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.

Pain trajectories after bilateral orthotopic lung transplantation surgery performed via a clamshell incision.

INTRODUCTION: The nature, intensity, and progression of acute pain after bilateral orthotopic lung transplantation (BOLT) performed via a clamshell incision has not been well investigated. We aimed to describe acute pain after clamshell incisions using pain trajectories for the study cohort, in addition to stratifying patients into separate pain trajectory groups and investigating their association with donor and recipient perioperative variables. METHODS: After obtaining IRB approval, we retrospectively included all patients ≥18 years old who underwent primary BOLT via clamshell incision at a single center between January 1, 2017, and June 30, 2022. We modeled the overall pain trajectory using pain scores collected over the first seven postoperative days and identified separate pain trajectory classes via latent class analysis. RESULTS: Three hundred one adult patients were included in the final analysis. Three separate pain trajectory groups were identified, with most patients (72.8%) belonging to a well-controlled, stable pain trajectory. Uncontrolled pain was either observed in the early postoperative period (10%), or in the late postoperative period (17.3%). Late postoperative peaking trajectory patients were younger (p = .008), and sicker with a higher lung allocation score (p = .005), receiving preoperative mechanical ventilation (p < .001), or VV-ECMO support (p < .001). CONCLUSION: Despite the extensive nature of a clamshell incision, most pain trajectories in BOLT patients had a well-controlled stable pain profile. The benign nature of pain profiles in our patient population may be attributed to the routine institutional practice of early thoracic epidural analgesia for BOLT patients unless contraindicated.

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.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Effectiveness of Simulation- Versus Didactic Video-Based Learning to Teach Advanced Lung Isolation Techniques.

OBJECTIVES: Mastery of lung isolation is crucial for optimal cardiothoracic anesthesia education. The authors tested the hypothesis that simulation- is more effective than didactic video-based learning (cognitive, affective, and psychomotor) to teach anesthesiology fellows advanced lung isolation techniques. DESIGN: A prospective randomized study. SETTING: At a single academic heart center, simulation laboratory. PARTICIPANTS: Thirty anesthesiology fellows with equivalent prior experience in basic lung isolation techniques. INTERVENTIONS: Randomized participants received 1 of 2 structured educational interventions of equivalent duration designed to teach advanced lung isolation skills, a simulation workshop, or a video-based didactic session. MEASUREMENTS AND MAIN RESULTS: To assess Bloom's taxonomy domains, performance measurements included pre- and postintervention cognitive tests and affective surveys and a postintervention psychomotor task (time to complete lung isolation). Changes in test and survey scores and time to completion were compared using the Mann-Whitney U test; p values < 0.05 were considered significant. Improvements in lung isolation learning assessments were greater in the simulation group, but significant differences only existed in the affective domain. Specifically, affective survey score increases were greater in the simulation group (simulation- versus video-based didactic: +19.0 v +4.0; p ≤ 0.001), whereas there was no significant difference in cognitive pre- to posttest scores (simulation- versus video-based: +28.6 v +19.1, p = 0.23), and time to achieve lung isolation (simulation- versus video-based: 32 v 36 seconds, p = 0.46). CONCLUSIONS: Although greater affective learning of advanced lung isolation skills occurred with simulation-based compared to didactic video-based education, the authors found no differences between the teaching approaches in cognitive and psychomotor learning among anesthesiology fellows.

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.

Pain Trajectories After Valve Surgeries Performed via Midline Sternotomy Versus Mini-Thoracotomy.

