Early extracorporeal photopheresis treatment is associated with better survival in patients with chronic or recurrent acute lung allograft dysfunction.

BACKGROUND: Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. METHODS: We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. RESULTS: Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). CONCLUSION: In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.

Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK).

BACKGROUND: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone. METHODS AND ANALYSIS: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials. ETHICS AND DISSEMINATION: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number 2022-002659-20; ISRCTN 10615985.

The diagnosis and management of chronic lung allograft dysfunction.

PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD. RECENT FINDINGS: Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD. SUMMARY: Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients.

Use of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Cardiac Transplantation: Results of an A Priori Ventless Approach.

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of an a priori peripheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival.

Outcomes of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first 30 days after lung transplantation and is also associated with worse long-term outcomes. Outcomes of patients with PGD grade 3 requiring extracorporeal membrane oxygenation (ECMO) support after lung transplantation have yet to be well described. We sought to describe short- and long-term outcomes for patients with PGD grade 3 who required ECMO support. METHODS: This is a single-center retrospective cohort study of patients undergoing lung transplantation. We stratified patients with PGD grade 3 into non-ECMO, venoarterial (VA) ECMO, and venovenous (VV) ECMO groups after transplantation. We then compared the outcomes between the groups. RESULTS: Of 773 lung transplant recipients, PGD grade 3 developed in 204 (26%) at any time in the first 72 hours after lung transplantation. Of these, 13 (5%) required VA ECMO and 25 (10%) required VV ECMO support. The 30-day, 1-year, and 5-year survival in the VA ECMO group was 62%, 54%, and 43% compared with 96%, 84%, and 65% in the VV ECMO group and 99%, 94%, and 71% in the non-ECMO group. Multivariable Cox regression analysis showed that VA ECMO was associated with increased mortality (hazard ratio, 2.37; 95% CI, 1.06-5.28; P = .04). CONCLUSIONS: Patients who required VA ECMO support for PGD grade 3 have significantly worse survival compared with those who did not require ECMO and those who required VV ECMO support. This suggests that VA ECMO treatment of patients with PGD grade 3 after lung transplantation can be a predictable risk factor for mortality.

Outcome of primary graft dysfunction rescued by venoarterial extracorporeal membrane oxygenation after heart transplantation.

BACKGROUND: Primary graft dysfunction remains the leading cause of 30-day mortality after heart transplantation. Few data have been published about the clinical outcome of severe primary graft dysfunction treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). AIM: To evaluate the prevalence and outcome of severe primary graft dysfunction requiring VA-ECMO, and to identify factors associated with hospital mortality. METHODS: We performed an observational analysis of our institutional database of VA-ECMO for primary graft dysfunction after heart transplantation. Patients with severe primary graft dysfunction, according to the International Society for Heart and Lung Transplantation classification, were included. The primary outcome was survival to hospital discharge. Risk factors for in-hospital mortality were searched with multiple logistic regression analysis using backward stepwise variable elimination. RESULTS: Of the 397 patients who had heart transplantation between January 2007 and December 2018, 60 (15.1%) developed severe primary graft dysfunction requiring VA-ECMO. The median age was 52 (interquartile range 39-59) years, and 73.3% were male. Thirty-nine (65.0%) patients were weaned after a mean duration of VA-ECMO support of 7.2±6.0 days. Thirty-two (53.3%) patients were alive at hospital discharge. Inotropic support in the recipient before heart transplantation (odds ratio [OR] 3.88, 95% confidence interval [CI] 1.04-14.44; P=0.04), total ischaemic time (OR 0.99, 95% CI 0.99-1.00; P=0.01) and 48-hour total blood transfusion (OR 1.14, 95% CI 1.04-1.26; P=0.01) were independent predictors of in-hospital mortality. CONCLUSIONS: Severe primary graft dysfunction requiring VA-ECMO is frequent after heart transplantation. Survival to hospital discharge after VA-ECMO for severe primary graft dysfunction is satisfactory in such a critically ill population.

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.

Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts.

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1-12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

Primary Graft Dysfunction after Heart Transplantation - Unravelling the Enigma.

Primary graft dysfunction (PGD) remains the main cause of early mortality following heart transplantation despite several advances in donor preservation techniques and therapeutic strategies for PGD. With that aim of establishing the aetiopathogenesis of PGD and the preferred management strategies, the new consensus definition has paved the way for multiple contemporaneous studies to be undertaken and accurately compared. This review aims to provide a broad-based understanding of the pathophysiology, clinical presentation and management of PGD.

Use of extracorporeal membrane oxygenation for heart graft dysfunction in adults: incidence, risk factors and outcomes in a multicentric study.

