tranexamic acid

[MTGas2B]

I'm wondering if anyone has experience using this stuff in trauma. I've read the CRASH-2 study and some of the other literature out there on it. I personally haven't had it available anywhere I've worked, and I know I don't have it now.

Specifically I'm wondering about the effects of giving the loading dose, and consequences of doing it faster than the 10 minutes. "I have this friend" who doesn't have access to IV pumps in his current austere practice environment. He's looking at getting TXA to use in his trauma population. The package insert mentions hypotension with rapid infusion. Anyone seen this? I've given amicar pretty quick in the past without a problem, and I presume this would be relatively safe in TXA. Any other real world insight on its use in trauma would be appreciated.

Thanks.

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[BISof60]

I have not used it in trauma patients. I have used it in elective ortho cases where lots of blood loss is expected. I have not noticed any profound hypotension despite giving the loading dose in much less than 10 minutes.

 

[Foodie]

Once I've given TXA over 1 min in a holy-$&;@-he's-bleeding-out trauma case. Did not see hypotension worsen. SBP stayed in 90's until the source of bleed was corrected. I don't give it rapidly during the usual ortho cases (hip replacements, mostly). Seems like the hot new thing to minimize blood loss by the ortho peeps.

Our cardiac surgeon requests Amicar given before he opens chest. We put 10g Amicar with 1g M in a 100 ml d5w bag and let it fly.

Don't ask me why d5w, though, I have no idea.

 

[proman]

Once I've given TXA over 1 min in a holy-$&;@-he's-bleeding-out trauma case. Did not see hypotension worsen. SBP stayed in 90's until the source of bleed was corrected. I don't give it rapidly during the usual ortho cases (hip replacements, mostly). Seems like the hot new thing to minimize blood loss by the ortho peeps.

Our cardiac surgeon requests Amicar given before he opens chest. We put 10g Amicar with 1g M in a 100 ml d5w bag and let it fly.

Don't ask me why d5w, though, I have no idea.

I give my Amicar bolus 10gm IV push, then 1gm/hr as the carrier. I'll give it before incision on non-coronary cases. CABG gets it after the heparin for the slim chance of causing thrombosis.

I thought that TXA wasn't available in the US. Is its availability a new development?

 

[lushmd]

I thought that TXA wasn't available in the US. Is its availability a new development?

We've been using it in place of aprotinin for the past several years.

 

[proman]

We've been using it in place of aprotinin for the past several years.

So after a very brief browse of pubmed, it seems that TXA and EACA are equally efficacious at reducing bleeding and the need for transfusion but that TXA is associated with significantly more neurologic adverse events (seizures) and that EACA has higher rate of renal dysfunction. I don't know how much TXA costs but EACA is about $1.25 per 5gm vial. As someone who has exclusively used EACA is there any reason for me to change?

 

[BLADEMDA]

Tranexamic acid for trauma
After its publication in July, 2010, the CRASH-2 study1
generated widespread interest in the early administration
of the antifi brinolytic agent tranexamic acid to
patients with traumatic bleeding. Tranexamic acid is an
inexpensive, easily used, and relatively safe drug, and it
seemed to have saved lives. However, how it did so was
unclear—the blood-transfusion requirements of the
tranexamic acid and placebo groups were similar and,
survival bias notwithstanding, the mortality benefi t might
have been attributable to an eff ect of tranexamic acid on
something other than acute traumatic coagulopathy.2
This issue is partly addressed with the publication in
The Lancet of a follow-up analysis that used the outcome
of death due to bleeding rather than all-cause mortality.3
The CRASH-2 collaborators3
report a 32% reduction in
death due to bleeding when tranexamic acid is given
within 1 h of injury. Although markers of coagulopathy
were not measured, the mortality benefi t is probably
mediated through antifi brinolytic eff ects on clot
stabilisation.4 While it will not prevent the massive
haemorrhage from disrupted vessels or organs that needs
surgical intervention, tranexamic acid appears to improve
survival through its eff ect on mild to moderate bleeding.
Early administration is necessary, however, and benefi t
was only seen in CRASH-2 when tranexamic acid was
administered within 3 h of injury. Unlike coagulopathy
that is secondary to haemodilution, hypothermia, or
acidosis, acute traumatic coagulopathy is a hyperacute
process in which systemic fi brinolysis releases D-dimers
that are detectable within 30 min of injury.5 While the
mechanisms are poorly understood, shock and tissue
injury seem to be important initiators.6 Not all severely
injured patients develop acute coagulopathy, but those
who do are much more likely to die and to die early.7 The
earlier that tranexamic acid is administered, the more
likely it might be to prevent full activation of fi brinolysis.
Once fully activated, fi brinolysis has been shown to
continue unabated until endogenous antifi brinolytic
elements are restored.8
Importantly, the CRASH-2 collaborators3
report
increased mortality due to bleeding in patients receiving
tranexamic acid when it is given more than 3 h after
injury. The cause of these deaths is unclear. Reports exist
of prothrombotic eff ects of each of the anti-fi brinolytic
drugs. Alternatively, it might refl ect some factor of the
patients who received it late. Whatever the mechanism,
the CRASH-2 collaborators3
have cautioned against the
use of tranexamic acid when more than 3 h have expired
after injury.
Who, then, should be treated with tranexamic
acid? Most of the 274 study sites in CRASH-2 were
in low-income and middle-income countries, where
other treatments directed at coagulopathy, such as
fresh frozen plasma, platelets, and cryoprecipitate,
are less available. Although many patients with
acute coagulopathy will die before reaching hospital,
tranexamic acid is a practical, aff ordable, and eff ective
treatment for bleeding trauma patients in such centres,
provided they receive it within 3 h of injury.
Far less clear is the place for tranexamic acid in high
income countries where massive transfusion protocols
incorporate fresh-frozen plasma that contains all the
endogenous antifi brinolytic elements in plasma.9
Plasma can cause harm as well as benefi t, and there
is little prospective evidence regarding its effi cacy.
However, because it is in widespread use, and because
late administration of tranexamic acid can be harmful, it
is unlikely that many clinicians in major trauma centres
will choose tranexamic acid as fi rst-line treatment.
The best place for tranexamic acid in developed
trauma systems might actually be in the prehospital
environment. Helicopter and road transport direct
to major trauma centres has reduced overall injury
mortality, but has extended the time before patients
reach hospital.10
Prehospital administration of blood
products, especially plasma, is uncommon in civilian
settings, resulting in little directed management of
coagulopathy. By contrast, tranexamic acid can be safely
stored in vehicles and simply administered. In view of the
new fi ndings from CRASH-2, the best outcomes might
be achieved with simple measures for haemorrhage
control and early inhibition of coagulopathy with
tranexamic acid, followed by rapid transport for
surgery or angiography and tailored management of
coagulopathy in hospital.
CRASH-2 was an extraordinary achievement, with
randomisation of more than 20 000 patients in
40 countries. It has established tranexamic acid as
an eff ective hospital-based treatment for traumatic
haemorrhage, provided that the drug is given within 3 h of
injury. In trauma systems that have advanced prehospital
services and that use other hospital-based treatments for
coagulopathy, CRASH-2 raises more questions—and more
possibilities—that are worth investigating.


http://download.thelancet.com/flatcontentassets/pdfs/S0140673611603966.pdf

 

[BLADEMDA]

So after a very brief browse of pubmed, it seems that TXA and EACA are equally efficacious at reducing bleeding and the need for transfusion but that TXA is associated with significantly more neurologic adverse events (seizures) and that EACA has higher rate of renal dysfunction. I don't know how much TXA costs but EACA is about $1.25 per 5gm vial. As someone who has exclusively used EACA is there any reason for me to change?

No. Your Cardiac Surgeon will likely insist on his preference for one vs. other based on anecdotal experience.

