Abstract
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 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.ResultsOf 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).ConclusionsWhile 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.
Highlights
The early recognition and management of sepsis improves outcomes
Biomarkers dynamics and progression toward sepsis To explore the dynamics of serial biomarker measurement throughout the study period, we modeled biomarker courses in the 3 days prior to endpoint adjudication committee (EAC) sepsis diagnoses by fitting a linear mixed-effect model with pancreatic stone protein (PSP), C-reactive protein (CRP), and PCT as response and the following explanatory variables: patient-specific random effect, group, day-to-event and group by day-to-event interaction as fixed-effects
Accuracy of individual biomarkers and their combination in sepsis diagnosis Areas under receiver operating characteristic curves (AUROCCs) on the day of sepsis diagnosis according to the blinded EAC were similar for all three biomarkers {PSP, 0.75 [95% confidence interval (CI) 0.67–0.82]; CRP, 0.77 [95% CI 0.69–0.84] PCT, 0.75 [95% CI 0.68–0.83]} (Table 3 and Additional file 3: Figure 2)
Summary
The early recognition and management of sepsis improves outcomes. Biomarkers may help in identify‐ ing 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). If not recognized and managed early, may evolve rapidly into life-threatening septic shock and multiple organ failure [1,2,3]. Guidelines systematically emphasize the early recognition and aggressive management of sepsis, with combined early antibiotic treatment and support to prevent organ dysfunction [1, 5, 6]. Even if CRP and PCT are commonly used in the context of the diagnosis of sepsis, both have shown suboptimal performance [8]
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