective Assessment of Donor Lung Acceptance
Outcome Age / yr PaO2/ FiO2 Neut. 103/ml IL-8 pg/l % culture positive
accepted
n = 14
36.7 63.2 44 810 9 (75)
excluded
n = 25
49.5
p=0.009
43.1
p=0.001
46
p=0.78
540
p=0.64
9 (43)
p=0.1
Selection criteria poor discriminators of injury and infection leading to exclusion of potentially usable lungs.
Fisher et al, Thorax 2004;59:434
Ex-Vivo Lung Perfusion
Ventilator
Reservoir
PumpMembrane Gas Exchanger
Leukocyte Depleting
FilterPA outflow
LA inflow
Perfusate Reservoir
Professor Stig Steen
Described successful reconditioning and transplantation of 6 out of 9 donor lungs deemed unusable for transplant. All 6 recipients survived the first 3 months 4 of the 6 were alive and well 12 months after transplant
Ann Thorac Surg. 2009 Jan;87(1):255-60.
Establishing an EVLP Programmein Newcastle
•Ethics committee approval•Hospital procedure approval•Non-clinical pilot phase•Consent of waiting list patients•Education of the transplant team•Manpower and logistics•Deciding the technique•Agreeing acceptance criteria
Courtesy of Ms Karen Redmond (Harefield Hospital)
At start of EVLP At end of EVLP
EVLP Good Ventilatory Performance
EVLP Poor Ventilatory Performance
Ex-vivo Metabolism
Ex-vivo Metabolism
Gas assessment after EVLP
Potential Impact of EVLP
• Increased offering of donor organs• Increased lung transplant activity• Reduced waiting list mortality• Reduced incidence of severe PGD?• Improved longterm outcomes?
– Less rejection?– Less infection?
• Platform for therapeutics
Normothermic ex vivo lung perfusion in clinical lung transplantation
New England Journal of Medicine 2011; 364(15), p 1431–1440.
Professor Shaf Keshavjee
Normothermic ex vivo lung perfusion in clinical lung transplantation
New England Journal of Medicine 2011; 364(15), p 1431–1440.
Phase I non-randomised safety study (n=20) XVIVO Perfusion System Completion date February 2010 Outcomes in the EVLP group were comparable to that
achieved with standard transplants: 15% incidence of Primary Graft Dysfunction (PGD) in EVLP
group at 72 hrs 30% incidence of PGD in the standard transplant group p=0.11
Commercial EVLP Systems
X-VIVO SystemVivoline SystemTransmedics OCS system
A Study of Donor Ex-vivo Lung Perfusionin United Kingdom Lung TransplantationA Study of Donor Ex-vivo Lung Perfusionin United Kingdom Lung Transplantation
FreemanHospital
PapworthHospital
HarefieldHospital
Queen Elizabeth Hospital
WythenshaweHospital
Andrew Fisher Chief Investigator (Newcastle)
Karen Redmond Surgical Lead (Dublin)Andre Simon PI (Harefield)Nizar Yonan PI (Manchester)Steven Tsui PI (Papworth)Jorge Mascaro PI (Birmingham)John Dark PI (Newcastle)Nandi Marczin ITU Lead (Imperial College)
Study Details• Design:
- Non-randomised, non-inferiority observational study with an adaptive design
• Funders: - NIHR Health Technology Assessment
Programme and CF Trust• Sponsor:
- The Newcastle upon Tyne Hospitals NHS Foundation Trust
Primary Objective:
To compare survival during the first 12 months after lung transplantation in recipients of EVLP assessed and reconditioned donor lungs (treatment group) compared to that of recipients of standard donor lungs (control group), in order to assess whether survival in the EVLP treatment group over that period is non-inferior to that in the standard control group.
Secondary Objectives:
• Assess early clinical outcomes• Measure quality of life (QOL)• To determine if EVLP is a cost-effective• Explore patients attitudes to and experiences
of EVLP• To collect biological samples during EVLP
reconditioning to support parallel mechanistic studies
Acknowledgements
Newcastle EVLP Clinical Research TeamProfessor John DarkDr Anders AndreassonMr Stephen ClarkDr Mahesh PrabuProfessor Paul CorrisMr Tanveer ButtMrs Gail Johnstone Retrieval SurgeonsTransplant SurgeonsTransplant Co-ordinatorsPerfusionistsTheatre Nurses
Thanks to all our Patientswaiting for a lung transplant
Institute of TransplantationFreeman Hospital, Newcastle Upon Tyne