OBJECTIVES: Controlling moderate-to-severe pain remains a major challenge after cardiothoracic surgery. Several outcomes have been compared extensively after valve surgery performed via midline sternotomy versus mini-thoracotomy, but postoperative pain (POP) was not adequately examined. Therefore, the authors tested the hypothesis that there is no difference in POP trajectories in patients undergoing valve surgery via midline sternotomy versus mini-thoracotomy. DESIGN: An Institutional Review Board-approved retrospective study. SETTING: At a single, large academic medical center. PARTICIPANTS: Adult patients who underwent mitral or aortic valve surgeries over a 5-year period. INTERVENTIONS: The authors compared the characteristics of pain between valve surgery patients receiving either midline sternotomy or mini-thoracotomy. To identify pain score trajectories, the authors employed latent class linear mixed models and then used multinomial regression models to study the association between incision type and pain trajectory class. MEASUREMENTS AND MAIN RESULTS: The authors' cohort consisted of 1,660 surgical patients-544 (33%) received a midline sternotomy, and 1,116 (66%) received a mini-thoracotomy. The authors identified the following 4 pain trajectory classes: stationary, rapidly improving, slowly improving, and acute worsening pain. Compared to the rapidly improving class, the odds of belonging to the stationary (adjusted odds ratio [aOR] [95% CI] 1.45 [1.01- 2.08]; p = 0.04) or the acute worsening class (aOR [95% CI] 1.71 [1.10-2.67] p = 0.02) were significantly higher for sternotomy patients compared to mini-thoracotomy. CONCLUSIONS: Midline sternotomies are associated with higher odds of having an acute worsening or stationary versus a rapidly improving pain trajectory compared to mini-thoracotomies. Therefore, the choice of incision may play an important role in determining POP trajectory after valve surgery.

Effect of mode of intraoperative support on primary graft dysfunction after lung transplant.

OBJECTIVE: To clarify the relationship between the use of extracorporeal life support during lung transplantation and severe primary graft dysfunction (PGD), we developed and analyzed a novel multicenter international registry. METHODS: The Extracorporeal Life Support in Lung Transplantation Registry includes double-lung transplants performed at 8 high-volume centers (>40/year). Multiorgan transplants were excluded. We defined severe PGD as grade 3 PGD (PGD3) observed 48 or 72 hours after reperfusion. Modes of support were no extracorporeal life support (off-pump), extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass (CPB). To assess the association between mode of support and PGD3, we adjusted for demographic and intraoperative factors with a stepwise, mixed selection, multivariable regression model, ending with 10 covariates in the final model. RESULTS: We analyzed 852 transplants performed between January 2016 and March 2020: 422 (50%) off-pump, 273 (32%) ECMO, and 157 (18%) CPB cases. PGD3 rates at time point 48-72 were 12.1% (51 out of 422) for off-pump, 28.9% for ECMO (79 out of 273), and 42.7% (67 out of 157) for CPB. The adjusted model resulted in the following risk profile for PGD3: CPB versus ECMO odds ratio, 1.89 (95% CI, 1.05-3.41; P = .033), CPB versus off-pump odds ratio, 4.24 (95% CI, 2.24-8.04; P < .001), and ECMO versus off-pump odds ratio, 2.24 (95% CI, 1.38-3.65; P = .001). CONCLUSIONS: Venoarterial ECMO is increasingly used at high-volume centers to support complex transplant recipients during double-lung transplantation. This practice is associated with more risk of PGD3 than off-pump transplantation but less risk than CPB. When extracorporeal life support is required during lung transplantation, ECMO may be the preferable approach when feasible.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2020 Part I - Lung Transplantation.

This special article focuses on the highlights in cardiothoracic transplantation literature in the year 2020. Part I encompasses the recent literature on lung transplantation, including the advances in preoperative assessment and optimization, donor management, including the use of ex-vivo lung perfusion, recipient management, including those who have been infected with coronavirus disease 2019, updates on the perioperative management, including the use of extracorporeal membrane oxygenation, and long-term outcomes.

Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.

Importance: Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication. Objective: To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO. Design, Setting, and Participants: This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation. Interventions: Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU). Main Outcomes and Measures: The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome. Results: A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes. Conclusions and Relevance: Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO. Trial Registration: ClinicalTrials.gov identifier: NCT03081052.

Lung transplantation using allografts with more than 8 hours of ischemic time: A single-institution experience.

