Pancreatitis

Plasma amylase: Amylase is one of the enzymes released into the circulation in pancreatitis; measurement is a simple laboratory investigation and is generally a reliable diagnostic test. A level above 1000 i.u. /ml is usually regarded as diagnostic of acute pancreatitis but levels are often lower in alcoholic pancreatitis, particularly during recurrent attacks. Any inflammatory upper abdominal condition near the pancreas (e.g. cholecystitis, perforated peptic ulcer or strangulated bowel) can cause a moderate rise in amylase, although this rarely reaches 1000 i.u. /ml. Levels rise rapidly at the outset of an attack, and readings of 10 000 i.u./ml or more may be recorded on admission to hospital. However, levels fall as the patient recovers so a diagnosis of pancreatitis should not rely on an arbitrary threshold; rather the amylase level at any moment should be interpreted in relation to how much time has elapsed since the onset.

The peak amylase level is not an indicator of disease severity, but persistently raised levels over several days warn of developing complications. Note that false negative amylase results may occur in lipaemic serum. In this case, true results can be obtained on diluted specimens.

On rare occasions, plasma amylase may be normal in acute pancreatitis. This occurs where most of the gland has been destroyed by severe pancreatitis. It may also occur if a patient presents several days into an attack, by which time the amylase may have returned to normal. If pancreatitis is strongly suspected but the amylase is normal, the diagnosis may be confirmed by appropriate radiological imaging (see next section).

Plasma lipase estimation has been recommended for diagnosing acute pancreatitis as it is more sensitive than amylase and has a longer half-life, so it is easier to detect later in the course of the disease. It is not as widely used but is often useful in difficult or late-presenting cases. In addition, elevated alanine aminotransferase (ALT) levels are highly specific for gallstone pancreatitis.

Once the patient is in the recovery phase, fasting bloods should be taken for calcium levels and for plasma lipids, particularly triglycerides. Viral antibody titres may be useful in cases of idiopathic pancreatitis.

Imaging: Plain X-rays of chest (erect) to look for free gas under the diaphragm, and abdomen (supine) are usually performed during the initial investigation. The latter may show a featureless ‘ground-glass’ appearance. Bowel gas tends to be absent except perhaps for a ‘sentinel loop’ of dilated adynamic small bowel in the centre. Note, however, that these signs are not specific for pancreatitis and are often absent. Rarely, radiopaque gallstones are visible.

An ultrasound scan of the biliary tree is essential but good images are not always obtained early; a delay of 48–72 hours may improve image quality. The goal is to look for small calculi in the gall bladder or bile ducts typically responsible for gallstone pancreatitis. If no definite cause for the pancreatitis is found, a repeat ultrasound should be performed following recovery.

CT scanning has a limited role in the diagnosis of acute pancreatitis. Initially, it is indicated only when clinical and biochemical findings are equivocal, particularly if amylase is normal and intra-abdominal pathology such as perforation or infarction needs to be excluded. CT scans performed too early cannot predict the final severity and are unlikely to influence management during the first week. In severe pancreatitis, contrast-enhanced CT is valuable for demonstrating necrosis, but this cannot be identified until at least 4 days after the onset of symptoms.

Endoscopy: In patients with severe acute gallstone pancreatitis, urgent ERCP and sphincterotomy should be carried out within 72 hours of the onset of pain. This is especially important in patients with cholangitis, jaundice or a dilated common bile duct. ERCP also has an important diagnostic role once the patient has fully recovered from the acute attack if a cause for pancreatitis is not evident from the history or initial imaging studies. In this group, a cause can be found in about 50%, e.g. small pancreatic or periampullary tumours, pancreatic duct stricture, gallstones, congenital pancreas divisum or a high-pressure sphincter of Oddi.

Mild acute pancreatitis: Mild attacks are common. The patient looks generally well with minimal systemic features. Nevertheless, there is often considerable pain. The abdomen is usually distended and diffusely tender but with little guarding. Bowel sounds are absent as a result of inflammatory ileus. The patient may be mildly jaundiced from periampullary oedema. The differential diagnosis includes biliary colic, acute cholecystitis, an acute exacerbation of a peptic ulcer or even a perforation of a peptic ulcer. Lower lobe pneumonia or an inferior myocardial infarction may sometimes present like this. Sometimes the pancreatitis diagnosis is made after plasma amylase is unexpectedly found to be elevated.

Severe acute pancreatitis: In a severe attack the patient looks apathetic, grey and shocked and there are typical abdominal signs of generalised peritonitis, i.e. extreme tenderness, guarding and rigidity. In this case, the differential diagnosis includes other major abdominal catastrophes, especially faecal peritonitis from perforated large bowel and concealed haemorrhage from a leaking aortic aneurysm or ruptured ectopic pregnancy. Massive bowel infarction due to arterial occlusion may present like this but abdominal signs are less marked. An important early and dangerous complication of severe acute pancreatitis is acute respiratory distress syndrome (ARDS).

Mild attacks: The management of acute pancreatitis has been the subject of several international consensus conferences, the most important of which took place in Atlanta in 1992. This codified many definitions and circumstances within acute pancreatitis. Another important consensus meeting was in Washington in 2004. Numerous sets of guidelines are available; in the UK, the most used are published by BSG, updated in 2005.

Mild attacks require no further emergency investigation once diagnosed on plasma amylase, and are managed by fluid resuscitation and analgesia: recovery is usually rapid. These patients need no dietary restriction. Later management is aimed at treating predisposing factors. Gallstones should be sought by ultrasonography; if present, cholecystectomy is the definitive treatment and is ideally performed on the same admission or at worst 2–4 weeks after recovery. Ductal stones should be removed endoscopically before discharge from hospital. Alcohol abuse must be discouraged.

Severe attacks: A severe attack is defined by referring to a specified list of criteria which should be evaluated on admission and over the next 48 hours (see Table 25.2 and Box 25.4). Patients with severe pancreatitis may die early in the attack because of profound systemic toxaemia (SIRS), shock and multiple organ dysfunction syndrome (MODS); see Chapter 3, p. 51. ARDS develops rapidly with little warning but a deteriorating arterial PO₂ may herald its onset. This is an indication for urgent ventilatory support before the condition becomes established.

Even when pancreatitis is severe, supportive measures are still the mainstay of treatment. These include oxygen supplementation and carefully planned intravenous fluid resuscitation. A nasogastric tube is passed to aspirate the stomach only if gastroparesis causes troublesome vomiting. Enteral nasogastric or nasojejunal feeding has been reported to significantly decrease morbidity. If enteral feeding is not tolerated because of ileus, then total parenteral nutrition may be necessary.

Gross fluid and electrolyte disturbances as well as hypocalcaemia are also likely to occur. Fluid balance in the shocked patient is complicated by massive losses of protein-rich fluid into the peritoneal cavity and interstitially (‘third space’). This sequestration of fluid needs to be countered by large amounts of intravenous fluids, carefully monitored by measuring central venous pressure and hourly urine output. Any patient with severe pancreatitis, or anyone with acute pancreatitis who develops signs of serious deterioration, should be admitted to an intensive care unit for close monitoring and vigorous treatment of cardiovascular, pulmonary, renal and septic complications. Box 25.5 lists recommended investigations to guide management.

There is probably little benefit in measuring plasma amylase again once the diagnosis is made. C-reactive protein (CRP) is more useful as it is a good indicator of systemic inflammation and hence developing necrosis and other complications. If the CRP is elevated > 150 after 48 hours, complications are more likely. Biochemical estimations, particularly liver transaminases and bilirubin, are charted regularly, looking chiefly for evidence of biliary obstruction; renal function tests are performed for evidence of acute renal insufficiency.

Prophylactic parenteral antibiotics are no longer recommended as there is no evidence that they reduce either infective complications or mortality.

Endoscopy and surgery in severe acute pancreatitis: All patients suspected of having or proven to have a gallstone aetiology should undergo urgent therapeutic ERCP, which should take place within 72 hours of the onset of pain. This applies whether severe pancreatitis is predicted or confirmed. All of these patients require sphincterotomy of the sphincter of Oddi whether or not stones are found in the common bile duct. If stones are seen or if cholangitis or jaundice is present, biliary stenting is usually required.

