Advances in prognostic factors in acute pancreatitis: a mini-review

Theodoros E Pavlidis, Efstathios T Pavlidis and Athanasios K Sakantamis

Thessaloniki, Greece

Advances in prognostic factors in acute pancreatitis: a mini-review

Theodoros E Pavlidis, Efstathios T Pavlidis and Athanasios K Sakantamis

Thessaloniki, Greece

BACKGROUND:Early assessment of the severity of acute pancreatitis is essential to the proper management of the disease. It is dependent on the criteria of the Atlanta classification system.

DATA SOURCES:PubMed search of recent relevant articles was performed to identify information about the severity and prognosis of acute pancreatitis.

RESULTS:The scoring systems included the Ranson's or Glasgow's criteria≥3, the APACHE II classification system≥8, and the Balthazar's criteria≥4 according to the computed tomography enhanced scanning findings. The single factors on admission included age >65 years, obesity, hemoconcentration (>44%), abnormal chest X-ray, creatinine >2 mg/dl, C-reactive protein>150 mg/dl, procalcitonin >1.8 ng/ml, albumin <2.5 mg/dl, calcium <8.5 mg/dl, early hyperglycemia, increased intra-abdominal pressure, macrophage migration inhibitory factor, or a combination of IL-10 >50 pg/ml with calcium <6.6 mg/dl.

CONCLUSION:The prediction of the severity of acute pancreatitis is largely based on well defined multiple factor scoring systems as well as several single risk factors.

(Hepatobiliary Pancreat Dis Int 2010; 9: 482-486)

acute pancreatitis; severity prediction; risk factor; prognostic sign; scoring system; infected necrosis

Introduction

A variety of prognostic factors and scoring systems have been proposed for accurate assessment of the severity of acute pancreatitis and reliable prediction of high risk and potentially fatal cases. However, most of them are based on small populations, usually from single specialist centres. So far, acute physiology and chronic health evaluation (APACHE) II, although complicated, ensures the highest positive predictive value up to 69%. This is quite important since the most prognostic variables are related to high but low negative predictive values. Except for the APACHE II, the other prognostic scoring systems are not adequately sensitive, specific in prediction.[1]

The severity of acute pancreatitis is determined to predict the prognosis of the disease and differentiate the less severe from severe patients who need monitoring in ICU. The currently used the classification system of Atlanta is based on the consensus of an international symposium held in 1992 in which severe acute pancreatitis is defined to be associated with specific clinical manifestations, Ranson's prognostic criteria ≥3 points or APACHE II ≥8, multiple organ dysfunction (MOD) in the course of systemic inflammatory response syndrome (SIRS), and pancreatic necrosis.[2-5]

The pancreatic necrosis is characterized by either pathologically confirmed necrosis of the parenchyma or fat in the interstitial space. There was no up-taking shown by the parenchyma contrast medium sized >3 cm or more than 30% of the gland on dynamic CT (Balthazar's criteria).

The clinical manifestations of acute pancreatitis included abdominal tenderness, guarding, flatulence, hypotension, respiratory distress, palpable mass, or bruising (Grey-Turner's sign periumbilically or Cullen's sign in the loin region, observed in only 1%-3% of cases after 48 hours).

Prognostic scoring systems

The Ranson's prognostic criteria (1974) include 11factors (age, white cell count, LDH, SGPT, glucose, fall in hematocrit, urea, calcium, PO2, base deficit, fluid replacement) (Table 1).[6]The Glasgow's prognostic criteria modified by Imrie (1978) includes 8 factors (white cell count, glucose, urea, PO2, calcium, LDH, transaminases, albumin) (Table 2).[7]

Formerly the criteria of APACHE system acute physiology and chronic health evaluation included 34 factors (1981), which are difficult to use. This promptedus to modify APACHE II (1985), which includes 12 factors widely used today (Table 3). These factors include age and other coexisting diseases. APACHE III (1991) includes 18 factors whereas APACHE-O (obesity-1996) includes the added one, obesity.[8-11]

