Opioid-free Anesthesia Protocol on the Early Quality of Recovery after Major Surgery (SOFA Trial): A Randomized Clinical Trial

Background. Opioid-free anesthesia (OFA) is increasingly being adopted to reduce opioid consumption, but its impact on early postoperative recovery following major surgery has not been evaluated in comparative trials. We hypothesized that an OFA protocol would enhance the early quality of recovery (QoR) for patients undergoing scheduled major surgery under general anesthesia.Methods. The SOFA study was a monocentric, randomized, controlled, assessor- and patient-blinded clinical trial conducted from July 10, 2021, to February 12, 2022. The eligible population included male and female patients undergoing scheduled major surgery, excluding bone procedure, that typically require opioids for postoperative pain management. Patients in the intervention group received a combination of at least two drugs among ketamine, lidocaine, clonidine, and magnesium sulfate, without opioids for anesthesia. The standard group received opioids. The primary outcome was early postoperative QoR, assessed by QoR-15 score at 24 hours (H24) after surgery. Secondary outcomes were QoR-15 at 48 hours (H48) and 72 hours (H72) after surgery, incidence of chronic pain, and quality of life at three months.Results. Of the 136 randomized patients, 135 were included in the primary analysis (mean age: 45.9±15.7 years; 116 females (87.2%); 85 underwent major plastic surgery (63.9%)), with 67 patients in the OFA group and 68 in the standard group. The mean QoR-15 at H24 was 114.9±15.2 in the OFA group versus 108.7±18.1 in the standard group (difference of 6.2, 95% CI, 0.4–12.0; p=0.026). QoR-15 scores also differed significantly at H48 (difference of 8.7, CI 95% 2.9–14.5); p=0.004) and at H72 (difference of 7.3, CI 95% 1.6–13.0, p=0.013). There was no difference in other secondary outcomes. No major adverse events were noticed.Conclusion. The OFA protocol improved QoR after major elective surgery in a statistically but not clinically significant manner when compared to standard anesthesia.