Aspects of risk factors, pathophysiology and outcomes in trauma

Trauma is a global health concern. Many trauma patients succumb on the scene or in the immediate phase after trauma. Patients surviving the initial phase may die at a later stage or suffer debilitating consequences in the post-resuscitation phase of trauma care in intensive care units. This thesis is focused on factors associated with outcomes and complications after trauma, as well as early recognition of these complications.

Trauma patients using β-adrenergic receptor antagonists (β-blockers) at the time of injury had more comorbidities and an increased mortality compared to non-users. However, when adjusting for relevant confounders no association between pre-traumatic β-blockade and mortality survival was seen. Previous research suggesting a protective effect of β-blockers in trauma could therefore not be supported.

We investigated thioredoxin (TRX), a potent endogenous antioxidant, and its associations with post-injury sepsis. TRX was elevated after an inflicted femur fracture and subsequent hemorrhage in an animal trauma model. Plasma-levels of thioredoxin was also evaluated in 83 severely injured trauma patients and were significantly higher when compared to healthy controls. This biomarker was associated with injury severity, shock on arrival and massive transfusion. Further, an association between TRX and post-injury sepsis was shown after adjustments for confounders.

The new sepsis definition, sepsis-3, was evaluated and compared with the previous definition, sepsis-2, in 722 severely injured trauma patients. Fewer patients were diagnosed with sepsis when using the new sepsis-3 definition as compared with the old sepsis-2 definition. No association was seen between sepsis, regardless of definition used and overall mortality. However, after censoring patients dying on the first day, before being at risk for sepsis, sepsis-3 was associated with 30-day mortality, whereas sepsis-2 was not. The new definition was feasible and had a stronger association with mortality.

Risk factors for post-injury sepsis as defined by the new sepsis-3 criteria included: age, spineand chest-injuries, shock on arrival and blood transfusion. Moreover, there was an association between blood alcohol at admission and later development of sepsis previously not described. Patients who developed post-injury sepsis had a complicated clinical course with an increased need for vasopressor treatment, mechanical ventilation and had more days with organ dysfunction. A significant association between post-injury sepsis and mortality was shown, but only after early censoring for trauma-related deaths.

Using a technique for longitudinal clustering, we identified five distinct trajectories of organ dysfunction after trauma. Each one with different baseline characteristics, evolution of organ dysfunction and outcomes. These trajectories had unequal times until stabilization, indicating that some trajectories are easier to identify in an early stage. The study underlines the heterogenous course after trauma and suggests that there exist subsets of traumatically injured patients that might benefit from targeted measures.

List of scientific papers

I. Effect of preadmission beta blockade on mortality in multiple trauma. Eriksson M, von Oelreich E, Brattström O, Eriksson J, Larsson E, Oldner A. British journal of surgery Open. 2018, 2, 392-399.
https://doi.org/10.1002/bjs5.83

II. Thioredoxin a novel biomarker of post-injury sepsis. Eriksson J, Gidlöf A, Eriksson M, Larsson E, Brattström O, Oldner A. Free Radical Biology and Medicine. 2017, 104, 138-143.
https://doi.org/10.1016/j.freeradbiomed.2017.01.016

III. Comparison of the sepsis-2 and sepsis-3 definitions in severely injured trauma patients. Eriksson J, Eriksson M, Brattström O, Hellgren E, Friman O, Gidlöf A, Larsson E, Oldner A. Journal of Critical Care. 2019, 54, 125-129.
https://doi.org/10.1016/j.jcrc.2019.08.019

IV. Postinjury sepsis - Associations with risk factors, impact on clinical course, and mortality: A retrospective observational study. Eriksson J, Lindström A-C, Hellgren E, Friman O, Larsson E, Eriksson M, Oldner A. Critical Care Explorations. 2021, v3(8), e0495.
https://doi.org/10.1097/CCE.0000000000000495

V. Temporal patterns of organ dysfunction after severe trauma. Eriksson J, Nelson D, Holst A, Hellgren E, Friman O, Oldner A. Critical Care. 2021, 25, 165.
https://doi.org/10.1186/s13054-021-03586-6