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

138 Participants Needed

Trial Summary

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 data supports the effectiveness of the drugs Mepivacaine and Bupivacaine for knee replacement surgery?

Research shows that Mepivacaine provides greater stability in heart rate and blood pressure during surgery, requires less pain medication afterward, and allows patients to walk sooner compared to Bupivacaine. Mepivacaine also facilitates a quicker recovery due to its shorter duration of action. ^{1 2 3 4 5}

Is Mepivacaine or Bupivacaine safe for use in humans?

Bupivacaine (also known as Marcaine) is generally safe when used in recommended doses for procedures like epidural anesthesia, with minimal side effects on mothers and newborns in obstetrics. Mepivacaine is considered a safe alternative to lidocaine for ambulatory procedures, with a lower incidence of transient neurologic symptoms (temporary nerve-related issues) than lidocaine. ^{6 7 8 9 10}

How does the drug Mepivacaine differ from Bupivacaine for knee replacement surgery?

Mepivacaine is unique because it facilitates a faster recovery after knee replacement surgery compared to Bupivacaine, making it a potentially better option for patients who prioritize a quicker return to normal activities. ^{3 5 8 11 12}

What is the purpose of this trial?

This study is a prospective, double-blind prospective randomized controlled trial comparing mepivacaine and bupivacaine spinal anesthesia for same-day discharge readiness following a unilateral primary elective TKA procedure. Study data will be collected during the patient's hospital stay for their TKA procedure, and the primary outcome of same-day discharge readiness will be assessed the day of surgery. Patients will also be contacted at Day 3 post-op to assess for any complications, current level of pain, and pain medication utilization.

Eligibility Criteria

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

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)

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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 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 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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[The effects of carbonation on 2% mepivacaine in epidural anesthesia]. [2013]

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

Comparison of Mepivacaine 2% and Isobaric Bupivacaine 0.5% Spinal Anesthetics for Total Knee Arthroplasty. [2023]

3. United States 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. [2022]

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

Mepivacaine Versus Bupivacaine Spinal Anesthesia for Primary Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. [2022]

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

Mepivacaine Spinal Anesthesia Facilitates Rapid Recovery in Total Knee Arthroplasty Compared to Bupivacaine. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. [2013]

7. Serbia pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

[Peridural analgesic therapy in orthopedic surgery: comparison of ropivacaine and bupivacaine]. [2018]

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

Dose response relationships for isobaric spinal mepivacaine using the combined spinal epidural technique. [2022]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. [2013]

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

Mepivacaine Versus Bupivacaine in Adult Surgical Patients: A Meta-analysis, Trial Sequential Analysis of Randomized Controlled Trials. [2023]

12. Netherlands 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. [2013]