Although acute tolerance to opioids, especially to remifentanil, has been demonstrated consistently in animal studies, the results of clinical trials in humans are controversial. The aim of this study was to determine whether intraoperative infusions of remifentanil used as an adjuvant in general anesthesia result in acute tolerance, an event manifested by increased postoperative pain and a higher opioid requirement than usual.

Sixty patients who underwent surgery under general anesthesia for spinal fusion were randomly assigned to receive sevoflurane-nitrous oxide-oxygen (group SO, n = 20), sevoflurane-remifentanil-nitrous oxide-oxygen (group SR, n = 20), or propofol-remifentanil-oxygen (group PR, n = 20) in a double-blinded manner. All patients within 1 hour after induction received PCA (fentanyl 0.4 µg/kg/ml and ondansetron 16 mg) administered intravenously at a basal infusion rate of 1 ml/h, after being intravenously injected with a loading dose of fentanyl (1 µg/kg). Data for fentanyl requirement, verbal Numerical Rating Scale (NRS) pain score at rest, and presence of nausea or vomiting were collected at 1, 24, and 48 hours after surgery.

We did not find any significant difference in postoperative PCA fentanyl requirements, NRS or side effects among the groups.

Remifentanil as an adjuvant to sevoflurane or propofol in general anesthesia for adults having surgery for spinal fusion does not appear to cause acute opioid tolerance or hyperalgesia in patients. However, further studies are needed to elucidate whether sevoflurane and propofol exert a clinically significant effect on opioid-induced tolerance or hyperalgesia and whether this effect is related to the age of the patient, the dose and duration of remifentanil given and the intensity of pain experienced postoperatively.