Post-operative Analgesic Effect of Oral Nefopam: a Randomized Controlled Trial
Post-operative Analgesic Effect of Oral Nefopam: a Randomized Controlled Trial
High tibial osteotomy is a common procedure in orthopedic surgery; it is highly standardized
 (incision location and size, the volume of periosteal lesion, implanted material). It is
 associated with short recovery period but intense postoperative pain during first 24 hours.
 The surgical wound has a comprehensive innervation by saphenous and a terminal muscular
 branches of tibial nerve. These conditions allow reproducible measurements of analgesic drugs
 effects in postoperative period.

 Nefopam is a non-opioid centrally acting analgesic drug used as a part of multimodal
 analgesia. The opioid-sparing effect of nefopam is still controversial across various
 surgical procedures. In France nefopam is only available as a parenteral formulation; however
 it is often administered orally. There is currently no study addressing the efficacy of oral
 nefopam for the postoperative pain management including pain prevention.

 We conduct a prospective, double-blinded randomized controlled study with the main objective
 to examine the effect of perioperative orally administered nefopam on postoperative pain
 after a high tibial osteotomy. Secondary objectives include the quantification of wound
 allodynia, analysis of adverse events, clinical outcomes, and a pharmacokinetic study of
 orally given nefopam (plasma and cerebrospinal fluid dosage).
Inclusion Criteria:

 -  adult patients scheduled for a high tibial osteotomy under spinal anesthesia at the
 Hopital de la Croix Rousse, Hospice Civils de Lyon, France.

 -  ASA (American Society of Anesthesiology) class between 1 et 3.

 -  written informed consent

 Exclusion Criteria:

 -  any contraindication for nefopam (known hypersensitivity, past medical history of
 seizures, urinary retention, benign prostate hyperplasia, angle glaucoma, ischemic
 cardiomyopathy waiting for revascularization, atrial fibrillation)

 -  medical conditions known to influence the pharmacokinetics of nefopam (chronic kidney
 failure with Glomerular Filtration Rate (GFR) <30mL/min/1,73m2, liver failure, current
 treatment with rifampicin, carbamazepine, azoles fungicides, macrolides)

 -  current treatment with benzodiazepines, anxiolytics, antidepressants, histamine H1
 antagonists, neuroleptics, baclofen, thalidomide, barbiturates

 -  medical history of gastric or esophageal surgery.

 -  phenylketonuria

 -  pregnancy or breastfeeding

 -  past use of oral nefopam