Wieruszewski, Patrick M

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

AbstractProfessional standards for academic health care system pharmacy departments and clinical pharmacists advocate for research and scholarly activities. Developing and sustaining a research program in a clinical pharmacy department is challenging. Over the span of a decade, a robust pharmacy research program was developed in an academic medical center not affiliated with a college of pharmacy. The aim of this manuscript is to provide a framework suitable for scaling research in pharmacy departments within an academic medical center. Objectives to accomplish the aim includes describing the structure and evolution of the clinical pharmacy department research program, listing measurable outputs and achievements of the pharmacists and the program and describing the barriers encountered and solutions that were enacted to overcome them. Elements critical to building and sustaining a research program in the pharmacy department included long‐term commitment from within the department, a departmental research infrastructure, support from institutional leadership, research funding from the institution, and a growth mindset in accordance with company initiatives to support evolving research needs. A research curriculum was developed for pharmacy residents and pharmacists, created electronic tools for research proposal scientific reviews and allocation of funds, and established departmental research career development awards that allowed for protected time to pursue research and professional development. Over the first 10 years of the program, publication rates grew more than three‐fold, faculty appointments and promotions increased approximately five‐fold, and pharmacist investigators obtained extramural federal funding. Further offsetting clinical workload relative to dedicated research time remains a challenge. The experience and success at this academic medical center suggest it is feasible to develop a robust, sustainable clinical pharmacy department research program.

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85–13.20) seconds compared to only a 3.81 (95% CI = 1.55–6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) (p interaction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38–5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05–1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63–0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25–0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82–0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin’s hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

This study described the outcomes of patients receiving topical, nebulized, endobronchial, or systemic tranexamic acid (TXA) for bleeding events while on extracorporeal membrane oxygenation (ECMO). We performed a single-center case series including adult patients >18 years old supported on either venovenous (VV) or venoarterial (VA) ECMO from January 1, 2014, to April 21, 2021. The primary outcome was hemostatic control defined as a composite of initial cessation of therapeutic interventions to mitigate bleeding or resumption of anticoagulation if previously held. Secondary outcomes included changes in transfusion requirements and lysis at 30-minute (LY30) values, venous thromboembolism (VTE) events, and seizures. In total, 47 patients were included for full analysis. There were 19 patients with surgical bleeds, 18 patients with medical bleeds, and 10 patients with multiple bleeds. Overall, initial hemostatic control was achieved in 79%, 67%, and 90% of patients, respectively. Pre- and post-TXA transfusion requirements were not significantly different (p = 0.2), although the intraindividual change in median LY30 was −5.1% compared with baseline (95% confidence interval [CI], −12.4% to −1.5%, p = 0.005). The occurrence of VTE and seizures was relatively low and similar among patient bleeding groups. Tranexamic acid provided initial hemostatic control in roughly three quarters of patients with bleeding events on ECMO and side effects were infrequent.