Evaluating Pharmacokinetics of Three Methadone Dosing Strategies During Cardiac Surgery With Cardiopulmonary Bypass
Wake Forest University Health Sciences
Summary
Cardiac surgery frequently leads to significant postoperative pain, with multiple different drug regimens being utilized (both opioid and non-opioid) in an attempt to alleviate this surgical pain. Methadone is currently one of the drugs that is being utilized to help control the pain. It can be given during and/or after surgery. This study hopes to identify the optimal dose of methadone to use to treat this surgical pain.
Description
The uncertainty regarding optimal methadone dosing and the necessity of post-cardiopulmonary bypass (CPB) supplementation provides a compelling rationale for this study. Specifically, it remains unknown whether a single higher initial dose of methadone can adequately maintain analgesic plasma concentrations throughout cardiac surgery and recovery, or if a split-dosing strategy administering a lower initial dose followed by an additional dose post-CPB might offer similar or improved analgesic outcomes with fewer side effects. This study will evaluate pharmacokinetics of methadone using three di…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Elective cardiac surgery requiring median sternotomy and cardiopulmonary bypass (CABG, valve, combined CABG/valve surgeries) * Anticipated extubation within 12 hours postoperatively * No prior opioid use within 30 days of surgery * Ability to provide informed consent Exclusion Criteria: * Severe liver or kidney dysfunction (Child-Pugh class B/C, eGFR \<30 mL/min/1.73m², creatinine \>2 mg/dL, dialysis) * Allergy to methadone or fentanyl * Use of CYP3A4 inducers (rifampin, phenytoin, carbamazepine), CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin, itraconaz…
Interventions
- DrugSingle dose of methadone
Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia
- DrugSplit dose of methadone
Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass
- DrugBalanced split dose of methadone
Balanced split dose of methadone 0.15 mg/kg actual body weight at induction and 0.15 mg/kg actual body weight post cardiopulmonary bypass
Location
- Wake Forest University Health SciencesWinston-Salem, North Carolina