Value of serum procalcitonin levels and intraabdominal pressure in prognosis of severe acute pancreatitis course

Abstract

Severe acute pancreatitis is associated with significant morbidity and mortality, primarily due to infected pancreatic necrosis, systemic inflammatory response syndrome, and multiple organ dysfunction, which can result in poor clinical outcomes. The identification of early prognostic biomarkers is essential for facilitating prompt and effective multidisciplinary intervention. Serum procalcitonin, which is recognized as a biomarker indicative of bacterial infection and systemic inflammation, and intra-abdominal pressure, a measure reflecting intra-abdominal hypertension and abdominal compartment syndrome, have been studied for their potential utility in predicting disease severity, prognosis, and, ultimately, clinical outcomes.

Key Words: Pancreas diseases; Acute abdomen; Acute necrotizing pancreatitis; Severe sepsis; Septic shock; Procalcitonin; Abdominal compartment syndrome; Intraabdominal hypertension; Prognostic markers

Core Tip: Severe acute pancreatitis is a serious medical condition with a high morbidity and mortality rates, making early prognostic evaluation crucial for guiding treatment decisions. Procalcitonin levels and intra-abdominal pressure measurements serve as highly reliable biomarkers for intensive patient monitoring and the prognostic assessment of clinical outcomes of infected acute necrotizing pancreatitis.

INTRODUCTION

Severe acute pancreatitis (SAP) represents a critical medical condition characterized by a significant mortality risk, wherein early prognostic assessment is essential for guiding therapeutic strategies, including the provision of intensive care and interventions targeting infected necrosis[1-5]. A recent well-constructed retrospective study by Zhao et al[1] provides valuable clinical insights from clinical experience with severe infected necrotizing pancreatitis, with a particular focus on the prognostic relevance of procalcitonin (PCT) levels and intra-abdominal pressure (IAP). These findings highlight the significant value of these parameters. We fully support their findings and aim to further clarify key issues by endorsing them. Conventional scoring systems have limitations in terms of both sensitivity and specificity[1,6-9]. PCT, a biomarker synthesized in response to systemic inflammatory processes and bacterial infections, is a promising early indicator of disease severity and infection necrosis[9-13]. Additionally, the measurement of IAP facilitates the detection of elevated IAP and acute compartment syndrome (ACS), which are correlated with poor clinical outcomes and increased mortality rates[14-18].

PROGNOSTIC INDICATORS

C-reactive protein (CRP) levels exceeding 170 mg/dL upon admission serve as a prognostic indicator of severe acute necrotizing pancreatitis (ANP). PCT concentrations above 0.5 ng/mL within the initial 24 hours are predictive of the onset of ANP. Furthermore, serial measurements of PCT provide valuable insights into disease progression. PCT levels greater than 1.8 ng/mL are indicative of infected ANP. Additionally, lactate concentrations greater than 18 mg/dL are associated with severe sepsis[16,19-22]. Single prognostic factors of severity in acute pancreatitis are sown in Table 1.

Table 1 Single prognostic factors of severity in acute pancreatitis.

n	Factor
1	C-reactive protein (> 170 mg/dL)
2	Procalcitonin (> 1.8 ng/mL)
3	Lactate concentrations (> 18 mg/dL)
4	Intraabdominal hypertension (> 25 mm Hg)
5	Neutrophil-to-lymphocyte ratio (> 3)

Patients hospitalized with SAP exhibit an increased likelihood of mortality and multiple organ dysfunction syndrome, including respiratory, renal, and cardiovascular dysfunction, when intra-abdominal hypertension (IAH) is present. Notably, IAH persists as a significant predictor of both mortality and respiratory dysfunction, even when ACS is absent. Consequently, the onset of IAH serves as a robust prognostic indicator of mortality and adverse clinical outcomes in these patients[23-25].

The neutrophil-to-lymphocyte ratio (NLR), PCT level, and computed tomography (CT) severity score have been utilized as predictive indicators for assessing the severity of acute pancreatitis[11,26-29].

The combined prognostic utility of hematocrit, PCT, albumin, and the Balthazar CT score with the Acute Physiology and Chronic Health Evaluation (APACHE II) score has traditionally been suggested for assessing disease severity[25,30-33]. The conventional prognostic scoring systems and combined factors in acute pancreatitis are shown in Table 2.

Table 2 Conventional prognostic scoring systems and combined factors in acute pancreatitis.

n	Factor
1	Balthazar computed tomography score ≥ 4
2	Pleural infusion
3	Hematocrit (hemoconcentration > 10%)
4	Creatinine > 2 mg/dL
5	Albumin < 2.5 mg/dL
6	Glasgow score ≥ 3
7	APACHE II score ≥ 8
8	BISAP score ≥ 3

APACHE II: Acute Physiology and Chronic Health Evaluation; BISAP: Bedside Index of Severity in Acute Pancreatitis.

PROGNOSTIC SIGNIFICANCE OF PROCALCITONIN

Serum PCT has been extensively investigated as a prognostic biomarker in acute pancreatitis. Elevated PCT levels reflect the host’s immunological response to cytokines and endotoxins[34-37]. Infected pancreatic necrosis is a critical factor that influences adverse outcomes in patients with SAP. Meta-analytical data indicate that PCT exhibits moderate sensitivity and specificity in predicting SAP and infected necrosis, with area under the curve values suggesting a predictive performance that is comparable to or exceeds that of conventional biomarkers such as CRP[19,38-40].

