Table of Contents  

Kaiyasah, Al-Suwaidi, Anwar, Al-Ozaibi, and El-Tayeb: Can serum procalcitonin be a reliable single biomarker in predicting the severity of acute pancreatitis?

Introduction

Acute pancreatitis is a common medical problem. It is defined as an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems. The disease can range from mild inflammation to severe extensive pancreatic necrosis and multiorgan failure, with mortality ranging from 20% to 30% or greater.13 The incidence of acute pancreatitis has increased over the past three decades.4

Despite improvements in intensive care treatment over the past few decades, the mortality rate has remained stable since the 1970s.5

The diagnosis of acute pancreatitis is generally made in the presence of two of the following three features:1

  1. characteristic abdominal pain

  2. serum amylase and/or lipase level three times or more the upper limit of normal

  3. characteristic findings of acute pancreatitis on computerized tomography (CT) or ultrasound scan.

A commonly used classification system (the Atlanta classification) divides acute pancreatitis into two broad categories:6

  • mild (oedematous and interstitial) acute pancreatitis

  • severe (usually synonymous with necrotizing) acute pancreatitis.

An early discrimination between mild and severe forms of the disease is of the utmost importance to provide optimal care to the patient.7

Approximately 15–25% of all patients with acute pancreatitis develop severe acute pancreatitis. The ability to predict its severity can help identifying patients at increased risk of morbidity and mortality, thereby assisting in appropriate early triage to intensive care units (ICUs) or selection of patients for specific interventions. Hence, severity stratification is a critical issue in acute pancreatitis that will strongly influence the diagnostic and therapeutic decision-making.8

According to the widely used Atlanta classification, it is important to differentiate between predicted and actual severity of acute pancreatitis. The predicted severity depends on either single biochemical markers, complex scoring systems [such as Glasgow (Imrie) score, Ranson’s criteria and Acute Physiology and Chronic Health Evaluation (APACHE) II] or CT scans, whereas the actual severity is based on admission to ICU, length of ICU or hospital stay, complications requiring medical or operative intervention or mortality.3

The criteria for severe acute pancreatitis include any of the following:3

  • a Ranson’s or Glasgow score of 3 or more;

  • an APACHE II score of 8 or more within the first 48 hours;

  • organ failure (respiratory, circulatory, renal and/or gastrointestinal bleeding);

  • local complications (pancreatic necrosis, abscess or pseudocyst).

Pancreatitis-specific scoring systems have been shown to be of value in predicting the subsequent course of acute pancreatitis, but cannot be applied any earlier than 48 hours after admission to hospital.9

In the last decade, studies have been designed with the aim of finding other prognostic markers to help establish severity stratification early in the course of admission of acute pancreatitis cases.

Several biochemical markers are available to be used as predictors of severity of acute pancreatitis, including C-reactive protein (CRP), serum PCT, urinary trypsinogen activation peptide (TAP) and serum calcium.

C-reactive protein is one of the acute-phase reactants made by the liver in response to interleukin-1 and interleukin-6. Its utility for predicting the severity of pancreatitis is best achieved when peaking at 48 hours. A cut-off point of > 150 mg/dl has been considered.10

The biochemical marker serum PCT is a relatively accurate and convenient method for predicting the severity in acute pancreatitis and is easily measured.11,12 Some studies revealed a strong relationship between an increased serum PCT and the severity of acute pancreatitis.11,13,14

Thus, we designed our retrospective study with two main objectives. First, to assess the clinical usefulness of serum PCT as a predictive marker for severity early in the course of acute pancreatitis, in comparison with Glasgow score and other routinely measured biochemical parameters, such as haematocrit and white blood cell count. Second, to evaluate the correlation of serum PCT with length of hospital stay.

Materials and methods

Study population

This retrospective study enrolled 200 patients, of both genders, with acute pancreatitis admitted to Rashid Hospital, Dubai, over a 3-year period (2011–2013). The diagnosis of acute pancreatitis was based on Atlanta classification of acute upper abdominal pain associated with a serum amylase and or a lipase level greater than three times the normal value, and radiological evidence of acute pancreatitis. All cases of acute pancreatitis were included irrespective of aetiology. Patients with double intra-abdominal pathology (e.g. acute cholecystitis or cholangitis) were excluded from the study as shown in Figure 1. Upon admission, the patients were treated using the accepted standard management of acute pancreatitis.15 All patients were fasted soon after admission and given fluids, electrolytes and analgesics parenterally. If necessary, systemic antibiotics were administered.

