More on use of DCD lungs: defining the limits for warm ischemic time

Most lung transplant centers using lungs donated after cardiac death (DCD) currently limit the interval from withdrawal of life supporting therapy (WLST) to when the lungs are flushed to a maximum of 60 minutes. This is on the assumption, extrapolating from other organs, that the duration of agonal phase, plus the warm ischemic time (defined as beginning when the systolic blood pressure is less than 50mm HG) negatively influences post-transplant lung function and survival.

Some recent literature however has suggested that lungs can be successfully transplanted even if warm ischemic time is extended to 120 minutes from the withdrawal of life support. (Krutsinger et al, 2015, Reeb et al, 2016)^{(1) (2)}

A comprehensive data-mining analysis of 507 DCD lung transplants from the ISHLT DCD Lung Transplant Registry throws further light on this issue (Levvey et al, 2019)⁽³⁾. Their data show that overall post-transplant survival of DCD lungs at 30-day and one year were excellent: 96% and 90% respectively. Survival was not statistically different according to agonal or WIT category or when three increasing intervals of WIT duration were taken into account. The authors conclude, “there was no obvious effect of the duration of donor agonal time and WIT on 30- and 365-day survival” and “for Category III DCD LTx, the limits of tolerability of agonal time and warm ischemia are beyond 60 minutes”.

These clinical findings are reinforced by a new laboratory study (Charles E J et al, 2018)⁽⁴⁾ on lungs from pigs which underwent hypoxic cardiac arrest, followed by 60, 90, or 120 minutes of warm ischemia before procurement and then by four hours of normothermic ex-vivo lung perfusion (EVLP). Their findings indicated that longer warm ischemia alone (up to 120 minutes) does not predict worse lung function at the conclusion of EVLP. The authors predict that, “Expanding acceptable (warm ischemia) after circulatory death may eventually allow for increased utilization of DCD lungs in procurement protocols.” It does seem that the lung is more tolerant of potential ischemia during DCD donation than had been assumed, and so the donor pool could be expanded.

References:

1. Krutsinger, D, Reed, R, Blevins, A et al. Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis. J Heart Lung Transplant. 2015; 34: 675–684
2. Reeb, J, Keshavjee, S, and Cypel, M. Successful lung transplantation from a donation after cardiocirculatory death donor taking more than 120 minutes to cardiac arrest after withdrawal of life support therapies. J Heart Lung Transplant. 2016; 35: 258–259)
3. Levvey B, et al, Influence of lung donor agonal and warm ischemic times on early mortality: Analyses from the ISHLT DCD Lung Transplant Registry. J Heart Lung Transplant. Jan 2019, 38, 1, p 26-34 https://doi.org/10.1016/j.healun.2018.08.006 (link to abstract)
4. Charles E J, et al, Ex Vivo Assessment of Porcine Donation After Circulatory Death Lungs That Undergo Increasing Warm Ischemia Times. Transplant Direct. 2018 Nov 12;4(12):e405. doi: 10.1097/TXD.0000000000000845. eCollection 2018 Dec. (link to abstract)

Xvivo Insights PB-2019-02-04