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

Abstract

Background: 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.

Methods: 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≥2/SOFA≥2/SOFA_change≥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.

Results: Of 791 patients, 369 (47%) were infected and 422 (53%) non-infected, with an in-hospital mortality of 39% and 15%. SIRS≥2 indicated sepsis in 90% of infected patients, SOFA≥2 in 99% and SOFA_change≥2 in 77%. In non-infected patients, SIRS, SOFA and SOFA_change were ≥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≥2 agreed with expected correlations in both subgroups (infected: r = 0.19; non-infected: r = 0.02).

Conclusions: SOFA≥2 yielded a more liberal sepsis diagnosis than SIRS≥2. None of the criteria showed an infection specific occurrence that would be essential for reliable sepsis detection. However, SIRS≥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.

Fig 1. Distribution of maximum Sequential Organ Failure Assessment (SOFA) scores among infected patients (n = 369) at infection onset and non-infected patients (n = 422) at evaluation time points.

All scores on shaded background fulfill the threshold ≥2 proposed by sepsis-3 as clinical sepsis criterion. SOFA was ≥2 in 93% of all patients (infected: 99%; non-infected patients: 88%). The x-axis is the score range, with SOFA truncated at 23 points for illustration.

Fig 2. Receiver Operating Characteristic (ROC) curves for Sequential Organ Failure Assessment (SOFA) score applications and Systemic Inflammatory Response Syndrome (SIRS) criteria discrimination for in-hospital mortality in infected (n = 369) and non-infected (n = 422) patients.

Discrimination capacity of SOFA for in-hospital mortality was significantly stronger in non-infected than in infected patients (p = 0.006). SIRS discriminated for in-hospital mortality in both subgroups with lower AUC compared to SOFA applications. If applied with the proposed threshold, SOFA≥2 was more sensitive and less specific for in-hospital mortality than SIRS≥2. AUC: Area Under the Curve; SIRS: Systemic Inflammatory Response Syndrome; SOFA: Sequential Organ Failure Assessment; sens: sensitivity; spec: specificity.