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Therapeutic benefits of placebo surgery and challenges in neuromodulation research.

We read with great interest the article by Niedermayer et al., titled “Remifentanil for abdominal surgery is associated with unexpectedly unfavorable outcomes.” They demonstrated that patients administered with remifentanil intraoperatively had higher pain scores and analgesic requirements in the postanesthesia care unit than those who did not receive remifentanil, and that this effect was independent of epidural anesthesia usage. They discouraged the indiscriminate use of remifentanil in surgical procedures with high postoperative pain. Although the association between remifentanil and opioid-induced hyperalgesia or opioid tolerance has been well documented, the results of the study need to be interpreted cautiously. First, it is unclear whether the postoperative pain intensity and analgesic requirements were augmented by remifentanil in this study because the authors have not stated the total doses of sufentanil and epidural analgesics administered intraoperatively. The remifentaniltreated patient might have received lower doses of sufentanil or limited epidural analgesia as compared with those who did not receive remifentanil; this difference could increase the pain intensity and the requirement for higher doses of rescue analgesics immediately after surgery. Second, the mean doses of remifentanil (0.11 and 0.13 mg/kg/minute for general anesthesia and combined general/epidural anesthesia, respectively) administered in this study are not indicative of “indiscriminate use.” Third, as the authors have stated, the difference in the numerical rating scale for assessing pain between the 2 groups (0.08-0.55 out of 0-10) seems less relevant clinically. Although an excessive dose of remifentanil may induce hyperalgesia/opioid tolerance, inadequate analgesia is detrimental and may lead to hypertension, severe postoperative pain, and ultimately, persistent postsurgical pain. Besides hyperalgesia, remifentanil may cause other unfavorable outcomes such as intraoperative hypotension, bradycardia, and postoperative shivering, which were not addressed in the article. It would be helpful if these clinical aspects are considered, especially when considering the application of such results in daily clinical practice.