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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 1
2 0 1 9 S A N A N T O N I O A D V A N C E D L U N G S Y M P O S I U M 2 0 1 9 S A N A N T O N I O A D V A N C E D L U N G S Y M P O S I U M
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How can we impact this patient outcome?2 0 1 9 S A N A N T O N I O A D V A N C E D L U N G S Y M P O S I U M
How can we impact this patient outcome?
Using ECMO to support patients while waiting for lungs
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Expanding the Donor Pool in Lung Transplantation Ex Vivo Lung Perfusion ( EVLP)Andres Pelaez, MD
Medical Director University of Florida Lung Transplant Program
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Disclosure
•Nothing to disclose
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 2
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The Problem: A Gap Exists Between Available Lungs and Waiting Recipients in the US
Removal Reason 2013 2014 2015
Transplant 1901 1916 2047
Improved, Transplant not needed 49 38 42
Patient refused transplant 13 14 10
Patient died 216 271 243
Patient too sick for transplant 135 132 148
Total with Poor Outcome 351 403 391
OPTN/SRTR 2015 Annual Data Report: Lung. AJT 2018
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CURRENT PRACTICE IN ORGAN SELECTION AND MANAGEMENT
Donor Management
Organ Procurement
Cold Static Preservation
Transplantation
Slows down death
Decision
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Prior to the insult of ischemia‐reperfusion, the lung may be injured by a number of events in the donor before lung retrieval
Cold ischemia storage
Aspiration
Mechanical ventilation
Brain death
Leading to “silent” injury, but enough to change the threshold for subsequent acute lung injury when another insult comes
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As an example, this donor chest radiograph at the time of procurement seems to be normal
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However, when the lung transplant team arrived for their consultation the donor lung looked abnormal
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CURRENT PRACTICE IN ORGAN SELECTION AND MANAGEMENT
Donor Management
Organ Procurement
Cold Static Preservation
Transplantation
Decline
Slows down deathUnable to assess function
(Questionable organs are declined at procurement)
Decision
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 3
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Could we consider this lungs for organ donation?2 0 1 9 S A N A N T O N I O A D V A N C E D L U N G S Y M P O S I U M
Lung Recruitment
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UNOS‐www.optn.org
Of all potential donors, lungs are procured from 16% of donors
So is the limitation to transplantation lack of donors or lack of optimization
of lung donors?
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Concept of Ex Vivo Evaluation
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Concept of Ex Vivo Evaluation
Donor Management
Organ Procurement
Cold Static Preservation
Ex vivo Evaluation
DeclineTransplantation
•Evaluate / re‐evaluate questionable organs•Decline unsuitable organs only •Useful for DCD
Decision
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Fundamental Problems with Current Donor Organ Management
• Focus has been on slowing cell death, rather than on facilitating recovery / regeneration
• Static cold preservation hinders the possibility of active metabolic processes / repair
• Find out how the organ works AFTER we implant it
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 4
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TORONTO EX VIVO LUNG PERFUSION (EVLP) SYSTEM
Perfusion : 40% COVentilation: 7cc/kg, 7BPM, PEEP 5, FiO2 = 21%
Cypel/Keshavjee J Heart Lung Transplant 2008; 27(12):1319‐25.
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EX VIVO LUNG PERFUSION ASSESSMENT
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EX VIVO LUNG PERFUSION ASSESSMENT
Hemodynamics Peak AirWay Pressure
Compliance Delta PO2
PA
LA
Stat
Dyn
0
2
4
6
8
10
12
14
1 2 3 4 5 0
5
10
15
20
25
30
1 2 3 4 5
0
50
100
150
1 2 3 4 50
100
200
300
400
500
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Concept of Ex Vivo Evaluation
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Formal Indications for EVLP
Machuca, Cypel and Keshavjee. Advances in Lung Preservation. Surg Clin N Am 2013
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April 14th 2011, vol. 364, no. 15, pp. 1431-1440.
