Impact of simultaneous heart procurement on outcomes of donation after circulatory death lung transplantation.

Donation after circulatory death (DCD) heart procurement is done using either direct procurement (DP) or thoracoabdominal normothermic machine perfusion (TA-NRP). Both approaches could impact lung transplant outcomes with combined heart and lung procurements from the same donor. The impact of such practice on DCD lung transplant remains unstudied. We performed a retrospective analysis using the United Network for Organ Sharing (UNOS) dataset, identifying DCD lung transplants where the donor also donated the heart (cardia lung donor [CD]). A cohort of noncardiac DCD lung donors (noncardiac lung donor [NCD]) from the same era, matched for donor and recipient characteristics, was used as a comparison group. Both immediate and long-term outcomes were examined. A subanalysis was performed comparing the distinct impact of DP or TA-NRP on DCD lung transplant outcomes. Overall graft survival did not significantly differ between CD and NCD. However, recipients in the CD group trended toward a lower P/F ratio at 72 hours (CD vs NCD: 284 vs 3190; P = .054). In the subanalysis, we identified 40 DP donors and 22 TA-NRP donors. We found the both cohorts had lower P/F ratio at 72 hours than the NCD control (P = .04). Overall, 1-year graft survival was equivalent among the TA-NRP, DP, and NCD cohorts.

Textbook Outcome: Definition and Analysis of a Novel Quality Measure in Lung Transplantation.

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.

Acid exposure time is sensitive for detecting gastroesophageal reflux disease and is associated with long-term survival after lung transplant.

Gastroesophageal reflux disease (GERD) is common in patients who have undergone lung transplantation and is associated with poorer outcomes, but guidelines are lacking to direct management strategies in this population. We assessed the diagnostic yield of impedance metrics compared to pH-metry alone for detecting GERD among lung transplant recipients and evaluated their association with clinical outcomes. We performed a retrospective cohort study of consecutive patients who underwent lung transplantation. Demographic data, acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallowing-induced peristaltic wave index (PSPWI), and clinical outcomes including mortality were collected. The relationship between GERD metrics and clinical outcomes was assessed using Wilcoxon signed-rank test and Fisher's exact test as appropriate. Of the 76 patients studied, 29 (38%) had GERD based on abnormal AET after lung transplantation. One (1.3%) patient had GERD based on elevated number of reflux episodes and abnormal distal MNBI detected GERD in 19 (26%) patients, resulting in 62% sensitivity and 94% specificity. Two (2.6%) patients had normal PSPWI. Patients with low distal MNBI had significantly decreased forced expiratory volume in 1 second (FEV1) at 3-year posttransplant compared to those without low distal MNBI (P = 0.03). Three-year survival was significantly worse among patients with elevated AET (66.7% vs. 89.1%, P = 0.03) but not with low distal MNBI (68.4% vs. 84.3%, P = 0.18). Abnormal AET is more sensitive for detecting GERD than other reflux metrics studied and is associated with survival, suggesting pH-metry alone may be sufficient to guide GERD management after lung transplant.

Development of New Donor-Specific and Human Leukocyte Antigen Antibodies After Transfusion in Adult Lung Transplantation.

OBJECTIVES: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. DESIGN: A retrospective observational study. SETTING: At a single academic tertiary center. PARTICIPANTS: Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). CONCLUSIONS: Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation.

Lung transplantation after ex vivo lung perfusion versus static cold storage: An institutional cost analysis.

Ex vivo lung perfusion (EVLP) is a novel lung preservation strategy that facilitates the use of marginal allografts; however, it is more expensive than static cold storage (SCS). To understand how preservation method might affect postoperative costs, we compared outcomes and index hospitalization costs among matched EVLP and SCS preserved lung transplant (LTx) recipients at a single, high-volume institution. A total of 22 EVLP and 66 matched SCS LTx recipients were included; SCS grafts were further stratified as either standard-criteria (SCD) or extended-criteria donors (ECD). Median total preservation time was 857, 409, and 438 min for EVLP, SCD, and ECD lungs, respectively (p < .0001). EVLP patients had similar perioperative outcomes and posttransplant survival compared to SCS SCD and ECD recipients. Excluding device-specific costs, total direct variable costs were similar among EVLP, SCD, and ECD recipients (median $200,404, vs. $154,709 vs. $168,334, p =  .11). The median direct contribution margin was positive for EVLP recipients, and similar to that for SCD and ECD graft recipients (all p > .99). These findings demonstrate that the use of EVLP was profitable at an institutional level; however, further investigation is needed to better understand the financial implications of EVLP in facilitating donor pool expansion in an era of broader lung sharing.

Lung Transplantation After Ex Vivo Lung Perfusion Early Outcomes From a US National Registry.

OBJECTIVE: The objective of this study was to examine early lung transplant outcomes following EVLP using a large national transplant registry. SUMMARY OF BACKGROUND DATA: Lung transplantation in the United States continues to be constrained by a limited supply of donor organs. EVLP has the potential to significantly increase the available pool of donor lung allografts through the reconditioning of "marginal" organs. METHODS: The united network for organ sharing registry was queried for all adults (age ≥18) who underwent first-time lung transplantation between March 2018 (when united network for organ sharing began collecting confirmed donor EVLP status) and June 2019. Transplants were stratified by EVLP use. The primary outcome was short-term survival and secondary outcomes included acute rejection before discharge and need for extracorpo-real membrane oxygenation support post-transplant. RESULTS: A total of 3334 recipients met inclusion criteria including 155 (5%) and 3179 (95%) who did and did not receive allografts that had undergone EVLP, respectively. On unadjusted descriptive analysis, EVLP and non-EVLP cohorts had similar 180-day survival (92% vs 92%, P = 0.9). EVLP use was associated with a similar rate of acute rejection (13% vs 9%, P = 0.08) but increased rate of early extracorporeal membrane oxygenation use (12% vs 7%, P = 0.04). After adjustment, EVLP use was not associated with significantly increased mortality (adjusted hazard ratio 0.99, 95% confidence interval 0.62-1.58) or acute rejection (adjusted odds ratio 0.89, 95% confidence interval 0.40-1.97) compared to non-EVLP use. CONCLUSIONS: In the largest national series of EVLP lung transplant recipients, EVLP is associated with early recipient outcomes comparable to that of non-EVLP recipients with similar baseline characteristics. Longer term follow-up data is needed to further assess the impact of EVLP on post-lung transplant outcomes.

Textbook surgical outcome in lung transplantation: Analysis of a US national registry.

INTRO: Textbook surgical outcome (TO) is a novel composite quality measure in lung transplantation (LTx). Compared to 1-year survival metrics, TO may better differentiate center performance, and motivate improvements in care. To understand the feasibility of implementing this metric, we defined TO in LTx using US national data, and evaluated its ability to predict post-transplant outcomes and differentiate center performance. METHODS: Adult patients who underwent isolated LTx between 2016 and 2019 were included. TO was defined as freedom from post-transplant length of stay > 30 days, 90-day mortality, intubation or extracorporeal membrane oxygenation at 72 h post-transplant, post-transplant ventilator support lasting ≥5 days, postoperative airway dehiscence, inpatient dialysis, pre-discharge acute rejection, and grade 3 primary graft dysfunction at 72 h. Recipient and donor characteristics and post-transplant outcomes were compared between patients who achieved and failed TO. RESULTS: Of 8959 lung transplant recipients, 4664 (52.1%) achieved TO. Patient and graft survival were improved among patients who achieved TO (both log-rank P < .0001). Among 62 centers, adjusted rates of TO ranged from 27.0% to 72.4% reflecting a wide variability in center-level performance. CONCLUSION: TO defined using national data may represent a novel composite metric to guide quality improvement in LTx across US transplant centers. SUMMARY: In this study we defined textbook outcome (TO) for lung transplantation (LTx) using US national data. We found that achievement of TO was associated with improved post-transplant survival, and wide variability in center-level LTx performance. These findings suggest that TO could be readily implemented to compare quality of care among US LTx centers.

Expanding donor availability in lung transplantation: A case report of 5000 miles traveled.

We present the case of a 41-year-old female who underwent bilateral lung transplantation after the donor lungs were placed on a normothermic ex vivo lung perfusion and ventilation device and flown nearly 5000 miles from Honolulu, Hawaii to Durham, North Carolina. The patient experienced no primary graft dysfunction. One year after transplantation she has remained rejection-free and exhibits excellent pulmonary function. This case highlights the challenge that active organ preservation systems pose to questions of organ allocation and geographic sharing.

Dual Procurement of Lung and Heart Allografts Does Not Negatively Affect Lung Transplant Outcomes.

BACKGROUND: The data that exists regarding multiorgan procurement outcomes is conflicted. Given the increasing demand for pulmonary allografts, it is critical to assess the impact of dual procurement on lung transplant recipient outcomes. METHODS: The United Network for Organ Sharing transplant registry was queried for all first-time adult (age ≥18) lung transplant recipients between 2006 and 2018 and stratified by concurrent heart donor status. Multiorgan transplant recipients and recipients with missing survival time were excluded. Donors were excluded if they were donating after circulatory death, did not consent or were not approached for heart donation, the heart was recovered for nontransplant purposes, or the heart was recovered for transplant but not transplanted. Post-transplant survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression. RESULTS: A total of 18,641 recipients met inclusion criteria, including 6230 (33.4%) in the nonheart donor group (NHD) and 12,409 (66.6%) in the heart donor group (HD). HD recipients demonstrated longer survival at 10 years posttransplant, with a median survival of 6.5 years as compared with 5.9 years in NHD recipients. On adjusted analysis, HD and NHD recipients demonstrated comparable survival (AHR 0.95, 95% CI 0.90-1.01). CONCLUSIONS: Concomitant heart and lung procurement was not associated with worse survival. This finding encourages maximizing the number of organs procured from each donor, particularly in the setting of urgency-driven thoracic transplantation.

Blood product transfusion and lung transplant outcomes: A systematic review.

The perioperative transfusion of blood products has long been linked to development of acute lung injury and associated with mortality across both medical and surgical patient populations.1,2 The need for blood product transfusion during and after lung transplantation is common and, in many instances, unavoidable. However, this practice may potentially be modifiable.3 In this systematic review, we explore and summarize what is known regarding the impact of blood product transfusion on outcomes following lung transplantation, highlighting the most recent work in this area. Overall, the majority of the literature consists of single center retrospective analyses or the work of multicenter working groups referencing the same database. In the end, there are a number of remaining questions regarding blood product transfusion and their downstream effects on graft function and survival.