Preoperative butorphanol and flurbiprofen axetil therapy attenuates remifentanil-induced hyperalgesia after laparoscopic gynaecological surgery: a randomized double-blind controlled trial

Abstract

Background: Several studies indicate that remifentanil exposure may engender opioid-induced hyperalgesia. Butorphanol and flurbiprofen axetil are proposed as adjunctive analgesics for postoperative pain control. This randomized double-blind controlled study was designed to investigate the antihyperalgesic effects of butorphanol combined with flurbiprofen axetil on opioid-induced hyperalgesia.

Methods: One hundred and twenty patients undergoing elective laparoscopic gynaecological surgery with sevoflurane anaesthesia were randomized to one of four groups, as follows: intraoperative sufentanil 0.30 µg kg-1 (Group S); remifentanil 0.30 µg kg-1 min-1 (Group R); intraoperative remifentanil and pre-anaesthesia butorphanol 20 µg kg-1 (Group B); or intraoperative remifentanil and pre-anaesthesia butorphanol 10 µg kg-1 combined with flurbiprofen axetil 0.5 mg kg-1 (Group BF). Sufentanil was used to control postoperative pain. The threshold and area of postoperative mechanical hyperalgesia were measured with Von Frey filaments. Pain intensity, sufentanil consumption, and side-effects were recorded for 24 h after surgery.

Results: Compared with Group S, remifentanil anaesthesia increased the pain score, postoperative sufentanil consumption, and area of hyperalgesia [mean 49.9 (sd 8.6) vs 60.5 (10.0) cm2, P<0.001] and reduced the hyperalgesia threshold on the dominant inner forearm [mean 89.5 (sd 23.4) vs 60.6 (22.6) g, P=0.004]. Compared with Group R, the pain score, sufentanil consumption, and area of hyperalgesia were reduced and hyperalgesia threshold was elevated likewise in Groups B and BF. However, the efficacy in Group BF was higher than in Group B (P=0.021).

Conclusions: The preoperative combination of butorphanol and flurbiprofen axetil effectively ameliorated opioid-induced hyperalgesia in patients undergoing laparoscopic gynaecological surgery under sevoflurane-remifentanil anaesthesia.

Clinical trial registration: NCT02043366.

Keywords: analgesics; butorphanol; complications; cyclo-oxygenase inhibitors; flurbiprofen axetil; hyperalgesia; opioid; opioid mixed agonist-antagonists; pain threshold; remifentanil.

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