A Trial Comparing Single Intra-op Dose of Methadone Versus Placebo in Patients Undergoing Spine Surgery

Study Overview
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Brief Summary
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Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA).

Detailed Description
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Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA). Methadone is an opioid with one of the longest elimination half-life and has been used as an effective analgesic for acute, chronic, neuropathic, and cancer pain in adults, children, and even neonates1-5. Its long duration of action and antagonism to the N-methyl-d-aspartate receptor may decrease the need for PCA use in the postoperative period. Gourlay2 demonstrated the effectiveness and utility of perioperative methadone including the advantages of longer analgesia with no serious side effects of respiratory depression. A recent study by Gottschalk2 in adult patients demonstrated a 50% reduction of postoperative opioids at 48 hours and lower pain scores after a single bolus of methadone before surgical incision. However, a major weakness of the study is that patients did not receive equipotent intraoperative opioids. In addition, the adolescent patient population will undergo a much larger surgical incision with potential for greater postoperative pain. Despite this potential benefit, methadone is seldom used in the perioperative setting. A more recent pharmacokinetic study of methadone in adolescents undergoing spine surgery failed to show a reduction in opioid consumption as it was powered to determine pharmacokinetics and not a secondary endpoint of postoperative opioid consumption. An appropriately powered study is still required to determine the efficacy of methadone in reducing postoperative pain after spine surgery.

Official Title
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A Randomized Blinded Prospective Trial Comparing Single Intraoperative Dose of Methadone Versus Placebo in Pediatric Patients Undergoing Spine Surgery.

Conditions
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Thoracolumbar Scoliosis

Intervention / Treatment
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* Drug: Methadone
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age 10 - 17 years Patients undergoing multilevel thoraco-lumbar spine surgery with instrumentation and fusion Exclusion Criteria: Preoperative methadone therapy Inability to use the PCA Allergy to methadone or morphine Morbid obesity with a body mass index >36.0 kg/m2 Patients with chronic renal failure defined by serum creatinine >2.0 mg/dL Liver failure defined as a history of cirrhosis or fulminant hepatic failure Preoperative congenital heart disease or arrhythmias Patient refusal to participate in study Pregnancy (It is standard of care for all post menarche female patients to undergo a urine pregnancy test prior to surgery).

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment group<br>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes. | Drug: Methadone<br>* The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes<br>* Other names: Treatment group;|
| Placebo Comparator: Control Group<br>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes | Drug: Normal Saline<br>* the control group will receive a 20 ml normal saline placebo infusion over 10 minutes<br>* Other names: Control Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Usage | Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively. | Admission to PACU to 72 hours post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores | The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively. | Admission to PACU to 72 hours post-operative |