Michael Lallemand, MD, Donald Moe, MD, John McClellan, Mike Loughren, PhD, Shannon Marko, DVM, Matthew Eckert, MD, Matthew Martin, MD. Madigan Army Medical Center
Objectives: The acute coagulopathy of trauma after massive hemorrhage is often accompanied by hyperfibrinolysis. Tranexamic acid (TXA) is capable of reversing this physiologic phenomenon and when given early decreases mortality from bleeding. The maximum effect on mortality is seen if given within one hour post-injury and there is potential harm if given beyond three hours from injury. Establishing IV access can be difficult in a tactical setting and intraosseous (IO) access is the preferred route of drug administration. To date there is no data on the relative efficacy of TXA administered by the IO route. We hypothesize intraosseous TXA will reverse hyperfibrinolysis similarly to IV TXA.
Methods: Using a porcine traumatic hemorrhage + ischemia-reperfusion (IR) model 16 swine underwent hemorrhagic shock followed by tissue plasminogen activator (tPA) infusion to induce hyperfibrinolysis, which was confirmed with Rotational Thromboelastometry (ROTEM). Animals were randomized to receive an IV or tibial IO TXA infusion over 10 minutes. Blood samples were analyzed using ROTEM to monitor reversal of hyperfibrinolysis. Serum samples were collected for analysis of drug concentrations.
Results: After hemorrhage and IR injury the IV and IO groups had similar physiologic derangements in MAP (48 vs 49.5), lactate (11.1 vs 10.8), and pH (7.20 vs 7.22), with all p-values being not-significant. Intraosseous administration of TXA showed a correction of the lysis index at 30 minutes to 100 in the extrinsic pathway and 98.3 in the intrinsic pathways, compared to 99.8 and 98.4 in the IV group (p=0.18, p=0.44). Peak serum levels of TXA after IV and IO administration show concentrations of 160.9µg/mL and 132.57µg/mL respectively (p=0.053). Peak levels occurred at 10 minutes after the start of the infusion (completion of infusion) in both groups. Drug levels were tracked for four hours after the start of the infusion. At the end of this monitoring phase the plasma concentrations of IV and IO administered TXA were equivalent at 20.59µg/mL and 23.53µg/mL respectively (p = 0.25). Both groups showed similar rates of dynamic clearance of the drug.
Conclusions: Intraosseous administration of TXA is equally as effective as intravenous administration in reversing hyperfibrinolysis in a porcine model of hemorrhagic shock. Intraosseous administration was associated with a slightly lower peak level versus IV, but otherwise similar serum TXA levels, pharmacokinetics, and clearance.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 79681
Program Number: MSS16
Presentation Session: Full-Day Military Surgical Symposium – Trauma/Critical Care Presentations
Presentation Type: MSSPodium
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