Usefulness of pancreatic stone protein measurement to screen and diagnose sepsis in the context of the Surviving Sepsis Campaign recommendations.

Abstract

Sepsis occurs yearly in 48.9 million people worldwide of whom 11 million will die. Sepsis is defined as a life-threatening dysregulated reaction of the body in response to a bacterial infection, leading to organ dysfunction. The Surviving Sepsis Campaign (SSC) made numerous recommendations for sepsis diagnosis and treatment using an evidence-based medicine approach. Frequently, levels of evidence of these recommendations are poor and lack clear clinical guidance. Interestingly, the SSC guidelines strongly recommend, with a moderate quality of evidence, screening of nosocomial sepsis in acutely ill hospitalized “high-risk patients”. The definition of acutely ill and high-risk patients is not specified, nor it is indicated which tools should be used. The diagnosis of infection and the subsequent administration of antibiotics relies solely on rapid clinical assessment, as recommended by the Best Practice Statement. Again, the elements used for clinical assessment are poorly defined, encompassing patient history, clinical examination, and tests for both infectious and non-infectious causes of acute illness. In the real world, only 30 to 40% of empiric broad-spectrum antibiotic administrations are appropriate, contributing to the emergence of antimicrobial resistant bacteria, toxicity related to antibiotic administration, and costs. The aim of this review article is to show that the use of biomarkers, such as the Pancreatic Stone Protein (PSP) as an example, helps in guiding the clinician to diagnose and manage sepsis. Over 600 peer-reviewed publications have studied the physiology of PSP and more than 50 evaluated its usefulness to screen for the development of nosocomial sepsis and diagnose sepsis.

Diagnostic and Prognostic Ability of Pancreatic Stone Protein: A Scoping Review

“…We included 24 studies from the PubMed and Embase databases, one study from clinical trials, and one from the Cochrane Library, but some studies were duplicates and so were removed. Afterward, we did a full-text assessment and Ventura et al [ 4 ] because it was a case report, and we excluded the study by Keel 2009 et al [ 3 ] due to its lack of clinical interest. Consecutively, we concluded with 22 studies ( Figure 1 ).…”

“…High-risk patients with acute illness and PSP values < 100 ng/dL are at very low risk of complications with septic episodes, whereas values > 300 ng/dL indicate that sepsis is more that 80% likely to occur. In patients with a clinical suspicion of sepsis at the time of assessment, a PSP value < 50 ng/dL can exclude sepsis with >90% NPV [ 4 ]. Nevertheless, the heterogeneity in methods and populations of studies used to determine the cut-offs weaken this recommendation.…”

“…Nevertheless, the heterogeneity in methods and populations of studies used to determine the cut-offs weaken this recommendation. Conversely, PSP measurement combined with other biomarkers, such as CRP, and prognostic scores, such as the SOFA score and the national early warning score (NEWS), is recommended for screening and rapid diagnosis of infection, organ failure, and sepsis [ 4 ]. Mai et al have recently estimated the pooled sensitivity and specificity of PSP in detecting sepsis (88% and 78%, respectively), but there are some fields of heterogeneity such as population and cut-off values that suggest that further research is needed [ 28 ].…”

“…Meanwhile, a prospective observational multi-center cohort study is counting daily PSP values to monitor ICU patients at risk of developing sepsis, aiming to determine whether the first-day measurement could predict sepsis development (NCT04105699). Additionally, PSP kinetics in specific populations, such as pregnant women, patients in hemodialysis, immunocompromised patients, and patients with chronic inflammation or patients with previous antibiotic or anti-inflammatory therapy exposure have not been studied yet [ 4 ]. In conclusion, there is burgeoning evidence that PSP is a useful point-of-care biomarker for the emergency department due to its ability to recognize bacterial infection and sepsis early, forewarning clinicians about a patient’s clinical course, and for the ICU to recognize the onset of a septic episode early, especially from repeated measurements, which increase diagnostic accuracy.…”