title: Binding of long-lasting local anesthetics to lipid emulsions.
abstract: BACKGROUND
  Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides.
  
  
  METHODS
  Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France).
  
  
  RESULTS
  The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics.
  
  
  CONCLUSIONS
  The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity, racemic bupivacaine and levobupivacaine seem to clear more rapidly than ropivacaine.
authors.affiliation: Université Paris-Sud, Laboratoire d'Anesthésie, Faculté de Médecine, Le Kremlin Bicêtre, France. jean-xavier.mazoit@u-psud.fr
authors.forename: Jean-Xavier
authors.initials: JX
authors.lastname: Mazoit
authors.forename: Régine
authors.initials: R
authors.lastname: Le Guen
authors.forename: Hélène
authors.initials: H
authors.lastname: Beloeil
authors.forename: Dan
authors.initials: D
authors.lastname: Benhamou
mesh_terms: D000465:Algorithms; D000577:Amides / Q000008:administration & dosage / Q000737:chemistry; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry*; D002021:Buffers; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry; D005217:Fat Emulsions, Intravenous / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D000077212:Ropivacaine; D012995:Solubility; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D002021:Buffers; D005217:Fat Emulsions, Intravenous; D014280:Triglycerides; D000077212:Ropivacaine; D002045:Bupivacaine