title: Propofol linearly reduces the vasoconstriction and shivering thresholds.
abstract: BACKGROUND
  Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 +/- 6% and 19 +/- 8%, respectively. (Skin temperature has long been known to contribute approximately 10% to the control of sweating). Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core-temperature thresholds at a single-designated skin temperature.
  
  
  METHODS
  Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micrograms/ml; (3) a target concentration of 4 micrograms/ml; and (4) a target concentration of 8 micrograms/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees C), the propofol concentration-response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model.
  
  
  RESULTS
  The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = -0.6 +/- 0.1 degrees C.micrograms-1.ml-1; r2 = 0.98 +/- 0.02) and shivering (slope = -0.7 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.95 +/- 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.46 +/- 0.39).
  
  
  CONCLUSIONS
  Advantages of this new model include its being nearly noninvasive and requiring relatively little core-temperature manipulation. Propofol only slightly alters the sweating threshold, but markedly reduces the vasoconstriction and shivering thresholds. Reductions in the shivering and vasoconstriction thresholds are similar; that is, the vasoconstriction-to-shivering range increases only slightly during anesthesia.
authors.affiliation: Thermoregulation Research Laboratory, University of California, San Francisco 94143-0648, USA.
authors.forename: T
authors.initials: T
authors.lastname: Matsukawa
authors.forename: A
authors.initials: A
authors.lastname: Kurz
authors.forename: D I
authors.initials: DI
authors.lastname: Sessler
authors.forename: A R
authors.initials: AR
authors.lastname: Bjorksten
authors.forename: B
authors.initials: B
authors.lastname: Merrifield
authors.forename: C
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000494:pharmacology*; D012768:Shivering / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D015742:Propofol