Acute pancreatitis

What is acute pancreatitis?

This is acute inflammation of the pancreas, releasing exocrine enzymes that cause autodigestion of the organ. There may be involvement of local tissues and distant organs.

It should not be confused with chronic pancreatitis. See the separate Chronic Pancreatitis article.

Acute pancreatitis epidemiology¹

• The incidence of acute pancreatitis is increasing over time. A UK population-based cohort study of primary care data reported that the age-standardised incidence of pancreatitis increased from 14.8 to 31.2 in 100,000 males and from 14.5 to 28.3 in 100,000 females over a 13-year period (1990-2013).

• A 12-year follow-up study of Welsh hospital admissions found the overall incidence of acute pancreatitis was 30 per 100,000 population, with an average annual increase in incidence of 2.7% per year.

• A systematic review of 10 population-based cohort studies of acute pancreatitis reported a global incidence estimate of 33.74 cases per 100,000 person-years. There was no gender difference in incidence.

• There is considerable geographical variation. The incidence in the UK and the Netherlands is relatively low compared to Scandinavian countries and the USA² .

Aetiology

Gallbladder disease and excess alcohol consumption account for most cases and typically cause periductal necrosis.

• Gallstones cause acute pancreatitis by blocking the bile duct, causing back pressure in the main pancreatic duct.

• Perilobular necrosis is less common and usually found in those with hypothermia and gross hypotension.

• Haemorrhagic, necrotic black discolouration is only found in the most severe cases of acute pancreatitis.

Studies suggest that in countries with high prevalence of acute pancreatitis the main cause is alcohol, whilst in low-prevalence countries it is mainly related to biliary disease³ .

Less common causes of acute pancreatitis include:

• Injury - post-endoscopic retrograde cholangiopancreatography (ERCP), blunt trauma.

• Viral - Coxsackie B, hepatitis and mumps (prodromal diarrhoea is indicative).

• Metabolic - hyperlipoproteinaemia, hyperparathyroidism, hypothermia, uraemia, anorexia.

• Drugs - thiazides, valproate, azathioprine, L-asparaginase, corticosteroids (all rare).

• Malignancy - peri-ampullary tumour, pancreatic carcinoma, metastases to the pancreas.

• Ischaemia - visceral thromboembolism, abdominal vascular surgery, cardiopulmonary bypass.

• Inflammatory bowel disease - one UK study found a seven-fold increase in acute pancreatitis in patients with inflammatory bowel disease taking mesalazine, although it is not known whether this was due to the disease, the drug or a combination of both⁴ .

• Other rarities - alpha-1-antitrypsin deficiency, sclerosing cholangitis, duodenal re-duplication, annular pancreas, vasculitis.

Acute pancreatitis presentation

Acute pancreatitis symptoms

Take careful history, including alcohol consumption and prodromal symptoms.

• Most commonly, this presents as severe upper abdominal pain of sudden onset with vomiting.

• Pain is focused in the left upper quadrant of the abdomen and penetrates to the back. Occasionally, it encircles the abdomen.

• Pain tends to decrease steadily over 72 hours.

Acute pancreatitis signs

• Take the patient's temperature to exclude hypothermia; mild pyrexia is more common.

• Look for evidence of hyperlipidaemia.

• Probable tachycardia with the patient unwell and dehydrated.

• Jaundice may be present in patients with common bile duct stones or, to a lesser degree, in those with alcohol-induced disease, compression of the lower bile duct, or hepatitis.

• Epigastric or generalised abdominal tenderness, often with rigidity.

• Bowel sounds are usually present in the early phase. Paralytic ileus, causing absent bowel sounds can last for >4 days and is a useful marker of disease severity.

• In severe cases of acute pancreatitis: gross hypotension, pyrexia, tachypnoea, acute ascites, pleural effusions, body wall staining around the umbilicus (Cullen's sign) or flanks (Grey Turner's sign).

• Hypoxaemia is characteristic of acute pancreatitis.

Investigations⁵

• Serum amylase three or more times normal is the traditional way of diagnosing acute pancreatitis. However, lipase levels are more sensitive and more specific^{6 7} .

• FBC, U&E, glucose and C-reactive protein (CRP) indicate prognosis⁷ :
  

  • Raised bilirubin and/or serum aminotransferase suggest gallstones.

  • Hypocalcaemia is relatively common.

• Plain erect (if possible) abdominal X-ray:
  

  • This excludes some other causes (eg, intestinal obstruction and perforation) and may show calcification.

  • CXR may show elevation of one hemidiaphragm, infiltrates ± acute respiratory distress syndrome (ARDS) or pleural effusions in severe cases.

• CT scan with contrast enhancement may be diagnostic where clinical and biochemical results are equivocal on admission. However, in stable patients with mild symptoms of acute pancreatitis it should not be performed for the sole purpose of assessing severity on admission:
  

  • The CT severity index (CTSI), derived by Balthazar et al, has become widely used for description of CT findings in acute pancreatitis. A modified index has been developed which is considered to be simpler to use and more accurate⁸ .

