Pancreatic Stone Protein: Earning its Place at the Front Door of the Emergency Department

Pancreatic stone protein (PSP) is a promising early biomarker for identifying infected patients at risk of deterioration, outperforming traditional inflammatory markers in the emergency department. Ongoing research will determine whether PSP-guided early treatment can improve outcomes by enabling earlier intervention.

For decades, the emergency department (ED) has relied on the same handful of inflammatory markers, namely white blood cell count, C-reactive protein (CRP), and procalcitonin (PCT), to sort the patient with infection who will do well from the one who is about to deteriorate. These tools are familiar and accessible, but every clinician at the front door knows their limits. They are non-specific for infection itself, and even once infection is confirmed, they offer little insight into which patient is about to deteriorate, often unconvincing precisely in the patient who looks deceptively stable. The unmet need is not another marker of whether infection is present, but an early, actionable signal of where the patient is heading.

Pancreatic stone protein (PSP) is one of the more compelling biomarkers to fill that gap. PSP is now understood as an acute-phase protein released in response to systemic stress and infection, with a direct role in neutrophil activation and innate immunity.^1,2 Two properties make it especially attractive for acute care. First, kinetics: serial studies have shown PSP rising as early as several days before sepsis-related organ dysfunction becomes clinically apparent.³ Second, its specificity for infection in patients exposed to sterile stress such as trauma, surgery, or burns, PSP does not rise in the absence of infection.⁴ Add to this a point-of-care platform that returns a quantitative whole-blood result in 7 minutes, PSP becomes a decision tool in the ED workflow rather than a result that arrives after the decision has been made.

A recent pilot study from the Attikon University Hospital ED in Athens illustrates the promise in a real-world ED population.⁵ Point-of-care PSP was measured at presentation in 102 consecutive patients with infection of heterogeneous origin and the cohort was followed for ten days, with PSP result not available for the treating teams so the marker could not influence patient management. PSP discriminated outcomes with moderate accuracy, reaching clear significance for the severe composite of death or septic shock. Levels were also higher in patients with documented bacteraemia, consistent with a marker that tracks the biological severity of infection.

The decision that troubles ED triage most concerns the grey zone; the patient with suspected infection whose clinical score looks reassuring, yet who may still be on a trajectory toward sepsis. A post-hoc analysis of a prospective multicentre emergency department study addressed exactly this group, examining patients with no more than one qSOFA point and a PSP at or above 300 ng/mL.^6,7 At that threshold, PSP was highly specific (94%) for subsequent sepsis, identifying a hidden high-risk subgroup among patients whom clinical scoring alone would have waved through. It is precisely this signal, a high PSP in a clinically reassuring patient, that turns PSP into the basis for an interventional question.

That question is now being taken up directly. Building on that signal, an upcoming interventional trial in the ED is designed to move PSP from prognosis to action. Planned across ten Greek EDs, it targets the same grey zone, namely patients presenting with suspected infection at qSOFA 1 or an intermediate NEWS score and uses a PSP at or above 300 ng/mL as the trigger for early antibiotic initiation (trial in preparation, unpublished). This new trial asks whether the same benefit follows when a rapid PSP test is the trigger at ED Triage.

This is the trajectory a strong biomarker should follow from association to prognostic accuracy, to a prospective trial of clinical benefit. With point-of-care measurement already in routine reach and a well-defined grey-zone target, this interventional study is positioned to answer the question that ultimately matters, namely whether acting earlier on a high PSP keeps patients from deteriorating. If it does, PSP will have moved from an interesting signal to a practical instrument at the front door of the ED, and triage of the patient with infection will look meaningfully different.

Key Points

• Traditional biomarkers (white blood cell count, CRP, and procalcitonin) have limited ability to predict clinical deterioration in infected patients.
• Pancreatic stone protein (PSP) rises early in sepsis, is relatively specific for infection, and can be measured at the point of care within 7 minutes.
• Pilot studies show PSP predicts severe outcomes, including septic shock, death, and bacteraemia, with moderate accuracy.
• A high PSP level (≥300 ng/mL) identifies high-risk patients who appear clinically stable despite low clinical severity scores.
• An upcoming multicentre trial will evaluate whether PSP-guided early antibiotic therapy improves outcomes in emergency department patients with suspected infection.

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Point-of-view articles are the sole opinion of the author(s) and are part of the ICU Management & Practice Corporate Engagement or Educational Community Programme.