Knoph Cecilie Siggaard, Joseph Nejo, Lucocq James, Olesen Søren Schou, Huang Wei, Dhar Jahnvi, Samanta Jayanta, Talukdar Rupjyoti, Capurso Gabriele, Preatoni Paoletta, Yadav Dhiraj, Windsor John, Drewes Asbjørn Mohr, Nayar Manu
Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Surgical and Translational Research Centre, University of Auckland, Auckland, New Zealand.
Pancreatology. 2025 Feb;25(1):12-19. doi: 10.1016/j.pan.2024.12.014. Epub 2024 Dec 29.
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.
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.
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).
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.
腹痛是急性胰腺炎（AP）的主要症状，常需使用阿片类药物治疗。本研究旨在探讨阿片类药物治疗与中度重症或重症AP之间的剂量依赖关系。
这是一项对前瞻性PAINAP数据库的事后分析，该数据库于2022年4月1日至6月30日期间从27个国家的118个中心招募首次发生AP的患者。提取基线人口统计学细节、阿片类药物治疗剂量和AP结局特征。根据每日剂量和持续时间计算每种使用的阿片类药物的静脉注射吗啡等效剂量（MEDs）。随后将它们汇总为累积MEDs。此外，记录每日平均静脉注射MEDs。使用多变量回归分析，探讨阿片类药物剂量与AP严重程度之间的关联。
最终队列包括1043例接受不同剂量阿片类药物的患者（51%为男性；中位年龄54岁）。大多数（79%）患者为轻度AP，14%为中度重症AP，7%为重症AP。累积MEDs中位数为20mg（四分位间距，8 - 48），而每日MEDs中位数为6（四分位间距，3 - 11），中位持续时间为3天（四分位间距，2 - 5）。中度重症或重症AP与每10mg累积静脉注射MEDs之间存在显著关联（比值比1.02（四分位间距1.00 - 1.03），P = 0.01）。考虑每日静脉注射MEDs时，这种关联不显著（P = 0.15）。
阿片类药物剂量与AP严重程度之间的关联在累积阿片类药物剂量方面呈剂量依赖性，但在每日剂量方面并非如此。在缺乏充分证据和潜在的反向因果关系偏倚的情况下，未来有必要开展研究以评估阿片类药物在AP中的安全性。
