title: Lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic doses.
abstract: OBJECTIVE
  Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics.
  
  
  METHODS
  The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10(-4) M levobupivacaine, 2×10(-3) M ropivacaine, and 7×10(-3) M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed.
  
  
  RESULTS
  Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10(-3) M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics.
  
  
  CONCLUSIONS
  Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 660-702, Korea. jtsohn@nongae.gsnu.ac.kr.
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.forename: Jongsun
authors.initials: J
authors.lastname: Yu
authors.forename: Mun-Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lim
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000577:Amides / Q000009:adverse effects; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D002045:Bupivacaine / Q000009:adverse effects / Q000031:analogs & derivatives; D004655:Emulsions / Q000737:chemistry* / Q000627:therapeutic use*; D000077554:Levobupivacaine; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008619:Mepivacaine / Q000009:adverse effects; D009638:Norepinephrine / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D004655:Emulsions; D008055:Lipids; D000077212:Ropivacaine; D000077554:Levobupivacaine; D008619:Mepivacaine; D009638:Norepinephrine; D002045:Bupivacaine
keywords: Lipid emulsion; local anesthetic-induced vasodilation; norepinephrine; systemic toxicity of local anesthetic