Page 82 - JSOM Winter 2019

Pharmacokinetics of Tranexamic Acid via
Intravenous, Intraosseous, and Intramuscular Routes in a
Porcine (Sus scrofa) Hemorrhagic Shock Model

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Erik S. DeSoucy, DO ; Anders J. Davidson, MD, MAS ; Guillaume L. Hoareau, DVM, PhD ;
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Meryl A. Simon, MD ; Emily M. Tibbits, MD ; Sarah-Ashley E. Ferencz, MD ;
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J. Kevin Grayson, DVM, PhD ; Joseph M. Galante, MD 8
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ABSTRACT
Background: Intravenous (IV) tranexamic acid (TXA) is an management of abdominal hemorrhage. However, none of
adjunct for resuscitation in hemorrhagic shock; however, IV these techniques will correct the acute coagulopathy associ-
access in these patients may be difficult or impossible. Intraos- ated with trauma.
seous (IO) or intramuscular (IM) administration could be
quickly performed with minimal training. We investigated the Trauma-induced coagulopathy (TIC) is a complex disorder
pharmacokinetics of TXA via IV, IO, and IM routes in a swine that may aggravate the effects of the original injury, leading
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model of controlled hemorrhagic shock. Methods: Fifteen to a higher risk of exsanguination and mortality. Acute co-
swine were anesthetized and bled of 35% of their blood vol- agulopathy is present in up to 25% of trauma patients and
ume before randomization to a single 1g/10mL dose of IV, IO, is associated with increased mortality compared with patients
or IM TXA. Serial serum samples were obtained after TXA without coagulopathy (46% vs 11%, respectively). TIC is as-
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administration. These were analyzed with high-pressure liquid sociated with various pathologic processes, including, but not
chromatography–mass spectrometry to determine drug con- limited to, dilutional coagulopathy, thrombocytopenia, plate-
centration at each time point and define the pharmacokinetics let dysfunction, hypofibrinogenemia, and hyperfibrinolysis.
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of each route. Results: There were no significant differences Early antifibrinolytic therapy with TXA, a lysine analog that
in baseline hemodynamics or blood loss between the groups. competitively inhibits plasminogen activation to plasmin, pre-
Peak concentration (C max ) was significantly higher in IV and venting fibrin degradation, has emerged as a potential solution
IO routes compared with IM (p = .005); however, the half-life to improve outcomes in trauma patients. IV TXA given within
of TXA was similar across all routes (p = .275). Conclusion: the first 3 hours after injury improves overall survival in pa-
TXA administration via IO and IM routes during hemorrhagic tients with traumatic hemorrhagic shock, and greater benefit
shock achieves serum concentrations necessary for inhibition is achieved with earlier administration. 9–11
of fibrinolysis and may be practical alternatives when IV ac-
cess is not available. Early administration of TXA was incorporated into Tactical
Combat Casualty Care (TCCC) protocols in 2011. However,
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Keywords: shock, hemorrhagic; tranexamic acid; intravenous the currently recommended dose (1g/100 mL over 10 minutes
access followed by 1g/100mL infusion over the next 8 hours) may
not be easily delivered intravenously in a combat setting due to
difficulty or inability to establish IV access. IO and IM routes
are rapidly accessed and readily available in the injured patient;
Introduction
additionally, IM administration requires minimal training. Al-
Hemorrhagic shock is the leading cause of preventable death though these routes would simplify TCCC protocols in austere
in civilian and combat trauma, accounting for 91% of po- environments, further pharmacokinetic (PK)/pharmacodynamic
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tentially survivable injuries. Among these patients, 87% of (PD) modeling in shock is needed to identify optimal dosing
deaths occurred before arrival at a medical treatment facility. strategies before field implementation by combat personnel. 13
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Tourniquets are already in use to control prehospital extrem-
ity and junctional hemorrhage. Additionally, there are newer In a pilot study, we established that IM and IO TXA adminis-
technologies such as intrabdominal in situ forming polymeric tration achieved serum concentrations similar to the standard
foam (ResQFOAM ) and resuscitative endovascular balloon IV route in normotensive swine; serum levels were comparable
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occlusion of the aorta, which may yet find a place in the field to values expected in humans. However, this model did not
Presented at the 76th Annual Meeting of the American Association for the Surgery of Trauma; 13–16 September 2017; Baltimore, MD.
*Correspondence to Erik S. DeSoucy, DO, Clinical Investigation Facility, 101 Bodin Circle, Fairfield, CA 94535 or erik.s.desoucy.mil@mail.mil
1 Maj DeSoucy is affiliated with Clinical Investigation Facility, David Grant USAF Medical Center, Travis Air Force Base, CA; and Department of
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Surgery, University of California Davis Medical Center, Sacramento, CA. Maj Davidson is affiliated with Clinical Investigation Facility, David
Grant USAF Medical Center, Travis Air Force Base, CA; and Department of Surgery, University of California Davis Medical Center, Sacramento,
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CA. Dr Hoareau is affiliated with Clinical Investigation Facility, David Grant USAF Medical Center, Travis Air Force Base, CA. Maj Simon is af-
filiated with Clinical Investigation Facility, David Grant USAF Medical Center, Travis Air Force Base, CA; and Department of Surgery, University
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of California Davis Medical Center, Sacramento, CA. Maj Tibbits is affiliated with Clinical Investigation Facility, David Grant USAF Medical
Center, Travis Air Force Base, CA; and Department of Surgery, University of California Davis Medical Center, Sacramento, CA. Dr Ferencz is
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affiliated with Department of Surgery, Wright State University, Dayton, OH. Dr Grayson is affiliated with Clinical Investigation Facility, David
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Grant USAF Medical Center, Travis Air Force Base, CA. Dr Galante is affiliated with Department of Surgery, University of California Davis
Medical Center, Sacramento, CA.
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