Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs

Abstract

Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.

Taking a Deep Breath: an Examination of Current Controversies in Surgical Procedures in Lung Transplantation

“…Mesenchymal stromal (stem) cells and their extracellular vesicles have also been proposed as a therapeutic for reconditioning ECD lungs and ameliorating ischemia-reperfusion injury [ 83 , 84 ]. Furthermore, novel approaches to improve EVLP are actively being investigated, such as negative pressure ventilation (NPV) and sub-normothermic temperatures to overcome some of the ventilator and metabolic injuries sustained during EVLP [ 85 , 86 ].…”

Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review

“…The aim was to develop a form of ESLP that reduced the incidence of ventilator-induced lung injury (VILI)-a mechanically induced pulmonary edema caused by high respiratory pressures and a documented consequence of prolonged PPV-ESLP [157][158][159]. A recent clinical trial demonstrated that NPV is safe when used to recondition extended criteria donor lungs from transplantation [160].…”

“…In 2020, Buchko et al established the clinical safety and feasibility of EVOSS technology through a single-center clinical trial of NPV-ESLP whereby twelve extended criteria donor lungs were successfully reconditioned and transplanted into recipients, resulting in 100% 30-day and 1-year survival [160]. Recruitment took place between October 2018 to July 2019.…”

A Computer Stereo Vision Method For Regional Dynamic Compliance Measurement During Ex-Vivo Lung Perfusion

“…Conceptually, it is the rate of change of the lung volume with respects to the applied pressure. For NPV, it can be found using (1).…”

“…Lung transplantation remains the best treatment option for end stage severe pulmonary conditions, such as pulmonary fibrosis caused by SARS-COVID-2 [1]. Unfortunately, this treatment option is underutilized in part due to high rates of donor lung rejection over concerns of transplant viability.…”