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showing harm, a more reasonable, if not practical, approach TXA matter sufficiently not to consider the nonpharmacoki-
has been advocated in the movement behind evidence-guided, netic benefits of IM administration? In truth, it might, and it
rationale-based medicine: the art of balancing what evidence likely depends on the nature of the hemorrhage and of the situ-
there is with a mixture of basic science and opinion, contextu- ation. But IM administration should certainly be considered
alized by gradients of biological plausibility, and tempered by as a treatment option, empowering our Medics to stay in the
consensus of experts in the field. Where robust studies exist to fight and potentially save more lives if IV or IO access cannot
guide practice, they should be used. However, in the absence be obtained safely or in a timely fashion. This has immediate
of definitive studies, the available literature should guide our applicability for MCI situations to enable Medics to assess,
practice, not define it. triage, and treat more casualties in less time. Furthermore, the
IM option allows for the potential of self-administration in
This report is a contemplation and argument to weigh an self-aid situations.
abundance of weak-to-moderate evidence, coupled with
strong biological plausibility and an extremely favorable cost Though there is limited evidence on IM bioavailability of
and safety profile, that supports a simple, time-sensitive, and TXA, what does exist suggests complete bioavailability com-
potentially lifesaving intervention in an extremely vulnerable pared with IV. The TXA drug monograph also references
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patient population. IM administration, though the original source is antiquated
and not immediately transferable to the context at hand.
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More specifically, from the abundance of literature on the use Beyond what is presented in this review, data pending pub-
of TXA in orthopedic, cardiovascular, obstetric, spinal sur- lication from Defense Research and Development Canada of
gery, and trauma literature presented in this report, one can the Department of National Defense of the Canadian Armed
conclude that despite the heterogeneity of subjects, TXA has Forces have provided additional confirmatory results of the
consistently been demonstrated to be at least safe with no ob- complete bioavailability of IM versus IV TXA in a domestic
servable increase in VTE or DVT in these high-risk patient swine model (personal communication). Furthermore, there is
populations. Furthermore, current data and physiological also no evidence to suggest IM administration is ineffective.
principles support the administration of TXA as early as pos- Finally, based on current formulations of the drug, TXA can
sible after the time of injury and, ideally, at the point of injury, safely be administered in 5mL doses, consistent with accepted
because the current philosophy of hemostatic resuscitation practice for large-volume IM administration, in one of either
supports the concept of “first clot is best clot.” the gluteus muscle group (not otherwise specified), ventroglu-
teal, rectus femoris, or vastus lateralis muscles sites, thus al-
From pharmacokinetic principles, TXA is a lysine analog that lowing for a total dosing of 1g.
competitively displaces plasminogen from fibrin, resulting in
inhibition of fibrinolysis. As a competitive analog, it follows Conclusion
that dose matters. In this review, studies included doses across
a broad range of medical and surgical patients, from 5mg/kg Tactical Combat and Emergency Casualty Care Guidelines ex-
to 259mg/kg IV. In the CRASH-2 trial, a 1g IV loading dose ist to provide guidance for evidenced-based or expert-guided
of TXA followed by 1g IV over 8 hours has been replicated interventions to reduce trauma mortality in high-threat envi-
by other prehospital groups. However, there are insufficient ronments. We concede that TXA is not the panacea that will
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data to guide the minimal, maximum, or optimal dose in pa- eliminate all preventable deaths from hemorrhagic shock. The
tients with trauma and hemorrhagic shock. The current pro- purpose of this report is not to detract from the emphasis that
tocol used by Vancouver/Abbotsford SWAT Medics is for 1g should rightly be placed on all the other accepted principles
of TXA administered IM, IV, or IO. For practical and tactical of trauma care, such as early extremity tourniquet applica-
reasons, an infusion is not started in the field. If vascular ac- tion; balanced hemostatic resuscitation with blood products
cess can be obtained quickly and safely at a later time, then IV (if available); mitigation of the triad of hypothermia, acidosis,
TXA can be administered. and coagulopathy; and rapid extrication to definitive care, to
name a few. But in parallel with these principles and protocols,
If we accept the premise that TXA is an agreed-upon and ap- in the setting of competing interests and the chaos of kinetic
propriate adjunct in the management of hemorrhagic shock, battlegrounds, our Medics should be empowered to consider
then the next question is, does route matter? Or, is the proposed alternate routes of TXA administration that optimize tactical
alternate route so unreasonable that it should be overlooked en- and operational priorities. To most effectively blend tactical
tirely? It is already common practice for TXA to be administered and medical practices to reduce potentially preventable mortal-
topically, intra-articularly, nebulized, and IV. For reasons of ity, we must question all assumptions and consider all options.
practicality and biological plausibility (i.e., time-sensitive patho-
physiologic process coupled with an available time-sensitive In conclusion, TXA should be administered as early as pos-
intervention), and based on similar pharmacokinetic data, IM sible from the point of injury as an adjunct to hemorrhage
epinephrine, glucagon, and atropine, pralidoxime, and diazepam control, as an evidence-guided, rationale-based recommenda-
are currently accepted standard practice in the management of tion. IM TXA represents a practical and simple application
anaphylaxis, hypoglycemia, and nerve agent or organophos- for early administration when balancing tactical priorities,
phate toxicity, respectively. This same sense of urgency applies feasibility, and proficiency of obtaining vascular access via IV
in the management of hemorrhagic shock: Stop the bleeding as or IO routes in kinetic and dynamic situations, while optimiz-
soon as possible, maintain perfusion to vital organs, and transfer ing situational awareness. It confers practical advantages in
to a trauma center for definitive source control. mass casualty situations where rescuer skill allocation and
span or control are constantly taxed; however, additional
Balancing all the moving parts of a combat or tactical envi- studies are required that look at the affect of IM TXA in high-
ronment, do the pharmacokinetics of IV versus IO versus IM threat environments and, in particular, the performance of the

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