Intraoperative
remifentanil infusion may paradoxically induce post-surgical
hyperalgesia.
Dexmedetomidine reportedly reduces
opioid-induced
hyperalgesia.
Nalmefene selectively reverses several side-effects of
opioids without impairing
analgesia. Herein, this randomized, double-blind controlled trial investigated whether
nalmefene,
dexmedetomidine, and both drugs combined prevent
remifentanil-induced
hyperalgesia. One hundred and fifty patients undergoing elective laparoscopic
gynecological surgery under
desflurane anesthesia randomly received either intraoperative
sufentanil 0.20 μg kg-1 (Group S), or
remifentanil 0.20 μg kg-1 min-1 (Group R), or
remifentanil and pre-
anesthesia nalmefene 0.20 μg kg-1 (Group N), or
remifentanil and pre-
anesthesia dexmedetomidine 0.50 μg kg-1 (Group D), or
remifentanil and the combination of
dexmedetomidine 0.25 μg kg-1 and
nalmefene 0.10 μg kg-1 (Group DN). The threshold of postoperative
mechanical hyperalgesia (primary outcome) was measured with von Frey filaments. We also recorded
pain intensity,
analgesic consumptions, hyperalgesic area, and side-effects for 24 h postoperatively. Compared with Group S,
remifentanil reduced hyperalgesic threshold on the forearm [mean 89.4 (SD 13.7) vs. 62.2 (10.7) g, p < 0.001] at postoperative 24 h. Pain threshold on the forearm at postoperative 24 h was significantly lower in Group R than in Groups N, D and DN [62.2 (10.7) vs. 71.1 (12.3), 72.4 (12.9) and 78.0 (13.8) g]. Compared with Group R,
Postoperative pain intensity,
analgesic consumption and hyperalgesic area were lower likewise in Groups D and DN. However, the incidence of intraoperative
bradycardia was lower and post-
anesthesia recovery time was shorter in Group DN than Group D. Preoperative
therapy of
dexmedetomidine and
nalmefene combined attenuates postoperative
hyperalgesia in patients undergoing laparoscopic
gynecological surgery under
desflurane-
remifentanil anesthesia.