Translational studies on mechanical hemostasis and coagulopathy in trauma

Trauma, in terms of physical injury, is the leading cause of death and disability among children and young adults worldwide. Hemorrhage and coagulation dysfunction are two important causes of preventable deaths after traumatic injuries. Novel methods for management of non-compressible hemorrhage and treatment of trauma induced coagulopathy (TIC) may reduce mortality.

In this thesis we investigate two fundamentally different methods for mechanical hemorrhage control after potentially lethal truncal hemorrhage: intravascular occlusion- and external compression of the aorta. The Abdominal Aortic and Junctional Tourniquet® (AAJT) and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) were initially introduced in military medicine as possible interventions to avoid exsanguination from large vessel injuries. We assessed these interventions during 60 to 240 minutes with the aim to identify specific physiological effects and suggest tolerable application times. The feasibility of a transition between the methods was studied.

We investigated the hemodynamic effects of crystalloid- and whole blood transfusion in conjunction with the interventions. Intermittent reperfusion during REBOA, with the aim to decrease organ damage was investigated. We introduced a method for advanced analyzation of viscoelastic tests by principal component analysis to detect TIC. The AAJT and REBOA were both effective to stop hemorrhage distal to the aortic bifurcation and restored critical circulation proximal to the aortic occlusion. Infra-renal REBOA required more crystalloid fluids to restore the circulation than AAJT. Both methods caused ischemic injuries which became significant after 1 hour of infra-renal aortic occlusion. The ischemic injuries were alleviated by intermittent reperfusion during thoracic REBOA application. TIC was detected in pigs by principal component analysis of rotational thromboelastometry, which comprised a new method for possible identification of TIC phenotypes.

In conclusion, mechanical hemostasis was effective by both abdominal tourniquet- and intravascular aortic occlusion. We also identified potentially severe complications due to hemodynamic- and metabolic consequences, particularly when application times exceed one hour.

List of scientific papers

I. Abdominal Aortic and Junctional Tourniquet release after 240 minutes is survivable and associated with small intestine and liver ischemia after porcine class II hemorrhage. Brännström A, Rocksén D, Hartman J, Nyman N, Gustavsson J, Arborelius UP, Günther M. J Trauma Acute Care Surg. 2018 Oct;85(4):717-724.
https://doi.org/10.1097/TA.0000000000002013

II. Increased crystalloid fluid requirements during zone 3 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) versus Abdominal Aortic and Junctional Tourniquet (AAJT) after class II hemorrhage in swine. Brännström A, Dahlquist A, Gustavsson J, Arborelius UP, Günther M. Eur J Trauma Emerg Surg. 2021 Jan 30:1-10.
https://doi.org/10.1007/s00068-020-01592-x

III. Transition from abdominal aortic and junctional tourniquet to zone 3 resuscitative endovascular balloon occlusion of the aorta is feasible with hemodynamic support after porcine class IV hemorrhage. Brännström A, Dahlquist A, Gustavsson J, Arborelius UP, Günther M. J Trauma Acute Care Surg. 2019 Oct;87(4):849-855.
https://doi.org/10.1097/TA.0000000000002426

IV. Improved Renal Blood Flow and Indices of Organ Function after 60 minutes Intermittent versus Continuous Zone 1 REBOA in an Animal Model of Lethal Hemorrhage. Brännström A, Hultström M, Gustavsson J, Aurfan Z, Günther M. [Manuscript]

V. The Swine as a vehicle for research in trauma-induced coagulopathy: Introducing principal component analysis for viscoelastic tests. Brännström A, von Oelreich E, Degerstedt LE, Dahlquist A, Hånell A, Gustavsson J, Günther M. J Trauma Acute Care Surg. 2021 Feb 1;90(2):360-368.
https://doi.org/10.1097/TA.0000000000002997