The impact of bleeding on outcomes following lung transplantation: a retrospective analysis using the universal definition of perioperative bleeding.

BACKGROUND: Lung transplantation (LT) represents a high-risk procedure for end-stage lung diseases. This study describes the outcomes of patients undergoing LT that require massive transfusions as defined by the universal definition of perioperative bleeding (UDPB). METHODS: Adult patients who underwent bilateral LT at a single academic center were surveyed retrospectively. Patients were grouped by insignificant, mild, or moderate perioperative bleeding (insignificant-to-moderate bleeders) and severe or massive perioperative bleeding (severe-to-massive bleeders) based on the UDPB classification. Outcomes included 1-year survival and primary graft dysfunction (PGD) of grade 3 at 72 h postoperatively. Multivariable models were adjusted for recipient age, sex, body mass index (BMI), Lung allocation score (LAS), preoperative hemoglobin (Hb), preoperative extracorporeal membrane oxygenation (ECMO) status, transplant number, and donor status. An additional multivariable model was created to find preoperative and intraoperative predictors of severe-to-massive bleeding. A p-value less than 0.05 was selected for significance. RESULTS: A total of 528 patients were included, with 357 insignificant-to-moderate bleeders and 171 severe-to-massive bleeders. Postoperatively, severe-to-massive bleeders had higher rates of PGD grade 3 at 72 h, longer hospital stays, higher mortality rates at 30 days and one year, and were less likely to achieve textbook outcomes for LT. They also required postoperative ECMO, reintubation for over 48 h, tracheostomy, reintervention, and dialysis at higher rates. In the multivariate analysis, severe-to-massive bleeding was significantly associated with adverse outcomes after adjusting for recipient and donor factors, with an odds ratio of 7.73 (95% CI: 4.27-14.4, p < 0.001) for PGD3 at 72 h, 4.30 (95% CI: 2.30-8.12, p < 0.001) for 1-year mortality, and 1.75 (95% CI: 1.52-2.01, p < 0.001) for longer hospital stays. Additionally, severe-to-massive bleeders were less likely to achieve textbook outcomes, with an odds ratio of 0.07 (95% CI: 0.02-0.16, p < 0.001). Preoperative and intraoperative predictors of severe/massive bleeding were identified, with White patients having lower odds compared to Black patients (OR: 041, 95% CI: 0.22-0.80, p = 0.008). Each 1-unit increase in BMI decreased the odds of bleeding (OR: 0.89, 95% CI: 0.83-0.95, p < 0.001), while each 1-unit increase in MPAP increased the odds of bleeding (OR: 1.04, 95% CI: 1.02-1.06, p < 0.001). First-time transplant recipients had lower risk (OR: 0.16, 95% CI: 0.06-0.36, p < 0.001), whereas those with DCD donors had a higher risk of severe-to-massive bleeding (OR: 3.09, 95% CI: 1.63-5.87, p = 0.001). CONCLUSION: These results suggest that patients at high risk of massive bleeding require higher utilization of hospital resources. Understanding their outcomes is important, as it may inform future decisions to transplant comparable patients.

Efforts to improve the billing accuracy of robotic-assisted thoracic surgery through education, updated procedure cards, and electronic medical record system changes.

Precise medical billing is essential for decreasing hospital liability, upholding environmental stewardship and ensuring fair costs for patients. We instituted a multifaceted approach to improve the billing accuracy of our robotic-assisted thoracic surgery programme by including an educational component, updating procedure cards and removing the auto-populating function of our electronic medical record. Overall, we saw significant improvements in both the number of inaccurate billing cases and, specifically, the number of cases that overcharged patients.

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.

Computed Tomography Volumetrics for Size Matching in Lung Transplantation for Restrictive Disease.

