Page 41 - JSOM Fall 2020

the hospital and be evaluated for possible ongoing hemorrhage Questions from the TXA User Community
before deciding whether or not to administer another dose of
TXA. A paper describing the prehospital use of TXA in three Can TXA Be Safely Given as a Slow (1-minute) IV Push
EMS systems in Cincinnati, Oklahoma City, and Tulsa notes Rather Than over 10 minutes?
that paramedics are encouraged to initiate TXA administration Combat medics and their supervising physicians have repeat-
when indicated, regardless of how close they are to a trauma edly posed the question about giving the first dose of TXA by
center. This paper goes on to note that none of these 3 systems slow IV push rather than as a 10-minute infusion, as was done
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call for a second dose of TXA in the prehospital setting, based in the CRASH-2 study. TXA was administered as an IV bo-
both on the relatively short transport times, but also on TXA’s lus in the MATTERs patient population without documented
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pharmacokinetics. TXA has a half-life of about two hours, adverse effects. The need for a 10-minute infusion of TXA
maintaining antifibrinolytic action in some tissues for up to 17 was mentioned as a possible factor in the reported poor com-
hours and in the blood for approximately 7–8 hours. 56 pliance with TCCC recommendations regarding TXA. One
of the co- authors reported personal experience with safe slow
Is TXA Effective When Administered IV push and advocated for this update to the TCCC Guide-
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IM to Bleeding Trauma Patients? lines. One paper that directly addressed clinically significant
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Although the CRASH-2 and MATTERS studies, as well as hypotension is from 1969. Two small porcine studies have
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most of the reports on pre-operative TXA in elective surgery, administered TXA over 5 minutes and by push without
call for TXA to be administered IV, authors have noted that adverse outcomes or observed hypotension. Neither the au-
it would be faster to administer TXA by autoinjector. 122,123 thors of the MATTERs study (also authors of this change)
th
Is there evidence to support this route of administration for nor the 75 Ranger Regiment have observed or reported any
TXA, in particular for casualties who may in hemorrhagic episodes of clinically significant hypotension with this dosing
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shock? An in-depth review of this topic in 2018 was unable strategy. We recommend that TXA administration should be
to specifically recommend for or against IM administration an IV/IO slow push. This bolus should be given over approx-
of TXA. There is very scarce literature evaluating the IM imately 1 minute.
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administration of TXA, and none of the studies included pa-
tients in shock. Bioavailability and pharmacokinetics studies Can TXA Be Given in the Same IV/IO Line
date back to the 1970s and 1980s. 124,125 In one study, 3 healthy as Blood or Blood Products?
volunteers were given TXA and bioavailability of IM and IV There are no specific studies addressing this concern and there
TXA was 100%. Peak serum concentrations of IM TXA were is no known contraindication to administration of TXA with
not noted until 40–60 minutes, whereas the peak levels of IV blood or blood products. There are also no reports of complica-
TXA were reached in 5 minutes. A 2019 meta-analysis of tions from TXA being administered with blood products. There
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available data regarding IM administration of TXA in healthy should be no compatibility problems expected, since TXA typ-
patients also found a total of 6 participants in 2 studies, which ically mixes with blood immediately after being given IV. The
demonstrates a continued lack of available human data. authors’ recommendations are to administer TXA as soon as
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Two recent studies of TXA pharmacokinetics in a porcine possible after injury. If blood or blood products are being given,
shock model have demonstrated similar bioavailability of IM the authors recommend giving TXA in the port closest to the
and IV TXA, but with inconsistent results of peak serum con- skin. The Ranger Regiment’s administration protocol uses TXA
centrations. One recent study noted peak concentration of IV as the flush after initial IV/IO access is obtained.
TXA at 5 minutes and IM TXA (given in two IM doses at
separate sites) at 10 minutes with another demonstrating Is There a Need for a Second Dose of TXA to be
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peak concentration of IV/IO TXA at 5 minutes and IM TXA Administered as Part of TCCC, Given the Discussion
at 60 minutes. The current TXA packaging is only avail- of the Pharmacokinetics of TXA Mentioned Above?
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able in 100mg/1mL, which would require IM dosing at 10mL And – If a Second dose of TXA Is, In Fact, Needed,
for each 1g of TXA to be administered. Given the time sensi- Should the Second Dose Be Given Like the First?
tive nature of TXA administration and the lack of consistent The CRASH-2 trial administered the second dose of TXA as
data evaluating TXA absorption in shock states, there is not 1g given over 8 hours. This dosing protocol was adopted from
enough evidence to recommend IM TXA administration in the cardiac surgery community and more current research
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TCCC at the present time. supports simplified administration protocols as discussed in
other areas of this paper.
Is TXA Effective When Administered
Via the IO Route to Bleeding Trauma Patients? Should the Second Dose of TXA Be Administered
The current TCCC Guidelines do not include IO adminis- If More Than 3 Hours Have Elapsed Since the Time
tration of TXA, but there are no known contraindications of Wounding
to administering intravenous medications intraosseously. IO The CRASH-2 timing subgroup analysis found that mortality
administration of TXA has been reviewed without identified was actually increased when TXA was given more than 3 hours
complications to 82 patients in the pre-hospital setting. The after the time of injury. Does the 3-hour caveat apply only to
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IO route of administration was also included in the Cal-PAT the first dose? There is no evidence to date suggesting that late
study, but was not discussed in depth. The 75 Ranger Reg- administration (>3 hours after injury) of TXA is beneficial.
th
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iment currently administers TXA via the IO route and has no
documented complications from this protocol. 131,132 What Is “Initial Fluid Resuscitation?”
as Mentioned in the TCCC Guidelines
In swine models, IO and IV TXA have been shown to have with Respect to TXA? And when does it end?
equivalent pharmacokinetics as well as anti-fibrinolytic The TCCC Guidelines (dated 1 August 2019) call for the sec-
activity. 129,133,134 ond 1g dose of TXA to be administered “after initial fluid

Tranexamic Acid in TCCC | 39