Effect of Dexmedetomidine of Gastrointestinal Motility
Condition: Anesthesia
Study type: Interventional
Phase: Phase 4

Summary: 
      Anorectal manometry requires that the patient be able to respond to command and not receive
      any medications which could alter muscle tone or motility. In the pediatric population,
      anorectal manometry can be psychologically challenging to parents and their child, as it is
      traditionally performed without adjuvant sedation or anesthesia. Sedatives and anesthesia can
      alter motility and smooth muscle activity, as well as render it difficult or impossible for
      the child to follow commands required of the study. Patient or parent non-compliance,
      inability to follow commands or to tolerate the procedure often renders the study invalid or
      impossible to complete. Dexmedetomidine is a sedative who's effect on anorectal musculature
      has not been studied nor determined. It would be important to determine whether it spares
      smooth muscle function, as it would provide a viable option to provide sedation to children
      while still preserving their ability to respond to command. The primary objective of this
      study is to examine the effects of dexmedetomidine on gastrointestinal smooth muscle by
      observing changes in anorectal manometry before and after dexmedetomdine administration.
    

Detailed description: 
      Primary objective:

      To examine the effects of dexmedetomidine on intra-anal pressure and the dose response curve
      to balloon distention by comparing the baseline measurements with those after dexmedetomidine
      administration.

      Dexmedetomidine is an alpha-2 agonist that is considered to be a smooth muscle relaxant. It's
      a potential use as a sedative for endoscopies has been considered. It is important to know
      whether or not it has effect on smooth muscle tone and would affect manometry studies in
      those patients who could receive it. The investigator hypothesizes that dexmedetomidine will
      have minimal effects in the dosing that is being administered.

      Background:

      Anorectal manometry requires that the patient be able to respond to command and not receive
      any medications which could alter muscle tone or motility. These patients typically have the
      manometry performed without any adjuvant sedatives, anesthetics or medications. In the
      pediatric population, anorectal manometry can be psychologically challenging to parents and
      their child, particularly without adjuvant sedation or anesthesia. There are some exceptional
      circumstances which require sedation/anesthesia administration for these procedures, either
      because the children are young (< 5 years), they have behavioral issues (like autism) or
      because they have severe anxiety. In those patients with severe issues even general
      anesthesia may be needed. The risk of administering any medication to these patients is that
      they can alter motility and smooth muscle activity, consequently artificially altering the
      results of the anal manometry. It is important to know which medications can be administered
      without affecting anal muscle tone. Dexmedetomidine is a newer sedative and anxiolytic. It
      could be valuable for anxiolysis for anal manometry. It's effect on anal smooth muscle,
      however, has never been studied. It would be important to determine whether it spares smooth
      muscle function, as it would provide a viable option to provide sedation to children while
      still preserving their ability to respond to command.

      Dexmedetomidine is one of the standard drugs administered for sedation in children who
      require sedation for diagnostic (gastroendoscopic upper and lower procedures) and radiologic
      diagnostic imaging studies (MRI, CT and Nuclear Medicine). Over 17,000 infants, children and
      developmentally compromised young adults have been sedated with dexmedetomidine at Boston
      Children's Hospital without a cardiac or respiratory arrest, or a need to provide positive
      pressure assisted ventilation.

      Methods:

      Patients will undergo the usual anal manometry study, with no adjuvant medications, per
      routine practice currently in the gastrointestinal unit. Following completion of manometry,
      0.5 mcg/kg DEX will be administered over 1 minute followed by an infusion of 0.15 mcg/kg/hr.
      Manometry measurements will be followed for 15 minutes in response to DEX.

      Definition of Primary Endpoint:

      Primary outcome: To examine the effects of dexmedetomidine on intra-anal pressure and the
      dose response curve to balloon distention by comparing the baseline measurements with those
      after dexmedetomidine administration. The pressure measurements will be recorded by the
      research team member who will be present, every 30 seconds starting from 5 minutes prior to
      DEX to 15 minutes following DEX administration.

      Data Analysis Plan:

      Data will be analyzed after the completion of the study. The manometry measurements will be
      done blindly by one of the investigators.

      The following endpoints will be analyzed at the completion of the study: time to meet
      modified Aldrete discharge criteria, adverse events, need for unplanned airway interventions,
      intravenous anesthetic duration of sedation, presence of agitation/delirium (PAED score), and
      time of BIS score to return to baseline (pre-sedation level).

      Statistical Power and Sample Considerations:

      The study was powered and sample size calculated assuming a mean intra-anal pressure of 90
      mmHg, with a mean reduction to 65 mmHg, and a standard deviation of 32. With a significance
      level of 0.05, it would require approximately 15 subjects to achieve power of 80.3%.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): Patients will undergo the usual anal manometry study, with no adjuvant medications, per routine practice currently in the gastrointestinal unit. Following completion of manometry, 0.5 mcg/kg DEX will be administered over 1 minute followed by an infusion of 0.15 mcg/kg/hr. Manometry measurements will be followed for 15 minutes in response to DEX.
Intervention MeSH terms: Dexmedetomidine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other