Protective effects of dexmedetomidine combined with flurbiprofen axetil on remifentanil-induced hyperalgesia: A randomized controlled trial

Abstract

High dosages of intra-operative remifentanil are associated with opioid-induced hyperalgesia (OIH). The aim of the present study was to investigate the effect of combined dexmedetomidine and flurbiprofen axetil treatment on remifentanil-induced hyperalgesia. Patients with an American Society of Anesthesiologists physical status of I-II who were diagnosed with hysteromyoma and scheduled for laparoscopic assisted vaginal hysterectomy (LAVH) were randomly divided into three groups. Group hyperalgesia (Group H, n=29) received intra-operative remifentanil, Group hyperalgesia and dexmedetomidine (Group HD, n=28) received remifentanil and a continuous infusion of dexmedetomidine, and Group hyperalgesia, dexmedetomidine and flurbiprofen axetil (Group HDF, n=29) received remifentanil, flurbiprofen axetil and dexmedetomidine. Mechanical pain thresholds were measured during the preoperative visit and postoperatively at 1, 6 and 24-h time points. Visual analog scale (VAS) scores, time to analgesic requirement, total sufentanil consumption and side effects were assessed postoperatively. Mechanical pain threshold at the incision site was significantly lower in Group H compared with Groups HD and HDF (both P<0.05), and significantly higher in Group HDF than in Group HD (P<0.05). The area of secondary hyperalgesia at the incision site was greater in Group H than in the other two groups (both P<0.05), and significantly smaller in Group HDF compared with Group HD (P<0.05). VAS scores and total sufentanil consumption were significantly higher in Group H compared with the other two groups (both P<0.05), and were significantly lower in Group HDF compared with Group HD (P<0.05). Dexmedetomidine combined with flurbiprofen axetil exhibits synergetic effects in the prevention of remifentanil-induced hyperalgesia in patients undergoing LAVH.

Keywords: dexmedetomidine; flurbiprofen axetil; opioid induced hyperalgesia; remifentanil.

Figure 1.

Consolidated Standards of Reporting Trials flowchart. Group H, high dose of remifentanil (0.3 µg/kg/min); Group HD, high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine; Group HDF, high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine and flurbiprofen axetil.

Figure 2.

Peri-incisional mechanical pain threshold around the umbilicus Values are expressed as means and the error bars indicate standard deviation. Group H, high dose of remifentanil (0.3 µg/kg/min); Group HD, high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine; Group HDF: high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine and flurbiprofen axetil. ⁺P<0.05 vs. Group H, ^#P<0.05 vs. Group HD.

Figure 3.

Postoperative pain scores measured with visualized analog scale values are expressed as medians and the error bars indicate the interquartile range. Group H, high dose of remifentanil (0.3 µg/kg/min); Group HD, high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine; Group HDF, high dose of remifentanil (0.3 µg/kg/min) plus dexmedetomidine and flurbiprofen axetil. ⁺P<0.05 vs. Group H, ^#P<0.05 vs. Group HD.