Introduction: alpha(2)-Adrenozeptoragonisten agonists have shown antinociceptive and analgesic effects, which are not antagonized by naloxone. Therefore, the mechanism of action should be independent of opioid receptors. Most studies on this topic have been performed using clonidine. Experimentally the analgesic effect of clonidine can be suppressed by the inhibition of central adrenergic receptors. Furthermore, clonidine has analgesic effects at the spinal level. During recent years numerous studies have shown the analgesic effect of spinally or epidurally administered clonidine in humans. However, only very few studies have investigated the analgesic effect of parenterally administered clonidine in humans.
Methods: After the approval of the local ethical committee had been obtained, 60 patients (ASA I-III, age 18-65 years) scheduled for elective orthopaedic procedures were included in this double-blind randomized study. All patients gave their written consent on the day before the operation. Premedication was standardized and involved benzodiazepines. Isoflurane was used as the sole anaesthetic. Postoperatively the pain level of the patients was controlled by a visual analogue scale (VAS 0-10). When the VAS reached at least 5 and the patients requested an analgesic, they were randomly assigned to either the morphine, tramadol or clonidine group. Twenty patients received 5 mg morphine i.v., 20 patients received 50 mg tramadol and 20 patients received 150 clonidine i.v. If the analgesic effect was insufficient, the above-mentioned dosage was repeated after 30 min. The therapy was classified as a failure if no sufficent analgesia could be achieved within 60 min. These patients received 7.5 mg piritramide i.v. VAS and sedation were measured at 10-min intervals during the 1 st h and at 15-min intervals during the following 2h. Heart rate, blood pressure and oxygen saturation were measured at 5-min intervals during the whole study period. Statistical analysis of the data was performed by ANOVA, Wilcoxon test, Student'st-test and chi-square test using a level of significance ofP<0.05.
Results: All groups were comparable as regards their basic clinical parameters. Morphine, tramadol and clonidine significantly reduced the VAS within 20 min. During the whole study period the analgesic effect of clonidine was comparable with that of morphine and tramadol. No significant differences were observed in the number of repetitions after 30 min or in the failure rate. After 2 h sedation was significantly higher in the morphine group. No clinically relevant cardiovascular or respiratory side-effects were observed in any of the patients.
Discussion: In our study the analgesic effect of 150 mug clonidine i.v. was equivalent to that of 5 mg morphine i.v. and 50 mg tramadol. Our results in humans confirm the dosage relationship of 1ratio30 found by Eisenach in sheep. Further studies on the use of parenteral clonidine for postoperative analgesia seem to be warranted.