BACKGROUND: The decision about whether to use venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiac graft dysfunction (GD) is usually made on a case-by-case basis and is guided by the team's experience. We aimed to determine the incidence of VA-ECMO use after heart transplantation (HT), to assess early- and long-term outcomes and to assess risk factors for the need for VA-ECMO and early mortality in these patients. METHODS: We included adults who underwent heart transplantation at 3 cardiac centres who met the most recent International Society for Heart and Lung Transplantation definition of graft dysfunction (GD) over a 10-year period. Pre-transplant, intraoperative and posttransplant characteristics of the heart recipients as well as donor characteristics were analyzed and compared among recipients with GD treated with and without VA-ECMO. RESULTS: There were 135 patients with GD in this study, of whom 66 were treated with VA-ECMO and 69 were not. The mean follow-up averaged 81.2 months (standard deviation 36 mo, range 0-184 mo); follow-up was complete in 100% of patients. The overall incidence of GD (30%) and of VA-ECMO use increased over the study period. We did not identify any predictive pre-transplantation factors for VA-ECMO use, but patients who required VA-ECMO had higher serum lactate levels and higher inotropes doses after HT. The overall survival rates were 83% and 42% at 1 year and 78% and 40% at 5 years among patients who received only medical treatment and those who received VA-ECMO, respectively. Delayed initiation of VA-ECMO and postoperative bleeding were strongly associated with increased in-hospital mortality. CONCLUSION: The incidence of GD increased over the study period, and the need for VA-ECMO among patients with GD remains difficult to predict. In-hospital mortality decreased over time but remained high among patients who required VA-ECMO, especially among patients with delayed initiation of VA-ECMO.

New Insights in Mechanisms and Therapeutics for Short- and Long-Term Impacts of Hepatic Ischemia Reperfusion Injury Post Liver Transplantation.

Liver transplantation has been identified as the most effective treatment for patients with end-stage liver diseases. However, hepatic ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post transplantation. Cell death, including apoptosis, necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft inflammation. The inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection, cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of cancer recurrence and fibrogenesis due to the long-term impact of inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.

Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: "ischemia reperfusion injury", "liver transplantation", "hepatocellular carcinoma", "preconditioning", "machine perfusion".

Risk Factors for Severe Primary Graft Dysfunction in Infants Following Heart Transplant.

Background Previous studies suggest that infant heart transplant (HT) recipients are at higher risk of developing severe primary graft dysfunction (PGD) than older children. We sought to identify risk factors for developing severe PGD in infant HT recipients. Methods and Results We identified all HT recipients aged <1 year in the United States during 1996 to 2015 using the Organ Procurement and Transplant Network database. We linked their data to ELSO (Extracorporeal Life Support Organization) registry data to identify those with severe PGD, defined by initiation of extracorporeal membrane oxygenation support for PGD within 2 days following HT. We used multivariable logistic regression to assess risk factors for developing severe PGD. Of 1718 infants analyzed, 600 (35%) were <90 days old and 1079 (63%) had congenital heart disease. Overall, 134 (7.8%) developed severe PGD; 95 (71%) were initiated on extracorporeal membrane oxygenation support on the day of HT, 34 (25%) the next day, and 5 (4%) the following day. In adjusted analysis, recipient congenital heart disease, extracorporeal membrane oxygenation, or biventricular assist device support at transplant, recipient blood type AB, donor-recipient weight ratio <0.9, and graft ischemic time ≥4 hours were independently associated with developing severe PGD whereas left ventricular assist device support at HT was not. One-year graft survival was 48% in infants with severe PGD versus 87% without severe PGD. Conclusions Infant HT recipients with severe PGD have poor graft survival. Although some recipient-level risk factors are nonmodifiable, avoiding modifiable risk factors may mitigate further risk in infants at high risk of developing severe PGD.

Percutaneous RVAD with the Protek Duo for severe right ventricular primary graft dysfunction after heart transplant.

Right ventricular primary graft dysfunction after heart transplant is a serious life-threatening condition. The severe form, refractory to maximal medical therapy, has traditionally required temporary mechanical support through veno-arterial extracorporeal membrane oxygenation or central right ventricular support. The Protek Duo is a dual lumen cannula recently introduced in the market, which allows for the institution of a percutaneous right ventricular support. We present the first promising case series of the use of this novel support in patients with right ventricular primary graft dysfunction after heart transplant.

Successful management of donor-acquired fat embolism after lung transplantation.

Fat embolism is a serious complication in patients with multiple traumatic injuries. It is often asymptomatic during the first hours of resuscitation, thus remains underdiagnosed in patients who progress to brain death. Lung transplantation issued from such grafts can lead to severe lung primary graft dysfunction, the management of which is deemed difficult. Herein, we report a successful management of donor-acquired fat embolism syndrome after lung transplant in a 22 years old woman for cystic fibrosis. Fat embolism was suspected because of the donor's traumatic injuries and confirmed by histopathological analysis. An immediate postoperative primary graft dysfunction was successfully managed with veno-arterial extracorporeal membrane oxygenation. The patient is alive 31 months after surgery.

Prone Positioning as a Bridge to Recovery From Refractory Hypoxemia After Oversized Lung Transplant.

