title: A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine.
abstract: We sought, in this observer-blinded study, to determine the lethal dose for each of the local anesthetics levobupivacaine (L), racemic bupivacaine (B), and ropivacaine (R), and to compare their respective effects on the QRS interval of the precordial electrocardiograph after intracoronary injection. Anesthetized swine were instrumented with a left anterior descending artery coronary angiography catheter and injected with increasing doses of L, B, or R according to a randomized protocol. The doses administered were 0. 375, 0.75, 1.5, 3.0, and 4.0 mg, with further doses increasing in 1-mg increments until death occurred. Plotting the mean maximum QRS interval as a function of the log(10) mmol dose allowed the following cardiotoxicity potency ratios to be determined for a doubling of QRS duration-B:L:R = 2.1:1.4:1. The lethal doses in millimoles (median/range) for L and R were (0.028/0.024-0.031) and (0.032/0.013-0.032), respectively, and were significantly higher than for B (0.015/0.012-0.019) - (P < 0.05, n = 7 for all groups). The lethal dose did not differ between R and L. Thus, the cardiotoxicity potency ratios for the three anesthetics based on lethal dose were: 2.1:1.2:1. If the anesthetic potencies for B and L are similar, the latter should have less potential for cardiotoxicity in the clinical situation.
  
  
  CONCLUSIONS
  Animal experiments have shown levobupivacaine and ropivacaine to be less cardiotoxic than racemic bupivacaine. This in vivo study, using a validated swine model, compared the relative direct cardiotoxicities of these three local anesthetics. The lethal dose did not differ between levobupivacaine and ropivacaine, but was lowest for racemic bupivacaine.
authors.affiliation: Department of Anesthesiology and Surgical Intensive Care, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. katrin.mignolet@planetinternet.be
authors.forename: S G
authors.initials: SG
authors.lastname: Morrison
authors.forename: J J
authors.initials: JJ
authors.lastname: Dominguez
authors.forename: P
authors.initials: P
authors.lastname: Frascarolo
authors.forename: S
authors.initials: S
authors.lastname: Reiz
mesh_terms: D000577:Amides / Q000633:toxicity*; D000758:Anesthesia; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006400:Hematocrit; D000077212:Ropivacaine; D013237:Stereoisomerism; D013552:Swine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine