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

Luis I. Cortinez, Yung Wei Hsu, Sam T. Sum-Ping, Christopher Young, John C. Keifer, David MacLeod, Kerri M. Robertson, David R. Wright, Eugene W. Moretti, Jacques Somma

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1077-1083
Number of pages7
JournalAnesthesiology
Volume101
Issue number5
DOIs
StatePublished - Nov 2004

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Dexmedetomidine
Analgesics
Healthy Volunteers
Sigmoid Colon
Visual Analog Scale
remifentanil
Hypnotics and Sedatives
Forearm
Analgesia
Adrenergic Receptors
Opioid Analgesics
Hot Temperature
Pain
Temperature

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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Dexmedetomidine pharmacodynamics : Part II - Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. / Cortinez, Luis I.; Hsu, Yung Wei; Sum-Ping, Sam T.; Young, Christopher; Keifer, John C.; MacLeod, David; Robertson, Kerri M.; Wright, David R.; Moretti, Eugene W.; Somma, Jacques.

In: Anesthesiology, Vol. 101, No. 5, 11.2004, p. 1077-1083.

Research output: Contribution to journalArticle

Cortinez, LI, Hsu, YW, Sum-Ping, ST, Young, C, Keifer, JC, MacLeod, D, Robertson, KM, Wright, DR, Moretti, EW & Somma, J 2004, 'Dexmedetomidine pharmacodynamics: Part II - Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers', Anesthesiology, vol. 101, no. 5, pp. 1077-1083. https://doi.org/10.1097/00000542-200411000-00006
Cortinez, Luis I. ; Hsu, Yung Wei ; Sum-Ping, Sam T. ; Young, Christopher ; Keifer, John C. ; MacLeod, David ; Robertson, Kerri M. ; Wright, David R. ; Moretti, Eugene W. ; Somma, Jacques. / Dexmedetomidine pharmacodynamics : Part II - Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. In: Anesthesiology. 2004 ; Vol. 101, No. 5. pp. 1077-1083.
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abstract = "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.",
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T2 - Part II - Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers

AU - Cortinez, Luis I.

AU - Hsu, Yung Wei

AU - Sum-Ping, Sam T.

AU - Young, Christopher

AU - Keifer, John C.

AU - MacLeod, David

AU - Robertson, Kerri M.

AU - Wright, David R.

AU - Moretti, Eugene W.

AU - Somma, Jacques

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N2 - 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.

AB - 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.

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