• Olivier Mimoz, Stéphane Chauvet, Nicolas Grégoire, Sandrine Marchand, Marie-Emmanuelle Le Guern, Ashraf Saleh, William Couet, Bertrand Debaene, and René H Levy.
• Réanimation Chirurgicale Polyvalente, CHU de Poitiers, Poitiers, France. o.mimoz@chu-poitiers.fr
• Anesth. Analg. 2010 Nov 1;111(5):1146-53.

BackgroundTreatment of intense postoperative pain in patients with end-stage renal disease (ESRD) is a recurrent problem for anesthesiologists because of the risk of accumulation of numerous molecules and their metabolites. Nefopam is a potent analgesic metabolized by the liver and weakly eliminated intact in urine that may offer advantages for use in patients with ESRD because it lacks respiratory-depressive effects. However, the effects of renal failure on nefopam disposition have never been investigated.MethodsWe studied 12 ESRD patients (creatinine clearance < 20 mL/min, mean age 57 ± 13 years) having surgery under general anesthesia to create or repair an arteriovenous fistula. Postoperatively, after complete recovery from anesthesia, each patient received a single 20-mg dose of nefopam IV over 30 minutes. Nefopam and desmethyl-nefopam concentrations in plasma samples obtained over 48 hours were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameter values obtained were compared with those of 12 healthy 50- to 60-year-old volunteers who also received a single 20-mg nefopam infusion over 30 minutes using a population pharmacokinetic approach.ResultsHealthy volunteers and ESRD patients had comparable demographic characteristics. In comparison with those volunteers, ESRD patients had a lower volume of central compartment (115 and 53 L vs. 264 L for patients not yet hemodialyzed and on chronic hemodialysis, respectively; P < 0.001) and lower mean nefopam clearance (37.0 and 27.3 L/h vs. 52.9 L/h, P < 0.001), resulting in higher mean nefopam peak concentration (121 and 223 ng/mL vs. 61 ng/mL, P < 0.001).ConclusionsNefopam distribution and elimination are altered in patients with ESRD, resulting in heightened exposure. To avoid too-high concentration peaks, it is suggested that the daily nefopam dose be reduced by 50%.

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