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 5
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J Thorac Cardiovasc Surg 2012
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J Heart Lung Transplant 2015
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Survival Curves
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Long‐Term Survival
Survival Freedom from CLAD
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Female, 49-yrs old, 187cm, 98kg Former-smoker, 10 pack-years, quit 10 years Lower limb pain (DVT) and shortness of breath 2 days before admission Admission – right side paralysis – stroke Intracranial bleedBrain Death
Machuca/Keshavjee, Am J Resp Crit Care Med 2013
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Donor Assessment
History Thromboembolic disease
ABG – P/F 266 mmHg
Chest X-ray No infiltrates
Transthoracic ECHO RVSP 52 mmHg + RV dysfunction, consistent with massive PE
Bronchoscopy Clear bilaterally
Intra-operative PAP 41/30 mmHg
Antegrade and Retrograde Flush Macroscopic clots extracted bilaterally
Concern: Thrombotic/embolic history, Elevated RVSP, RV dysfunction, Heart turned down, PAH acute or chronic?
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 6
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Significant improvement of Pulmonary Hemodynamics after treatment
treatment
Response monitoring
diagnosis
Alteplase
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Donor vs. Recipient post‐reperfusion
P/F 266 mmHgRVSP 50 mmHgRight Ventricular dysfunctionIntra‐operative PAP 41/30 mmHg
P/F > 500 mmHgPAP 28/9 mmHgExtubation 12 hours
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Recipient pre and post‐transplant
Pre‐transplant chest X‐ray Discharge chest X‐ray
CT: No vascular abnormalities
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IMPROVING OUTCOMES IN TRANSPLANTATION:ORGAN RESUSCITATION AND REPAIR
Good
Better
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The Future of Organ Preservation
Donor selection and management. Snell G et al; Seminars Resp Crit Care Med 2012.
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What about Donation After Circulatory Death (DCD) Lungs?
2011 OPTN/SRTR Annual Report
325 DCD livers
19 DCD lungs
351 deaths on the lung transplant waitlist
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 7
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Am J Transplant 2015
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Similar Survival Curves ALL DCD vs. ALL NDD
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DCD EVLP Activity
DCD EVLP 1y‐survival 92%DCD no EVLP 1y‐survival 77%
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The UF Ex Vivo Lung Perfusion Program Experience
20%
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Growing volume come with a very aggressive but thoughtful donor lung approach
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Short stature represents a significant disparity in access to lung transplantation
•UNOS database 2005 to 2011•< 162 cm
•34% lower lung transplant rate•62% higher waitlist mortality •42% higher rate of respiratory failure
Sell et al, Am R Resp Crit Care Med 2016
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 8
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91 days
210 days
21 days
38 days
Early 2010‐2015Current 2016‐2019
SS < 162 cmRS > 162 cm
Proactive Size Reduction
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Using lobar transplantation to allow access to short stature patients
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University of Florida Lung Transplant Program
1y survival 91%
YTD 84
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Waitlist Mortality US
rank center volume 2018 waitlist mortality 1‐y survival
10 University of Florida 70 4% 90.05%
5 Duke University 97 14.6% 88.69%
3 U Penn 112 16.9% 89.64%
8 UCLA 78 17.5% 89.44%
6 UPMC 92 18.2% 87.63%
1 Temple 144 21.7% 85.39%
4 St. Joseph Arizona 104 24.8% 91.30%
2 Cleveland Clinic 113 24.9% 85.48%
9 Wash U 74 25.6% 94.98%
7 NY Presbiterian 82 26% 89.79%
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Conclusions
1. DCD donors represent a valuable source of lungs
2. Provide similar outcomes to NDD lungs
3. EVLP is an important technique to assess and increase the utilization of extended criteria DCDs
4. Outcomes of DCD EVLP are very encouraging
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Donor Management
Organ Procurement
Cold Static Preservation
Ex vivo Optimization
• Organ-Specific Injury Repair• Immunologic Preparation
TransplantationDecline
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Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD
San Antonio Advanced Lung SymposiumDecember 7, 2019 9
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