 

[BLADEMDA]

Corey Slovis, MD, chairman of emergency medicine at Vanderbilt University in Nashville, noted that "widespread use of tranexamic acid in the trauma patients would be a major and dramatic change in practice In general."
And in the U.S., Slovis explained in an e-mail, such a change might not be justified because the regionalization of trauma care in this country has led to outstanding results. There are "trauma centers and surgeons who essentially do nothing but trauma. Most countries have general surgeons at local hospitals and even some advanced European countries do not always rush people to trauma centers. Think Princess Diana -- in the U.S.A. she would have been a 'scoop and run' and spent 10 minutes or less on scene."
The randomized, double-blind, placebo-controlled CRASH-2 trial, which was conducted in 40 countries, randomized 20,211 adult trauma patients who were at high risk for significant bleeding to tranexamic acid or placebo. Randomization took place within eight hours of injury.
Tranexamic acid was given at a loading dose of 1 g over 10 minutes and then an infusion of 1 g over eight hours.
The primary endpoint was inhospital death within four weeks of injury.
Tranexamic acid use was not associated with a significant difference in deaths due to multiorgan failure, head trauma, or other causes, the researchers reported.
They noted that the trial provided only limited "insight into how tranexamic acid reduces the risk of death in bleeding trauma patients," because they did not measure fibrinolytic activity and therefore they "cannot conclude that this agent acts by reducing fibrinolysis rather than another mechanism."
There was no difference in the rates of transfusion between the two treatment groups, but Roberts and Shakur wrote that measuring blood loss and tracking transfusion rates is difficult among trauma patients.
Bleeding at the scene and in the hospital "is often difficult to quantify, such as, for example, bleeding into the chest, abdomen, pelvis, and soft tissues," they wrote.
Thus, the lack of difference in transfusion rates could simply be "an indication of the difficulty of accurate estimation of blood loss in trauma patients when assessing the need for transfusion."
The observed mortality benefit did not vary substantially according to the time from injury, but "there was some suggestion that early treatment might be more effective," they wrote.
Based on the study's results, "tranexamic acid should be considered for use in bleeding trauma patients," they concluded.
In a commentary that accompanied the study, Jerrold H. Levy, MD, of Emory University, wrote that the results showed that "inhibition of fibrinolysis with tranexamic acid after major trauma is an important mechanism to reduce mortality."
He also pointed out that "caution is needed before extrapolation of the results of CRASH-2 to other antifibrinolytic agents until they have been studied in a similarly robust manner."

 

[BLADEMDA]

I'm wondering if anyone has experience using this stuff in trauma. I've read the CRASH-2 study and some of the other literature out there on it. I personally haven't had it available anywhere I've worked, and I know I don't have it now.

Specifically I'm wondering about the effects of giving the loading dose, and consequences of doing it faster than the 10 minutes. "I have this friend" who doesn't have access to IV pumps in his current austere practice environment. He's looking at getting TXA to use in his trauma population. The package insert mentions hypotension with rapid infusion. Anyone seen this? I've given amicar pretty quick in the past without a problem, and I presume this would be relatively safe in TXA. Any other real world insight on its use in trauma would be appreciated.

Thanks.

Hypotension in a trauma patient? Really? Who would have guessed that? When and If I start giving TXA to trauma patients it will be a bolus dose of 1 gram over 30-60 seconds. I suspect that's the way many of us will be dosing the initial TXA. Remember, our patients will be under GA and we have pressors readily available (Phenylephrine, Vasopressin, Epi)

 

[MTGas2B]

Hypotension in a trauma patient? Really? Who would have guessed that? When and If I start giving TXA to trauma patients it will be a bolus dose of 1 gram over 30-60 seconds. I suspect that's the way many of us will be dosing the initial TXA. Remember, our patients will be under GA and we have pressors readily available (Phenylephrine, Vasopressin, Epi)

I figured the hypotension issue was FDA labeling BS. I was just looking for some real world experience on giving TXA. I just wanted to make sure someone didn't say, "Holy $h1t, that stuff can make people can tank like a rapid push of dilantin."

 

[proman]

No. Your Cardiac Surgeon will likely insist on his preference for one vs. other based on anecdotal experience.

You don't quite understand the question. But I don't really see a reason to use TXA over EACA, particularly when EACA is so cheap and safe to use.

 

[dhb]

I figured the hypotension issue was FDA labeling BS. I was just looking for some real world experience on giving TXA. I just wanted to make sure someone didn't say, "Holy $h1t, that stuff can make people can tank like a rapid push of dilantin."

I've had it happen a couple of times when i was pushing 1g but it's hard to attribute it 100% to TXA and it's relatively mild (not profound hypotension)

 

[sevoflurane]

You don't quite understand the question. But I don't really see a reason to use TXA over EACA, particularly when EACA is so cheap and safe to use.

