HEMODYNAMIC AND ANALGESIC PROFILE AFTER INTRATHECAL CLONIDINE IN HUMANS - A DOSE-RESPONSE STUDY

Background: Epidural clonidine produces effective postoperative analge sia in humans. Observed side effects include hypotension, bradycardia, sedation, and dryness of the mouth. A recent clinical study demonstra ted that 150 mu g intrathecal clonidine administered postoperatively a s the sole analgesic agent was effective but produced hypotension and sedation. Animal studies have provided evidence of a biphasic effect o n blood pressure after intrathecal clonidine administration, but no da ta concerning this effect in humans currently exist. This study was pe rformed to evaluate the dose-response hemodynamic and analgesic profil es of intrathecal clonidine administered after a standard surgical int ervention, without perioperative administration of additional analgesi cs, local anesthetics, or tranquilizers. Methods: In a randomized pros pective double-blind study, 30 women who underwent elective cesarean s ection during general anesthesia with thiopental, nitrous oxide, and h alothane were studied. Forty-five minutes after tracheal extubation, a lumbar intrathecal puncture was performed, and the patients received 150 (group 1), 300 (group 2), or 450 (group 3) mu g clonidine. Postope rative analgesia was assessed on a visual analog scale at rest and aft er deep cough at standard time points up to 24 h. At the same time poi nts, blood pressure, heart rate, sedation, and respiratory rate also w ere recorded. Results: Intrathecal clonidine decreased pain in all thr ee groups both at rest and with coughing very shortly after injection, in a dose-dependent fashion. Clonidine 450 and 300 mu g reduced pain scores significantly earlier (3rd and 6th min after intrathecal inject ion respectively), compared with 150 mu g clonidine. Pain relief, defi ned as the time to first request for supplemental analgesic by patient s, lasted 402 +/- 75 min in group 1,570 +/- 76 min in group 2, and 864 +/- 80 min in group 3; significant differences among all groups; P < 0.01-0.001). Clonidine reduced mean arterial pressure compared with ba seline only in group 1 (21 +/- 13%, P < 0.05). Delayed hypotension or bradycardia were not encountered after any of the three dose studies. Sedation was evident in all groups, but group 3 patients were signific antly more sedated than group 1 and 2 patients. Respiratory rate and m otor activity of the lower extremities were unaffected in all three gr oups (differences not significant). Conclusions: These results demonst rate dose-dependent analgesia after intrathecal clonidine at doses as great as 450 mu g. The nearly immediate analgesic effect observed afte r intrathecal injection of 300 and 450 mu g clonidine strongly argues for a spinal rather than a systemic site of action of this alpha(2)-ad renergic agonist. After 300 and 450 mu g intrathecal clonidine a relat ive hemodynamic stability is observed, suggesting a presser effect at peripheral sites.