Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. (September 2016)

• Record Type: Journal Article
• Authors: Dureau, Pauline; Charbit, Beny; Nicolas, Nathalie; Benhamou, Dan; Mazoit, Jean-Xavier
• Is Part Of: Anesthesiology. Volume 125:Number 3(2016)
• Publication Date: 2016-09
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000001230
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : Background: 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. Methods: 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. Results: 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. Conclusions: 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. Abstract : In a crossover study conducted in 16 volunteers, a lipid emulsion infusion begun 2 min after initiating an infusion of ropivacaine or levobupivacaine did not affect the times to early signs of central nervous system toxicity. Peak local anesthetic concentrations at the end of the local anesthetic infusions decreased by 26 to 30% due to an increase in the central volume of a multicompartmental pharmacokinetic model. Pharmacokinetic simulations suggest that a lipid emulsion might prevent the rapid increase of local anesthetic concentrations after extravascular administration.Supplemental Digital Content is available in the text.