title: Comparative electrophysiologic and hemodynamic effects of several amide local anesthetic drugs in anesthetized dogs.
abstract: Large and equipotent doses of several local anesthetics were administered in a cardiac electrophysiologic model on closed-chest dogs. Five groups of pentobarbital-anesthetized dogs were each given intravenously 16 mg/kg lidocaine, 12 mg/kg mepivacaine, 4 mg/kg or 8 mg/kg etidocaine, and 4 mg/kg bupivacaine. Lidocaine induced bradycardia, slowing of atrioventricular node conduction (AH), and marked hemodynamic depression, represented by a decrease in mean aortic pressure (MAoP), in the peak of first derivative of left ventricular pressure (LVdP/dt(max)) and by an increase in left ventricular end-diastolic pressure (LVEDP). Atrial pacing at pacing cycle length (PCL) of 298 ms did not enhance the alteration of variables of ventricular conduction (His ventricle [HV] interval and QRS duration). Mepivacaine induced slight alteration of electrophysiologic variables. Atrial pacing at PCL of 312 ms did not enhance the alteration of HV and QRS duration. Mepivacaine induced transient hemodynamic depression. Etidocaine (4 mg/kg) induced electrophysiologic and hemodynamic alterations similar to mepivacaine but artrial pacing at PCL of 330 ms enhanced HV lengthening and QRS widening (P < 0.05). Etidocaine (8 mg/kg) induced marked impairment of PR, HV, QRS, and QT, and dramatic hemodynamic depression represented by a decrease in MAoP from 123.5 +/- 16.2 at baseline to 36.5 +/- 8.3 mm Hg at 1 min (P < 0.001) and of LVdP/dtmax) from 1446 +/- 379 to 333 +/- 93 mm Hg/s (P < 0.001). Bupivacaine induced dramatic impairment of electrophysiologic variables. Bupivacaine also decreased LVDP/dtmax (from 1333 +/- 347 to 617 +/- 299,P < 0.001) and increased LVEDP. We conclude that mepivacaine induced moderate cardiotoxicity. In contrast, lidocaine induced dramatic hemodynamic depression while etidocaine and bupivacaine markedly impaired both electrophysiologic and hemodynamic variables. This double impairment could explain the great difficulty in resuscitating patients who have had cardiotoxic accidents induced by etidocaine or bupivacaine.
authors.affiliation: Department of Anesthesiology, Critical Care, and Emergency, University-Hospital of Nîmes, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Bruelle
authors.forename: J Y
authors.initials: JY
authors.lastname: LeFrant
authors.forename: J E
authors.initials: JE
authors.lastname: de La Coussaye
authors.forename: P A
authors.initials: PA
authors.lastname: Peray
authors.forename: G
authors.initials: G
authors.lastname: Desch
authors.forename: A
authors.initials: A
authors.lastname: Sassine
authors.forename: J J
authors.initials: JJ
authors.lastname: Eledjam
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D016275:Atrial Function / Q000187:drug effects; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D002036:Bundle of His / Q000187:drug effects; D002045:Bupivacaine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D003864:Depression, Chemical; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005041:Etidocaine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008619:Mepivacaine / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D008012:Lidocaine; D008619:Mepivacaine; D005041:Etidocaine; D002045:Bupivacaine