Local Anesthetic Injection for High Blood Pressure

Overseen By Jeff C Gadsden, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must not be taking: Opioids

Disqualifiers: Chronic pain, Addiction, Psychiatric disorders, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage high blood pressure caused by prolonged surgery with a tourniquet on the leg. Researchers are testing whether injecting a local anesthetic, mepivacaine, near a key artery in the leg can reduce this type of blood pressure spike. Participants will receive either the anesthetic or a saltwater solution for comparison. The trial seeks individuals undergoing ankle replacement surgery who do not have chronic pain or regularly use opioids. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using opioids daily or have certain health conditions, you may not be eligible to participate.

What is the safety track record for Mepivacaine and Perifemoral Injection of Local Anesthetic?

Research has shown that mepivacaine, the local anesthetic used in this study, is generally safe. However, it should be used carefully in people with high blood pressure, as the Mayo Clinic notes that side effects may be more likely for those with hypertension.

Studies have found that using mepivacaine without a vasoconstrictor (a substance that narrows blood vessels) is safe for people with high blood pressure. It does not cause significant changes in blood pressure levels, indicating that mepivacaine is well-tolerated, especially in controlled settings like this study.

The trial uses an injection method that targets the anesthetic directly where needed. This method has been studied for its ability to manage blood pressure spikes during surgeries that use a tourniquet for a long time. Although specific safety data on this method is limited, the trial's later phase suggests some confidence in its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the use of local anesthetic mepivacaine for high blood pressure because it offers a novel approach to treatment. Unlike standard oral medications that typically target the heart or blood vessels, this treatment involves administering mepivacaine directly around the femoral artery, potentially providing a more localized effect. This perifemoral injection method could lead to faster results and fewer systemic side effects, making it an innovative alternative to traditional therapies like ACE inhibitors or beta-blockers. Additionally, using a local anesthetic in this way could open up new avenues for managing blood pressure with minimal invasiveness.

What evidence suggests that this trial's treatments could be effective for high blood pressure?

Research has shown that mepivacaine, a local pain reliever, can influence blood pressure. In this trial, participants in the Mepivacaine Block Group will receive an infiltration of mepivacaine above and beside the femoral artery. Studies have found that mepivacaine, when used without other substances that narrow blood vessels, does not significantly increase blood pressure in people with controlled high blood pressure. Some research even suggests that systolic blood pressure, the top number in a blood pressure reading, might slightly decrease after using mepivacaine. These effects suggest it could help manage certain blood pressure issues, such as ischemic hypertension, which results from reduced blood flow. Mepivacaine's potential to lower blood pressure in some situations makes it a promising option for studies on blood pressure control. ^{1 5 6 7 8}

Who Is on the Research Team?

Amanda Kumar, MD, PhD

Principal Investigator

Duke University

William M Bullock, MD, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-75 with good overall health (ASA 1-3) who are getting a total ankle replacement. It's not for pregnant women, those over 75 or under 18, people allergic to local anesthetics, underweight individuals (<50 kg), or anyone with conditions that could complicate surgery.

Exclusion Criteria

I cannot communicate my pain levels or need for pain relief.

You have an allergy or cannot tolerate local anesthetics.

You have severe anxiety, schizophrenia, or other mental health conditions that may affect your ability to participate in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive an injection of local anesthetic or saline by the femoral artery to assess impact on blood pressure during surgery

24 hours

1 visit (in-person)

Follow-up

Participants are monitored for changes in blood pressure, pain scores, opioid consumption, and quadriceps motor function

2 hours after admission to PACU

What Are the Treatments Tested in This Trial?

Interventions

• Mepivacaine
• Perifemoral Injection of Local Anesthetic

Trial Overview

The study tests if injecting a local anesthetic near the femoral artery can reverse high blood pressure caused by a tourniquet during ankle surgery. Participants will be randomly chosen to receive either saline or mepivacaine through a catheter and won't know which one they get.

How Is the Trial Designed?

Group I: Mepivacaine Block Group Experimental Treatment 2 Interventions

Infiltration of local anesthetic (mepivacaine) above and beside the femoral artery through a perineural catheter.

Group II: Saline Sham Group Placebo Group 2 Interventions

Infiltration of salt water (saline) above and beside the femoral artery through a perineural catheter.

Mepivacaine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Mepivacaine for:

• Local anesthesia for surgical procedures
• Dental anesthesia

Approved in European Union as Mepivacaine for:

• Local anesthesia for surgical procedures
• Regional anesthesia

Approved in Canada as Mepivacaine for:

• Local anesthesia for surgical procedures
• Dental anesthesia

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

3% mepivacaine hydrochloride injection provides a quick onset of anesthesia (average 111 seconds) and effective pain relief (pain-free time of 134 minutes), comparable to 2% lidocaine with adrenaline.

The use of 3% mepivacaine showed minimal side effects on the cardiovascular system, with no significant changes in systolic blood pressure compared to lidocaine, indicating its safety for use in patients with and without hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of 3% mepivacaine hydrochloride injection for oral local anesthesia]. Ding, S., Zhu, YQ., Wu, YN., et al.[2019]

In a study of 72 patients undergoing total knee arthroplasty, those receiving a multimodal cocktail periarticular injection with steroids showed significantly improved Knee Society Knee Scores at one and three months post-surgery compared to those without steroids.

Patients in the steroid group also had a shorter duration of celecoxib usage, indicating faster rehabilitation and potentially reduced reliance on non-steroidal anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of multimodal cocktail periarticular injection with or without steroid in total knee arthroplasty. Yue, DB., Wang, BL., Liu, KP., et al.[2022]

In a study of 42 patients undergoing total hip arthroplasty (THA), adding a pre-incision intra-articular injection of local anesthetic did not show any significant benefits over the standard post-incision peri-articular injection alone in terms of postoperative outcomes.

The study suggests that while ultrasound-guided injections are a cost-effective method for administering local anesthetics, the combination of pre- and post-incision injections does not improve pain management or recovery metrics compared to the standard approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain After Preoperative Ultrasound Guided Hip Injections for Total Hip Arthroplasty: A Pilot Randomized Controlled Trial. Holbert, SE., Fowler, B., West, M., et al.[2023]

In a study of 256 patients with arterial hypertension, 4% articaine with a vasoconstrictor was found to be highly effective for dental anesthesia, providing significant pain relief during treatment.

The efficacy of 3% mepivacaine without vasoconstrictors was 86.4%, but could be improved to 93.3% by administering non-steroidal anti-inflammatory drugs before the procedure, highlighting a potential strategy to enhance pain management in hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Out-patient dental care in patients with arterial hypertension]. Axamit, LA., Anisimova, EN., Orekhova, IV., et al.[2018]

Polocaine, a brand of mepivacaine hydrochloride, is shown to be a safe and effective short-acting local anesthetic based on a study involving 40 healthy volunteers.

The study also found that Polocaine can induce local vasodilation for up to 24 hours, enhancing its utility in medical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of the sympathetic effects of polocaine in a regional hallux block. Burns, S., Quist, T., Sowell, RK.[2013]

Nociceptors, which are pain-sensing fibers, are densely located in specific areas of the knee and hip joints, such as the infrapatellar fat pad and labral base, suggesting that targeted injections in these areas could enhance pain relief after surgeries.

The study highlights that using a combination of local anesthetics, anti-inflammatory agents, and possibly opioids in periarticular injections can improve pain management after knee and hip arthroplasties, with liposomal anesthetics potentially offering longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periarticular Injections in Knee and Hip Arthroplasty: Where and What to Inject. Ross, JA., Greenwood, AC., Sasser, P., et al.[2022]

In a study involving 10 cardiovascular patients, both articaine and mepivacaine with epinephrine were found to significantly increase heart rate and blood pressure during dental procedures, indicating a cardiovascular response to these anesthetics.

Despite these changes, no severe side effects or ischemic complications were observed, suggesting that while caution is warranted, the use of these anesthetics in cardiovascular patients can be safe under controlled conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effect of dental anesthesia with articaine (40 mg with epinefrine 0,5 mg % and 40 mg with epinefrine 1 mg%) versus mepivacaine (30 mg and 20 mg with epinefrine 1 mg%) in medically compromised cardiac patients: a cross-over, randomized, single blinded study. Torres-Lagares, D., Serrera-Figallo, MÁ., Machuca-Portillo, G., et al.[2021]

Four patients mistakenly injected with 1:1000 adrenaline instead of local anesthetic experienced severe cardiovascular symptoms, including elevated Troponin T and CPK levels, indicating heart stress or damage.

Over a five-year follow-up, all patients reported long-term effects such as tremor, muscle weakness, and shortness of breath, highlighting potential serious complications from this medical error that are not commonly documented in existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adrenaline toxicity following accidental administration of the 1:1000 solution during dental procedures: Four case reports. Fernando, DM., Dayaratne, KM.[2013]

Intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin significantly improved anesthetic success rates for first molars and second premolars when used as a supplement to an inferior alveolar nerve (IAN) block, achieving 100% success in these teeth.

Both 2% mepivacaine and 2% lidocaine with 1:100,000 epinephrine showed equivalent efficacy in anesthesia and heart rate increase, with an average heart rate increase of 23-24 beats per minute observed in 80% of subjects after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anesthetic efficacy and heart rate effects of the supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin. Guglielmo, A., Reader, A., Nist, R., et al.[2019]

In a study involving 60 patients, both 4% articaine with 1:100,000 epinephrine and 4% articaine with 1:200,000 epinephrine provided high anesthetic success rates (96.8% and 93.1%, respectively), indicating that both concentrations are effective for dental procedures.

The study found that the concentration of epinephrine did not significantly impact the anesthetic efficacy of articaine, and both formulations resulted in minimal changes in cardiovascular parameters during the procedure, suggesting they are safe options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Pereira, LA., Groppo, FC., Bergamaschi, Cde C., et al.[2022]

In a study of 102 patients undergoing surgery for femoral fractures, a multimodal analgesic injection containing ropivacaine, epinephrine, and morphine significantly reduced postoperative pain levels compared to a control group, as measured by visual analog scale (VAS) scores at multiple time points.

The injection group also required significantly less narcotic medication in the first 8 hours post-surgery, with no observed adverse effects from the local anesthetic, indicating both safety and efficacy of this pain management approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Surgical-Site, Multimodal Drug Injection Following Operative Management of Femoral Fractures: A Randomized Controlled Trial. Koehler, D., Marsh, JL., Karam, M., et al.[2022]

In a study involving 200 patients undergoing total knee arthroplasty, there was no significant difference in narcotic consumption between those receiving intra-articular bupivacaine HCl via the ON-Q Pain Relief System and those receiving liposomal bupivacaine (Exparel).

While the ON-Q group reported slightly lower pain levels during walking and physical therapy, these differences were minimal and likely not clinically significant, suggesting that both anesthetic methods are similarly effective post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periarticular Liposomal Bupivacaine Injection Versus Intra-Articular Bupivacaine Infusion Catheter for Analgesia After Total Knee Arthroplasty: A Double-Blinded, Randomized Controlled Trial. Smith, EB., Kazarian, GS., Maltenfort, MG., et al.[2022]

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Mepivacaine (injection route) - Side effects & uses

Blood vessel disease or; Heart disease or; Hypertension (high blood pressure)—Use with caution. The chance of side effects may be increased.