title: Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine.
abstract: It is unclear whether the mechanism of death from local anesthetic (LA) intoxication is primarily a consequence of cardiac arrhythmias or myocardial contractile depression, and whether LAs might differ in this susceptibility to these two mechanisms. By using programmable electrical stimulation (PES) protocols in anesthetized, ventilated dogs, we compared the arrhythmogenic potential of bupivacaine (BUP), ropivacaine (ROP), levobupivacaine (LBUP), and lidocaine (LIDO). Open-chest dogs were randomized to receive escalating incremental infusions of the four local anesthetics until cardiovascular collapse. We assumed a concentration relationship of 4:1 for LIDO/BUP, LBUP, and ROP. The effective refractory period did not change significantly until the dose increment corresponding to target concentrations of 8 and 32 microg/mL for BUP, LBUP, ROP, and LIDO, respectively. Thirty percent to 50% increases in effective refractory period occurred in surviving dogs at this dose. The incidence of spontaneous or PES-induced ventricular tachycardia and ventricular fibrillation did not differ among groups. Compared with LIDO, the incidence of PES-induced extrasystoles was more frequent for BUP- and LBUP-treated dogs (P: < 0.05). ROP-treated dogs did not differ from LIDO-treated dogs with respect to PES-induced extrasystoles. At the dose increment preceding cardiovascular collapse, all LAs produced significant increases in heart rate and reductions in blood pressure compared with their respective baseline values. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with BUP does not differ from the incidence that occurs with the single S:(-) enantiomers LBUP and ROP, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity.
  
  
  CONCLUSIONS
  Progressive bupivacaine intoxication in anesthetized, ventilated dogs does not produce early arrhythmogenic events. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with bupivacaine does not differ from the incidence that occurs with the single S:(-) enantiomers levobupivacaine and ropivacaine, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. lgroban@wfubmc.edu
authors.forename: L
authors.initials: L
authors.lastname: Groban
authors.forename: D D
authors.initials: DD
authors.lastname: Deal
authors.forename: J C
authors.initials: JC
authors.lastname: Vernon
authors.forename: R L
authors.initials: RL
authors.lastname: James
authors.forename: J
authors.initials: J
authors.lastname: Butterworth
mesh_terms: D000577:Amides / Q000097:blood / Q000633:toxicity; D000779:Anesthetics, Local / Q000097:blood / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000097:blood / Q000633:toxicity; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D062787:Drug Overdose; D008012:Lidocaine / Q000097:blood / Q000633:toxicity; D000077212:Ropivacaine; D017180:Tachycardia, Ventricular / Q000139:chemically induced*; D014693:Ventricular Fibrillation / Q000139:chemically induced*
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine