Five Questions With: Martin Schreiber on EMS Giving TXA to TBI Patients

Martin Schreiber, MD, FACS, FCCM, is the Director of Donald D. Trunky Center for Civilian and Combat Casualty Care at Oregon Health & Science University.  Schreiber and his co-authors just published in JAMA a landmark study showing positive outcomes for traumatic brain injury (TBI) patients who received 2 grams of tranexamic acid (TXA) in the out-of-hospital setting.  EMS World interviews Schreiber about the fine print of this important research.

EMS World: Can you summarize the overall results of the TXA for TBI study? 

Schreiber: We performed a three-armed prospective randomized trial in trauma patients with moderate to severe TBI as defined by head injury and a GCS between 3-12. Patients were randomized in the field to one of three groups. Group 1 got a 2-gram bolus of TXA and normal saline infusion over 8 hours in the hospital; Group 2 got a 1-gram bolus of TXA and in-hospital TXA 8-hour infusion; Group 3 got a placebo bolus out-of-hospital and 8-hour placebo infusion in the hospital.

The most important finding is that those who received the 2-gram bolus showed a 12% improvement in survival.  Most of that benefit occurred in first 10 hours after their injury.  These boluses were started at a median 42 minutes after injury by EMS providers in the field.  In the JAMA article, it’s all shown at the end of the results, in the "Exploratory Analysis of Subgroups."  Figure 2 shows the survival benefit as does the bottom of Table 4.  You have to look pretty hard but it’s there.

The key is the drug works in patients with intracranial hemorrhage.  Based on the way, we planned the study, we included all of the patients in the primary analysis and only 56% had intracranial bleeding, so on the surface it looks like a negative study.  We are writing another manuscript including only patients with intracranial hemorrhage.

Many systems using TXA currently are likely basing their 1-gram dosing of TXA (and then another 1-gram infusion in the hospital) on protocols suggested for patients having elective surgery.  The history goes back 50 years, with some of the first uses in obstetrics. TXA is cheap and our study showed paramedics could comply with the procedures 95% of the time.

What are the most important takeaways for EMS treating patients with TBI?

That’s easy: EMS providers have the capacity by using this drug to save lives.  When we dug deeper into the patient population, we found that only 56% of the suspected TBI patients actually had a brain injury.  But for those who didn’t, receiving TXA caused no long term harm.  

Many EMS providers have been using TXA for hemorrhage already.  Can you talk about the dose differences in this trial as well as explain the mechanism of action of TXA that may be responsible for improving outcomes?

The key is to give the total dose of 2 grams of TXA up front.  The work hasn’t yet been done in hemorrhagic shock but needs to be done. 

TXA is designed as an antifibrinolytic so it prevents lysis of a clot and then the clot is not broken down.  TXA also affects the endothelial barrier, decreasing cerebral edema to help prevent herniation, or at least that’s what we are hypothesizing.  TXA works best when it is given in a higher dose up front meaning a higher peak concentration. 

You worked closely with Multnomah Co. (Ore.) EMS medical director Jon Jui and the EMS providers who conducted this trial.  Can you talk about how the trial was set up for EMS and more importantly, what advice you have for EMS agencies interested in helping with research like this?

The real key to this is the long-standing Resuscitation Outcomes Consortium (ROC), in existence for over 10 years. All of the sites around the country found their own way to get this done and helped to train the EMS agencies.  

The Portland region is a four-county system with multiple agencies and many different set ups.  The key to making research work is that it has to be tailored to your own agency.  We have a monthly EMS research conference where these groups get together and discuss research collaboration.

What spurred this research? Why did you decide on this topic? 

For me, it started in Afghanistan where I was the joint theater trauma system director. When the TXA research came out of the CRASH-2 trial, I got a call from the Pentagon.  “Why aren’t you giving TXA to warfighters?” they asked. My answer? 1. We don’t have the drug and 2. I had concerns about the validity of the study. 

Brain injury is my research interest.  We haven’t had anything that has improved outcomes in brain injured patients. I want to make it possible for every warfighter to carry a 2-gram TXA bolus and inject themselves or buddy intramuscularly.  You could make the same argument for patients in hemorrhagic shock.  Warfighters all carry tourniquets right now, and we could easily make room for TXA.  You could give this right away.  Everything points to better outcomes. 

*Author's note: a more detailed explanation of the study's benefits have been added to Schreiber's first answer.

Hilary Gates, MAEd, NRP, is the senior editorial and program director for EMS World.