Philippe Eggimann1, Bruno François2,3, Jérôme Pugin4, Thomas Daix5, Jean-Luc Pagani6, Davide Morri7, Angelo Giacomucci8, Pierre-François Dequin9, Christophe Guitton10, Yok-Ai Que11, Gianluca Zani12, David Brealey13, Alain Lepape14, Ben Creagh-Brown15, Duncan Wyncoll16, Daniela Silengo17, Irina Irincheeva18, Laurie Girard19, Fabien Rebeaud19, Iwan Maerki19. 1. Department of Locomotor System, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 2. Medical-Surgical Intensive Care Unit, Inserm CIC 1435 and UMR 1092, Dupuytren Teaching Hospital, Limoges, France. bruno.francois@chu-limoges.fr. 3. Réanimation Polyvalente, CHU Dupuytren, 2 avenue Martin Luther King, 87042, Limoges Cedex, France. bruno.francois@chu-limoges.fr. 4. Service des soins intensifs, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 5. Medical-Surgical Intensive Care Unit, Inserm CIC 1435 and UMR 1092, Dupuytren Teaching Hospital, Limoges, France. 6. Service of Intensive Care Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 7. Unità Operativa Anestesia e Rianimazione, Ospedale Infermi Rimini, AUSL della Romagna, Rimini, Italy. 8. Unità di Terapia Intensiva, Azienda Ospedaliera di Perugia, Perugia, Italy. 9. Médecine Intensive, Réanimation, Centre Hospitalier Régional Universitaire de Tours, Tours, France. 10. Service de Réanimation Médico Chirurgicale and USC, Centre hospitalier Le Mans, Le Mans, France. 11. Universitätsklinik für Intensivmedizin, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 12. Terapia Intensiva, Ospedale Santa Maria delle Croci, Ravenna, Italy. 13. Division of Critical Care and National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College Hospital, London, UK. 14. Services de soins Critiques, Hôpital Lyon-Sud, Lyon, France. 15. Intensive Care Medicine, Royal Surrey County Hospital, Guildford, UK. 16. Department of Critical Care, Guy's and St Thomas' Hospital, London, UK. 17. Servizio Anestesia e Rianimazione, Ospedale San Giovanni Bosco, Turin, Italy. 18. Clinical Trial Unit (CTU) Bern, University of Bern, Bern, Switzerland. 19. Abionic SA, Lausanne, Switzerland.
Abstract
BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .
BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically illpatients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .
Entities:
Keywords:
Biomarker; C-reactive protein; Diagnostic; Pancreatic stone protein; Procalcitonin; Sepsis
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