Anesthesia, Post-operative Pain
Conditions
Keywords
fentanyl, morphine, methadone
Brief summary
The μ-opioid receptor agonist methadone is frequently used in adult anesthesia and adult pain therapy. Methadone has an extremely long half-life, which confers therapeutic advantage by providing more stable plasma concentrations and long-lasting pain relief. Methadone perioperative pharmacokinetics and effectiveness in perioperative pain relief in inpatients is well characterized. There is, however, no information on methadone use in an ambulatory surgery setting and outpatient procedures. This pilot investigation will determine effectiveness of intraoperative methadone in reducing postoperative opioid consumption and providing improved pain relief in patients undergoing moderately painful, ambulatory surgical procedures.
Interventions
DRUGmethadone
Escalating dose of methadone up to .3mg/kg.
DRUGControl (Intra-operative administration of opioids, other than methadone)
Intra-operative administration of opioids, other than methadone
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years * Undergoing general anesthesia and moderately painful, ambulatory surgical procedures with anticipated overnight, postop hospital stay of \< 24 hours * Signed, written, informed consent
Exclusion criteria
* History of or known liver or kidney disease. * Females who are pregnant or nursing. * Opioid tolerant patients (e.g. preoperative methadone therapy or use of fentanyl transdermal patches) * History of allergy to methadone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative Opioid Administration | Administered at induction of anesthesia | Data on opioids administered intraoperatively will be collected from the subject's EMR. |
| Postoperative Opioid Administration | EMR reviewed at 24 hours post-administration or at hospital discharge | Data on opioids administered postoperatively will be collected from the subject's EMR. Pain severity will be assessed using Numeric Rating Scale and colored-visual analogue scale. Pain relief postoperatively will be assessed using a 5 point scale \[0-no relief, 4-complete relief\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Consumption Within First 30 Postoperative Days | 30 days | Daily opioid consumption for approx 30 days following surgery (from hospital discharge until postop clinic visit). |
| Pain Relief Within First 30 Postoperative Days | 30 days | Daily pain self-assessments using a numeric (0-10) rating scale were recorded in a home diary for approx 30 days following surgery (from hospital discharge until postop clinic visit). Zero was no pain and 10 was the worst possible pain. Patient's 30-day post-discharge scores were averaged individually and compared in between groups. In addition, participants recorded pain interference with 7 activities of daily living - mood, ability to walk or move, sleep, normal work outside the home, normal work at home, recreational activities, and enjoyment of life on a 5-point Likert scale. Questions were based on the Patient-Reported Outcomes Measurement Information System Pain Behavior and Pain Interference item banks. Patients also recorded opioid and nonopioid analgesic use, sedation, and time to return to work. |
Countries
United States
Participant flow
Recruitment details
Recruitment was done between March 2015-May 2016.
Pre-assignment details
We withdrew 4 patients after consenting - two of patients met exclusion criteria, one patient withdrew consent, one anesthesia provider refused to participate the study.
Participants by arm
| Arm | Count |
|---|---|
| Control Control (Intra-operative administration of opioids, other than methadone)
Control (Intra-operative administration of opioids, other than methadone): Intra-operative administration of opioids, other than methadone | 21 |
| Treatment Methadone 0.1 mg/kg methadone 0.1 mg/kg
methadone: Escalating dose of methadone up to .3mg/kg. | 18 |
| Treatment Methadone 0.15 mg/kg methadone: Escalating dose of methadone up to .3mg/kg. | 21 |
| Total | 60 |
Baseline characteristics
| Characteristic | Control | Treatment Methadone 0.1 mg/kg | Treatment Methadone 0.15 mg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 18 Participants | 21 Participants | 60 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 13 | 37 years STANDARD_DEVIATION 11 | 40 years STANDARD_DEVIATION 11 | 40 years STANDARD_DEVIATION 2.52 |
| ASA status ASA I | 1 units on a scale | 0 units on a scale | 0 units on a scale | 1 units on a scale |
| ASA status ASA II | 16 units on a scale | 17 units on a scale | 21 units on a scale | 54 units on a scale |
| ASA status ASA III | 4 units on a scale | 1 units on a scale | 0 units on a scale | 5 units on a scale |
| body weight - kg | 85 Kg STANDARD_DEVIATION 16 | 88 Kg STANDARD_DEVIATION 42 | 86 Kg STANDARD_DEVIATION 26 | 86 Kg STANDARD_DEVIATION 1.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 18 Participants | 21 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 12 Participants | 40 Participants |
| Region of Enrollment United States | 21 participants | 18 participants | 21 participants | 60 participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 21 Participants | 55 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 18 | 0 / 21 |
| other Total, other adverse events | 0 / 21 | 0 / 18 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 18 | 0 / 21 |
Outcome results
Primary
Intraoperative Opioid Administration
Data on opioids administered intraoperatively will be collected from the subject's EMR.
Time frame: Administered at induction of anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Intraoperative Opioid Administration | 25 morphine equivalents mg |
| Treatment Methadone 0.1 mg/kg | Intraoperative Opioid Administration | 5.6 morphine equivalents mg |
| Treatment Methadone 0.15 mg/kg | Intraoperative Opioid Administration | 8.6 morphine equivalents mg |
p-value: 0.0001Chi-squared
Primary
Postoperative Opioid Administration
Data on opioids administered postoperatively will be collected from the subject's EMR. Pain severity will be assessed using Numeric Rating Scale and colored-visual analogue scale. Pain relief postoperatively will be assessed using a 5 point scale \[0-no relief, 4-complete relief\]
Time frame: EMR reviewed at 24 hours post-administration or at hospital discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Postoperative Opioid Administration | 10 morphine equivalents mg |
| Treatment Methadone 0.1 mg/kg | Postoperative Opioid Administration | 5.4 morphine equivalents mg |
| Treatment Methadone 0.15 mg/kg | Postoperative Opioid Administration | 3.3 morphine equivalents mg |
p-value: 0.01Kruskal-Wallis
Secondary
Opioid Consumption Within First 30 Postoperative Days
Daily opioid consumption for approx 30 days following surgery (from hospital discharge until postop clinic visit).
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Opioid Consumption Within First 30 Postoperative Days | 10 total postdischarge opioid pills used |
| Treatment Methadone 0.1 mg/kg | Opioid Consumption Within First 30 Postoperative Days | 7 total postdischarge opioid pills used |
| Treatment Methadone 0.15 mg/kg | Opioid Consumption Within First 30 Postoperative Days | 5 total postdischarge opioid pills used |
p-value: 0.001Kruskal-Wallis
Secondary
Pain Relief Within First 30 Postoperative Days
Daily pain self-assessments using a numeric (0-10) rating scale were recorded in a home diary for approx 30 days following surgery (from hospital discharge until postop clinic visit). Zero was no pain and 10 was the worst possible pain. Patient's 30-day post-discharge scores were averaged individually and compared in between groups. In addition, participants recorded pain interference with 7 activities of daily living - mood, ability to walk or move, sleep, normal work outside the home, normal work at home, recreational activities, and enjoyment of life on a 5-point Likert scale. Questions were based on the Patient-Reported Outcomes Measurement Information System Pain Behavior and Pain Interference item banks. Patients also recorded opioid and nonopioid analgesic use, sedation, and time to return to work.
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Pain Relief Within First 30 Postoperative Days | 1 score on a scale |
| Treatment Methadone 0.1 mg/kg | Pain Relief Within First 30 Postoperative Days | 1 score on a scale |
| Treatment Methadone 0.15 mg/kg | Pain Relief Within First 30 Postoperative Days | 0 score on a scale |
p-value: 0.02Kruskal-Wallis