Beyond the ventilator: rethinking donor ventilation duration in lung transplantation

Lung transplantation remains the definitive therapy for end-stage pulmonary diseases; however, the lack of available donors restricts access and increases waitlist mortality. Duration of donor ventilation (DDV) refers to the total length of time a donor receives mechanical ventilation before organ procurement. A DDV of more than 7 days is considered a prolonged DDV (1). Concerns about an extended DDV is one reason for organ underutilization. Many centers reject lungs from donors who have received support for a long time because prolonged mechanical ventilation has historically been linked to ventilator-induced lung damage, ventilator-associated pneumonia, and systemic inflammatory reactions.

McCullough et al. retrospectively analyzed 7,856 adult lung transplants recorded in the United Network for Organ Sharing Standard Transplant Analysis and Research (UNOS STAR) database between 2006 and 2023 (1). Using propensity score matching to balance donor, recipient, and center variables, their results revealed no significant differences between groups with short and long DDV in terms of primary graft dysfunction, graft survival, and recipient survival up to 5 years. Additionally, continuous modeling of the DDV showed no crucial threshold linked to elevated risk. Those authors concluded that the DDV should not be considered a reason to reject donor lungs.

The UNOS STAR database, upon which this study is based, has the advantage of a massive amount of data, providing an important foundation for statistical analysis. However, its limitations cannot be ignored. For example, it lacks detailed information about the donor lung status (ventilation parameters, dynamic changes in oxygenation, bronchoscopic or imaging results, etc.), and these variables can significantly impact the research conclusions. In addition, the evolution of lung transplantation practices over different eras can also affect the generalizability of the research conclusions to some extent.

According to most current studies, the DDV has little effect on survival and complications in patients after lung transplantation. Both Sugimoto et al. and Hirji et al. reported no significant adverse impact of prolonged ventilation on graft survival (2,3). Jawitz et al. also found no correlation between the duration of donor brain death and transplant outcomes, reinforcing the idea that prolonged support does not necessarily equate to inferior grafts (4). Recent donor scoring systems also minimize the DDV as an outcome indicator. Using the Lung Donor Risk Index, validated in 2024, donor age, smoking history, ischemia time, and comorbidities were identified as major predictors of graft failure; however, the DDV was not found to be independently significant. Thus, the DDV is not currently considered a factor that affects lung transplant outcomes (5).

Currently, many methods are used to protect donor lungs, so the DDV alone does not directly affect prognosis. First, lung protective ventilation strategies have been shown to mitigate ventilator-induced injury and may explain the benign outcomes observed even with a prolonged DDV (2). Advances in lung protective ventilation, characterized by low tidal volumes, appropriate positive end-expiratory pressure, and minimization of barotrauma, have transformed donor management. Second, meticulous donor management is essential, which includes water balance control, positional drainage, and bronchoscopic toileting if required. Such basic donor management strategies are important to prevent or treat atelectasis and pneumonia. Finally, emerging donor lung protection technologies may improve outcomes in lung transplantation. Ex-vivo lung perfusion has been shown to enable safe transplantation of selected marginal lungs, including those exposed to prolonged ventilation (6,7). Storing donor lungs at 10 ℃ is also proven to be a superior donor lung preservation strategy (6,7). Advances in perioperative infection control have reduced the risk of lung infection brought on by a prolonged DDV (8).

Owing to donor lung shortage, maximizing the use of donor lungs is of paramount importance for patients with end-stage lung disease awaiting transplantation. In the United States and worldwide, hundreds of patients die annually while awaiting lung transplantation. Rejecting lungs solely on the basis of the DDV may unnecessarily exacerbate this crisis. Incorporating more nuanced donor evaluation metrics, such as the Lung Donor Risk Index, could better balance risk against the urgent need for organs. Professional societies, including the International Society for Heart & Lung Transplantation, have already begun shifting toward consensus-based, multifactorial approaches in their candidate and donor selection guidelines (8).

Although the evidence increasingly supports relaxing current DDV thresholds, future research on the DDV can focus on the following aspects. First, studies on lung injury biomarkers and lung protection techniques for donors may offer a theoretical foundation for expanding the pool of possible lung transplant donors. Second, because chronic lung allograft dysfunction is the main cause of late mortality, studies should explore whether the DDV contributes indirectly to chronic lung allograft dysfunction. Finally, studies including a larger sample size and that are based on more advanced algorithms, such as machine learning, can provide additional evidence for donor lung assessment.

McCullough et al. demonstrated that donor ventilation duration is not an independent factor in transplant outcomes. Their results confirm that the DDV should not be a reason to discard potential donor lungs. With the help of protective ventilation, advanced donor management, and ex-vivo perfusion, prolonged ventilation should no longer be considered a contraindication for transplantation. Discarding lungs on the basis of prolonged DDV may exacerbate the global organ shortage and deprive patients of life-saving transplants. Instead, more individualized, evidence-based research assessments are needed to safely and effectively expand the donor pool.

Acknowledgments

We thank Analisa Avila, MPH, ELS, of Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-51/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-51/coif). The authors have no conflicts of interest to declare.

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