Protective Mechanical Ventilation in Organ Donors: A Lifesaving Maneuver.

Lung transplantation has become an effective lifesaving intervention for patients with end-stage lung disease. However, the number of available organs does not meet the current demand, with only around 15–25% of lungs being procured from potential donors (1), leading to persistently high mortality rates on the waiting list. Thus, strategies to enhance lung procurement have been suggested as means to reduce the mismatch between organ demand and supply (2) and include extended lung-donor selection criteria (1), ex vivo lung perfusion (EVLP) (3), and optimization of donor management (4).

Use of extended lung-donor selection criteria may easily increase the availability of organs within the donor pool. Nonetheless, it may increase the risk of post–lung transplantation primary graft dysfunction, which occurs in about 20% of recipients and is associated with increased morbidity and mortality (5). EVLP has shown excellent reliability for donor lung assessment. Organs that would be declined for transplantation according to standard criteria can be maintained viable for up to 6 hours in clinical settings but up to 24 hours in experimental conditions. This allows a rigorous anatomical, mechanical, functional, and biological evaluation of the donor lung properties, which can more accurately inform the risk–benefit profile of transplantation. This approach has resulted in an impressive increase in the number of lung transplantations worldwide with encouraging long-term outcome (6). However, EVLP is a complex strategy and requires specific skills and advanced resources.

Optimizing management of the lung in the donor may be the strategy that can provide the greatest expansion in organs suitable for transplant without significant increase in resource utilization. Potential lung donors are prone to develop acute lung injury from the exposure to a series of potential mechanical and inflammatory insults, including brain death, atelectasis, lung trauma, aspiration pneumonitis, and ventilator-associated pneumonia (7, 8). These conditions make donor lungs particularly vulnerable and susceptible to the so-called ventilator-induced lung injury (VILI) (9). Mechanical ventilation, although necessary in donors to ensure adequate oxygenation to protect organs potentially suitable for transplant, can itself cause lung injury from excessive regional alveolar stress and strain and tidal recruitment, with the consequent exacerbation of pulmonary and systemic inflammation (9). Lung-protective mechanical ventilation strategies aiming to avoid VILI can hence potentially determine a great impact on lung availability for transplantation.

A prior landmark randomized clinical trial (10) implementing low Vt (6–8 ml/kg of predicted body weight [PBW]), higher positive end-expiratory pressure (PEEP; 8–10 cm H2O), and derecruitment preventive strategies (inline suctioning and continuous positive airway pressure during the apnea test) showed increased rates of organ procurement with similar survival rates. However, the trial was stopped earlier than planned, thereby introducing an important bias in the analysis of its findings.

In this issue of the Journal, Mal and colleagues (pp. 250–258) assessed in organ donors the impact of lung-protective ventilation, defined as PEEP ≥8 cm H2O and Vt ≤8 ml/kg PBW, on the rate of lung procurement and recipient survival (11). The authors carried a nationwide cohort observational study in France, including brain-dead donors with at least one procured organ, mainly focusing on respiratory management. The association between lung procurement and lung-protective ventilation was assessed by multivariate logistic regression analysis stratified by propensity score quintiles, and recipient survival was assessed at 1 year.

The study population included 1,626 potential lung donors, out of which 1,109 (68%) had at least one lung proposed for transplant, and 678 (61%) then proceeded to lung procurement. Interestingly, only 25% of donors were ventilated with a protective ventilation strategy as described. The majority of potential donors (53%) were ventilated with PEEP <8 cm H2O, and around 13% had PEEP <8 cm H2O and Vt >8 ml/kg PBW. After adjusting for confounders and propensity score, the chance of lung procurement was significantly higher (odds ratio, 1.43; 95% confidence interval, 1.03–1.98; P = 0.03) in the group receiving protective ventilation. Lung transplant recipient survival did not differ according to the use or not of lung-protective ventilation.

These results from a large multicenter cohort of patients are clinically very important because they confirm the findings of the randomized controlled trial conducted by Mascia and colleagues (10). It is therefore now established that avoiding VILI in organ donors with the delivery of lung-protective mechanical ventilation significantly increases the number of lungs suitable for lung transplantation. Considering the low percentage of organ donors receiving lung-protective ventilation in this observational study (about 25%), the delivery of optimal mechanical ventilation settings could potentially result in a remarkable increase of donor lung procurements.

However, the best strategy to avoid VILI in this population needs further investigation.

It is still unclear whether the improvement in organ procurement is associated with the combination of lower Vt and higher PEEP or to the separate effect of each component. In this regard, the study of Mal and colleagues failed to show increased organ procurement rates in the complementary analysis using Vt ≤8 ml/kg PBW alone as definition of protective ventilation. The consequent change in sample size in this complementary analysis may explain the different findings, as mentioned by the authors. Alternatively, these results may indicate that reducing the risk of regional alveolar overdistension by limiting Vt alone may not be sufficient to protect donor lungs from VILI. Instead, avoiding atelectasis with higher PEEP may provide the main benefit. Indeed, several experimental evidences demonstrate that the presence of atelectasis in donor lungs, especially during the time of cold static preservation, results in worst pulmonary function, likely from the deleterious consequences of localized parenchymal hypoxia. In addition, avoiding atelectasis results in a more homogeneous distribution of the mechanical forces during artificial ventilation, thereby reducing the risk of regional overdistension. Even safe levels of alveolar distending pressure can be converted into locally injurious stress by the presence of areas of atelectasis and lung inhomogeneity (12). In this regard, a very effective strategy to improve lung recruitment and reduce alveolar inhomogeneity is prone positioning, a strategy that should be further investigated in multiorgan donors.

In a large body of clinical and experimental evidences, prone positioning has been demonstrated to be beneficial during mechanical ventilation for patients with acute respiratory distress syndrome in improving oxygenation, in reducing VILI, and improving survival (13). In a recent preclinical study, we demonstrated in a pig model of lung donation after cardiac death that prone positioning during warm ischemic time prevented lung atelectasis, inflammation, and cell death, leading to significantly improved lung function during EVLP (14).

Mal and colleagues should be congratulated for confirming in a large cohort study the evidence of VILI in potential organ donors. Future research needs to focus on rapidly identifying the best strategy to avoid VILI in this population to ultimately improve outcomes of patients with end-stage lung diseases.