Summary

The study utilizes a 3-arm placebo-controlled RCT to study the effectiveness of ketamine in reducing chronic post-mastectomy pain. Participants randomized to the first arm will receive a 0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (up to a maximum of 6 hours) and continued for 2 hours postoperatively. Participants in the second arm will receive a single dose of 0.6 mg/kg of ketamine in the post-anesthesia care unit, and the final group will serve as the control group and receive saline (no ketamine).

Age: 18 Years and older

Gender: Female

Start Date: 01/04/2022

Primary Completion Date (Estimated): 05/28/2025

Study Completion Date (Estimated): 08/31/2026

Accepts Healthy Volunteers: No

Trial Purpose and Description

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to study the effectiveness of ketamine in reducing PMPS. In a 3-arm, parallel-group study, approximately 750 adult women undergoing mastectomy or prophylactic mastectomy for oncologic reasons will be randomized to one of three arms. Participants in the first arm will receive continuous ketamine infusion starting after anesthetic induction (0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (with a maximum infusion of 6 hours) plus a postoperative saline dose, and continuation of 0.25 mg/kg/hr ketamine infusion for 2 hours postoperatively). Participants in the second arm will receive a dose of saline after induction, followed by a saline infusion during the surgery plus a single dose of 0.6 mg/kg of ketamine in the PACU, and 2 hours of saline infusion after surgery. The final group will serve as the control group and receive an intraoperative dose of saline, followed by saline infusion plus a postoperative saline dose and 2 hours of saline infusion after surgery. Participants will be followed at 1 and 7 days and 1, 3, 6, and 12 months after surgery.

Eligibility Criteria

Age: 18 Years and older

Gender: Female

Accepts Healthy Volunteers: No

Inclusion criteria:

Woman 18 years of age or older

Undergoing elective breast surgery for oncologic indication as follows: unilateral or bilateral mastectomy, prophylacticmastectomy, +/- lymph node dissection, +/- immediate or delayed reconstruction.

No distant metastases

Exclusion criteria:

History of cognitive impairment or clinical signs of altered mental status (AMS) that may interfere with adherence to study procedures and/or participant safety. Clinical signs of AMS may include but are not limited to: confusion, amnesia, disorientation, fluctuating levels of alertness, etc.

Past ketamine or phencyclidine misuse or abuse

Schizophrenia or history of psychosis

History of post-traumatic stress disorder

Known sensitivity or allergy to ketamine

Liver or renal insufficiency

History of uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine

Lamotrigine, alfentanil, physostigmine, or 4-aminopyridine use

Currently Pregnant

Body mass index (BMI) greater than 35

Non-English or non-Spanish speaker

Currently participating in another pain interventional trial

Unwilling to comply with all study procedures and be available for the duration of the study

Patient is American Society of Anesthesiologists (ASA) physical status 4, 5, or 6

Patient has started or undergone hormone therapy for gender transition into male.

Patient scheduled for any bilateral (or greater) flap reconstruction