Clinical Pharmacokinetics and Impact of Hematocrit on Monitoring and Dosing of Tacrolimus Early After Heart and Lung Transplantation
AbstractThe calcineurin inhibitor tacrolimus is an effective immunosuppressant and is extensively used in solid organ transplantation. In the first week after heart and lung transplantation, tacrolimus dosing is difficult due to considerable physiological changes because of clinical instability, and toxicity often occurs, even when tacrolimus concentrations are within the therapeutic range. The physiological and pharmacokinetic changes are outlined. Excessive variability in bioavailability may lead to higher interoccasion (dose-to-dose) variability than interindividual variability of pharmacokinetic parameters. Intravenous tacrolimus dosing may circumvent this high variability in bioavailability. Moreover, the interpretation of whole-blood concentrations is discussed. The unbound concentration is related to hematocrit, and changes in hematocrit may increase toxicity, even within the therapeutic range of whole-blood concentrations. Therefore, in clinically unstable patients with varying hematocrit, aiming at the lower therapeutic level is recommended and tacrolimus personalized dosing based on hematocrit-corrected whole-blood concentrations may be used to control the unbound tacrolimus plasma concentrations and subsequently reduce toxicity.
Publication date: Available online 25 January 2020Source: Best Practice &Research Clinical AnaesthesiologyAuthor(s): Miriam Zeillemaker - Hoekstra, Carlijn I. Buis, Vlado Cernak, Koen MEM. ReyntjensAbstractThe combined transplantation of a thoracic organ and the liver is performed in patients with dual-organ failure in whom survival is not expected with single-organ transplantation alone. Although uncommonly performed, the number of combined liver-lung and liver-heart transplants is increasing. Anesthetic management of this complex procedure is challenging. Major blood loss, prolonged operation time, difficult weaning ...
Recipients of solid organ transplant (SOT) are at risk of viral infection and development of viral-driven malignancy (EBV-PTLD) due to immunosuppressive medications to prevent organ rejection. Treatments are limited by poor efficacy and organ toxicity, and reduction in immunosuppression to enable the patient's immune system fight the infection risks organ rejection. Allogeneic viral specific T-cells (VST) have been used to treat viral infections after stem cell transplant, and here we evaluated VST for the treatment of CMV, ADV, EBV-PTLD and BK in six SOT (heart, liver, kidney, lung) recipients.
Prior research has suggested that the prevalence and outcomes of pulmonary arterial hypertension (PAH) may vary by race or ethnicity. However, these studies have been limited by small sample size or methodological techniques relying on epidemiologic data. The purpose of this study is to evaluate the relationship between race/ethnicity and survival in a large U.S.-based prospective multicenter registry.
Mechanical circulatory support (MCS) evolved from an engineering dream to clinical reality during the 1980s when increasing numbers of patients were dying on heart transplant wait lists. Following the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Trial,1 the US Food and Drug Administration (FDA) approved a pulsatile implantable left ventricular assist device (LVAD) for long-term implantation in 2002. When the FDA approved the first US continuous flow (CF) LVAD in 2008, the landscape had changed dramatically.
The increasing life expectancy of humans has led to a growing numbers of patients with chronic diseases and end-stage organ failure. Transplantation is an effective approach for the treatment of end-stage organ failure; however, the imbalance between organ supply and the demand for human organs is a bottleneck for clinical transplantation. Therefore, xenotransplantation might be a promising alternative approach to bridge the gap between the supply and demand of organs, tissues, and cells; however, immunological barriers are limiting factors in clinical xenotransplantation. Thanks to advances in gene-editing tools and immun...
Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the non-invasive French risk assessment approach (number of low-risk criteria based on the ESC/ERS guidelines) and REVEAL 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH.
Despite advances in drug development, life expectancy in idiapathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient's outcome is still unfavorable.
Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival after durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival in those requiring pre-operative TCS.
Lung transplantation (LTx) offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of LTX offer acceptance, and to ascertain the associated contribution to observed differences in per-center waitlist mortality.
In this study, we determined whether symptomatic respiratory viral infections in post-lung transplantation induce circulating exosomes that contain lung-associated self-antigens, and to assess whether these exosomes activate immune responses to self-antigens.