Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study

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 .

Keywords: Biomarker; C-reactive protein; Diagnostic; Pancreatic stone protein; Procalcitonin; Sepsis.

Fig. 1

Flow of patient enrollment. There were 4 (0.14%) missing values for PSP (0; 0.0% after imputation), 8 (0.35%) for CRP (1; 0.04% after imputation) and 8 (0.28%) for PCT (2; 0.07% after imputation). CRP C-reactive protein, EAC endpoint adjudication committee, ICU intensive care unit, PCT procalcitonin, PSP pancreatic stone protein

Fig. 2

Association of pancreatic stone protein, procalcitonin and C-reactive protein increase with sepsis. Daily mean values ± standard errors of the mean for the sepsis group are from the 6 days preceding the endpoint adjudication committee diagnosis of sepsis. For the no-sepsis group, day 0 was set as intensive care unit day 7 or the day of discharge for intensive care unit stays < 7 days. The p values are for the association of clinical sepsis diagnosis with a continuous biomarker increase in the preceding 3 days (pancreatic stone protein, p = 0.003; procalcitonin, p = 0.025; C-reactive protein, p = 0.009). ns are numbers of observations per day and group. PSP pancreatic stone protein, PCT procalcitonin, CRP C-reactive protein, EAC endpoint adjudication committee, ICU intensive care unit