Influence of lung donor agonal and warm ischemic times on early mortality: Analyses from the ISHLT DCD Lung Transplant Registry.

In this study we aimed to assess the impact of agonal time and warm ischemic time on early survival in Category III donation-after-circulatory-death (DCD) donor lung transplants (LTxs) using data reported to the International Society for Heart and Lung Transplantation (ISHLT) DCD Lung Transplant Registry. In this retrospective study, data were analyzed for 507 DCD LTxs done between January 2005 and June 2015. DCD lung donor agonal time (defined as withdrawal of life support to cessation of cardiac output) and warm ischemic time (WIT; defined as donor systolic blood pressure <50 mm Hg to cold pulmonary artery flush) were divided into 3 clinical timing categories (<30 minutes, 30 to 60 minutes, >60 minutes) and 3 tertiles. Univariate analysis was undertaken for all categorizations, and Day 30/Day 365 Kaplan‒Meier survival rates were calculated and compared. Multivariable analysis included Cox proportional hazards regression models to estimate hazard of 365-day mortality. Four hundred sixty-five and 301 DCD LTxs had data to analyze in the agonal and warm ischemic time groups, respectively. Day 30 and Day 365 post-transplant survival overall were 96% and 90%, respectively, and not statistically different according to agonal or WIT category or tertile. Current experience with DCD Category III LTx does not show a relationship between the duration of donor agonal phase or warm ischemic time up to 60 minutes and early survival. These results suggest the true limits of clinical DCD allograft warm ischemic times may not yet be reached. Global variations in clinical DCD practice are apparent. Continued accurate recording and analyses of DCD processes is warranted.

Levvey B ，Keshavjee S ，Cypel M ，Robinson A ，Erasmus M ，Glanville A ，Hopkins P ，Musk M ，Hertz M ，McCurry K ，Van Raemdonck D ，Snell G ... -  《-》

Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry.

This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD). We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model. The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61). This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality.

Van Raemdonck D ，Keshavjee S ，Levvey B ，Cherikh WS ，Snell G ，Erasmus M ，Simon A ，Glanville AR ，Clark S ，D'Ovidio F ，Catarino P ，McCurry K ，Hertz MI ，Venkateswaran R ，Hopkins P ，Inci I ，Walia R ，Kreisel D ，Mascaro J ，Dilling DF ，Camp P ，Mason D ，Musk M ，Burch M ，Fisher A ，Yusen RD ，Stehlik J ，Cypel M ，International Society for Heart and Lung Transplantation ... -  《-》

International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report.

The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD). In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation. There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant [NS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11). This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant.

Cypel M ，Levvey B ，Van Raemdonck D ，Erasmus M ，Dark J ，Love R ，Mason D ，Glanville AR ，Chambers D ，Edwards LB ，Stehlik J ，Hertz M ，Whitson BA ，Yusen RD ，Puri V ，Hopkins P ，Snell G ，Keshavjee S ，International Society for Heart and Lung Transplantation ... -  《-》

Missed opportunities for DCD kidney donors: Evaluation of warm ischemic time and associated functional warm ischemic time.

Many transplant centers utilize a hard cutoff of 2 hours of warm ischemic time (WIT), defined as the time from withdrawal of life-sustaining measures to cold organ flush, to exclude donation after circulatory determination of death (DCD) kidney donation. As a result, almost a quarter of withdrawals to retrieve DCD organs fail to produce kidney transplants in Ontario. In order to assess our ability to increase organ yield, we wanted to characterize WIT and functional WIT (fWIT, time from systolic blood pressure <50 mm Hg to cold organ flush), as well as determine the time at which potential donors eventually die in those that did not become organ donors. A retrospective review of all DCD kidney donors in Ontario was performed utilizing the Trillium Gift of Life Database from April 2013 to February 2018. Of 350 DCD kidney donors analyzed, 46.9% had < 0.5 hours, 51.7% between 0.5 and 2 hours, and 1.4% >2 hours of WIT. In each of these categories (WIT <0.5 hours, 0.5-2 hours and >2 hours), the percentage of patients with fWIT <30 minutes was 100%, 94.4%, and 100%, respectively (P = NS). There were 106 potential donors who did not end up donating due to WIT >2 hours. Of these, 20.8% died between 2 and 4 hours, 10.4% between 4 and 6 hours, and 68.8% beyond 6 hours. The percentage of donors with fWIT >30 minutes did not increase with increasing WIT in DCD donors that went on to donate organs. These data support assessment of waiting up to 4 hours for DCD kidney donation as long as fWIT remains low.

Law J ，Hornby K ，Payne C ，Sener A ，Luke PP ... -  《-》

Onset of Donor Warm Ischemia Time in Donation After Circulatory Death Liver Transplantation: Hypotension or Hypoxia?

The aim of this study was to investigate the impact of hypoxia and hypotension during the agonal phase of donor warm ischemia time (DWIT) on hepatic ischemia/reperfusion injury (IRI) and complications in donation after circulatory death (DCD) liver transplantation. A retrospective single-center study of 93 DCD liver transplants (Maastricht type III) was performed. DWIT was divided into 2 periods: the agonal phase (from withdrawal of treatment [WoT] until circulatory arrest) and the asystolic phase (circulatory arrest until cold perfusion). A drop to <80% in peripheral oxygenation (SpO2 ) was considered as hypoxia in the agonal phase (SpO2 -agonal) and a drop to <50 mm Hg as hypotension in the agonal phase (SBP-agonal). Peak postoperative aspartate transaminase level >3000 U/L was considered as severe hepatic IRI. SpO2 dropped within 2 minutes after WoT <80%, whereas the systolic blood pressure dropped to <50 mm Hg after 9 minutes, resulting in a longer SpO2 -agonal (13 minutes) than SBP-agonal (6 minutes). In multiple logistic regression analysis, only duration of SpO2 -agonal was associated with severe hepatic IRI (P = 0.006) and not SBP-agonal (P = 0.32). Also, recipients with long SpO2 -agonal (>13 minutes) had more complications with a higher Comprehensive Complication Index during hospital admission (43.0 versus 32.0; P = 0.002) and 90-day graft loss (26% versus 6%; P = 0.01), compared with recipients with a short SpO2 -agonal (≤13 minutes). Furthermore, Cox proportional hazard modeling identified a long SpO2 -agonal as a risk factor for longterm graft loss (hazard ratio, 3.30; 95% confidence interval, 1.15-9.48; P = 0.03). In conclusion, the onset of hypoxia during the agonal phase is related to the severity of hepatic IRI and postoperative complications. Therefore, SpO2 <80% should be considered as the start of functional DWIT in DCD liver transplantation.

Kalisvaart M ，de Haan JE ，Polak WG ，N M IJzermans J ，Gommers D ，Metselaar HJ ，de Jonge J ... -  《-》