Acute Pancreatitis

• Incidence - Between 150 and 420 per million UK population per year.¹
• It accounts for 3% of all cases of abdominal pain admitted to hospital.
• In 80% of cases the acute pancreatitis is mild and resolves without serious complications.²

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

• Gall-stones cause 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.

Biliary disease and alcohol abuse together account for 70%-80% of cases, 10% patients have both. 25% of cases are idiopathic.
Less common causes include:

• Injury - post endoscopic retrograde cholangio-pancreatogram (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) the mean peak
• Malignancy - Periampullary tumour, pancreatic carcinoma, metastases to pancreas
• Ischaemia - Visceral thromboembolism, abdominal vascular surgery, cardiopulmonary bypass
• Other rarities - Alpha-1-antitrypsin deficiency, sclerosing cholangitis, duodenal re-duplication, annular pancreas, vasculitis

Symptoms

Take careful history including alcohol consumption and prodromal symptoms.

• Most commonly presents as severe upper abdominal pain of sudden onset with vomiting.
• Pain is focused in the left upper quadrant of the epigastrium and penetrates to the back. Occasionally encircles the abdomen.
• Pain tends to decrease steadily over 72 hours.

Signs

• Take temperature to exclude hypothermia; mild pyrexia is more common.
• Look for evidence of hyperlipidaemia.
• Probable tachycardia with 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 early phase. Paralytic ileus, causing absent bowel sounds can last for > 4 days and is a useful marker of disease severity.
• In severe cases: gross hypotension, pyrexia, tachypnoea, acute ascites, pleural effusions, body wall staining around umbilicus (Cullen's sign) or flanks (Grey Turner's sign).
• Hypoxaemia is characteristic of acute pancreatitis.

• Serum amylase >4 x normal:
  • Amylase rises within a few hours after onset, returning to normal 3-5 days after attack.²
  • Amylase P, pancreatic isozyme is more specific
  • Lipase 2 x normal diagnostic as no other source than pancreas, but is not always available. Levels remain higher for longer than amylase
  • Presence of urinary amylase is diagnostic.
• Full blood count, U+E, glucose, CRP indicate prognosis. CRP value is significantly lower in drug-induced acute pancreatitis.³
  • Raised bilirubin and/or serum aminotransferase suggest gall stones.
  • Hypocalcaemia is relatively common.
• Plain erect (if possible) abdominal x-ray:
  • This excludes some other causes e.g. intestinal obstruction, perforation and may show calcification.
  • Chest x-ray may show elevation of one hemidiaphragm, infiltrates ± acute respiratory distress syndrome or pleural effusions in severe cases.
• CT with contrast enhancement may be diagnostic where clinical and biochemical results are equivocal on admission. CT after 4 days can help in the assessment of complications.²
  • It may show swelling, fluid collection and change in density of gland.
  • British Society of Gastroenterologists (BSG) guidelines¹ recommend patients predicted with severe attack have dynamic enhanced CT scans to show areas of pancreatic necrosis and peri-pancreatic/intra-abdominal fluid collections, if intervention is being considered on basis of results.⁴
  • Contrast enhanced CT can provide reliable evidence of need for surgery.
• Ultrasound
  • Pancreas poorly visualised in 25-50% of cases.
  • Can show swollen pancreas, dilated common bile duct, and free peritoneal fluid.
  • Useful to detect presence of gallstones.
• Peritoneal aspiration >20 ml free fluid without bacterial contamination indicates severe disease.
• Laparoscopy or laparotomy can reveal diagnosis where suspicion is high but tests are inconclusive.

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

• Gall stones
• Alcoholism
• Hyperlipidaemia
• Hypothermia

• Prediction is difficult and unreliable.
• Clinically apparent organ failure (pulmonary, circulatory or renal insufficiency) usually indicates a severe attack. However, the BSG guidelines state that organ failure present within the first week which resolves within 48 hours should not be considered an indicator of a severe attack of acute pancreatitis.¹
• Scoring systems do increase accuracy.
• Initially assessing the severity of an attack into mild or severe has important implications for management - and may prevent deaths.¹ BSG guidelines recommend the use of the full Atlanta criteria as per the original publication,⁵ to define severity.
• Use of the Glasgow/Ranson/Apache II scores can indicate prognosis particularly if combined with measurement of CRP >150 mg/l.

An APACHE II score of 8 or more is severe.