You are correct proman. I find no real significant difference except for cost. I use it as you do: I give 5gms bolus up front (after induction/prior to heparin) and run an infusion until CVICU. TXA is more expensive.... but I don't remember how much more.

 

[nimbus]

Timely thread. We were just informed by our pharmacy that EACA will be unavailable until late Sept. TXA apparently $70-80/gm vial. Anyone else experiencing EACA shortage?

 

[dchz]

As a Ca-1, I was doing a total hip (the surgeon requested 1 g before the start and 1 g on closing) and the pt was just getting gradually hypotensive. I could not figure out why for the life of me... it turns out it was the TXA infusion... even at a slow drip it caused hypotension in the pt.

It's been pretty inconsequential for me after that, as long as i know its' the TXA causing the hypotension, i can alwasy counteract it. We have been using TXA for our bypass runs to prevent fibrinolysis because of the national EACA shortage.

Last night we were doing a hip nail on a demented 94 F, I couldn't get the TXA because the hypotension from the spinal and the small dose propofol sedation was just enough to make it difficult to get the TXA in. Eventually I got it in, but it was a good reminder of this side effect.

Also seizures and kidney damage.

 

[anbuitachi]

As a Ca-1, I was doing a total hip (the surgeon requested 1 g before the start and 1 g on closing) and the pt was just getting gradually hypotensive. I could not figure out why for the life of me... it turns out it was the TXA infusion... even at a slow drip it caused hypotension in the pt.

It's been pretty inconsequential for me after that, as long as i know its' the TXA causing the hypotension, i can alwasy counteract it. We have been using TXA for our bypass runs to prevent fibrinolysis because of the national EACA shortage.

Last night we were doing a hip nail on a demented 94 F, I couldn't get the TXA because the hypotension from the spinal and the small dose propofol sedation was just enough to make it difficult to get the TXA in. Eventually I got it in, but it was a good reminder of this side effect.

Also seizures and kidney damage.

I find it hard to attributed hypotension to txa when it's infusion since spinal is causing and propofol infusion if running.

Either way I give 10mg to 50mg per kg of txa for big Ortho cases

 

[drmwvr]

Timely thread. We were just informed by our pharmacy that EACA will be unavailable until late Sept. TXA apparently $70-80/gm vial. Anyone else experiencing EACA shortage?

We've used TXA on and off for Amicar shortage, but the latter is our stock AF for CPB cases. No more hypotension with either that is greater than a slug of heparin. No difference in bring backs either.

 

[Psai]

I slam in TXA like it owes me money. No hypotension yet.

 

[kidthor]

I give peds patients large TXA doses all the time and haven't seen any noteworthy hypotension, and absolutely haven't seen any seizures. The interesting thing is that many of my kids have seizure disorders, yet all that TXA hasn't seemed to induce any perioperative seizure activity.

 

[deleted162650]

I slam in TXA like it owes me money. No hypotension yet.

 

[vector2]

Timely thread. We were just informed by our pharmacy that EACA will be unavailable until late Sept. TXA apparently $70-80/gm vial. Anyone else experiencing EACA shortage?

We're also out of amicar. Been giving TXA 10 mg/kg bolus and 1 mg/kg/h infusion for hearts.

 

[CUBR]

We've been predominately using TXA for our hearts 12.5mg/kg bolus over 10 min and 6.5mg/h/hr and scale it down for renal dysfunction. Very rarely use amicar, but per our pharmacists, we're down to just couple vials too. Having been giving TXA for PPH after the WOMAN trial came out?

 

[OB1🤙]

I've been using TXA since the last amicar shortage a few years ago. Honestly I've never seen hypotension that I've attributed to TXA.

 

[Noyac]

Has anyone had any vision issues after giving TXA? Contraindicated in color blind pts.

Also, I am reluctant to give to pts with h/o DVT. What’s the current thought on this? I know that it was considered safe but studies are starting to show increased incidence of DVT in this population.

 

[pgg]

I'm not sure if I've ever seen significant hypotension I could credibly attribute to TXA.

Our protocol for combat casualties included a loading dose of 1 g, minutes after they hit the trauma bay, and a lot of those guys were way volume down, cold, had tourniquets on, etc. IIRC the protocol said something like "over 10 minutes" but everybody got it a lot faster than that.

