Comparison of automated sepsis identification methods and electronic health record-based sepsis phenotyping: improving case identification accuracy by accounting for confounding comorbid conditions.
Open accessAbstract
Objective: To develop and evaluate a novel strategy that automates the retrospective identification of sepsis using electronic health record data. Design: Retrospective cohort study of emergency department and in-hospital patient encounters from 2014 to 2018. Setting: One community and two academic hospitals in Maryland. Patients: All patients 18 years old or older presenting to the emergency department or admitted to any acute inpatient medical or surgical unit including patients discharged from the emergency department. Interventions: None. Measurements and Main Results: From the electronic health record, 233,252 emergency department and inpatient encounters were identified. Patient data were used to develop and validate electronic health record–based sepsis phenotyping, an adaptation of “the Centers for Disease Control Adult Sepsis Event toolkit” that accounts for comorbid conditions when identifying sepsis patients. The performance of this novel system was then compared with 1) physician case review and 2) three other commonly used strategies using metrics of sensitivity and precision relative to sepsis billing codes, termed “billing code sensitivity” and “billing code predictive value.” Physician review of electronic health record–based sepsis phenotyping identified cases confirmed 79% as having sepsis; 88% were confirmed or had a billing code for sepsis; and 99% were confirmed, had a billing code, or received at least 4 days of antibiotics. At comparable billing code sensitivity (0.91; 95% CI, 0.88–0.93), electronic health record–based sepsis phenotyping had a higher billing code predictive value (0.32; 95% CI, 0.30–0.34) than either the Centers for Medicare and Medicaid Services Sepsis Core Measure (SEP-1) definition or the Sepsis-3 consensus definition (0.12; 95% CI, 0.11–0.13; and 0.07; 95% CI, 0.07–0.08, respectively). When compared with electronic health record–based sepsis phenotyping, Adult Sepsis Event had a lower billing code sensitivity (0.75; 95% CI, 0.72–0.78) and similar billing code predictive value (0.29; 95% CI, 0.26–0.31). Electronic health record–based sepsis phenotyping identified patients with higher in-hospital mortality and nearly one-half as many false-positive cases when compared with SEP-1 and Sepsis-3. Conclusions: By accounting for comorbid conditions, electronic health record–based sepsis phenotyping exhibited better performance when compared with other automated definitions of sepsis.
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This study used Sepsis-3 clinical criteria to label sepsis cases, an approach that has imperfect concordance with the criterion standard approach of manual physician review.
“First, this study used Sepsis-3 clinical criteria to label sepsis cases, an approach that has imperfect concordance with the criterion standard approach of manual physician review.25,26,27,28”
From Multicenter Prospective Validation of an Updated Proprietary Sepsis Prediction Model (2026) · cites this paper as [26]
The Discussion reports that automated Sepsis-3 can identify many false-positive cases, supporting imperfect agreement with physician assessment. But it says no gold standard for sepsis exists and physician case review is subjective. The paper also reports a direct physician-review comparison for ESP, not Sepsis-3, so it does not establish the stated criterion-standard comparison for Sepsis-3. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe three-hour window for timely evaluation was chosen to match the treatment window recommended by the Centers for Medicare and Medicaid Services (CMS) sepsis core measure (SEP-1) and the Surviving Sepsis Campaign guidelines.
“The three hour window was chosen to match the treatment window recommended by the Centers for Medicare and Medicaid Services (CMS) sepsis core measure (SEP-1) and the Surviving Sepsis Campaign guidelines 36,62,63 .”
From Factors driving provider adoption of the TREWS machine learning-based early warning system and its effects on sepsis treatment timing (2022) · cites this paper as [36]
The Methods section on Sepsis Definitions identifies SEP-1 as a sepsis core measure, but does not state a three-hour treatment window or a rationale for choosing a three-hour evaluation window. Searches for “three hours” and “Surviving Sepsis Campaign” found no passage in our copy addressing the claimed recommendation. (LLM, conf=0.74)
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Cites
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Cited by
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Adams, R., Henry, K. E., Sridharan, A., Soleimani, H., Zhan, A., Rawat, N., Johnson, L., Hager, D. N., Cosgrove, S. E., Markowski, A., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01894-0 · Cited by 365 · see citing works
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Multicenter Prospective Validation of an Updated Proprietary Sepsis Prediction Model
Wong, A., Currey, D., Schwinne, M., Park-Egan, B., Meyer, S., Gutting, A., Cao, J., Khan, S., Dantes, R., Pan, T., et al. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.0181 · Cited by 21 · see citing works
- Authors
- Henry, K. E., Hager, D. N., Osborn, T. M., Wu, A. W., & Saria, S.
- Affiliations
- Johns Hopkins University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Saria, Suchi
- Venue
- Critical Care Explorations
- Published
- 2019-10
- Volume
- 1
- Issue
- 10
- Pages
- e0053
- ISSN
- 2639-8028 (ISSN-L)
- PMC
- PMC7063888
- OpenAlex
- W2981186100
- Cited by
- 22
- References
- 5
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 3
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Critical Care Explorations (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Gordon and Betty Moore Foundation
- American Heart Association
- Johns Hopkins University
- Marcus Foundation
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Advanced Research Projects Agency
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
- Health Sciences › Health Professions › Health Information Management › Electronic Health Records Systems
- Keywords
- sepsis recognition, comorbidities, billing codes, emergency department, case review, sensitivity and predictive value, sepsis surveillance, sepsis mortality
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