Early United States experience with lung donation after circulatory death using thoracoabdominal normothermic regional perfusion
2023; Elsevier BV; Volume: 42; Issue: 6 Linguagem: Inglês
10.1016/j.healun.2023.03.001
ISSN1557-3117
AutoresAlice L. Zhou, Jessica M. Ruck, Alfred J. Casillan, Emily L. Larson, Benjamin L. Shou, Alexander Karius, Jinny S. Ha, Pali D. Shah, Christian A. Merlo, Errol L. Bush,
Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoThoracoabdominal normothermic regional perfusion (TA-NRP) has recently begun being utilized in the United States for recovery of cardiothoracic allografts from some donors after circulatory death (DCD), but data on lungs recovered in this method is limited to case reports. We conducted a national retrospective review of lung transplants from DCD donors recovered using TA-NRP. Of the 434 total DCD lung transplants performed between January 2020 and March 2022, 17 were recovered using TA-NRP. Compared to direct recovery DCD transplants, recipients of TA-NRP DCD transplants had lower likelihood of ventilation >48 hours (23.5% vs 51.3%, p = 0.027) and similar likelihood of predischarge acute rejection, requirement for extracorporeal membrane oxygenation at 72 hours, hospital lengths of stay, and survival at 30, 60, and 90 days post-transplant. These early data suggest that DCD lung recovery using TA-NRP might be a safe way to further expand the donor pool and warrant further study. Thoracoabdominal normothermic regional perfusion (TA-NRP) has recently begun being utilized in the United States for recovery of cardiothoracic allografts from some donors after circulatory death (DCD), but data on lungs recovered in this method is limited to case reports. We conducted a national retrospective review of lung transplants from DCD donors recovered using TA-NRP. Of the 434 total DCD lung transplants performed between January 2020 and March 2022, 17 were recovered using TA-NRP. Compared to direct recovery DCD transplants, recipients of TA-NRP DCD transplants had lower likelihood of ventilation >48 hours (23.5% vs 51.3%, p = 0.027) and similar likelihood of predischarge acute rejection, requirement for extracorporeal membrane oxygenation at 72 hours, hospital lengths of stay, and survival at 30, 60, and 90 days post-transplant. These early data suggest that DCD lung recovery using TA-NRP might be a safe way to further expand the donor pool and warrant further study. Donation after circulatory death (DCD) has been increasingly used to address the organ shortage and has demonstrated excellent outcomes in lung transplants.1Copeland H Hayanga JWA Neyrinck A et al.Donor heart and lung procurement: a consensus statement.J Heart Lung Transplant. 2020; 39: 501-517https://doi.org/10.1016/j.healun.2020.03.020Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar,2Siddique A Urban M Strah H et al.Controlled DCD lung transplantation: circumventing imagined and real barriers: time for an international taskforce?.J Heart Lung Transplant. 2022; 41: 1198-1203https://doi.org/10.1016/j.healun.2022.06.007Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar For cardiac transplantation, however, DCD has not been as widely adopted given the ischemic insult to myocardial tissue.3Hoffman JRH McMaster WG Rali AS et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418https://doi.org/10.1016/j.healun.2021.06.022Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar A novel strategy involving thoracoabdominal normothermic regional perfusion (TA-NRP) for recovery of cardiothoracic allografts has been increasingly utilized in the United States, primarily driven by cardiac recovery teams to increase the availability of cardiac allografts from DCD donors. TA-NRP involves in situ reperfusion of thoracic and abdominal organs via extracorporeal membrane oxygenation prior to organ retrieval. Following declaration of death and a 2 to 5 min standoff time, chest entry is performed, the right atrium and ascending aorta are cannulated, and extracorporeal flow is established with a reperfusion time of up to 90 min, after which cross clamp and recovery are performed in identical fashion as a brain-dead donor recovery.1Copeland H Hayanga JWA Neyrinck A et al.Donor heart and lung procurement: a consensus statement.J Heart Lung Transplant. 