Ex Vivo Lung Perfusion for Lung TransplantationAndres Pelaez, MD

San Antonio Advanced Lung SymposiumDecember 7, 2019 1

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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

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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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