Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind placebo-controlled study of 40 patients.

We compared analgesic effects and pharmacokinetics of intraarticular versus intravenous administration of morphine after arthroscopic anterior cruciate ligament surgery. In a double-blind placebo-controlled study, 40 patients were randomly allocated to one of four treatment groups. Group I received 1 mg morphine intraarticularly and saline intravenously; group II received 5 mg morphine intraarticularly and saline intravenously; group III received 5 mg saline intraarticularly and morphine intravenously and group IV, the control group, received saline both intraarticularly and intravenously. The pain scores were significantly lower in groups I and II at 24 hours postoperatively than in group IV, and in group II during the rest of the postoperative period, as compared to groups III and IV. After intraarticular injection of 1 mg and 5 mg morphine, respectively, low concentrations of morphine-6-glucuronide (M6G) were found in the circulation, while morphine-3-glucuronide (M3G) appeared late after the injection in concentrations that considerably exceeded those of morphine in groups I and II. The analgesic effect of intraarticular morphine together with the low levels of morphine and morphine-6-glucuronide in plasma further strengthens the view that opioids have a peripheral mechanism of action.