Analgesic Effect of Peripheral Dexmedetomidine
Condition: Third Molar Extraction
Intervention: local dexmedetomidine; Peripheral normal saline; IV dexmedetomidine
Intervention description: Preoperative normal saline infusion and 1mcg/kg dexmedetomidine infiltrated locally to wound at the end of operation.; Same volume of normal saline as dexmedetomidine is infiltrated and IV infusion.; IV dexmedetomidine 1mcg/kg peroperative and normal saline infiltrated to wound at the end of operation
Intervention MeSH terms: Dexmedetomidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Analgesia; Dental pain; Dexmedetomidine; Pain; Peripheral effects

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  American Society of Anesthesiologists (ASA) physical status I and II

          -  Age between 18 and 50 years of age with 4 bilateral impacted third molar teeth
             scheduled for extraction under general anaesthesia

        Exclusion criteria:

          -  Clinical history or electrocardiographic evidence of heart block

          -  Ischaemic heart disease

          -  Asthma

          -  Sleep apnoea syndrome

          -  Impaired liver or renal function

          -  Alcohol consumption in excess of 28 units per week

          -  Pregnancy

          -  Patient refusal

          -  Known psychiatric illness

          -  Chronic sedative or analgesic use, and regular use of or known allergy to
             dexmedetomidine, paracetamol or dextropropoxypheneopioids

          -  Patients with preoperative inflammation at the site of surgery were also excluded