Analgesic Effect of Peripheral Dexmedetomidine
Dexmedetomidine is an alpha 2-adrenoreceptor agonist, which provides sedation, analgesia and anxiolysis in clinical practice (Cortinez et al., 2004,Hall et al., 2000). Three types of alpha 2-adrenergic receptor subtypes are found in the human body and they have been designated alpha 2A, alpha 2B and alpha 2C. The alpha 2A subtype is most likely responsible for the analgesic properties of dexmedetomidine in both peripheral and central sites (Kingery et al., 2000, Smith et al., 2001). Activation of central alpha 2-adrenoreceptors in the locus ceruleus (Correa-Sales et al., 1992) and the dorsal horn of the spinal cord (Gaumann et al., 1992b) are responsible for both analgesic and sedative effects. Dexmedetomidine has a very high alpha 2 to alpha 1 selectivity, 1620 to 1, or approximately 8 times that of clonidine. It is also 4 to 6 times more potent than clonidine by weight (Bhana et al., 2000).
Although dexmedetomidine produces dose dependent sedation upon intravenous administration, its the analgesic effect is of dexmedetomidine is more variable and controversial. In an ischaemic pain model in healthy volunteers, a single bolus of dexmedetomidine produced a 50% reduction in pain scores when compared to placebo (Jaakola et al., 1991). In another volunteer study using the cold pressor test, dexmedetomidine 1 µg/kg over 10 minutes followed by an infusion of 0.2 to 0.6 µg/kg/hour reduced pain by approximately 30% (Hall et al., 2000). However, when administered as a target controlled infusion at concentrations ranging from 0.09 to 1.23 ng/mL, dexmedetomidine had no analgesic effect in human volunteers subjected to heat and electrical pain, although sedation was produced (Memis et al., 2004).
Clonidine and dexmedetomidine are two common alpha 2 agonists used clinically. Although clonidine former has been used successfully in regional analgesia and anesthesia (Gabriel et al., 2001)., There are only very few studies evaluating the peripheral analgesic effects of dexmedetomidine. Since acute postoperative dental pain is a common analgesia model (Cooper, 1991; US Food and Drug Administration 1992), the investigators conducted this study, aiming to assess the postoperative analgesic efficacy of peripheral dexmedetomidine after bilateral third molar surgery under general anaesthesia. The analgesic effects were compared up to the 72nd hour postoperatively in order to evaluate any potential preventive analgesic effect.
|Third Molar Extraction||Drug: local dexmedetomidine Drug: Peripheral normal saline Drug: IV dexmedetomidine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effectiveness of Peripheral Dexmedetomidine for Bilateral Third Molar Surgery Under General Anaesthesia|
- Pain intensity on resting and during mouth opening after dental operation [ Time Frame: 2 years ]
- Analgesic consumption, time to first analgesics, side effects, recovery from general anesthesia, satisfaction score [ Time Frame: 2 years ]
|Study Start Date:||February 2006|
|Study Completion Date:||March 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
|Active Comparator: Local Dexmedetomidine||
Drug: local dexmedetomidine
Preoperative normal saline infusion and 1mcg/kg dexmedetomidine infiltrated locally to wound at the end of operation.
Other Name: Precedex
|Placebo Comparator: Normal Saline||
Drug: Peripheral normal saline
Same volume of normal saline as dexmedetomidine is infiltrated and IV infusion.
|Active Comparator: IV dexmedetomidine||
Drug: IV dexmedetomidine
IV dexmedetomidine 1mcg/kg peroperative and normal saline infiltrated to wound at the end of operation
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