TY - JOUR
T1 - No Effect of Methylnaltrexone on Acute Pancreatitis Severity
T2 - A Multicenter Randomized Controlled Trial
AU - Knoph, Cecilie Siggaard
AU - Cook, Mathias Ellgaard
AU - Novovic, Srdan
AU - Hansen, Mark Berner
AU - Mortensen, Michael Bau
AU - Juul Nielsen, Liv Bjerre
AU - Høgsberg, Irene Maria
AU - Salomon, Celina
AU - Lindqvist Neergaard, Celine Emilie
AU - Aajwad, Aseel Jabbar
AU - Pandanaboyana, Sanjay
AU - Sørensen, Lone Schmidt
AU - Thorlacius-Ussing, Ole
AU - Frøkjær, Jens Brøndum
AU - Olesen, Søren Schou
AU - Drewes, Asbjørn Mohr
N1 - Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
PY - 2024/6/25
Y1 - 2024/6/25
N2 - INTRODUCTION: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality.RESULTS: In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated.DISCUSSION: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.
AB - INTRODUCTION: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality.RESULTS: In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated.DISCUSSION: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.
U2 - 10.14309/ajg.0000000000002904
DO - 10.14309/ajg.0000000000002904
M3 - Journal article
C2 - 38916223
SN - 0002-9270
VL - 119
SP - 2307
EP - 2316
JO - The American journal of gastroenterology
JF - The American journal of gastroenterology
IS - 11
ER -