Suzetrigine for Non-Mastectomy Breast Surgery: A Non-Randomized, Prospective Study With Historic Controls

Following written, informed consent, the investigators will collect baseline anthropomorphic information (e.g., age, sex, height, and weight). For individuals of childbearing potential, a sample of urine will be collected before any study interventions to confirm a non-pregnant state (this is standard procedure for all surgical patients).

The University of California San Diego Investigational Drug Service will distribute the study medication (suzetrigine) to the investigators (7 suzetrigine tablets, each 50 mg) and labeled with the appropriate dosing. The first dose of study medication (2 tablets = 100 mg) will be delivered preoperatively: 2 tablets to the participant. In addition, all participants will be given oral acetaminophen (975-1000 mg) per our standard-of-care.

Paravertebral nerve blocks (standard of care). All subjects will have a peripheral intravenous catheter inserted, standard noninvasive monitors applied, and oxygen delivered by facemask. The paravertebral nerve block site(s) will be cleansed with chlorhexidine gluconate and isopropyl alcohol. Intravenous sedation/analgesia with midazolam and/or fentanyl will be titrated for patient comfort as is standard for peripheral nerve block administration. A low-frequency curvilinear ultrasound transducer (6-2 MHz) will be used to identify the T1 through T5 transverse processes and paravertebral spaces. The target nerves will be visualized with ultrasound using a transverse cross-sectional (short axis) view and a skin wheal of local anesthetic will be raised inferior to the transducer to anesthetize the skin and then the track towards the target. A 20-gauge Tuohy needle will be inserted into the appropriate plane/space under direct ultrasound guidance via an in-plane parasagittal approach. Local anesthetic (0.5% ropivacaine) with 1:400,000 of epinephrine will be injected at the appropriate levels after negative aspiration (20 mL for unilateral surgery, 16 mL on each side for bilateral surgery). A two-level injection technique will be performed: T2 and T4 for surgeries involving axillary work or T3 and T5 for surgeries not involving axillary work. Blocks will be considered successful if, within 30 min, the subject experiences decreased sensation to cold temperature over the level of the ipsilateral fourth thoracic dermatome at the level of anterior axillary line. For subjects undergoing a bilateral surgical procedure, blocks using the same protocol will be administered on the contralateral side.

Intraoperative and postoperative management. Surgery will be performed under general anesthesia with a combination of inhaled and intravenous anesthetics. Intraoperative fentanyl will be administered at the discretion of the masked anesthesia team based on cardiovascular responsiveness to noxious stimuli, and total fentanyl use will be recorded. Subjects will be extubated, taken to the postanesthesia care unit and received by a nurse masked to treatment group assignment. A standard postoperative opioid algorithm will be used which involves: 1) intravenous fentanyl 25 µg for Numeric Rating Scale (NRS) pain scores of less than 5, 2) intravenous fentanyl 50 µg for NRS of 5 or greater, 3) intravenous hydromorphone 0.5 mg for NRS of 5 or greater if fentanyl deemed ineffective, and 4) oxycodone 5 mg for NRS of 4 to 6 if able to tolerate oral medications. It is rare that patients with a paravertebral nerve block require any analgesics in the recovery room. Participants and their caretakers will have the study protocol reviewed with them and then be discharged home with 5 tablets of study medication (suzetrigine 50 mg), a prescription for rescue oxycodone, and written instructions. Participants will be instructed to take 1 tablet every 12 hours following the initial dose through the evening of postoperative day 2. They will be instructed to avoid food or drink containing grapefruit until postoperative day 4 (contraindicated with suzetrigine).

Comparison group. The collected data will be compared with study participants from two previously completed randomized, controlled trials in which half of all participants received a placebo/sham intervention. Therefore, the historic controls all received University of California San Diego's standard analgesics and no investigational intervention [1,2]