Opioid-sparing Effect of Intranasal Dexmedetomidine
Condition: Tonsillar Hypertrophy
MeSH terms: Hypertrophy
Study type: Interventional

Summary: 
      Background: Management of postoperative pain in paediatric patients undergoing tonsillectomy
      remains a challenge that faces anesthesiologists in their daily practice. High dose of
      opioids are usually necessary and are responsible for side effects like nausea, vomiting,
      constipation, delayed hospital discharge and more importantly respiratory depression and
      sleep apnea. Dexmedetomidine is a selective alpha two agonist that has an analgesic and
      anxiolytic effect with minimal effects on respiratory drive.

      Goal of the study: The aim of this study is to assess the opioid sparing effect of
      preoperative intranasal dexmedetomidine as part of multimodal analgesia in the paediatric
      population undergoing tonsillectomy.

      Methods: This will be a prospective, randomised, controlled, double blinded clinical trial
      with 50 participants who will be randomised between two groups: dexmedetomidine group and
      control group. The dexmedetomidine group will receive intranasal dexmedetomidine in the
      preoperative holding area while the other group will receive the placebo.

      The primary endpoint will be the total fentanyl consumption in the perioperative period.
      Additionally, we will look at postoperative pain scores at 10, 30 and 60 minutes after
      recovery as well as the time to first opioid rescue analgesic and agitation scores as
      secondary endpoints. Blood pressure and hart rate will also be recorded throughout the study
      period.
    

Detailed description: 
      Tonsillectomy surgery is both common and painful in paediatric patients, usually requiring
      high doses of opioids, which are associated with many adverse effects. Dexmedetomidine is a
      sedative intravenous drug with analgesic and opioid-sparing effects but with side effects
      including (usually minor) bradycardia and hypotension which might delay hospital discharge.
      Intranasal dexmedetomidine, although off-label, has been extensively studied for its sedative
      effect as well as its safety profile and is associated with much less side effects
      (bradycardia and hypotension). It has however not being studied for its analgesic effects in
      children. The hypothesis is that preoperative intranasal dexmedetomidine will decrease total
      perioperative fentanyl consumption in children undergoing tonsillectomy.

      Fifty ASA 1 or 2 patients aged from 3 yo to 6 yo scheduled for tonsillectomy (+/-
      adenoidectomy +/- myringotomy) will be included in this prospective, randomised, controlled,
      double blind trial and then randomised in two groups: dexmedetomidine group (DG) and control
      group(CG).

      Exclusion criteria are: allergy to dexmedetomidine, paracetamol, ondansetron or
      dexamethasone, hepatic dysfunction, raised intracranial pressure or altered GCS or
      neuromuscular disease in addition to abnormal neurological development.

      Upon arrival in the operating theater holding area, the patients will receive either 2mcg/kg
      of dexmedetomidine (DG) or the equivalent volume of normal saline (CG), both administered
      intranasally with a mucosal atomizer device attached to the syringe and equally distributed
      in both nostrils. Although intranasal dexmedetomidine is off-label, it is routinely
      administered as a premedication including in our institution. The syringes of dexmedetomidine
      and normal saline will be prepared by a nurse and both the patients and the anaesthetists
      will be blinded of the content of the syringes. The patients will then be moved to the
      operating room and a proper monitoring will be applied (ECG, pulse oximeter, non-invasive
      blood pressure and capnograph). Anaesthesia will be induced with inhalation of Sevoflurane
      without nitrous oxide and fentanyl 1 mcg/kg as well as a neuromuscular blocking agent (at the
      discretion of the anaesthetist) will all be administered as soon as an intravenous cannula is
      inserted. The trachea will then be intubated before the start of surgery. During the surgery,
      the anaesthetist in charge will give boluses of 1 mcg/kg of fentanyl when deemed necessary
      (tachycardia, hypertension, movements of the patient). All the patients will receive the
      usual analgesia regimen of SKMC consisting of paracetamol (15 mg/kg), dexamethasone (0.15
      mg/kg) and ondansetron (0.1 mg/kg) before extubation.

      In the Post-Anaesthesia Care Unit (PACU), the patients will be administered 0.5 mcg/kg of
      fentanyl q10min if their pain score (measured by the FLACC scale) is > 2/10 and repeated
      until the score is < 3. The PACU nurses will be blinded to which group the patients belong.

      The patrients will be randomised in two arms, randomised 1:1, the dexmedetomidine arm (DG)
      and the control arm (CG). The patients of the DG will receive 2 mcg/kg of dexmedetomidine
      while the patients of the CG will receive normal saline instead, both will be administered
      intranasally with a mucosal atomiser device and equally distributed in each nostril. The
      sample size calculation was made according to the available literature on the opioid-sparing
      effect of intranasal dexmedetomidine with a type I error rate (alpha) of 5% and a type II
      error rate (power) of 80%. The result is 25 patients in each arm.

      Demographic data will be compared between CG and DG with a Student's t-test or a Chi-square
      test when appropriate. The total fentanyl consumption as well as the pain and agitation
      scores of the DG and the CG will be compared using a Student's t-test for mean comparison. A
      p<0.05 will be considered significant.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): Intranasal administration Dosage 2 mcg/kg
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment