This phase IV trial compares methadone versus hydromorphone given in the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord (intrathecal) for postoperative pain relief in patients with gynecologic cancer undergo surgery. Methadone binds to opioid receptors in the central nervous system and is a long-acting opioid pain medication. Intrathecal hydromorphone works by changing the way the brain and nervous system respond to pain and is similar to an epidural. This trial may help researchers determine if methadone works as well as intrathecal hydromorphone for pain relief after surgery in patients with gynecologic cancer.

PRIMARY OBJECTIVE:

I. To determine whether intravenous methadone can provide comparable analgesia to an intrathecal injection of hydromorphone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive methadone intravenously (IV) during induction of general anesthesia for standard of care (SOC) surgery.

ARM II: Patients receive hydromorphone intrathecally (IT) prior to induction of general anesthesia for SOC surgery.

After completion of study intervention, patients are followed up at 1 month.

Inclusion Criteria:

• Undergoing surgery with a laparotomy for gynecologic malignancy
• Planned inpatient admission greater than 24 hours

Exclusion Criteria:

• Chronic pain requiring greater than 20 morphine milligram equivalents of opioid medications as an outpatient
• Prolonged corrected QT interval (QTc) > 500ms
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) < 30 milliliters per minute (mL/min)
• Documented cirrhosis
• Preoperative platelets (PLT) < 100
• Preoperative international normalized ratio (INR) > 1.1
• Inappropriate cessation of anticoagulation medications prior to surgery
• Intolerance to hydromorphone or methadone
• Contraindication to administration of liposomal bupivacaine
• Subsequent surgeries after index surgery