Opioids for abdominal pain in acute pancreatitis

The pancreas is a gland behind the stomach and close to the first part of the small intestine. It produces digestive juices, amylase, secreted into the small intestine and releases hormones, insulin and glucagon, into the bloodstream. Acute pancreatitis refers to a sudden inflammation of the pancreas. It happens when digestive juices become active inside the pancreas, causing swelling, bleeding and damage to the pancreas and its blood vessels. It is a serious condition and can lead to further problems. Common symptoms are severe pain in the upper abdomen, nausea, and vomiting. Treatment is usually a few days in hospital for fluids, antibiotics, and medicines to relieve pain, delivered by drip.

If there is severe pain, at least one type of pain relief (e.g. paracetamol, non-steroidal anti-inflammatory drugs, opioids) is generally used. Opioids, such as morphine and its derivatives, are commonly used, but without firm evidence for their effectiveness and safety. It is possible that they may hide the resolution of the disease, and may increase pain by causing spasms. The aim of this review is to clarify the appropriate use of opioids for abdominal pain in acute pancreatitis.

We searched a number of electronic databases up to June 2013. We include five randomised clinical trials (RCTs), with a total of 227 participants in this review. The opioids evaluated were buprenorphine, pethidine, pentazocine, fentanyl and morphine.

For participants needing additional pain relief, combined analysis of opioids (pentazocine and morphine) showed a significant benefit when compared with non-opioid treatments. Two trials showed that buprenorphine and pentazocine were each more effective than procaine. Our confidence in the stability of these effects is low, however, due to limitations in the number of studies and participants, and the low quality of the way the trials were run and reported. No serious or life-threatening adverse events were linked to the drugs being studied. One death was reported, in a procaine group, across all the included trials.

On the evidence so far, opioids may be an appropriate treatment option and might have the advantage of decreasing the need for additional pain relief. We found no clear difference in the risk of pancreatitis complications or serious adverse event between opioids and other pain relief treatments. However, the findings of this review are limited by the lack of information to allow full appraisal of the risk of bias, the measurement of relevant outcomes and the small numbers of participants covered by the trials.

Authors' conclusions: 

Opioids may be an appropriate choice in the treatment of acute pancreatitis pain. Compared with other analgesic options, opioids may decrease the need for supplementary analgesia. There is currently no difference in the risk of pancreatitis complications or clinically serious adverse events between opioids and other analgesia options.

Future research should focus on the design of trials with larger samples and the measurement of relevant outcomes for decision-making, such as the number of participants showing reductions in pain intensity. The reporting of these RCTs should also be improved to allow users of the medical literature to appraise their results accurately. Large longitudinal studies are also needed to establish the risk of pancreatitis complications and adverse events related to drugs.

Read the full abstract...

Acute pancreatitis is an acute inflammatory process of the pancreas that may also involve adjacent tissues and/or remote organ systems. Abdominal pain is the main symptom and is usually accompanied by nausea, vomiting and fever. Opoids are commonly used to manage pain in acute pancreatitis but there are still some uncertainties about their clinical effectiveness and safety.


To assess the effectiveness and safety of opioids for treating acute pancreatitis pain.

Search strategy: 

The search strategy included the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 6), MEDLINE (from 1950 to June 2013) and EMBASE (from 1980 to June 2013). There were no restrictions by language or publication status.

Selection criteria: 

We considered randomised clinical trials (RCTs) assessing the effectiveness of any opioid drug used for treating acute pancreatitis pain.

Data collection and analysis: 

Two review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RRs) for dichotomous data and calculated a 95% confidence interval (CI) for each RR. We performed an intention-to-treat (ITT) analysis. We undertook meta-analysis for some outcomes.

Main results: 

We included five RCTs with a total of 227 participants (age range 23 to 76 years; 65% men) with acute pancreatitis pain. The opioids assessed were intravenous and intramuscular buprenorphine, intramuscular pethidine, intravenous pentazocine, transdermal fentanyl and subcutaneous morphine.

One RCT, comparing subcutaneous morphine with intravenous metamizole reported non-significant reduction in the number of participants with improvements in pain intensity (primary outcome) (RR 0.50, 95% CI 0.19 to 1.33). Three studies compared analgesia using opioids with non-opioid treatments. After excluding one study that used opioids through continuous intravenous infusion, there was a decrease in the number of patients requiring supplementary analgesia (RR 0.53, 95% CI 0.30 to 0.93). In a single study, there were no differences in the number of patients requiring supplementary analgesia between buprenorphine and pethidine (RR 0.82, 95% CI 0.61 to 1.10).

Pancreatitis complications were not associated with a significant difference between the drugs tested. No clinically serious or life-threatening adverse events occurred related to treatment. No differences for this outcome were found between opioid and non-opioid treatments, or for type of adverse event (nausea-vomiting and somnolence-sedation). One death in the procaine group was reported across all the trials.

One RCT comparing pethidine with intramuscular buprenorphine reported non-significant differences of supplementary analgesic, adverse events or deaths. One RCT comparing fentanyl with placebo found no difference in adverse events.

The findings of this review are limited by the lack of information to allow full appraisal of the risk of bias, the measurement of relevant outcomes and the small numbers of participants and events covered by the trials.