Intralipid® 20% for Local Anesthetic Reversal

Overseen By Justas Lauzadis, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Hospital for Special Surgery, New York

Must not be taking: Opioids, Benzodiazepines, Antipsychotics, others

Disqualifiers: ASA III, Pregnant, Allergies, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 visits

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

In order to determine if Intralipid 20% can be used to reverse the effects of local anesthetics, the investigators will recruit 18 volunteers who will be asked to come to HSS for two study visits. Small amounts of local anesthetics will be injected into the volunteers' thighs during both visits. During one visit volunteers will receive Intralipid 20% and during the other visit they will receive a saline solution. The study team will measure how quickly normal sensation returns to the thighs when the volunteers get Intralipid 20% compared to saline.

Will I have to stop taking my current medications?

The trial requires that you do not use drugs that affect the sensorium, such as opioids, benzodiazepines, antipsychotics, and gabapentinoids.

Is Intralipid® 20% safe for use in humans?

Intralipid® 20% has been used safely in humans to treat toxicities from local anesthetics and other drugs, with case reports showing successful outcomes in reversing drug overdoses. It is considered a standard treatment for severe local anesthetic toxicity, suggesting a favorable safety profile in these contexts. ^{1 2 3 4 5}

How does Intralipid® 20% differ from other treatments for local anesthetic toxicity?

Intralipid® 20% is unique because it acts as a 'lipid sink' to absorb and neutralize local anesthetics in the bloodstream, which is different from traditional resuscitation methods that do not specifically target the anesthetic itself. This lipid emulsion is administered intravenously and is particularly used when other treatments fail to reverse the toxicity. ^{3 4 5 6 7}

What data supports the effectiveness of the drug Intralipid 20% Solution for reversing local anesthetic toxicity?

Intralipid 20% Solution has been shown to be effective in treating local anesthetic toxicity, as it is recommended as a first-line treatment by several international anesthesia organizations. Additionally, case reports have documented successful reversal of local anesthetic-induced toxicity using Intralipid, and it has also been effective in treating toxicities from other drug classes. ^{1 3 6 7 8}

Who Is on the Research Team?

Stavros Memtsoudis, MD/PhD

Principal Investigator

Hospital for Special Surgery, New York

Are You a Good Fit for This Trial?

This trial is for healthy English-speaking volunteers with a BMI of 18-25 and body weight between 50-100kg. It's not suitable for pregnant women, those with significant medical conditions (ASA III or higher), allergies to lidocaine, bupivacaine, soybeans, eggs, or those using drugs that affect the senses like opioids.

Inclusion Criteria

English speaking

My BMI is between 18-25 and I weigh between 50-100kg.

Exclusion Criteria

I am currently taking medication that affects my awareness or consciousness.

ASA III or higher

You are pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive injections of local anesthetics and either Intralipid 20% or saline during two study visits

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for the return of normal sensation after treatment

up to 24 hours

What Are the Treatments Tested in This Trial?

Interventions

• Intralipid® 20% Solution

Trial Overview The study tests if Intralipid® 20%, an intravenous fat emulsion, can reverse numbness from local anesthetics faster than saline solution. Volunteers will receive small doses of local anesthetics in their thighs and then either Intralipid® or saline to compare recovery times.

How Is the Trial Designed?

Group I: Intralipid 20% IV Bolus Experimental Treatment 6 Interventions

This is 1 out of the 2 study visits. The patient will receive 6 injections (3 in each thigh). The 6 injections are: 1. lidocaine 1% 2. lidocaine 2% 3. bupivacaine 0.5% 4. bupivacaine 0.25% 5. saline 6. no injection Each test solution will be injected over 5 seconds through a 27G needle and tuberculin syringe at a 30 degree angle. The patient will also receive an intravenous bolus in the arm of Intralipid 20%. Participant will be blindfolded for these activities so they will not know what they received during the visit.

Group II: Saline Placebo Group 6 Interventions

This is 2 out of the 2 study visits. The patient will receive 6 injections (3 in each thigh). The 6 injections are: 1. lidocaine 1% 2. lidocaine 2% 3. bupivacaine 0.5% 4. bupivacaine 0.25% 5. saline 6. no injection Each test solution will be injected over 5 seconds through a 27G needle and tuberculin syringe at a 30 degree angle. The patient will also receive an intravenous bolus in the arm of Saline. Participant will be blindfolded for these activities so they will not know what they received during the visit.

Who Is Running the Clinical Trial?

Hospital for Special Surgery, New York

Lead Sponsor

Trials

257

Recruited

61,800+

Published Research Related to This Trial

A survey of 36 anesthesiology departments in China revealed that only 22% had intravenous lipid emulsions readily available for treating Local Anesthetic Systemic Toxicity (LAST), despite it being a recommended first-line treatment.

