Review of anticoagulation considerations in extracorporeal membrane oxygenation support.

Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.

Pharmacotherapy of chronic lung allograft dysfunction post lung transplantation.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains the primary cause of death in lung transplant recipients (LTRs) despite improvements in immunosuppression management. Despite advances in knowledge regarding the pathogenesis of CLAD, treatments that are currently available are usuallyineffective and delay progression of disease at best.There are currently no evidence-based guidelines and minimal publications regarding the optimal treatment ofCLAD. OBJECTIVE: To complete a comprehensive review of the literature for the prevention and medical management of CLAD. METHODS: We identified the major domains of the medical management of CLAD and conducted a comprehensive search of PubMed and Embase databases to identify articles published from inception to December 2021 related to CLAD in LTRs. Studies published in English pertaining to the pharmacologic prevention and treatment of CLAD were included; highest priority was given to prospective, randomized, controlled trials if available. Prospective observational and retrospective controlled trials were prioritized next, followed by retrospective uncontrolled studies, case series, and finally case reports if the information was deemed to be pertinent. Reference lists of qualified publications were also reviewed to find any other publications of interest that were not found on initial search.In the absence of literature published in the aforementioned databases, additional articles were identified by reviewing abstracts presented at the International Society for Heart and Lung Transplantation and American Transplant Congress annual meetings between 2010-2021. CONCLUSION: CLAD should be identified as early as possible along with prompt intervention to optimize the possibility of stabilizing or improving lung function. More robust clinical data is needed to validate the use of all currently available and investigational treatment options for CLAD to identify the optimal pharmacotherapy management for this patient population.

Outcomes of Lung Transplantation for Cystic Fibrosis in the Setting of Extensively Drug-Resistant Organisms.

INTRODUCTION: Since the largest study on extensively drug-resistant organisms and lung transplantation in patients with cystic fibrosis, there have been innovations and advancements in the treatment of Pseudomonas aeruginosa. RESEARCH QUESTION: What differences exist for patients with cystic fibrosis with a history of extensively drug-resistant infections who undergo lung transplantation despite treatment advances with antimicrobial therapy? STUDY DESIGN: Two-center, retrospective, cohort study conducted in 44 patients with cystic fibrosis chronically infected with extensively drug-resistant organisms who received a lung transplant from January 2008 through August 2016. Patients in the resistant cohort were chronically infected with pan-resistant P aeruginosa, polymyxin-sensitive only, or sensitive to 2 antibiotic classes (polymyxin plus one other); remaining patients with more susceptible P aeruginosa or no P aeruginosa remained in the control cohort. The primary outcome is a composite of patient survival, retransplantation, chronic lung allograft dysfunction, and acute rejection 12 months posttransplant. Categorical variables were analyzed using χ2 testing. The independent samples t test was utilized for continuous variables. RESULTS: There was no difference in the primary outcome (40% vs 37%, P = .831). Differences between patient survival (84% vs 95%, P = .487), the incidence of acute rejection (20% vs 33%, P = .323), and the incidence of chronic lung allograft rejection (12% vs 5%, P = .441) were not different between groups. DISCUSSION: Recipients chronically infected with an extensively resistant P aeruginosa had similar outcomes compared to those infected with more sensitive organisms.

Factor VIIa administration in orthotopic heart transplant recipients and its impact on thromboembolic events and post-transplant outcomes.

Recombinant, activated factor VIIa (rFVIIa) is used during cardiac surgeries to mitigate refractory coagulopathic bleeding. The purpose of this study was to examine whether rFVIIa use in orthotopic heart transplant (OHT) recipients was associated with a higher incidence of thromboembolic (TE) events compared to patients who did not. A single-center, retrospective, cohort study was performed on OHT recipients who received rFVIIa for refractory coagulopathic bleeding from January 2013 to December 2015. Patients were evaluated for up to 6 months after transplantation and assessed for TE events, rejection, readmissions, graft survival, and patient survival. Categorical variables were analyzed using the Chi square test while student's t or ANOVA testing was utilized for continuous variables. Of the 62 patients who met inclusion criteria, 27 patients received rFVIIa, and 35 patients were selected for the control group. The overall incidence of TE events was not significantly different between patients who received rFVIIa compared to patients in the control group (14.8% vs 11.4%) (p = 0.69). Within 14 days, 14.81% of rFVIIa patients suffered a TE event compared to 5.7% of the control group (p = 0.23). Rejection, readmissions, graft survival, and patient survival were not significantly different at any time points. Use of rFVIIa in heart transplantation showed no difference in the overall rate of TE events, however, there was a nonsignificant trend toward higher risk of early TE development in the rFVIIa group compared to the control group.

Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report.

Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis. CONCLUSION: Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

Opportunistic Pulmonary Infections in the Solid Organ Transplant Recipient: A Focus on Drug Therapy.

Immunosuppression required to prevent allograft rejection in the solid organ transplant recipient increases vulnerability to infections. Given continuous environmental exposure, the lungs are increasingly susceptible to bacterial, viral, and fungal opportunistic infections. Drug therapy options for the treatment of opportunistic pulmonary infections are used infrequently. These medications are often classified as high risk with specific administration instructions, as well as a multitude of toxicities. Therefore, in this article, we will discuss select pulmonary opportunistic infections and their associated drug therapies.