title: Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.
abstract: There is no information comparing the ability to reverse the cardiotoxic effects associated with incremental overdosage of bupivacaine (BUP) to levobupivacaine (LBUP), ropivacaine (ROP), or lidocaine (LIDO). Open-chest dogs were randomized to receive incremental escalating infusions of BUP, LBUP, ROP, and LIDO to the point of cardiovascular collapse (mean arterial pressure [MAP] < or = 45 mm Hg). Hypotension and arrhythmias were treated with epinephrine, open-chest massage, and advanced cardiac life support protocols, respectively. Outcomes were defined as the following: successful (stable rhythm and MAP > or = 55 mm Hg for 20 min), successful with continued therapy (stable rhythm and MAP <55 mm Hg after 20 min), or death. Continued therapy was required in 86% of LIDO dogs compared with only 10%-30% of the other dogs (P < 0.002). Mortality from BUP, LBUP, ROP, and LIDO was 50%, 30%, 10%, and 0%, respectively. Myocardial depression was primarily responsible for the profound hypotension, as the occurrence of lethal arrhythmias preceding resuscitation was not different among local anesthetics. Epinephrine-induced ventricular fibrillation occurred more frequently in BUP-intoxicated dogs than in dogs given LIDO or ROP (P < 0.05). The unbound plasma concentrations at collapse were larger for ROP, 19.8 microg/mL (10-39 microg/mL), compared with BUP, 5.7 microg/mL (3-11 microg/mL); whereas the concentrations of LBUP, 9.4 microg/mL (5-18 microg/mL) and BUP were not significantly different from each other.
  
  
  CONCLUSIONS
  There were consistent differences among the local anesthetics, the sum of which suggests that larger doses and blood concentrations of ropivacaine (ROP) and lidocaine will be tolerated as compared with bupivacaine (BUP) and levobupivacaine (LBUP). Lidocaine intoxication results in myocardial depression from which resuscitation is consistently successful but will require continuing drug support. After BUP, LBUP, or ROP, resuscitation is not always successful, and the administration of epinephrine may lead to severe arrhythmias. The unbound plasma concentrations at collapse were larger for ROP compared with BUP, whereas the concentrations of LBUP and BUP were not significantly different from each other. Furthermore, larger plasma concentrations of ROP than BUP are present after resuscitation, suggesting a wider margin of safety when large volumes and large concentrations are used to establish upper or lower extremity nerve blocks for surgical anesthesia and during long-term infusions for pain management.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. lgroban@wfumc.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*; D000813:Anilides / Q000097:blood / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000628:therapy; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000097:blood / Q000633:toxicity; D016887:Cardiopulmonary Resuscitation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004554:Electric Countershock; D004837:Epinephrine / Q000494:pharmacology; D006336:Heart Massage; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000628:therapy; D008012:Lidocaine / Q000097:blood / Q000633:toxicity; D000077212:Ropivacaine; D012770:Shock, Cardiogenic / Q000139:chemically induced; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000813:Anilides; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine; D004837:Epinephrine