Thoracolumbar Scoliosis
Conditions
Brief summary
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
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.
Interventions
DRUGMethadone
The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes
DRUGNormal Saline
the control group will receive a 20 ml normal saline placebo infusion over 10 minutes
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
1. Patient age 10 - 17 years 2. Patients undergoing multilevel thoraco-lumbar spine surgery with instrumentation and fusion
Exclusion criteria
1. Preoperative methadone therapy 2. Inability to use the PCA 3. Allergy to methadone or morphine 4. Morbid obesity with a body mass index \>36.0 kg/m2 5. Patients with chronic renal failure defined by serum creatinine \>2.0 mg/dL 6. Liver failure defined as a history of cirrhosis or fulminant hepatic failure 7. Preoperative congenital heart disease or arrhythmias 8. Patient refusal to participate in study 9. Pregnancy (It is standard of care for all post menarche female patients to undergo a urine pregnancy test prior to surgery).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Usage | Admission to PACU to 72 hours post-operative | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores | Admission to PACU to 72 hours post-operative | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes | 32 |
| Control Group The control group will receive a 20 ml normal saline placebo infusion over 10 minutes
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes | 30 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Surgery cancelled/changed | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Treatment Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 14.09 years STANDARD_DEVIATION 1.69 | 14.33 years STANDARD_DEVIATION 1.69 | 14.21 years STANDARD_DEVIATION 1.67 |
| ASA Status I | 7 Participants | 3 Participants | 10 Participants |
| ASA Status II | 22 Participants | 27 Participants | 49 Participants |
| ASA Status III | 3 Participants | 0 Participants | 3 Participants |
| Body Mass Index | 22.45 kg/m^2 STANDARD_DEVIATION 3.78 | 20.29 kg/m^2 STANDARD_DEVIATION 3.89 | 21.41 kg/m^2 STANDARD_DEVIATION 3.92 |
| Height | 160.64 cm STANDARD_DEVIATION 9.98 | 162.48 cm STANDARD_DEVIATION 8.07 | 161.53 cm STANDARD_DEVIATION 9.01 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 32 participants | 30 participants | 62 participants |
| Sex: Female, Male Female | 26 Participants | 22 Participants | 48 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
| Weight | 58.26 kg STANDARD_DEVIATION 12.72 | 53.95 kg STANDARD_DEVIATION 13.2 | 56.18 kg STANDARD_DEVIATION 12.92 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 |
| other Total, other adverse events | 15 / 32 | 14 / 30 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 |
Outcome results
Primary
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.
Time frame: Admission to PACU to 72 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Group | Opioid Usage | PACU | 0.41 mg/kg |
| Treatment Group | Opioid Usage | 24 Hours | 0.58 mg/kg |
| Treatment Group | Opioid Usage | 48 Hours | 0.58 mg/kg |
| Treatment Group | Opioid Usage | 72 Hours | 0.10 mg/kg |
| Control Group | Opioid Usage | 72 Hours | 0.04 mg/kg |
| Control Group | Opioid Usage | PACU | 0.47 mg/kg |
| Control Group | Opioid Usage | 48 Hours | 0.55 mg/kg |
| Control Group | Opioid Usage | 24 Hours | 0.55 mg/kg |
Secondary
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.
Time frame: Admission to PACU to 72 hours post-operative
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Pain Scores | PACU | 0.53 units on a scale | Standard Deviation 0.76 |
| Treatment Group | Pain Scores | 24 Hours | 0.14 units on a scale | Standard Deviation 0.4 |
| Treatment Group | Pain Scores | 48 Hours | 0.24 units on a scale | Standard Deviation 0.45 |
| Treatment Group | Pain Scores | 72 Hours | 0.16 units on a scale | Standard Deviation 0.18 |
| Control Group | Pain Scores | 72 Hours | 0.29 units on a scale | Standard Deviation 0.64 |
| Control Group | Pain Scores | PACU | 0.65 units on a scale | Standard Deviation 0.7 |
| Control Group | Pain Scores | 48 Hours | 0.36 units on a scale | Standard Deviation 0.62 |
| Control Group | Pain Scores | 24 Hours | 0.42 units on a scale | Standard Deviation 0.66 |