Tag Archives: TXA

Resuscitation

Giving TXA Via An Intraosseous Line?

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Seriously injured patients frequently develop coagulopathy, which makes resuscitation (and survival) more challenging. A few years ago, the CRASH-2 study lent support for using tranexamic acid (TXA) in select trauma patients to improve survival. This drug is cheap and has antifibrinolytic properties that may be beneficial if given for life-threatening bleeding within 3 hours of initial injury. It’s typically given as a rapid IV infusion, followed by a slower followup infusion. The US military has adopted its routine use at forward combat hospitals.

But what if you don’t have IV access? This can and does occur with military type injuries. Surgeons at Madigan Army Medical Center in Washington state tried using a common alternative access device, the intraosseous needle, to see if the results were equivalent. This study used an adult swine model with hemorrhage and aortic crossclamping to simulate military injury and resuscitation. Half of the animals then received IV TXA, the other half had it administered via IO. Only the bolus dose was given. Serum TXA levels were monitored, and serial ROTEM determinations were performed to evaluate coagulopathy.

Here are the factoids:

  • The serum TXA peak and taper curves were similar. The IV peak was higher than IO and approached statistical significance (0.053)
  • ROTEM showed that the animals were significantly hyperfibrinolytic after injury, but rapidly corrected after administration of TXA. Results were the same for both IV and IO groups.

Bottom line: This was a very simple and elegant study. The usual animal study issues come into play (small numbers, pigs are not people). But it would be nearly impossible to have such a study approved in humans. Even though the peak TXA concentration via IO is (nearly significantly) lower, this doesn’t appear to matter. The anti-fibrinolytic effect was very similar according to ROTEM analysis.

From a practical standpoint, I’m not recommending that we start giving TXA via IO in civilian practice. We don’t typically see military style injuries, and are usually able to establish some type of IV access within a reasonably short period of time. But for our military colleagues, this could be a very valuable tool!

Reference: No intravenous access, no problem: Intraosseous administration of tranexamic acid is as effective as intravenous in a porcine hemorrhage model. J Trauma 84(2):379-385, 2018.

Abstracts, Prehospital

Best Of EAST 2023 #11: Prehospital Use Of TXA

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More stuff on TXA! I published two posts back in December on TXA hesitancy. This Friday, the trauma group at Wake Forest is presenting an abstract on TXA use by prehospital trauma professionals.

It is very likely that EMS carries tranexamic acid (TXA) in your area. Each agency has its own policy on when to administer, but the primary indication is hemorrhagic shock. A few ALS services may infuse for serious head injury as well.

The Wake Forest group was concerned that TXA administration might be occurring outside of the primary indication, hemorrhagic shock. They reviewed their experience using a six-year retrospective analysis of their trauma registry. The patients’ physiologic state before and after arrival at the hospital was assessed, as were the interventions performed in both settings.

Here are the factoids:

  • Of 1,089 patients delivered by 20 EMS agencies, one-third (406) had TXA initiated by EMS
  • Only 58% of patients who received prehospital TXA required transfusion after arrival
  • TXA administration based on BP criteria were as follows:
  • Similar compliance was noted when examining only high-volume EMS services

The authors concluded that TXA use is common in the prehospital setting but is being used outside of literature-driven indications.

Bottom line: This is an interesting snapshot of TXA use surrounding a single Level I trauma center. As such, it can’t be automatically applied to all. However, my own observations suggest that this drug is being used more liberally nationwide.

Clearly, the prehospital providers are starting TXA on patients who do not fit the category of severe hemorrhagic shock. Only 30% of patients receiving it had SBP < 90. Is this a bad thing? Referring back to my conversation on TXA hesitancy, I think not. But do keep in mind that giving any drug when not indicated adds no benefit and can certainly increase risk. The good news is that TXA is very benign when it comes to side effects.

However, policies are designed for a reason: safety. And if the EMS agency policy says to give TXA only for SBP < x, then that’s when it should be given. The prehospital PI process (or the trauma center’s) should identify variances and work to correct them. If EMS is “overusing” TXA in your area, your trauma center should add this as a new prehospital PI filter and let them know when it happens.

