Mepivacaine vs Bupivacaine for Knee Replacement Surgery

Overseen By Kyle J Adams, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Prisma Health-Upstate

Must not be taking: Insulin, Anticoagulants, Narcotics

Disqualifiers: Bilateral TKAs, Diabetes, Renal insufficiency, others

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: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether mepivacaine or bupivacaine is more effective in enabling patients to go home the same day after knee replacement surgery. It will compare the effectiveness of each drug during surgery and recovery, focusing on pain management and any complications. Individuals who can walk at least 10 feet independently and are scheduled for a single knee replacement may be suitable candidates. As a Phase 4 trial, this research involves FDA-approved treatments and seeks to understand how they benefit more patients, offering an opportunity to contribute to improving post-surgery recovery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those using pre-operative narcotics, except for tramadol, and those with certain conditions like diabetes requiring insulin.

What is the safety track record for these treatments?

Research has shown that both mepivacaine and bupivacaine are safe and effective for numbing areas during surgery. Studies indicate they have low and similar rates of side effects, such as difficulty urinating, so patients usually do not experience trouble urinating after surgery with either drug.

For mepivacaine, research suggests it may lead to shorter recovery times compared to bupivacaine, possibly reducing hospital stays. Adjusting the mepivacaine dose based on the expected duration of surgery, rather than just patient details, has also proven safe and effective.

Both drugs have been used in surgeries like knee replacements with few complications, indicating they are well-tolerated by patients. Overall, both anesthetics have a strong safety record in clinical use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using mepivacaine and bupivacaine for knee replacement anesthesia because they offer different benefits compared to traditional options. Mepivacaine, with its 1.5% or 2% dosage, is noted for its quicker onset and shorter duration, which can be advantageous for faster recovery and less lingering numbness. Bupivacaine, on the other hand, is used in a hyperbaric form at a 0.75% dose, which provides a longer-lasting effect ideal for extended procedures and pain relief. These options might give patients and doctors more flexibility in managing pain and recovery times during knee replacement surgeries.

What evidence suggests that this trial's treatments could be effective for knee replacement surgery?

This trial will compare the effectiveness of mepivacaine and bupivacaine for spinal anesthesia during knee replacement surgery. Research has shown that both anesthetics work well for this purpose. Participants in the mepivacaine arm may recover faster and experience fewer issues with urinary retention compared to those in the bupivacaine arm. Specifically, patients receiving mepivacaine have been found to walk and regain movement sooner. Meanwhile, participants in the bupivacaine arm may benefit from strong pain relief and a reduced need for painkillers after surgery. Both anesthetics are effective, but they may offer different benefits depending on each patient's needs. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults scheduled for knee replacement surgery who are healthy enough to be discharged on the same day. Participants must not have conditions that would interfere with spinal anesthesia or recovery, such as allergies to local anesthetics, bleeding disorders, infection at the injection site, or severe heart or neurological issues.

Inclusion Criteria

I am 18 or older and scheduled for a first-time knee replacement.

I can walk at least 10 feet on my own without help.

Patient must be a candidate for same day discharge as determined by American Society of Anesthesiologists (ASA) Physical Status Classification I and II

Exclusion Criteria

I am scheduled for knee replacement surgery on both knees.

Workers' Compensation patient

I am allergic to or cannot take NSAIDs due to other medications I'm on.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Patients receive either mepivacaine or bupivacaine spinal anesthesia during their total knee arthroplasty procedure

1 day

1 visit (in-person)

Immediate Post-operative Monitoring

Patients are monitored for same-day discharge readiness and post-operative recovery, including pain management and motor function assessment

24 hours

Follow-up

Participants are contacted at Day 3 post-op to assess for complications, pain levels, and medication usage

3 days

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Mepivacaine

Trial Overview The study compares two types of spinal anesthesia drugs: Mepivacaine and Bupivacaine. It's designed to see which one allows patients to be ready for discharge sooner after knee replacement surgery. Patients will be randomly assigned a drug without knowing which one they receive (double-blind).

How Is the Trial Designed?

Group I: Bupivacaine Active Control 1 Intervention

Standard dose of hyperbaric bupivacaine anesthesia (0.75%) for total knee arthroplasty procedure

Group II: Mepivacaine Active Control 1 Intervention

Standard dose of mepivacaine anesthesia (1.5% or 2%) for total knee arthroplasty procedure

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

Approved in United States as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in European Union as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in Canada as Sensorcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Who Is Running the Clinical Trial?

Prisma Health-Upstate

Lead Sponsor

Trials

91

Recruited

47,500+

Published Research Related to This Trial

Bupivacaine with a vasoconstrictor has a shorter onset time for local anesthesia compared to bupivacaine without a vasoconstrictor, but the duration of anesthesia is longer without the vasoconstrictor.

Using bupivacaine without a vasoconstrictor resulted in lower postoperative pain levels and better blood circulation, which is beneficial for the osseointegration of dental implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. Duka, M., Lazić, Z., Stamatović, N., et al.[2019]

In a study of 30 patients undergoing knee arthroscopic surgery, the use of alkalinized 2% mepivacaine resulted in fewer marked dermatomes compared to non-alkalinized mepivacaine, indicating a more focused sensory blockade.

While alkalinization improved the quality of the nerve blockade and reduced the time until surgery could start, the overall clinical significance of these findings was minimal, suggesting that widespread use may not be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effects of carbonation on 2% mepivacaine in epidural anesthesia]. Tisner, ML., Cabrerizo, P., de Diego, R.[2013]

Patients undergoing total knee arthroplasty (TKA) with spinal mepivacaine experienced a shorter hospital stay (28.1 hours) and fewer urinary retention issues compared to those receiving bupivacaine (33.6 hours and 16.5% urinary retention).

