Investigations
1st investigations to order
serum lipase or amylase
Test
Use serum lipase testing (if available) in preference to serum amylase.[18]
Serum lipase and amylase have similar sensitivity and specificity but lipase levels remain elevated for longer (up to 14 days after symptom onset vs. 5 days for amylase), providing a higher likelihood of picking up the diagnosis in patients with a delayed presentation.[58]
Practical tip
Beware false positive and false negative results. Always take account of the full clinical picture.
Sensitivity of lipase/amylase results:
Up to one quarter of people with acute pancreatitis have lipase/amylase levels that remain within the normal range, leading to a risk of missing the diagnosis.[58] Have a low threshold for admitting patients whose symptoms are suggestive of acute pancreatitis, even if serum lipase and/or amylase tests are normal. Abdominal imaging, such as contrast-enhanced computed tomography (CECT), is recommended for patients in whom there is diagnostic doubt.[18][48]
Serum pancreatic enzyme levels may remain in the normal range in alcohol-related acute pancreatitis (particularly in cases of acute-on-chronic pancreatitis) and in patients with hypertriglyceridaemia (a rare cause).[18]
Specificity of lipase/amylase results:
Around 1 in 10 patients with acute-onset abdominal pain due to another condition will have lipase/amylase levels above the diagnostic threshold for acute pancreatitis. Always consider other possible acute surgical emergencies.
Serum pancreatic enzyme levels can be raised in a variety of acute surgical and other conditions (e.g., impaired renal function, acute appendicitis, cholecystitis, intestinal obstruction, peptic ulcer, salivary gland disease).[18] It is therefore important to consider alternative diagnoses even if lipase/amylase level is elevated.[58]
Patients with diabetes have higher median lipase levels.
This group may need a higher diagnostic threshold (>3-5 times upper limit of normal).[18]
The accuracy of these tests decreases with time since symptom onset.
Ask for additional investigations if you still suspect acute pancreatitis, regardless of the test result.[58]
Evidence: Sensitivity and specificity of lipase/amylase
Lipase and amylase have similar sensitivity and specificity.
A Cochrane review of 10 studies covering 5056 patients presenting to the emergency department with acute-onset abdominal pain found:[58]
A sensitivity on admission of 72% for amylase (95% CI, 59% to 82%) and 79% for lipase (95% CI, 54% to 92%), based on the accepted diagnostic threshold (>3 times upper limit of normal).
A specificity on admission of 93% for amylase (95% CI, 66% to 99%) and 89% for lipase (95% CI, 46% to 99%), based on the accepted diagnostic threshold for acute pancreatitis (>3 times upper limit of normal).[58]
FBC and differential
Test
Leukocytosis with left shift (increase in ratio of immature to mature neutrophils and macrophages) is often seen.
WBC count >12 x 109L or <4 x 109L is one of the four criteria for identifying SIRS (two or more must be present).[55]
An elevated haematocrit (>44%) on presentation is a predictor of poor prognosis.
Result
leukocytosis
haematocrit >44% indicates poorer prognosis
C-reactive protein (CRP)
Test
Sometimes used as an early indicator of severity and to monitor progression of inflammation.[61]
CRP >200 mg/L indicates a high risk of developing pancreatic necrosis.[62]
However, there is ongoing doubt over the diagnostic test accuracy of CRP for predicting pancreatic necrosis.[62] It may take 72 hours after symptom onset to become accurate as an inflammatory marker.[18][63] CRP ≥150 mg/L on day 3 of presentation can be used as a prognostic factor for severe acute pancreatitis.[29]
Result
if >200 mg/L, is associated with pancreatic necrosis
urea/creatinine
Test
Elevated levels suggest dehydration/hypovolaemia and increased risk for development of severe disease.[18]
Result
elevated in severe cases
pulse oximetry
Test
Patients may be hypoxaemic and require supplemental oxygen.
Patients with acute pancreatitis are at high risk of hypoxia because of one or more of abdominal splinting, atelectasia, pulmonary oedema, acute respiratory distress syndrome.
Consider the need for blood gas analysis (arterial or venous) if the patient shows signs of deterioration.
Result
hypoxaemia
LFTs
Test
Elevated alanine aminotransferase (ALT) levels strongly suggest gallstones as the cause.
