Methadone Pharmacokinetics in Cardiac Surgery

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, itraconazole), SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine) * Body mass index \>40 kg/m² * Corrected QT interval interval \>500 milliseconds * Intubation anticipated \>12 hours * History of illicit drug use or alcohol or opioid abuse use disorder within last 12 months * Mechanical circulatory support, heart transplant, deep hypothermic circulatory arrest procedures * Left Ventricular Ejection Fraction \<30% * Pulmonary disease requiring oxygen therapy * Preoperative inotropic support or intra-aortic balloon pump * Emergency surgery * Postoperative regional anesthesia * Hemofiltration during cardiopulmonary bypass