Is the quality of reconditioned donor organs as good as the standard ones?

1. Lung transplantation after ex vivo lung perfusion:
Is the quality of reconditioned donor organs as
good as the standard ones?
16TH EUROPEAN CONFERENCE ON PERFUSION EDUCATION AND
TRAINING IN BARCELONA
1 OCTOBER 2016
MIRA KLEIN, HIRSLANDEN ZURICH, KALAIDOS UNIVERSITY
MARIANNE SCHÄRLI, KALAIDOS UNIVERSITY
Mira Klein 16th ECoPEaT, Barcelona, 1 October 2016 1

2. DISCLOSURE OF CONFLICT OF INTEREST
THERE IS NO CONFLICT OF INTEREST!
Mira Klein 16th ECoPEaT, Barcelona, 1 October 2016 2

3. Mira Klein 3
INTRODUCTION
• Lung transplantation (LTX) the only chance for long-term survival for
patients with end-stage lung diseases
• Only 15 – 30 % of available donor lungs are suitable for transplantation
(van Raemdonck et al., 2009)
• To expand the usage of suitable organs, ex vivo lung perfusion (EVLP) has
been established for marginal donor lungs
• Three different protocols used worldwide: «Toronto», «Lund», «Organ-
Care-System»
• Equipment, perfusate composition, perfusion and ventilation strategy
16th ECoPEaT, Barcelona, 1 October 2016

4. Mira Klein 16th ECoPEaT, Barcelona, 1 October 2016 4
RESEARCH QUESTION
«Has a pre-treatment of donor lungs with ex vivo lung
perfusion an impact on the early clinical outcome after
lung transplantation compared to lungs conventionally
transplanted?»

5. Mira Klein 5
LUNG TRANSPLANTATION – STANDARD CRITERIA
(ISHLT INTERNATIONAL SOCIETY OF HEART AND LUNG TRANSPLANTATION)
• Donor age < 55 years
• < 20 pack-years smoking history
• Matching size donor/recipient
• PF ratio (paO2 / FiO2) > 300 mmHg (40 kPa)
• Absence of infection
• Absence of purulent bronchial secretion
• Compatibility of blood groups
• No history of chest trauma
• No history of cardio-pulmonary surgery
16th ECoPEaT, Barcelona, 1 October 2016

6. Mira Klein 6
LUNG TRANSPLANTATION – STANDARD
PROCEDURE – COLD STORAGE
• After explantation: Cold flush ante- and retrograde 60 ml/kg donor weight
• Extracellular solution (contains dextran 40, sodium, potassium, glucose –
Perfadex®; Vitrolife, Gothenburg, Sweden)
• Cold storage for transport, 4 – 8 °C
• Inflation to 50% of total capacity with FiO2 50%
• Ischemic time < 6 h (< 8 h)
• Relative risk for 1-year-mortality increasing after 4.5 h (Christie, Edwards &
Kucheryavaya; 2010)
16th ECoPEaT, Barcelona, 1 October 2016

7. Mira Klein 16th ECoPEaT, Barcelona, 1 October 2016 7
EX VIVO LUNG PERFUSION - GOALS
• Increase number of usable donor lungs by reconditioning and reassessing
marginal organs primarily rejected for transplantation
• Safe usage of doubtful donor lungs
• Decrease mortality on the waiting lists

8. Mira Klein 8
EX VIVO LUNG PERFUSION - STRATEGY
• Simulation of physiologic in vivo situation
• Ventilation and perfusion of the normothermic lung
• Recruitment of atelectasis
• Reconditioning under physiologic circumstances
• Reassessment of organ function
• Bronchoscopic clearence
• Removal of pulmonary thrombus
• Improvement of microvascular circulation
• Recovering by preservation of normal metabolism
16th ECoPEaT, Barcelona, 1 October 2016

9. Mira Klein 9
EX VIVO LUNG PERFUSION - CONCEPT
• Reconditioning: Perfusion with oxygenated Steen Solution® (XVIVO
Perfusion, Sweden) and ventilation
• After reaching normothermia reassessment of organ function
• During reassessment perfusion with a deoxygenated solution (oxygenator
is «ventilated» with gas-mixture of 93% CO2 and 7% N2) to imitate venous
blood composition in the pulmonary artery
• FiO2 100% and pO2 > 40 kPa (300 mmHg) or FiO2 21% and pO2 > 13 kPa
(98 mmHg) and pCO2 < 6 kPa (45 mmHg) lungs will be accepted to be
transplantable
• Conservation of lungs until transplantation
16th ECoPEaT, Barcelona, 1 October 2016

10. Mira Klein 10
MATERIALS AND METHODS
• Systematic literature review; selection of 11 clinical trails (2009 – 2015)
• Identification of two compareable groups: Standard procedure (StLTX) and
LTX after EVLP (EVLP-LTX)
• Analysis of early clinical outcomes after Lung Transplantation
• Parameters: Postoperative ventilation hours (MV), postoperative length of
ICU (LOS-ICU) and hospital stay (LOS-HOS), postoperative 30-day/1-year
survival
• Interviews with four experts to validate findings from literature research
16th ECoPEaT, Barcelona, 1 October 2016

11. Mira Klein 1116th ECoPEaT, Barcelona, 1 October 2016

12. No significant differences could be found between the two groups
(EVLP-LTX and StLTX)
Mira Klein 12
RESULTS AND FINDINGS
16th ECoPEaT, Barcelona, 1 October 2016

13. Mira Klein 13
DISCUSSION
• EVLP offers a reliable tool to expand donor pool for lung transplantation
• Safety and reliability of the procedure were shown in different studies
• But… The procedure is expensive, demands time and requires a number of
specialized staff
• Usability depends on the location of transplantation center, social and
health systems of the country
• No significant differences between the three used EVLP-protocols could be
found
• All procedures are comparable to the standard protocol
• Experts confirm the findings of literature
• Individual motivation for choosing a protocol
16th ECoPEaT, Barcelona, 1 October 2016

14. Mira Klein 16th ECoPEaT, Barcelona, 1 October 2016 14
CONCLUSION
• Treatment of donor lungs with EVLP has no negative impact on the early
postoperative outcome after lung transplantation.
• The number of available and useable donor lungs increased after
implementation of EVLP.

15. Mira Klein 15
REFERENCES
Aigner, C., Slama, A., Hötzenecker, K., Scheed, A., Urbanek, B., Schmid, W., et al. (2012). Clinical Ex Vivo Lung Perfusion – Pushing the Limits. American Journal of Transplantation (12), 1839-1847.
Boszo, S., Vasanthan, V., Luc, J. G., Kinaschuk, K., Freed, D., & Nagendran, J. (2015). Lung Transplantation From Donors After Circulatory death Using Ex Vivo Lung Perfusion. Canadian Respiratory
Journal, 22 (1), 47-51.
Christie, J., Edwards, L., & Kucheryavaya, A. (2010), 27th official adult lung and heart-lung transplant report. The Registry of the International Society for Heart and Lung Transplantation (29),
1104-1118.
Cypel, M., Yeung, J. C., & Keshavjee, S. (2011). Novel Approaches to Expanding the Lung Donor Pool: Donation after Cardiac Death and Ex Vivo Conditioning. Clinics in Chest Medicine (32), S.
233-244.
Cypel, M., Yeung, J., Machuca, T., Chen, M., Singer, L., Yasufuku, K., et al. (2012). Experience with the first 50 ex vivo lung perfusions in clinical transplantation. The journal of thoracic and
cardiovascular surgery (144), S. 1200-1206.
Fildes, J. E., Archer, L. D., Blaikley, J., Ball, A., Stone, J., Sjöberg, T., et al. (2015). Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo Lung Perfusion Compared to
Standard Lung Transplantation. Transplantation Journal, 99 (5), 1078-1083.
Henriksen, I. S., Möller-Sörensen, H., Holdflod Möller, C., Zemtsovski, M., Nilsson, J. C., Seidelin, C. T., et al (2014). First Danish Experience with Ex Vivo Lung Perfusion of Donor Lungs Before
Transplantation. Danish Medical Journal, 61 (3), 4809-4814.
Lindtstedt, S., Hlebowicz, J., Koul, B., Wierup, P., Sjögren, J., Gustafsson, R., et al. (2011). Comparative Outcome of Double Lung Transplantation Using Conventional Donor Lungs and Non-
acceptable Donor Lungs Reconditioned Ex Vivo. Interactive Cardiovascular and Thoracic Surgery (12), 162-165.
Munshi, L., Keshavjee, S., & Cypel, M. (2013). Donor management and lung preservation for lung transplantation. The Lancet Respiratory Medicine (1), 318-328.
Sage, E., Mussot, S., Trebbia, G., Puyo, P., Stern, M., Dartevelle, P., et al. (2014). Lung Transplantation from Initially Rejected Donors After Ex Vivo Lung Reconditioning: The French Experience.
European Journal of Cardio-Thoracic Surgery (46), 794-799.
Sommerwerck, U., Rabis, T., Fleimisch, P., Carstens, H., Teschler, H., & Kamler, M. (2014). Lungentransplantation. Herz (39), 74-83.
Valenza, F., Rosso, L., Coppala, S., Froio, S., Palleschi, A., Tosi, D., et al. (2014). Ex Vivo Lung Perfusion to Improve Donor Lung Function and Increase the Number of Organs Available for
Transplantation. Transplant International (27), 553-561.
Van Raemdonck, D., Neyrinck, A., Verleden, G., Dupont, L., Coosemans, W., Decaluwe, H., et al. (2009). Lung donor selection and management. Proceedings of the American Thoracic Society (6), S.
28.
Wallinder, A., Ricksten, S. E., Silverborn, M., Hansson, C., Riise, G. C., Liden, H., et al. (2013). Early Results in Transplantation of Initially Rejected Donor Lungs After Ex Vivo Lung Perfusion: A Case
Control Study. European Journal of Cardio-Thoracic Surgery, 45 (2014), 40-45.
Warnecke, G., Moradiellos, J., Tudorache, I., Kühn, C., Avsar, M., Wiegmann, B., et al. (2012). Normothermic perfusion of donor lungs for preservation and assessment with Organ Care System before
bilateral transplantation: a pilot study of 12 patients. Lancet, 380, S. 1851-1858.
Zych, B., Popov, A. F., Stavri, G., Bashford, A., Bahrami, T., Amrani, M., et al. (2012). Early Outcomes of Bilateral Sequential Single Lung Transplantation After Ex Vivo Lung Evaluation and
Reconditioning. The Journal of Heart and Lung Transplantation (31), 274-281.
16th ECoPEaT, Barcelona, 1 October 2016

16. HIRSLANDEN AG
KLINIK HIRSLANDEN
WITELLIKERSTRASSE 40
CH-8032 ZÜRICH
THANK YOU
Mira Klein 16
MIRA KLEIN
ECCP, MAS IN CP, RN
MIRA.KLEIN@SWISSPERFUSION.CH
16th ECoPEaT, Barcelona, 1 October 2016

17. The Hirslanden Private Hospital Group:
Hirslanden Klinik Aarau - Klinik Beau-Site, Bern - Klinik Permanence, Bern - Praxiszentrum am Bahnhof, Bern - Salem-Spital, Bern
- AndreasKlinik, Cham Zug - Klinik Am Rosenberg, Heiden - Clinique la Colline, Genève - Clinique Bois-Cerf, Lausanne - Clinique
Cecil, Lausanne - Klinik St. Anna, Luzern - St. Anna am Bahnhof, Luzern - Hirslanden Klinik Meggen - Klinik Birshof,
Münchenstein Basel - Klinik Belair, Schaffhausen - Klinik Stephanshorn, St. Gallen - Klinik Hirslanden, Zürich - Klinik Im Park,
Zürich
www.hirslanden.ch
Mira Klein 1716th ECoPEaT, Barcelona, 1 October 2016