Acute pancreatitis is a frequent gastrointestinal disease, often characterized by severe abdominal pain. As such, pain control is crucial for managing the disease. Opioids are considered effective for pain control, but safety apprehensions have been raised in acute pancreatitis. Nevertheless, there is a significant paucity of international recommendations for pain control in acute pancreatitis. Peripherally acting µ-opioid antagonists, such as methylnaltrexone, may counteract harmful effects induced by opioids, but their role in acute pancreatitis has never been explored.

This thesis aimed to explore global opioid use and its association with morbidity, as well as to examine the effects of continuous intravenous methylnaltrexone in patients with acute pancreatitis. For this, two clinical studies were conducted: the observational PAINAP study, involving 2,119 patients across 118 centers, and the randomized clinical PAMORA-AP trial, involving 105 Danish patients.

In study I, it was shown that opioids are often utilized for pain management with significant intercontinental differences (paper I). Associations between opioid use and more severe disease are likely affected by confounding by indication (paper II). In study II, 48 hours of continuous intravenous infusions with methylnaltrexone did not change the outcome of acute pancreatitis (paper III). Methylnaltrexone also did not affect the gastrointestinal transit time, as measured by a simple CT-based radiopaque marker method (paper IV).

In conclusion, opioids are commonly used for pain management in acute pancreatitis, and peripheral opioid antagonism does not alter the disease outcome. Further studies on the efficacy and safety of opioid use as well as international guidelines on pain management in acute pancreatitis are needed.