Collaborative Management Strategies for Drug Shortages in Neurocritical Care.

Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients.

Comparative effectiveness of epsilon-aminocaproic acid and tranexamic acid on postoperative bleeding following cardiac surgery during a national medication shortage.

STUDY OBJECTIVE: The aim of this study was to compare the effectiveness of epsilon-aminocaproic acid (εACA) and tranexamic acid (TXA) in contemporary clinical practice during a national medication shortage. DESIGN: A retrospective cohort study. SETTING: The study was performed in all consecutive cardiac surgery patients (n=128) admitted to the cardiac-surgical intensive care unit after surgery at a single academic center immediately before and during a national medication shortage. MEASUREMENTS: Demographic, clinical, and outcomes data were compared by descriptive statistics using χ2 and t test. Surgical drainage and transfusions were compared by multivariate linear regression for patients receiving εACA before the shortage and TXA during the shortage. MAIN RESULTS: In multivariate analysis, no statistical difference was found for surgical drain output (OR 1.10, CI 0.97-1.26, P=.460) or red blood cell transfusion requirement (OR 1.79, CI 0.79-2.73, P=.176). Patients receiving εACA were more likely to receive rescue hemostatic medications (OR 1.62, CI 1.02-2.55, P=.041). CONCLUSIONS: Substitution of εACA with TXA during a national medication shortage produced equivalent postoperative bleeding and red cell transfusions, although patients receiving εACA were more likely to require supplemental hemostatic agents.

OTC tranexamic acid for heavy menstrual bleeding?

Tranexamic acid, an oral antifibrinolytic, is due to become available soon for purchase from pharmacies without prescription for the self-management of heavy menstrual bleeding. It is the first over-the-counter (OTC) medicine licensed specifically for this condition.1 The Medicines and Healthcare products Regulatory Agency (MHRA) views such availability of tranexamic acid (to be sold as Cyklo-F) as "an important step for women, helping improve their quality of life and providing them with the greater convenience of better access to medicines".1 Here we review the efficacy and safety of tranexamic acid and discuss whether its OTC availability is a helpful development.

Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy in cardiac surgery.

Antifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).

Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of perceived risk and product licensing on effectiveness.

OBJECTIVE: To determine current use of vitamin K (VK) prophylaxis in newborns and review the efficacy and effectiveness of regimens used. DESIGN: Efficacy and effectiveness calculated using current practice details, data from Southern Ireland and two previous surveys, together with contemporaneous studies of vitamin K deficiency bleeding (VKDB). SETTING: Current survey: United Kingdom (Great Britain and Northern Ireland). Efficacy and effectiveness tables: United Kingdom and Southern Ireland. MAIN OUTCOME MEASURES: Current VK prophylaxis following uncomplicated term deliveries. Relative risk of VKDB calculated for the VK actually received and for "intention to treat". RESULTS: Questionnaire response rate 95% (n = 243), all recommending VK prophylaxis. No association between unit size and route of administration. For uncomplicated term deliveries, 60% recommended intramuscular (IM) prophylaxis, 24% oral and 16% offered both routes without bias. All units offering IM gave a single dose, mostly 1 mg Konakion Neonatal. Oral regimens showed more variation: two thirds gave 2 mg (range 0.5-2 mg), the number of doses ranged from 1 to 11 and many used preparations off-licence or the unlicensed Orakay. IM prophylaxis, if given, provided the best protection (most efficacious) against VKDB. However, on an intention-to-treat basis (effectiveness), there is no statistically significant difference between the risks of VKDB after intended IM VK and after oral prophylaxis intended to continue beyond a week. CONCLUSIONS: Although the principles of VK prophylaxis is now accepted by all, there is no uniformity in practice. Omission of prophylaxis appears to be a greater problem for IM than for multi-dose oral prophylaxis, affecting overall effectiveness.