Host response and outcome of sepsis in the critically ill

Sepsis is a major cause of morbidity and mortality worldwide. It is a life-threatening condition that is characterized by a dysregulated host response to infection, leading to tissue and organ damage. Important features of the septic host response include activation of the cytokine network, the vascular endothelium and the coagulation system. This thesis describes studies with specific research questions within the MARS cohort, a large prospective observational study conducted in the intensive care units of the Academic Medical Center in Amsterdam and the University Medical Center Utrecht. We studied several “external” and host factors that might influence sepsis outcome and the accompanying host response, particularly chronic medication (antiplatelet agents, calcium channel blockers, statins) and comorbidity (HIV infection). None of these factors had a major impact on the host response to sepsis, while only the use of calcium channel blockers was associated with an altered (improved) outcome. In addition, we examined the influence of hypothermia, an acute manifestation of severe infection, on sepsis outcome and the host response, revealing an independent association between hypothermia and mortality without evidence for an altered immune response. Finally, the research presented in this thesis provides evidence that a disturbed host response towards a more hyperinflammatory phenotype renders sepsis patients more vulnerable to develop a secondary infection while on the intensive care unit.