Ex Vivo Lung Perfusion Resuscitated Donor Lungs and Subsequent Acute Rejection and Airway Complications: A Systematic Review and Meta-Analysis
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PURPOSE: Ex Vivo Lung Perfusion (EVLP) resuscitates donor lungs for use in lung transplant. Acute rejection can occur in more than 30% of all lung transplant recipients and is a risk factor of chronic allograft dysfunction, which is the primary cause of long-term morbidity and mortality in recipients. Airway complications can occur in up to 18% of recipients, with a risk factor being prolonged hypo-perfusion or ischemia to the bronchus. A published systematic review and meta-analysis comparing clinical benefits and complications for EVLP resuscitated donor lungs has not been identified. METHODS: We conducted a systematic review in MEDLINE, Clinicaltrials.gov, and Cochrane from database inception through August 2019 of studies which included EVLP and non-EVLP comparisons, assessed risk of bias using the Newcastle-Ottawa scale, performed meta-analyses for primary outcomes with forest plots and evaluated the certainty of the evidence (CoE) with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Twelve cohort studies included the use of EVLP to resuscitate human donor lungs for transplantation. When compared with non-EVLP, EVLP may result in little to no difference in acute rejection (Relative Risk [RR]: 0.95, 95% confidence interval (CI) 0.82-1.09; low CoE) or Primary Graft Dysfunction (PGD) grade 3 at 72 hours (RR: 0.99, 95% CI 0.56-1.75, low CoE). Additionally, when compared with non-EVLP, we are very uncertain about the effects of EVLP on airway complications (RR: 1.83, 95% CI 0.65-5.17; very low CoE) or one-year post-transplant survival (RR: 1.00; 95% CI 0.95-1.05, very low CoE). The overall body of evidence was rated as low certainty. (Table) CONCLUSION: Acute rejection and PGD outcomes are similar for EVLP and non-EVLP, and airway complications and one-year post-transplant survival do not show certain harm, suggesting EVLP as a promising intervention to increase patient access to transplant.