BACKGROUND: There is no consensus on the optimal allograft sizing strategy for lung transplantation in restrictive lung disease. Current methods that are based on predicted total lung capacity (pTLC) ratios do not account for the diminutive recipient chest size. The study investigators hypothesized that a new sizing ratio incorporating preoperative recipient computed tomographic lung volumes (CTVol) would be associated with postoperative outcomes. METHODS: A retrospective single-institution study was conducted of adults undergoing primary bilateral lung transplantation between January 2016 and July 2020 for restrictive lung disease. CTVol was computed for recipients by using advanced segmentation software. Two sizing ratios were calculated: pTLC ratio (pTLCdonor/pTLCrecipient) and a new volumetric ratio (pTLCdonor/CTVolrecipient). Patients were divided into reference, oversized, and undersized groups on the basis of ratio quintiles, and multivariable models were used to assess the effect of the ratios on primary graft dysfunction and survival. RESULTS: CTVol was successfully acquired in 218 of 220 (99.1%) patients. In adjusted analysis, undersizing on the basis of the volumetric ratio was independently associated with decreased primary graft dysfunction grade 2 or 3 within 72 hours (odds ratio, 0.42; 95% CI, 0.20-0.87; P =.02). The pTLC ratio was not significantly associated with primary graft dysfunction. Oversizing on the basis of the volumetric ratio was independently associated with an increased risk of death (hazard ratio, 2.27; 95% CI, 1.04-4.99; P =.04], whereas the pTLC ratio did not have a significant survival association. CONCLUSIONS: Using computed tomography-acquired lung volumes for donor-recipient size matching in lung transplantation is feasible with advanced segmentation software. This method may be more predictive of outcome compared with current sizing methods, which use gender and height only.

Short-term outcomes after third-time lung transplantation: A single institution experience.

BACKGROUND: Reoperative lung transplantation (LTx) survival has improved over time such that a growing number of patients may present for third-time LTx (L3Tx). To understand the safety of L3Tx, we evaluated perioperative outcomes and 3-year survival after L3Tx at a high-volume US LTx center. METHODS: This retrospective study included all patients who underwent bilateral L3Tx at our institution. Using an optimal matching technique, a primary LTx (L1Tx) cohort was matched 1:2 and a second-time LTx (L2Tx) cohort 1:1. Recipient, operative, and donor characteristics, perioperative outcomes, and 3-year survival were compared among L1Tx, L2Tx, and L3Tx groups. RESULTS: Eleven L3Tx, 11 L2Tx, and 22 L1Tx recipients were included. Among L3Tx recipients, median age at transplant was 37 years and most (73%) had cystic fibrosis. L3Tx was performed median 6.0 and 10.6 years after L2Tx and L1Tx, respectively. Compared to L1Tx and L2Tx recipients, L3Tx recipients had greater intraoperative transfusion requirements, a higher incidence of postoperative complications, and a higher rate of unplanned reoperation. Rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation at 72 hours, reintubation, and in-hospital mortality were similar among groups. There were no differences in 3-year patient (log-rank p = 0.61) or rejection-free survival (log-rank p = 0.34) after L1Tx, L2Tx, and L3Tx. CONCLUSIONS: At our institution, L3Tx was associated with similar perioperative outcomes and 3-year patient survival compared to L1Tx and L2Tx. L3Tx represents the only safe treatment option for patients with allograft failure after L2Tx; however, further investigation is needed to understand the long-term survival and durability of L3Tx.

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.

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.

Same-teams versus different-teams for long distance lung procurement: A cost analysis.

OBJECTIVE: In an era of broader lung sharing, different-team transplantation (DT, procuring team from nonrecipient center) may streamline procurement logistics; however, safety and cost implications of DT remain unclear. To understand whether DT represents a safe means to reduce lung transplant (LTx) costs, we compared posttransplant outcomes and lung procurement and index hospitalization costs among matched DT and same-team transplantation (ST, procuring team from recipient center) cohorts at a single, high-volume institution. We hypothesized that DT reduces costs without compromising outcomes after LTx. METHODS: Patients who underwent DT between January 2016 to May 2020 were included. A cohort of patients who underwent ST was matched 1:3 (nearest neighbor) based on recipient age, disease group, lung allocation score, history of previous LTx, and bilateral versus single LTx. Posttransplant outcomes and costs were compared between groups. RESULTS: In total, 23 DT and 69 matched ST recipients were included. Perioperative outcomes and posttransplant survival were similar between groups. Compared with ST, DT was associated with similar lung procurement and index hospitalization costs (DT vs ST, procurement: median $65,991 vs $58,847, P = .16; index hospitalization: median $294,346 vs $322,189, P = .7). On average, procurement costs increased $3263 less per 100 nautical miles for DT versus ST; DT offered cost-savings when travel distances exceeded approximately 363 nautical miles. CONCLUSIONS: At our institution, DT and ST were associated with similar post-LTx outcomes; DT offered cost-savings with increasing procurement travel distance. These findings suggest that DT may mitigate logistical and financial burdens of lung procurement; however, further investigation in a multi-institutional cohort is warranted.

