title: Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts.
abstract: Lidocaine, phenytoin, and bupivacaine are sodium channel blockers. Lidocaine displaces bupivacaine from its receptor on the sodium channel. However, lidocaine does not seem to decrease bupivacaine toxicity. Phenytoin also has been used to treat bupivacaine cardiotoxicity. To test the hypothesis that lidocaine or phenytoin might be used for the treatment of bupivacaine overdose, we compared the effects of bupivacaine on intraventricular conduction in the isolated heart of rabbits with bupivacaine and with either phenytoin or lidocaine added to bupivacaine. Twenty-four rabbit hearts were retrogradely perfused in a nonrecirculating Langendorff apparatus. The duration of QRS was measured without any drug and 10 min after infusion of 3 microM bupivacaine. Saline (control group) or increasing concentrations of either lidocaine or phenytoin was then added by 10-min-step increments. QRS duration was measured for each concentration at the end of a 10-min step. It was also determined 10 min after discontinuation of bupivacaine and after a period of washout for all drugs. QRS duration was significantly increased by adding phenytoin or lidocaine to bupivacaine. These drugs should not be used to treat the manifestations of bupivacaine toxicity.
  
  
  CONCLUSIONS
  The effects of lidocaine and phenytoin on bupivacaine-related increases in cardiac conduction time have been studied in an isolated heart preparation. Both drugs increased the QRS widening induced by bupivacaine. We conclude that none of these drugs should be used for treating bupivacaine intoxication.
authors.affiliation: Laboratoire d'Anesthésie UPRES EA 392, Université Paris-Sud, Faculté de Médecine du Kremlin-Bicêtre, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Simon
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kariya
authors.forename: Emilie
authors.initials: E
authors.lastname: Pelle-Lancien
authors.forename: Jean-Xavier
authors.initials: JX
authors.lastname: Mazoit
mesh_terms: D000779:Anesthetics, Local / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002045:Bupivacaine / Q000493:pharmacokinetics / Q000633:toxicity*; D004357:Drug Synergism; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D010672:Phenytoin; D008012:Lidocaine; D002045:Bupivacaine