ALT >3 times the upper limit of normal predicts gallstones as the cause of acute pancreatitis.[48][49]
However, the specificity for pancreatitis is low.[2]
In the absence of choledocholithiasis, LFTs are usually normal.
A slight increase in alkaline phosphatase and bilirubin may be seen.
Result
if >3 times the upper limit of normal, predicts gallstone disease as aetiology
CXR
transabdominal ultrasound
Test
Abdominal imaging is not needed for diagnosis in most patients.
The diagnosis is usually made based on clinical symptoms and serum lipase/amylase levels.
Request a right upper quadrant abdominal ultrasound on admission for any patient with a diagnosis of acute pancreatitis, to look for biliary aetiology.[18][29][48]
Early detection of gallstones will ensure a plan is put in place for their definitive management, usually by cholecystectomy, to prevent further attacks of pancreatitis and potential biliary sepsis.[18]
Ultrasound is inexpensive, easy to perform at the bedside, and allows examination of the gallbladder and bile duct system. Its sensitivity in detecting pancreatitis is 62% to 95%. However, it is limited by obesity and bowel gas, and is operator-dependent.[67][68] It also has poor sensitivity, with a high risk of false negatives during the acute phase.[69]
Result
confirms or excludes gallstones
may show pancreatic inflammation, peri-pancreatic stranding, calcifications, or fluid collections
serum calcium
Test
Hypercalcaemia, a rare cause of acute pancreatitis, may be identified.
Result
hypercalcaemia
Investigations to consider
serum triglycerides
abdominal CT scan (CECT)
Test
Abdominal imaging is not needed for diagnosis in most patients.
Most patients do not need contrast-enhanced computed tomography (CECT) as diagnosis is usually based on clinical presentation and serum lipase/amylase.[48]
CECT has a sensitivity of 87% to 90% and specificity of 90% to 92% for confirming acute pancreatitis.[52]
There is no evidence to suggest that routine early CT improves clinical outcomes in acute pancreatitis. Conversely, there is some evidence to suggest that early (inappropriate) CT scanning has low diagnostic yield without influencing ongoing management decisions and can result in a longer hospital stay.[48][70][71]
Request CECT where there is diagnostic doubt, for example:[18][29][48][49]
An atypical clinical presentation.
Equivocal serum lipase/amylase results (more likely in patients who present late).
To rule out bowel ischaemia or intra-abdominal perforations in a patient presenting with both acute pancreatitis and acute abdomen.
Note that an early CECT scan for diagnosis should never be used to assess disease severity because necrosis generally takes around 5 days to develop.
Evidence: Early CECT
Routine use of early CECT may be detrimental.
There is no evidence to suggest that routine early CT improves clinical outcomes in acute pancreatitis. Conversely, there is some evidence to suggest that early (inappropriate) CT scanning has low diagnostic yield without influencing ongoing management decisions and can result in a longer hospital stay.[29][48][70][71]
CECT is indicated in patients who fail to improve within 48 to 72 hours from onset of symptoms.[29]
Use CECT to assess disease severity and detect complications in any patient with presumed acute pancreatitis who fails to improve or if there is clinical deterioration.[48]
In UK practice, in line with recommendations from the International Association of Pancreatology/American Pancreatic Association and the World Society of Emergency Surgery, CECT for the purpose of assessing disease severity is not performed until 72 to 96 hours after the onset of symptoms, by which time the complete extent of necrosis should be visible.[29][48] An earlier CECT for assessing disease severity might be appropriate if there is clinical concern. Follow your local protocols.
Late-phase CECT (>1 week) can identify local complications.
Result
findings may include diffuse or segmental enlargement of the pancreas with irregular contour and obliteration of the peri-pancreatic fat, necrosis, or pseudocysts
endoscopic ultrasound (EUS)
Test
Use EUS or MRCP in preference to CECT to screen for choledocholithiasis if it is highly suspected in the absence of cholangitis and/or jaundice.[18]
EUS is indicated in patients considered to have idiopathic acute pancreatitis to exclude strictures, occult biliary microlithiasis, neoplasms, and chronic pancreatitis.[48]
A patient is considered to have idiopathic acute pancreatitis after a negative routine work-up including laboratory tests (including lipid and calcium level) and imaging (transabdominal ultrasound and CECT).[48]
Evidence: EUS for diagnosis of idiopathic acute pancreatitis
EUS performs well in establishing the aetiology of idiopathic cases.
