SYSTEMIC AND CENTRAL EFFECTS OF MORPHINE ON GASTRODUODENAL MOTILITY

Gastrointestinal side effects still constitute a major drawback in bot h acute and chronic use of opioids. The exact mechanism behind the gas trointestinal effects is not known, but experimental studies indicate both central and peripheral actions. In an attempt to clarify to what extent the systemic effects of morphine after epidural administration contribute to the action on gastrointestinal motility, a study aiming to resemble the situation with epidural morphine was designed. Twenty healthy male volunteers were randomly allocated to two groups. Group o ne (n=10) received intrathecal (0.4 mg) and intramuscular (4 mg) morph ine (IT-IM-group). Group two (n=10) received intrathecal (0.4 mg) morp hine and i.m. saline F-group). Gastroduodenal activity was assessed by gastric emptying, manometry and electrogastrography. The plasma and u rine concentrations of morphine and its inactive metabolite morphine-3 - and active metabolite morphine-6-glucuronide were also determined. D uring the fasted state the gastrointestinal activity is characterised by a cyclic pattern with a duration of 80-120 min in the duodenum comp rising three different phases with intense activity during Phase III. This pattern was seen in all volunteers. After the intrathecal adminis tration the Phase III activity occurred significantly earlier in the I T-IM group (median 31 min; IR 34 min) compared to IT group (82 min; 37 min) (P<0.01). The number of Phase ms was higher in the IT-IM group d uring the first 4 h after the morphine administration, compared to the IT group. However, after 6 h, there was no difference between the gro ups. The propagation velocity of Phase III decreased significantly in both groups (P<0.001), but there was no difference between the groups. Tachygastria increased significantly with time in both groups. The ac etaminophen absorption test showed that the area under the concentrati on curve (120 min) was significantly smaller in the IT-IM group compar ed to the IT group (P<0.05). There were no measurable plasma concentra tions of morphine or the glucoronidated metabolites M3G and M6G in the group that only received intrathecal morphine. This study showed that intrathecal morphine (0.4 mg) influenced gastroduodenal motility and that intramuscular morphine (4 mg) gave additional effects. These resu lts might be applicable to the epidural situation and are indirect evi dence that the gastroduodenal effects of epidural morphine are caused by both central and systemic effects of morphine.