Decrease Emergence Agitation and Provide Pain Relief for Children Undergoing Tonsillectomy & Adenoidectomy
Condition: Obstructive Sleep Apnea
MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Emergence Delirium
Study type: Interventional
Phase: Phase 3

Summary: 
      Pediatric tonsillectomy (with or without adenoidectomy) is a brief but painful surgery
      carried out in children who very often also present with obstructive sleep apnea. To provide
      pain relief, i.e. analgesia, current practice relies on opioids , e.g., morphine or fentanyl.
      These narcotics are known to depress respiration and to increase the incidence of
      post-operative nausea and vomiting. These side effects are worrisome in this patient cohort.
      An alternative medication, dexmedetomidine, may have an opiate sparing effect and has a high
      safety profile in adults as well as in sedation in children. The purpose of this study is to
      determine if intravenous dexmedetomidine given as an infusion during general anesthesia for
      tonsillectomy or adenotonsillectomy reduces the incidence and severity of emergence
      agitation, improves analgesia and reduces nausea and vomiting in the 60 minutes following
      surgery.
    

Detailed description: 
      Emergence agitation (EA) from general anesthesia is a frequent phenomenon in children age
      1-10 yrs recovering from anesthesia that demands increasing nursing care in the PACU, delays
      reunion with parents and often causes dissatisfaction for parents, and may lead to adverse
      sequelae in some cases such as physical harm to the child, in particular to the site of
      surgery (1). Emergence agitation is a state of non purposeful restlessness an
      inconsolability. This state is often accompanied by thrashing, screaming, prolonged crying
      and disorientation. Children are generally unaware of their surroundings and cannot be
      consoled by the caregivers/parents. It is very disturbing for parents to observe this
      behavior in their children. It is also a safety issue for children and staff. These negative
      effects of EA have motivated clinicians to investigate possible etiologies and potential
      treatments for EA.

      EA may be in part due to the relative paucity of inhibitory neurotransmitters in children's
      central nervous system (CNS). As well, all modern anesthetics have been designed to be
      rapidly eliminated resulting in abrupt change from a state of anesthesia to a state of
      responsiveness. The result is a difficult problem managing these patients over a 30-50 minute
      period following pediatric anesthesia.

      We propose studying patients scheduled for tonsillectomy or adenotonsillectomy.
      Adenotonsillar hypertrophy may produce upper airway obstruction, dysphagia, dental
      malocclusion, altered orofacial growth, altered eustachian tube function, or pulmonary
      hypertension with cor pulmonale. Obstructive sleep apnea (OSA) is associated with loud
      snoring during sleep with periods of respiratory pauses terminated with gasping and agitated
      arousal and has been suggested to have developmental consequences including ADHD, failure to
      thrive, and nocturnal enuresis (2). Obstructive sleep apnea syndrome is most commonly
      associated with adenotonsillar hypertrophy and more children are now presenting for
      adenotonsillectomy (3). Tonsillectomy and adenotonsillectomy are highly successful in
      eliminating OSA in children and is considered first-line therapy if the family is amenable
      and there are no specific contraindications, and is approximately 85-95% effective in
      eliminating OSA in children (4). All children undergoing tonsillectomy or adenoidectomy
      should be considered to be at increased risk for perioperative airway problems (5). Opioids
      may cause respiratory depression, and thus present an added risk in patients undergoing
      tonsillectomy and adenotonsillectomy, especially in children with OSA (6).

      The purpose of this study is to determine if intravenous dexmedetomidine given as an infusion
      during general anesthesia for tonsillectomy or adenotonsillectomy reduces the incidence and
      severity of emergence agitation in the 60 minutes following surgery compared to normal
      practice. A second outcome is whether the need for intra-operative and postoperative
      analgesic narcotic medications is reduced.

      Dexmedetomidine, a specific alpha 2-adrenergic receptor agonist, has recently been studied
      for its sedative, amnestic, and analgesic properties and has been shown to be effective in
      providing sedation, decreased anesthetic requirements during surgery and in postanesthesia
      care units, and reduction in emergence agitation (7, 8, 9). Dexmedetomidine has been shown to
      enhance the analgesic action of nitrous oxide and furthermore it has also been shown to be
      effective as a total intravenous anesthetic agent in certain patients if doses are increased
      to a high enough level, with no respiratory depression (10, 11). If dexmedetomidine can be
      shown to reduce or eliminate emergence agitation, and provide effective intraoperative and
      postoperative analgesia without respiratory depression, this would give anesthesiologists a
      better option in the management of patients undergoing tonsillectomy and adenotonsillectomy.

      The dosing regimen for Dexmedetomidine in a loading dose of 1ug/kg with with a continuous
      infusion of 0.2-0.7 ug/kg is recommended for sedation in the Intensive Care Unit for adults.
      There is an increasing body of experience with use of Dexmedetomidine in pediatrics both for
      sedation and to reduce kg/hr. They observed a mean decline in heart rate (HR) and blood
      pressure (BP) from pre-sedation values of 15%, with 70% of patients showing a decline between
      1-30%. Despite the drop in HR and BP, all changes were still within the clinical range of
      normal for age (10). We are proposing 2 ug/kg as a loading dose with a maintenance dose of
      0.7ug/kg/hr during surgery, since we intend to use dexmedetomidine during tonsillectomy and
      adenotonsillectomy, a surgery which can stimulate a pain response and the surgery starts soon
      after the patient is intubated with no surgical preparation time . 2ug/kg is higher than the
      usual recommended dose, but has been used in children in the above study without any
      significant adverse events.
    

Intervention name(s): dexmedetomidine; fentanyl
Intervention type(s): Drug; Drug
Intervention description(s): 2 micrograms/kilogram as a bolus then 0.7 micrograms/kilogram infusion; 1 microgram/kilogram as a bolus
Other intervention name(s): Precedex; Sublimaze
Intervention MeSH terms: Fentanyl; Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: obstructive sleep apnea; tonsillectomy; adenoidectomy