Impact of different consensus definition criteria on sepsis diagnosis in a cohort of critically ill patients—Insights from a new mathematical probabilistic approach to mortality-based validation of sepsis criteria

Sepsis-3 definition uses SOFA score to discriminate sepsis from uncomplicated infection, replacing SIRS criteria that were criticized for being inaccurate. Eligibility of sepsis-3 criteria for sepsis diagnosis and the applied validation methodology using mortality as endpoint are topic of ongoing debate. We assessed the impact of different criteria on sepsis diagnosis in our ICU and devised a mathematical approach for mortality-based validation of sepsis criteria. As infectious status is often unclear at clinical deterioration, we integrated non-infected patients into analysis. Suspected infection, SOFA and SIRS were captured for an ICU cohort of a university center over one year. For raw scores (SIRS/SOFA) and sepsis criteria (SIRS[greater than or equal to]2/SOFA[greater than or equal to]2/SOFA_change[greater than or equal to]2) frequencies and associations with in-hospital mortality were assessed. Using a mathematical approach, we estimated the correlation between sepsis and in-hospital mortality serving as reference for evaluation of observed mortality correlations of sepsis criteria. Of 791 patients, 369 (47%) were infected and 422 (53%) non-infected, with an in-hospital mortality of 39% and 15%. SIRS[greater than or equal to]2 indicated sepsis in 90% of infected patients, SOFA[greater than or equal to]2 in 99% and SOFA_change[greater than or equal to]2 in 77%. In non-infected patients, SIRS, SOFA and SOFA_change were [greater than or equal to]2 in 78%, 88% and 58%. In AUROC analyses neither SOFA nor SIRS displayed superior mortality discrimination in infected compared to non-infected patients. The mathematically estimated correlation of sepsis and in-hospital mortality was 0.10 in infected and 0 in non-infected patients. Among sepsis criteria, solely SIRS[greater than or equal to]2 agreed with expected correlations in both subgroups (infected: r = 0.19; non-infected: r = 0.02). SOFA[greater than or equal to]2 yielded a more liberal sepsis diagnosis than SIRS[greater than or equal to]2. None of the criteria showed an infection specific occurrence that would be essential for reliable sepsis detection. However, SIRS[greater than or equal to]2 matched the mortality association pattern of a valid sepsis criterion, whereas SOFA-based criteria did not. With this study, we establish a mathematical approach to mortality-based evaluation of sepsis criteria.