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

Background: Dexmedetomidine is a highly selective α 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 41° to 50°C) 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 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients γ during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T ₅₀ to 47.2°C) and a decrease in the steepness of the curve (decreased γ 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 γ). 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.