There is no role for surgery during the acute attack but in patients with stones, laparoscopic cholecystectomy with operative cholangiography should be performed before discharge from hospital. This is because deferring cholecystectomy until months later increases the risk of another attack. In the small group of critically ill patients with infected necrotic tissue and infected peripancreatic fluid collections, surgical debridement with or without continuous peritoneal irrigation is unavoidable, but mortality remains high.

Mortality: About 15% of patients admitted to hospital with acute pancreatitis have severe disease, which carries a high risk of potential complications. However, about a further 10% initially diagnosed with mild pancreatitis deteriorate markedly during admission and become severe. In severe pancreatitis, mortality is 10–30%, i.e. 2–5% of all cases, and obese patients have a higher mortality. About half of those that die, do so within the first week, usually of ARDS and pulmonary failure. Other early life-threatening complications are associated with multiple organ dysfunction (MODS). Manifestations include cardiovascular collapse aggravated by fluid shifts, renal insufficiency made worse by hypotension, and disseminated intravascular coagulopathy. If death occurs after the first week, infective complications of pancreatic necrosis added to existing organ failure are the usual cause.

Pancreatic necrosis and infection: In severe pancreatitis, pancreatic and peripancreatic necrosis may manifest during the first 2 weeks of the attack (see Fig. 25.1). Necrosis is identified using intravenous contrast-enhanced CT scanning in which necrotic pancreas does not opacify, having lost its blood supply. Infection of devitalised pancreatic and peripancreatic tissues occurs in about one-third of patients with severe pancreatitis, and is often lethal. Infection may be suspected on CT by gas bubbles in pancreatic fluid collections but can only be confirmed by percutaneous aspiration (with microscopy and culture of the aspirate), usually performed under CT guidance. In proven infected cases, operative debridement, drainage and sometimes continuous peritoneal irrigation may be necessary, along with aggressive organ support.

Fluid collections around the pancreas: During the initial attack, acute peripancreatic fluid collections may develop. Most resolve spontaneously, but for those that do not, CT-guided percutaneous drainage is valuable. Fluid collections persisting for longer than 6 weeks are termed pancreatic pseudocysts (see below). Late in the course of the disease, a pancreatic abscess may appear. This is a well-localised collection of pus within the gland, and contrasts with infected necrotising pancreatitis which appears earlier and is not localised.

Pancreatic pseudocyst: A pancreatic pseudocyst is a collection of pancreatic enzymes, inflammatory fluid and necrotic debris, usually encapsulated within the lesser sac. Pseudocysts appear in 1–8% of cases of acute pancreatitis and are less likely to resolve spontaneously than the early acute fluid collections. A pseudocyst is not a true cyst (i.e. there is no epithelial lining) although the surrounding tissues become thickened by the inflammatory response. Pseudocysts may occur after even a moderate attack of pancreatitis and sometimes reach the size of a football! An upper abdominal mass may be palpable. If a pseudocyst is suspected, CT scanning is the investigation of choice (see Fig. 25.2).

Management varies according to the size of the cyst. Larger cysts, especially those larger than 10 cm, are unlikely to resolve. Those around 6 cm can be safely observed for up to 6 months, provided they have a typical appearance on CT scanning and are asymptomatic. If the cyst has failed to resolve by then, operative intervention should be considered. Operation, either by laparoscopy or an open approach, involves ‘marsupialising’ the pseudocyst into the posterior wall of the stomach. This can be performed after about 6 weeks, when the wall of the pseudocyst has ‘matured’ enough to hold sutures.

Pancreatic abscess: Pancreatic abscesses occur in 1–4% of cases of acute pancreatitis. Certain patients remain systemically well despite pancreatic necrosis, with an illness that may grumble on for several weeks. There is a recurrent high swinging fever indicating the presence of an abscess. By that time, the necrotic pancreas is likely to have formed a discrete grey mass lying free within the pancreatic bed and bathed in pus. Pus may extend widely in retroperitoneal tissues. Surgery is then required to remove the necrotic tissue and drain the abscesses.

Complications of severe acute pancreatitis: Severe acute pancreatitis can cause wide-ranging complications in almost every body system:

Late complications of acute pancreatitis: Diabetes mellitus, and intestinal malabsorption due to loss of pancreatic secretions sometimes occur after severe attacks that have caused substantial pancreatic necrosis and loss of pancreatic tissue.