Grant: Operating Grant

Severe sepsis (ie. life-threatening infections) is triggered by harmful microorganisms or their toxins in the blood or tissues. These harmful agents damage the lining of blood vessels which can lead to inflammation, blood clot formation, and vessel obstruction. In Canada, there are approximately 90,000 patients with severe sepsis each year. Of these, 30% to 50% will die. The identification of highly reliable outcome predictors in severe sepsis patients is important for several reasons including: to help describe the severity of sepsis, to classify patients for enrolment in clinical studies, and to monitor a patient's response to treatment and procedures. In our lab, we examined the incremental usefulness of adding multiple biomarkers to clinical scoring systems for predicting ICU mortality in patients with severe sepsis. In a preliminary study of 80 patients with sepsis, we found that high levels of plasma DNA predicted ICU death better than any other clinical or biological factor. In this grant, we propose to confirm these findings in an external group of 400 patients in a blinded fashion. We also plan to study how plasma DNA levels change over time and whether high plasma DNA levels can be used to distinguish sepsis from other critically ill conditions. Finally, we will examine how high levels of plasma DNA cause death using a mouse model of sepsis. Our research thus has the potential to significantly improve the management and treatment of septic patients.