Pain
Conditions
Keywords
spinal surgery, Methadone
Brief summary
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
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.
Interventions
DRUG0.3mg/kg IV methadone HCl
Group I will receive 0.3mg/kg IV methadone HCl
DRUG0.4mg/kg IV methadon HCl
Group II will receive 0.4mg/kg IV methadone HCl.
OTHERcontrol no methadone
The control group will not receive methadone.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Consumption (Morphine Equivalent) | 6 days | Measure of overall morphine consumption |
| Pain Scores | 6 days | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of R and S Methadone | 96 hours | 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. |
Countries
United States
Participant flow
Pre-assignment details
53 signed consents however, 2 participants withdrew prior to randomization: 1 per family request 1 unable to complete
Participants by arm
| Arm | Count |
|---|---|
| Methadone 0.3 mg/kg 0.3mg/kg IV methadone
0.3mg/kg IV methadone : Group I will receive 0.3mg/kg IV methadone | 20 |
| Methadone 0.4 mg/kg 0.4mg/kg IV methadone
0.4mg/kg IV methadone: Group II will receive 0.4mg/kg IV methadone . | 14 |
| Control Group control no methadone, standard of care opioids.
control no methadone: The control group will not receive methadone. | 17 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Control Group | Methadone 0.3 mg/kg | Methadone 0.4 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 14.3 Years STANDARD_DEVIATION 1.8 | 14.5 Years STANDARD_DEVIATION 1.9 | 13.7 Years STANDARD_DEVIATION 1.5 | 14.8 Years STANDARD_DEVIATION 1.9 |
| American Society of Anesthesiologists (ASA) Physical Satus ASA 1 -A normal healthy patient | 28 Participants | 6 Participants | 16 Participants | 6 Participants |
| American Society of Anesthesiologists (ASA) Physical Satus ASA 2 - A patient with mild systemic disease | 23 Participants | 11 Participants | 4 Participants | 8 Participants |
| BMI | 21.7 kg/m^2 scale STANDARD_DEVIATION 3.8 | 22.4 kg/m^2 scale STANDARD_DEVIATION 4.8 | 21.6 kg/m^2 scale STANDARD_DEVIATION 3.8 | 21.3 kg/m^2 scale STANDARD_DEVIATION 2.4 |
| Expected Post-operative Pain Score | 7.2 0-10 units on a Visual Analog scale STANDARD_DEVIATION 2 | 7.5 0-10 units on a Visual Analog scale STANDARD_DEVIATION 1.9 | 7.9 0-10 units on a Visual Analog scale STANDARD_DEVIATION 2.1 | 6.9 0-10 units on a Visual Analog scale STANDARD_DEVIATION 2 |
| Pre-operative pain score | 1.4 units on a scale STANDARD_DEVIATION 2.3 | 1.9 units on a scale STANDARD_DEVIATION 3.1 | 1.6 units on a scale STANDARD_DEVIATION 2.1 | .6 units on a scale STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Caucasian | 44 Participants | 14 Participants | 18 Participants | 12 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 3 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | 51 participants | 17 participants | 20 participants | 14 participants |
| Sex: Female, Male Female | 35 Participants | 10 Participants | 14 Participants | 11 Participants |
| Sex: Female, Male Male | 16 Participants | 7 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 6 / 20 | 6 / 14 | 8 / 16 |
| serious Total, serious adverse events | 0 / 20 | 0 / 14 | 0 / 16 |
Outcome results
Primary
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 .
Time frame: 6 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone HCl 0.3 mg/kg | Pain Scores | 4.7 score on a scale | Standard Deviation 2.4 |
| Methadone HCl 0.4 mg/kg | Pain Scores | 4.6 score on a scale | Standard Deviation 2.9 |
| Control Group | Pain Scores | 4.5 score on a scale | Standard Deviation 2.4 |
p-value: 0.962ANOVA
Primary
Total Opioid Consumption (Morphine Equivalent)
Measure of overall morphine consumption
Time frame: 6 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone HCl 0.3 mg/kg | Total Opioid Consumption (Morphine Equivalent) | 2.22 mg/kg | Standard Deviation 0.84 |
| Methadone HCl 0.4 mg/kg | Total Opioid Consumption (Morphine Equivalent) | 2.37 mg/kg | Standard Deviation 0.86 |
| Control Group | Total Opioid Consumption (Morphine Equivalent) | 3.28 mg/kg | Standard Deviation 0.93 |
p-value: 0.002ANOVA
Secondary
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.
Time frame: 96 hours
Population: Methadone clearance was only measured in the two groups that received methadone
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone HCl 0.3 mg/kg | Cmax of R and S Methadone | R- Methadone | 97 ng/ml | Standard Deviation 37 |
| Methadone HCl 0.3 mg/kg | Cmax of R and S Methadone | S- Methadone | 127 ng/ml | Standard Deviation 43 |
| Methadone HCl 0.4 mg/kg | Cmax of R and S Methadone | R- Methadone | 175 ng/ml | Standard Deviation 93 |
| Methadone HCl 0.4 mg/kg | Cmax of R and S Methadone | S- Methadone | 226 ng/ml | Standard Deviation 113 |