Here are my questions and comments for the presenter/authors:

  • Is using the need for transfusion a valid measure of the need for TXA? You found that half of the patients receiving TXA were not transfused. The decision to transfuse depends on surgeon preference, and they don’t always use objective criteria. And hey! Maybe the TXA worked, obviating the need for blood!

This is a straightforward and intriguing paper. I’m excited to hear more details on how you sliced and diced this data.

Reference: ARE DATA DRIVING OUR AMBULANCES? LIBERAL USE OF TRANEXAMIC ACID IN THE PREHOSPITAL SETTING. EAST 2023 Podium paper #34.

Complications

TXA Hesitancy: Part II

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In my last post, I reviewed a huge systematic review and meta-analysis of the use of tranexamic acid (TXA)  by all medical disciplines using it. There were more than 125,000 cases included and showed the incidence of thrombotic complications in TXA vs non-TXA patients was exactly the same at about 2%.

Our orthopedic surgery colleagues have been using TXA to reduce bleeding in their cases for decades. There is nothing close to the degree of “TXA hesitancy” in orthopedic surgeons than I see in surgical practices across trauma centers. What do the orthopods know that we don’t?

Trauma orthopedic groups in Malta and the UK published a paper just this month in which they performed a systematic review and meta-analysis of the use of TXA in hip fracture surgery. They focused on randomized, controlled trials published after 2010. A standard approach was used in the analysis, which looked specifically at the impact of IV TXA on transfusion requirements in surgery. Only adults were studied, and eligible studies compared TXA with a placebo, or TXA with no TXA.

Here are the factoids:

  • Out of 85 studies initially identified, only 13 met all criteria
  • Across these trials, a total of 1194 patients were enrolled
  • The need for blood transfusion was reduced by more than 50% when the transfusion threshold was Hgb 8g/dl, which was highly statistically significant
  • When a higher transfusion threshold was used (between 8-10 g/dl Hbg) the risk reduction was only 23% which was not significant
  • The incidence of thrombotic events was identical for TXA and no-TXA groups

Bottom line: This paper presents more high-quality evidence that the use of TXA in surgically induced injury (hip fracture repair) significantly reduces the need for transfusion in the group with the most blood loss. 

However, as with any meta-analysis the results are only as good as the quality of the individual papers. There were differences in how the TXA was given. It was also not possible to separate out results from the various types of hip surgery performed. And obviously, these are not major, multi-trauma patients.

Most TXA hesitant surgeons are either concerned with the efficacy of TXA, or the potential risks. This paper shows that, overall, TXA is effect in these patients despite the mix of doses and timing of delivery. And it clearly shows that the risk for thrombotic complications was identical to that of not giving it.

We have a cheap, effective tool to reduce the need for blood transfusion (read “blood loss”) in trauma patients that has a totally neutral risk profile for thrombosis. We all need to ask ourselves, “why are we not using it?”

Reference: The Use of Tranexamic Acid in Hip Fracture Surgery — A
Systematic Review and Meta-analysis . J Orthop Trauma, 36(2):e442-3448, 2022.

Complications

TXA Hesitancy: Part I

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I’ve visited several hundred trauma centers over the past 25 years, and recently I’ve begun to appreciate that there are two tribes when it comes to the use of tranexamic acid: the TXA believers and the TXA hesitant.

There have been a number of large studies that seem to suggest a benefit with respect to survival from major hemorrhage, particularly if given soon after injury (CRASH-2, MATTERs). This drug is dirt cheap and has been around a long time, so it has a clearly defined risk profile.

However, many of those hesitant to use it point to the possibility of thromboembolic events that have been sporadically reported. Several years ago, I did my own literature review and found that the number of thrombotic events from TXA was nearly identical to that of transfusing plasma.

JAMA Surgery published a large systematic review, meta-analysis, and meta-regression last year that sought to examine the association between thromboembolic events (TE) in patients of any age and involving all medical disciplines, not just trauma.

The anesthesia group at the University Hospital Frankfurt in German did a systematic search of the Cochrane Central Register of Controlled Trials, as well as MEDLINE, for randomized controlled trials involving TXA. They covered all published studies through December 2020.

The authors adhered to standard guidelines for conducting reviews and meta-analysis (PRISMA). They specifically searched for outcomes involving TEs, such as venous thromboembolism, myocardial infarction or ischemia, limb ischemia, mesenteric thrombosis, and hepatic artery thrombosis. They also tallied the overall mortality, bleeding mortality, and non-bleeding mortality.