BACKGROUND: Size matching is an important challenge in lung transplantation. Although the survival rate after lung transplantation with an oversized allograft was improved, it is associated with substantial immediate postoperative morbidity and mortality. Prone positioning is a rescue therapy showing improved outcomes in acute respiratory distress syndrome. We present a case of immediate postoperative refractory hypoxemia after oversized lung transplantation treated by prone positioning. METHODS: A 62-year-old man was transferred to our hospital by our extracorporeal membrane oxygenation (ECMO) transport team because of acute exacerbation of idiopathic pulmonary fibrosis. He underwent bilateral lung transplantation through bilateral anterior thoracotomy. For size matching between donor and recipient, multiple wedge resection and lingular segmentectomy were performed, but an oversized lung was implanted. On the immediate postoperative day, chest radiography revealed haziness in the left lower quadrant and the patient had an increased O2 requirement; he could not be weaned from venovenous (VV) ECMO. Chest computed tomography revealed left lower lobar atelectasis and primary graft dysfunction. To revert the atelectatic portion, improve ventilation/perfusion mismatch, and avoid high ventilation pressure, we performed the recruitment maneuver. Despite this, his blood gas profile did not improve. Therefore, we applied prone positioning with VV ECMO. After conversion to the prone positioning, the hypoxia corrected and the tidal volume increased. After 20 hours, he was changed to the supine position. Thereafter, arterial blood gas analyses were stable and he could be weaned from ECMO. He was discharged on postoperative day 57 and maintained good respiratory function. CONCLUSIONS: This case demonstrated the safety and feasibility of prone positioning during the immediate postoperative period after lung transplant by bilateral anterior thoracotomy. Prone positioning successfully reversed postoperative atelectasis and improved primary graft dysfunction after oversized lung transplant.

Use of Organs for Heart Transplantation after Rescue Allocation: Comparison of Outcome with Regular Allocated High Urgent Recipients.

BACKGROUND: The number of patients waiting for heart transplantation (HTx) is exceeding the number of actual transplants. Subsequently, waiting times are increasing. One possible solution may be an increased acceptance of organs after rescue allocation. These organs had been rejected by at least three consecutive transplant centers due to medical reasons. METHODS: Between October 2010 and July 2019, a total of 139 patients underwent HTx in our department. Seventy (50.4%) of the 139 patients were transplanted with high urgency (HU) status and regular allocation (HU group); the remaining received organs without HU listing after rescue allocation (elective group, n = 69). RESULTS: Donor parameters were comparable between the groups. Thirty-day mortality was comparable between HU patients (11.4%) and rescue allocation (12.1%). Primary graft dysfunction with extracorporeal life support occurred in 26.9% of the elective group with rescue allocated organs, which was not inferior to the regular allocated organs (HU group: 35.7%). No significant differences were observed regarding the incidence of common perioperative complications as well as morbidity and mortality during 1-year follow-up. CONCLUSIONS: Our data support the use of hearts after rescue allocation for elective transplantation of patients without HU status. We could show that patients with rescue allocated organs showed no significant disadvantages in the early perioperative morbidity and mortality as well at 1-year follow-up.

Extracorporeal Membrane Oxygenation after Heart Transplantation: Impact of Type of Cannulation.

BACKGROUND: Primary graft dysfunction (PGD) is a common cause of early death after heart transplantation (htx). The use of extracorporeal life support (ECLS) after htx has increased during the last years. It is still discussed controversially whether peripheral cannulation is favorable compared to central cannulation. We aimed to compare both cannulation techniques. METHODS: Ninety patients underwent htx in our department between 2010 and 2017. Twenty-five patients were treated with ECLS due to PGD (10 central extracorporeal membrane oxygenator [cECMO] and 15 peripheral extracorporeal membrane oxygenator [pECMO] cannulation). Pre- and intraoperative parameters were comparable between both groups. RESULTS: Thirty-day mortality was comparable between the ECLS-groups (cECMO: 30%; pECMO: 40%, p = 0.691). Survival at 1 year (n = 18) was 40 and 30.8% for cECMO and pECMO, respectively. The incidence of postoperative renal failure, stroke, limb ischemia, and infection was comparable between both groups. We also did not find significant differences in duration of mechanical ventilation, intensive care unit stay, or in-hospital stay. The incidence of bleeding complications was also similar (cECMO: 60%; pECMO: 67%). Potential differences in support duration in pECMO group (10.4 ± 9.3 vs. 5.7 ± 4.7 days, p = 0.110) did not reach statistical significance. CONCLUSIONS: In patients supported for PGD, peripheral and central cannulation strategies are safe and feasible for prolonged venoarterial ECMO support. There was no increase in bleeding after central implantation. With regard to the potential complications of a pECMO, we think that aortic cannulation with tunneling of the cannula and closure of the chest could be a good option in patients with PGD after htx.

Ventilation parameters and early graft function in double lung transplantation.

BACKGROUND: Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU). METHODS: A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (PIP), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest. RESULTS: In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (PIP, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679. CONCLUSIONS: The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.