BackgroundThe 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).MethodsThis 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 associations 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.ResultsOf the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3–8 days). The association of clinical sepsis diagnosis with an increase in a biomarker value in the 3 days preceding this diagnosis was stronger for PSP (p = 0.003) than for PCT (p = 0.025) and CRP (p = 0.009). 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).ConclusionsWhile the diagnostic accuracy for sepsis of PSP, CRP and PCT were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary for a clinical diagnosis the 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 registrationThe 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