Methadone in Pediatric Anesthesiology II

Study Overview
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Brief Summary
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Three arm randomized controlled trial to evaluate the efficacy of a single dose of intraoperative methadone in reducing post-operative pain and opioid consumption in adolescents undergoing posterior spinal fusion. Our secondary goal is to determine the pharmacokinetics of IV methadone in children (0.3 and 0.4 mg/kg).

Detailed Description
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Randomized, controlled, modified dose-escalation design. Patients receive standard monitoring for anesthesia and postoperative care. Surgical and anesthesia (except for opioid use) care are not altered for study purposes. All patients are induced by propofol and muscle relaxants. In the first cohort (n=30 evaluable), subjects are randomized 1:2 to either control (standard intraop opioid at anesthesiologists' discretion) or methadone HCl (0.4 mg/kg ideal body weight, IBW). In the second cohort (n=30 evaluable), subjects are randomized 1:2 to either control (standard intraop opioid) or methadone HCl (0.3 mg/kg ideal body weight, IBW). Subjects in the study groups will receive methadone (IV bolus, after induction of anesthesia) as their primary intraoperative opioid, rather than leaving the choice of intraoperative opioid to the anesthesiologist. Intraoperative breakthrough pain will be treated at the discretion of the anesthesiologist with fentanyl. In the control groups, intraoperative opioid administration will be left at the discretion of the anesthesia providers. Patient controlled analgesia as prescribed by the clinical team, using hydromorphone or morphine, will be used to treat postoperative pain relief.

Official Title
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Methadone in Pediatric Anesthesia II

Conditions
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Pain

Intervention / Treatment
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* Drug: 0.3mg/kg IV methadone HCl
* Drug: 0.4mg/kg IV methadon HCl
* Other: control no methadone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. Age 11-18 years Undergoing general anesthesia and idiopathic posterior spinal surgery with anticipated postop inpatient stay of > 3 days Signed, written, informed consent from legal guardians and assent from patient Exclusion Criteria. History of or known liver or kidney disease. Females who are pregnant or nursing. Children with developmental delay Children undergoing surgery for scoliosis of musculoskeletal origin

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: methadone HCl 0.3 mg/kg<br>0.3mg/kg IV methadone HCl | Drug: 0.3mg/kg IV methadone HCl<br>* Group I will receive 0.3mg/kg IV methadone HCl<br>* Other names: methadone HCl, dolophine;|
| Experimental: methadone HCl 0.4 mg/kg<br>0.4mg/kg IV methadon HCl | Drug: 0.4mg/kg IV methadon HCl<br>* Group II will receive 0.4mg/kg IV methadone HCl.<br>* Other names: methadone HCl, dolophine;|
| Active Comparator: control group<br>control no methadone, standard of care opioids. | Other: control no methadone<br>* The control group will not receive methadone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Opioid Consumption (Morphine Equivalent) | Measure of overall morphine consumption | 6 days | 
| Pain Scores | Assessments are made in the postoperative period by a trained member of the research team blinded to intraoperative use of methadone. These will be conducted on each post-operative day until discharge or post op day 6, whichever comes first. Pain intensity is assessed using the numeric pain score (0-10) scale employed by the inpatient nursing staff and previously validated . | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of R and S Methadone | Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose. | 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal surgery, Methadone