title: Bupivacaine-induced cardiotoxicity in hypoxic and acidotic sheep.
abstract: Awake, unanesthetized, and paralyzed sheep made hypoxic and acidotic were given equivalent low and high intravenous doses of lidocaine and bupivacaine over 10 sec. Within 30 sec of injections, all animals had electroencephalographic evidence of convulsions. After administration of low-dose lidocaine, arrhythmias associated with significant hemodynamic changes did not occur; after administration of high-dose lidocaine, half of the animals became hypotensive but had no arrhythmias other than sinus tachycardia. However, after administration of low-dose bupivacaine, all sheep had evidence of serious electrocardiographic changes or arrhythmias, and one animal died. After administration of high-dose bupivacaine, serious electrocardiographic changes occurred in all animals, and despite resuscitative efforts, all died. The most common abnormality after bupivacaine administration was a wide-QRS-complex bradycardia, occurring in most animals regardless of dose. Two-thirds of the animals given high-dose bupivacaine had electromechanical dissociation and subsequent refractory asystole. Although the mechanism of action is not known, bupivacaine appears to be more cardiotoxic than lidocaine. This toxicity is enhanced in animals by the presence of hypercarbia, acidosis, and hypoxia.
mesh_terms: D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008012:Lidocaine / Q000097:blood / Q000633:toxicity; D012756:Sheep
chemical_list: D008012:Lidocaine; D002045:Bupivacaine