This is a randomized, double-blinded, placebo-controlled trial to compare the effectiveness of IV oxytocin infusion to placebo on peri-operative opioid consumption and reducing post-operative pain following a minimally invasive hysterectomy under general anesthesia.

152 women will be randomized into one of two arms; participants in the first arm (Intervention) will receive oxytocin infusion, 30 IU in 500 ml IV infusion at a rate of 5 IU/h (83.33 ml/h), the second arm (Control) will receive 0.9% normal saline 500 ml IV infusion at the same rate of 83.3 ml/h. The primary care team (anesthesia, surgery, and nursing), the research team, and the patient will all be blinded to the research arm.

The investigational research pharmacy will perform randomization; participants will be randomized in a 1:1 ratio to receive either Oxytocin or Placebo (0.9% normal saline). Randomization will be blinded to investigators to prevent bias and ensure balance in treatment arms throughout the study. Participants, surgeons, clinicians, and raters will be blinded with respect to treatment assignments. The investigational pharmacy will prepare the study drug based on the randomization assignment received.

The investigators will identify patients who have been scheduled for an elective, minimally invasive hysterectomy at Brigham and Women's Hospital by reviewing the operating room booking schedule.

Patients will be pre-screened for inclusion and exclusion criteria. Subsequently, they will be recruited for participation in this study by phone/ MGB Zoom and will be consented by electronic consent.

Once the patient is recruited and consented, they will be randomized for either the intervention group (oxytocin IV infusion) or the control group (0.9% normal saline IV infusion).

An email will be sent to those who consent with a link to the secure REDCap system containing a set of baseline questionnaires to assess relevant medical and surgical history, pre-operative pain, analgesic medication use, and psychosocial variables.

Both groups (intervention and control) will be treated pre-operatively with the following Early Recovery After Surgery (ERAS) medications, as per usual institutional practice:

• acetaminophen 1,000 mg orally
• celecoxib 400 mg orally The Investigational Research Pharmacy will be informed and prepare blinded infusions for perioperative administration (oxytocin or placebo).

The primary anesthesiology team will receive either the study medication or placebo in a 500 ml bag labeled as "Oxytocin Study Drug for IV infusion".

A recommended "Intra-Operative Analgesia Management" algorithm will be given to the primary anesthetic team. The recommended algorithm for intra-operative analgesia management will include the following:

• Fentanyl 100 mcg IV for induction.
• Dexamethasone 8 mg IV after induction but prior to skin incision.
• Small, titrated doses of Hydromorphone IV boluses (0.2-0.4 mg) during the operation and before emergence, according to primary team judgment.
• Ketorolac 30 mg IV prior to skin closure, unless otherwise contraindicated.
• Avoidance of other multimodal analgesic agents not included in this protocol to limit confounders.

The infusion will be started after the skin incision and will continue until the infusion is completed or the post-anesthesia care unit (PACU) criteria are met, whichever occurs first.

Other aspects of each patient's routine clinical care will continue as per standard care at the attending physician's discretion under whom the patient is admitted, regardless of treatment arm status.

In the PACU, a brief postoperative pain questionnaire will be performed, including the Surgical Pain Scales (SPS).

The SPS is a validated scale consisting of 4 items that measure pain at rest, during normal activities, and during work/exercise and quantify the unpleasantness of worst pain. This scale has been validated in a number of different types of postoperative pain, including women after gynecologic surgery.

Vital signs, numeric rating scale (NRS) pain scores, and opioid consumption in PACU will be collected from the patient's medical record.

Patients whose surgery was converted to open, estimated blood loss (EBL) >500 ml, or any other surgical complication that necessitates hospitalization will be excluded from the trial.

For secondary outcomes, including total opioid consumption in 24, 48, and 72 hours and pain scores at postoperative day (POD)1, 2, and 3, an online survey will be done at POD1, 2, and 3, and follow-up will continue until 3 months post-op.

Inclusion Criteria:

• Ages 18-65 years old
• ASA category 1-3
• Scheduled to undergo minimally invasive hysterectomy
• No documented allergy to oxytocin

Exclusion Criteria:

• American Society of Anesthesiologists (ASA) group 4 or greater
• Age >65 years old
• Additional surgical procedures including but not limited to minor laparotomy, omentectomy, cystectomy, vaginectomy, and/or ablation of endometriosis.
• Active opioid prescription of the equivalent of oxycodone >10 mg /day
• Opioid use disorder, including patients in treatment receiving naltrexone or Suboxone (Buprenorphine-naloxone)
• Allergies to any study medication: acetaminophen, celecoxib, ketorolac, fentanyl, hydromorphone, or oxycodone.
• Epidural/Regional anesthesia for intra-operative or post-operative pain.
• Inability to understand the questionnaires
• Intra-operative and post-operative exclusion: Procedure converted to open or extension of primary surgery, Intra-operative EBL >500 ml., Placement of epidural catheter or regional anesthesia at PACU for pain management, Hospitalization of the patient due to surgical or anesthetic complications

Randomization of the study medication will be performed by the investigational drug pharmacy and the unblinded key will be stored in a secure location in the pharmacy.