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

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 mu g kg(-1) (Group S); remifentanil 0.30 mu g kg(-1) min(-1) (Group R); intraoperative remifentanil and pre-anaesthesia butorphanol 20 mu g kg(-1) (Group B); or intraoperative remifentanil and pre-anaesthesia butorphanol 10 mu g 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) cm(2), 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.