Skip to main content
Top
Published in: Intensive Care Medicine 7/2018

01-07-2018 | Original

Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study

Authors: Marianna Parlato, François Philippart, Alexandra Rouquette, Virginie Moucadel, Virginie Puchois, Sophie Blein, Jean-Pierre Bedos, Jean-Luc Diehl, Olfa Hamzaoui, Djillali Annane, Didier Journois, Myriam Ben Boutieb, Laurent Estève, Catherine Fitting, Jean-Marc Treluyer, Alexandre Pachot, Minou Adib-Conquy, Jean-Marc Cavaillon, Benoît Misset, The Captain Study Group

Published in: Intensive Care Medicine | Issue 7/2018

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
17.
go back to reference von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 147:573–577CrossRef von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 147:573–577CrossRef
19.
go back to reference Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRefPubMed Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRefPubMed
20.
go back to reference Vincent JL, de Mendonça A, Cantraine F et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800CrossRefPubMed Vincent JL, de Mendonça A, Cantraine F et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800CrossRefPubMed
22.
go back to reference Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Methodol 58:267–288 Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Methodol 58:267–288
23.
go back to reference Rubin DB (2004) Multiple imputation for nonresponse in surveys. Wiley, Chichester Rubin DB (2004) Multiple imputation for nonresponse in surveys. Wiley, Chichester
25.
go back to reference Messer J, Eyer D, Donato L et al (1996) Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection. J Pediatr 129:574–580CrossRefPubMed Messer J, Eyer D, Donato L et al (1996) Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection. J Pediatr 129:574–580CrossRefPubMed
26.
go back to reference Kofoed K, Andersen O, Kronborg G et al (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 11:R38. https://doi.org/10.1186/cc5723 CrossRefPubMedPubMedCentral Kofoed K, Andersen O, Kronborg G et al (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 11:R38. https://​doi.​org/​10.​1186/​cc5723 CrossRefPubMedPubMedCentral
29.
go back to reference Ruokonen E, Ilkka L, Niskanen M, Takala J (2002) Procalcitonin and neopterin as indicators of infection in critically ill patients. Acta Anaesthesiol Scand 46:398–404CrossRefPubMed Ruokonen E, Ilkka L, Niskanen M, Takala J (2002) Procalcitonin and neopterin as indicators of infection in critically ill patients. Acta Anaesthesiol Scand 46:398–404CrossRefPubMed
37.
Metadata
Title
Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study
Authors
Marianna Parlato
François Philippart
Alexandra Rouquette
Virginie Moucadel
Virginie Puchois
Sophie Blein
Jean-Pierre Bedos
Jean-Luc Diehl
Olfa Hamzaoui
Djillali Annane
Didier Journois
Myriam Ben Boutieb
Laurent Estève
Catherine Fitting
Jean-Marc Treluyer
Alexandre Pachot
Minou Adib-Conquy
Jean-Marc Cavaillon
Benoît Misset
The Captain Study Group
Publication date
01-07-2018
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 7/2018
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-018-5228-3

Other articles of this Issue 7/2018

Intensive Care Medicine 7/2018 Go to the issue