Recent studies have revealed that PCT levels assessed at early time points, such as upon admission or within 24 hours to 72 hours, more effectively identify patients at risk of adverse outcomes than do CRP levels, which typically peak later in the disease trajectory. PCT measured at 72 hours, with a threshold of approximately 1.26 ng/mL, had a sensitivity of 75% and a specificity of 68% for predicting mortality. These findings underscore the utility of PCT as a dynamic biomarker that reflects ongoing systemic inflammation and progression toward organ dysfunction[19,38,41-43]. Conversely, a separate investigation demonstrated that an initial PCT concentration exceeding 1.0 ng/mL is correlated with adverse clinical outcomes. Furthermore, a PCT concentration greater than 2.25 ng/mL, coupled with the inability to reduce PCT levels to less than 60% of the baseline value by day 7 following intervention, serves as a prognostic indicator for patients at elevated risk of mortality[44].

Individual studies have demonstrated variability in reported threshold values and predictive accuracy, with some indicating that slight increases in PCT levels may occur in noninfectious inflammatory conditions. This variability contributes to heterogeneity in diagnostic performance across different patient cohorts and underscores the importance of interpreting PCT results in conjunction with the clinical context and additional diagnostic data. Furthermore, recent extensive retrospective analyses have shown that integrating PCT measurements with other biomarkers, such as the NLR and CT severity score, improves prognostic accuracy beyond that achieved by any single biomarker alone[7,11,19,25,45].

Existing evidence therefore endorses PCT as an important supplementary tool in risk stratification[46]. However, the lack of standardized cutoff thresholds and optimal timing for measurement is a significant limitation that requires further investigation[3,10].

PROGNOSTIC ROLE OF INTRAABDOMINAL PRESSURE

The measurement of IAP has become an important clinical modality for the identification of IAH and ACS in patients with SAP. Elevated IAP results from factors such as visceral edema, aggressive fluid resuscitation, paralytic ileus, and peripancreatic fluid collection, all of which impair organ perfusion and lead to multiple organ dysfunction[47-49] as shown in Figure 1. Empirical evidence has consistently demonstrated a correlation between elevated IAP and adverse clinical outcomes, including increased mortality rates, organ dysfunction, and prolonged intensive care unit stays. Certain patient cohorts with the highest IAP values had significantly reduced survival rates, highlighting the utility of IAP as a physiological indicator of disease severity[50-53]. The clinical manifestations of increased intraabdominal pressure and abdominal compartment syndrome are shown in Figure 2.

Figure 1  Scheme of pathophysiological consequences of increased intraabdominal pressure in acute pancreatitis.

Figure 2  Scheme of clinical manifestations of increased intraabdominal pressure and abdominal compartment syndrome.

In comparison with biochemical markers, IAP measurements offer distinctive insights into the mechanical and perfusion-related complications associated with SAP that are not adequately captured by systemic biomarkers alone. Elevated IAP can exacerbate renal and respiratory dysfunction by decreasing abdominal perfusion pressure and limiting diaphragmatic movement, thereby intensifying the systemic inflammatory response. As IAH and ACS often necessitate different therapeutic approaches, such as decompressive interventions, early identification through IAP monitoring may have a direct effect on clinical management decisions[15,54,55].

IAH may serve as an independent predictor of mortality and adverse outcomes in patients with SAP, prompting some researchers to recommend routine IAP measurement in individuals at high risk. Although IAP monitoring has been less extensively investigated than PCT monitoring, it provides a complementary perspective in severity assessment by reflecting the mechanical burden imposed by severe inflammation[56]. The threshold for performing decompressive laparotomy is 25 mmHg, which corresponds to the initial onset of renal dysfunction[57,58]. Furthermore, anticoagulants play a role in the management of IAH in patients with SAP[59].

COMBINED PROGNOSTIC ASSESSMENT

In the context of SAP, prognostic approaches increasingly emphasize multimodal strategies that integrate biomarkers such as PCT with physiological parameters such as IAP, clinical scoring systems (including the APACHE II and Bedside Index of Severity in Acute Pancreatitis) and imaging-based severity indices[25]. The combined assessment of PCT and IAP improves the predictive accuracy, likely because these indicators capture distinct yet interrelated pathophysiological mechanisms, including systemic inflammatory response and intra-abdominal mechanical stress[1,15]. Elevated PCT levels typically indicate systemic inflammation or infection, whereas increased IAP reflects the potential for organ dysfunction secondary to abdominal hypertension. Together, these markers provide superior identification of patients at increased risk for complicated clinical trajectories compared with the use of either parameter in isolation[50].

LIMITATIONS AND CHALLENGES

Although PCT and IAP have been identified as valuable prognostic indicators, several limitations warrant careful consideration. First, there is considerable variability in the thresholds and timing of measurements across studies, attributable to differences in patient populations, sampling protocols, and analytical techniques. Second, elevations in PCT levels are not entirely specific, as mild to moderate increases may also be observed in severe sterile inflammatory states and other conditions, thereby diminishing its specificity. Third, the assessment of the IAP poses practical challenges due to the requirement of specialized technical expertise and equipment that may not be readily accessible in all clinical environments. Fourth, despite the reinforcement of severity assessment in forthcoming guidelines (such as the 2025 updates), there remains a lack of consensus regarding the formal incorporation of PCT and IAP into standardized prognostic scoring systems[16].

However, several challenges remain. There is no consensus regarding optimal threshold values for PCT and IAP, and both markers are influenced by confounding variables such as noninfectious inflammatory states and variations in fluid management protocols. Additionally, heterogeneity in study designs complicates the comparability of findings across investigations. To address these limitations, large-scale, multicenter prospective studies using standardized methodologies are essential for the validation and refinement of prognostic algorithms in SAP[19,35,44,60,61].

CONCLUSION

The combined assessment of PCT and IAP is highly clinically significant. Future research should focus on establishing standardized threshold values, incorporating PCT and IAP into validated prognostic models, and determining whether clinical interventions guided by these biomarkers lead to improved patient-centered outcomes.