Does Pre and Postoperative Dextromethorphan Reduce Post-tonsillectomy Pain in Children?

Study Overview
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Brief Summary
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With Institutional ethics board and Health Canada approval, pediatric patients (ages 3-12) undergoing tonsillectomy or adenotonsillectomy (under standardized anesthesia) will be randomized to receive dextromethorphan hydrobromide (1mg/kg orally) 30 min preoperatively and again 8 hours postoperatively OR placebo (syrup identical in taste, appearance and volume) at the same time points. The primary outcome is an integrated assessment of perioperative pain scores and opioid use for 24 hours postoperatively. Secondary outcomes include nausea, vomiting, respiratory depression, and bleeding for 24 hours postoperatively. Our hypothesis is that dextromethorphan will decrease the incidence/severity of post-tonsillectomy pain. The improved pain control will be apparent through reduced opioid consumption and integrated pain scores. This will result in a reduced incidence of opioid-related side effects and adverse events.

Detailed Description
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With Institutional ethics board and Health Canada approval and parental consent and child assent, pediatric patients (ages 3-12) undergoing tonsillectomy or adenotonsillectomy (under standardized anesthesia) will be randomized to receive dextromethorphan hydrobromide (1mg/kg orally) 30 min preoperatively and again 8 hours postoperatively OR placebo (syrup identical in taste, appearance and volume) at the same time points. The primary outcome is an integrated assessment of perioperative pain scores and opioid use for 24 hours postoperatively. Pain scores were collected preoperatively at rest and then at 1,2,3,8,9,10 and 24 hours postoperatively using the validated Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). Secondary outcomes include nausea, vomiting, respiratory depression, and bleeding recorded by blinded observers for 24 hours postoperatively. Our hypothesis is that dextromethorphan will decrease the incidence/severity of post-tonsillectomy pain. The improved pain control will be apparent through reduced opioid consumption and integrated pain scores. This will result in a reduced incidence of opioid-related side effects and adverse events.

Official Title
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A Prospective Randomized Double-blind Placebo Controlled Trial; Does Pre and Postoperative Dextromethorphan Reduce Post-tonsillectomy Pain in Children?

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologist's (ASA) physical classification I and II tonsillectomy or adenotonsillectomy admission to extended postoperative care unit Exclusion Criteria: use of monoamine oxidase inhibitors, serotonin reuptake inhibitors or tricyclic antidepressants requirement of preoperative sedation recent dextromethorphan use (<24 h before surgery) intolerance, sensitivity or contraindication to any agents used in the study pre-existing chronic pain or chronic analgesic use body mass index (BMI) for age percentile greater than 90 confounding procedural factors which might affect the validity of the data inability to adhere to study protocol contraindication to volatile anesthetics

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dextromethorphan<br>1 mg/kg of dextromethorphan syrup orally 30 min preoperatively and then again 8 hours post-tonsillectomy | Drug: Dextromethorphan<br>* Dextromethorphan is a drug of the morphinan class with sedative, dissociative, and stimulant properties (at higher doses). Dextromethorphan has been explored for a number other uses in medicine, including pain relief (as either the primary analgesic, or an opioid potentiator).<br>* Other names: dextromethorphan hydrobromide;|
| Placebo Comparator: Placebo<br>30 min preoperatively and then again 8 hours postoperatively, received inactive placebo syrup identical in volume, appearance and taste as the experimental group | Drug: Placebo<br>* Placebo syrup identical to active comparator in taste, appearance and volume but is inactive. Placebo comparator will be used in the placebo arm of the trial.<br>* Other names: control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| integrated assessment of pain scores and opioid use | The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) will be measured at rest 24 hours postoperatively and this will be integrated with total opioid consumption at 24 hours postoperatively. This will be achieved by converting both pain scores and opioid consumption to % change. The % differences for each of the 2 variables are then added together on a per-subject basis to provide a summated % difference. The individual and summated % differences can then be plotted on a single graph and the integrated ranks of the experimental and control groups can be compared with standard statistical tests.(1) | 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| opioid-related adverse effects | nausea, vomiting, respiratory depression, bleeding | up to 24 hours postoperatively | 
| pain scores | Pain scores at rest on the CHEOPS pain scale | 1,2,3,8,9 and 10 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid analgesics,, opioid consumption, adverse effects, postoperative pain, tonsillectomy