FIGURE 1

Flow chart of the methodology.

8-3-5-fig1.jpg

Serum procalcitonin and biochemical testing

Blood samples for PCT were collected on admission and biochemical tests for the Glasgow scoring system were performed on admission (Day 0) and within 48 hours (Day 2).

For serum PCT, blood samples were centrifuged for 10 minutes at 3000 rotations per minute at –4°C. The serum was removed and stored at –80°C until biochemical analysis. The serum PCT concentration was measured using a chemiluminescent immunoassay (LUMItest PCT, Brahms Diagnostica, Berlin, Germany). The reference value cut-off point established for this method was < 0.05 ng/ml. All patients were classified as having mild or severe acute pancreatitis according to the modified Glasgow score16 (Table 1). The cut-off point for PCT was 0.5 ng/ml. Ethical approval was obtained from the Institutional Review Board of Dubai Health Authority, Dubai, UAE.

Data collection was through a computerized data system in our institution (SAM system), as well as from patients’ records.

TABLE 1

Modified Glasgow severity scoring system for acute pancreatitis

Age > 55 years
White cell count > 15 000/mm3
PaO2 < 60 mmHg
Serum lactate dehydrogenase > 600 U/l
Serum aspartate aminotransferase > 200 U/l
Serum albumin < 3.2 g/dl
Serum calcium < 8 mg/dl
Serum glucose > 180 mg/dl
Serum urea > 45 mg/dl

Results

A total of 166 patients were enrolled in the study: 120 men and 46 women. The median patient age was 40.8 years. According to the Glasgow criteria, 136 patients were classified as mild acute pancreatitis and 30 as severe acute pancreatitis. The causes of acute pancreatitis were alcoholism, biliary, hyperlipidaemia and idiopathic or miscellaneous; differences were not significant (P = 0.465). Six patients died: four of multiple organ failure and two of severe necrotizing pancreatitis; all six had severe acute pancreatitis.

The duration of admission was longer in the severe acute pancreatitis group, with a median hospital stay of 24.8 days compared with 8.5 days in the group with mild acute pancreatitis. Of the 30 cases with severe acute pancreatitis, 10 were admitted to ICU.

The median value for serum PCT at the time of admission was 0.72 ng/ml in those with acute pancreatitis and 3.1 ng/ml in those with severe acute pancreatitis. The median haematocrit value was 43% in the mild acute pancreatitis group and 41% in the severe acute pancreatitis group. White blood cell median value was 13.54 × 103/µl and 17.39 × 103/µl in the mild and severe groups, respectively (Table 2).

TABLE 2

Characteristics of the patients with acute pancreatitis

Mild Severe Total
Glasgow criteria 136 30 166
Men/women 100/36 20/10 166
Duration of admission (days) 8.5 24.8
ICU admission 3 10 13
Aetiology
Alcoholism 41 10 51
Biliary 44 9 53
Hyperlipidaemia 9 1 10
Idiopathic 37 8 45
Miscellaneous 5 2 7
Biochemical markers
PCT (ng/dl) 0.72 (0.02–10.6) 3.1 (0.06–22.09)
Haematocrit (%) 42.7 (27.1–58) 40.8 (25.7–51.8)
White blood cell count (× 103/µl) 13.54 17.39

In predicting the severity of acute pancreatitis at the time of admission, sensitivity and specificity of serum PCT were 60% and 82%, respectively. The 95% confidence interval for sensitivity was 41% to 77% and for specificity 74% to 88%.

Out of the 30 cases with severe acute pancreatitis, 19 had undergone a CT scan. Only 7 of the 19 patients with severe acute pancreatitis, based on the Glasgow score, had pancreatic necrosis. Among these 30 cases who had severe acute pancreatitis, a CT scan was carried out for only those who did not improve within 48–72 hours, in terms of haemodynamic instability and persistence of clinical symptoms.

