Should Donor Ventilator Duration Even Be on our Radar?

The ability to fine-tune donor selection criteria in lung transplantation remains an ever-evolving and moving target. Unlike kidney transplantation, which is highly quantified and predictive, lung transplant donor quality is significantly more multimodal and relies much more on clinical intuition. Hence, there continues to be variability in standards among programs regarding which lungs are considered transplantable. Several scoring systems to date have been published, including but not limited to the Oto Donor Score,1 and the United Network for Organ Sharing-Maryland Score.2 Recently, validation studies of the available scores have shown construct validity as they correlate with relevant outcomes such as 1- and 12-mo survival, yet the time-dependent area under the curve for these scores ranges on the order of only 0.6, indicating a relatively limited ability to discern good from marginal donors.3 These limitations have led investigators to search for missing aspects of donors, which may better alert clinicians to which donors are acceptable. One of the more contentious of these variables has been the duration of mechanical ventilation for a prospective donor. Several decades of clinical research in critical care have revealed the double-edged sword of mechanical ventilation. Although it clearly can save lives, positive-pressure ventilation is not physiologic, and even when perfectly used can lead to barotrauma and volutrauma, subsequently triggering a myriad of downstream forms of lung injury. As a result, the time a donor has been on a ventilator is often considered as part of the selection calculus with the notion that longer is worse. Encouragingly, a recent United Network for Organ Sharing registry study with 17 y of data shows that donor ventilation >7 d was not associated with survival even out to 5 y post–lung transplant.4 Although registry data can give us broad safety signals, it may miss more nuanced findings. What remains unaddressed is the extent to which donor ventilation time impacts potential recipient lung function. In this edition of Transplantation, the effect of donor ventilation on subsequent recipient lung function is addressed. Fioretti et al5 from the University of Alberta report here a study in which donors ventilated for 5 d. Their main outcome was lung function measured by spirometry. With a total cohort of 588 patients, they did not find any discernible effect on either absolute or predicted forced expiratory volume in 1 s at 1 y posttransplant. This is the most robust study on donor ventilation and recipient lung function to date and is consistent with what is already known about donor ventilation time and overall survival. The findings of this article importantly show that we should not be quick to dismiss lung transplant donors simply because of ventilation time. Does this mean that we should never worry about ventilator time? Unfortunately, this question does not have a simple answer. Both very large-scale registry studies and more focused single-center studies are limited by the issue of survivorship bias. In other words, donors made it to the point of offer acceptance had good transplant outcomes. What we can never get from these studies is the outcomes of donors who never made it to the point of organ transplant. Although this may not be a factor in Alberta, Canada, it could lead to unanticipated issues when applied to systems with more complexity, such as those in Europe or the United States. In the case of the study reported here, Alberta is 1 of only 4 main centers in a country with very low population density. In Canada, the allocation occurs at the regional level and is based on a limited number of status designations. This allows a center such as Alberta to highly curate which donors they choose. Conversely, the adoption of continuous distribution in the United States in 2023 dramatically changed the landscape of lung transplantation. Within the composite allocation score (CAS), only 10% of the score is devoted to travel and proximity. Since the CAS went live, travel distances for donor lungs in the United States have nearly doubled, and presumably have made it more complicated for individual programs to work directly with local organ procurement agencies to take a contemplative and holistic approach to each donor.6 In the United States, organ procurement centers face incentives to place lungs. The Centers for Medicare and Medicaid Services 2020 final rule rewards transplant volume rather than outcome. Furthermore, the Organ Procurement and Transplantation Network flags lung transplant programs that accept fewer lungs than expected. Therefore, there are policy headwinds that may compel programs to accept marginal donors already. From our own center’s experience, the unprecedented increase in donor offers after CAS has made it virtually impossible to use donor ventilation time as a major criterion for lung selection. In Europe, several distinct allocation systems exist, ranging from country-specific systems, such as England, to broader consortiums, such as Scandiatransplant. These European systems generally mirror the original lung allocation score system, but, importantly, are also evolving. France, for example, has moved to a system that incorporates some degree of continuous distribution.7 As a result, they have improved transplant access more broadly, but may have limited their individual centers from finely scrutinizing every aspect of a potential donor. Collectively, it is important to recognize that region-specific allocation rules—that are always subject to change—can create scenarios in which donor ventilation time no longer becomes a major variable in donor selection decisions.