INTRAVENOUS LIDOCAINE AND BUPIVACAINE DOSE-DEPENDENTLY ATTENUATE BRONCHIAL HYPERREACTIVITY IN AWAKE VOLUNTEERS

Background: In standard textbooks, intravenous lidocaine is recommende d for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bro nchial hyperreactivity in humans is unknown. Accordingly, nine awake v olunteers with known bronchial hyperreactivity were subjected to an in halational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double -blinded fashion. Methods: Baseline acetylcholine threshold concentrat ions were determined 3-5 days before initiation of the investigation, The response to the acetylcholine challenge was defined as hyperreacti ve, if forced expiratory volume in 1 s decreased by at least 20%. In a ddition, the acetylcholine threshold for a 100% increase in airway res istance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30-min intra venous infusion period of three doses of lidocaine (1, 3, and 6 mg . m in(-1)) or bupivacaine (0.25, 0.75, and 1.5 mg . min(-1)), during sali ne placebo infusion, respectively. Acetylcholine-threshold concentrati ons were presented with the respective plasma concentrations of the lo cal anesthetic. Results: The infusion of lidocaine and bupivacaine res ulted in plasma concentrations (means +/- SD) of 0.29 +/- 0.11, 1.14 /- 0.39, and 2.02 +/- 0.5 mu g . ml(-1) for lidocaine and 0.11 +/- 0.0 4, 0.31 +/- 0.09, and 0.80 +/- 0.18 mu g . ml(-1) for bupivacaine, res pectively. Compared to baseline, the acetylcholine threshold for a 20% decrease of forced expiratory volume in 1 s as well as the threshold for a 100% increase in total airway resistance increased significantly with increasing plasma concentrations of both local anesthetics. Comp ared to placebo, acetylcholine threshold was almost quadrupled for lid ocaine and tripled for bupivacaine with the highest plasma concentrati on of each local anesthetic. Conclusions: In awake humans, intravenous lidocaine and bupivacaine both dose-dependently attenuated the hyperr eactive response to a nonspecific inhalational challenge with acetylch oline.