Dexmedetomidine pharmacodynamics: Part II - Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers

Background: Dexmedetomidine is a highly selective alpha(2)-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods: This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41degrees to 50degreesC) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results: Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T-50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1degreesC at baseline to 48.4degrees and 49.1degreesC during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients gamma during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T-50 to 47.2degreesC) and a decrease in the steepness of the curve (decreased gamma from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T-50 and gamma). Conclusion: As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.