Table 1. Prognostic criteria of Ranson

Table 2. Prognostic criteria of Glasgow

The prognostic criteria of Balthazar (1985) are based on the findings of CT and classified into 5 grades (A: normal findings, B: focal or diffuse swelling of the pancreas, C: inflammation of the pancreas and peripancreatic fat, D: one peripancreatic fluid collection, and E: two or more collections or endo/peri-pancreatic air presence). They are scored from 0-4 points, respectively.[12]The same author later in 1990, based on the findings of dynamic CT with intravenous contrast medium, added one more criterion (F: degree of necrosis 30%, 50% or more), giving 2, 4 or 6 extra points, respectively.[13]

Also, dynamic CT is useful in predicting local complications in patients with pancreatic necrosis by assessing some well-defined factors for infected pancreatic necrosis development, i.e. the extent of pancreatic necrosis and the presence of peripancreatic necrosis. The finding of transparenchymal necrosis with up-stream viable (enhancing), pancreatic and no peripancreatic necrosis, is yet another factor for pseudocyst formation.[14]

Single prognostic factors

As individual predictors of severe acute pancreatitis are now considered, obesity with body mass index (BMI): 25-30 kg/m2(+), >30 kg/m2(++), pleural effusion or pulmonary infiltration within the first 24 hours is associated withincreased mortality, increased serum creatinine level (>2 mg/dl).[15-17]Also, the composition of peritoneal fluid (amount, color) after 8 hours is considered as a prognostic criterion in equal value with the Ranson's and Glasgow's criteria.[2]The hemoconcentration, reflected by an increase in hematocrit on admission, is associated with the development of severe necrotizing pancreatitis. Thus it is considered as a simple, useful and early prognostic marker. The patients with no hemoconcentration have minimal risk to develop organ failure or death.[18-21]

Table 3. APACHE II scoring system

Much effort, nowadays, has been concentrated on simple prognostic scoring systems. In a recent study[22]independent prognostic factors associated with poor prognosis have been determined, i.e. age above 65 years, leukocyte count above 13 000/mm3, serum albumin level below 2.5 mg/dl, serum calcium below 8.5 mg/dl and C-reactive protein (CRD) above 150 mg/dl.

Apart from these some prognostic factors in serum are used separately to determine the severity of acute pancreatitis. The main factors include those that determine the inflammatory response and consist of acute phase proteins CRP (150 mg/dl is currently the limit of discrimination of the severe from mild one) and amyloid A, polymorphonuclear elastase, cytokines (IL-6, IL-8, IL-10), phospholipase A2, thrypsin, antithrypsin, thrypsinogen activation peptide, carboxypeptidase activation peptide, beta2 macroglobulin and procalcitonin (1.8 ng/ml is the threshold to distinguish between infected and non-infected pancreatic necrosis).[2]Between acutephase proteins (such as serum amyloid A, CRP) and procalcitonin as prognostic factors in acute pancreatitis, the latter gained the best prognostic value with a cutoff level at 0.5 ng/ml; also, some single parameters such as total calcium concentration, lactic acid activity and glucose concentration share equal prognostic value.[23]

However, the CRP has the best practical value and is widely used as a predictor of severe acute pancreatitis; but it should be increased at least 48 hours after elapse from the onset of the episode. Its value is comparable to that of system APACHE II.[15,16]Instead of this, the procalcitonin could be used as a predictor of severe acute pancreatitis in the first 24 hours; even the monitoring of changes reflects the course of the disease.[24,25]

The markers that determine the extent of pancreatic lesion via the activation of pancreatic enzymes are mainly used in research and have not yielded yet relevant clinical application.

