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.

The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review.

STUDY OBJECTIVE: To synthesize the evidence on the effect of a bolus dose of etomidate on adrenal function, mortality, and health services utilization compared with other induction agents used for rapid sequence intubation. METHODS: We developed a systematic search strategy and applied it to 10 electronic bibliographic databases. We hand searched journals; reviewed conference proceedings, gray literature, and bibliographies of relevant literature; and contacted content experts for studies comparing a bolus dose of etomidate with other induction agents. Retrieved articles were reviewed and data were abstracted with standardized forms. Data were pooled with the random-effects model if at least 4 clinically homogenous studies of the same design reported the same outcome measure. All other data were reported qualitatively. RESULTS: From 3,083 titles reviewed, 20 met our inclusion criteria. Pooled mean cortisol levels were lower in elective surgical patients induced with etomidate compared with those induced with other agents between 1 and 4 hours postinduction. The differences varied from 6.1 microg/dL (95% confidence interval [CI] 2.4 to 9.9 microg/dL; P=.001) to 16.4 microg/dL (95% CI 9.7 to 23.1 microg/dL; P<.001). Two studies in critically ill patients reported significantly different cortisol levels up to 7 hours postinduction. None of the studies reviewed, nor our pooled estimate (odds ratio 1.14; 95% CI 0.81 to 1.60), showed a statistically significant effect on mortality. Only one study reported longer ventilator, ICU, and hospital lengths of stay in patients intubated with etomidate. CONCLUSION: The available evidence suggests that etomidate suppresses adrenal function transiently without demonstrating a significant effect on mortality. However, no studies to date have been powered to detect a difference in hospital, ventilator, or ICU length of stay or in mortality.