Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study
Open accessAbstract
Purpose Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. Aim To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. Methods The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. Results During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]). Conclusions The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.
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Most of the investigated biomarkers failed to show discriminative power or clinical relevance.
“Additionally, most of the investigated biomarkers failed to show discriminative power or clinical relevance [42, 43].”
From Machine learning for the prediction of sepsis: a systematic review and meta-analysis of diagnostic test accuracy (2020) · cites this paper as [42]
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- Authors
- The Captain Study Group, Parlato, M., Philippart, F., Rouquette, A., Moucadel, V., Puchois, V., Blein, S., Bedos, J.-P., Diehl, J.-L., Hamzaoui, O., Annane, D., Journois, D., Ben Boutieb, M., Estève, L., Fitting, C., Treluyer, J.-M., Pachot, A., Adib-Conquy, M., Cavaillon, J.-M., & Misset, B.
- Affiliations
- Institut Pasteur (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital André Mignot (FR)
- Inserm (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Hôpital Charles-Nicolle (FR)
- Corresponding author
- Misset, Benoît
- ORCID
- Venue
- Intensive Care Medicine
- Published
- 2018-06-30
- Volume
- 44
- Issue
- 7
- Pages
- 1061-1070
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2809709076
- Cited by
- 85
- References
- 38
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 17 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 9 · 2019: 15
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
- Funders
- Ministère des Affaires Sociales et de la Santé (PHRC 09143)
- Institut Mérieux-Institut Pasteur
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- sepsis, circulating biomarkers, early infection detection, C-reactive protein, leukocyte surface markers, plasma biomarkers, whole blood RNA, LASSO, biomarker discrimination, intensive care unit patients
- MeSH terms
- Aged, Diagnosis, Differential, Female, Humans, Intensive Care Units, Male, Middle Aged, Prospective Studies, Biomarkers, Systemic Inflammatory Response Syndrome, Sepsis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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