 

[dchz]

Well, I'm glad we have this exchange of ideas. I stand corrected.

I'd have to re-examine my scientific method; I do lack controls and have a lot of confounding in my attribution of the hypotension to TXA.

Glad we had this discussion.

 

[Psai]

Has anyone had any vision issues after giving TXA? Contraindicated in color blind pts.

Also, I am reluctant to give to pts with h/o DVT. What’s the current thought on this? I know that it was considered safe but studies are starting to show increased incidence of DVT in this population.

Just a resident but it was provoked I would discuss with surgeon and probably give it but if unprovoked then I would shy away.

 

[kidthor]

FYI our peds dosing is 50mg/kg bolus (maxing out at around 2-2.5grams) with 5-10mg/kg/hr infusion. These are very large doses compared to the adult doses I've used before, which tend to be 1 gram up front with a repeat 1 gram at some point (I've even seen the ortho people inject TXA randomly into stuff too).

I've still yet to see any side effects or complications. But it's certainly possible...

 

[Laryngophed]

I'm not sure if I've ever seen significant hypotension I could credibly attribute to TXA.

Our protocol for combat casualties included a loading dose of 1 g, minutes after they hit the trauma bay, and a lot of those guys were way volume down, cold, had tourniquets on, etc. IIRC the protocol said something like "over 10 minutes" but everybody got it a lot faster than that.

The time honored anesthesia practice of taking pharmacy's administration recommendations as suggestions?

 

[Noyac]

The time honored anesthesia practice of taking pharmacy's administration recommendations as suggestions?

Exactly. I actually can’t remember a time when the pharmacist had some enlightening input in my practice.

 

[waterbottle10]

Has anyone had any vision issues after giving TXA? Contraindicated in color blind pts.

Also, I am reluctant to give to pts with h/o DVT. What’s the current thought on this? I know that it was considered safe but studies are starting to show increased incidence of DVT in this population.

We recently had a case in our institution that was reviewed by QI committee. One thing that came up was the use of TXA in that patient (the reason for review had nothing to do with TXA) who had a history of DVT in the past. The QI committee decided the attending went against standard of care and DVTs are contraindications to TXA use. Their reason is that one of the contraindications is "Active intravascular clotting" and therefore DVT is a contraindication. I was honestly surprised by their decision. My interpretation of 'active' intravascular clotting is something along the lines of DIC/acute thrombosis (PE, stroke, DVT). Simply having a history of DVT in the past is not active clotting in my opinion, but obviously the QI committee disagreed.
My understanding of TXA use in patients with history of DVT has always been to use with caution and weigh the benefit vs potential risks. If it's a 15 level spinal fusion, I will use it, but if its a toe amp, I won't but clearly my institution disagrees with me.

 

[Psai]

We recently had a case in our institution that was reviewed by QI committee. One thing that came up was the use of TXA in that patient (the reason for review had nothing to do with TXA) who had a history of DVT in the past. The QI committee decided the attending went against standard of care and DVTs are contraindications to TXA use. Their reason is that one of the contraindications is "Active intravascular clotting" and therefore DVT is a contraindication. I was honestly surprised by their decision. My interpretation of 'active' intravascular clotting is something along the lines of DIC/acute thrombosis (PE, stroke, DVT). Simply having a history of DVT in the past is not active clotting in my opinion, but obviously the QI committee disagreed.
My understanding of TXA use in patients with history of DVT has always been to use with caution and weigh the benefit vs potential risks. If it's a 15 level spinal fusion, I will use it, but if its a toe amp, I won't but clearly my institution disagrees with me..

It's never good to practice protocolized medicine without any thought allowed. We go to medical school to learn how to make decisions that are best for each individual patient. Did they even distinguish between provoked and unprovoked?

 

[T-burglar]

I wouldn't give TXA to someone with a known DVT. Clot extension is an unacceptable risk in my opinion. Much worse of a complication than a little extra bleeding. It's not like TXA is a miracle cure for blood loss anyway.

 

[Noyac]

I wouldn't give TXA to someone with a known DVT. Clot extension is an unacceptable risk in my opinion. Much worse of a complication than a little extra bleeding. It's not like TXA is a miracle cure for blood loss anyway.

We need more of this thinking.