Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis
Abstract
Background
The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen‐2, and urinary amylase for the diagnosis of acute pancreatitis, so that an informed decision can be made as to whether the person with abdominal pain has acute pancreatitis. There is currently no Cochrane review of the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen‐2, and urinary amylase for the diagnosis of acute pancreatitis.
Objectives
To compare the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen‐2, and urinary amylase, either alone or in combination, in the diagnosis of acute pancreatitis in people with acute onset of a persistent, severe epigastric pain or diffuse abdominal pain.
Search methods
We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.
Selection criteria
We included all studies that evaluated the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen‐2, and urinary amylase for the diagnosis of acute pancreatitis. We excluded case‐control studies because these studies are prone to bias. We accepted any of the following reference standards: biopsy, consensus conference definition, radiological features of acute pancreatitis, diagnosis of acute pancreatitis during laparotomy or autopsy, and organ failure. At least two review authors independently searched and screened the references located by the search to identify relevant studies.
Data collection and analysis
Two review authors independently extracted data from the included studies. The thresholds used for the diagnosis of acute pancreatitis varied in the trials, resulting in sparse data for each index test. Because of sparse data, we used ‐2 log likelihood values to determine which model to use for meta‐analysis. We calculated and reported the sensitivity, specificity, post‐test probability of a positive and negative index test along with 95% confidence interval (CI) for each cutoff, but have reported only the results of the recommended cutoff of three times normal for serum amylase and serum lipase, and the manufacturer‐recommended cutoff of 50 mg/mL for urinary trypsinogen‐2 in the abstract.
Main results
Ten studies including 5056 participants met the inclusion criteria for this review and assessed the diagnostic accuracy of the index tests in people presenting to the emergency department with acute abdominal pain. The risk of bias was unclear or high for all of the included studies. The study that contributed approximately two‐thirds of the participants included in this review was excluded from the results of the analysis presented below due to major concerns about the participants included in the study. We have presented only the results where at least two studies were included in the analysis.
Serum amylase, serum lipase, and urinary trypsinogen‐2 at the standard threshold levels of more than three times normal for serum amylase and serum lipase, and a threshold of 50 ng/mL for urinary trypsinogen‐2 appear to have similar sensitivities (0.72 (95% CI 0.59 to 0.82); 0.79 (95% CI 0.54 to 0.92); and 0.72 (95% CI 0.56 to 0.84), respectively) and specificities (0.93 (95% CI 0.66 to 0.99); 0.89 (95% CI 0.46 to 0.99); and 0.90 (95% CI 0.85 to 0.93), respectively). At the median prevalence of 22.6% of acute pancreatitis in the studies, out of 100 people with positive test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 74 (95% CI 33 to 94); 68 (95% CI 21 to 94); and 67 (95% CI 57 to 76) people have acute pancreatitis, respectively; out of 100 people with negative test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 8 (95% CI 5 to 12); 7 (95% CI 3 to 15); and 8 (95% CI 5 to 13) people have acute pancreatitis, respectively. We were not able to compare these tests formally because of sparse data.
Authors' conclusions
As about a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with the evaluated tests, one should have a low threshold to admit the patient and treat them for acute pancreatitis if the symptoms are suggestive of acute pancreatitis, even if these tests are normal. About 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, therefore it is important to consider other conditions that require urgent surgical intervention, such as perforated viscus, even if these tests are abnormal.
The diagnostic performance of these tests decreases even further with the progression of time, and one should have an even lower threshold to perform additional investigations if the symptoms are suggestive of acute pancreatitis.
PICOs
Plain language summary
Blood and urine tests for the diagnosis of acute pancreatitis (sudden inflammation of pancreas)
Background
The pancreas is an organ in the abdomen (tummy) that secretes several digestive enzymes (substances that break down the food we eat) into the pancreatic ductal system, which empties into the small bowel. The pancreas also contains the islets of Langerhans, which secrete several hormones such as insulin (which helps regulate blood sugar). Acute pancreatitis is sudden inflammation of the pancreas, which can lead to damage of the heart, lungs, and kidneys and cause them to fail. Acute pancreatitis usually manifests as upper abdominal pain radiating to the back. However, there are several potential causes of upper abdominal pain. It is important to determine if someone with abdominal pain has acute pancreatitis or another illness in order to start appropriate treatment. Blood tests such as serum amylase and serum lipase, as well as urine tests such as urinary trypsinogen‐2 and urinary amylase, can be used to determine if someone with abdominal pain has acute pancreatitis. It is usually the case that a patient is considered to have acute pancreatitis only when amylase or lipase levels are three times the upper limit of normal. With regard to urinary trypsinogen‐2, a level of more than 50 ng/mL of trypsinogen‐2 in the urine is considered an indication of acute pancreatitis. With regard to urinary amylase, there is no clear‐cut level beyond which someone with abdominal pain is considered to have acute pancreatitis. At present it is unclear whether these tests are equally effective or if one of the tests is better than the other in the diagnosis of acute pancreatitis in people with sudden‐onset abdominal pain. We determined to resolve this question by performing a literature search for studies reporting the accuracy of the above mentioned blood and urine tests. We included studies reported until 20 March 2017.
Study characteristics
We identified 10 studies reporting information on 5056 people with abdominal pain that started suddenly. The studies included pancreatitis due to all causes.
Quality of evidence
All of the studies were of unclear or low methodological quality, which may result in arriving at false conclusions. We excluded the study that contributed approximately two‐thirds of the participants included in this review from the results of the analysis presented below due to concerns about whether the participants included in the study are typical of those seen in the emergency department.
Key results
The accuracy of serum amylase, serum lipase, and urinary trypsinogen‐2 in making the diagnosis of acute pancreatitis was similar. About a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with these tests. The patient should be admitted and treated as having acute pancreatitis, even if these tests are normal, if there is a suspicion of acute pancreatitis. As about 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, it is important to consider other conditions that require urgent surgery, even if these tests are abnormal. The diagnostic performance of these tests decreases even further with the progression of time, and additional investigations should be performed if there is a suspicion of acute pancreatitis.
