Lidocaine + Epinephrine for Local Anesthesia

Overseen By Kira Minkis, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Weill Medical College of Cornell University

Must not be taking: MAOIs, Antidepressants

Disqualifiers: Pregnancy, Breastfeeding, Anesthetic allergy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 4 hours

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the duration of pain relief using varying amounts of a common numbing medication (lidocaine with epinephrine) during skin surgeries. Researchers will compare two amounts of the medication on different sides of the nose to assess which lasts longer. Ideal participants are adults with normal skin sensation in their nose and no known allergies to the anesthetics used in the study. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits more patients.

Will I have to stop taking my current medications?

If you are taking monoamine oxidase inhibitors (MAOI) or certain antidepressants like triptyline or imipramine, you cannot participate in the trial. For other medications, the protocol does not specify if you need to stop taking them.

What is the safety track record for Lidocaine + Epinephrine?

Studies have shown that lidocaine with epinephrine is generally safe and well-tolerated. It often numbs areas for surgeries, and most people do not experience serious side effects when used in the right amounts. Research indicates that the maximum safe dose for adults is 7 mg per kilogram of body weight.

However, rare side effects can occur. Some individuals might develop methemoglobinemia, a condition that affects how well blood carries oxygen, which is more likely in young children and older adults. Additionally, those allergic to lidocaine or similar anesthetics should avoid its use.

Overall, lidocaine with epinephrine is considered safe when used properly. Following guidelines and informing the medical team about any allergies or health issues is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores how different doses of lidocaine with epinephrine affect the duration of local anesthesia in procedures involving the nasal area. Lidocaine with epinephrine is already a common choice for local anesthesia due to its ability to numb areas quickly and reduce bleeding. This study focuses on the potential benefits of varying the volume of this combination, aiming to optimize how long the numbing effect lasts. By comparing 0.5 ml and 1.0 ml doses, researchers hope to find a more efficient way to manage anesthesia, potentially leading to improved patient comfort and outcomes during surgeries or medical procedures involving the nose.

What is the effectiveness track record for Lidocaine + Epinephrine in local anesthesia?

Research has shown that using lidocaine with epinephrine effectively numbs an area during medical procedures. Studies have found that adding epinephrine reduces bleeding and decreases the risk of lidocaine side effects. This combination also accelerates the onset of the numbing effect. Patients often temporarily lose feeling in the area, which is normal and expected. In this trial, participants will receive different volumes of buffered lidocaine with epinephrine to compare their effectiveness in providing anesthesia. These findings support its reliability in providing anesthesia during surgeries. ^{2 6 7 8 9}

Who Is on the Research Team?

Kira Minkis, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for individuals who require local anesthesia, possibly for dermatologic procedures. Specific eligibility criteria are not provided, so it's assumed that participants should be in good health and suitable for receiving local anesthetics.

Inclusion Criteria

Ability to provide informed consent

Normal skin sensation at both nasal ala assessed by pinprick

Exclusion Criteria

Previous adverse reaction to local anesthetic or any components of the local anesthetics being evaluated

Pregnant or breastfeeding volunteers (assessed by self-report)

I am currently taking MAOI or certain types of antidepressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive injections of lidocaine with epinephrine at different volumes on each side of the nasal ala. Sensation is tested every 15 minutes until return of sharp sensation.

Up to 4 hours

1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects and the effectiveness of the anesthetic post-treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Lidocaine + Epinephrine

Trial Overview

The study is testing the duration of pain relief from two different volumes of lidocaine mixed with epinephrine (0.5 ml and 1.0 ml) at sites with a lot of blood vessels to see if more anesthetic means longer pain relief.

How Is the Trial Designed?

Group I: 1.0 ml Lidocaine with epinephrine vs 0.5 ml Lidocaine with epinephrine Experimental Treatment 2 Interventions

Each side of the nasal ala will be tested for normal sensation using sterile 30-gauge needles. Other eligibility criteria will be confirmed. Participants in this arm will receive an injection of 1.0ml of Xylocaine + epinephrine 1:100,000 (lidocaine + epinephrine 1:100,000), buffered 1/10 with sodium bicarb into one side of the nose (nasal ala) and 0.5 ml of Xylocaine + epinephrine 1:100,000 (lidocaine + epinephrine 1:100,000), buffered 1/10 with sodium bicarb into the opposite nasal ala. Laterality of each anesthetic volume administration will be randomly assigned for each patient. Subjects will be evaluated for duration of effect of anesthesia every 15 minutes on both sides of the face, until the patient reports return of a sharp sensation upon the pinprick test.

Group II: 0.5 ml Lidocaine with epinephrine vs. 1.0 ml Lidocaine with epinephrine Experimental Treatment 2 Interventions

Each side of the nasal ala will be tested for normal sensation using sterile 30-gauge needles. Other eligibility criteria will be confirmed. Participants in this arm will receive an injection of 0.5ml of Xylocaine + epinephrine 1:100,000 (lidocaine + epinephrine 1:100,000), buffered 1/10 with sodium bicarb into one side of the nose (nasal ala) and 1.0 ml of Xylocaine + epinephrine 1:100,000 (lidocaine + epinephrine 1:100,000), buffered 1/10 with sodium bicarb into the opposite nasal ala. Laterality of each anesthetic volume administration will be randomly assigned for each patient. Subjects will be evaluated for duration of effect of anesthesia every 15 minutes on both sides of the face, until the patient reports return of a sharp sensation upon the pinprick test.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

A review of 48 reported cases of digital gangrene linked to local anesthetics revealed that only 21 involved epinephrine, and many cases had other complicating factors, suggesting that the prohibition against epinephrine may not be well-founded.

Extensive studies indicate that using commercial lidocaine with epinephrine is safe for digital anesthesia, with no documented cases of gangrene since its introduction in 1948, highlighting the need for a reevaluation of current practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of epinephrine in the finger: to do or not to do. Denkler, K.[2019]

In a study involving 42 patients undergoing third molar surgery, 1% etidocaine with epinephrine provided a comparison to 2% lidocaine, focusing on various aspects of local anesthesia such as onset time and duration.

The evaluation highlighted patient preferences and postoperative pain experiences, suggesting that the choice of anesthetic can significantly impact patient comfort during and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advantages of long-acting local anesthesia using etidocaine hydrochloride. Jensen, OT., Upton, LG., Hayward, JR., et al.[2013]

The combination of bupivacaine and lidocaine for local dental anesthesia results in a longer duration of anesthetic effect compared to lidocaine alone, although the onset time is similar for both preparations.

Using the combination of lidocaine and bupivacaine leads to lower systemic levels of both lidocaine and epinephrine, which may enhance safety during dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of lidocaine with and without bupivacaine for local dental anesthesia. Oka, S., Shimamoto, C., Kyoda, N., et al.[2018]

Ropivacaine 0.75% provided significantly longer-lasting soft tissue anesthesia compared to lidocaine 2% with epinephrine, leading to lower pain scores at various postoperative intervals for the lidocaine group.

Despite its longer duration of anesthesia, ropivacaine was associated with more postoperative bleeding, indicating a potential trade-off in safety when choosing this anesthetic for dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can local anesthesia with ropivacaine provide postoperative analgesia in extraction of impacted mandibular third molars? A randomized clinical trial. Amorim, KS., Gercina, AC., Ramiro, FMS., et al.[2021]

In a review of 1,127 Mohs micrographic surgery cases, no serious adverse events requiring emergency interventions occurred when using lidocaine with epinephrine, even in patients with significant comorbidities.

The study suggests that when lidocaine with epinephrine is administered below FDA-recommended maximum doses, the presence of crash carts and emergency equipment may not be necessary during outpatient procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intradermal/Subcutaneous Lidocaine With Epinephrine Use in Dermatologic Surgery. Hirshburg, JM., Diven, DG., Edmiston, C., et al.[2021]

In a study of 32 patients with ischemic heart disease undergoing reconstructive surgery, the use of 10 ml of 2% lidocaine with 1:100,000 epinephrine was found to be safe, showing no significant disturbances in blood pressure or myocardial ischemic changes during and after the procedure.

The patients experienced effective anesthesia without early complications, indicating that this local anesthetic combination can provide hemodynamic stability and adequate pain control in cardiac patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evaluation of perioperative safety of local anesthesia with lidocaine containing epinephrine in patients with ischemic heart disease. Sanatkar, M., Sadeghi, M., Esmaeili, N., et al.[2013]

In a study of 120 patients undergoing eyelid surgery, the 2% lidocaine with epinephrine-bupivacaine mixture resulted in higher pain scores compared to 2% lidocaine alone, indicating that the addition of epinephrine may increase pain perception.

The study found that while the mixture of lidocaine with epinephrine and bupivacaine did not significantly differ in subjective pain scores from the lidocaine with epinephrine alone, both combinations were less effective than plain lidocaine in minimizing pain during the first injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Comparative Study of the Pain of Local Anesthesia Using 2% Lidocaine, 2% Lidocaine With Epinephrine, and 2% Lidocaine With Epinephrine-Bupivicaine Mixture for Eyelid Surgery. Han, JW., Nah, SK., Lee, SY., et al.[2018]

Epinephrine significantly enhances the distribution and retention of lidocaine in the dental pulp, with levels more than twice as high when combined with epinephrine compared to lidocaine alone, indicating improved efficacy for local anesthesia.

The use of epinephrine also reduced pulpal blood volume by 63.1% after 20 minutes, suggesting that it effectively prolongs the anesthetic effect by limiting blood flow in the area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epinephrine on lidocaine pharmacokinetics and blood volume in the dental pulp. Hashimoto, S., Yamashiro, M., Fujita, K., et al.[2014]

In a study of 90 adult patients undergoing sinus surgery, local infiltration of lidocaine with epinephrine resulted in significant hemodynamic changes, including a decrease in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI), along with an increase in heart rate (HR) and cardiac index (CI).

The hemodynamic effects were more pronounced with higher doses of epinephrine (20 and 40 micrograms) compared to no epinephrine, indicating that while epinephrine enhances analgesia and hemostasis, it also affects cardiovascular parameters during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epinephrine infiltration on nasal field causes significant hemodynamic changes: hypotension episode monitored by impedance-cardiography under general anesthesia. Yang, JJ., Zheng, J., Liu, HJ., et al.[2013]

Using lidocaine with clonidine as a vasoconstrictor resulted in less tachycardia and more stable heart function compared to lidocaine with adrenaline, indicating a safer option for local anesthesia in patients with moderate hypertension.

The combination of clonidine with lidocaine helps to reduce sympathetic tension and prevent hypertensive reactions during surgery, making it an effective alternative to traditional vasoconstrictors like adrenaline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined use of local anesthetic with clonidine in cases of tooth extraction]. Mishunin, IuV., Ostreĭkov, IF., Nazarov, NA., et al.[2013]

Epinephrine and levonordefrin reduced the toxicity and lethality of procaine in mice, suggesting they can enhance the safety profile of this local anesthetic.

Epinephrine increased the toxicity and lethality of bupivacaine and tetracaine, indicating that while it can be beneficial for some anesthetics, it may pose risks for others, particularly in certain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of local anesthetic toxicity by vasoconstrictors. Taylor, SE., Dorris, RL.[2018]

In a study of 50 patients with moderate hypertension undergoing tooth extraction, the combination of lidocaine with clonidine provided similar anesthetic effects to lidocaine with epinephrine, but with better hemodynamic stability.

Patients receiving lidocaine with clonidine experienced significantly less postoperative pain and required fewer analgesics compared to those receiving lidocaine with epinephrine, suggesting clonidine may be a safer alternative for hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension? Patil, PM., Patil, SP.[2013]

Epinephrine significantly enhances the intensity and duration of analgesia provided by lidocaine in peripheral nerve blocks, increasing the effectiveness of pain relief in a rat model.

The mechanism behind this enhancement includes both pharmacodynamic effects, which temporarily boost lidocaine's potency, and pharmacokinetic effects that alter how lidocaine is distributed within the nerve, leading to a greater amount of lidocaine remaining in the nerve over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve block. Sinnott, CJ., Cogswell III, LP., Johnson, A., et al.[2022]

The study involved 17 healthy patients undergoing impacted third molar surgery, where lidocaine with epinephrine was used as a local anesthetic.

Results showed that lidocaine-epinephrine is effective for anesthesia during the procedure and did not cause significant adverse hemodynamic effects or important adverse events in the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery. Meral, G., Tasar, F., Sayin, F., et al.[2013]

In a study involving 25 healthy volunteers, the addition of dexmedetomidine to lidocaine significantly reduced the onset time of anesthesia and prolonged its duration compared to lidocaine with epinephrine.

Patients receiving lidocaine with dexmedetomidine reported less pain perception and required fewer analgesics postoperatively, while vital signs remained stable, indicating a safe profile for dexmedetomidine as an adjunct in dental anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an Additive to Local Anesthesia: A Step to Development in Dentistry. Singh, V., Thepra, M., Kirti, S., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6050998/

Comparison of Efficacy Outcomes of Lidocaine Spray, Topical ...

Topical lidocaine anesthesia had the same postoperative pain relief and the least adverse events as local and general lidocaine anesthesia. MeSH Keywords: ...

2.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2017/006488s095_s090lbl.pdf

Xylocaine-MPF (Epinephrine and Lidocaine Hydrochloride)

When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of ...

3.

journals.lww.com

journals.lww.com/dermatologicsurgery/fulltext/2022/02000/effective_use_of_lidocaine_with_epinephrine_during.31.aspx

Effective Use of Lidocaine With Epinephrine During a...

The lack of epinephrine in lidocaine will lead to higher bleeding rates, increased risk of lidocaine toxicity, and decreased onset of action of local anesthesia ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04732104

Efficacy of Lidocaine and Xylometazoline Intranasal Spray ...

If profound local anesthesia was still not achieved the case was labeled as failure of intranasal spray anesthesia and local anesthesia was ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2007333/

Anesthetic efficacy of a combination of hyaluronidase and ...

The purpose of this prospective, randomized, double-blind study was to determine the anesthetic efficacy of a buffered lidocaine with epinephrine solution

6.

septodont-en.ca

septodont-en.ca/wp-content/uploads/sites/10/2022/11/Lidocaine-Epinephrine-2021-SDS_3.pdf?x67568

MATERIAL SAFETY DATA SHEET

OSHA Regulatory Status: Epinephrine bitartrate (epinephrine salt) is not listed as a hazardous product in the RCRA (EPA) and CERCLA (EPA) regulations.

7.

henryschein.ca

henryschein.ca/MSDS/105Y345_CA_MSDS_01.pdf

DENTSPLY International Safety Data Sheet

LD50 for Lidocaine Hydrochloride: 317 mg/kg oral rat. LD50 for Epinephrine Bitartrate: 4 mg/kg oral mouse. Reproductive Toxicity Data: No significant effects ...

8.

labeling.pfizer.com

labeling.pfizer.com/ShowLabeling.aspx?id=4499

LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE

Lidocaine Hydrochloride and Epinephrine Injections are contraindicated in patients with a known hypersensitivity to lidocaine or to any local anesthetics of the ...

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/lidocaine-and-epinephrine-injection-route/description/drg-20452177

Lidocaine and epinephrine (injection route) - Mayo Clinic

This medicine may cause a rare, but serious blood problem called methemoglobinemia. The risk may be increased in children younger than 6 months of age, elderly ...