title: Effect of lipid emulsion on the central nervous system and cardiac toxicity of bupivacaine and levobupivacaine in awake rats.
abstract: OBJECTIVE
  Despite numerous studies examining the effect of lipid emulsion on bupivacaine-induced cardiac toxicity, few studies have examined its effect on central nervous system (CNS) toxicity of local anesthetics. We investigated the effect of lipid emulsion on the CNS and cardiac toxicity of bupivacaine and levobupivacaine in awake, spontaneously breathing rats.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly allocated to control-bupivacaine (CB), control-levobupivacaine (CL), lipid-bupivacaine (LB), and lipid-levobupivacaine (LL) groups (n = 8 in each group). After infusion of saline (CB and CL groups) or 20 % lipid emulsion (LB and LL groups) for 5 min, bupivacaine (CB and LB groups) or levobupivacaine (CL and LL groups) was administered IV at 1 mg/kg/min. Cumulative dose of anesthetics and their plasma concentrations at the onset of convulsions and cardiac arrest were measured.
  
  
  RESULTS
  The doses of bupivacaine for inducing convulsions and cardiac arrest in the LB group (8.8 ± 1.7 and 10.2 ± 1.5 mg/kg, respectively) were significantly larger than those in the CB group (5.9 ± 1.1 and 7.1 ± 1.3 mg/kg, respectively, p < 0.001 for both). The doses of levobupivacaine for inducing convulsions and cardiac arrest in the LL group (10.0 ± 2.0 and 13.7 ± 3.6 mg/kg, respectively) were significantly larger than those in the CL group (7.7 ± 1.6 and 9.4 ± 2.4 mg/kg, p = 0.03 and p = 0.02, respectively). Plasma concentrations of bupivacaine at the onset of convulsions and cardiac arrest in the LB group (12.9 ± 2.9 and 41.4 ± 5.2 μg/ml, respectively) were significantly higher than those in the CB group (7.9 ± 1.2 and 21.6 ± 3.3 μg/ml, respectively, p < 0.001 for both). Plasma concentrations of levobupivacaine at the onset of convulsions and cardiac arrest in the LL group (17.5 ± 1.5 and 47.6 ± 6.1 μg/ml, respectively) were significantly higher than in the CL group (10.9 ± 2.2 and 29.2 ± 3.5 μg/ml, respectively, p < 0.001 for both).
  
  
  CONCLUSIONS
  Lipid emulsion decreased CNS and cardiac toxicity of both bupivacaine and levobupivacaine.
authors.affiliation: Department of Anesthesiology, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abeno-ku, Osaka, 545-8586, Japan. odayou@msic.med.osaka-cu.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D002490:Central Nervous System / Q000187:drug effects*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000633:toxicity*; D006323:Heart Arrest / Q000139:chemically induced*; D000077554:Levobupivacaine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D000077554:Levobupivacaine; D002045:Bupivacaine