The Impact of Opioid Treatment on Regional Gastrointestinal Transit

Abstract

Background/AimsTo employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GI transit times using the 3-dimensional (3D)-Transit system. MethodsTwenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. Adverse GI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab ® graphical user interface. ResultsGI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P = 0.001). No associations between questionnaire scores and segmental transit times were detected. ConclusionsSelf-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation.

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

“…11 For the PR naloxone period, our results are somewhat in contrast to a scintigraphic transit study by Smith et al, 22 who showed that a single dose of 10 mg PR naloxone in combination with 20 mg PR oxycodone significantly reduced colonic transit compared to PR oxycodone alone. The reason for this discrepancy between the studies remains obscure, but may reflect the different methodologies used to assess transit times.…”

“…27 In our previous study, the BFI score increased 34 points during PR oxycodone treatment. 11 Thus, both treatments seem to have a minor positive effect on BFI compared to our previous study, although the difference may not be significant. It could also be argued that neither of the treatments was successful in reducing the constipating effects of oxycodone assessed by the BFI scores.…”

“…Interestingly, macrogol treatment did not decrease transit time in comparison to the study where we administered PR oxycodone alone. 11 The pathophysiological basis for OIC is caused by hyperpolarization of enteric neurons and reduction in neurotransmitter release thereby inhibiting motility. 23 Macrogol acts by increasing stool volume through increased hydration, thereby triggering colonic motility.…”

“…The recently suggested definition for OIC by the Rome IV working group is an important step towards easier comparison of trials evaluating OIC treatment, 10 but these should ideally also include objective assessments. We have previously developed a model of OIC in healthy volunteers and shown that oxycodone causes symptoms of OIC, prolongs regional GI transit times, 11 and increases colorectal volumes. 12 The model for OIC in healthy volunteers allows for interventional studies of OIC not influenced by confounders such as comorbidity, activity level or concomitant drug that can all cause constipation and hence make studies in patients difficult to interpret.…”

Peripherally acting &mu;-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

“…The use of opioids for 5 days produced nearly twofold patient-reported symptoms of constipation in opioid-treated patients vs placebo patients ( P <0.001) and an objectively measured 41% segmental colorectal volume increase in the cecum and/or ascending colon ( P =0.005 vs placebo) 2. After 5 days of oxycodone therapy, the median gastrointestinal (GI) transit time increased from 22.2 hours to 43.9 hours ( P <0.001) 3. Thus, the short- as well as long-term use of opioids can result in bowel-related symptoms, most notably OIC.…”