Effect of A Single Dose of Lorazepam on Salivary Cortisol Response in Children Undergoing Digestive Endoscopy:
Condition: Anxiety
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the effect of a single dose of Lorazepam on
      salivary cortisol in children undergoing digestive endoscopy. To do so, the patients will be
      randomized in three groups. The first group receives the Lorazepam, the second group receives
      a placebo and the last group receives no intervention. Each patient will have three saliva
      samples taken at three different time point on the day of the endoscopy and will be asked to
      fill out questionnaires on anxiety and overall satisfaction of the procedure.
    

Detailed description: 
      Background: Pediatric digestive endoscopies (gastroscopy and colonoscopy) are invasive
      procedures. All endoscopic procedure are conducted in the operating room either under
      intravenous (IV) sedation or general anesthesia. More than 50% of procedures are performed
      using IV sedation. The current sedation protocol in the endoscopy suite is a combination of
      Midazolam (0.1 mg/kg) and Fentanyl (1 microgram/kg) in all children. The children undergoing
      colonoscopies receive and additional administration of Ketamine (0.5 mg/kg).

      In a previous study performed in children 10-18 years undergoing upper and lower endoscopy,
      the investigators found that despite this regimen, 25% of the children expressed a
      significantly high level of pain during endoscopy under IV sedation.

      Because general anesthesia is not available for all children, it is important to investigate
      strategies that could help in minimizing the discomfort and pain during the procedure.

      Salivary cortisol (sCortisol) has been used in several pediatric studies to determine the
      level of stress in children prior to various medical procedures. In another study done at our
      site, the investigators have found sCortisol to be a reliable biomarker of stress for
      children undergoing digestive endoscopies. Furthermore, the mean baseline sCortisol levels
      were higher in the group that experienced procedural pain.

      Lorazepam is a a rapid onset benzodiazepine that has anxiolytic and sedative properties that
      has been approved by Health Canada as an adjunct therapy for the relief of excessive anxiety
      that might be present prior to surgical interventions.

      Objective:

      The primary objective is to investigate the effect of Lorazepam as compared to placebo on the
      change of the level of sCortisol between baseline (C1) and immediately before endoscopy (C2)
      in adolescents undergoing a gastroscopy or a colonoscopy. The investigators think that it
      might be possible to modulate the stress response with the administration of a benzodiazepine
      as soon as the children arrives at the hospital. Thus children could have a better experience
      of the digestive endoscopic procedure (less pain and more comfort).

      The secondary outcome measure will be:

      (1) the proportion of children experiencing procedural pain, (2) the duration of endoscopic
      procedures, (3) children satisfaction, (4) physician and nurse satisfaction (5) the total
      dose of Fentanyl and Ketamine per kilogram body weight delivered during the procedure and (6)
      the mean change between pre-op and postop cortisol levels between the two groups.

      Safety outcomes measures: The following adverse events will be sought before and during the
      endoscopy: prolonged drowsiness, hypotension, hypertension, desaturation, bradycardia.

      Exploratory outcomes: the mean change between pre-op and postop cortisol levels in the Group
      C (No intervention) compared to Group A and B.

      Methods:

      In this randomized controlled trial children will be assigned to one of the three following
      groups (no intervention, placebo and active drug). The investigators will collect salivary
      samples to measure the levels of sCortisol and investigate their variation between three
      timepoint ( at arrival at the hospital, right before the procedure and right after the
      procedure). sCortisol levels will be correlated to a questionnaire evaluating the anxiety
      level in the patient. The research team will also evaluate the pain experienced during the
      procedure using the Nurse-Assessed Patient Comfort Score (NAPCOMS): a validated tool for the
      evaluation of pain in subjects undergoing endoscopies).
    

Intervention name(s): Lorazepam; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Patient receives one or two tablet of 0,5mg Lorazepam according to body weight; Patient receive one of two tablet of Placebo according to body weight
Other intervention name(s): Apo-Lorazepam
Intervention MeSH terms: Lorazepam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment