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Comment & Response
March 25, 2020

Should All Donors Be Treated by Ex Vivo Lung Perfusion?—Reply

Author Affiliations
  • 1Toronto Lung Transplant Program, University Health Network, Toronto, Ontario, Canada
JAMA Surg. Published online March 25, 2020. doi:10.1001/jamasurg.2020.0049

In Reply We thank Tian et al for their letter and interest in our article.1 We agree with the authors that ex vivo lung perfusion (EVLP), regardless of platform, has consistently been shown to provide short-term outcomes similar to those of conventional lung transplantation.2,3 In our article, we focused on the longer-term outcomes, and these too were similar between EVLP-treated and non-EVLP donor lungs.

One of the questions raised in the letter was whether the donor lungs we placed on EVLP were truly marginal given that the preprocurement arterial oxygen tension/inspired oxygen fraction (P/F) ratio was a median of 348 mm Hg, and what was the outcome of donor lungs with a P/F ratio of less than 300 mm Hg. We had 65 donor lungs in the EVLP group and 47 donor lungs that were transplanted directly with a P/F ratio of less than 300 mm Hg at the time of procurement. There were no significant differences in allograft survival when we compared the greater than 300 mm Hg and less than 300 mm Hg groups (log-rank, 0.38 for EVLP-treated lungs and 0.68 for non-EVLP lungs).

In our experience, P/F ratio alone is not a good prognosticator of donor lung function after lung transplant, and 42% of donor lungs (47 of 112) in our study with a preprocurement P/F ratio less than 300 mm Hg were actually transplanted without EVLP. We therefore completely agree with the notion that using a low P/F ratio alone to decline donor lungs is not advisable and will lead to underuse of donor lungs. However, low P/F ratio is not the most common reason lung transplant centers decline lungs. A very large subset of donor lungs is declined for transplant, even with P/F greater than 300 mm Hg, owing to many risk factors such as confirmed or suspected aspiration, trauma, infection, blood clots in pulmonary circulation, and macroscopic or imaging abnormalities. We have been able to expand use of donor lungs for these indications. In addition, we have been able to prolong wait times to death in deceased-after-cardiac-death donors to up to 3 hours because EVLP allows us safe assessment of the function of the donor lungs. We have also started using uncontrolled deceased-after-cardiac-death donors where EVLP enables proper assessment of the function of these lungs that would otherwise not be transplantable. With the help of EVLP, we have been able to increase our lung transplant numbers significantly and have now been able to offer lung transplantation for more than 200 patients this year alone and essentially eliminated wait-list mortality.

With regards to the other question posed by the authors, we do not believe EVLP should be standard of care for all donor lungs at this stage, given its complexity and elevated costs in the absence of evidence to support that EVLP improves the outcomes of standard-criteria donor lungs. However, EVLP does allow for organ-specific treatment of the donor prior to transplant, and as we develop treatment strategies to modify donor lungs on EVLP, we may reconsider expanding use of this technology to all donors aiming at improving short-term and long-term outcomes of patients receiving this life-saving procedure.

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Article Information

Corresponding Author: Jussi M. Tikkanen, MD, PhD, Toronto General Hospital, 200 Elizabeth St, Toronto, ON M5G2C4, Canada (jussi.tikkanen@mail.utoronto.ca).

Published Online: March 25, 2020. doi:10.1001/jamasurg.2020.0049

Conflict of Interest Disclosures: Dr Cypel reported personal fees from Lung Bioengeneering, other support from Perfusix Canada, and in kind support from Xvivo Perfusion during the conduct of the study. No other disclosures were reported.

References
1.
Divithotawela  C, Cypel  M, Martinu  T,  et al.  Long-term outcomes of lung transplant with ex vivo lung perfusion.  JAMA Surg. 2019;154(12):1-9. doi:10.1001/jamasurg.2019.4079PubMedGoogle Scholar
2.
Tikkanen  JM, Cypel  M, Machuca  TN,  et al.  Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation.  J Heart Lung Transplant. 2015;34(4):547-556. doi:10.1016/j.healun.2014.09.044PubMedGoogle ScholarCrossref
3.
Warnecke  G, Van Raemdonck  D, Smith  MA,  et al.  Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study.  Lancet Respir Med. 2018;6(5):357-367. doi:10.1016/S2213-2600(18)30136-XPubMedGoogle ScholarCrossref
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