The Impact of Opioid Treatment on Regional Gastrointestinal Transit

Abstract

Background/aims: To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact ofopioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GItransit times using the 3-dimensional (3D)-Transit system.

Methods: Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. AdverseGI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipationsymptom 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.

Results: GI 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.

Conclusions: Self-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.

Keywords: Analgesics; Constipation; Gastrointestinal transit; Opioid.

Figure 1

Study enrolment and randomisation.

Figure 2

Example of 3-dimensional trajectory of colonic passage of a single capsule illustrated in the custom designed interactive graphical user interface. “Start” marks the ileocecal passage and “End” marks the expulsion of the capsule. A red line represents a progression of less than 50 mm the last 10 minutes. A blue line represents a progression of more than 50 mm during the last 10 minutes. Hepatic flexure, splenic flexure, and descending end can be marked in the trajectory in order to calculate segmental colonic transits.

Figure 3

Bowel function index (BFI) and total gastrointestinal symptom rating scale (GSRS) results. From the left the first figure depicts the average BFI scores from day 1 and day 5 for both treatments. The second figure shows the total GSRS. Data are presented as means ± SEM.