title: 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-1min-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-1combined 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.
  
  
  BACKGROUND
  NCT02043366.
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Shu
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China wangguolinghad@hotmail.com.|Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D002077:Butorphanol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013509:Gynecologic Surgical Procedures; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D010535:Laparoscopy; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects*; D000077208:Remifentanil
chemical_list: D010880:Piperidines; D005480:Flurbiprofen; C504422:flurbiprofen axetil; D000077208:Remifentanil; D002077:Butorphanol
keywords: analgesics; butorphanol; complications; cyclo-oxygenase inhibitors; flurbiprofen axetil; hyperalgesia; opioid; opioid mixed agonist-antagonists; pain threshold; remifentanil