Assessing the clinical utilization of tranexamic acid by paramedics for patients with major trauma (ACUTE).

OBJECTIVES: This study aimed to characterize the clinical utilization of tranexamic acid (TXA) by paramedics in British Columbia (BC) for acute major trauma and to quantify the percentage of patients who received TXA among those who met the indications for administration. METHODS: A quality assurance review of eligible trauma patients across the province was performed using a convenience sample. Trauma patients between April 1, 2016 and March 31, 2017 with suspected or actual hemorrhage were selected if they met inclusion criteria (systolic blood pressure < 90 mm Hg ± heart rate > 120 beats per minute) and exclusion criteria (age < 16 years, injuries exclusively to the extremities). RESULTS: 35 of the 100 eligible patients assessed in this review received a dose of TXA from paramedics. All 35 of the patients received TXA within 180 min of injury regardless of their original location of injury in BC (mean: 50 min; range: 15-140 min). CONCLUSIONS: 35% of eligible patients identified in this study received TXA, which is an improvement over rates cited by previous Canadian literature. With further education opportunities for paramedics in BC and other EMS systems, there is potential to continue improving pre-hospital TXA administration rates.

RéSUMé: OBJECTIFS: Cette étude visait à caractériser l'utilisation clinique de l'acide tranexamique (TXA) par les ambulanciers paramédicaux de la Colombie-Britannique pour les traumatismes aigus majeurs et à quantifier le pourcentage de patients qui ont reçu du TXA parmi ceux qui répondaient aux indications d'administration. MéTHODES: Un examen de l'assurance qualité des patients traumatisés admissibles dans toute la province a été effectué à l'aide d'un échantillon de commodité. Les patients traumatisés entre le 1er avril 2016 et le 31 mars 2017 présentant une hémorragie suspectée ou réelle ont été sélectionnés s'ils répondaient aux critères d'inclusion (pression artérielle systolique < 90 mm Hg ± fréquence cardiaque > 120 battements par minute) et aux critères d'exclusion (âge < 16 ans, blessures exclusivement aux extrémités). RéSULTATS: 35 des 100 patients admissibles évalués dans le cadre de cet examen ont reçu une dose de TXA des ambulanciers paramédicaux. Les 35 patients ont tous reçu du TXA dans les 180 min suivant la blessure, quel que soit le lieu de leur blessure initiale en Colombie-Britannique (moyenne: 50 min; intervalle: 15 à 140 min). CONCLUSIONS: 35% des patients admissibles identifiés dans le cadre de cette étude ont reçu du TXA, ce qui représente une amélioration par rapport aux taux cités dans les publications canadiennes précédentes. Grâce aux possibilités de formation continue pour les ambulanciers en Colombie-Britannique et dans d'autres systèmes d'Aide médicale urgente (AMU), il est possible de continuer à améliorer les taux d'administration de la TXA en milieu préhospitalier.

Intramuscular Tranexamic Acid in Tactical and Combat Settings.

BACKGROUND: Uncontrolled hemorrhage remains a leading cause of preventable death in tactical and combat settings. Alternate routes of delivery of tranexamic acid (TXA), an adjunct in the management of hemorrhagic shock, are being studied. A working group for the Committee for Tactical Emergency Casualty Care reviewed the available evidence on the potential role for intramuscular (IM) administration of TXA in nonhospital settings as soon as possible from the point of injury. METHODS: EMBASE and MEDLINE/PubMed databases were sequentially searched by medical librarians for evidence of TXA use in the following contexts and/or using the following keywords: prehospital, trauma, hemorrhagic shock, optimal timing, optimal dose, safe volume, incidence of venous thromboembolism (VTE), IM bioavailability. RESULTS: A total of 183 studies were reviewed. The strength of the available data was variable, generally weak in quality, and included laboratory research, case reports, retrospective observational reviews, and few prospective studies. Current volume and concentrations of available formulations of TXA make it, in theory, amenable to IM injection. Current bestpractice guidelines for large-volume injection (i.e., 5mL) support IM administration in four locations in the adult human body. One case series suggests complete bioavailability of IM TXA in healthy patients. Data are lacking on the efficacy and safety of IM TXA in hemorrhagic shock. CONCLUSION: There is currently insufficient evidence to support a strong recommendation for or against IM administration of TXA in the combat setting; however, there is an abundance of literature demonstrating efficacy and safety of TXA use in a broad range of patient populations. Balancing the available data and risk- benefit ratio, IM TXA should be considered a viable treatment option for tactical and combat applications. Additional studies should focus on the optimal dose and bioavailability of IM dosing of patients in hemorrhagic shock, with assessment of potential downstream sequelae.

Munc18b is a major mediator of insulin exocytosis in rat pancreatic ß-cells.

Sec1/Munc18 proteins facilitate the formation of trans-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes that mediate fusion of secretory granule (SG) with plasma membrane (PM). The capacity of pancreatic ß-cells to exocytose insulin becomes compromised in diabetes. ß-Cells express three Munc18 isoforms of which the role of Munc18b is unknown. We found that Munc18b depletion in rat islets disabled SNARE complex formation formed by syntaxin (Syn)-2 and Syn-3. Two-photon imaging analysis revealed in Munc18b-depleted ß-cells a 40% reduction in primary exocytosis (SG-PM fusion) and abrogation of almost all sequential SG-SG fusion, together accounting for a 50% reduction in glucose-stimulated insulin secretion (GSIS). In contrast, gain-of-function expression of Munc18b wild-type and, more so, dominant-positive K314L/R315L mutant promoted the assembly of cognate SNARE complexes, which caused potentiation of biphasic GSIS. We found that this was attributed to a more than threefold enhancement of both primary exocytosis and sequential SG-SG fusion, including long-chain fusion (6-8 SGs) not normally (2-3 SG fusion) observed. Thus, Munc18b-mediated exocytosis may be deployed to increase secretory efficiency of SGs in deeper cytosolic layers of ß-cells as well as additional primary exocytosis, which may open new avenues of therapy development for diabetes.