Lidocaine induces a reversible decrease in alveolar epithelial fluid clearance in rats.
BACKGROUND
Lidocaine is widely used in patients with acute cardiac disorders and has also been recently implicated as a possible cause of pulmonary edema after liposuction. The objective of this study was to assess the effect of lidocaine on alveolar fluid clearance, the primary mechanism responsible for the resolution of alveolar edema.


METHODS
Alveolar fluid clearance was measured in 29 ventilated rats using our well-validated method over 1 h using a 5% albumin solution instilled into the distal air spaces of the lung. Lidocaine was added to the instilled albumin solution (10(-5) M) or administered intravenously at a dose estimated to achieve a clinically relevant plasma concentration of 10(-5) M. Standard agonists and antagonists were used to determine the effect of lidocaine on alveolar fluid clearance. To determine whether lidocaine acted predominantly on the apical or basal surface, we also used QX314, lidocaine n-ethyl bromide quaternary salt, an analog of lidocaine, which is unable to cross the alveolar epithelium. The effect of lidocaine on the apical epithelial sodium channel transfected in Xenopus oocytes was also studied.


RESULTS
Alveolar or intravenous lidocaine decreased alveolar fluid clearance by 50%, an effect that was reversible with the beta2 agonist, terbutaline. Lidocaine acted predominantly on the basal surface of the epithelium because n-ethyl bromide quaternary salt decreased alveolar fluid clearance only when it was given intravenously and because lidocaine did not inhibit the apical epithelial sodium channel when expressed in oocytes.


CONCLUSIONS
Lidocaine decreased alveolar fluid clearance by 50%, an effect that may have major clinical implications in the care of patients with cardiac disease or during the perioperative period in some patients. Importantly, the effect of lidocaine was completely reversible with beta2-adrenergic therapy.
Laffon
Marc
M
Cardiovascular Research Institute and the Department of Anesthesia, University of California, San Francisco, California 94142-0130, USA.
Jayr
Christian
C
Barbry
Pascal
P
Wang
Ybing
Y
Folkesson
Hans G
HG
Pittet
Jean-Francois
JF
Clerici
Christine
C
Matthay
Michael A
MA
D000584:Amiloride / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001826:Body Fluids / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus
D000779:Anesthetics, Local; D004232:Diuretics; D011506:Proteins; D015222:Sodium Channels; C012647:QX-314; D000584:Amiloride; D008012:Lidocaine