BACKGROUND: Six hours was historically regarded as the limit of acceptable ischemic time for lung allografts. However, broader sharing of donor lungs often necessitates use of allografts with ischemic time >6 hours. We characterized the association between ischemic time ≥8 hours and outcomes after lung transplantation using a contemporary cohort from a high-volume institution. METHODS: Patients who underwent primary isolated bilateral lung transplantation between 1/2016 and 5/2020 were included. Patients bridged to transplant with extracorporeal membrane oxygenation or mechanical ventilation, and ex-vivo perfusion cases were excluded. Recipients were stratified by total allograft ischemic time <8 hours (standard) vs ≥8 hours (long). Perioperative outcomes and post-transplant survival were compared between groups. RESULTS: Of 358 patients, 95 (26.5%) received long ischemic time (≥8 hours) lungs. Long ischemic time recipients were more likely to be male and have donation after circulatory death donors than standard ischemic time recipients. On unadjusted analysis, long and standard ischemic time recipients had similar survival, and similar rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation post-transplant, acute rejection within 30 days, reintubation, and post-transplant length of stay. After adjustment, long and standard ischemic time recipients had comparable risks of mortality or graft failure. CONCLUSIONS: In a modern cohort, use of lung allografts with "long" ischemic time ≥8 hours were associated with acceptable perioperative outcomes and post-transplant survival. Further investigation is required to better understand how broader use impacts post-lung transplant outcomes and the implications for smarter sharing under an evolving national allocation policy.

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.

The Association of Increased FFP:RBC Transfusion Ratio to Primary Graft Dysfunction in Bleeding Lung Transplantation Patients.

OBJECTIVES: Lung transplantation is associated with a significant risk of needed transfusion. Although algorithm-based transfusion strategies that promote a high fresh frozen plasma:red blood cells (FFP:RBC) ratio have reduced overall blood product requirements in other populations, large-volume transfusions have been linked to primary graft dysfunction (PGD) in lung transplantation, particularly use of platelets and plasma. The authors hypothesized that in lung transplant recipients requiring large-volume transfusions, a higher FFP:RBC ratio would be associated with increased PGD severity at 72 hours. DESIGN: Observational retrospective review. SETTING: Single tertiary academic center. PARTICIPANTS: Adult patients undergoing bilateral or single orthotopic lung transplantation and receiving >4 U PRBC in the first 72 hours from February 2014 to March 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, operative characteristics, blood transfusions, and outcomes including PGD scores and length of stay were collected. Eighty-nine patients received >4U PRBC, had available 72-hour PGD data, and were included in the study. These patients were grouped into a high-ratio (>1:2 units of FFP:RBC, N = 38) or low-ratio group (<1:2 units of FFP:RBC, N = 51). Patients in the high-ratio group received more transfusions and factor concentrates and had significantly longer case length. The high-ratio group had a higher rate of severe PGD at 72 hours (60.5% v 23.5%, p = 0.0013) and longer hospital length of stay (40 v 32 days, p = 0.0273). CONCLUSIONS: In bleeding lung transplantation patients at high risk for PGD, a high FFP:RBC transfusion ratio was associated with worsened 72-hour PGD scores when compared with the low-ratio cohort.

The Year in Thoracic Anesthesia: Selected Highlights from 2019.

THIS special article is the 4th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan; the associate editor-in-chief, Dr. Augoustides; and the editorial board for the opportunity to expand this series, the research highlights of the year that specifically pertain to the specialty of thoracic anesthesia. The major themes selected for 2019 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in this specialty for 2019 include updates in the preoperative assessment and optimization of patients undergoing lung resection and esophagectomy, updates in one lung ventilation (OLV) and protective ventilation during OLV, a review of recent meta-analyses comparing truncal blocks with paravertebral catheters and the introduction of a new truncal block, meta-analyses comparing nonintubated video-assisted thoracoscopic surgery (VATS) with those performed using endotracheal intubation, a review of the Society of Thoracic Surgeons (STS) recent composite score rating for pulmonary resection of lung cancer, and an update of the Enhanced Recovery After Surgery (ERAS) guidelines for both lung and esophageal surgery.