Page 66 - JSOM Spring 2018

Intramuscular Tranexamic Acid in
Tactical and Combat Settings

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1
Erik N. Vu, MSM, MD *; Wilson C. Y. Wan, MD ;
1
Titus C. Yeung, MD ; David W. Callaway, MD 2

ABSTRACT
Background: Uncontrolled hemorrhage remains a leading setting of massive hemorrhage has been a challenge since Wil-
cause of preventable death in tactical and combat settings. liam Harvey first described the circulatory system in the early
Alternate routes of delivery of tranexamic acid (TXA), an 1600s. The subject of trauma resuscitation consistently invites
adjunct in the management of hemorrhagic shock, are be- animated debate challenging old treatment paradigms in the
ing studied. A working group for the Committee for Tacti- face of new concepts, devices, and philosophies.
cal Emergency Casualty Care reviewed the available evidence
on the potential role for intramuscular (IM) administration Tranexamic acid (TXA) is one such drug that has its feet firmly
of TXA in nonhospital settings as soon as possible from the planted in both camps: At one end, an abundance of litera-
point of injury. Methods: EMBASE and MEDLINE/PubMed ture and experience with this inexpensive and safe drug can be
databases were sequentially searched by medical librarians for traced back decades in orthopedic, obstetrical, gynecological,
evidence of TXA use in the following contexts and/or using and cardiovascular surgical literature, to name a few; at the
the following keywords: prehospital, trauma, hemorrhagic other end, it has recently been thrust in the spotlight as a con-
shock, optimal timing, optimal dose, safe volume, incidence temporary adjunct in the management of hemorrhagic shock
of venous thromboembolism (VTE), IM bioavailability. Re- trauma and massive transfusion resuscitation paradigms. The
sults: A total of 183 studies were reviewed. The strength of CRASH-2 (Clinical Randomization of an Antifibrinolytic in
the available data was variable, generally weak in quality, Significant Hemorrhage) and MATTERs (Military Applica-
and included laboratory research, case reports, retrospective tion of Tranexamic Acid in Trauma Emergency Resuscitation)
observational reviews, and few prospective studies. Current studies are the most often referenced articles in the body of
volume and concentrations of available formulations of TXA evidence on the use of the TXA in trauma patients. 3,4
make it, in theory, amenable to IM injection. Current best-
practice guidelines for large-volume injection (i.e., 5mL) sup- Much of the reviews, commentary, and rationale for imple-
port IM administration in four locations in the adult human menting TXA into treatment protocols are also based on these
body. One case series suggests complete bioavailability of IM two studies. CRASH-2 studied 20,211 adult trauma patients
TXA in healthy patients. Data are lacking on the efficacy and with, or at risk of, significant bleeding in 274 hospitals from
safety of IM TXA in hemorrhagic shock. Conclusion: There 40 countries. Patients within 8 hours of injury were randomly
is currently insufficient evidence to support a strong recom- assigned to TXA (1g intravenously [IV] over 10 minutes, then
mendation for or against IM administration of TXA in the 1g IV over 8 hours) or placebo. All-cause mortality (14.5%
combat setting; however, there is an abundance of literature versus 16.0%) and risk of death due to bleeding (4.9% versus
demonstrating efficacy and safety of TXA use in a broad range 5.7%) were significantly reduced in the TXA treatment group.
of patient populations. Balancing the available data and risk– A post hoc analysis showed early treatment with TXA versus
benefit ratio, IM TXA should be considered a viable treatment the placebo group (within 1 hour of injury, 5.3% versus 7.7%;
option for tactical and combat applications. Additional stud- and between 1 and 3 hours of injury, 4.8% versus 6.1%) sig-
ies should focus on the optimal dose and bioavailability of IM nificantly reduced the risk of death due to bleeding. MATTERs
dosing of patients in hemorrhagic shock, with assessment of retrospectively studied 896 consecutive patients who received
potential downstream sequelae. at least 1 unit of packed red blood cells within 24 hours of ad-
mission after combat-related injury at Camp Bastion in south-
Keywords: intramuscular; tranexamic acid; hemorrhagic shock; ern Afghanistan from 1 January 2009 to 31 December 2010.
Tactical Combat Casualty Care; Tactical Emergency Casualty Before 2010, TXA was given on the basis of clinical judgment.
Care Starting in 2010, TXA was incorporated as part of the major
hemorrhage protocol and clinical practice guideline. TXA was
given as an 1g IV bolus and repeated, if thought indicated by
the managing clinician. This was a retrospective case-control
Introduction
study with matched combat casualty cohorts who received care
Uncontrolled hemorrhage is the leading cause of potentially at the busiest medical treatment facility in the US Central Com-
1,2
preventable death. The imperative to stop the bleeding in the mand that uses standardized advanced trauma resuscitation,
*Address correspondence to erik.vu@vch.ca
1 Drs Vu, Wan, and Yeung are at the Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada. Dr Callaway is associate professor, Emergency Medicine; director, Operational and Disaster Medicine,
2
Carolinas Medical Center, Charlotte, NC.
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