Am. J. Respir. Crit. Care Med., Vol 151, No. 4, 04 1995, 1239-1243.
Prevention of bronchoconstriction by an orally active local anesthetic
RH Brown, W Robbins, P Staats and C Hirshman
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Stimulation of airway irritant receptors produces reflex
bronchoconstriction that can be prevented by pretreatment with
anticholinergic drugs or local anesthetics delivered by aerosol or
intravenously. We compared therapeutic doses of an orally administered
local anesthetic, mexiletine hydrochloride, and intravenously administered
lidocaine at blocking histamine-induced bronchoconstriction in five
basenji-greyhound dogs, using high- resolution computed tomography (HRCT)
to directly measure changes in airway size. In the dogs given placebo, a
histamine infusion decreased airway area to 61 +/- 2% (mean +/- SEM) of
control (p < 0.01). Mexiletine pretreatment completely prevented
histamine-induced airway constriction, with an airway area that was 94 +/-
4% of the control value during the histamine infusion (p = 0.07 compared
with baseline). Mexiletine serum levels were therapeutic (1.7 +/- 0.3
mg/L). Similarly, pretreatment with lidocaine significantly blunted the
airway constriction provoked by intravenous histamine. In
lidocaine-pretreated dogs, histamine decreased airway area to 79 +/- 4% of
baseline (p < 0.01). As in the case of mexiletine, lidocaine serum
levels were also therapeutic (2.4 +/- 0.3 mg/L). Mexiletine was more
effective than lidocaine at preventing histamine-induced
bronchoconstriction (p = 0.02). These data suggest that orally administered
local anesthetics may be useful in preventing irritant-induced
bronchoconstriction in humans.