Mild cases

• Manage on general ward.
• Pain relief with pethidine or buprenorphine ± IV benzodiazepines. Morphine relatively contraindicated because of possible spastic effect on sphincter of Oddi.
• IV fluids with nil by mouth.
• Nasogastric tube only for severe vomiting.
• Antibiotics for specific infections.
• No other treatment necessary or CT scans.
• When pain and other symptoms have resolved and blood tests normal, oral fluids then solids resumed. If gall stones are the cause then common bile duct clearance and cholecystectomy after recovery, preferably during original admission.

Severe case

BSG guidelines suggest <30% mortality in severe cases.¹ One third of these occur in first week from multiple organ failure and remainder from infected pancreatic necrosis.

• Treat in ITU or high dependency unit.
• Where there is evidence of significant pancreatic necrosis, intravenous antibiotics should be given, preferably following percutaneous aspiration of peritoneal fluid for culture.¹ The role of routine prophylactic antibiotics for severe cases is less clear. A Cochrane review⁶ found evidence of reduced 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 definitively answer this question.⁷
• Feed with enteral nutrition (EN) via nasogastric tube placed beyond the ligament of Trietz (if no ileus). There is no evidence to support the routine use of parenteral nutrition, according to a Cochrane review, until further, sufficiently powered trials are conducted.⁸ Patients with acute severe pancreatitis should begin EN early because it modulates the stress response, promotes more rapid resolution of the disease process, and results in better outcome.⁹ The positive benefits may be enhanced by supplementation with modulators of inflammation and systemic immunity.
• Where there are gallstones and predicted severe attack, early ERCP± sphincterotomy has been shown to be beneficial by a Cochrane review.¹⁰
• Surgery only required where there is infection and necrosis. When infection develops - open surgical debridement. Postoperative lavage or abdominal packing with partial or non-closure of abdomen, if large volume of venous oozing. Establish feeding jejunostomy.
• Hyperbaric oxygen therapy - administration of 100% oxygen at a pressure of 2.5 atmospheres for 90 min twice daily for 5 days has been shown to improve APACHE II and CTSI grading scores.¹¹ Further study is required.

• Pancreatic necrosis - if infected trebles mortality risk.
  • Rising CRP suggests necrosis confirmed by dynamic CT.
  • Infection occurs in 30%-70% cases of necrosis (can reduce risk with gut decontamination).
  • Take special care of aseptic technique with invasive procedures.
  • Where 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.
  • Standard is aggressive surgical pancreatic debridement (necrosectomy) involving drain placement and re-operation as required.
  • Open or semi-open management uses repeat laparotomy or open packing with wound exposed.
  • Closed management uses large bore drainage tubes for high volume, continuous irrigation after closure.
• Acute Fluid Collections are common in patients with severe pancreatitis (occurring in 30%-50%).
  • The majority will resolve spontaneously and in an otherwise stable patient they do not require treatment.
  • Unnecessary percutaneous procedures risk introducing infections.
• Pancreatic abscess is a collection of pus adjacent to pancreas presenting several months after attack.
  • It requires surgery.
• Acute pseudocyst contains pancreatic juice in a wall of fibrous or granulation tissue.
  • Arises 4 weeks after attack.
  • Can rupture or haemorrhage.
  • Requires surgery.
• Pancreatic ascites occurs when a pseudo-cyst collapses into peritoneal cavity or major pancreatic duct breaks down and releases pancreatic juices into peritoneal cavity.
  • Treat with IV feeding plus synthetic somatostatin or surgical excision of segment of pancreas drained by broken duct.

Systemic complications

• Respiratory:
  • Pulmonary oedema
  • Pleural effusions
  • Consolidation
  • ARDS
• Cardiovascular:
  • Hypovolaemia
  • Shock
• Disseminated intravascular coagulopathy (DIC)
• Renal dysfunction due to hypovolaemia, intra-vascular coagulation. Usually avoided by adequate fluid replacement plus/minus low-dose dopamine but acute tubular or cortical necrosis can follow.
• Metabolic:
  • Hypocalcaemia
  • Hypomagnesaemia
  • Hyperglycaemia
• GI:
  • Haemorrhage
  • Ileus
• Weber Christian disease:
  • Subcutaneous fat necrosis - relapsing febrile nodular nonsuppurative panniculitis. Recurring crops of tender nodules in skin and subcutaneous fat of trunk, thighs and buttocks, which is more common in middle-aged women.
  • Often ulcerate and scar on healing.
  • Difficult to treat - try prednisolone or immunosuppressives.
• Splenic vein thrombosis

• 5% mortality in mild cases, <30% mortality in severe cases.
• Severe cases may be deficient in pancreatic enzymes for up to 2 years, but only those with steatorrhoea and weight loss need treatment.
• Subtle glucose intolerance is common, but diabetes uncommon.

• Avoid alcohol
• Treat gallstones in patients who present with acute pancreatitis