Here are the factoids:

  • A total of 216 eligible trials were identified that included over 125,000 patients (!)
  • Total TEs in the TXA group were 1,020 (2.1%) vs 900 (2.0%) in the control group
  • Studies at lowest risk for selection bias showed similar results

Bottom line: The authors concluded that IV TXA, irrespective of the dose, does not increase the risk of thromboembolic events. Period.

In my next post I’ll describe an even more recent systematic review and meta-analysis in orthopedic patients. Our orthopedic colleagues have been using this drug successfully for hip surgery for decades. Let’s see what they think.

Reference: Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality A Systematic Review, Meta-analysis, and Meta-regression. JAMA Surgery 156(6):3210884, 2021.

Prehospital, Resuscitation

Best Of EAST #16: More On TXA

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Here’s another abstract dealing with TXA. But this one deals with the classic CRASH-2 use for patients with major bleeding. The original patient showed that TXA improves survival if given within 3 hours of injury. More and more prehospital units (particularly aeromedical services) have been administering TXA enroute to the trauma center to ensure that this drug is given as early as possible.

Many of these same services carry packed cells (or in rare cases, whole blood) so that proper resuscitation can be started while enroute as well. A multicenter group led by the University of Pittsburgh evaluated the utility of giving both TXA and blood during prehospital transport.

Their study summarizes some of the results of the Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial (STAAMP Trial). This study ran from 2015 to 2019 and randomized patients to receive either TXA or placebo during air or ground transport to a trauma center. It included blunt or penetrating patients at risk for hemorrhage within 2 hours of injury who were either hypotensive or tachycardic. Outcome measures included 30-day mortality, 24-hour mortality, and a host of complications.

This abstract outlines a secondary analysis that retrospectively reviewed the impact of using prehospital packed red cells (pRBC) in addition to the TXA/placebo during transport. 

Here are the factoids:

  • There were 763 patients in total, broken down as follows
    • TXA only – 350
    • pRBC only – 35
    • TXA + pRBC – 22
    • Neither – 356
  • Patients who received blood with or without TXA were more severely injured with ISS 22 vs 10-12 in the non-pRBC groups
  • Mortality was higher in the pRBC (23%) and TXA+pRBC groups (29%)
  • TXA alone did not decrease mortality
  • TXA + pRBC resulted in a 46% reduction in 30-day mortality but not at 24 hours
  • packed cells alone decreased 24-hour mortality by 47%

The authors concluded basically what was stated in the results: short term mortality was decreased by pRBC alone, and 30-day mortality with TXA + pRBC. They recommended further work to elucidate the mechanisms involved.

Bottom line: This abstract may also suffer from the “low numbers” syndrome I’ve written about so many times before. The conclusions are based on two small groups that make up only 7% of the entire study group. And these are the two groups with more than double the ISS of the rest of the patients. The authors used some sophisticated statistics to test their hypotheses, and they will need to explain how and why they are appropriate for this analysis. Nevertheless, the mortalities in the blood groups number only in the single digits, so I worry about these statistics.

Here are my questions for the authors and presenter:

  • How do you reconcile the significantly higher ISS in the two (very small) groups who got blood? How might this skew your conclusions regarding mortality? Couldn’t the TXA just be superfluous?
  • How confident are you with the statistical analysis? Could the results be a sampling error given that red cells were given to only 7% of the overall study group?
  • I am having a difficult time understanding the conclusion that mortality was reduced in the blood groups. Specifically, it is stated that 24-hour mortality is reduced by 47% in the blood-only group.  But the mortality is 14% (5 patients)! Reduced 47% from what? I don’t see any other numbers to compare with in the table. Confusing!

Obviously, there must be more information that was not listed in the abstract. Can’t wait to see it!

Reference: PREHOSPITAL SYNERGY: TRANEXAMIC ACID AND BLOOD TRANSFUSION IN PATIENTS AT RISK FOR HEMORRHAGE. EAST 35th ASA, oral abstract #39.

 

 

Reference: PREHOSPITAL SYNERGY: TRANEXAMIC ACID AND BLOOD TRANSFUSION IN PATIENTS AT RISK FOR HEMORRHAGE. EAST 35th ASA, oral abstract #39.