Pharmacological interventions for managing acute pancreatitis

The prevalence of acute pancreatitis is between 5 and 30 per 100,000 population worldwide. It also represents the most common cause for gastrointestinal hospital admission in the United States.² The main causes of acute pancreatitis are alcohol and gall stones. Mortality rates are as high as 4.2% worldwide due to acute pancreatitis. In Australia, a recent study reported a mortality rate of 0.08%. The reported low incidence is most likely due to early diagnosis and supportive care.^2,3

The diagnosis of acute pancreatitis relies on having at least two of the following symptoms: increased serum lipase or amylase activity (at least three times higher than the normal range), confirmation of characteristics of acute pancreatitis using contrast enhanced computed tomography (CECT) and less commonly magnetic resonance imaging (MRI) or transabdominal ultrasonography and acute and persistent epigastric pain which is radiating to lower back.⁴

The management of acute pancreatitis relies on aggressive hydration with intravenous fluids and fasting. The main aim is to reduce morbidity and mortality associated with the disease. Current pharmacological management includes agents such as somatostatin or octreotide that decrease pancreatic secretions; protease inhibitors such as gabexate mesilate, aprotinin, ulinastatin and nafamostat; antioxidants such as vitamin C and selenium; platelet activating factors such as lexipafant; other agents that modulate the inflammatory pathway such as steroids and tumour necrosis factor-alpha (TNF-) antibody; probiotics; and antibiotics.⁵ This evidence summary presents the best available evidence regarding the effectiveness of these medications in reducing mortality.

Characteristics of the studies

Randomised, double-blind, placebo-controlled studies that described any of the above-mentioned medications were included in the review. Participants with acute pancreatitis irrespective of the severity or the type of acute pancreatitis were included.

Quality of the research Studies included in the report had a low or unclear risk of bias. Overall, the quality of the evidence ranged from low to moderate depending on the outcomes reported in the studies. The main sources of bias were selective reporting and incomplete outcome of data. A total of 21 studies had high risk of bias regarding funding of the studies.

Results

• The following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). The references of all the included trials were searched for further trials.
• The primary outcome measures included short-term mortality (for up to three months) and long-term mortality (follow-up for up to one year).
• The review included 84 RCTs with 8,234 participants. Six trials (658 participants) did not report on any of the outcomes of interest.
• The review examined many interventions including antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs, octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control.
• Most studies had a small number of participants except for the study with antibiotics. The majority of the studies included patients with severe acute pancreatitis.
• None of the studies found consistent benefits of the interventions in reducing mortality due to acute pancreatitis.
• Adverse events were reported in very few studies. Serious side effects were generally lower in patients taking octreotide, somatostatin plus omeprazole than the control group.
• The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430).
• None of the studies reported on patients’ quality of life.

Conclusion: Implication for practice

The review found there were no consistent benefits in any of the medications studied. Most of the studies had wide confidence intervals of either increasing or decreasing mortality. Further research with a large number of participants is required with a long follow-up.

DR HANAN KHALIL is the Director of the Centre for Chronic Disease Management, a collaborating centre of the Joanna Briggs Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, and a reviewer for the consumer group of the Cochrane Collaboration. She is also Editor in Chief of the International Journal of Evidenced Based HealthCare.

The purpose of this evidence summary is to present the best available evidence regarding the effectiveness of pharmacological interventions for the management of acute pancreatitis.

For the full review, please refer to Moggia E, Koti R, Belgaumkar AP, et al.¹

References

1. Moggia E, Koti R, Belgaumkar AP, et al. Pharmacological interventions for acute pancreatitis. Cochrane Database of Systematic Reviews 2017;(4): Art.No.: CD011384. doi: 10.1002/14651858.CD011384.pub2.
2. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas 2006;33:323-330.
3. Jacob AO, Stewart P, Jacob O. Early surgical intervention in severe acute pancreatitis: Central Australian experience. ANZ J Surg 2014; doi: 10.1111/ans.12707.
4. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis– 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62(1):102–11.
5. Bang UC, Semb S, Nojgaard C, et al. Pharmacological approach to acute pancreatitis. World Journal of Gastroenterology 2008;14(19):2968–76.