Extracorporeal membrane oxygenation (ECMO) is a well-established treatment for severe cardiopulmonary failure. Patients undergoing ECMO support through femoral vessels are prone to vascular ...complications. The aim of this study was to evaluate such complications to outline basic technical principles for their prevention.
From January 2005 to December 2009, 174 patients underwent ECMO support through cannulation of the femoral vessels. The primary outcome was any vascular complication. Secondary outcomes were 30-day mortality and 1-year survival. A logistic regression analysis including ECMO duration, peripheral arterial disease, ECMO access (percutaneous versus open), and diabetes mellitus identified predictors for vascular complications.
The venoarterial mode was used in 143 patients (82%), and venovenous in 31 patients (18%). Of the 17 (10%) observed vascular complications, 15 (88%) occurred in patients with venoarterial access, whereas 2 (12%) occurred after venovenous access (p=0.50) Two patients who had extremity ischemia required limb amputation. Thirty-day mortality and 1-year survival rates were 63% and 26%, respectively. Peripheral arterial disease was the only strong predictor of vascular complications (odds ratio, 6.95; 95% confidence interval, 1.89 to 25.59; p=0.003). Vascular complications were not associated with early or late mortality.
The incidence of vascular complications in venovenous cannulation was low, whereas in arterial cannulation, it is still considerable. Peripheral arterial disease remains a risk factor, and early involvement of vascular surgeons for open vascular exposure or alternative vascular access sites can be recommended. Vascular complications after ECMO support are not associated with higher mortality rates.
The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in ...all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.
Previous studies have demonstrated substantial genetic diversification of Pseudomonas aeruginosa across sub-compartments in cystic fibrosis (CF) lungs. Here, we isolate P. aeruginosa from five ...different sampling areas in the upper and lower airways of an explanted CF lung, analyze ex vivo transcriptional profiles by RNA-seq, and use colony re-sequencing and deep population sequencing to determine the genetic diversity within and across the various sub-compartments. We find that, despite genetic variation, the ex vivo transcriptional profiles of P. aeruginosa populations inhabiting different regions of the CF lung are similar. Although we cannot estimate the extent to which the transcriptional response recorded here actually reflects the in vivo transcriptomes, our results indicate that there may be a common in vivo transcriptional profile in the CF lung environment.
Objectives Patients requiring extracorporeal cardiorespiratory support during lung transplantation can be treated with conventional cardiopulmonary bypass (CPB) or venoarterial extracorporeal ...membrane oxygenation (ECMO). In a retrospective analysis, we compared the postoperative course and outcomes of patients treated using these approaches. Methods Between August 2008 and September 2011, 92 consecutive patients underwent lung transplantation with extracorporeal support (CPB group, n = 46; and, since February 2010, ECMO group, n = 46) at our institution. We evaluated survival, secondary organ failure, bleeding complications, and the need for blood and platelet transfusions in these 2 patient populations. Results Intraoperatively, the CPB group required more packed red blood cell transfusions (12 ± 11 vs 7 ± 9 U; P = .01) and platelet concentrates (2.5 ± 1.6 vs 1.5 ± 1 U; P < .01) than the ECMO group. In-hospital mortality (39% vs 13%; P = .004), the need for hemodialysis (48% vs 13%; P < .01), and new postoperative ECMO support (26% vs 4%; P < .01) were greater in the CPB group than in the ECMO group, respectively. After propensity score analysis, multivariate analysis identified retransplantation (odds ratio, 7; 95% confidence interval, 1-43; P = .034) and transplantation with CPB support (odds ratio, 4.9; 95% confidence interval, 1.2-20; P = .026) as independent risk factors for in-hospital mortality. The survival rate at 3, 9, and 12 months was 70%, 59%, and 56% in the CPB group and 87%, 81%, and 81% in the ECMO group ( P = .004). Conclusions Intraoperative ECMO allows for better periprocedural management and reduced postoperative complications and confers a survival benefit compared with CPB, mainly because of lower in-hospital mortality. It is now the standard of care in our lung transplantation program.
