title: Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.
abstract: We compared the systemic toxicity of bupivacaine, levobupivacaine, and ropivacaine in anesthetized rats. We also compared the ability to resuscitate rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine, or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while electrocardiogram, electroencephalogram, and arterial pressure were continuously monitored. When asystole was recorded, drug infusion was stopped and a resuscitation sequence was begun. Epinephrine 0.01 mg/kg was administered at 1-min intervals while external cardiac compressions were applied. Resuscitation was considered successful when a systolic arterial pressure > or =100 mm Hg was achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine that produced seizures were similar and were larger than those of bupivacaine. The cumulative doses of levobupivacaine that produced dysrhythmias and asystole were smaller than the corresponding doses of ropivacaine, but they were larger than those of bupivacaine. The number of successful resuscitations did not differ among groups. However, a smaller dose of epinephrine was required in the Ropivacaine group than in the other groups. We conclude that the systemic toxicity of levobupivacaine is intermediate between that of ropivacaine and bupivacaine when administered at the same rate and that ropivacaine-induced cardiac arrest appears to be more susceptible to treatment than that induced by bupivacaine or levobupivacaine.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, School of Medicine, Kanazawa University, Kanazawa, Japan. ohmura@med.kanazawa-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Ohmura
authors.forename: M
authors.initials: M
authors.lastname: Kawada
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000577:Amides / Q000008:administration & dosage / Q000633:toxicity*; D000758:Anesthesia; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002493:Central Nervous System Diseases / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D000077212:Ropivacaine; D013237:Stereoisomerism
chemical_list: D000316:Adrenergic alpha-Agonists; D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D009638:Norepinephrine; D002045:Bupivacaine