Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction

Background: Lidocaine inhalation, in subjects with bronchial hyperreactivit y, attenuates evoked bronchoconstriction but also irritates airways. Whethe r salbutamol pretreatment can mitigate airway irritation and whether combin ed treatment offers more protection than treatment with either drug alone i s unknown. Therefore, we evaluated the effects of the inhalation of lidocai ne, salbutamol, lidocaine and salbutamol combined, and placebo on an inhala tional histamine challenge. Methods: Fifteen patients with mild asthma were selected by a screening pro cedure tie, a provocative concentration of a substance [histamine aerosol o f < 18 mg/mL] causing a 20% fall in FEV1 [PC20]). On 4 different days after pretreatment with the inhalation of lidocaine (5 mg/kg), inhalation of sal butamol (1.5 mg), combined treatment, or placebo, the histamine challenge w as repeated. Results: The baseline FEV1 after lidocaine inhalation but prior to the hist amine challenge decreased by > 5% in 7 of 15 volunteers, with a mean (+/- S D) decrease from 3.82 +/- 0.90 to 3.54 +/- 0.86 L (p = 0.0054). The baselin e PC20 for histamine was 6.4 +/- 4.3 mg/mL. Both lidocaine and salbutamol i nhalation significantly increased PC20 more than twofold (14.9 +/- 13.7 and 16.8 +/- 10.9 mg/mL, respectively; p = 0,0007) at a Lidocaine plasma conce ntration of 0.7 +/- 0.3 mu g/mL. Combined treatment quadrupled the PC20 to 29.7 +/- 20.3 mg/mL (vs lidocaine, p = 0.002; vs salbutamol, p = 0.003). Conclusions: Thus, histamine-evoked bronchoconstriction, as a model of refl ex bronchoconstriction, can be significantly attenuated by salbutamol or li docaine inhalation. However, lidocaine inhalation causes significant initia l bronchoconstriction. The combined inhalation of salbutamol and lidocaine prevents the initial bronchoconstriction observed with lidocaine alone and offers even more protection to a histamine challenge than either lidocaine or salbutamol alone. Therefore, the combined inhalation of lidocaine and sa lbutamol can be recommended to mitigate bronchoconstriction when airway ins trumentation is required.