Thread by @DogICUma

The @PATCHTrial, led by @RussellGruen, a study of pre-hospital TXA for severe trauma in adults at high risk of acute traumatic coagulopathy treated in advanced trauma systems, has been published today in @NEJM. #CCR23 Here’s a summary of what we did...
nejm.org/doi/full/10.10…

...& what we found (and a Poll to ask what you think).
@karimbrohi @HawkmoonHEMS @CritCareReviews @QldAmbulance @NSWAmbulance @AmbulanceVic @MedSTAR_SA @MazurStef @AmbVicMedic @ClinResearchNZ @HRCNewZealand @nhmrc @WgtnFree @StJohnNZ @VACAR_AV

The effect of in-hospital TXA in trauma was evaluated in the Clinical Randomisation of an Antifibrinolytic in Significant Hemorrhage (CRASH)-2 trial. TXA,
administered within 3 hours of injury, was reported to reduce 28-day mortality
thelancet.com/journals/lance…

Patients in CRASH-2 were mainly recruited patients in countries without regional trauma systems that facilitate early access to blood products, interventional radiology and critical care.

CRASH-2 was a practice-changing trial but it left gaps. 1st, the balance of risks and benefits of tranexamic acid in advanced trauma systems remained uncertain. 2nd, patients were not followed up beyond 28 days & the effect of TXA on functional outcomes was not reported.

We undertook the @PATCHTrial to test the hypothesis that TXA, initiated pre-hospital in advanced trauma systems, would increase survival with a favourable functional outcome at six months.

We enrolled adults with severe traumatic injuries who had a high risk of acute trauma-related coagulopathy based on a COAST score of at least 3: pubmed.ncbi.nlm.nih.gov/21600687

We succeeded in enrolling a very sick group of trauma patients (many of whom had marked haemodynamic instability at the time of randomisation).

Patients were randomly allocated in a 1:1 ratio to TXA (1gm pre-hospital followed by an infusion over 8 hours) or placebo.

With respect to the effect of TXA on mortality, our findings were consistent with the CRASH 2 trial. Early mortality was significantly lower in patients allocated to TXA.

In part this appeared to be due to a lower rate of death due to bleeding in patients allocated to TXA (hazard ratio 0.66 (95% CI, 0.43 to 1.01).

In our trial, for every 100 patients treated with TXA instead of placebo, there were approximately 4 extra patients who were alive at six months. However, all of these “extra survivors” were categorised as having a poor outcome:

This meant that survival with a favourable functional outcome at 6 months occurred in 53.7% of patients in the TXA group and 53.5% in the placebo group (risk ratio (RR) 1.00; 95% CI, 0.90 to 1.12; P=0.95).

Another important finding was that, despite screening for lower limb DVT, we did not observe a significant increased risk of DVT with TXA treatment

Like all trials, this trial has limitations. Some patients were lost to follow-up, protocol compliance was imperfect, & we likely lacked power to detect heterogeneity in some important subgroups (e.g. penetrating trauma).

There are some important uncertainties. For example, we do not know how many patients with a “poor outcome” at six months subsequently improved to have a good outcome. It is likely that some improve but that many will not ever recover to have good function pubmed.ncbi.nlm.nih.gov/28678814/

It seems almost certain, based on the totality of evidence, that pre-hospital TXA reduces early deaths from bleeding; however, to six months at least, TXA appears only to increase the number of people who survive in a highly dependent state.

So, should we implement (or continue to use) pre-hospital TXA going forward?

Here are some things to think about…

First, even in the absence of formal cost-effectiveness analysis, it is evident that the costs of care associated with this therapy are likely to be extremely high (because ongoing care for patients who are dependent is very expensive).

Second, whatever decision we make, we need to live with uncertainty about recovery trajectories for TXA-treated patients after six months.

Third, although no-one wants to survive with a bad outcome, but it is important to remember that many people who survive in a dependent state are glad to be alive.

So, based on all of that, you tell me, should we implement (or continue to use) pre-hospital TXA in advanced trauma systems for adults at risk of acute traumatic coagulopathy?

Interested in thoughts, comments, and criticisms.