Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction.
BACKGROUND
Lidocaine inhalation, in subjects with bronchial hyperreactivity, attenuates evoked bronchoconstriction but also irritates airways. Whether salbutamol pretreatment can mitigate airway irritation and whether combined treatment offers more protection than treatment with either drug alone is unknown. Therefore, we evaluated the effects of the inhalation of lidocaine, salbutamol, lidocaine and salbutamol combined, and placebo on an inhalational histamine challenge.


METHODS
Fifteen patients with mild asthma were selected by a screening procedure (ie, a provocative concentration of a substance [histamine aerosol of < 18 mg/mL] causing a 20% fall in FEV(1) [PC(20)]). On 4 different days after pretreatment with the inhalation of lidocaine (5 mg/kg), inhalation of salbutamol (1.5 mg), combined treatment, or placebo, the histamine challenge was repeated.


RESULTS
The baseline FEV(1) after lidocaine inhalation but prior to the histamine challenge decreased by > 5% in 7 of 15 volunteers, with a mean (+/- SD) decrease from 3.82 +/- 0.90 to 3.54 +/- 0.86 L (p = 0.0054). The baseline PC(20) for histamine was 6.4 +/- 4.3 mg/mL. Both lidocaine and salbutamol inhalation significantly increased PC(20) more than twofold (14.9 +/- 13.7 and 16.8 +/- 10.9 mg/mL, respectively; p = 0, 0007) at a lidocaine plasma concentration of 0.7 +/- 0.3 microg/mL. Combined treatment quadrupled the PC(20) 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 reflex bronchoconstriction, can be significantly attenuated by salbutamol or lidocaine inhalation. However, lidocaine inhalation causes significant initial 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 salbutamol can be recommended to mitigate bronchoconstriction when airway instrumentation is required.
Abteilung für Anästhesiologie und Intensivmedizin, Universität Essen, Germany. harald.groeben@uni-essen.de
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Groeben
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Silvanus
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Beste
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Peters
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000769:Anesthesia, Inhalation / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009330:Nebulizers and Vaporizers; D012018:Reflex / Q000187:drug effects
D000336:Aerosols; D000779:Anesthetics, Local; D001993:Bronchodilator Agents; D006632:Histamine; D008012:Lidocaine; D000420:Albuterol