Ex-vivo lung perfusion versus standard protocol lung transplantation—mid-term survival and meta-analysis

Abstract

Background: While extended criteria lung donation has helped expand the lung donor pool, utilization of lungs from donors of at least one other solid organ is still limited to around 15-30%. Ex-vivo lung perfusion (EVLP) offers the ability to expand the number of useable lung grafts through assessment and reconditioning of explanted lungs, particularly those not initially meeting criteria for transplantation. This meta-analysis aimed to examine the mid-to long-term survival and other short-term outcomes of patients transplanted with EVLP-treated lungs versus standard/cold-storage protocol lungs.Methods: Literature search of ten medical databases was conducted for original studies involving "ex-vivo lung perfusion" and "EVLP". Included articles were assessed by two independent researchers, survival data from Kaplan-Meier curves digitized, and individual patient data imputed to conduct aggregated survival analysis. Meta-analyses of suitably reported outcomes were conducted using a random-effects model. Results: Thirteen studies met inclusion criteria, with a total of 407 EVLP lung transplants and 1,765 as per standard/cold storage protocol. One study was a randomized controlled trial while the remainder were single-institution cohort series of varying design. The majority of donor lungs were from brain death donors, with EVLP lungs having significantly worse PaO 2 /FiO 2 ratio and significantly greater rate of abnormal chest X-ray. Aggregated survival analysis of all included studies revealed no significant survival difference for EVLP or standard protocol lungs (hazard ratio 1.00; 95% confidence interval: 0.79-1.27, P=0.981). Survival at 12, 24, and 36 months for the EVLP cohort was 84%, 79%, and 74%, respectively. Survival at 12, 24, and 36 months for the standard protocol cohort was 85%, 79%, and 73%, respectively. Meta-analysis did not find a significant difference in risk of 30-day mortality or primary graft dysfunction grade 3 at 72 hours between cohorts. Conclusions:There was no significant difference in mid-to long-term survival of EVLP lung transplant patients when compared to standard protocol donor lungs. The incidence of 30-day mortality and primary graft dysfunction grade 3 at 72 hours did not differ significantly between groups. EVLP offers the potential to increase lung donor utilization while providing similar short-term outcomes and mid-to long-term survival.

Minimizing Ischemia Reperfusion Injury in Xenotransplantation

“…Minimizing IRI by ex vivo organ perfusion has allowed expansion of the donor pool in allotransplantation, and specifically enabled safer use of DCD organs. In addition, there is considerable evidence that IRI minimization by machine perfusion of ‘marginal’ kidneys, lungs, and livers is associated with improved allotransplant outcomes ( 288 , 319 , 356 ). To the extent that the major injury mechanisms are shared between xenograft injury and allograft IRI, including complement activation, endothelial dysfunction, and a profound inflammatory response, it is logical that genetic engineering modifications targeting these mechanisms should also attenuate XIRI ( 27 , 146 , 147 , 155 , 325 , 326 ).…”

Evaluation of the efficacy of a novel perfusion solution for normothermic ex vivo lung perfusion compared with Steen solution™ (animal experimental study)

“…3. Динамический комплаенс ляции, контаминация больничной флорой, последствия неэффективной гемодинамики, агрессивная кардиореспираторная реанимация и прочие обстоятельства приводят к повреждению легких донора, в результате чего отвергается около 70% потенциальных легочных трансплантатов ввиду их непригодности, и всего лишь 20-30% расцениваются как пригодные к трансплантации [4,8,16]. Появление процедуры нормотермической перфузии донорских легких ex vivo открыло новые горизонты в развитии трансплантации легких во всем мире [17,18,23] [7,14,18].…”

“…Небольшое количество трансплантаций легких обусловлено сложностью хирургического вмешательства и в большей степени высокими требованиями, предъявляемыми к состоянию потенциального донора легких и непосредственно к качеству донорского органа, что в итоге приводит к значительному ограничению количества оптимальных доноров. Для обеспечения большей части пациентов, нуждающихся в пересадке легких, рассматривается возможность использова-ния легких от субоптимальных доноров [4]. Главным требованием к легким от субоптимальных доноров является функциональная способность обеспечивать достаточную оксигенацию крови реципиента [11].…”

“…ex lung perfusion -EVLP) [10,12]. Технология EVLP имеет широкое распространение в ведущих трансплантационных центрах Европы и Северной Америки, позволяет значительно расширить пул донорских легких и тем самым обеспечить большее количество пациентов, нуждающихся в трансплантации легких [2,4] Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases.…”

Lung Transplantation in Patients with Cystic Fibrosis

“…A lung donor score (LDS) based upon past medical history, smoking history, age, arterial blood gases, chest X-ray, and bronchoscopy findings, that accurately predicts the likelihood of organ acceptance and recipient mortality may facilitate donor risk assessment and patient selection [32]. Ex-vivo lung perfusion (EVLP) is now an established therapy to repair and evaluate marginal lungs for transplantation with comparable post-transplant outcomes [33][34][35].…”