Effects of halothane, propofol, and thiopental on peripheral airway reactivity.
BACKGROUND
General anesthetics modify airway responsiveness by several mechanisms, including direct effects on airway smooth muscle and reductions in neural reflex activity. Halothane has been shown to reduce responsiveness through both of these mechanisms. The airway effects of barbiturates are controversial, and the effects of propofol are unknown.


METHODS
To compare the direct effects of halothane, thiopental, and propofol in vivo, canine peripheral airways were constricted with two stimuli, histamine and hypocapnia, which are thought to directly contract smooth muscle. The authors then investigated the role of ATP-sensitive potassium (KATP) channels as a mechanism for attenuating these responses. Basenji-Greyhound (BG) dogs were anesthetized with either halothane (1.5 MAC), thiopental (7.5 mg.kg-1 x min-1 intravenously) plus fentanyl (25 micrograms intravenously every 20-30 min), or propofol (0.6 mg.kg-1 x min-1 intravenously). A wedged bronchoscope technique was used to measure peripheral airway resistance (RP). After a stable baseline was obtained, dose-response curves to histamine (50, 100, or 200 micrograms intravenous bolus) or hypocapnia (0% CO2 for 2 min with 100, 200, or 400 ml/min collateral flow) were constructed. On separate occasions, the same sublobar segments were pretreated with glibenclamide (2 mg/ml aerosol), a KATP channel blocker, and dose-response curves to hypocapnia were repeated.


RESULTS
Dose-response curves to histamine were similar during all three anesthetics. Halothane decreased airway responsiveness to hypocapnia, compared with either thiopental or propofol (P < 0.05). Pretreatment with glibenclamide abolished the effect of halothane on hypocapnia-induced airway constriction.


CONCLUSIONS
These results indicate that propofol afforded no benefit over thiopental or halothane in reducing peripheral airway responsiveness. Furthermore, the beneficial effects of halothane in reducing responsiveness to hypocapnia appear to be mediated by the opening of KATP channels.
Mehr
E H
EH
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Lindeman
K S
KS
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D015221:Potassium Channels; D015742:Propofol / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology*
D015221:Potassium Channels; D006632:Histamine; D013874:Thiopental; D006221:Halothane; D015742:Propofol