A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs.

INTRODUCTION: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. METHODS: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). RESULTS: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. CONCLUSIONS: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.

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.

Textbook outcome in lung transplantation: Planned venoarterial extracorporeal membrane oxygenation versus off-pump support for patients without pulmonary hypertension.

BACKGROUND: Planned venoarterial extracorporeal membrane oxygenation (VA ECMO) is increasingly used during bilateral orthotopic lung transplantation (BOLT) and may be superior to off-pump support for patients without pulmonary hypertension. In this single-institution study, we compared rates of textbook outcome between BOLTs performed with planned VA ECMO or off-pump support for recipients with no or mild pulmonary hypertension. METHODS: Patients with no or mild pulmonary hypertension who underwent isolated BOLT between 1/2017 and 2/2021 with planned off-pump or VA ECMO support were included. Textbook outcome was defined as freedom from intraoperative complication, 30-day reintervention, 30-day readmission, post-transplant length of stay >30 days, 90-day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, post-transplant ECMO, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Textbook outcome achievement was compared between groups using multivariable logistic regression. RESULTS: Two hundred thirty-seven BOLTs were included: 68 planned VA ECMO and 169 planned off-pump. 14 (20.6%) planned VA ECMO and 27 (16.0%) planned off-pump patients achieved textbook outcome. After adjustment for prior BOLT, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was associated with higher odds of textbook outcome than planned off-pump support (odds ratio 3.89, 95% confidence interval 1.58-9.90, p = 0.004). CONCLUSIONS: At our institution, planned VA ECMO for isolated BOLT was associated with higher odds of textbook outcome than planned off-pump support among patients without pulmonary hypertension. Further investigation in a multi-institutional cohort is warranted to better elucidate the utility of this strategy.

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases.

We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.

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.

Factors associated with short- versus long-term survival after lung transplant.

OBJECTIVE: A small but growing proportion of lung transplant recipients survive longer than a decade post-transplant. The aim of this study was to identify factors associated with survival beyond a decade after lung transplant. METHODS: We queried the United Network for Organ Sharing registry for adult (age ≥18 years) recipients undergoing first-time isolated lung transplantation between the introduction of the Lung Allocation Score in 2005 and 2009. Recipients were stratified into 3 cohorts: those who survived less than 1 year, 1 to 10 years, and greater than 10 years. Multivariable logistic regression was used to identify factors independently associated with early mortality (<1 year) and long-term (>10 years) survival. RESULTS: A total of 5171 lung transplant recipients and their associated donors met inclusion criteria, including 964 (18.6%) with early mortality, 2843 (55.0%) with intermediate survival, and 1364 (26.3%) long-term survivors. Factors independently associated with early mortality included donor Black race, cigarette use, arterial oxygen partial pressure/fractional inspired oxygen ratio, diabetes, recipient Lung Allocation Score, total bilirubin, extracorporeal membrane oxygenation bridge requirement, single lung transplantation, and annual lung transplant center volume. The only factors independently associated with long-term survival among those who survived at least 1 year was donor age and single lung transplantation. CONCLUSIONS: Of patients undergoing lung transplantation after the implementation of the Lung Allocation Score, approximately one-quarter survived 10 years post-transplant. There was minimal overlap between the factors associated with 1-year and 10-year survival. Of note, the Lung Allocation Score was not associated with long-term survival. Further research is needed to better refine patient selection and optimize management strategies to increase the number of long-term survivors.

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.