Ground truth labels challenge the validity of sepsis consensus definitions in critical illness

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator

“…This facilitated our trend analysis. Although we cannot extrapolate from our results to events beyond the follow-up period, we had previously shown that half of the overall sepsis cases in our ICU occur by day six (8) and in our polytrauma patients in particular by day seven (67). We also consider our conservative assessment of statistical significance by applying the correction for multiple testing and the absolute rather than relative quantitation of blood plasma concentrations as strengths.…”

“…The emulation of this clinical challenge, i.e., the early differential diagnosis of sepsis in this setting, with high fidelity in an observational study is complicated by the strong heterogeneity of the patient population and the presentation of the syndrome. Moreover, we previously determined that 93% of the patient days in our ICU were associated with a SOFA > 2 compared to 68% with SIRS, regardless of infection (8).…”

“…Both SIRS and organ dysfunction are highly prevalent in the intensive care unit (ICU) (8), where sepsis is the leading cause of death regardless, which of the above definitions is applied, and with the lung as the primary site of infection (9,10). SIRS and sepsis can be considered clinical phenotypes of the host response's failure to contain local tissue inflammation after sterile and infectious tissue injury, respectively.…”

Comparative Analyses of the Impact of Different Criteria for Sepsis Diagnosis on Outcome in Patients with Spontaneous Subarachnoid Hemorrhage

“…Furthermore, we presented a modified scoring method of the SOFA score for sepsis diagnosis by Sepsis-3 criteria, accounting for SAH-specific induced hypertension. Finally, we proposed alternative criteria to detect a sepsis-associated organ dysfunction as a need for enhancements of the Sepsis-3 criteria has been identified in general [17][18][19]26,44,45] and, specifically, in the context of SAHs [1].…”

S-Adenosylhomocysteine Is a Useful Metabolic Factor in the Early Prediction of Septic Disease Progression and Death in Critically Ill Patients: A Prospective Cohort Study

“…Before study initiation, a pre-analysis was performed to increase the probability of observing a shift from SIRS/sepsis into severe sepsis/septic shock within the foreseen prospective study period of five consecutive days following patient inclusion [ 34 ]. This retrospective pre-analysis included all patients who had been treated in the ICU between May 2016 and December 2016, using the Ground Truth for Sepsis Questionnaire (GTSQ) [ 37 ]. Accordingly, the treating senior intensivists rated every patient admitted to the ICU daily at 2–3 pm by five working diagnoses in accordance with the concept of the sepsis-1/2 consensus definition.…”