Local Anaesthetics Toxicity and Intralipid®
Condition: Toxicity; Adverse Effects
Study type: Interventional
Phase: Phase 2

Summary: 
      The systemic toxicity of local anaesthetics may be treated using lipid emulsions ("lipid
      rescue"). However, there is no evidence-based proof of the efficacy of the treatment. The aim
      of the intended protocol is to study the effect of the emulsion Intralipid® on the toxicity
      prodromes in volunteers receiving either levobupivacaine or ropivacaine. After a
      sensitization session with lidocaine, subjects will receive in a double blind, crossover
      manner an i.v. infusion of levobupivacaine or ropivacaine followed by a rapid infusion of
      Intralipid®. The primary outcome will be the time of appearance of early neurologic signs of
      toxicity. In addition, the EEG and ECG will be monitored and blood sampling will be performed
      in order to evaluate the changes in pharmacokinetics induced by the emulsion.
    

Detailed description: 
      Regional anaesthesia may induce toxic neurologic and cardiac reactions related to inadvertent
      intravenous injection or rapid absorption of local anaesthetics. Despite the appearance of
      the less toxic agents ropivacaine and levobupivacaine, the problem remains. Recently, a new
      therapeutics called "lipid rescue" emerged. This rapid injection of a lipid emulsion is
      supposed to act as a lipid sink, thus delaying the release of the toxic molecules to the
      target organs. Animal studies as well as clinical reports seem to favour this treatment.
      However, there is no evidence-based proof of the efficacy of this "lipid rescue".

      The aim of the study is 1) to verify the efficacy of a lipid emulsion (Intralipid® 20%) on
      the toxicity induced by the local anaesthetics ropivacaine and levobupivacaine and 2) to
      compare the effect of the emulsion on the two agents.

      Sixteen volunteers with strictly normal ECG and EEG will participate to the study.

      After a sensitization session with lidocaine, the subjects will receive levobupivacaine or
      ropivacaine i.v. at a rate of 8 mg/min (max 120 mg) followed two minutes after the beginning
      of infusion by a bolus injection of Intralipid® 20% or of saline 120 mL in 1 minute. The
      infusion of local anaesthetics will be stopped immediately at the appearance of the early
      signs of toxicity. In addition to the recognition of the signs by the subject (trained by the
      sensitization session), an anaesthesiologist will ask if the subject has any symptom. A
      continuous monitoring of the EEG and of the ECG will be performed.

      Sixteen subjects completing the study have been considered necessary to achieve a power of 90
      % with an alpha risk of 5 %. A mean time to first signs of 3.8 ± 1.2 min has been considered
      in the placebo groups. A 45 % difference in the primary outcome has been considered. The
      study will be double blind crossover as a Latin square (four treatments, four sessions, four
      replications).

      The investigators will consider the time between infusion initiation and appearance of the
      early signs of toxicity as primary outcome. The secondary outcomes will be the changes in ECG
      and EEG variables and the pharmacokinetic parameters observed. For that purpose, blood will
      be sampled until the 8th hour after the beginning of local anaesthetic infusion.
    

Intervention name(s): placebo; Intralipid®
Intervention type(s): Drug; Drug
Intervention description(s): Levobupivacaine 8 mg/min ropivacaine 8 mg/min; Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min
Other intervention name(s): levobupivacaine; ropivacaine
Intervention MeSH terms: Ropivacaine; Levobupivacaine; Soybean oil, phospholipid emulsion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Anesthetics, local; Toxicity; Adverse effects