Effects of Nefopam on Hyperalgesia After Cardiac Surgery (NefalCard)
|Hyperalgesia Pain, Postoperative Pain, Chronic Disease||Drug: Nefopam Drug: néfopam Drug: Placebo comparator||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Study of the Effects of Nefopam on Hyperalgesia Following Sternotomy in Cardiac Surgery|
- Nociceptive threshold evaluated with Von Frey mechanical dynamic stimulation. This will start 10cm far from the wound on a perpendicular line to the wound and will be conducted by 1cm step to the wound until the patient explains the stimulation [ Time Frame: H 24 ]
- static hyperalgesia with Von Frey stimulation 1cm far from the middle of the wound, on the right side of the wound. [ Time Frame: 1, 2, 4 and 7 days after intervention ]
- Morphine consumption [ Time Frame: over the 48 H postoperative ]
- Pain scores evaluation [ Time Frame: Acute pain (1, 2, 4 and 7 days after intervention) / Chronic Pain (3, 6 and 12 month) ]
- Cognitive functions evaluation [ Time Frame: 1, 2, 4 and 7 days after intervention ]
|Study Start Date:||December 2006|
|Study Completion Date:||November 2008|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48
0,3mg/kg IV bolus preoperative and 65 µg/kg/h during H48 postoperative
nefopam administration will start at the end of the surgery and will be continued until postoperative H48
bolus Néfopam (0,3mg/kg) during 10 min at the end of surgery and 65 µg/kg/h during postoperative H48
Placebo Comparator: 3
control group that will receive a placebo from the induction time of anesthesia until H48
Drug: Placebo comparator
bolus NaCl during 10 min at the end of surgery and during postoperative H48
Postoperative pain is not only a consequence of the surgical lesion, but is also related to sensitization processes that appear in peripheral and central nerves. This sensitization induce clinically hyperalgesia and allodynia. From an experimental viewpoint it comes mainly from a central activation of NMDA receptors in neurons that conduct the nociceptive message.
Recent studies have shown that high-dose opioids were able, via NMDA receptors, to enhance postoperative hyperalgesia and to increase pain scores and morphine consumption after surgery. Nevertheless per operative use of opioid is still necessary to avoid per operative stress and systemic consequence of the surgical stimulation.
Some drugs (ketamine, nitrous oxide…) succeeded in reducing postoperative hyperalgesia and pains scores and acute morphine tolerance. They also were able to decrease pain chronicization.
Nefopam, well known as an analgesic since the 80's, presents both analgesic and anti hyperalgesic properties as lately demonstrated in experimental trials. Nevertheless these anti hyperalgesic properties have never been evaluated in humans scheduled for cardiac surgery. Nefopam administration could reduce acute morphine tolerance and could enhance postoperative pain management by reducing sensitization processes and hyperalgesia.
The main purpose of this clinical trial will be to evaluate in patients scheduled for cardiac surgery with sternotomy the nefopam effects on the nociceptive threshold evaluated with dynamic Von Frey mechanical stimulation.
The secondary objectives will evaluate static hyperalgesia, postoperative pain scores, morphine consumption, cognitive functions, and development of chronic pain and dysesthesia.
Prospective, randomized, double-blind study that will compare three parallel groups that will receive the same per operative anesthesia except for the nefopam doses.
Group 1: nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48. Group 2: nefopam administration will start at the end of the surgery and will be continued until postoperative H48. Group 3: control group that will receive a placebo from the induction time of anesthesia until H48. All patients will receive postoperatively morphine infusion following the Patient Controlled Analgesia concept.
Number of patients to be included : 90 Duration of the study : 2 years Start : second semester of 2006
Expected result :
Reduction of the extend of hyperalgesia around the wound evaluated with dynamic Von Frey mechanical stimulation more than 20%.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413257
|Département d'Anesthésie-Réanimation II - Hôpital cardiologique - Groupe Hospitalier Sud, CHU de Bordeaux - 4, Av de Magellan|
|Pessac, France, 33604|
|Principal Investigator:||Philippe RICHEBE, Dr||University Hospital, Bordeaux|
|Study Chair:||Antoine BENARD, Dr||University Hospital, Bordeaux|