Assessment of unintended volume loss of six closed system transfer devices.

INTRODUCTION: Closed system transfer devices (CSTDs) are used to prepare and administer hazardous drugs. Previous studies have explored the vapor and fluid containment performance of CSTDs. A less obvious consideration is the effect of CSTD use on the intended dose for small volume administrations. We assessed six CSTDs to determine if they contribute to volume loss and delivery of less than the intended dose during simulated drug administration. METHODS: Using an analytical balance, we obtained the mass of each CSTD at four points during simulated drug preparation and subcutaneous administration using sterile water. We used the masses to determine the average volume loss (VL) for each CSTD. RESULTS: Using ANOVA, we identified significant differences in volume loss (VL) among the mean VL (F(6,59) = 18.45, p = 6.19 × 10-12) for the six CSTDs and control (no CSTD). Four CSTDs had a VL that was statistically different than the control (p < 0.05); the VL for two CSTDs was not statistically different than the control (p > 0.05). Volume loss did not depend on administration volume. CONCLUSION: Volume loss performance varied among CSTDs. Volume loss may be clinically significant for small volumes but is not likely clinically significant for larger volumes. It is the authors' opinion that 3 mL represents a reasonable administration threshold below which volume loss should be considered clinically significant. Users should consider volume loss in context of the tasks, drugs, users, and environments where CSTDs will be used. The United States Pharmacopeia (USP) General Chapter <800>: Hazardous Drugs-Handling in Healthcare Settings recognizes the lack of CSTD performance standards. USP <800> recommends independent performance evaluation of CSTDs based on peer-reviewed studies. Our study adds to the comparative performance evaluations of CSTDs available on the market at the time of this review.

Ximelagatran: an oral direct thrombin inhibitor.

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of ximelagatran, an oral direct thrombin inhibitor (DTI), and to review available comparative clinical trial data evaluating its efficacy and safety relative to other antithrombotic agents in the prevention and treatment of thromboembolism. DATA SOURCES: A search of the PubMed and Cochrane databases (1995-August 2004), supplemented by a manual search of article bibliographies, conference abstracts, and data on file from the manufacturer, was conducted. Key search terms were ximelagatran, melagatran, H376/95, and direct thrombin inhibitors. STUDY SELECTION AND DATA EXTRACTION: Pertinent information from available clinical trials, including study design, patient demographics, dosing regimens, anticoagulant comparators, methods for evaluating effectiveness, treatment outcomes, adverse events, and pharmacokinetic and pharmacodynamic evaluations, was extracted. DATA SYNTHESIS: Ximelagatran is an orally administered DTI under development for use in the treatment of venous thromboembolism (VTE), long-term prevention of a second VTE event, stroke secondary to atrial fibrillation, prevention of VTE after orthopedic procedures, and recurrent ischemic events after acute myocardial infarction. CONCLUSIONS: Ximelagatran, in twice-daily doses of 24 or 36 mg, is an alternative to low-molecular-weight heparins or warfarin in thromboprophylaxis following orthopedic knee replacement, atrial fibrillation, or initial treatment of VTE. Improved outcomes versus placebo were seen in the long-term prevention of VTE in patients who completed an initial 6 months of treatment. Liver-related effects need further clarification.

Developing an algorithm for treating heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a serious and common complication of heparin therapy that can lead to significant losses of life and limb. It is often under-recognized and, therefore, goes untreated until thrombosis develops. This article is meant to provide specific recommendations for treating patients with immune-mediated HIT, whether or not it is associated with thrombosis. These recommendations are based on our clinical experience treating patients with HIT and our evaluation of the published data on the efficacy and safety of lepirudin and argatroban, the 2 drugs approved by the Food and Drug Administration for treating HIT. Based on these criteria, we consider lepirudin the treatment of choice in all patients with HIT except those with severe or deteriorating renal function.

Antithrombotic agents: implications in dentistry.

Thrombosis and the complicating emboli that can result are important causes of illness and death. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Agents such as heparin, low-molecular weight heparin, warfarin, aspirin, ticlopidine, clopidogrel, and tirofiban are used to prevent venous or arterial thrombosis. Patients taking these antithrombotic agents may be at risk for excessive bleeding after invasive dental procedures. The current antithrombotic agents used in medicine are reviewed, and the dental management of patients taking these agents is discussed.