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Acute necrotizing pancreatitis

Created: 26/10/2006
Updated: 17/3/2007

Acute necrotizing pancreatitis

Dr John Griffiths DICM MRCP FRCA MA
CriticalCareUK Editor

Focus on pancreatic necrosis and its diagnosis

Prognostication of acute pancreatitis is provided by the Ranson score (Tables 1 and 2). Necrosis of pancreatic tissue occurs in 20-30% of cases of acute pancreatitis. Mortality is unusual in patients without necrosis whereas those with necrosis have a mortality of approximately 10%, rising to 30% should the necrotic tissue become infected. If sterile necrosis is accompanied by a marked systemic inflammatory response and multi organ failure then the mortality rate rises to over 50%.

Contrast enhanced abdominal CT scanning is the gold standard non-invasive method of diagnosing pancreatic necrosis. Non-viable tissue fails to enhance due to the abnormal microvasculature in this tissue. This technique is more than 90% accurate if there is more than 30% gland necrosis. This test is best performed several days after pancreatitis has been diagnosed as necrosis develops early in the course of the disease and is usually established 96 hours after the onset of symptoms. Although the identification of necrosis has prognostic implications, there are no randomised trials documenting improved outcome if CT scanning is performed early in the course of the disease. The routine use of CT in early pancreatitis has been questioned, and guidelines have recently been proposed (Table 3). However, an excellent correlation exists between the CT depiction of necrosis and the development of complications and death (Table 4).

Table 1: Ranson’s adverse factors for prognostication

On admission

Within 48 hrs of hospitalisation

Age >55 yrs

Decrease in HCT > 10%

WCC > 16 000/mm3

Increase in blood urea > 1.8 mmol/l

Glucose >11 mmol/l

Calcium < 2 mmol/l

LDH > 400 IU/l

PaO2 < 8 kPa

AST > 250 IU/l

Base deficit > 4 mmol/l

Fluid deficit > 6 l

Table 2: Relationship of Ranson’s score to mortality

Risk factor

Mortality rate


< 1%







Focus on surgical intervention versus a conservative approach

There are at present no reliable investigations or scoring systems to prognosticate which patients will benefit from early or late surgical intervention. The current recommendation is that, in patients with signs of sepsis, CT or ultrasonographically guided aspiration of fluid should be performed for examination and culture to confirm infected necrosis. CT guided fine needle aspiration is safe, sensitive (96%) and specific (99%) and can be repeated at regular intervals. If infected necrosis is confirmed, surgical necrosectomy is recommended. Figure 1 shows the surgical decision making tree that is currently recommended.

Conservative therapy usually involves aggressive organ support, prophylactic antibiotics, early jejunal feeding, and repeated surveillance of the pancreatic necrosis. Selective gut decontamination, ERPC and novel therapies may have a role.

Focus on prophylactic antibiotics

Early studies investigating the role of systemic antibiotics in the prevention of infection in pancreatitis showed no benefit, but most included patients with a low level of disease severity and employed agents (e.g. ampicillin) with inefficient penetration into pancreatic tissue. A more recent open, randomised, multicentre, clinical trial of imipenem in 74 patients with necrotising pancreatitis on CT scanning found that patients assigned to receive prophylactic imipenem (500 mg i.v. 8 hourly for 14 days) had a 2.5-fold decrease in the incidence in pancreatic infectious complications and a trend toward a decreased mortality (7 versus 12%).

A Cochrane review of all relevant trials concluded that despite variations in drug agent, case mix, duration of treatment and methodological quality (especially the lack of double blinded studies), there was strong evidence that intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk of superinfection of necrotic tissue and mortality in patients with severe acute pancreatitis with proven pancreatic necrosis at CT. Further studies are required provide more information on adverse effects, to address the choice of antibacterial agents and effects of varying duration of therapy, and whether outcome is related to aetiology.

Focus on Nutrition

Traditionally, patients with severe acute pancreatitis have been treated with parenteral nutrition (TPN), because enteral feeding was thought to stimulate pancreatic secretion and worsen pancreatic injury. However, a number of recent prospective randomised studies have examined the role of enteral feeding, initiated within 48 hours of onset of severe acute pancreatitis, administered via a jejunal tube. These studies which total approximately 100 patients, suggest that enteral nutrition results in fewer total and septic complications, significantly improves acute phase responses and disease severity scores, and can be delivered at up to a third of the cost of TPN. A recent metaanalysis by Marik et al also suggest enteral nutrition to be superior to TPN.

Focus on SSD

Pancreatic contamination primarily comes from the colonic flora. A metaanalysis of selective digestive decontamination (SDD) suggests that there are clear trends toward a reduction in mortality in critically ill patients. A survival benefit was demonstrated in a multicentre randomised controlled trial of 102 patients with severe acute pancreatitis randomised patients to receive either selective gut decontamination (oral and rectal norfloxacin, colistin and amphotericin; and intravenous cefotaxime 500 mg every 8 hours) or standard treatment. Selective decontamination reduced the need for laparoscopy and reduced late (> 2 week) mortality due to a significant reduction of gram-negative pancreatic infection (p=0.003). Overall mortality fell from 35% in controls, to 22% in the group receiving SSD (p<0.05). It is interesting to note that the SDD group also received systemic cefuroxime that may have confounded the mortality benefit. Moreover, fears of the emergence of resistant gram-positive cocci have prevented the widespread institution of SSD.

Focus on ERPC

ERCP is firmly established as the most valuable method of diagnosing and treating ductal stone. However, its role in the management of acute pancreatitis is debatable. Initial studies of urgent ERCP (performed within 72 hours of admission) and biliary sphincterotomy in patients with acute gallstone pancreatitis and choledocholithiasis showed an improved outcome only in the group of patients who presented with clinically severe acute pancreatitis. ERPC should be used with caution as it may cause contamination of sterile tissue. It should be reserved for patients with biliary obstruction, a raised bilirubin and evidence of cholangitis.

Focus on treatment with pharmacological agents

There is insufficient evidence at present to support the use of octreotide or somatostatin, or the proteolytic enzyme inhibitors aprotonin and gabexate in the treatment of patients with moderate to severe pancreatitis.

Table 3. Guidelines for the efficacious use of CT scanning in suspected acute pancreatitis

a) Patients in whom the clinical diagnosis is in doubt

b) Patients with hyperamylasaemia and severe clinical pancreatitis, abdominal distension, tenderness, high fever and leucocytosis

c) Patients with a Ranson score >3 or APACHE II >8

d) Patients showing lack of improvement after 72 hours of initial conservative therapy

e) Acute deterioration following an initial clinical improvement

Table 4: Grades of pancreatitis as shown on CT scan

A Normal pancreas

B Focal or diffuse enlargement of the pancreas

C Pancreatic gland abnormalities associated with peripancreatic inflammation

D Single fluid collection

E 2 or more fluid collections

Key References

Ranson JH, Rifkind KM, Roses DF et al.
Prognostic signs and the role of operative management in acute pancreatitis.
Surg Gynecol Obstet 1974. 139(1): p. 69-81.

Balthazar EJ, Freeny PC, vanSonnenberg E.
Imaging and intervention in acute pancreatitis.
Radiology 1994. 193(2): p. 297-306.

Dervenis C, Johnson CD, Bassi C et al.
Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference.
Int J Pancreatol 1999. 25(3): p. 195-210.

Yousaf M, McCallion K, Diamond T.
Management of severe acute pancreatitis.
Br J Surg, 2003. 90(4): p. 407-20.

Wyncoll DL.
The management of severe acute necrotising pancreatitis: an evidence-based review of the literature.
Intensive Care Med 1999. 25(2): p. 146-56.

D'Amico R, Pifferi S, Leonetti C et al.
Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials.
Bmj 1998. 316(7140): p. 1275-85.

Luiten EJ, Hop WC, Lange JF et al.
Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis.
Ann Surg 1995. 222(1): p. 57-65.

Marik PE, Zaloga GP.
Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis.
Bmj 2004. 328(7453): p. 1407.

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