Effects of Nefopam on Early Postoperative Hyperalgesia After Cardiac Surgery

ObjectiveThe purpose of this randomized, double-blind placebo-controlled study was to evaluate the effect of nefopam, a centrally acting antinociceptive compound, on the development of hyperalgesia after sternotomy. Preventive strategy giving nefopam from the early stage of anesthesia was compared with a postoperative strategy only and placebo.DesignThis study was double-blinded and randomized.SettingIt was conducted in a single university hospital.ParticipantsNinety American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery.InterventionsPatients were assigned randomly to receive a 0.3-mg/kg bolus of nefopam at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G1), a 0.3-mg/kg bolus of nefopam at the end of surgery followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G2), or a placebo (G3). Postoperative analgesia was based on morphine patient-controlled analgesia and rescue analgesia when necessary. Postoperative hyperalgesia, pain scores, morphine consumption, and postoperative cognitive dysfunction were assessed for the first 48 hours and thereafter on postoperative days 4 and 7.Measurements and Main ResultsThe postoperative extent of dynamic hyperalgesia and the decrease of the nociceptive threshold evaluated by von Frey filaments at the sternal midline were smaller in group 1 and group 2 compared with the placebo group at the 24th hour. The primary objective was the extent of hyperalgesia at the midline given as the mean (standard deviation [SD]) (4.4 [2.5] cm for G1, 4.1 [2.7] for G2, and 6.1 [2.7] cm for G3. The punctuate is given as mean (SD) (64 [43] g for G1, 68 [40.8] g for G2, and 32 [27] g for G3; with p < 0.05 for the comparisons of extent and punctuate hyperalgesia between G1 and G3 and G2 and G3). The extent of hyperalgesia was not significantly different among the 3 groups on days 2, 4, and 7 after surgery. There were no significant differences in pain scores, morphine consumption, or postoperative cognitive dysfunctions.ConclusionsNefopam administered during the perioperative period slightly reduced acute hyperalgesia after cardiac surgery, but this was not associated with improved analgesic efficacy.