The length of time donor lungs could be preserved prior to transplant could be safely extended to more than 12 hours--more than double the average 5-6 hour standard time [1]--without jeopardising recipient outcomes, by using a combination of cold preservation and a new technique called ex-vivo lung perfusion (EVLP), whereby the lung is kept alive outside the body and supported by a supply of oxygen and nutrients.
The new study, published in The Lancet Respiratory Medicine, found that patients who received a donor lung preserved for more than 12 hours had similar survival at 1 year post transplant to those who received lungs preserved for less than 12 hours. The findings suggest that this new approach could increase the availability of donor organs by reducing geographical limitations on donors and recipients, and enabling organs to be transported over longer distances to recipients further away than previously viable.
Currently, about 200 adults are waiting for a lung transplant in Canada, and over 1500 in the USA [1]. About a quarter of those on the waiting list will die before they receive a transplant. Lung transplantation requires the donor organ to be stored and transported from the donor to the recipient. Traditionally, donor lungs have been flushed and preserved at cold temperatures to reduce tissue decomposition during transport. But the generally accepted maximum time from when an organ is removed from the donor, cooled, and then transplanted into the recipient is 6 to 8 hours.
The recent development and use of EVLP around the world has completely altered the basic theory of lung preservation from slowing tissue death to preserving life, in order to allow and enhance recovery. This new technique involves continuously perfusing or pumping a bloodless solution containing oxygen, proteins, and nutrients into donor lungs to give doctors the opportunity to protect, assess and treat the lungs while they are outside the body and make them suitable for transplantation.
"We have been using EVLP as standard practice to assess high-risk donor lungs for the last decade and almost 300 patients have benefited from this technology at our centre to date", explains lead author Dr Marcelo Cypel, Thoracic Surgeon at Toronto General Hospital, University of Toronto, Toronto, Canada. "Donor lungs are transported cold to the hospital where they are warmed, evaluated and then cooled again until they are transplanted into the recipient. Because assessing the lungs using EVLP takes at least 4 hours, total preservation times have regularly exceeded 8 hours."[2]
Intrigued by the technique's possibilities for extending overall preservation times, Cypel and his team retrospectively examined data on the outcomes of 906 patients (aged 18 or older) who received a lung transplant at Toronto General Hospital between 2006 and 2015. They compared patients who had received a lung that had been preserved (i.e. the sum of cold preservation and normal temperature EVLP) for more than 12 hours (97 patients; 95% donor organs underwent EVLP) with those who were given lungs preserved for less than 12 hours (809; 5% underwent EVLP).
They found that despite the use of higher-risk lungs in the more than 12-hour group, the average length of time recipients spent in the intensive care unit and in hospital post-transplant were similar in both groups (table 2). Additionally, the life-threatening complication of immediate graft dysfunction and survival at 1 year did not differ between the two groups (figure 2). Further analysis also showed that cold preservation and EVLP time did not affect survival (table 4). Older recipient age was the only factor that was linked with reduced survival.
"It is important to remember that the lungs preserved for more than 12 hours using EVLP started out as more injured lungs. In fact, many of them might have been turned down for transplantation in the past. That they performed similar to conventional lungs with shorter preservation times suggests EVLP provides additional benefit over cold preservation", says first author Dr Jonathan Yeung, also from Toronto General Hospital [2].
The authors point to several limitations including the study's retrospective nature and the fact that it was conducted at a single institution. Additionally, the maximum safe preservation time for human lung transplantation remains unknown. They say that clinical trials are now needed to understand the optimum combination of cold and normal temperature EVLP lung preservation methods.
According to Dr Cypel, "At a time when there is a critical shortage of lungs available for transplantation, combining cold preservation and EVLP will hopefully make a lot more donor lungs available for successful transplantation. This approach has allowed our Toronto-based programme to essentially abolish any geographical boundaries to donor lung retrieval in North America. The safe extension of preservation time not only has the potential to give clinicians extra time to evaluate, but also to treat and recondition donated organs that would otherwise not be used. Extra preservation time also allows additional flexibility in planning recipient surgery and gives more time to transport the donor lung from the EVLP site to the recipients' operating room."[2]
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NOTES TO EDITORS:
Jonathan C Yeung (JCY), Thorsten Krueger (TK), Shaf Keshavjee (SK), and Marcelo Cypel (MC) conceived the study and contributed to its design. All authors participated in the acquisition, analysis, and interpretation of data. JCY, Thomas K Waddell (TKW), and MC contributed to the statistical analysis. JCY, SK, and MC contributed to drafting the paper. MC, TKW, and SK are co-founders of Perfusix Canada, XOR Labs Toronto, and consultants for Lung Bioengineering, United Therapeutics.
[1] Data from United Network for Organ Sharing, USA https://www.unos.org/
[2] Quotes direct from authors and cannot be found in text of Article.
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Journal
The Lancet Respiratory Medicine