Late mortality after sepsis

An overview of the debate and evidence surrounding whether high long-term mortality after sepsis is caused by the infection or pre-existing comorbidities.

Read the full open access paper: bmj.com/content/353/bmj.i2375 Sepsis, an inflammatory response to infection, is a leading cause of admission to hospital in the developed world. While mortality in hospital is falling, longer term mortality after sepsis has remained high as many patients die in the subsequent months. Some argue that this late mortality is simply a reflection of the underlying comorbidity burden of patients who develop sepsis, whereas others argue it is the result of sepsis itself. Previous studies have provided evidence on both sides of the debate. Several studies explicitly assert that late mortality after critical illness is largely because of pre-existing comorbid disease. Quartin and colleagues, however, showed that risk of mortality remained higher for up to five years after sepsis, even compared with carefully matched controls in hospital with similar burden of comorbidity at baseline. To guide the development of future treatments, we measured the excess late (31 days to two years) mortality directly attributable to sepsis—and not to the comorbidities and sociodemographic factors that predispose one to developing sepsis. We looked at patients with sepsis compared with three control groups: adults not currently in hospital, patients in hospital with non-sepsis infection, and patients in hospital with an acute sterile inflammatory process. These comparisons allowed us to determine the excess mortality associated with sepsis (including that associated with admission to hospital) and the incremental excess mortality associated with sepsis, beyond what is associated with admission for the two cardinal features of sepsis: infection (by comparing sepsis with inflammatory conditions not caused by infection) and inflammation (by comparing sepsis with infections without evidence of inflammatory storm). We examined an ongoing longitudinal prospective cohort, in which we could assess the health of a national sample of older Americans independent of whether they were admitted to hospital for sepsis. This allowed us to assess not just traditional risk factors for sepsis but also a range of potential confounders.