Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly being used for acute respiratory distress syndrome and as a bridge to lung transplantation. After initiation of venovenous ECMO, ...systemic anticoagulation therapy is traditionally administered and can cause bleeding diathesis. Here, we investigated whether venovenous ECMO can be administered without continuous systemic anticoagulation administration for patients with acute respiratory distress syndrome.
This is a retrospective review of an institutional ECMO database. We included consecutive patients from January 2015 through February 2019. Overall, 38 patients received low levels of continuous systemic anticoagulation (AC+) whereas the subsequent 36 patients received standard venous thromboprophylaxis (AC−). Published Extracorporeal Life Support Organization guidelines were used for the definition of outcomes and complications.
Overall, survival was not different between the two groups (P = .58). However, patients in the AC+ group had higher rates of gastrointestinal bleeding (28.9%, vs AC− group 5.6%; P < .001). The events per patient-day of gastrointestinal bleeding was 0.00025 in the AC− group and 0.00064 in the AC+ group (P < .001). In addition, oxygenator dysfunction was increased in the AC+ group (28.9% and 0.00067 events per patient-day, vs AC− 11.1% and 0.00062 events per patient-day; P = .02). Furthermore, the AC+ group received more transfusions: packed red blood cells, AC+ group 94.7% vs AC− group 55.5% (P < .001); fresh frozen plasma, AC+ 60.5% vs AC− 16.6% (P = .001); and platelets, AC+ 84.2% vs AC− 27.7% (P < .001). There was no circuit thrombosis in either groups throughout the duration of ECMO support.
Our results suggest that venovenous ECMO can be safely administered without continuous systemic anticoagulation therapy. This approach may be associated with reduced bleeding diathesis and need for blood transfusions.
Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) ...attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.
We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.
Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.
The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.
National Institutes of Health. VIDEO ABSTRACT.
The use of continuous-flow left ventricular assist devices (CF-LVADs) to treat advanced heart failure is increasing. Although risk scores, such as Model for End-Stage Liver Disease and the HeartMate ...II Risk Score, require the use of the international normalized ratio, many patients are on anticoagulation before CF-LVAD implantation. This study evaluated the ability of the Model of End-Stage Liver Disease-eXcluding International Normalized Ratio (MELD-XI) scoring system to predict clinical outcomes in patients with advanced heart failure who undergo CF-LVAD implantation.
A single-center retrospective review was performed of 524 patients who were implanted with the HeartMate II LVAD (Thoratec Corporation, Pleasanton, CA) or the HeartWare HVAD (HeartWare International Inc, Framingham, MA) between 2004 and 2016. Patients were stratified into two cohorts: those with a MELD-XI score of less than 14 (n = 301) and 14 or higher (n = 223).
Patients with the higher-risk MELD-XI score of 14 or higher demonstrated lower survival rates at 1, 3, 6, 12, and 24 months (p < 0.001 for all) and increased risk of early right heart failure and infections compared with patients with MELD-XI score of less than 14. MELD-XI was not significantly inferior at predicting 90-day mortality compared with the HeartMate II Risk Score (p = 0.92). Patients with elevated MELD-XI scores at follow-up demonstrated higher rates of mortality.
These findings suggest that a MELD-XI score of 14 or higher was associated with a higher postoperative mortality rate than that seen in patients with a lower MELD-XI score. The MELD-XI scoring system can be used to predict outcomes in patients with advanced heart failure who undergo CF-LVAD implantation.
Background
Lung transplantation for situs inverse is considered technically challenging because of the reverse positioning of the organs. By providing a detailed description of the surgical ...procedure, perioperative care, and post-transplant follow-up, we aim to contribute valuable information to the existing knowledge base. We presented two cases of successful bilateral sequential lung transplantation in situs inverse patients.
Case presentation
Our first patient was a 28-year-old, non-smoking woman with Kartagener syndrome and advanced bronchiectasis that developed into pneumonia and required repeated hospital admissions. She underwent double lung transplantation. During the lung transplant procedure, venoarterial extracorporeal membrane oxygenation (VA ECMO) support was provided. The recipient’s morphologically right (anatomically left) lung was explanted. The right main bronchus was anastomosed, followed by the pulmonary artery and left atrial anastomoses. Afterward, we proceeded with the left side. Similar to the right side, left pneumonectomy and implantation were performed using the same methods. The duration of VA ECMO support was 147 min with a 328-min ischemic time. Because of the significant size mismatch, nonanatomic lung volume reduction over the right middle and left upper lobes was necessary. The patient had no complications postoperatively and was discharged on post-operative day (POD) 12. Our second patient was a 51-year- old man with scleroderma-associated interstitial lung disease with situs inversus. Bilateral sequential lung transplantation was performed. Similar to case 1, a clamshell incision was made at the fourth intercostal space entry. The patient then received VA ECMO support identical to that in case 1. The total VA ECMO support time was 155 min with 295 min of ischemic time. The patient recovered uneventfully and was discharged on POD 13.
