title: A comparison of the effects of propofol and sevoflurane on the systemic toxicity of intravenous bupivacaine in rats.
abstract: We compared the effects of propofol and sevoflurane on bupivacaine-induced central nervous system and cardiovascular toxicity in rats. Thirty-four male Sprague-Dawley rats were anesthetized with 70% N2O/30% O2 plus the 50% effective dose (ED50) of propofol (propofol group, n = 12); 70% N2O/30% O2 plus ED50 of sevoflurane (sevoflurane group, n = 11); or 70% N2O/30% O2 (control group, n = 11). Bupivacaine was infused at a constant rate of 2 mg x kg(-1) x min(-1) while electrocardiogram, electroencephalogram, and invasive arterial pressure were continuously monitored. The cumulative doses of bupivacaine that induced dysrhythmias, seizures, and 50% reduction of heart rate were larger in the propofol and sevoflurane groups than in the control group. The cumulative dose of bupivacaine that induced a 50% reduction in the mean arterial blood pressure was larger in the propofol group than in the sevoflurane and control groups. The margin of safety, assessed by the time between the onset of dysrhythmias and 50% reduction of mean arterial blood pressure, was wider in the propofol group than in the sevoflurane group. We conclude that propofol and sevoflurane attenuate bupivacaine-induced dysrhythmias and seizures and that propofol has a wider margin of safety than sevoflurane.
  
  
  CONCLUSIONS
  In anesthetized patients, dysrhythmias may be the only warning sign of intravascular injection of bupivacaine. Because propofol has a wider margin of safety than sevoflurane, life-threatening cardiovascular depression may be prevented by stopping the injection of bupivacaine at the onset of dysrhythmias during propofol anesthesia.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kanazawa University, Japan. ohmura@med.kanazawa-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Ohmura
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: D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D018686:Anesthetics, Intravenous / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D015742:Propofol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D008738:Methyl Ethers; D000077149:Sevoflurane; D002045:Bupivacaine; D015742:Propofol