Esben Bolvig Mark1,2,3, Mette Winther Klinge4, Debbie Grønlund1,3, Jakob Lykke Poulsen1,3, Vincent Schlageter5, S Mark Scott6, Klaus Krogh4, Asbjørn Mohr Drewes1,3. 1. Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark. 2. Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark. 3. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 4. Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aalborg, Denmark. 5. Motilis Medica SA, Lausanne, Switzerland. 6. Neurogastroenterology Group (GI Physiology Unit) Queen Mary University, London, UK.
Abstract
BACKGROUND: Opioid treatment often causes debilitating constipation. However, it is not well described how opioids affect colonic motility and whether opioid-induced constipation is due to either a decrease of powerful peristaltic contractions or "uncoordinated" peristalsis. The present study aims to investigate the effect of oxycodone on parameters of colonic motility and to determine whether motility is normalized by the opioid antagonist naloxegol. METHODS: In two randomized, double-blind crossover trials, oxycodone or placebo was administered to 25 healthy males (Trial A), while another 24 healthy males were administered oxycodone with naloxegol or placebo (Trial B). Colonic motility was assessed by tracking the progression of an electromagnetic capsule throughout the large intestine. Segmental colonic transit times and capsule movements were calculated using displacement distance and velocity. KEY RESULTS: In Trial A, colonic transit time increased during oxycodone treatment compared with placebo (39 vs 18 hours, P < .01). Displacement during long fast antegrade movements was shorter during oxycodone treatment than with placebo (10 vs 20 cm, P = .03). In Trial B, colonic transit time was faster during oxycodone + naloxegol than during oxycodone + placebo (40 vs 55 hours, P = .049), mainly caused by an increase of the percentwise fraction of distance covered by fast movements in the left colon (P = .001). CONCLUSION & INFERENCES: Oxycodone treatment impaired colonic motility, manifested as increased transit time, specifically decreased long fast antegrade movements, and addition of naloxegol improved motility dynamics. In humans, the increased transit time during opioid treatment is caused by a decrease in long fast movements rather than uncoordinated peristalsis.
RCT Entities:
BACKGROUND: Opioid treatment often causes debilitating constipation. However, it is not well described how opioids affect colonic motility and whether opioid-induced constipation is due to either a decrease of powerful peristaltic contractions or "uncoordinated" peristalsis. The present study aims to investigate the effect of oxycodone on parameters of colonic motility and to determine whether motility is normalized by the opioid antagonist naloxegol. METHODS: In two randomized, double-blind crossover trials, oxycodone or placebo was administered to 25 healthy males (Trial A), while another 24 healthy males were administered oxycodone with naloxegol or placebo (Trial B). Colonic motility was assessed by tracking the progression of an electromagnetic capsule throughout the large intestine. Segmental colonic transit times and capsule movements were calculated using displacement distance and velocity. KEY RESULTS: In Trial A, colonic transit time increased during oxycodone treatment compared with placebo (39 vs 18 hours, P < .01). Displacement during long fast antegrade movements was shorter during oxycodone treatment than with placebo (10 vs 20 cm, P = .03). In Trial B, colonic transit time was faster during oxycodone + naloxegol than during oxycodone + placebo (40 vs 55 hours, P = .049), mainly caused by an increase of the percentwise fraction of distance covered by fast movements in the left colon (P = .001). CONCLUSION & INFERENCES: Oxycodone treatment impaired colonic motility, manifested as increased transit time, specifically decreased long fast antegrade movements, and addition of naloxegol improved motility dynamics. In humans, the increased transit time during opioid treatment is caused by a decrease in long fast movements rather than uncoordinated peristalsis.
Authors: Paul T Heitmann; Paul F Vollebregt; Charles H Knowles; Peter J Lunniss; Phil G Dinning; S Mark Scott Journal: Nat Rev Gastroenterol Hepatol Date: 2021-08-09 Impact factor: 46.802