Current pharmaceutical design
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Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion-related mortality in most developed countries. Despite this fact, well-designed investigations on specific management strategies for TRALI are lacking. Indeed, current recommendations are primarily based on data extrapolated from trials of the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress Syndromes. ⋯ Specifically, conservative transfusion practices and deferral of high-plasma component donors who have, or at high risk of having, anti-human leukocyte antigen and/or anti-human neutrophil antigen antibodies have meaningfully impacted the incidence of TRALI. Future considerations for patients who are at increased risk for developing TRALI may include therapies such as anti-platelet agents and alternatives to traditional blood components such as prothrombin complex concentrates (PCC). However, these potential TRALI prevention strategies are insufficiently studied, have unclear risk/benefit profiles and cannot be currently recommended.
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Fospropofol is an intravenous sedative-anesthetic agent that is FDA-approved for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. As a prodrug of propofol, fospropofol's pharmacologic activity results from its breakdown by alkaline phosphatase and release of propofol, which is the active molecule. It exhibits a longer time to peak clinical effect and a more prolonged action compared to propofol. ⋯ Available evidence demonstrates that fospropofol in MAC sedation is successful in patients undergoing esophagogastroscopy, colonoscopy and flexible bronchoscopy. The use of fospropofol is also now being explored in many other perioperative settings. In light of current shortages of many anesthetic drugs, whether forspropofol can take the place of propofol in ICUs and operating rooms remains to be determined.
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Underlying cardiovascular disease is a potentially modifiable risk factor that contributes significantly to perioperative morbidity and mortality. Reducing perioperative and long-term morbidity and mortality requires risk modifying perioperative management. This, in turn, requires preoperative identification of patients with, or at risk of having cardiovascular disease. ⋯ Not all of them can reliably be predicted or modified in a way which improves outcome. However, recognition of such factors and aggressive attempts at appropriate intervention may reduce overall risk more than preoperative evaluation in isolation. Without defining and subsequently targeting intra- and postoperative risk factors, the benefit of preoperative cardiac evaluation will be limited.
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Anti-platelet agents have left an indelible impression in the management of a wide range of pathologies. From the earliest therapeutic agents such as aspirin, to the cutting edge agents still undergoing development, they have the capability to powerfully manipulate platelet biology, a central player in thrombosis. ⋯ Both have recently received licensing for use in acute coronary syndromes and promise to improve outcomes for patients. Here, we examine the rationale for the development and clinical integration of antiplatelet agents focusing upon prasugrel and ticagrelor.
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This paper will summarize the clinical features of transfusion-related acute lung injury (TRALI) before the experimental and clinical literature on the pathogenesis of TRALI is reviewed. Several mechanisms by which leukocyte antibodies induce TRALI have been unraveled. ⋯ In contrast, the pathomechanism behind non-immune TRALI (associated with the transfusion of blood components which do not contain antibodies) is less well understood, especially since the relevance of mechanisms proposed earlier is questioned by recent findings. The diversity of newly described factors contributing to TRALI supports the previously proposed threshold model of TRALI, and an extension of that model including newly defined multipliers and attenuators of TRALI is emerging.