Studies Show Prehospital Tranexamic Acid Benefit in Trauma, Promise of IM Administration

By Marilynn Larkin

October 07, 2020

NEW YORK (Reuters Health) - Trauma patients have lower 30-day mortality when they receive intravenous (IV) tranexamic acid (TXA) in the field, and the intramuscular (IM) route is a promising option for administering the drug, new studies reveal.

In the phase 3 STAAMP trial (Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport), published in JAMA Surgery to coincide with a presentation at the virtual clinical congress of the American College of Surgeons, 927 patients (mean age, 42; 74% men) were randomized to prehospital infusions of 1 g TXA or placebo. Participants had hypotension (systolic blood pressure, 90 mm Hg or less) or tachycardia (heart rate,110/min) before arriving at a U.S. level-1 trauma center within an estimated two hours of injury.

Dr. Jason Sperry of the University of Pittsburgh and colleagues found that overall, 30-day mortality did not differ between the groups, except when TXA was given within one hour of injury (4.6% vs. 7.6% for placebo). Further, a subgroup with prehospital severe shock (systolic blood pressure, 70 mm Hg or less) who received IV TXA also had a lower 30-day mortality compared with the placebo group (18.5% vs. 35.5%).

In a separate report in the British Journal of Anesthesia, Dr. Ian Roberts of the London School of Hygiene and Tropical Medicine and colleagues describe an open-label pharmacokinetic study of IM TXA in two UK hospitals.

Thirty bleeding trauma patients (mean age, 26, 87% men, 80% white) received a loading dose of IV TXA 1 g, as per guidelines, then a second dose given as two 5 ml (0.5 g each) IM injections.

IM TXA was well tolerated, with only mild injection site reactions. Therapeutic concentrations after a single IM injection were reached within 15 minutes. Blood lactate and signs of shock had no apparent impact on the rate of absorption.

"This result could be a game changer for trauma care world-wide," Dr. Roberts told Reuters Health by email. "In acute severe bleeding, minutes count."

"In low- and middle-income countries often lacking formal pre-hospital paramedic care, IM TXA could be given by basic ambulance crews or even lay first responders like police officers - especially if it was packaged into pre-filled syringes or an autoinjector," he noted. "Longer term, we need simple-to-use autoinjectors that could be used by lay first responders. Rapid treatment will save lives."

The results of STAAMP and the earlier CRASH-2 and CRASH-3 global trials (https://bit.ly/2GHn2uy and https://bit.ly/3jBMOPF) for which Roberts was chief investigator "confirm that early administration of TXA is life saving (and) that time to treatment is critical," he said.

"Although there were about 20% fewer deaths in the TXA-treated group (in STAAMP), this result was not statistically significant," he acknowledged. "But 20% fewer deaths is good news and similar to the benefit we showed in the 20 times larger CRASH-2 trial, where the reduction in deaths was statistically significant. IM TXA can help with this."

Commenting on the IM study, Dr. Jeremy Cannon, Trauma Medical Director and Section Chief of Trauma at Penn Medicine, told Reuters Health that although injection site reactions were noted, "I would be more interested in the systemic effects of this medication, including clot formation in areas where you do not want clots, such as the extremities or the lungs (deep vein thrombosis or pulmonary embolism, respectively). Thrombotic complications are the Achilles heel of all of these pro-coagulant medications, including TXA."

"Clinicians should be aware that this is a very preliminary study looking at the pharmacology of the medication in trauma patients, including some who were in shock and needed blood transfusion," he said by email. "The findings are interesting, but were not directly compared to the standard IV regimen for TXA currently in use (1 gram bolus over 10 min followed by 1 gram infusion over 8 hours)."

Dr. Carrie Sims, Division Director, Trauma, Critical Care and Burn at The Ohio State University Wexner Medical Center in Columbus also commented by email. "It is unclear why the IV route was chosen initially, and while there appears to be rapid absorption, it is unclear if these patients were still in shock by the time the IM (dose) was administered."

Nonetheless, she told Reuters Health, "Although further research is needed regarding the pharmacokinetics of IM TXA in hemorrhaging patients, this paper demonstrates that IM dosing is possible and likely effective."

SOURCES:

https://bit.ly/3jD2BxA and https://bit.ly/3d3U2t6

JAMA Surgery, online October 5, 2020

https://bit.ly/33C9Gsy British Journal of Anesthesia, online

September 30, 2020.

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