title: Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects.
abstract: BACKGROUND
  The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.
  
  
  METHODS
  Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34 degrees C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.
  
  
  RESULTS
  Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9 degrees C. microg-1. ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0 degrees C. microg-1. ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3 degrees C. microg-1. ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4 degrees C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds.
  
  
  CONCLUSIONS
  Most drugs with thermoregulatory actions-including anesthetics, sedatives, and opioids-synchronously reduce the vasoconstriction and shivering thresholds. However, nefopam reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulations of vasoconstriction and shivering can be separated is of clinical and physiologic interest.
authors.affiliation: Department of Anesthesia, Hôpital Ambroise Paré, Assistance Publique-Hopitaux de Paris, France. pascal.alfonsi@apr.ap-hop-paris.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Alfonsi
authors.forename: Frederic
authors.initials: F
authors.lastname: Adam
authors.forename: Andrea
authors.initials: A
authors.lastname: Passard
authors.forename: Bruno
authors.initials: B
authors.lastname: Guignard
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Marcel
authors.initials: M
authors.lastname: Chauvin
mesh_terms: D000328:Adult; D000465:Algorithms; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000494:pharmacology*; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009340:Nefopam / Q000009:adverse effects / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D012768:Shivering / Q000187:drug effects*; D013546:Sweating / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D009340:Nefopam; D010100:Oxygen