Local Anaesthetics Toxicity and Intralipid®

NCT ID: NCT01602250

Last Updated: 2016-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-08-31

Brief 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.

Conditions

Toxicity; Adverse Effects

Keywords

Anesthetics, local; Toxicity; Adverse effects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

levobupivacaine placebo

levobupivacaine placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Levobupivacaine 8 mg/min ropivacaine 8 mg/min

levobupivacaine Intralipid®

levobupivacaine Intralipid®

Group Type: EXPERIMENTAL

Intralipid®

Intervention Type: DRUG

Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min

ropivacaine Intralipid®

ropivacaine Intralipid®

Group Type: EXPERIMENTAL

Intralipid®

Intervention Type: DRUG

Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min

ropivacaine placebo

ropivacaine placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Levobupivacaine 8 mg/min ropivacaine 8 mg/min

Interventions

placebo

Levobupivacaine 8 mg/min ropivacaine 8 mg/min

Intervention Type: DRUG

Intralipid®

Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min

Intervention Type: DRUG

Other Intervention Names

levobupivacaine; ropivacaine

Eligibility Criteria

Inclusion Criteria

• Volunteers ASA1

Exclusion Criteria

• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Benhamou

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

CIC plurithématique Paris-Est (CIC-9304)

Paris, , France

Countries

France

References

Dureau P, Charbit B, Nicolas N, Benhamou D, Mazoit JX. Effect of Intralipid(R) on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. Anesthesiology. 2016 Sep;125(3):474-83. doi: 10.1097/ALN.0000000000001230.

Reference Type: RESULT

PMID: 27404223 (View on PubMed)

Other Identifiers

P100501

Identifier Type: -

Identifier Source: org_study_id