A 2018 meta-analysis comparing EUS with MRCP in idiopathic acute pancreatitis found both had a role in establishing the aetiology but EUS had higher diagnostic accuracy than MRCP (64% vs. 34%) and should be preferred for establishing possible biliary disease or chronic pancreatitis.[72]
A systematic review of five studies (416 patients) with idiopathic acute pancreatitis reported a diagnostic yield of 32% to 88% for EUS in detecting biliary sludge, common bile duct stones, or chronic pancreatitis.[73]
Guidelines differ on the role of endoscopic investigations in patients with idiopathic acute pancreatitis for which an aetiology remains unclear after initial laboratory and imaging tests. The International Association of Pancreatology/American Pancreatic Association 2013 guideline recommends EUS in this scenario.[48] However, the American College of Gastroenterology (ACG) 2013 guideline recommends limiting the use of endoscopic investigations in this patient group on the basis that the balance of risks and benefits remains unclear. Where such investigations are performed, the ACG recommends they should only take place at pancreatic disease centres of excellence.[18]
Result
findings may include stones, biliary sludge, pancreatic divisum, and other abnormalities of the pancreatobiliary ducts
magnetic resonance cholangiopancreatography (MRCP)
Test
Use MRCP if CECT is contraindicated (e.g., renal insufficiency, contrast allergy).
MRCP and CECT are comparable in the early assessment of acute pancreatitis.[74]
MRCP is gaining favour over CECT in some centres, due to better imaging of biliary and pancreatic stones (down to 3 mm diameter), as well as better characterisation of solid versus cystic lesions.[75]
EUS or MRCP is preferred to CECT to screen for choledocholithiasis if it is highly suspected in the absence of cholangitis and/or jaundice.[18]
In patients with idiopathic acute pancreatitis who have had a negative routine work-up (laboratory tests, repeat abdominal ultrasound, and CECT) and negative endoscopic ultrasound, secretin-stimulated MRCP is recommended to identify rare morphological abnormalities or pancreatobiliary tumour. This is usually done after the patient has recovered fully from the acute phase.[18][48]
Evidence: MRCP for diagnosis of idiopathic acute pancreatitis
Secretin-stimulated MRCP is useful in diagnosing anatomical causes.
A 2018 meta-analysis comparing EUS with MRCP in idiopathic acute pancreatitis found that although EUS had higher diagnostic accuracy than MRCP overall (64% vs. 34%), secretin-stimulated MRCP was superior to EUS and standard MRCP in diagnosing anatomical alterations in the biliopancreatic duct system (e.g., pancreatic divisum).[72]
Result
findings may include stones, diffuse or segmental enlargement of the pancreas with irregular contour and obliteration of the peri-pancreatic fat, necrosis, or pseudocysts
arterial blood gas
Test
Patients may be hypoxaemic and require supplemental oxygen.
Result
hypoxaemia and disturbances in acid-base balance
PaO2 <60 mmHg is a sign of organ failure
Emerging tests
urinary trypsinogen-2
Test
Urinary trypsinogen-2 (>50 nanograms/mL) shows promise as a diagnostic test.
Elevated urinary trypsinogen-2 (>50 nanograms/mL) seems to be at least as sensitive and specific as serum lipase and amylase (both at the standard threshold of 3 times the upper limit of normal) for the diagnosis of acute pancreatitis.[48][58]
Urinary trypsinogen-2 is a rapid and non-invasive bedside test but is not yet widely available for clinical use.
A meta-analysis reported a pooled sensitivity of 82% and specificity of 94% for diagnosing acute pancreatitis.[76]
Result
elevated (>50 nanograms/mL)
serum IL-6 and IL-8
Test
Interleukin-6, interleukin-8, and interleukin-10 may be predictive markers for the development of severe acute pancreatitis.[77][78]
One study reported a sensitivity of 81% to 88% and specificity of 75% to 85% for IL-6 and a sensitivity of 65% to 70% and specificity of 69% to 91% for IL-8 for prediction of severe acute pancreatitis.[77]
Result
elevated levels may indicate increased risk of severe disease
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