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Plasma coadministration improves resuscitation with tranexamic acid or prothrombin complex in a porcine hemorrhagic shock model

Kuckelman, John DO; Barron, Morgan MD; Moe, Donald MD; Lallemand, Michael MD; McClellan, John MD; Marko, Shannon DVM; Eckert, Matthew MD; Martin, Matthew J. MD

Journal of Trauma and Acute Care Surgery: July 2018 - Volume 85 - Issue 1 - p 91–100
doi: 10.1097/TA.0000000000001942
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BACKGROUND Traumatic coagulopathy has now been well characterized and carries high rates of mortality owing to bleeding. A "factor-based" resuscitation strategy using procoagulant drugs and factor concentrates in lieu of plasma is being used by some, but with little evidentiary support. We sought to evaluate and compare resuscitation strategies using combinations of tranexamic acid (TXA), prothrombin complex concentrate (PCC), and fresh frozen plasma (FFP).

METHODS Sixty adult swine underwent 35% blood volume hemorrhage combined with a truncal ischemia-reperfusion injury to produce uniform shock and coagulopathy. Animals were randomized to control (n = 12), a single-agent group (TXA, n = 10; PCC, n = 8; or FFP, n = 6) or combination groups (TXA-FFP, n = 10; PCC-FFP, n = 8; TXA-PCC, n = 6). Resuscitation was continued to 6 hours. Key outcomes included hemodynamics, laboratory values, and rotational thromboelastometry. Results were compared between all groups, with additional comparisons between FFP and non-FFP groups.

RESULTS All 60 animals survived to 6 hours. Shock was seen in all animals, with hypotension (mean arterial pressure, 44 mm Hg), tachycardia (heart rate, 145), acidosis (pH 7.18; lactate, 11), anemia (hematocrit, 17), and coagulopathy (fibrinogen, 107). There were clear differences between groups for mean pH (p = 0.02), international normalized ratio (p < 0.01), clotting time (CT; p < 0.01), lactate (p = 0.01), creatinine (p < 0.01), and fibrinogen (p = 0.02). Fresh frozen plasma groups had significantly improved resuscitation and clotting parameters (Figures), with lower lactate at 6.5 versus 8.4 (p = 0.04), and increased fibrinogen at 126 versus 95 (p < 0.01). Rotational thromboelastometry also demonstrated shortened CT at 60 seconds in the FFP group vs 65 seconds in the non-FFP group (p = 0.04).

CONCLUSION When used to correct traumatic coagulopathy, combinations of FFP with TXA or PCC were superior in improving acidosis, coagulopathy, and CT than when these agents are given alone or in combination without plasma. Further validation of pure factor-based strategies is needed.

Department of Surgery (J.K., M.B., D.M., M.L., J.M., M.E., M.J.M.), Madigan Army Medical Center, Tacoma, Washington; Department of Clinical Investigations (S.M.), Madigan Army Medical Center, Tacoma, Washington; and Trauma and Emergency Surgery Service (M.J.M.), Legacy Emanuel Medical Center, Portland, Oregon.

Submitted: November 27, 2017, Revised: February 3, 2018, Accepted: April 6, 2018, Published online: April 19, 2018.

This paper was accepted for a podium presentation at the 2018 annual Eastern Association for the Surgery of Trauma meeting in Orlando, FL, on January 10, 2018 as a Raymond H. Alexander Resident paper competition nominee.

Address for reprints: Matthew J. Martin, MD, Trauma Medical Director, Department of Surgery, Madigan Army Medical Center, 9040-A Fitzsimmons Ave, Tacoma, Washington 98431; email: matthew.j.martin16.mil@mail.mil.

© 2018 Lippincott Williams & Wilkins, Inc.