Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis.
In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient\'s condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived.
We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the \"worst\" working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively.
GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

BACKGROUND: Since its introduction in 2016, the Sepsis-3 guidelines, with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score, have generated much debate and controversy. It is recognised that the new definitions require validation in specific clinical settings and have yet to be universally adopted. We aim to validate new Sepsis-3 guidelines in acute hepatobiliary infection.
METHODS: A prospective cohort of patients admitted with acute hepatobiliary infection from the emergency department from July 2016 to June 2017 was studied. The Systemic Inflammatory Response Syndrome (SIRS) criteria, SOFA and qSOFA scores were calculated and predictive performance evaluated with area under the receiver operating characteristic (AUROC) curves for predictive ability of these indices for critical care unit admission and morbidity.
RESULTS: 124 patients with a median age of 64.5 years and majority males (n = 75, 60.5%) were admitted with acute hepatobiliary infection during the study period. Acute cholecystitis was the most common admission diagnosis (n = 83, 66.9%) and most patients were managed in general ward (n = 91, 73.3%) with median length of stay of 6 days (range 1-40). On multivariate analysis, diabetes mellitus (p = 0.003) predicted high dependency unit (HDU) admission, while age (p = 0.001), positive blood culture (p = 0.012), positive fluid culture (p = 0.015) and SOFA score (p = 0.002) predicted length of hospital stay. The sensitivity of SIRS in predicting HDU admission (60% vs. 4%), intensive care unit (ICU) admission (62.5% vs. 0%) and morbidity (66.7% vs. 0%) was higher than qSOFA score. The specificity of qSOFA in predicting HDU admission (100% vs. 49.5%), ICU admission (99.1% vs. 53.3%) and morbidity (99.2% vs. 47.9%) was higher than SIRS criteria.
CONCLUSIONS: The SIRS criteria has high sensitivity and the qSOFA score has high specificity in predicting outcomes of patients with acute hepatobiliary infection.