Tranexamic acid has been dubbed the little injection that could. Unfortunately, no one is giving this wonder drug much of a chance to prove its worth, despite a survival advantage being shown in soldiers wounded in Iraq and Afghanistan. More than a decade later, however, the drug is still not being widely adopted by EMS here at home.
Tranexamic acid (TXA) surfaced in studies to determine which battlefield techniques seemed to be life-preserving. It now ranks on a list of proven approaches, according to one comprehensive analysis. (J Trauma Acute Care Surg 2012;73[6 Suppl 5]:S395.) And when the U.S. Army recently launched an investigation into TXA studies for trauma and hemorrhage — the Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study, known simply as MATTERs — the results showed that TXA indeed does matter. (Arch Surg 2012;147:113.) The difference between life and death was most striking, in fact, when TXA was given to those with massive injury.
So why aren't most U.S. emergency medical services using it? “TXA is still quite novel in its use in civilian EMS,” explained Jeffrey Goodloe, MD, a professor of emergency medicine and the director of EMS at the University of Oklahoma School of Community Medicine in Tulsa. He supports the approach for patients who are correctly screened by paramedics — if the trauma-center destination utilizes the MATTERs study protocol and the largest study on TXA to date, the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage, known as CRASH-2, which involved nearly 20,000 trauma victims in Great Britain. (Health Technol Assess 2013;17:1.)
TXA is considered so safe as a result of CRASH-2 that it is often recommended for all multitrauma patients by hospitals in the United Kingdom, regardless of severity or instability. At $10 a dose and with essentially no significant side effects compared with control groups, the use of TXA in the United States needs “more of a groundswell of support, and I hope we can build it,” said Howard Mell, MD, the medical director of the Newark, OH, Fire Department, which was one of the first ground units in the United States to use it. The protocol there is based on CRASH-2, which demonstrated life-saving benefits when the drug is administered intravenously within an hour of injury over 10 minutes' time and then again over an eight-hour period. That is just how it is being used in his system, Dr. Mell said.
It wasn't easy to implement despite the data. That necessary second dose essentially means the IV also has to be given during hospitalization. “So I had to find a working partner,” Dr. Mell said. The first hospital he approached turned him down flat, citing concerns about using something so new, even though CRASH-2 “is just an amazing study” with compelling results, he said.
His luck changed at Ohio State Medical Center, which had a trauma pharmacist who looked at TXA's track record and agreed. “The thing that becomes clear when you evaluate this is that the most injured people may be the ones most likely to be saved by it,” Dr. Mell pointed out. A slight but significant difference in survival is seen when all trauma victims are considered, and that significance becomes stronger as the severity of injury increases.
“If you give this drug 23 times for an injury, you will end up saving one life. But if you give it to the most seriously injured, you'll save one of every seven lives,” he stressed. TXA is utilized in Newark's system in a more limited way, typically in Level I and II traumas that are hemodynamically unstable.
One clear advantage: It can effectively prevent the continual internal bleeding that may go undetected in the torso from high-impact collisions or falls, including the kind seen in rock climbers who plummet from mountainsides and then seem to be uninjured or bikers who slide along the roadway after losing control yet appear to be unscathed.
The EMS programs using it so far seem to be few and far-flung across the country, with utilization the result of TXA advocates like Drs. Mell and Goodloe. The American College of Emergency Physicians is “aware of at least two emergency physicians using the drug in their protocols,” noted Rick Murray, the EMS and disaster preparedness director for the college.
“In this early era of its use, I believe it is very helpful to closely follow the outcomes of these patients in terms of correct screening for its use by paramedics,” Dr. Goodloe said. The two major studies, CRASH-2 and MATTERs, indicate that venous thromboembolism can occur, although it occurred in TXA and non-TXA cohorts. Still, “continued observation is warranted to best establish the safety of TXA in a larger population over time,” he cautioned. “As increasing numbers of EMS agencies utilizing TXA in their standard of care occur, it will be harder to accurately capture data due to so many disparate variables in local trauma care and systems,” Dr. Goodloe pointed out. “That said, larger systems more likely to have higher TXA usage should, in my opinion, be capturing this clinical data and be willing to share [it] through formal study presentation at academic emergency medicine and surgical association symposiums.”
He added that current experience to date indicates that applying the CRASH-2 selection criteria “will likely yield few patients in most urban environments, and it may take years before a large-scale civilian cohort in the United States, particularly initially treated with TXA by EMS, can be reported.”