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Preoperative But Not Postoperative Flurbiprofen Axetil Alleviates Remifentanil-induced Hyperalgesia After Laparoscopic Gynecological Surgery: A Prospective, Randomized, Double-blinded, Trial

Zhang, Linlin PhD, MD; Shu, Ruichen PhD; Zhao, Qi PhD; Li, Yize PhD; Wang, Chunyan PhD; Wang, Haiyun PhD; Yu, Yonghao PhD, MD; Wang, Guolin MD

The Clinical Journal of Pain: May 2017 - Volume 33 - Issue 5 - p 435–442
doi: 10.1097/AJP.0000000000000416
Original Articles

Background: Acute remifentanil exposure during intraoperative analgesia might enhance sensitivity to noxious stimuli and nociceptive responses to innocuous irritation. Cyclooxygenase inhibition was demonstrated to attenuate experimental remifentanil-induced hyperalgesia (RIH) in rodents and human volunteers. The study aimed to compare the effects of preoperative and postoperative flurbiprofen axetil (FA) on RIH after surgery.

Materials and Methods: Ninety patients undergoing elective laparoscopic gynecologic surgery were randomly assigned to receive either intravenous placebo before anesthesia induction (Group C); or intravenous FA (1.0 mg/kg) before anesthesia induction (Group F1) or before skin closure (Group F2). Anesthesia consisted off sevoflurane and remifentanil (0.30 μg/kg/min). Postoperative pain was managed by sufentanil titration in the postanesthetic care unit, followed by sufentanil infusion via patient-controlled analgesia. Mechanical pain threshold (primary outcome), pain scores, sufentanil consumption, and side-effects were documented for 24 hours postoperatively.

Results: Postoperative pain score in Group F1 was lower than Group C. Time of first postoperative sufentanil titration was prolonged in Group F1 than Group C (P=0.021). Cumulative sufentanil consumption in Group F1 was lower than Group C (P<0.001), with a mean difference of 8.75 (95% confidence interval, 5.21-12.29) μg. Mechanical pain threshold on the dominant inner forearm was more elevated in Group F1 than Group C (P=0.005), with a mean difference of 17.7 (95% confidence interval, 5.4-30.0) g. Normalized hyperalgesia area was decreased in Group F1 compared to Group C (P=0.007). No statistically significant difference was observed between Group F2 and Group C.

Conclusions: Preoperative FA reduces postoperative RIH in patients undergoing laparoscopic gynecologic surgery under sevoflurane-remifentanil anesthesia.

*Tianjin Research Institute of Anesthesiology

Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, P.R. China

L.Z., H.W., and G.W.: conceived and designed the experiment. L.Z., R.S., Q.Z., and Y.L.: performed the experiment and collected the data. L.Z., C.W., and Y.Y.: analyzed the data. L.Z. and G.W.: wrote the paper.

Supported by research grants from the National Natural Science Foundation of China (81371245, 81301025, 81400908, and 81571077), Tianjin, China. The authors declare no conflict of interest.

Reprints: Guolin Wang, MD, Tianjin Research Institute of Anesthesiology and Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China (e-mail:

Received February 29, 2016

Received in revised form August 5, 2016

Accepted July 4, 2016

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.