Combined N-acetylcysteine and tranexamic acid attenuate acidosis and fibrinolysis in a swine polytrauma model.

BACKGROUND

Traumatic coagulopathy is a major contributor to mortality after severe hemorrhage. Tranexamic acid (TXA) reduces fibrinolysis, and N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. Both agents have shown benefit individually, but their combined effect has not been previously investigated in trauma. We hypothesized that early administration of NAC with TXA during resuscitation could attenuate acidosis and fibrinolysis in an experimental study with a hemorrhagic shock and polytrauma swine model.

METHODS

Thirty-six male Landrace pigs (28.3 ± 3.0 kg) were randomized into five groups: Sham (n = 5), Ringer lactate (n = 5), NAC (n = 6), TXA (n = 6), and NAC+TXA (n = 6). Animals underwent experimental standardized polytrauma (femur fracture, controlled hemorrhage of 60% blood volume), followed by immediate resuscitation and a grade IV liver injury. Standard physiological parameters, blood gases, lactate, coagulation tests, fibrinogen, and thromboelastometry (ROTEM parameters) were assessed at baseline, post-shock, post-resuscitation, post-liver injury, and final.

RESULTS

All trauma groups developed profound shock physiology compared with Sham. The NAC+TXA group demonstrated the most complete correction of acid-base status, achieving the highest final pH (7.5 ± 0.03), significantly greater than Ringer lactate (7.3 ± 0.09), NAC (7.3 ± 0.06), and TXA (7.3±0.11) ( p = 0.001). Lactate and base deficit showed directionally similar improvements.Thromboelastometry showed attenuated fibrinolysis with combined therapy. The NAC+TXA group exhibited lower maximum lysis after liver injury compared with NAC (10 ± 3% vs 16 ± 4%, p = .008). Other ROTEM parameters displayed directionally similar trends toward improved clot formation.

CONCLUSIONS

In this swine polytrauma model, the combined administration of NAC and TXA was associated with improved in acid-base status and attenuation of fibrinolysis. While these physiological effects are preliminary, they support additional experimental investigations to clarify mechanisms, reproducibility, and potential translational relevance of NAC+TXA as an adjunct in damage control resuscitation. ( J Trauma Acute Care Surg . 2026;101: 297-305. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.