Intravenous lidocaine and oral mexiletine block reflex bronchoconstriction in asthmatic subjects.
Stimulation of the airways of asthmatic individuals causes severe bronchoconstriction, which is in part neurally mediated via the vagus nerve. Local anesthetics are commonly administered to prevent this reflex-induced bronchoconstriction. Therefore, in a double-blind, placebo-controlled prospective study, we tested the effectiveness of oral mexiletine and intravenous lidocaine at blocking histamine-induced reflex bronchoconstriction. Fifteen subjects with mild asthma were selected (for whom the provocative concentration of histamine aerosol causing a 20% decrease in FEV1 (PC20) was less than 18 mg/ml). Subsequently, the subjects were pretreated with oral mexiletine, intravenous lidocaine, or placebo, and the histamine challenges were repeated. The baseline PC20 for histamine was 8.8 +/- 1.8 mg/ml. Mexiletine and lidocaine at therapeutic serum concentrations blocked reflex bronchoconstriction. Oral mexiletine increased the PC20 to 21.1 +/- 5.0 mg/ml (serum concentration: 0.7 +/- 0.05 microg/ml). Likewise, intravenous lidocaine increased the PC20 to 24.5 +/- 4.9 mg/ml (serum concentration: 2.6 +/- 0.15 microg/ml). Oral mexiletine and intravenous lidocaine block reflex-induced bronchoconstriction. Furthermore, mexiletine may have additional airway benefits when selected for the treatment of dysrhythmias or chronic pain in patients with coexisting lung diseases.
Department of Anesthesiology and Environmental Health Services, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
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Groeben
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Foster
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Brown
D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006632:Histamine; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology*; D011292:Premedication; D011446:Prospective Studies; D012018:Reflex / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D000779:Anesthetics, Local; D008801:Mexiletine; D006632:Histamine; D008012:Lidocaine