Characterising factors associated with susceptibility to infection in severely injured patients

Infections after trauma complicate the patients clinical course, leading to longer critical care and hospital stays. Patients who develop infection as a result of injury have decreased functional status and increased healthcare usage up to a year after injury. Infections also place considerable cost pressures on health care providers and hospital acquired infections continue to raise safety concerns for patients. Whilst increased age, invasive devices and multiple blood transfusions are reported to increase the risk of infection, the specific predictors after severe injury are under-reported.

Project aims

The overall objective of this research was to characterise factors predictive of infection in severely injured patients. We aimed to describe the burden of infections associated with severe injury and try to determine the admission characteristics of those who develop infection. We also wished to establish whether there is an association between changes in the coagulation system and immune cells following injury and the subsequent development of infection. Finally we aimed to evaluate the early use of antifibrinolytics on the development of infection following severe injury.

Key research findings:

Admission characteristics associated with infection

Infection was a significant burden for severely injured patients. Almost 50% of patients developed at least one infection whilst in hospital. The most prevalent infections affected the respiratory tract, and these occurred earliest, on average at 4-5 days from admission. There were no significant differences in age, gender, mechanism of injury or injury severity between patients who developed infection, and those who did not. Hypoperfusion was the only early admission characteristic associated with the development of infection, and a dose dependent relationship was observed between severity of admission shock and increased percentage of infection.

Early coagulation changes and infection

There is a high degree of crosstalk between coagulation and inflammation therefore we wanted to investigate if changes to clotting were associated with infection. We chose to measure this at 24 hours post injury when initial resuscitation and operative interventions would have been completed.

At this time point, the patients had normal functional clotting, however the anticoagulant protein C was significantly lower in those who developed infection (Infection: 70.2 iu/dL vs. No infection: 83.3 iu/dL p=0.02), and there was a dose dependent increase in the development of infection as levels of PC decreased. Increased fibrinolysis at 24 hours after injury (measured by plasmin antiplasmin levels) was almost 50% higher in patients who subsequently developed infection (Infection: 6156 µg/L vs. No infection: 3324 µg/L p=0.03), again with a dose dependent increase in infection as plasmin was generated. Haemorrhagic shock may activate pathways that predispose patients to infection and may help in the clinical prediction.

Inflammatory response and infection

We examined lymphocyte counts after injury as changes to these have previously been associated with other inflammatory outcomes, namely multiple organ failure. After injury lymphocyte levels will fall and then usually return to normal counts by 24-48 hours. We found that lymphopenia prolonged to day four post injury was strongly predictive of early infection (OR 0.10, CI 0.02-0.48, p<0.01). Persistently lowered lymphocyte counts after injury were also significantly associated with earlier, more severe infections such as ventilator associated pneumonia and bacteraemia. Prolonged lymphopenia after injury may have utility in identification of patients at risk of infection and other adverse outcomes.

Antifibrinolytic/anti-inflammatory TXA and infection

Tranexamic acid (TXA) is an antifibrinolytic drug with anti-inflammatory mechanisms. TXA is given to trauma patients who are known to be or suspected of bleeding. As a result of our previous findings where haemorrhage and coagulation changes were strongly predictive of infection, we wanted to evaluate if using TXA reduced infection after bleeding. In those patients who were shocked on admission there was a trend to a beneficial relationship between TXA and infection, however this was not significant. TXA was however independently associated with reduced organ failure and mortality.