Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study
Jérôme Pugin,
Thomas Daix,
Jean-Luc Pagani,
Davide Morri,
Angelo Giacomucci,
Pierre-François Dequin,
Christophe Guitton,
Yok-Ai Que,
Gianluca Zani,
David Brealey,
Alain Lepape,
Ben Creagh-Brown,
Duncan Wyncoll,
Daniela Silengo,
Irina Irincheeva,
Laurie Girard,
Fabien Rebeaud,
Iwan Maerki,
Philippe Eggimann,
Bruno François
Affiliations
Jérôme Pugin
Service des soins intensifs, Hôpitaux Universitaires de Genève
Thomas Daix
Medical-Surgical Intensive Care Unit, Inserm CIC 1435 and UMR 1092, Dupuytren Teaching Hospital
Jean-Luc Pagani
Service of Intensive Care Medicine, Lausanne University Hospital and University of Lausanne
Davide Morri
Unità Operativa Anestesia e Rianimazione, Ospedale Infermi Rimini, AUSL della Romagna
Angelo Giacomucci
Unità di Terapia Intensiva, Azienda Ospedaliera di Perugia
Pierre-François Dequin
Médecine Intensive, Réanimation, Centre Hospitalier Régional Universitaire de Tours
Christophe Guitton
Service de Réanimation Médico Chirurgicale and USC, Centre hospitalier Le Mans
Yok-Ai Que
Universitätsklinik für Intensivmedizin, Inselspital, Bern University Hospital, University of Bern
Gianluca Zani
Terapia Intensiva, Ospedale Santa Maria delle Croci
David Brealey
Division of Critical Care and National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College Hospital
Alain Lepape
Services de soins Critiques, Hôpital Lyon-Sud
Ben Creagh-Brown
Intensive Care Medicine, Royal Surrey County Hospital
Duncan Wyncoll
Department of Critical Care, Guy’s and St Thomas’ Hospital
Daniela Silengo
Servizio Anestesia e Rianimazione, Ospedale San Giovanni Bosco
Irina Irincheeva
Clinical Trial Unit (CTU) Bern, University of Bern
Laurie Girard
Abionic SA
Fabien Rebeaud
Abionic SA
Iwan Maerki
Abionic SA
Philippe Eggimann
Department of Locomotor System, Centre Hospitalier Universitaire Vaudois
Bruno François
Medical-Surgical Intensive Care Unit, Inserm CIC 1435 and UMR 1092, Dupuytren Teaching Hospital
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 .
