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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Isoflurane produces marked and nonlinear decreases in the vasoconstriction and shivering thresholds
1Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Background:
Desflurane decreases the vasoconstriction and shivering thresholds disproportionately at high anesthetic concentrations. This result contrasts with the authors' previous report that isoflurane decreases the vasoconstriction threshold linearly. It is surprising that the basic shape of the concentration-response curve should differ with these two otherwise similar anesthetics. Therefore, the hypothesis that isoflurane produces a nonlinear reduction in the vasoconstriction threshold was tested. Because the effect of isoflurane on shivering remains unknown, the extent to which isoflurane reduces the shivering threshold also was determined.
Methods:
Eight men volunteered to be studied on four randomly ordered days: (1) a target end-tidal isoflurane concentration of 0.55%, (2) a target concentration of 0.7%, (3) control (no anesthesia) and a target end-tidal concentration of 0.85%, and (4) a target end-tidal concentration of 1.0%. Volunteers were surface-cooled until peripheral vasoconstriction and shivering were observed. We arithmetically compensated for changes in skin temperature using the established linear cutaneous contributions to control for each response. From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), the concentration-response relation was determined.
Results:
Isoflurane administration produced a dose-dependent reduction in the vasoconstriction and shivering thresholds, decreasing each approximately 4.6 degrees C at an end-tidal concentration of 1%. Residual analysis indicated that the vasoconstriction and shivering thresholds were decreased in a nonlinear fashion during isoflurane administration. The vasoconstriction-to-shivering range was 1.5 +/- 0.8 degree C without isoflurane, and did not change significantly during isoflurane administration.
Conclusions:
The vasoconstriction-to-shivering range remained unchanged by isoflurane administration. In this regard, the effects of isoflurane are similar to those of desflurane, propofol, and alfentanil. The current data differ from the authors' previous report, in that the dose-dependence for vasoconstriction was nonlinear, with isoflurane reducing the threshold disproportionately at higher anesthetic concentrations. Differing dose-dependence in the two studies may result either because the current study's volunteers were not exposed to surgical stimulation and were given less isoflurane, or because of design limitations in the previous protocol.
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