The CT scan findings of severe acute pancreatitis (acute necrotizing collection, acute necrotizing pancreatitis) were correlated with serum PCT levels (62% sensitivity and 71% specificity), and it was comparable with the Glasgow score (54% sensitivity and 83% specificity).

Procalcitonin levels, which were high at the beginning, gradually decreased and were within normal limits at discharge.

The correlation between PCT and length of hospital stay was 0.3505, indicating a moderate degree of positive correlation, shown clearly in the linear regression curve (Figure 2).

FIGURE 2

The association between length of hospital stay and PCT level.

8-3-5-fig2.jpg

The association between PCT and ICU admissions is considered extremely statistically significant (P < 0.0001).

Discussion

Acute pancreatitis continues to be a clinical challenge that places a considerable burden on the health care system.17 In the majority of cases, the clinical course of acute pancreatitis is usually mild and it often resolves without complications. However, 10–20% of patients experience a severe acute pancreatitis attack, resulting in an intense inflammatory response, a variety of local and systemic complications, a prolonged hospital course and significant morbidity and mortality.18 Predicting the severity of acute pancreatitis is of great importance. First, in order to tailor management for each patient and, second, for the early identification of those patients who will need to be admitted to the ICU. This course of action might ultimately avoid possible deleterious local and systemic complications. Over the past few decades, several scoring systems have been established to achieve this goal, each of which is formed of multiple biochemical variables. Among these are the Glasgow, Ranson’s, APACHE II and the bedside index of severity in acute pancreatitis (BISAP) scoring systems. On the other hand, many single biochemical markers have been tested to predict the severity of acute pancreatitis.19

One such marker is serum PCT. It was introduced as a prognostic marker of acute pancreatitis, focusing on systemic inflammation and organ failure in the early stages of acute pancreatitis. PCT is a 116-amino-acid peptide with a sequence identical to that of the prohormone of calcitonin.11

Multiple recent studies have been conducted to assess the effectiveness of serum PCT measurement as a predictor of severity of acute pancreatitis. Most of the results were promising.12 It has gained the best prognostic value with a cut-off level at 0.5 ng/ml for determination of severe acute pancreatitis; in addition, PCT > 1.8 ng/ml can indicate infected pancreatic necrosis.13 Even the monitoring of changes in PCT levels reflects the course of the disease.14,20 In 2008, Gurda Duda et al.14 stated that the early prediction of severe acute pancreatitis was achievable by measuring PCT, and many subsequent studies reported the efficacy of PCT as a predictor of acute pancreatitis.

In a paper by Purkayastha et al.,21 entitled ‘Does serum procalcitonin have a role in evaluating the severity of acute pancreatitis? A question revisited’, the meta-analysis revealed an overall sensitivity and specificity of 74% (ranging from 66% to 81%) and 83% (ranging from 79% to 87%), respectively.

Our study revealed that serum PCT might have a prognostic value in predicting the severity of acute pancreatitis with a sensitivity of 60% and a specificity of 82% at the time of admission.

Other studies revealed that the prognostic value of serum PCT is higher in detecting infected cases of severe necrotizing pancreatitis with sensitivity and specificity of 80% and 91%, respectively.15

Some authors have recommended haematocrit upon admission, daily sequential organ failure assessment score, PCT, CRP on Day 3 and CT severity index beyond the first week. These scoring tools, together with close clinical follow-up of the patient, ultimately lead to an optimized treatment for this challenging disease.16

In the presence of confirmed pancreatic necrosis, serum PCT can be used to predict infected pancreatic necrosis.22 Although higher PCT concentrations suggest a systemic bacterial infection, serum PCT concentrations do not correlate with the severity of sepsis or with mortality.23

In recent studies, intra-abdominal pressure (IAP) was used along with serum PCT levels to predict pancreatitis severity. Increased IAP was shown to be accompanied by increased PCT serum concentration in patients with acute pancreatitis. Therefore, both can be used as early markers of acute pancreatitis severity.24

Conclusion

Serum measurements of PCT may be valuable in predicting the severity of acute pancreatitis early in the disease process.

Acknowledgements

Special acknowledgement to Professor Abdul Jabbar Saleh and Dr Mahera Abdulrahman for their great support and guidance.

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