title: Intravenous lidocaine and bupivacaine dose-dependently attenuate bronchial hyperreactivity in awake volunteers.
abstract: BACKGROUND
  In standard textbooks, intravenous lidocaine is recommended for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bronchial hyperreactivity in humans is unknown. Accordingly, nine awake volunteers with known bronchial hyperreactivity were subjected to an inhalational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double-blinded fashion.
  
  
  METHODS
  Baseline acetylcholine threshold concentrations were determined 3-5 days before initiation of the investigation. The response to the acetylcholine challenge was defined as hyperreactive, if forced expiratory volume in 1 s decreased by at least 20%. In addition, the acetylcholine threshold for a 100% increase in airway resistance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30-min intravenous infusion period of three doses of lidocaine (1, 3, and 6 mg.min(-1)) or bupivacaine (0.25, 0.75, and 1.5 mg.min(-1)), during saline placebo infusion, respectively. Acetylcholine-threshold concentrations were presented with the respective plasma concentrations of the local anesthetic.
  
  
  RESULTS
  The infusion of lidocaine and bupivacaine resulted in plasma concentrations (means +/- SD) of 0.29 +/- 0.11, 1.14 +/- 0.39, and 2.02 +/- 0.5 microg.ml(-1) for lidocaine and 0.11 +/- 0.04, 0.31 +/- 0.09, and 0.80 +/- 0.18 microg.ml(-1) for bupivacaine, respectively. 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. Compared to placebo, acetylcholine threshold was almost quadrupled for lidocaine and tripled for bupivacaine with the highest plasma concentration of each local anesthetic.
  
  
  CONCLUSIONS
  In awake humans, intravenous lidocaine and bupivacaine both dose-dependently attenuated the hyperreactive response to a nonspecific inhalational challenge with acetylcholine.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Düsseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Groeben
authors.forename: A
authors.initials: A
authors.lastname: Schwalen
authors.forename: S
authors.initials: S
authors.lastname: Irsfeld
authors.forename: S
authors.initials: S
authors.lastname: Stieglitz
authors.forename: P
authors.initials: P
authors.lastname: Lipfert
authors.forename: H B
authors.initials: HB
authors.lastname: Hopf
mesh_terms: D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D002045:Bupivacaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D013564:Sympathetic Nervous System / Q000187:drug effects; D014851:Wakefulness
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine; D002045:Bupivacaine