Conclusions
Lung transplantation for situs inverse can be a viable treatment option without modifying established transplantation procedures.
Extended duration extracorporeal membrane oxygenation (ECMO), using dual-lumen cannulas, is being used with increased frequency to support patients, including those with COVID-19; both as a bridge to ...transplant and lung recovery. During such an extended duration of support, there are several factors that might lead to the attrition of the physical structure of the ECMO cannulas, predisposing them to the risk of fracture. Although rare, fracture of the ECMO cannula can be a potentially lethal event. Here, we present a case where fracture of a dual lumen cannula during veno-venous (VV) ECMO support resulted in a cerebrovascular accident. We discuss the potential contributing factors and suggest steps to mitigate the risks for such a complication.
Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In ...syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1β-mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.
Abstract Background Although male gender, aging, hypertension, dyslipidemia, and smoking are common risk factors for abdominal aortic aneurysm, diabetes mellitus is an independent negative risk ...factor. In aneurysm tissue, matrix metalloproteinases expressed by activated macrophages degrades extracellular matrix proteins. In our previous experimental study, we demonstrated that the aneurysmal formation and macrophage activity were suppressed by inhibiting mimicking hyperglycemia (HG) through upregulation of glucose-sensing nuclear receptor, Nr1h2. Here in this study, we focused on the role of HG-induced altered glucose uptake on macrophage activation. Methods and results RAW264.7 murine macrophage cells were pretreated in cultures containing HG (HG group, 15.5 mM) or normal glucose (NG) concentrations (NG group, 5.5 mM) for 7 d. The culture medium was then changed in both groups to NG conditions, and the cells were stimulated with recombinant murine soluble receptor activator of NF-κB ligand. Macrophage activation was confirmed by tartrate-resistant acid phosphatase staining. Compared with the NG group, matrix metalloproteinase-9 expression in the HG group was significantly suppressed. Glucose uptake was increased in the NG group but not in the HG group during macrophage activation. To determine the mechanism of activation, we studied the expression and distribution of glucose transporters (Gluts) in the macrophages. Although Glut expression was unaffected by glucose pretreatment, membrane translocation of Glut-1 was significantly enhanced in macrophages in the NG group but not in the HG group during activation. Insulin receptor and insulin receptor substrate-1 (IRS-1) messenger RNA, known stimulate to membrane translocation of Gluts, were both decreased by the HG condition but not by the NG condition. Conclusions HG pretreatment suppressed the macrophage activation. Recombinant murine soluble receptor activator of NF-κB ligand increased macrophage glucose uptake at NG concentrations, which was impaired by HG pretreatment through the inhibition of Glut1 membrane translocation and the insulin receptor and IRS-1 gene transcription. These data suggest that HG suppressed macrophage activation, through attenuation of glucose uptake via the suppression of the membrane translocation of Glut1 and insulin signaling.
An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been ...previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.
Postoperative right-sided heart failure (RHF) is a common complication after continuous-flow left ventricular assist device implantation. Studies have examined RHF in the perioperative period, but ...few have assessed late-onset RHF. We analyzed the incidence of early and late RHF in patients with HeartMate II and HeartWare left ventricular assist devices and associated morbidity, mortality, and independent predictors of RHF. We retrospectively analyzed records of 526 patients with chronic heart failure who underwent continuous-flow left ventricular assist device implantation; 147 (27.9%) developed RHF (early RHF, n = 87, 16.5%; late RHF, n = 74, 14.4%). We examined demographics, postoperative complications, and long-term survival rate. Patients with RHF or late RHF had higher mortality (p <0.001) than those without RHF. Patients with RHF had a higher incidence of acute kidney injury (20.4% vs 11.9%, p = 0.01). Device type did not affect the incidence of early, late, or overall RHF. Patients with severe RHF requiring right ventricular assist device support had a low success of bridge to transplantation (11.1% vs 33.3%, p = 0.02). In Cox regression models, RHF was an independent predictor of mortality (hazard ratio = 1.69, 95% confidence interval = 1.28 to 2.22, p <0.001), but no predictive variables of RHF were identified. RHF was significantly associated with increased mortality and a higher incidence of postoperative acute kidney injury. RHF decreased the success rate of bridging patients to transplantation when a right ventricular assist device was required.
Mechanical circulatory support may result in sufficient myocardial recovery to allow for explantation of the left ventricular assist device (LVAD). The duration of support associated with left ...ventricular recovery has generally been 6–12 months. In this report, we present a patient in whom the left ventricle recovered after 5 years of support with a LVAD. Our report demonstrates that long-term monitoring for left ventricular recovery is prudent and may allow for late device explantation.