Combined intravenous lidocaine and inhaled salbutamol protect against bronchial hyperreactivity more effectively than lidocaine or salbutamol alone

Abstract

Background: Airway instrumentation in persons with asthma is linked to the risk of life-threatening bronchospasm. To attenuate the response to airway irritation, intravenous lidocaine is recommended (based on animal experiments) and mitigates the response to histamine inhalation in asthmatic volunteers. However, the effects of lidocaine have not been compared with standard prophylaxis with β-sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol, combined treatment, and placebo control were tested in awake volunteers with bronchial hyperreactivity. Methods: After approval from the local ethics committee, 15 persons, who were selected because they showed a decrease in forced expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a placebo-controlled, double-blind, and randomized study. The challenge was repeated on four different days and the volunteers were pretreated with either intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also measured. Statistical analyses included the Friedman test and Wilcoxon's rank slam. Results: The baseline PC20 was 6.4 ± 4.3 mg/ml. Intravenous lidocaine and salbutamol aerosol both significantly increased the histamine threshold to 14.2 ± 9.5 mg/ml and 16.8 ± 10.9 mg/ml, respectively (mean ± SD). However, the combination of lidocaine and salbutamol significantly increased the PC20 even further to 30.7 ± 15.7 mg/ml than did salbutamol or lidocaine alone. Conclusions: In volunteers with bronchial hyperreactivity, both lidocaine and salbutamol attenuate the response to an inhalational histamine challenge, and their combined administration has much greater effects than does either drug alone. Accordingly, pretreatment of patients with bronchial hyperreactivity with both β-mimetic aerosol and intravenous lidocaine is recommended before airway irritation.