2020; 39: 501-517https://doi.org/10.1016/j.healun.2020.03.020Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar,4Pasrija C, Tipograf Y, Shah AS, Trahanas JM. Normothermic regional perfusion for donation after circulatory death donors. Curr Opin Organ Transplant. https://doi.org/10.1097/MOT.0000000000001038Google Scholar With increased interest in utilizing TA-NRP for cardiac transplant,3Hoffman JRH McMaster WG Rali AS et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418https://doi.org/10.1016/j.healun.2021.06.022Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar,5Smith DE Kon ZN Carillo JA et al.Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States.J Thorac Cardiovasc Surg. 2022; 164 (e1): 557-568https://doi.org/10.1016/j.jtcvs.2021.07.059Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar we sought to evaluate the early outcomes of lung transplants from TA-NRP DCD donors in the United States. We retrospectively reviewed adult (≥18 years) lung-only transplants from DCD donors between January 1, 2020 and March 31, 2022 in the United Network for Organ Sharing (UNOS) database. To determine organ recovery during which TA-NRP was likely utilized, we considered a transplant to have used TA-NRP if the interval between asystole and aortic cross-clamp time was ≥50 min. This interval was chosen based on the 2020 ISHLT consensus statement, which suggests a TA-NRP interval of 45 to 90 min.1Copeland H Hayanga JWA Neyrinck A et al.Donor heart and lung procurement: a consensus statement.J Heart Lung Transplant. 2020; 39: 501-517https://doi.org/10.1016/j.healun.2020.03.020Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar,3Hoffman JRH McMaster WG Rali AS et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418https://doi.org/10.1016/j.healun.2021.06.022Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar,5Smith DE Kon ZN Carillo JA et al.Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States.J Thorac Cardiovasc Surg. 2022; 164 (e1): 557-568https://doi.org/10.1016/j.jtcvs.2021.07.059Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The time between asystole and cross-clamp includes stand-off time after declaration of death (2-5 min), chest entry (2 min), and, in the cases of TA-NRP, the reperfusion interval prior to cross-clamp. All other DCD transplants were considered direct recovery transplants. Our threshold of 50 min captures nearly all TA-NRP donors described by Hoffman et al3Hoffman JRH McMaster WG Rali AS et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418https://doi.org/10.1016/j.healun.2021.06.022Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar and Smith et al,5Smith DE Kon ZN Carillo JA et al.Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States.J Thorac Cardiovasc Surg. 2022; 164 (e1): 557-568https://doi.org/10.1016/j.jtcvs.2021.07.059Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar while minimizing the number of direct recovery donors captured. Baseline characteristics and outcomes were assessed using Wilcoxon rank sum and chi-square testing for continuous and categorical variables, respectively. Post-transplant survival at 30, 60, and 90 days was assessed using time-to-event analysis and log-rank tests. This study was deemed exempt for the need for institutional review board approval by the Johns Hopkins Institutional Review Board. Of the 434 total DCD lung transplants, 17 (3.9%) were recovered using TA-NRP by 12 lung transplant centers (Figure 1). TA-NRP donors had a lower median age than direct recovery donors (28 [21-36] vs 40 [29-49] years, p = 0.003; Table 1), similar time from withdrawal of life support to asystole (23.5 [16-31] vs 20 [15-26] min, p = 0.2), and, by definition, longer asystole to aortic cross-clamp time (100 [72-117] vs 7 [4-9] min, p < 0.001). Ex vivo lung perfusion (EVLP) was utilized in 1 (5.9%) TA-NRP and 86 (20.6%) direct recovery transplants (p = 0.2).Table 1Baseline Donor, Recipient, and Lung Transplant Characteristics between Direct Recovery vs Thoracoabdominal Normothermic Regional Perfusion (TA-NRP) Donation After Circulatory Death (DCD) Transplants in the United States. Significant Values (p < 0.05) are BoldedVariable, n (%)Direct recovery (n = 417)TA-NRP(n = 17)p-valueDonor characteristicsAge (years), median (IQR)40 (29-49)28 (21-36)0.003Male sex247 (59.2%)16 (94.1%)0.004Race/Ethnicity0.24 White298 (71.5%)12 (70.6%) Black47 (11.3%)0 (0.0%) Hispanic61 (14.6%)5 (29.4%) Other11 (2.6%)0 (0.0%)Cause of death0.44 Anoxia163 (39.1%)9 (52.9%) Cerebrovascular/Stroke119 (28.5%)2 (11.8%) Head trauma126 (30.2%)6 (35.3%) Other9 (2.2%)0 (0.0%)Abnormal chest x-ray289 (69.3%)13 (76.5%)0.53≥20 pack year smoking history29 (7.0%)0 (0.0%)0.62PaO2/FiO2 ratio <30040 (9.6%)0 (0.0%)0.39Ex vivo lung perfusion86 (20.6%)1 (5.9%)0.21Recipient characteristicsAge (years), median (IQR)62 (54-67)62 (58-64)0.86Male sex248 (59.5%)14 (82.4%)0.059Ethnicity0.88 White323 (77.5%)14 (82.4%) Black46 (11.0%)1 (5.9%) Hispanic37 (8.9%)2 (11.8%) Other11 (2.6%)0 (0.0%)Diagnosis0.32 Obstructive disease120 (28.8%)6 (35.3%) Pulmonary vascular disease12 (2.9%)0 (0.0%) Cystic fibrosis8 (1.9%)0 (0.0%) Restrictive disease264 (63.3%)9 (52.9%) Other13 (3.1%)2 (11.8%)Lung allocation score, median (IQR)38.7 (34.6-50.4)37.9 (34.2-39.3)0.27Total days on waitlist, median (IQR)31 (10-119)42 (12-76)0.90Transplant characteristicsIschemic time (hours), median (IQR)7.1 (5.7-9.7)5.1 (4.4-6.0)<0.001Donor to recipient hospital distance (miles), median (IQR)179 (76-359)142 (9-331)0.40Withdrawal of life support to asystole time (min), median (IQR)20 (15-26)23.5 (16-31)0.20Agonal time (min), median (IQR)16 (11-22)17.5 (14-25)0.35Asystole to clamp time (min), median (IQR)7 (4-9)100 (72-117)<0.001Abbreviations: TA-NRP, thoracoabdominal normothermic regional perfusion; IQR, interquartile range. Agonal time defined as time between systolic blood pressure <80 mm Hg or O2 saturation <80% and asystole.Continuous variables were compared using Wilcoxon rank sum testing and expressed as median (interquartile range). Categorial variables were compared using Chi-square testing and expressed as number (percent). Open table in a new tab Abbreviations: TA-NRP, thoracoabdominal normothermic regional perfusion; IQR, interquartile range. Agonal time defined as time between systolic blood pressure <80 mm Hg or O2 saturation 48 hours (23.5% vs 51.3%, p = 0.027) and trended towards shorter hospital lengths of stay (15 [10-28.5] vs 23 [15-39] days, p = 0.060; Table 2). Recipients of TA-NRP grafts had similar rates of intubation (30.8% vs 46.7%, p = 0.4) and extracorporeal membrane oxygenation at 72 hours (7.7% vs 17.3%, p = 0.7), as well as predischarge acute rejection (11.8% vs 7.0%, p = 0.4). On Kaplan–Meier analysis, TA-NRP versus direct recovery recipients had similar 30-day (100% vs 96.4%, p = 0.4), 60-day (100% vs 95.4%, p = 0.4), and 90-day (92.9% vs 93.6%, p > 0.9) survival.Table 2Outcomes Following Transplantation with Lung Donors after Circulatory Death (DCD) Recovered Using Direct Recovery vs Thoracoabdominal Normothermic Regional Perfusion (TA-NRP) in the United States. Significant Values (p < 0.05) are BoldedVariable, n (%)Direct recovery(n = 417)TA-NRP(n = 17)p-valueVentilatory support >48 h214 (51.3%)4 (23.5%)0.027Intubation at 72 h184 (46.7%)4 (30.8%)0.40ECMO at 72 h68 (17.3%)1 (7.7%)0.71Predischarge acute rejection29 (7.0%)2 (11.8%)0.35Dialysis50 (12.0%)1 (5.9%)0.71Hospital length of stay (days), median (IQR)23 (15-39)15 (10-28.5)0.060Survival at 30-d post-transplant15 (100%)390 (96.4%)0.43Survival at 60-d post-transplant14 (100%)380 (95.4%)0.38Survival at 90-d post-transplant13 (92.9%)372 (93.6%)0.99Abbreviations: TA-NRP, thoracoabdominal normothermic regional perfusion; IQR, interquartile range; ECMO, extracorporeal membrane oxygenation.Continuous variables were compared using Wilcoxon rank sum testing and expressed as median (interquartile range). Categorial variables were compared using Chi-squared testing and expressed as number (percent). Post-transplant survival was assessed using Kaplan Meier time-to-event analysis and log-rank tests. Open table in a new tab Abbreviations: TA-NRP, thoracoabdominal normothermic regional perfusion; IQR, interquartile range; ECMO, extracorporeal membrane oxygenation. Continuous variables were compared using Wilcoxon rank sum testing and expressed as median (interquartile range). Categorial variables were compared using Chi-squared testing and expressed as number (percent). Post-transplant survival was assessed using Kaplan Meier time-to-event analysis and log-rank tests. This is the first national study of lung transplant outcomes using TA-NRP DCD allografts. Currently, the effects of TA-NRP on lung allograft function are largely unknown; particular concerns include the limited lung perfusion prior to return of cardiac activity, the potential for reperfusion with byproducts from the abdominal compartment6Urban M Castleberry AW Markin NW et al.Successful lung transplantation with graft recovered after thoracoabdominal normothermic perfusion from donor after circulatory death.Am J Transplant. 2022; 22: 294-298https://doi.org/10.1111/ajt.16806Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, and the ethics surrounding this technique.7DeCamp M Snyder Sulmasy L Fins JJ. Point: does normothermic regional perfusion violate the ethical principles underlying organ procurement? Yes.Chest. 