Application of the Third International Consensus Definitions for Sepsis (Sepsis-3) Classification: a retrospective population-based cohort study

Abstract

Background: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) present clinical criteria for the classification of patients with sepsis. We investigated incidence and long-term outcomes of patients diagnosed with these classifications, which are currently unknown.

Methods: We did a retrospective analysis using data from 30 239 participants from the USA who were aged at least 45 years and enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Patients were enrolled between Jan 25, 2003, and Oct 30, 2007, and we identified hospital admissions from Feb 5, 2003, to Dec 31, 2012, and applied three classifications: infection and systemic inflammatory response syndrome (SIRS) criteria, elevated sepsis-related organ failure assessment (SOFA) score from Sepsis-3, and elevated quick SOFA (qSOFA) score from Sepsis-3. We estimated incidence during the study period, in-hospital mortality, and 1-year mortality.

Findings: Of 2593 first infection events, 1526 met SIRS criteria, 1080 met SOFA criteria, and 378 met qSOFA criteria. Incidence was 8·2 events (95% CI 7·8-8·7) per 1000 person-years for SIRS, 5·8 events (5·4-6·1) per 1000 person-years for SOFA, and 2·0 events (1·8-2·2) per 1000 person-years for qSOFA. In-hospital mortality was higher for patients with an elevated qSOFA score (67 [23%] of 295 patients died) than for those with an elevated SOFA score (125 [13%] of 960 patients died) or who met SIRS criteria (128 [9%] of 1392 patients died). Mortality at 1 year after discharge was also highest for patients with an elevated qSOFA score (29·4 deaths [95% CI 22·3-38·7] per 100 person-years) compared with those with an elevated SOFA score (22·6 deaths [19·2-26·6] per 100 person-years) or those who met SIRS criteria (14·7 deaths [12·5-17·2] per 100 person-years).

Interpretation: SIRS, SOFA, and qSOFA classifications identified different incidences and mortality. Our findings support the use of the SOFA and qSOFA classifications to identify patients with infection who are at elevated risk of poor outcomes. These classifications could be used in future epidemiological assessments and studies of patients with infection.

Funding: National Institute for Nursing Research, National Center for Research Resources, and National Institute of Neurological Disorders and Stroke.

Figure 1

Study population flowchart Sepsis classifications not mutually exclusive, events can belong to multiple groups (as indicated by the dotted line). Non-sepsis infections defined as infections not meeting any criteria for sepsis (mutually exclusive from any sepsis events). Sepsis-SIRS defined as infection event meeting ≥ 2 SIRS criteria. Sepsis-SOFA defined as infection event with ≥ 2 SOFA points. Sepsis-qSOFA defined as infection event meeting ≥ 2 qSOFA criteria. “First Events” represent the first event for a given participant (each participant represented once). “Total Events” include recurrent events (each participant can be included multiple times). REGARDS = REasons for Geographic and Racial Differences in Stroke study; SIRS = systemic inflammatory response syndrome; SOFA = sepsis-related organ failure assessment; qSOFA = “quick” sepsis-related organ failure assessment; SBP = systolic blood pressure.

Figure 2

Incidence of events over study period by sepsis classification Panel A) Kaplan-Meier failure curves for time to event after study enrollment; Panel B) Age-standardized event incidence by time period. Includes first events only (Total N = 29,692). “All Infections” includes sepsis events as well as non-sepsis events. Sepsis classifications not mutually exclusive, events can belong to multiple groups. Sepsis-SIRS defined as infection event meeting ≥ 2 SIRS criteria. Sepsis-SOFA defined as infection event with ≥ 2 SOFA points. Sepsis-qSOFA defined as infection event meeting ≥ 2 qSOFA criteria. Incidence rates reported provided per 1,000 person years of follow-up. Error bars (Panel B) represent 95% confidence interval limits) and rates for each time period directly standardized to the overall cohort age distribution. SIRS = systemic inflammatory response syndrome; SOFA = sepsis-related organ failure assessment; qSOFA = “quick” sepsis-related organ failure assessment; IR = incidence rate; SIR = standardized incidence ratio; CI = confidence interval.

Figure 3

Kaplan-Meier failure curves for mortality following event by sepsis classification A) 28-day mortality relative to the date of encounter; B) 1-year mortality relative to discharge date. Includes first infection events only. “All Infections” includes sepsis events and non-sepsis events. Sepsis classifications not mutually exclusive, events can belong to multiple groups. Sepsis-SIRS defined as infection event meeting ≥ 2 SIRS criteria. Sepsis-SOFA defined as infection event with ≥ 2 SOFA points. Sepsis-qSOFA defined as infection event meeting ≥ 2 qSOFA criteria. 28-day mortality (Panel A) includes in-hospital mortality, excludes events with no follow-up after the date of encounter and deaths occurring on the first day of admission (zero follow-up time). One-year mortality (Panel B) excludes in-hospital mortality as well as events with no follow-up after the date of discharge and deaths occurring on the first day of discharge (zero follow-up time). Mortality rates provided per 100 person years. SIRS = systemic inflammatory response syndrome; SOFA = sepsis-related organ failure assessment; qSOFA = “quick” sepsis-related organ failure assessment; MR = mortality rate; CI = confidence interval.

Figure 4

Measures of association for sepsis classification by outcome Includes first infection events only (Total N = 2,593). Sepsis classifications not mutually exclusive, events can belong to multiple groups. Sepsis-SIRS defined as infection event meeting ≥ 2 SIRS criteria. Sepsis-SOFA defined as infection event with ≥ 2 SOFA points. Sepsis-qSOFA defined as infection event meeting ≥ 2 qSOFA criteria. All models include the events not meeting a given sepsis criteria as the reference group and are adjusted for age, gender, race, hypertension, dyslipidemia, chronic kidney disease, history of stroke, history of myocardial infarction, and diabetes. Error bars represent 95% confidence interval limits. Total N = 2,386 for analysis of one-year mortality, excludes events with in-hospital mortality, no follow-up after the date of encounter, and deaths occurring on the first day of discharge (zero follow-up time). SIRS = systemic inflammatory response syndrome; SOFA = sepsis-related organ failure assessment; qSOFA = “quick” sepsis-related organ failure assessment; OR = odds ratio; HR = hazard ratio.