Methadone Versus Morphine for Orthopedic Surgery Patients
Primary Purpose
Fracture, Pain, Postoperative
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Methadone
Morphine
Sponsored by
About this trial
This is an interventional treatment trial for Fracture focused on measuring Surgery, Orthopedic, Pain, Postoperative
Eligibility Criteria
Inclusion Criteria:
- ASA I-III
- Ages 18-65 years
- Presenting for lower extremity orthopedic surgery involving fracture of long bones at University of Louisville Hospital
- Surgery expected to last more than one hour
- Patient expected to have moderate to severe post-operative pain
- Patient refused regional anesthesia or has a contraindication to regional anesthesia
Exclusion Criteria:
- Any known contraindications to methadone including hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.
- Difficulty or inability to understand the study or protocol
- Known renal or hepatic dysfunction
- BMI> 35
- Known respiratory or cardiovascular problems, such as obstructive sleep apnea or oxygen saturation of less than 92% on room air
- Taking any of the known drugs that induce or inhibit the cytochrome p450 enzyme systems. Common examples of these drugs are antifungal, antiretroviral, barbiturates, dexamethasone, and macrolide antibiotics.
- Pregnancy
- Taking preoperative opioids for more than 2 weeks before the surgery
Sites / Locations
- University of Louisville Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Methadone
Control
Arm Description
Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg of methadone IV with induction of general anesthesia.
Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg morphine (standard of care)
Outcomes
Primary Outcome Measures
Opioid Consumption During the 48 Hours After Surgery
The amount of opioid required for postoperative pain relief
Secondary Outcome Measures
Number of Participants With Post Operative Nausea and Vomiting
rates subjects experienced PONV
Visual Pain Score
Patients rated their pain with the numerical VPS from 0 to 10, with 10 being the worst pain possible and 0 being no pain
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00892606
Brief Title
Methadone Versus Morphine for Orthopedic Surgery Patients
Official Title
Effectiveness of Pre-Operative Methadone Versus Morphine for Post-Operative Analgesia in Orthopedic Surgery Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Louisville
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The investigators propose to compare analgesia by methadone and ketamine with a combination of morphine and ketamine in orthopedic surgery patients with moderate to severe pain. The investigators hypothesize that when given with ketamine before surgical incision, methadone is more effective than morphine in reducing postoperative morphine consumption and reducing pain during movement.
Detailed Description
Patients will receive 1-4 mg midazolam before being transferred to the operating room. All patients will receive standard ASA monitoring. In the operating room, the anesthesiologist will open a randomization envelope to determine patient group assignment (see below). Patients will be anesthetized with 0.2 mg/kg ketamine, 2 µg/kg fentanyl and propofol or etomidate IV. Muscle relaxant of the anesthesiologist's choice will be given and the patient will be intubated. After intubation, the computer-generated randomization codes stored in opaque envelopes will be opened. The patients will be randomized to one of two groups:
Methadone group: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation
Control group: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation
The unblinded investigator will draw the drug and dilute to a total volume of 10 cc. This syringe will be handed to the anesthesia provider, who will administer the medication after induction. They will be maintained with oxygen, air and an inhalational agent of anesthesiologist's choice, targeted at BIS between 40 and 60. Additional analgesia will be provided with fentanyl in 50 µg increments as required throughout surgery. At the end of surgery the neuromuscular block will be reversed and patients will breathe spontaneously. Fentanyl will be titrated to maintain a respiratory rate of 12-15 breaths per minute to obtain an O2 saturation > 95% and the other extubation criteria are met before tracheal extubation . The intraoperative use of narcotics, sedatives and anesthetic drugs will be noted. The type of surgery, the duration of surgery and use of additional analgesics and antiemetics will be noted.
An investigator blinded to randomization will track the patients in the PACU. If rescue medication is necessary, morphine IV will be given in 2-4 mg increments up to a total of 20 mg. If the patients continue to report pain (VAS > 4), IV hydromorphone will be given in 0.5 mg dose every 10-15 minutes until the patient has adequate analgesia (VAS < 4), as decided by the PACU nurse.
Patients will receive morphine patient-controlled analgesia (PCA) for pain relief as the primary analgesic. Percocet (Acetaminophen/Oxycodone 325 mg/5 mg) or Lortab (Acetaminophen/Hydrocodone 325/5 mg) will be prescribed as needed to maintain VRS < 4.
In the PACU, vital signs including respiratory rate, heart rate, non-invasive blood pressure, sedation score and oxygen saturation will be recorded every 15 minutes. VAS scores for pain will be obtained from the patient every 15 minutes until the patient is discharged to the floor. VAS (visual analog scale) is a 100-mm scale where 0 = no pain and 100 = worst pain imaginable. The investigator will record sedation scores every 15 minutes using the following scale until patient is discharged to the floor:
0-Patient is fully alert
Patient has intermittent sedation
Patient sedated but responsive to verbal stimuli
Patient unresponsive to verbal stimuli
Patients will be seen at 8 am and 4 pm on the following day and will be contacted at home or in the hospital on POD 2 and 3 for information regarding pain scores and analgesic requirement. The initial dose of rescue analgesic and time it is given will be recorded. VAS at rest and on movement will be recorded, when the patients are seen or VRS will be recorded via phone contact. Morphine or other analgesics required during the first 24 and 48 hours after surgery, and times to first ambulation, first fluid, solid and flatus will be recorded, as will incidence and severity of postoperative nausea and vomiting be recorded.
Our primary outcome will be opioid consumption during the 48 hours after surgery. All analgesics consumed will be converted to morphine equivalent.
The secondary outcomes will be
Overall rescue analgesic, converted into equipotent doses compared between the two groups
Side effects with special attention paid to respiratory rate and possible respiratory depression, and PONV
Visual pain score at 48 h post-op.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fracture, Pain, Postoperative
Keywords
Surgery, Orthopedic, Pain, Postoperative
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Methadone
Arm Type
Experimental
Arm Description
Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg of methadone IV with induction of general anesthesia.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg morphine (standard of care)
Intervention Type
Drug
Intervention Name(s)
Methadone
Other Intervention Name(s)
Symoron, Dolophine, Amidone, Methadose, Physeptone, Heptadon, 6-(Dimethylamino)-4,4-diphenylheptan-3-one (IUPAC name)
Intervention Description
Patients will receive 0.2 mg/kg of methadone IV immediately after intubation
Intervention Type
Drug
Intervention Name(s)
Morphine
Other Intervention Name(s)
Opiate, (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Intervention Description
Patients will receive 0.2 mg/kg of morphine IV immediately after intubation
Primary Outcome Measure Information:
Title
Opioid Consumption During the 48 Hours After Surgery
Description
The amount of opioid required for postoperative pain relief
Time Frame
48 hours
Secondary Outcome Measure Information:
Title
Number of Participants With Post Operative Nausea and Vomiting
Description
rates subjects experienced PONV
Time Frame
48 hours
Title
Visual Pain Score
Description
Patients rated their pain with the numerical VPS from 0 to 10, with 10 being the worst pain possible and 0 being no pain
Time Frame
48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
ASA I-III
Ages 18-65 years
Presenting for lower extremity orthopedic surgery involving fracture of long bones at University of Louisville Hospital
Surgery expected to last more than one hour
Patient expected to have moderate to severe post-operative pain
Patient refused regional anesthesia or has a contraindication to regional anesthesia
Exclusion Criteria:
Any known contraindications to methadone including hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.
Difficulty or inability to understand the study or protocol
Known renal or hepatic dysfunction
BMI> 35
Known respiratory or cardiovascular problems, such as obstructive sleep apnea or oxygen saturation of less than 92% on room air
Taking any of the known drugs that induce or inhibit the cytochrome p450 enzyme systems. Common examples of these drugs are antifungal, antiretroviral, barbiturates, dexamethasone, and macrolide antibiotics.
Pregnancy
Taking preoperative opioids for more than 2 weeks before the surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anupama Wadhwa, MD
Organizational Affiliation
University of Louisville
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11159249
Citation
Wadhwa A, Clarke D, Goodchild CS, Young D. Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. Anesth Analg. 2001 Feb;92(2):448-54. doi: 10.1097/00000539-200102000-00032.
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Methadone Versus Morphine for Orthopedic Surgery Patients
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