By conducting a monocentric, randomized, controlled, assessor- and patient-blinded clinical trial of 136 patients who underwent major surgery, Léger et al.  compared the effects of opioid-free anesthesia and standard anesthesia protocols on the quality of recovery assessed by the Quality of Recovery-15 (QoR-15) score in the first 72 h after surgery. They showed that the opioid-free anesthesia protocol improved the quality of early postoperative recovery in a statistically but not clinically significant manner. As primary outcome of this study, however, the authors did not provide the preoperative QoR-15 scores and state whether they were comparable between groups in baseline characteristics of patients. Available evidence indicates that preoperative baseline QoR-15 scores are positively associated with early postoperative QoR-15 scores.  Because the difference between preoperative and postoperative QoR-15 scores may display the features of patient’s perioperative experience changes, moreover, it has been used to compare the influence of anesthetic methods on the quality of early postoperative recovery.  Although this is a randomized controlled trial and preoperative QoR-15 scores should not be significantly different between groups, we are still concerned that a significant between-group imbalance in this unknown factor would have biased the main findings of this study.

Second, most of the study subjects were healthy patients, with a mean age of 44 to 48 yr and American Society of Anesthesiologists Physical Status classification I or II. However, we noted that the mean QoR-15 scores at 72 h postoperatively were only 129.2 in the opioid-free anesthesia group and 121.9 in the standard anesthesia group, with large SDs. These results indicate that a substantial subset of patients in the two groups do not achieve a good quality of recovery with a QoR-15 score of 122 or more at 3 days postoperatively.  Similarly, most of the included patients in this study underwent nondigestive surgery, but median times to bowel movement in the two groups were up to 5 days, with an interquartile range of 4 to 8 days. This cannot be accepted in the context of current enhanced recovery after surgery practices. As the quality of postoperative recovery and time to gastrointestinal recovery are the important outcomes of patient comfort deemed by the Standardized Endpoints in Perioperative Medicine initiative we would like to know possible causes of these delayed recovery outcomes.

Finally, unlike recent other works that assessed the clinical benefits of the opioid-free anesthesia protocol including intraoperative and postoperative periods the timeframe of interest for this study was limited to the intraoperative period and not extended to the postoperative stage. According to the opioid-free anesthesia protocol published by the authors and the data provided in table 3 of their article we found that this study actually used an opioid-based postoperative analgesia strategy including morphine and oxycodone but without a scheduled administration of no-opioid analgesics, such as acetaminophen and nonsteroidal anti-inflammatory drugs. Furthermore, median opioid consumption in the first day postoperatively in the opioid-free anesthesia group was 21.0 (interquartile range, 6.0 to 36.0) milligram morphine equivalents. Other than the risk of drug abuse, postoperative opioid use is also associated with a serial of adverse effects that can delay postoperative recovery and compromise the quality of recovery.  Thus, we argue that such a study design of restricting the application of opioid-free anesthesia to the intraoperative period may have partly offset the potential benefits of the intervention.