Septic shock is a life-threatening condition in which timely treatment substantially reduces mortality. Reliable identification of patients with sepsis who are at elevated risk of developing septic shock therefore has the potential to save lives by opening an early window of intervention. We hypothesize the existence of a novel clinical state of sepsis referred to as the “pre-shock” state, and that patients with sepsis who enter this state are highly likely to develop septic shock at some future time. We apply three different machine learning techniques to the electronic health record data of 15,930 patients in the MIMIC-III database to test this hypothesis. This novel paradigm yields improved performance in identifying patients with sepsis who will progress to septic shock, as defined by Sepsis- 3 criteria, with the best method achieving a 0.93 area under the receiver operating curve, 88% sensitivity, 84% specificity, and median early warning time of 7 hours. Additionally, we introduce the notion of patient-specific positive predictive value, assigning confidence to individual predictions, and achieving values as high as 91%. This study demonstrates that early prediction of impending septic shock, and thus early intervention, is possible many hours in advance.
This content will become publicly available on October 9, 2025
- Award ID(s):
- 1954532
- PAR ID:
- 10556776
- Publisher / Repository:
- Elsevier B.V.
- Date Published:
- Journal Name:
- Intelligencebased medicine
- Edition / Version:
- 10
- ISSN:
- 2666-5212
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
BACKGROUND Timely interventions, such as antibiotics and intravenous fluids, have been associated with reduced mortality in patients with sepsis. Artificial intelligence (AI) models that accurately predict risk of sepsis onset could speed the delivery of these interventions. Although sepsis models generally aim to predict its onset, clinicians might recognize and treat sepsis before the sepsis definition is met. Predictions occurring after sepsis is clinically recognized (i.e., after treatment begins) may be of limited utility. Researchers have not previously investigated the accuracy of sepsis risk predictions that are made before treatment begins. Thus, we evaluate the discriminative performance of AI sepsis predictions made throughout a hospitalization relative to the time of treatment. METHODS We used a large retrospective inpatient cohort from the University of Michigan’s academic medical center (2018–2020) to evaluate the Epic sepsis model (ESM). The ability of the model to predict sepsis, both before sepsis criteria are met and before indications of treatment plans for sepsis, was evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Indicators of a treatment plan were identified through electronic data capture and included the receipt of antibiotics, fluids, blood culture, and/or lactate measurement. The definition of sepsis was a composite of the Centers for Disease Control and Prevention’s surveillance criteria and the severe sepsis and septic shock management bundle definition. RESULTS The study included 77,582 hospitalizations. Sepsis occurred in 3766 hospitalizations (4.9%). ESM achieved an AUROC of 0.62 (95% confidence interval [CI], 0.61 to 0.63) when including predictions before sepsis criteria were met and in some cases, after clinical recognition. When excluding predictions after clinical recognition, the AUROC dropped to 0.47 (95% CI, 0.46 to 0.48). CONCLUSIONS We evaluate a sepsis risk prediction model to measure its ability to predict sepsis before clinical recognition. Our work has important implications for future work in model development and evaluation, with the goal of maximizing the clinical utility of these models. (Funded by Cisco Research and others.)more » « less
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This article is categorized under:
Diagnostic Tools > Biosensing