During recent years, continuous technological innovation has provoked an increase of extracorporeal life support (ECLS) use for perioperative cardiopulmonary support in lung transplantation. Initial ...results were disappointing, due to ECLS-specific complications and high surgical risk of the supported patients. However, the combination of improved patient management, multidisciplinary team work and standardization of ECLS protocols has recently yielded excellent results in several case series from high-volume transplant centres. Therein, it was demonstrated that, although the prevalence of complications remains higher in supported patients, there may be no difference in long-term graft function between supported and non-supported patients. These results are important, because most of the patients who require ECLS support in lung transplantation are young and have no other chance to survive, but to be transplanted. Moreover, there is no device for "bridging to destination" therapy in lung transplantation. Of note, the evidence in favour of ECLS support in lung transplantation was never validated by randomized controlled trials, but by everyday experience at the patient bed-side. Here, we review the state-of-the-art ECLS evidence for intraoperative and postoperative cardiopulmonary support in lung transplantation.
Summary Background Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of ...donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs. Methods Between Feb 18, and July 1, 2011, 12 patients were transplanted at two academic lung transplantation centres in Hanover, Germany and Madrid, Spain. Lungs were perfused with low-potassium dextran solution, explanted, immediately connected to the OCS Lung, perfused with Steen's solution supplemented with two red-cell concentrates. We assessed donor and recipient characteristics and monitored extended criteria donor lung scores; primary graft dysfunction scores at 0, 24, 48, and 72 h; time on mechanical ventilation after surgery; length of stays in hospital and the intensive-care unit after surgery; blood gases; and survival of grafts and patients. Findings Eight donors were female and four were male (mean age 44·5 years, range 14–72). Seven recipients were female and five were male (mean age 50·0 years, range 31–59). The preharvest donor ratio of partial pressure of oxyen (PaO2 ) to fractional concentration of oxygen in inspired air (FI O2 ) was 463·9 (SD 91·4). The final ratio of PaO2 to FI O2 measured with the OCS Lung was 471·58 (127·9). The difference between these ratios was not significant (p=0·72). All grafts and patients survived to 30 days; all recipients recovered and were discharged from hospital. Interpretation Lungs can be safely preserved with the OCS Lung, resulting in complete organ use and successful transplantation in our series of high-risk recipients. In November, 2011, we began recruitment for a prospective, randomised, multicentre trial (INSPIRE) to compare preservation with OCS Lung with standard cold storage. Funding TransMedics and German Federal Ministry of Education and Research.
Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disorder often caused by cigarette smoke. Cigarette smoke contains hundreds of toxic substances. In our study, we wanted ...to identify initial mechanisms of cigarette smoke induced changes in the distal lung. Viable slices of human lungs were exposed 24 h to cigarette smoke condensate, and the dose–response profile was analyzed. Non-toxic condensate concentrations and lipopolysaccharide were used for further experiments. COPD-related protein and gene expression was measured. Cigarette smoke condensate did not induce pro-inflammatory cytokines and most inflammation-associated genes. In contrast, lipopolysaccharide significantly induced IL-1α, IL-1β, TNF-α and IL-8 (proteins) and IL1B, IL6, and TNF (genes). Interestingly, cigarette smoke condensate induced metabolism- and extracellular matrix–associated proteins and genes, which were not influenced by lipopolysaccharide. Also, a significant regulation of CYP1A1 and CYP1B1, as well as MMP9 and MMP9/TIMP1 ratio, was observed which resembles typical findings in COPD. In conclusion, our data show that cigarette smoke and lipopolysaccharide induce significant responses in human lung tissue ex vivo, giving first hints that COPD starts early in smoking history.
Despite the scarcity of donor lungs, most potential donor organs are not offered by organ procurement organizations or are turned down by transplant centers because no suitable recipient is found ...according to regular allocation. Although extended criteria donors (ECDs) have recently been considered by many programs, the lung utilization rate remains < 30% in most countries. The allocation policy of Eurotransplant for donor lungs that have been turned down for donor-related medical reasons by 3 centers is to attempt a rescue offer, for which centers choose the recipients themselves. At Hannover Medical School we systematically divert these organs to more stable recipients to avoid adverse transplant outcomes. We follow up on these transplants and compare them with those following regular allocation.
This study is an analysis of all organ offers and corresponding recipients at our center during the period from January 2010 to August 2011.
A total of 183 lung transplantations were performed, 111 regular donor lung offers were accepted for their intended recipient, whereas a total of 72 rescue lung offers, including all extended criteria donors, were accepted for recipients selected by our center. Donor characteristics differed between the 2 groups accordingly. Median age of ECD organ donors was significantly higher than that of regular donors (46.0 IQR 21 vs 40.0 IQR 22 years, p = 0.02). Donor mechanical ventilation time did not differ (3.5 ± 4.8 vs 3.0 ± 4.0 days, p = 0.33, not statistically significant NS). Donor oxygenation ratio (PaO2:FIO2) at time of organ offer was significantly lower (398.3 ± 110.3 vs 423.0 ± 97.6 mm Hg, p = 0.02). Recipients of rescue allocation organs were older than regularly selected recipients (53.7 ± 11.7 vs 46.7 ± 15.4 years, p = 0.0003), needed a shorter time for mechanical ventilation post-operatively (19.5 ± 306.6 vs 68.5 ± 718.8 hours, p = 0.02), and had shorter hospital stays (24.0 ± 23.4 vs 47.0 ± 43.4 days, p > 0.0001). Intensive care stay length did not differ significantly (2.0 ± 14.5 vs 5.0 ± 23.7 days, p = 0.21 NS). Post-operative survival up to 27 months after transplantation was not worse in recipients receiving rescue allocation when compared with standard allocation lung offers (81.62% vs 80.76%, p = 0.89 NS). The pre-operative status of the 2 recipient cohorts differed considerably, as indicated by the standard allocation group consisting of 65.8% "high-urgency" (HU)-listed patients, whereas the rescue offers were used for only 11.1% of HU-listed recipients, reflecting our center's policy.
Rescue allocation donor lungs can be used safely for transplantation and therefore salvaged for the donor pool. The data support our policy of accepting marginal donor lungs for stable recipients. This practice leads to very good overall survival.
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease harboring significant morbidity and mortality despite recent advances in therapy. Regardless of disease severity acute ...exacerbations (IPF-AEs) may occur leading to considerable loss of function and are the leading cause of death in IPF. Histologic features of IPF-AE are very similar to acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the role of the NLRP3 inflammasome in IPF and IPF-AE. Bronchoalveolar lavage (BAL) cells were sampled from patients with IPF (n = 32), IPF-AE (n = 10), ARDS (n = 7) and healthy volunteers (HV, n = 37) and the NLRP3-inflammasome was stimulated
. We found the NLRP3 inflammasome to be hyper-inducible in IPF compared to HV with increased IL-1ß and pro-IL-1ß levels on ELISA upon stimulation as well as increased caspase-1 activity measured by caspase-1p20 immunoblotting. In IPF-AE, IL-1ß was massively elevated to an extent similar to ARDS. To evaluate potential mechanisms, we co-cultured BAL cells with radiated A549 cells (a model to simulate apoptotic alveolar epithelial cells), which led to increased NLRP3 mRNA expression and increased caspase-1 dependent IL-1ß production. In the presence of a reactive oxygen species (ROS) inhibitor (diphenyleneiodonium) and a cathepsin B inhibitor (E64D), NLRP3 expression was suppressed indicating that induction of NLRP3 activation following efferocytosis of apoptotic A549 cells is mediated
ROS and cathepsin-B. In summary, we present evidence of involvement of the NLRP3 inflammasome-caspase pathway in the pathogenesis of IPF-AE, similarly to ARDS, which may be mediated by efferocytosis of apoptotic alveolar epithelial cells in IPF.
Aims
Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a ...nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany.
Methods and results
A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%;
p
= 0.014), arrhythmias (50.0% vs. none;
p
= 0.012), and thromboembolic events (50.0% vs. none;
p
= 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (
p
= 0.017 and
p
< 0.001, respectively).
Conclusion
Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.
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