  • Contrast-enhanced CT scanning can identify pancreatic swelling, fluid collection and change in density of gland. Such criteria can have prognostic value and predict the need for surgery.

• Ultrasound:
  

  • The pancreas is poorly visualised in 25-50% of cases.

  • Ultrasound can show a swollen pancreas, dilated common bile duct and free peritoneal fluid.

  • It is useful to detect the presence of gallstones.

  • Endoscopic ultrasound is a safe minimally invasive technique which is more accurate than transabdominal ultrasound and can accurately detect bile duct stones and other causes of recurrent acute pancreatitis.

• MRI may reveal acute abdominal wall oedema which may be a supplementary indicator of severity⁹ .

• Peritoneal aspiration of free fluid without bacterial contamination is a risk factor for mortality¹⁰ .

• Laparoscopy can reveal diagnosis where suspicion is high but tests are inconclusive¹¹ .

Differential diagnosis

Other causes of raised amylase

• Renal failure.

• Ectopic pregnancy.

• Diabetic ketoacidosis.

• Perforated duodenal ulcer.

• Mesenteric ischaemia/infarction (but will show bacterial contamination of peritoneal aspirate).

Other causes of similar pain

• Small bowel perforation/obstruction.

• Ruptured or dissecting aortic aneurysm.

• Atypical myocardial infarction.

Associated diseases

• Gallstones.

• Alcohol dependency.

• Hyperlipidaemia.

• Hypothermia.

Severity and prognostic assessment

• Scoring systems increase accuracy of prognosis.

• Use of the Glasgow Prognostic Score/Ranson's Criteria/Acute Physiology and Chronic Health Evaluation II (APACHE II) Score can indicate prognosis, particularly if combined with measurement of CRP >150 mg/L.

An APACHE II score of 8 or more is severe¹² .

The Atlanta Classification - revised in 2012 - allows comparison of these scoring systems and of clinical trials¹³ .

• The Classification identifies two phases - early (within the first two weeks) and late (thereafter).

• Severity of disease is classified into three levels: mild (no complications), moderately severe (complications lasting for less than two days, local complications and/or recurrence of co-existing disease) and severe (organ failure lasting for more than two days).

• Local complications are usually detected by CT and may include peripancreatic fluid collection, pseudocysts and necrosis.

• Clinically apparent organ failure includes pulmonary, circulatory or renal insufficiency.

There has been criticism of current scoring systems as being unwieldy and difficult to interpret. Procalcitonin (PCT) and Bedside Index for Severity in Acute Pancreatitis (BISAP) have been mooted as possible candidates in the search for a more simplified approach. Studies have shown that low PCT levels are associated with better outcomes in acute pancreatitis¹⁴ . A meta-analysis showed that compared with Ranson's Criteria and the APACHE II Score, the BISAP Score showed higher specificity and lower sensitivity for mortality and severe acute pancreatitis¹⁵ . A further analysis in elderly patients suggested that BISAP produced the best predictive results. APACHE II and Ranson were more effective for younger patients¹⁶ .

Acute pancreatitis management^{1 17}

• Pain should be controlled with intravenous analgesia.

• IV fluids with nil by mouth.

• Nasogastric tube only for severe vomiting.

• Antibiotics should not be given prophylactically but only for specific infections.

• In mild cases, when pain and other symptoms have resolved and blood tests are normal, oral fluids and then solids, can be resumed. If gallstones are the cause then consider common bile duct clearance and cholecystectomy after recovery, preferably during original admission.

• Treat severe cases in ITU or a high dependency unit.

• Where there is evidence of significant pancreatic necrosis, IV antibiotics should be given, preferably following percutaneous aspiration of peritoneal fluid for culture . The role of routine prophylactic antibiotics for severe cases is less clear. A Cochrane review found evidence that imipenem (a beta-lactam) when used as monotherapy may reduce the incidence of superinfection of necrotic tissue, if given for 10-14 days in cases with CT-proven necrosis. However, the studies used differing agents and aetiology/use of surgical debridement may have influenced results; so, more research is needed to answer this question definitively¹⁸ .

• Offer people with acute pancreatitis an endoscopic approach for managing infected or suspected infected pancreatic necrosis when anatomically possible.

• Offer a percutaneous approach when an endoscopic approach is not anatomically possible.

• When deciding on how to manage infected pancreatic necrosis, balance the need to debride promptly against the advantages of delaying intervention.

• Feed with enteral nutrition (EN) via a nasogastric tube placed beyond the ligament of Treitz, provided there is no ileus (this ligament connects the duodenum to the diaphragm and feeding here is less likely to stimulate the pancreas). A Cochrane review found that EN significantly reduced mortality, multiple organ failure, systemic infections and the need for operative interventions and was associated with shorter hospital stays¹⁹ .

• A Cochrane review supports early ERCP for patients with co-existing cholangitis or biliary obstruction²⁰ .

• Surgery is only required where there is infection and necrosis. Open surgical debridement is being largely replaced by newer minimally invasive techniques such as transgastric endoscopy and video-assisted translumbar retroperitoneal necrosectomy followed by closed lavage of infected pancreatic necrosis²¹ . Refinement of techniques may lead to exclusive use of drainage procedures, without the need for necrosectomy²² .

