Sepsis 3 Cohort

Sepsis-3 Cohort Identification

The Sepsis-3 definition (Singer et al. 2016) identifies sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. This is a conceptual definition; the operationalization is a proxy:

• Suspected infection (antibiotics + culture within time window) AND
• SOFA score >= 2 (within 48h before to 24h after suspected infection)

Related Sepsis-3 Constructs

• qSOFA (quick SOFA): Bedside screening tool for patients outside the ICU (RR >= 22, altered mentation, SBP <= 100). Not a diagnostic criterion — meant to prompt further assessment. Sensitivity is limited; a negative qSOFA does not rule out sepsis.
• Septic Shock: Sepsis with vasopressor requirement to maintain MAP >= 65 mmHg AND lactate > 2 mmol/L despite adequate fluid resuscitation. Carries substantially higher mortality than sepsis alone.

When to Use This Skill

• Creating sepsis patient cohorts for research
• Sepsis outcome studies
• Quality improvement and benchmarking
• Comparing sepsis populations across studies
• Validating machine learning models on sepsis data

Sepsis-3 Definition Details

Suspected Infection Criteria

A patient has suspected infection when:

1. Antibiotics are administered (systemic, excluding topical) AND
2. Cultures are obtained within a time window:
   • Culture within 72h BEFORE antibiotic, OR
   • Culture within 24h AFTER antibiotic

See suspicion-of-infection for detailed matching logic.

SOFA Criteria

SOFA >= 2 points, where SOFA is calculated using 24-hour worst values:

• Must occur within 48h before to 24h after suspected infection time

See sofa-score for SOFA component details.

Baseline SOFA Assumption

Baseline SOFA is assumed to be 0 for all patients. The true Sepsis-3 definition requires an acute change of >= 2 points from baseline, but pre-hospital baseline organ function is rarely available in retrospective data. This assumption may over-classify patients with chronic organ dysfunction (e.g., chronic kidney disease, cirrhosis) as having sepsis.

Critical Implementation Notes

1. ICU-Only by Design: SOFA requires ICU-level monitoring data (vasopressors, mechanical ventilation status, hourly urine output). This inherently limits Sepsis-3 operationalization to ICU stays. ED sepsis and floor sepsis are not captured.

2. Time of Sepsis Onset: Defined as the earliest suspected_infection_time. This is typically the culture time if culture preceded antibiotics, or the antibiotic time if antibiotics came first.

3. First Event: A patient may have multiple antibiotic-culture pairs. Implementations typically return the first (earliest) suspected infection event per ICU stay.

4. Culture Positivity Not Required: Sepsis-3 does not require positive cultures. Clinical suspicion (antibiotics ordered + cultures sent) is sufficient.

5. SOFA Time Window: The [-48h, +24h] window around suspected infection time is the Seymour et al. operationalization. Some studies use narrower windows.

General Limitations

1. Baseline SOFA Unknown: Assumes baseline SOFA = 0. Patients with pre-existing organ dysfunction (CKD, cirrhosis, chronic respiratory failure) may be over-classified as septic.

2. ICU-Only: Cannot identify ED sepsis, floor sepsis, or sepsis present on ICU admission. This systematically excludes patients who die before ICU transfer or are managed on the floor.

3. Antibiotic-Dependent: Requires antibiotic administration — may miss untreated infections or patients who die before antibiotics are started.

4. Culture-Dependent: Requires cultures obtained — may miss clinically diagnosed infections where cultures were not sent (e.g., empiric treatment of pneumonia without sputum culture).

5. Does Not Capture Septic Shock: The sepsis3 derived table identifies sepsis only. Septic shock identification requires additional vasopressor and lactate criteria.

Dataset Availability

MIMIC-IV

Sepsis-3 is available as a pre-computed derived table. Materialize with:

m4 init-derived mimic-iv          # All derived tables including sepsis3

SELECT
    subject_id,
    stay_id,
    antibiotic_time,
    culture_time,
    suspected_infection_time,
    sofa_time,
    sofa_score,
    respiration, coagulation, liver, cardiovascular, cns, renal,
    sepsis3
FROM mimiciv_derived.sepsis3;

BigQuery users already have this table via physionet-data.mimiciv_derived.sepsis3 without running init-derived.

MIMIC-IV implementation details:

• The derived tables originate from the MIT-LCP mimic-code repository. The full SQL query is in scripts/mimic-iv.sql.
• Joins mimiciv_derived.suspicion_of_infection (infection component) with mimiciv_derived.sofa (organ dysfunction component).
• Returns one row per ICU stay (earliest suspected infection event with SOFA >= 2).
• The sepsis3 boolean flag is TRUE when both criteria are met.
• SOFA uses 24-hour rolling worst values (sofa_24hours from derived SOFA table).

MIMIC-IV limitations:

• Depends on upstream derived tables (sofa, suspicion_of_infection). Any limitations in those tables propagate here.
• SOFA components draw from ICU charting tables — onset timing is relative to ICU admission, not hospital admission.

eICU

Sepsis-3 is not pre-computed in eICU. Building it requires constructing both components from raw tables:

Suspected infection component:

SOFA component sources:

eICU limitations:

• Center variability in missingness: Charting practices, medication naming, and data completeness vary substantially across the 208 hospitals. Missingness is not random — it correlates with hospital size, teaching status, and EHR system. This affects both infection identification and SOFA computation.
• Medication naming: medication.drugname is free-text and varies across sites. The same antibiotic may appear as "Vancomycin", "VANCOMYCIN", "vancomycin 1g IV", etc. Antibiotic identification requires extensive text matching.
• Culture timing: microlab.culturetakenoffset provides timing in minutes from unit admission. The antibiotic-culture pairing logic must be rebuilt for the eICU offset-based time system.
• SOFA computation: Each component comes from a different table with different naming conventions. The eicu-code repository provides pivoted tables (pivoted_lab, pivoted_bg, pivoted_score, pivoted_uo) that can simplify extraction.
• APACHE IV alternative: eICU provides pre-computed APACHE IV scores in apachepatientresult, which includes a severity/mortality prediction. While not the same as Sepsis-3, APACHE IV combined with an infection flag may serve as a pragmatic alternative for eICU sepsis studies.

An eICU script is not yet available.

Example: Identify Sepsis Cohort

SELECT
    s.stay_id,
    ie.subject_id,
    ie.hadm_id,
    s.suspected_infection_time AS sepsis_onset,
    s.sofa_score,
    adm.hospital_expire_flag AS mortality
FROM mimiciv_derived.sepsis3 s
INNER JOIN mimiciv_icu.icustays ie ON s.stay_id = ie.stay_id
INNER JOIN mimiciv_hosp.admissions adm ON ie.hadm_id = adm.hadm_id
WHERE s.sepsis3 = TRUE;

Example: Sepsis Severity Distribution

SELECT
    CASE
        WHEN sofa_score < 5 THEN 'Mild (SOFA 2-4)'
        WHEN sofa_score < 10 THEN 'Moderate (SOFA 5-9)'
        WHEN sofa_score < 15 THEN 'Severe (SOFA 10-14)'
        ELSE 'Very Severe (SOFA 15+)'
    END AS severity,
    COUNT(*) AS n_patients,
    ROUND(AVG(adm.hospital_expire_flag), 3) AS mortality_rate
FROM mimiciv_derived.sepsis3 s
INNER JOIN mimiciv_icu.icustays ie ON s.stay_id = ie.stay_id
INNER JOIN mimiciv_hosp.admissions adm ON ie.hadm_id = adm.hadm_id
WHERE s.sepsis3 = TRUE
GROUP BY 1
ORDER BY 1;

Related Skills

• suspicion-of-infection — Infection component (antibiotic + culture timing)
• sofa-score — Organ dysfunction component
• sirs-criteria — Historical pre-Sepsis-3 inflammatory response criteria

References

• Singer M et al. "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)." JAMA. 2016;315(8):801-810.
• Seymour CW et al. "Assessment of Clinical Criteria for Sepsis." JAMA. 2016;315(8):762-774.
• Shankar-Hari M et al. "Developing a New Definition and Assessing New Clinical Criteria for Septic Shock." JAMA. 2016;315(8):775-787.