title: Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study.
abstract: Rapid intravenous administration of lipid emulsion has become the standard treatment of severe local anesthetic systemic toxicity. This experiment in volunteers aimed at determining the effect of Intralipid® administration on the time to neurologic symptoms.
  
  
  
  Ropivacaine or levobupivacaine was infused intravenously in 16 volunteers (8 mg/min up to 120 mg) with 120 ml Intralipid® 20% (Fresenius, Paris France) or placebo infused at T + 2 min). Each subject received all four treatments in a crossover manner. The infusion was stopped after the intended dose had been administered or on occurrence of incipient neurologic signs of toxicity. The primary outcome was time-to-event. In addition, blood ropivacaine and levobupivacaine concentrations were measured.
  
  
  
  The dose infused was not different whether volunteers received placebo (81.7 ± 22.3 vs. 80.8 ± 31.7 mg, ropivacaine vs. levobupivacaine) or Intralipid® (75.7 ± 29.1 vs. 69.4 ± 26.2 mg, ropivacaine vs. levobupivacaine), P = 0.755, Intralipid® versus placebo groups. Plasma concentrations were best modeled with an additional volume of distribution associated with Intralipid®. Simulations suggested that decreased peak concentrations would be seen if Intralipid® was given during a period of increasing concentrations after extravascular administration.
  
  
  
  At modestly toxic doses of ropivacaine or levobupivacaine, we were unable to find any effect of the infusion of Intralipid® on the time to early signs of neurologic toxicity in volunteers. Peak concentration was decreased by 26 to 30% in the subjects receiving Intralipid®. Simulations showed that Intralipid® might prevent the rapid increase of local anesthetic concentration after extravascular administration.
authors.affiliation: From the Département d'Anesthésie-Réanimation, Hôpitaux Universitaires Paris-Sud AP-HP, Paris, France (D.B., J.-X.M.); Faculté de Médecine, Laboratoire d'Anesthésie, INSERM UMR 788, Université Paris-Sud, Bicêtre Cedex, Paris, France (D.B., J.-X.M.); and Centre d'Investigation Clinique Paris-Est Hôpital de la Pitié-Salpêtrière AP-HP, Paris, France (P.D., B.C., N.N.). Current position: Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire, Reims, France (B.C.).
authors.forename: Pauline
authors.initials: P
authors.lastname: Dureau
authors.forename: Beny
authors.initials: B
authors.lastname: Charbit
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolas
authors.forename: Dan
authors.initials: D
authors.lastname: Benhamou
authors.forename: Jean-Xavier
authors.initials: JX
authors.lastname: Mazoit
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D004655:Emulsions / Q000494:pharmacology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077554:Levobupivacaine; D008297:Male; D010092:Oximetry / Q000706:statistics & numerical data; D010743:Phospholipids / Q000494:pharmacology*; D012016:Reference Values; D000077212:Ropivacaine; D013024:Soybean Oil / Q000494:pharmacology*
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D004655:Emulsions; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D000077212:Ropivacaine; D013024:Soybean Oil; D000077554:Levobupivacaine; D002045:Bupivacaine