Abstract
Background
Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction. However, it is unknown if the inhibition can be reduced by opioid antagonism with oral naloxone, and how this compares to osmotic laxative treatment.
Aims
To compare the effects of oxycodone and macrogol 3350 treatment (OX + PEG) versus combined oral oxycodone and naloxone (OXN) on anal sphincter function and gastrointestinal symptoms.
Methods
A randomised, double-blind, crossover trial was conducted in 20 healthy, male volunteers. Participants were randomised to five days treatment of OX + PEG or OXN. Anal resting pressure, anal canal distensibility, and rectoanal inhibitory reflex-induced sphincter relaxation were evaluated at baseline and on day 5. The Patient Assessment of Constipation questionnaire (PAC-SYM), stool frequency, and stool consistency were assed daily.
Results
Sphincter relaxation was reduced after OX + PEG treatment compared to OXN (difference = −17.6% [95% Cl;−25.2, −10.2]; P < 0.001). Anal resting pressure and anal canal distensibility did not differ between the treatments. PAC-SYM abdominal symptom subscale increased during OX + PEG compared to OXN (cumulated score: 3.2±2.3 vs. 0.2±1.8; P =0.002). Number of bowel movements was higher during OX + PEG vs. OXN (5.4±1.5 vs. 4.2±1.2; P = 0.035), but there was no difference in stool consistency (3.5±0.5 vs. 3.2±0.4; P = 0.14).
Conclusions
Sphincter relaxation was significantly reduced after OX + PEG compared to OXN. Evaluation of the rectoanal inhibitory reflex may serve as an important objective measure in future trials on treatment of opioid-induced bowel dysfunction.