The anti-inflammatory cytokines (IL-10, receptor antagonist of IL-1 and soluble receptors of TNF), which reflect the degree of immune response, are increased early and now gain an intense research interest. The combination of anti-inflammatory cytokine interleukin 10 (IL-10 >50 pg/ml) and serum calcium (Ca <6.6 mg/dl) within 12 hours after the onset is considered currently as the best predictor of impending multiple organ failure with high diagnostic accuracy.[26]

Recent interesting aspects

It has been postulated that the degree of inflammation and pancreatic necrosis in severe acute pancreatitis may be associated with the risk of disease recurrence.[27]Also, in patients with severe acute pancreatitis, as independent prognostic factors for arterial injury (pseudo-aneurysm) and gastrointestinal complications (duodenal perforations) the persistent elevation of CRP and the high Balthazar's CT severity score are determined.[28]

The above mentioned parameters including hematocrit, urea, creatinine, matrix metalloproteinase-9 (MMP-9) and amyloid A have been used nowadays, as early predictors of severity of acute pancreatitis within the first 24 hours.[29]Early hyperglycemia in acute pancreatitis is a prognostic indicator of severe episode. Although, obesity is not an independent risk factor for organ failure, it correlates with early hyperglycemia, which may predispose to organ failure development increasing the mortality.[30,31]

Infected pancreatic necrosis is associated with high mortality and surgery is the cornerstone in its management. Some independent predictors of survival have been defined in such surgery. Thus, pancreatic necrosectomy has been found to be related to higher mortality in patients with increased APACHE II score (mean score 14) on admission, presence of early persistent SIRS (within the first 48 hours) and MOD within two weeks after admission.[32]

APACHE II score >8, LDH >667 U/L, base excess>5, CT severity index >3, and CRP>142 mg/L reported to be of prognostic value.[33]Six factors have been used recently to develop another prognostic scoring system, i.e. arterial pH, age, serum urea, mean arterial pressure, PaO2/FiO2 ratio, AND total serum calcium.[34]

As acute pancreatitis is one of the main causes of increased intra-abdominal pressure and compartment syndrome, this pressure has been used as a reliable marker of disease severity.[35]

Another simple scoring system has been proposed according to the three prognostic factors i.e. serum urea nitrogen (≥25 mg/dl), serum LDH (≥900 IU/l), and pancreatic necrosis in contrast-enhanced CT.[36]

Recently, serum macrophage migration inhibitory factor as a potentiator of cytokine response has been proposed as an early (within 24 hours) marker ofpancreatic necrosis; but most importantly, it promises the development of novel therapeutic agents to ameliorate SIRS in acute pancreatitis.[37]

Conclusions

The risk of severe acute pancreatitis is increased at Glasgow's or Ranson's score ≥3 in 48 hours, APACHE II on admission ≥8, BMI ≥30, abdominal wall bruising, abnormal chest radiograph and serum creatinine >2 mg/dl on admission, Balthazar's score ≥4, CRP >150 mg/dl at 48 hours, and hematocrit >44%. Likewise, the risk of dying is increased at Glasgow's or Ranson's score ≥3 in 48 hours, APACHE II ≥15, abnormal chest radiograph and serum creatinine >2 mg/dl on admission, and Balthazar's score ≥7. In our opinion, the better single factor useful in daily practice is CRP >150 mg/dl or procalcitonin >0.5 ng/ml for determination of severe acute pancreatitis; also, procalcitonin >1.8 ng/ml can indicate infected pancreatic necrosis.

Funding:None.

Ethical approval:Not needed.

Contributors:PTE wrote the main body of the article with the help of PET under the supervision of SAK. PET provided advice on literature data and their interpretation, while SAK provided advice on medical aspects. PTE is the guarantor.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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June 28, 2010

Accepted after revision September 2, 2010

Author Affiliations: Surgical Propedeutical Department, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Konstantinoupoleos 49, 54642 Thessaloniki, Greece (Pavlidis TE, Pavlidis ET and Sakantamis AK)

Theodoros E Pavlidis, MD, PhD, Associate Professor of Surgery, A Samothraki 23, 54248 Thessaloniki, Greece (Tel: +302310-992861; Fax: +302310-992932; Email: pavlidth@otenet.gr; pavlidth@med.auth.gr; pavlidth@auth.gr)

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