EFFECT OF A SINGLE DOSE OF LORAZEPAM ON SALIVARY CORTISOL RESPONSE IN CHILDREN UNDERGOING DIGESTIVE ENDOSCOPY: A RANDOMIZED DOUBLE-BLINDED STUDY.
Rational: In a previous study, we found that nearly one third of children undergoing colonoscopy under intravenous (IV) sedation expressed a significant level of pain during colonoscopy despite the sedation regimen. The baseline levels of preoperative salivary cortisol (sCortisol) were very high for these patients. In a subsequent pilot randomized controlled trial (RCT), we demonstrated the feasibility of the administration of Lorazepam (an anxiolytic drug) as compared to placebo as oral premedication.
Hypothesis: by mediating the stress response using Lorazepam, children will be prone to less pain or discomfort during endoscopy.
Objectives : The primary objective is to investigate the effect of Lorazepam, as adjuvant therapy, on the level of pain during colonoscopy. The secondary objectives will be to investigate the sedation levels, procedure duration, physician satisfaction, changes in the levels of sCortisol between baseline and after administration of the study agent and the rate of adverse events in the two groups.
Methods: The ENDOLORA study is a double-blinded RCT. Children aged 9-18 years undergoing a colonoscopy under IV sedation, will be randomly assigned to one of the two following groups (Lorazepam or Placebo). According to the body weight, children will receive the study drug (two hours before the procedure) as follow: 1) Group A (active arm): Lorazepam administered according to the body weight. A single dose of 0.5 mg in children with body weight > 20 and ≤ 30 kg; A single dose of 1 mg in children with body weight > 30 and ≤ 60 kg. A single dose of 1.5 mg in children with body weight > 60 kg This body weight cut-off corresponds to a dose of Lorazepam ≈ 0.025 mg/kg. 2) Group B (control arm): lactose powder (number of tablets similar to the active arm according to body weight). Randomization will be done by block of random sizes of 4 and 6 and stratification will be performed on sex (male/female) and previous endoscopy (no previous procedure/at least one previous procedure). The primary end-point will be a Nurse-Assessed Patient Comfort Score (NAPCOMS) pain subscale ≥ 6.
The NAPCOMS is a validated pain score for colonoscopies. Statistical analysis: Descriptive statistics for demographic data and outcome variables will be presented using the means (standard deviations) for continuous variables or the medians (interquartile range) for non-normal distribution numeric variables and frequency tables for categorical variables. Baseline measures will be compared between arms to assess balance between the two arms.
Analysis of primary outcome: The primary analysis will be conducted under the intention to treat principle (ITT). The proportion of children with a NAPCOMS score ≥ 6 will be compared between the treatment groups (Lorazepam and Placebo) using the 2-sided Cochran–Mantel–Haenszel (CMH) test with stratification by sex (male/female) and previous endoscopy (no previous procedure/at least one previous procedure).
Anticipated outcomes: We expect that the number of children experiencing pain during colonoscopy will be lower in the intervention arm as compared to the placebo arm. Since general anesthesia is not easily available to all children, this trial will enable us to develop a new approach to improve patient’s experience when undergoing digestive endoscopy under intravenous sedation.