Ex Vivo Lung Perfusion for Preserving Donated Lungs
December 9, 2016 | Emerging Technology Reports
Proprietary names: XVIVO Perfusion System™ (XPS™), STEEN Solution™, XVIVO Organ Chamber™, VivoLine® LS1, TransMedics™ Organ Care System, OCS™ Lung, Lung Assist.
Generic names: Ex vivo lung perfusion (EVLP), lung in a box, machine perfusion, normothermic perfusion, organ care system, organ assist.
For patients with end-stage lung disease, lung transplant is the only life-saving therapy.1-3 The most common conditions resulting in end-stage lung disease are chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis.2 Patients are typically referred for lung transplant when their estimated chance of surviving an additional 24 to 36 months is lower than 50% and despite optimal medical treatment have symptoms similar to those of patients with New York Heart Association Class III and IV heart failure.2
Annually, the number of lung transplant candidates exceeds the number of lungs available for transplant, and more patients are added to the lung transplant waiting list than transplants performed.1,4 As a result, 20% to 30% of patients on the lung transplant waiting list die each year waiting for suitable lungs.1,4,5 Two main factors contribute to this disparity: (1) an increase in lung transplant candidates while donor rates remain unchanged and (2) low utilization rates of donated lungs because of stringent donor-selection criteria due to limitations of the standard lung-preservation method, cold static storage (CSS).
CSS preserves lungs at hypothermic conditions (1°C to 4ºC). After lung harvest, expedient (within minutes) lung preservation is critical for reducing lung injury and preserving lung function.1,5,6 CSS reduces lung metabolic function to 5% to 10% of normal, substantially reduces the organ's cellular functions, and reduces the donor tissue's need for oxygen.3,5 However, anaerobic metabolism is ongoing, and storage time exceeding four to six hours predisposes the donor lung to ischemia-reperfusion injury and increases the risk of primary graft dysfunction, which is the largest contributor to early death after transplant.1
When a potential lung donor is identified, a lung-transplant team member travels to the donor hospital to assess the donor lungs.7 Transplant surgeons assess donor lungs from brain death and controlled cardiac death donors during donor end-of-life treatment and after donor death.6,7 To assess donor lungs, transplant surgeons perform a bronchoscopy and assess donor lungs for infection, good gas exchange, and healthy appearance on chest radiographs and chest computed tomography scans.6,8 If the lungs are considered suitable for transplant after the initial assessment, the transplant surgeon performs an intraoperative evaluation after the donor's death to examine the pleural space and the lungs for lung trauma that could not be otherwise visualized, bullous disease, or a mass lesion.6 The final decision for lung harvest depends on the transplant surgeons' overall judgement of lung performance.9,10
To place donor lungs in CSS, after donor death the transplant team first systemically administers heparin to prevent coagulation1 and a vasodilator to reduce blood pressure8 and then flushes the lungs with cold preservation solution (e.g., Perfadex®).1,7 To improve oxygenation and clear any blood clots, red blood cells, or fat emboli, the transplant team flushes the lungs with preservation solution in anterograde (infusion through the pulmonary artery) and retrograde (infusion starting at the pulmonary veins) directions.7 Most centers use a perfusion volume of 60 mL/kg, and the process takes about five minutes.1,7 To reduce damage from warm ischemic time, the team fills the pleural cavity with ice crystalloid solution while flushing the lungs.7 The procurement team then inflates the excised lungs to an inspired oxygen concentration of 30% to 50% before placing the lungs in CSS.1
Approximately 80% of donor lungs are unsuitable for transplant partly because of CSS's limitations. Lungs sustain injuries during donor end-of-life care (from aspiration, resuscutation attempts, ventilation) and after donor death (e.g., neurogenic edema,inflammatory responses).1,3,10 Transplant teams cannot reassess lungs in CSS and cannot predict how marginal-quality lungs and lungs that sustained injuries will perform until after transplant. Additionally, lungs in CSS cannot recover from injuries sustained during donor end-of-life care.9,10 Therefore, lung procurement teams adopt a conservative approach9,10 for lung selection and decline marginal-quality lungs because of high complication rates for patients who receive poor-performing lungs.4,11
Stringent donor selection criteria also contribute to low donor-lung utilization rates. Most lung transplant centers continue to use donor selection guidelines established in 19939,12 despite a 2003 pulmonary council of the International Society for Heart and Lung Transplantation (ISHLT) consensus report suggesting the need to expand donor criteria.1,11,12 To increase the donor pool, some transplant centers have independently leveraged their experience and expertise to relax one or more conventional donor selection criteria.6,7 As a result, donor selection criteria remain grounded in the 1993 guidelines but often vary among transplant centers.1,4,6
In 2012, according to the Scientific Registry of Transplant Recipients, 1,783 lung transplants were performed and 2,186 new candidates were added to the lung transplant list.5,13,14 As of December 31, 2012, 1,616 patients remained on the lung transplant list, of whom 317 became inactive (no longer eligible for a lung transplant).13 In the same year, approximately 6,500 donor lungs were declined for transplant. In the United States, the number and age of lung transplant candidates added to the lung...