Sepsis in the intensive care unit: epidemiology, outcome and host response

Sepsis is a life-threatening syndrome that arises when a dysbalanced patient response to an infection causes damage to the body’s own organs and tissues. Sepsis is, to date, still a major cause of morbidity and mortality worldwide. A detailed understanding of the pathogenesis of sepsis is likely to aid future individualized sepsis treatment. Early detection of causative pathogens and the development of new molecular techniques for early prognostication can be essential in individualized care for, and treatment of, patients with sepsis. In patients with sepsis, multiple risk factors for unfavorable outcome have been suggested, such as age, gender, premorbid conditions, acute disease conditions and the increased susceptibility to nosocomial infections. In this thesis, we studied the relationship of these host factors with disease severity, host response and outcome. We found that gender and premorbid diabetes were not associated with alterations in the host response, disease severity or outcome in critically ill sepsis patients. However, factors that were of influence included advanced age, dysregulated glucose levels and thrombocytopenia. In addition to this, ICU-acquired infections did not occur more often in patient admitted with sepsis and bear an overall low attributable mortality. The studies described in this thesis are unique in that they integrated detailed clinical and microbiological data with comprehensive host response measurements in one of the largest sepsis cohorts in the world, the MARS cohort.