Thioredoxin a novel biomarker of post-injury sepsis.

BACKGROUND: Thioredoxin (TRX), an endogenous anti-oxidant protein induced in inflammatory conditions, has been shown to increase in plasma and to be associated with outcome in septic patients. This biomarker has never been studied in a trauma setting. We hypothesized that TRX would be increased after trauma and associated with post-injury sepsis.

METHODS: Single-centre prospective observational study conducted at the intensive care unit (ICU) at the Karolinska University Hospital, Stockholm, Sweden, a level-1 trauma centre. Eighty-three severely injured trauma patients, 18 years or older, with an ICU stay of three days or more were included. Plasma samples were obtained on day 1 and 3 after informed consent. Clinical, physiological and outcome data were retrieved from the trauma and ICU research registries. Plasma samples were also obtained from 15 healthy subjects. In addition, a standardized porcine trauma model was conducted where a femur fracture followed by a controlled hemorrhage period were inflicted in four pigs.

RESULTS: In pigs, however not significant, there was a continuing increase in plasma-TRX after femur fracture and sequential hemorrhage despite near normalisation of cardiac index and lactate levels. In patients, median injury severity score was 29 and 48 patients developed sepsis during their ICU stay. A three-fold increase in initial TRX was seen in trauma patients when compared to healthy volunteers. Thioredoxin was significantly higher in patients in shock on admission, those subject to massive transfusion and in the most severely injured patients. No difference was seen between survivors and non-survivors. Plasma-TRX on day 1 was significantly increased in patients who later developed post-injury sepsis. In a logistic regression analysis including TRX, C-reactive protein, injury severity, massive transfusion, and admission blood pressure, TRX was the only variable independently associated with post-injury sepsis.

CONCLUSIONS: This study demonstrates that TRX is released into plasma in response to severe trauma and independently associated with post-injury sepsis. The use of TRX as a biomarker in trauma patients needs further evaluation in larger studies.

LEVEL OF EVIDENCE: Retrospective cohort study, level III.