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February 7, 2017

Sepsis-3 Criteria for In-Hospital Mortality: What's the Prognostic Accuracy?


The Sepsis-3 consensus provided a new definition for sepsis and new diagnostic criteria. This international task-force of experts defined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1-3]. The Sepsis-3 consensus now recommends that diagnosis of sepsis should be based on the increase of at least 2 points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score in patients with a suspicion of infection. Moreover,  Sepsis-3 introduced the quick SOFA (qSOFA) score, a surrogate for SOFA in settings in which all components of SOFA are not routinely measured. Its main purpose is to allow early diagnosis of sepsis for instance in the emergency department and in the ward. 

Freund et al. [4] conducted a 4-week long international prospective cohort study (in France, Spain, Belgium, and Switzerland) between May and June 2016 at 30 emergency departments (EDs), including consecutive patients who visited the EDs with suspected infection. All variables from previous (SIRS and severe sepsis) and new definitions of sepsis (qSOFA, SOFA) were collected. Primary outcome was mortality at hospital discharge, although patients still hospitalised outside of ICU after 28 days were considered as not meeting the endpoint of in-hospital mortality. The authors also analysed three secondary endpoints: admission to ICU, length of ICU stay >72 hours, and a composite of death or ICU stay >72 hours.

The study included 879 patients and showed an overall in-hospital mortality of 8%. A qSOFA score ≥2 was reported in 218 patients (25%), SOFA ≥2 in 297 patients (34%), SIRS ≥2 in 653 patients (74%) and severe sepsis criteria (≥2 SIRS elements and blood lactate >2 mmol/L) in 176 patients (20%).    

Mortality was 3% for those with a qSOFA <2 vs 24% if qSOFA ≥ 2. This accounted for the highest absolute difference in mortality (21%, as compared with 15% for SOFA, 8% for SIRS and 14% for severe sepsis). SOFA score showed similar prognostic accuracy than qSOFA (AUROC 0.77 and 0.80, respectively). The qSOFA performed better than both SIRS and severe sepsis criteria in predicting in-hospital mortality (AUROC 0.65 for both SIRS and severe sepsis, both p<0.001 for comparison with qSOFA). Interestingly, the authors found no prognostic benefit in adding blood lactate >2 mmol/L to the qSOFA (AUROC remained 0.80). The hazard ratio of qSOFA score for in-hospital mortality was 6.2 as compared with 3.5 for severe sepsis, confirming the greater prognostic accuracy for in-hospital mortality of qSOFA than SIRS or SIRS and severe sepsis criteria. Such greater accuracy was confirmed also for the secondary analyses (ICU admission, ICU stay >72 hours, or composite of death or ICU stay >72 hours). 

It is known that having at least 2 elements of SIRS does not discriminate well for organ dysfunction [5], but one of the concern regarding the qSOFA was the risk of missing critically ill patients with such criteria. In this regard, it is worth noting the very low in-hospital mortality rate (3%) in patients with qSOFA <2, which highlights a very low risk of under-diagnosis using the qSOFA. 

This multicentre study was well conducted and provides prospective data in support of the prognostic accuracy of qSOFA, with similar figures to the one reported by Sepsis-3 in non-ICU encounters.

The importance of early diagnosis of sepsis cannot be overemphasised and the utilisation of a reliable and easy tool for the early diagnosis of sepsis in the ED may contribute to improving patient outcomes. In this context, the results reported very recently by Mayr et al. [6] are very interesting. These authors provided shocking preliminary data showing that sepsis is the leading cause of unplanned 30-day hospital readmissions, length of stay during unplanned readmission and associated costs, with figures higher than other conditions such as acute myocardial infarction, heart failure, COPD and pneumonia (related figures are reported in the review of Raith et al. here).

Article review submitted by EJRC member Filippo Sanfilippo.

1.    Shankar-Hari M, Phillips GS, Levy ML, et al.: Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:775-787, 2016.
2.    Singer M, Deutschman CS, Seymour CW, et al.: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA  315:801-810, 2016.
3.    Seymour CW, Liu VX, Iwashyna TJ, et al.: Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:762-774, 2016.
4.    Freund Y, Lemachatti N, Krastinova E, et al.: Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department. JAMA 317:301-308, 2017.
5.    Kaukonen KM, Bailey M, Pilcher D, et al.: Systemic inflammatory response syndrome criteria in defining severe sepsis. NEJM 372:1629-1638, 2015.
6.    Mayr FB, Talisa VB, Balakumar V, et al.: Proportion and Cost of Unplanned 30-Day Readmissions After Sepsis Compared With Other Medical Conditions. JAMA 2017.

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