While patients receiving mepivacaine reported slightly higher pain scores and morphine consumption immediately post-surgery, there were no significant differences in pain control or complications afterwards, indicating that mepivacaine is a safe and effective option for spinal anesthesia in TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepivacaine Spinal Anesthesia Facilitates Rapid Recovery in Total Knee Arthroplasty Compared to Bupivacaine. Mahan, MC., Jildeh, TR., Tenbrunsel, TN., et al.[2022]

In a study involving 44 patients undergoing Unicompartmental Knee Replacement, an intra-articular injection of 20 ml 0.5% bupivacaine significantly reduced pain scores compared to a saline control, both immediately and 6 hours post-injection.

Patients receiving bupivacaine reported much higher satisfaction levels, indicating that this local anaesthetic bolus improves pain management and overall experience after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular local anaesthetic on the day after surgery improves pain and patient satisfaction after Unicompartmental Knee Replacement: a randomised controlled trial. Weston-Simons, JS., Pandit, H., Haliker, V., et al.[2013]

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

In a study of 75 patients undergoing knee arthroscopy, 45 mg of isobaric mepivacaine provided effective spinal anesthesia with a satisfactory response in all patients, while also allowing for a timely discharge.

Mepivacaine was associated with a lower incidence of transient neurologic symptoms (7.4%) compared to lidocaine, making it a safer alternative for ambulatory procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose response relationships for isobaric spinal mepivacaine using the combined spinal epidural technique. Zayas, VM., Liguori, GA., Chisholm, MF., et al.[2022]

In a study involving 20 patients who underwent knee surgery, ropivacaine was found to be more effective than bupivacaine for postoperative analgesia when administered epidurally.

Both local anesthetics were given at the same concentration (0.15%) using an elastomeric pump, but ropivacaine provided better pain control, suggesting it may be a preferable option for managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peridural analgesic therapy in orthopedic surgery: comparison of ropivacaine and bupivacaine]. Fattorini, F., Pascarella, MA., Rinaldi, F., et al.[2018]

Mepivacaine spinal anesthesia leads to a quicker return to motor function (154 minutes vs. 170 minutes) and a shorter length of stay (25.95 hours vs. 29.96 hours) compared to bupivacaine in total joint arthroplasty, based on a systematic review of 5 studies involving 1,550 patients.

Patients receiving mepivacaine also experienced less urinary retention (7.15% vs. 10.58%) without significant differences in pain levels or mobility, suggesting that mepivacaine may enhance recovery and facilitate outpatient procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepivacaine Versus Bupivacaine Spinal Anesthesia for Primary Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. Siddiqi, A., Mahmoud, Y., Secic, M., et al.[2022]

In a study involving 30 patients, two forms of 0.5% bupivacaine hydrochloride (Anecaine and Marcaine) were compared for epidural anesthesia, revealing differences in how quickly and effectively they provided pain relief.

Anecaine showed a shorter onset of analgesia at the catheter site but a delayed effect in peripheral areas compared to Marcaine, indicating that even the same active ingredient can behave differently based on the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. Kozlov, SP., Vashchinskaia, TV., Svetlov, VA.[2013]

Mepivacaine leads to a quicker return of motor function and shorter length of stay after surgery compared to bupivacaine, based on a meta-analysis of 7 randomized controlled trials involving 672 patients.

While mepivacaine requires more postoperative analgesics, it does not show significant differences in transient neurologic symptoms, pain scores, complications, or patient satisfaction compared to bupivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepivacaine Versus Bupivacaine in Adult Surgical Patients: A Meta-analysis, Trial Sequential Analysis of Randomized Controlled Trials. Fu, Z., Tang, X., Wang, D., et al.[2023]

In a study of 32 patients undergoing total knee arthroplasty, those receiving mepivacaine for spinal anesthesia experienced a significantly faster return of both sensory and motor function compared to those receiving bupivacaine, with times of 164 minutes vs 212 minutes and 153 minutes vs 200 minutes, respectively.

Patients in the mepivacaine group also had fewer urinary retention episodes and a quicker time to urination, along with achieving discharge readiness 71 minutes earlier than those in the bupivacaine group, indicating a more efficient recovery process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time of return of neurologic function after spinal anesthesia for total knee arthroplasty: mepivacaine vs bupivacaine in a randomized controlled trial. Mahan, MC., Jildeh, TR., Tenbrunsel, T., et al.[2022]

In a study comparing mepivacaine 2% and isobaric bupivacaine 0.5% for spinal anesthesia in total knee arthroplasty, mepivacaine provided better hemodynamic stability, maintaining heart rate and blood pressure within 20% of baseline during the first 30 minutes after administration.

Patients receiving mepivacaine required less opioid medication for pain management and were able to ambulate significantly sooner after the procedure, indicating its efficacy as a spinal anesthetic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Mepivacaine 2% and Isobaric Bupivacaine 0.5% Spinal Anesthetics for Total Knee Arthroplasty. Bettin, NF., Crawford, KL., Peterson, JJ.[2023]

Citations

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Liposomal bupivacaine versus conventional anesthetics in ... The primary findings revealed that LB provided superior pain relief and reduced opioid consumption compared to conventional anesthetics on POD 0 ...

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Outcomes of Patients Undergoing Total Knee Arthroplasty... Previous literature indicates that mepivacaine used for spinal anesthesia may lead to reduced recovery time and urinary retention compared to bupivacaine.

8. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2790975

Efficacy of Liposomal Bupivacaine and ... This study found that liposomal bupivacaine did not improve postoperative recovery or pain compared with bupivacaine hydrochloride alone among patients ...