Preoperative Oral Methadone for Patients Undergoing Cardiac Surgery: Reduction of Postoperative Pain
Keywords
Abstract
Description
Investigators propose a prospective, randomized, double-blind, placebo-controlled trial to investigate the effects of preoperative oral methadone on postoperative pain. The trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), and University of Saskatchewan Research Ethics Committee principles using an intent-to-treat model. The primary endpoint will be postoperative pain in the ICU, and secondary outcomes will include morphine requirements as measured by Patient Controlled Analgesia (PCA). Secondary endpoints include opioid consumption at 15 minutes and at 2, 4, 8, 12, 24, 48, and 72 hours post extubation. Other secondary endpoints include the following: pain with cough (using a 0-10 verbal pain scale) measured at the time of extubation then daily until post-op day three. Secondary outcomes that will be recorded from nursing assessment records include: incidence of nausea and/or vomiting requiring antiemetics, pruritus, hypoventilation (respiratory rate less than 8 breaths/min), hypoxemia (oxygen saturation less than 90%), time to extubation, and sedation (Richmond Agitation-Sedation Scale of -4 or -5).
Patients will receive a dose of either oral methadone or placebo prior to entering the operating room. The dose given will be 0.3 mg/kg (to a maximum of 30 mg) or equivalent volume of placebo. An blinded research assistant will receive an envelope the morning of surgery outlining if the patient is in group A or B as well as their weight in kg. For the methadone arm the research assistant will prepare the appropriate amount of methadone, which is dispensed as 10 mg/mL, and dilute it to a total volume of 5 mL in sugary syrup to mask its taste. For the placebo arm a similar volume will be mixed at a 0.3 mg/kg volume and diluted to a total volume of 5 mL of sugary syrup. The methadone or placebo will be given to the researcher in a syringe. The researcher will give syringe to the patient and the patient will administer the solution to themself orally prior to entering the operating room.
Dates
| Last Verified: | 11/30/2017 |
| First Submitted: | 04/05/2016 |
| Estimated Enrollment Submitted: | 05/11/2016 |
| First Posted: | 05/16/2016 |
| Last Update Submitted: | 12/27/2017 |
| Last Update Posted: | 01/01/2018 |
| Actual Study Start Date: | 03/31/2016 |
| Estimated Primary Completion Date: | 07/31/2016 |
| Estimated Study Completion Date: | 11/30/2017 |
Condition or disease
Intervention/treatment
Drug: Methadone
Drug: Placebo
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Methadone Methadone 0.3 mg/kg (to a maximum of 30 mg) will be given to the patient preoperatively. | Drug: Methadone 0.3mg/kg of methadone given preoperatively (to maximum of 30mg) |
| Placebo Comparator: Placebo Equivalent volume (5mL) of syrup will be given to the patient preoperatively. | Drug: Placebo equivalent volume (5mL) of syrup given preoperatively |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - presenting for elective first-time CABG cardiac surgery with anticipated extubation within 12 hours Exclusion Criteria: - < 18 years of age - preoperative renal failure requiring dialysis or serum creatinine greater than 176 µmol/L - significant hepatic dysfunction (liver function tests more than twice the upper limit of normal) - ejection fraction less than 30% - corrected QT interval (QTc) on ECG > 440ms for men and 450ms for women - pulmonary disease necessitating home oxygen therapy - preoperative requirement for inotropic agents or intra-aortic balloon pump to maintain hemodynamic stability - emergency surgery - allergy to methadone - use of preoperative opioids or recent history of opioid abuse |
Outcome
Primary Outcome Measures
1. Pain score (VRS) [24 hours]
Secondary Outcome Measures
1. Total Morphine Consumption (mg) [72 hours]
2. Pain score (VRS) [Up to 72 hours postoperative]
3. Time to extubation [up to 24 hours postoperative]
4. Level of sedation [up to 72 hours postoperative]
5. Incidence of opioid-related side effects [up to 72 hours postoperative]
