Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study

Background: Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited. Objectives: The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery. Study design: We used a randomized, double-blinded, placebo study design. Setting: This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016. Methods: A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery. Results: For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up. Limitations: There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment. Conclusions: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients’ quality of life. Key words: Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol