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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Intralipid 20% can restore normal skin sensation more quickly after using local anesthetics, which numb a small area of the body. Participants will receive injections of local anesthetics in their thighs and will receive either Intralipid 20% (a lipid emulsion) or a saline solution through an IV in their arm. The researchers will measure the speed of sensation return. Eligible participants should speak English, have a BMI between 18 and 25, and weigh between 50-100 kg. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand its benefits for more patients.

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.

What is the safety track record for Intralipid 20% Solution?

Research has shown that Intralipid 20% is generally safe for people. This treatment often addresses issues caused by local anesthetics. Studies have found it effectively treats harmful reactions from these anesthetics, which can affect the heart and nervous system. Reports from these studies suggest that Intralipid 20% is safe for this purpose.

Doctors commonly use Intralipid 20% to manage serious side effects of local anesthetics, indicating their trust in it for emergencies. So far, no major safety concerns have arisen for people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Intralipid® 20% is unique because it offers a potential solution for reversing the effects of local anesthetics like lidocaine and bupivacaine. Unlike standard treatments, which typically involve waiting for the anesthetic to wear off, Intralipid® 20% is administered intravenously and may actively reverse anesthetic effects more rapidly. Researchers are excited about this treatment because its lipid-based mechanism could provide a faster and more efficient option for patients experiencing prolonged or unwanted numbness following local anesthesia. Additionally, using a common intravenous lipid solution could make the transition to clinical practice smoother, as it builds on existing medical supplies and knowledge.

What evidence suggests that Intralipid 20% might be an effective treatment for local anesthetic reversal?

Previous studies have shown that Intralipid 20% helps with problems caused by local anesthetics by absorbing them in the blood, reducing their effects. Research suggests it is recommended for reversing heart and nerve issues caused by these drugs. In animal studies, Intralipid proved more effective than other similar treatments in reversing serious effects like heart stoppage. In this trial, participants will receive either an intravenous bolus of Intralipid 20% or a saline placebo to evaluate its effectiveness in speeding up the return to normal sensation after using local anesthetics. ^{1 2 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

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6001420/

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

Lipid emulsion has been shown to be an effective treatment for systemic toxicity induced by local anesthetics, which is reflected in case reports.

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK499964/

Local Anesthetic Toxicity - StatPearls - NCBI Bookshelf - NIH

Intravenous lipid emulsion aids in resuscitation by sequestering and redistributing local anesthetics while also enhancing cardiac output ...

3.

withpower.com

withpower.com/trial/phase-4-6-2019-5bd25

Intralipid® 20% for Local Anesthetic Reversal

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 ...

4.

emedicine.medscape.com

emedicine.medscape.com/article/1844551-treatment

Local Anesthetic Toxicity Treatment & Management

Current guidelines recommend the intravenous (IV) infusion of lipid emulsion to reverse the cardiac and neurologic effects of local anesthetic toxicity.

5.

frontiersin.org

frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.756866/full

Mechanisms and Efficacy of Intravenous Lipid Emulsion ...

Lipid emulsion enters the blood system to form a lipid depot, which can absorb highly fat-soluble drugs (local anesthetics and nonlocal anesthetics) to clear ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01602250

NCT01602250 | Local Anaesthetics Toxicity and Intralipid®

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 ...

7.

pch.health.wa.gov.au

pch.health.wa.gov.au/For-health-professionals/Emergency-Department-Guidelines/Lipid-infusion

Lipid infusion (Intralipid 20%®) for local anaesthetic toxicity

Intravenous lipid emulsion administration is an established clinical practice for treating local anaesthetic systemic toxicity.

8.

journal.chestnet.org

journal.chestnet.org/article/S0012-3692(16)41750-2/fulltext

Intravenous Lipid Emulsion Rescue for Severe Central ...

CONCLUSION: Intravenous Intralipid appears to be safe and effective for use in treatment of life-threatening CNS and cardiovascular adverse reactions related ...