Effect of nebulized lidocaine on ventilatory response to CO₂ in healthy subjects

Partial vagal blockade produced by inhalation of a local anesthetic aerosol has enhanced CO₂ responsiveness in some studies but not in others. The effect of inhaled local anesthetic may depend on the amount of drug depositing in the central airways, i.e., the degree of airway anesthesia. We examined the ventilatory response to CO₂ rebreathing in 11 healthy subjects before and after inhalation of 4% lidocaine and a normal saline control solution. Lidocaine and control solutions were aerosolized via two different nebulizers: one produced particles with a mass median aerodynamic diameter of 5.28 μm, and the other produced particles with a mass median aerodynamic diameter of 1.76 μm. The ventilatory response to CO₂ was not affected by the control solution. In contrast, the ventilatory response to CO₂ was significantly increased after aerosolized lidocaine when administered via the moderate-particle-size nebulizer (2.13 ± 0.66 vs. 1.83 ± 0.54 l · min^-1 · Torr^-1 during control, P = 0.01) but not via the small-particle-size nebulizer (1.96 ± 0.82 vs. 1.94 ± 0.84 l · min^-1 · Torr^-1 during control, P = NS). The increase in ventilation was achieved predominantly by an increase in frequency (P = 0.01) while tidal volume was unchanged. In conclusion, airway receptors accessible to inhaled local anesthetic play a role in the control of breathing during CO₂ rebreathing. Previous negative studies may be due to differences in nebulizer technique, affecting the amount of drug depositing within the central airways.