Intraoperative Methadone for the Management of Postoperative Pain in Patients With Head and Neck Cancers

Inclusion Criteria:

* Adults 18-89
* Patients with biopsy proven head and neck cancer\*. Diagnosis will be confirmed by Otolaryngology-Head and Neck Surgery (OTOHNS) team at our center

  * Oral cavity, oropharyngeal, hypopharyngeal, laryngeal
* Undergoing surgical intervention with ablative and/or reconstructive OTOHNS surgeons for one of the following:

  * Free flap reconstruction (single or double flaps including: radial forearm free flap \[RFFF\], osteocutaneous radial forearm flap \[OCRFF\], fibula free flap \[FFF\], anterolateral thigh \[ALT\], scapula flap, latissimus, gracilis, rectus sheath, pectoralis)
  * Resections with pedicled flaps (e.g., pectoralis major, latissimus) with an expected case time of \> 4 hours

    * Expected time of surgery is found in the surgery request and in our department, the surgeon puts in these orders

Exclusion Criteria:

* Patients will be excluded if they do not consent, are minors, are deemed part of a vulnerable population or lack decision-making capacity
* Current use of long-acting opioids
* Pain patients treated with opioids for pathology unrelated to head and neck cancer and/or chronic pain patients, i.e. chronic back pain
* Positive screening at interview for illicit drug use, not including marijuana

  * Drug screening is not routinely acquired prior to anesthesia per our institution's standard of care and policies. Any suspected abuse or use is guided by clinical evaluation. Patients with evidence of acute intoxication or concern for prior abuse history will be excluded per clinical judgement
* Contraindications to methadone (American Society of Addiction Medicine \[ASAM\] criteria): hypersensitivity, severe respiratory depression, paralytic ileus - in which only hypersensitivity is relevant, since individuals undergoing surgery would not present with the latter
* Currently on CYP therapies noted in the Food and Drug Administration (FDA) methadone pamphlet to have either decreased efficacy of therapy or reduced metabolism of methadone with concurrent use

  * Rifampin, phenytoin, phenobarbital, carbamazepine, voriconazole, abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, tipranavir+ritonavir combination, didanosine, stavudine, zidovudine
* Extensive surgical interventions that require additional assistance from outside services at the time of reconstruction (i.e. hypopharyngeal cancer also requiring esophagectomy)
* Head and neck cancers with intracranial components (direct, primary tumor extension, metastatic disease)
* Body mass index (BMI) \> 40
* Sleep apnea with an apnea-hypopnea index \> 30 without planned tracheostomy
* Stage 3b chronic kidney disease or higher (estimated glomerular filtration rate \< 45)
* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than two times the upper limit of normal
* Patients with a history of corrected QT interval (QTc) prolongation \> 500 ms