Extended Post EVLP Cold Preservation Increases Risk of Primary Graft Dysfunction and Mortality

PURPOSE EVLP allows for reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool. Standard cold preservation is followed by normothermic EVLP, then lungs undergo a second cold preservation prior to implantation. Paucity of data exist on how the sequence of cold-normothermic-cold preservations affect outcomes. We investigated the effects of preservation times in transplanted EVLP lungs. METHODS Data from the NOVEL trial (110pts) was retrospectively analyzed. Duration of the 3 preservation phases was measured: cold pre EVLP; EVLP; cold post EVLP. Donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD were calculated using Cox-proportional hazards and logistic regression models to adjust for baseline characteristics. RESULTS Using the highest quartile, pts were stratified in extended (>287 min, n=27) and non-extended (<287 min, n=89) cold post-EVLP time. Age, LAS, cold pre-EVLP, EVLP time, type of Tx, gender and recipient diagnosis were similar between groups. The rates of PGD ≥2-3 (20.5% vs 52%, p=0.002) and PGD 3 (8.4% vs 29.6%, p=0.005) at 72hrs post-Tx were increased in the extended group. The 1-year survival was lower for patients with extended cold post-EVLP (91.6% vs 70.4%, p=0.013) as was 3-year survival (75.9% vs 55.6%, p=0.023). After adjusting for age, LAS, diagnosis, cold pre-EVLP, donor smoking history, donor last PaO2, and type of Tx, the extended group remained an independent predictor of PGD ≥2-3 (OR: 6.35, 95% CI: 1.98-19.73, P=0.002) and PGD 3 (OR: 10.47, 95% CI: 2.2-49.9, P=0.003) at 72 hrs and of 1-year mortality (HR: 10, 95% CI2.35-39.9, P=0.001). Cold Pre-EVLP and EVLP time were not significant predictors of outcomes. CONCLUSION Extended cold post EVLP preservation (5 hrs or more) associated with risk for PGD and 1-year mortality. These findings from a multicenter trial should caution on the implementation of extended cold preservation post EVLP.