Effects of nefopam on early postoperative hyperalgesia after cardiac surgery.
OBJECTIVE
The 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.


METHODS
This study was double-blinded and randomized.


METHODS
It was conducted in a single university hospital.


METHODS
Ninety American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery.


METHODS
Patients 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.


RESULTS
The 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.


CONCLUSIONS
Nefopam administered during the perioperative period slightly reduced acute hyperalgesia after cardiac surgery, but this was not associated with improved analgesic efficacy.
Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Seattle, WA 98195-6540, USA. prichebe@u.washington.edu
Philippe
P
Richebé
Walter
W
Picard
Cyril
C
Rivat
Srdjan
S
Jelacic
Olivier
O
Branchard
Sandy
S
Leproust
Alex
A
Cahana
Gérard
G
Janvier
D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000758:Anesthesia / Q000009:adverse effects; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009340:Nefopam / Q000627:therapeutic use*; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold; D010149:Postoperative Pain / Q000188:drug therapy*; D019990:Perioperative Care; D011183:Postoperative Complications / Q000453:epidemiology; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology
D018712:Analgesics, Non-Narcotic; D009340:Nefopam