• Percutaneous catheter drainage with saline irrigation can sometimes avoid surgery²³ .

• Hyperbaric oxygen therapy - administration of 100% oxygen at a pressure of 2.5 atmospheres for 90 minutes twice-daily for five days has been shown to improve APACHE II and CTSI grading scores²⁴ . Hyperbaric oxygen treatment acted by normalising the pancreatic microvasculature²⁵ .

• The poly(ADP-ribose) polymerase (PARP) enzyme system responsible for the control of cellular processes, such as DNA repair, mitochondrial functions and programmed cell death, is involved in the pathological processes causing cellular damage in acute pancreatitis. One study reported the successful combination of a PARP inhibitor - 3-aminobenzamide (3-AB) - in combination with hyperbaric oxygen in the management of acute pancreatitis²⁶ .

• Human adipose-derived stromal/stem cells may provide a valuable tool for cell-based therapy²⁷ .

Acute pancreatitis complications

• Pancreatic necrosis - if infected, this trebles mortality risk:
  

  • Rising CRP suggests necrosis and is confirmed by dynamic CT.

  • Infection occurs in 30-70% of cases of necrosis (the risk can be reduced by gut decontamination)²⁸ .

  • Take special care of aseptic technique with invasive procedures.

  • Where the patient suddenly deteriorates or worsens with intensive support, use CT-guided fine-needle aspiration for culture and microscopy.

• Infected necrosis - is almost always fatal without intervention:
  

  • The standard is IV antibiotics and aggressive surgical pancreatic debridement (necrosectomy) involving drain placement. In many cases, this can be accomplished using minimally invasive techniques, even if necrosis is severe.

• Acute fluid collections - are common in patients with severe acute pancreatitis (occurring in 30-50%)²⁹ :
  

  • The majority will resolve spontaneously and, in an otherwise stable patient, they do not require treatment for acute pancreatitis.

  • Unnecessary percutaneous procedures risk introducing infections.

• Pancreatic abscess - is a collection of pus adjacent to the pancreas, presenting several months after an attack:
  

  • It requires surgery.

• Acute pseudo-cyst - contains pancreatic juice in a wall of fibrous or granulation tissue:
  

  • It arises four weeks after attack.

  • It can rupture or haemorrhage.

  • It requires surgery.

• Pancreatic ascites - occurs when a pseudo-cyst collapses into the peritoneal cavity or major pancreatic duct breaks down and releases pancreatic juices into the peritoneal cavity:
  

  • Treat with IV feeding plus synthetic somatostatin or surgical excision of the segment of pancreas drained by the broken duct.

• Acute cholecystitis - complicates approximately 10% of patients with severe acute pancreatitis in the late stage³⁰ .

Systemic complications

• Respiratory:
  

  • Pulmonary oedema.

  • Pleural effusions.

  • Consolidation.

  • ARDS.

• Cardiovascular:
  

  • Hypovolaemia.

  • Shock.

• Disseminated intravascular coagulopathy (DIC).

• Renal dysfunction due to hypovolaemia, intravascular coagulation. Usually avoided by adequate fluid replacement plus/minus low-dose dopamine; however, acute tubular or cortical necrosis can follow.

• Metabolic:
  

  • Hypocalcaemia.

  • Hypomagnesaemia.

  • Hyperglycaemia.

  • Frank diabetes is rare, but does occasionally occur. The National Institute for Health and Care Excellence (NICE) has updated its guidance on acute pancreatitis to highlight the importance of reminding patients to rotate insulin injection sites within the same body region, in line with an MHRA Drug Safety Update on insulins (all types)^{17 31} . This precaution reduces the risk of cutaneous amyloidosis at injection sites.

• Gastrointestinal:
  

  • Haemorrhage.

  • Ileus.

• Weber-Christian disease:
  

  • Subcutaneous fat necrosis - relapsing febrile nodular nonsuppurative panniculitis. Recurring crops of tender nodules in the skin and subcutaneous fat of the trunk, thighs and buttocks, which is more common in middle-aged women.

  • These often ulcerate and then scar on healing.

  • Difficult to treat - try prednisolone or immunosuppressives.

• Splenic vein thrombosis.

Acute pancreatitis prognosis

• 80% of patients have mild acute pancreatitis and recover without complications³² .

• An American study found that 22% of patients admitted with a first attack of pancreatitis subsequently had one or more attacks. However, progression to chronic pancreatitis occurred in only 6% of patients and this was normally against a background of recurrent attacks, alcohol or smoking³ .

• 5% mortality in mild cases; up to 30% mortality in severe cases.

• Severe cases may be deficient in pancreatic enzymes for up to two years but only those with steatorrhoea and weight loss need treatment.

• Subtle glucose intolerance is common but diabetes is uncommon.

Prevention

• Avoid alcohol.

• Treat gallstones in patients who present with acute pancreatitis.

• Plasmapheresis may help to reduce the incidence of acute pancreatitis in patients with severe hypertriglyceridaemia.