Effect of Cold Ischemic Time on the Incidence of High-Grade Primary Graft Dysfunction (PGD): A Multicenter Analysis

Abstract

Prior studies have explored the effects of cold ischemic time on survival but its effect on PGD is unclear. The current study analyzed an international multicenter ECLS in lung transplantation registry to clarify the effects of cold ischemic time on PGD. The ECLS in lung transplantation registry includes data on bilateral lung transplants from 8 high volume (>40 transplants/yr) transplant centers (2 from Europe, 6 from United States). This registry excludes single lung transplants and multi-organ transplants and the current analysis excluded Ex Vivo Lung Perfusion (EVLP) cases. We defined primary graft dysfunction according to the 2016 ISHLT consensus document and considered PGD3 at time 48 or 72 hours as high-grade primary graft dysfunction (PGD). We defined cold ischemic time as the interval between donor cross clamp (cardiac arrest for donation after circulatory death cases) and the longest reperfusion time in the recipient. We explored the effect of the cold ischemic time on PGD and death within 90 days using univariate and multivariate logistic regression analysis. We identified 511 entries with complete ischemic times between January 2016 and August of 2019. The overall incidence of PGD was 30.7%. The mean cold ischemic time in the group that developed PGD was 406 minutes and 428 minutes in the group that did not develop PGD. Univariate regression analysis showed no effect of ischemic time on the incidence of PGD (P=0.12). ROC analysis yielded an area under the curve for cold ischemic time and PGD of 0.55 further suggesting that cold ischemic time was poorly predictive of PGD. Our adjusted analysis showed no effect of total ischemic time on PGD (P=0.75). Finally, both univariate and multivariate analysis failed to show significance for the effect of total ischemic time on death within 90 days (P=0.33 and P=0.54, respectively). In a large multicenter registry, we could not identify an effect of duration of cold ischemic time on incidence of PGD or 90-day mortality. Practitioners should avoid using cold ischemic times in isolation to accept or decline a potential organ, although its effects on early reperfusion and long-term graft function require further study as does the extent of tolerable cold ischemia.