Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study

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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.

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