2022; 162: 288-290https://doi.org/10.1016/j.chest.2022.03.012Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar TA-NRP in lung transplantation has only been described in case reports by Urban et al6Urban M Castleberry AW Markin NW et al.Successful lung transplantation with graft recovered after thoracoabdominal normothermic perfusion from donor after circulatory death.Am J Transplant. 2022; 22: 294-298https://doi.org/10.1111/ajt.16806Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar,8Urban M Bishawi M Castleberry AW et al.Novel use of mobile ex-vivo lung perfusion in donation after circulatory death lung transplantation.Prog Transpl. 2022; 32: 190-191https://doi.org/10.1177/15269248221087437Crossref PubMed Scopus (2) Google Scholar and Vandendriessche et al9Vandendriessche K Tchana-Sato V Ledoux D et al.Transplantation of donor hearts after circulatory death using normothermic regional perfusion and cold storage preservation.Eur J Cardiothorac Surg. 2021; 60: 813-819https://doi.org/10.1093/ejcts/ezab139Crossref PubMed Scopus (29) Google Scholar Our results on the early national experience with TA-NRP lungs demonstrated satisfactory outcomes, with no differences in perioperative outcomes and short-term post-transplant survival, though with younger and more nonsmoking donors. These results support the further study of lung grafts recovered using TA-NRP. While recovery using TA-NRP has increased over the last 2 years, uptake of this practice for lung transplantation lags behind other organs. Of the total 146 TA-NRP donors, only 17 (11.6%) lungs were transplanted. Lungs from an additional 8 (5.5%) TA-NRP donors were recovered for transplant but discarded, resulting in a discard rate of 32%, compared to a discard rate of 24.4% for DCD donors previously reported.10Choi AY Jawitz OK Raman V et al.Predictors of nonuse of donation after circulatory death lung allografts.J Thorac Cardiovasc Surg. 2021; 161 (e3): 458-466https://doi.org/10.1016/j.jtcvs.2020.04.111Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Meanwhile, hearts were transplanted from 110 TA-NRP donors (75.3%), kidneys from 134 (91.8%), and livers from 82 (56.2%). Hearts were transplanted from 23 of the 25 donors (92%) in which lungs were recovered. Although standard recovery may be preferred for DCD lungs, our study suggests that the lungs from DCD donors with TA-NRP performed for cardiac transplant might currently be underutilized and may offer a safe way to further expand the donor pool, particularly as interest in TA-NRP for cardiac transplant continues to grow.4Pasrija C, Tipograf Y, Shah AS, Trahanas JM. Normothermic regional perfusion for donation after circulatory death donors. Curr Opin Organ Transplant. https://doi.org/10.1097/MOT.0000000000001038Google Scholar Additionally, TA-NRP may act as an alternative to EVLP, allowing for assessment of marginal DCD donor lungs without the added costs associated with EVLP and increasing accessibility of marginal DCD lungs to programs without a dedicated EVLP team. This study has several limitations. Given the novelty of TA-NRP, it is not yet available as a variable in the UNOS database and therefore our identification of patients using asystole and cross-clamp time might result in misclassification. The registry database also does not have more granular information on pulmonary function during the TA-NRP phase or reasoning for discarding the TA-NRP lungs. Lastly, the recent uptake of this procedure limits the available follow-up time. In conclusion, we report on the outcomes of the first 17 lung transplants performed following TA-NRP recovery in the United States. Our analysis demonstrates satisfactory perioperative outcomes and short-term survival. Future studies should continue to assess the safety and organ utilization rate of this technique. Errol Bush discloses participation in an Innovation Advisory Board for Ethicon, Inc. A.Z.: conception and design of work, interpretation of data, drafting. J.R.: conception and design of work, drafting. A.C.: design of work, revising. E.L.: design of work, revising. B.S.: interpretation of data, revising. A.K.: analysis of data, revising. J.H.: design of work, revising. P.S.: design of work, revising. C.M.: design of work, revising. E.B.: conception and design of work, interpretation of data; revising. All authors provided final approval and agreed to be accountable for all aspects of the work.
Referência(s)