No definite associations between opioid doses and severity of acute pancreatitis - Results from a multicentre international prospective study

Background: Abdominal pain is the cardinal symptom of acute pancreatitis (AP), often requiring opioid therapy. This study aimed to investigate the dose-dependent relationship between opioid therapy and moderately severe or severe AP.

Methods: This was a post-hoc analysis of the prospective PAINAP database, which recruited patients with first-time AP from 118 centres across 27 countries between April-June 30, 2022. Baseline demographic details, opioid treatment dose, and AP outcome characteristics were extracted. The intravenous morphine-equivalent doses (MEDs) of each opioid administered were calculated based on daily doses and duration. They were subsequently summarised into cumulative MEDs. Furthermore, mean daily intravenous MEDs were registered. Using multivariable regression analysis, associations between opioid doses and the severity of AP were explored.

Results: The final cohort consisted of 1,043 patients receiving various doses of opioids (51 % male; median age 54 years). Most (79 %) patients had mild, 14 % moderately severe, and 7 % severe AP. Median cumulative MED was 20 mg (IQR, 8-48), whereas median daily MED was 6 (IQR, 3-11), and median duration was 3 days (IQR, 2-5). There was a significant association between moderately severe or severe AP and cumulative intravenous MEDs per 10 mg (OR 1.02 (IQR 1.00-1.03), P = 0.01). When considering daily intravenous MEDs, this association was non-significant (P = 0.15).

Conclusions: The association between opioid doses and AP severity was dose-dependent with cumulative opioid doses but not with daily doses. In the absence of adequate evidence and potential reverse causation bias, future studies are warranted to assess the safety of opioids in AP.