Among the departments with lipid emulsion, 11 patients were successfully resuscitated from LAST, indicating that while the treatment is effective, its limited availability highlights a need for increased adoption and awareness of lipid rescue therapy in China.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional anesthesia and lipid resuscitation for local anesthetic systemic toxicity in China: results of a survey by the orthopedic anesthesia group of the Chinese Society Of Anesthesiology. Xu, M., Jin, S., Li, Z., et al.[2018]

In a study involving 60 rats, Intralipid (LCT emulsion) was found to be more effective than Lipovenoes (LCT/MCT emulsion) in reversing cardiac arrest caused by bupivacaine, with fewer instances of repeated asystole after resuscitation.

The LCT emulsion also resulted in lower plasma and myocardial bupivacaine concentrations, suggesting it may be a safer option for treating bupivacaine-related cardiotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion. Li, Z., Xia, Y., Dong, X., et al.[2013]

Intralipid, a 20% lipid emulsion, has been suggested as a potential treatment for local anesthetic toxicity, especially when traditional resuscitation methods fail.

A case report demonstrated a positive response in a patient experiencing local anesthetic toxicity after receiving Intralipid, highlighting its potential efficacy in such critical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The successful use of intralipid for treatment of local anesthetic-induced central nervous system toxicity: Some considerations for administration of intralipid in an emergency. Espinet, AJ., Emmerton, MT.[2013]

Intravenous lipid emulsion (ILE) therapy, commonly used for local anesthetic toxicity, has shown effectiveness in reversing toxicities from various drug classes, including antipsychotics and antidepressants, based on a review of 31 case reports involving 49 overdose cases.

The findings highlight the need for increased clinician awareness about the diverse applications of Intralipid therapy beyond local anesthetics, as it can be beneficial in treating multiple drug toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of intravenous lipid emulsion therapy. Muller, SH., Diaz, JH., Kaye, AD.[2018]

In a study involving 11 Yorkshire swine, those treated with a 20% lipid emulsion after receiving ropivacaine showed significantly higher postmortem serum levels of both total and free ropivacaine compared to those that received ropivacaine alone, indicating altered drug distribution after lipid therapy.

The lipid-treated swine experienced an earlier onset of death (asystole) and showed a significant decrease in ropivacaine concentrations in lung, kidney, and brain tissues postmortem, suggesting that lipid emulsion therapy may complicate the interpretation of drug levels in cases of local anesthetic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of lipid emulsion infusion on postmortem ropivacaine concentrations in swine: endeavoring to comprehend a soldier's death. Buckenmaier, CC., Capacchione, J., Mielke, AR., et al.[2018]

Intravenous lipid emulsion therapy has been shown to effectively reverse severe cardiac issues caused by local anesthetic toxicity, including arrhythmias and cardiac arrest, based on systematic reviews and case reports.

While there is less evidence for its effectiveness against neurological toxicities, the low risk of major adverse events makes intravenous lipid emulsion a recommended treatment option in settings where large doses of local anesthetics are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous lipid emulsion for treatment of local anesthetic toxicity. Kosh, MC., Miller, AD., Michels, JE.[2021]

Lipofundin® was found to sequester local anesthetics (bupivacaine, ropivacaine, and mepivacaine) more effectively than Intralipid®, with extraction rates of 34.7% vs. 22.3% for bupivacaine, indicating that the choice of lipid emulsion can significantly impact treatment efficacy in reversing cardiac toxicity.

The study suggests that the effectiveness of lipid emulsions in extracting anesthetics from serum is not significantly affected by pH changes, challenging recent guidelines that recommend delaying treatment until pH normalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion. Ruan, W., French, D., Wong, A., et al.[2013]

In a study involving 16 volunteers, the administration of Intralipid® did not significantly affect the time to onset of neurologic symptoms from modestly toxic doses of ropivacaine or levobupivacaine.

However, Intralipid® infusion was associated with a 26 to 30% reduction in peak plasma concentrations of the local anesthetics, suggesting it may help mitigate rapid increases in drug levels after extravascular administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. Dureau, P., Charbit, B., Nicolas, N., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Regional anesthesia and lipid resuscitation for local anesthetic systemic toxicity in China: results of a survey by the orthopedic anesthesia group of the Chinese Society Of Anesthesiology. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

The successful use of intralipid for treatment of local anesthetic-induced central nervous system toxicity: Some considerations for administration of intralipid in an emergency. [2013]

4. Japan pubmed.ncbi.nlm.nih.gov

Clinical applications of intravenous lipid emulsion therapy. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of lipid emulsion infusion on postmortem ropivacaine concentrations in swine: endeavoring to comprehend a soldier's death. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous lipid emulsion for treatment of local anesthetic toxicity. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. [2022]