Flow-controlled ventilation during EVLP improves oxygenation and preserves alveolar recruitment

Abstract

Background Ex vivo lung perfusion (EVLP) is a widespread accepted platform for preservation and evaluation of donor lungs prior to lung transplantation (LTx). Standard lungs are ventilated using volume-controlled ventilation (VCV). We investigated the effects of flow-controlled ventilation (FCV) in a large animal EVLP model. Fourteen porcine lungs were mounted on EVLP after a warm ischemic interval of 2 h and randomized in two groups (n = 7/group). In VCV, 7 grafts were conventionally ventilated and in FCV, 7 grafts were ventilated by flow-controlled ventilation. EVLP physiologic parameters (compliance, pulmonary vascular resistance and oxygenation) were recorded hourly. After 6 h of EVLP, broncho-alveolar lavage (BAL) was performed and biopsies for wet-to-dry weight (W/D) ratio and histology were taken. The left lung was inflated, frozen in liquid nitrogen vapors and scanned with computed tomography (CT) to assess regional distribution of Hounsfield units (HU). Results All lungs endured 6 h of EVLP. Oxygenation was better in FCV compared to VCV (p = 0.01) and the decrease in lung compliance was less in FCV (p = 0.03). W/D ratio, pathology and BAL samples did not differ between both groups (p = 0.16, p = 0.55 and p = 0.62). Overall, CT densities tended to be less pronounced in FCV (p = 0.05). Distribution of CT densities revealed a higher proportion of well-aerated lung parts in FCV compared to VCV (p = 0.01). Conclusions FCV in pulmonary grafts mounted on EVLP is feasible and leads to improved oxygenation and alveolar recruitment. This ventilation strategy might prolong EVLP over time, with less risk for volutrauma and atelectrauma.

Flow-controlled ventilation – a new and promising method of ventilation presented with a review of the literature

“…Furthermore, FCV has been used for preservation of donor lungs during ex vivo lung perfusion (EVLP). FCV led to improved oxygenation and alveolar recruitment compared with VCV, with a higher proportion of well-aerated and less atelectatic lung areas [ 46 ]. Therefore, FCV may be a potential strategy to prolong EVLP over time.…”

The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs

“…MVe settings impact PGD development, most likely through volu- and atelectrauma. FCV improved oxygenation, lung compliance and wet-to-dry ratio ( 88 – 90 ). NPV reduces secretion of pro-inflammatory cytokines and PGD rates in clinical studies ( 92 , 93 ).…”

“…show that in a porcine EVLP model, FCV provides significantly better oxygenation and improved lung compliance in a larger area of ventilated lung tissue. Despite these superior functional results, total lung injury did not differ in comparison to volume controlled ventilation ( 90 ).…”

Expanding Donor Options for Lung Transplant: Extended Criteria, Donation After Circulatory Death, ABO Incompatibility, and Evolution of Ex Vivo Lung Perfusion

“…For example, Ali et al 121 recently demonstrated that with repeated EVLP and cold ischemic preservation, they could extend total preservation time to 3 d. Other experiments have demonstrated that EVLP time can be extended by modifying aspects of EVLP protocols such as ventilator settings, perfusate composition, perfusion flow, temperature, and supplemented nutrients. [122][123][124][125][126][127][128] If this concept of extended EVLP for prolonged graft preservation can be successfully demonstrated in clinical EVLP, it would be absolutely advantageous for broader graft sharing. Additionally, acutely damaged lungs, for example, from an active infection, aspiration, or traumatic injury, raise substantial concerns for favorable transplant outcomes and cannot be used for transplant currently.…”