Efficacy of propofol to prevent bronchoconstriction: effects of preservative.
BACKGROUND
The authors previously showed that propofol attenuates bronchoconstriction. Recently, a newer formulation of propofol with metabisulfite preservative has been introduced. metabisulfite causes airway narrowing in asthmatics. Therefore, we tested whether the preservative metabisulfite abolishes the ability of propofol to attenuate bronchoconstriction. The authors used a sheep model in which anesthetic agents could be directly administered to the airways via the bronchial artery.


METHODS
After Internal Review Board approval, seven sheep were anesthetized (pentobarbital 20 mg x kg(-1) x h(-1)) and paralyzed (pancuronium 2 mg), and the lungs were ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, propofol with and without metabisulfite, lidocaine (5 mg/ml), or metabisulfite alone (0.125 mg/ml) was infused into the bronchial artery at a rate of 0.06, 0.2, or 0.6 ml/min. After 10 min, airway resistance (Raw) was measured before and after vagal nerve stimulation (30 Hz, 30-ms duration at 30 V for 9 s.) and methacholine challenge (2 microg/ml at 2 ml/min in the bronchial artery). Data were expressed as a percent of maximal response and analyzed by analysis of variance with correction and with significance accepted at P < or = 0.05.


RESULTS
Raw at baseline was not significantly different among the four drugs (P = 0.87). Infusion of lidocaine and propofol without metabisulfite into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction (P = 0.001). Propofol with metabisulfite had no effect on vagal nerve stimulation-induced bronchoconstriction (P = 0.40). There was a significant difference in the ability of propofol without metabisulfite compared with propofol with metabisulfite to attenuate vagal nerve stimulation-induced (P = 0.0001) and methacholine-induced bronchoconstriction (P = 0.0001).


CONCLUSIONS
Propofol without metabisulfite and lidocaine attenuated vagal nerve stimulation-induced bronchoconstriction in a dose-dependent fashion. Propofol without metabisulfite also decreased direct airway smooth muscle constriction. The preservative used for propofol can have a dramatic effect on its ability to attenuate bronchoconstriction.
Brown
R H
RH
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA. rbrown@welchlink.welch.jhu.edu
Greenberg
R S
RS
Wagner
E M
EM
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D012756:Sheep; D013447:Sulfites / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D013447:Sulfites; D016210:Methacholine Chloride; C030981:metabisulfite; D008012:Lidocaine; D015742:Propofol