Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Vitamin K Antagonist Reversal: Does One Dose Fit All?

Four-factor prothrombin complex concentrate (4F-PCC) has emerged as the preferred option for emergent reversal of vitamin K antagonists (VKAs); however, the optimal dosing strategy is unknown. Although several studies have attempted to determine the optimal dose of 4F-PCC using a variety of dosing regimens, no dosing strategy has been found to be superior. Many of these studies have evaluated a low, fixed dose of 4F-PCC rather than individualized dosing as recommended in product labeling. The purpose of this review was to evaluate the efficacy and safety of various fixed-dose strategies of 4F-PCC for emergent VKA reversal and to assess limitations of the existing literature. A search of the PubMed database was performed from the earliest available date through 2018 for relevant articles describing fixed-dose 4F-PCC for VKA reversal. Reference lists of relevant articles were also manually reviewed. Most currently available studies are primarily observational and heterogeneous in design. A very low fixed dose of 500 IU is likely inadequate for successful VKA reversal, but increased fixed doses of 1000-1500 IU have found some degree of success and may be considered for VKA reversal. However, many of these studies consistently identified a trend toward international normalized ratio (INR) reversal failure in patients presenting with high baseline INR values or intracranial hemorrhage, suggesting that higher 4F-PCC doses are needed in these patients. Available studies are underpowered to determine whether a dose-dependent association with thrombotic risk exists. Additional large, randomized studies are needed to determine the optimal dosing strategy and ascertain the role for fixed-dose 4F-PCC.

Role of Bedside Preparation in Reducing "Door-to-Needle" Tissue-Type Plasminogen Activator (Alteplase) Administration Times and Association with Patient Outcomes.

INTRODUCTION: The purpose of this study is to assess the benefit of bedside alteplase preparation as a component of the acute stroke process. METHODS: A retrospective, single center study, designed to evaluate the impact of a bedside alteplase preparation protocol. Stroke patients receiving intravenous (IV) alteplase prepared at bedside were compared to pre-bedside alteplase preparation patients. The primary outcome was to compare door-to-needle (DTN) times between the groups. The secondary outcomes included comparison of pre-bedside alteplase preparation to post-bedside alteplase preparation on the following variables: imaging-to-drug times, order entry to drug administration times, percentage of patients achieving the 60 minute DTN goal, rate of intracranial hemorrhage (ICH), and patient discharge disposition. RESULTS: Patients in the pre-bedside preparation group included those who received IV alteplase between Jan. 1, 2012 and Jan. 31, 2015 and post-bedside preparation patients between Feb. 1, 2015 and March 31, 2016. Thirty-one patients were enrolled in the study, 16 in the pre-bedside preparation group and 15 in the post-beside preparation group. The mean DTN time in the post-bedside alteplase preparation group was significantly reduced, as compared to the pre-bedside preparation group (66.6 minutes vs. 95.9 minutes, p=0.024). Percent of patients meeting the 60 minute DTN time goal was significantly improved when alteplase was prepared at bedside (53.3 percent vs. 18.8 percent) (p=0.044). Rates of ICH were not significantly different between the two populations. CONCLUSIONS: Bedside alteplase preparation significantly reduced DTN times in an academic hospital emergency department.

Treatment of clinical aspiration: a reappraisal.

PURPOSE: The treatment of clinical aspiration is reviewed. SUMMARY: The common definition of aspiration is the inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract. Pulmonary aspiration frequently occurs in both the hospital and community settings and can affect patients of all ages. Aspiration can often lead to pulmonary complications, which can be divided into two main pathophysiological processes: chemical pneumonitis and aspiration pneumonia. These processes differ based on the aspirate contents, which ultimately dictate the physiological pathway and enduring symptoms. While these processes are clearly divergent, the clinical presentation may be indistinguishable, often leading to inappropriate or unnecessary treatment. Despite the widespread use of antibiotic therapy for aspiration complications, the literature supporting this treatment is quite limited. A literature review of clinical trials was conducted to address core aspects of aspiration complications, including bacteriology and empirical antibiotic treatment. The findings reveal that many of the current antibiotic practices used to treat clinical aspiration stem from limited studies dating back to the 1970s or before. Newer data have begun to refute these standard antibiotic regimens and provide a case for tailored empirical treatment. The treatment of aspiration should be largely focused on the underlying etiology and tailored to individual patients and their symptoms. CONCLUSION: The management of aspiration should largely focus on whether the underlying problem is pneumonitis or pneumonia. Recent studies on aspiration pneumonia have begun to show a difference in culture-isolated bacteria and therefore optimal treatment regimens, compared with pivotal human trials completed more than 40 years ago.