Impact of Cold Ischemic Time on Morbidity and Mortality after Lung Transplantation. An Updated Analysis of the International Multicenter Extracorporeal Life Support in Lung Transplantation Registry

Purpose Cold ischemic time (CIT) may adversely affect clinical outcomes after lung transplantation (LTx). Most centers restrict CIT to less than 6-8 hours. However, to improve donor utilization, centers are increasingly pushing the envelope of CIT. To clarify the effect of CIT on graft function and clinical outcomes, we analyzed the international multicenter ECLS in LTx registry. Methods the ECLS registry collects LTx data from 6 US and 2 European centers between January 2016 and March 2020. Single LTx, ex vivo lung perfusion, and multiple organ transplants were excluded. CIT was analyzed as a continuous variable and divided in balanced tertiles. The reperfusion of the second lung was considered the end of the CIT. Models were adjusted by 11 clinical factors. Our endpoints were PGD at T0, T24, T48 and T72 hours according to the 2016 ISHLT consensus. Length of stay, death within 90 days and at one year of follow-up was investigated. A univariate and multivariate analysis was performed. Pearson correlation analysis was used to assess effect of CIT on length of stay (LOS). Results The inclusion criteria were met by 798 patients. The mean and median CIT was 418 and 397 min, respectively. Adjusted analysis suggests that total CIT was not associated with PGD grade 3 at 48 and 72 hours (OR1.24, 0.87-1.75). However, CIT was associated with several other markers of graft dysfunction and resource utilization including PGD3 T0 (OR1.5, 1.06-2.13), tracheostomy (OR1.93, 1.3-2.87), post-op ECMO (OR3.47, 2.21-5.45), renal failure requiring dialysis (OR1.8, 1.13-2.86), death within 90 days (2.41, 1.42-4.09), death in hospital (OR2.53, 1.47-4.35), and death within one year (OR 2.37, 1.43-3.94). Total ischemic time was also independently associated with LOS (P Conclusion In a multicenter international registry, increasing CIT was associated with increased PGD at T0, higher postoperative morbidity and worse first year survival. Although patients can be transplanted with extended cold ischemic times when absolutely needed, this practice is associated with greater resource utilization and likely impact on survival.